Azithromycin

Rev Med Chil, 2000 May, 128(5), 509 - 12
{Triple therapy of short-term with azithromycin, amoxycillin and omeprazole for the eradication of Helicobacter pylori}; Flores S et al.; BACKGROUND: The high cost and complexity of therapeutic schemes for the eradication of Helicobacter pylori has stimulated the search of simpler and cheaper treatment options . AIM: To evaluate the efficacy of 3 days of azithromycin 500 mg od, 7 days of amoxycillin 750 mg tid and omeprazole, 20 (Group A) or 40 mg (Group B) on randomization, as a treatment for Helicobacter pylori infection in patients with endoscopically diagnosed peptic ulcer . METHODS: H . pylori status of peptic ulcer patients was pathologically confirmed by the examination of five gastric biopsies using the Giemsa stain and by rapid urease testing in two gastric biopsies . H . pylori status was reassessed not less than 28 days after completing treatment . Adverse events and compliance were evaluated . RESULTS: Fifty four patients (29 men, 25 women, mean age 48 years) were enrolled, 28 in Group A and 27 in Group B . Per protocol the infection was cured in 58.8% of patients (30/51; 95% CI: 45-73%) . On an intention to treat basis, H pylori infection was cured in 55% . Minor side effects including diarrhea and nausea were reported by 32% of patients . Ninety-five per cent of patients consumed more than 95% of prescribed medications . H . pylori was successfully eradicated in 61% of group A and 57% of group B patients (p = NS) . CONCLUSION: Short term therapy with azithromycin was poorly effective in curing H . pylori infection . The compliance was excellent . Increasing Omeprazole from 20 to 40 mg/day did not improve treatment effectiveness.

JAMA, 2000 Sep 27, 284(12), 1516 - 8
Postexposure prophylaxis for HIV after sexual assault; Myles JE et al.; PIP: This paper presents the findings of a retrospective review of charts of sexual assault survivors who were offered postexposure prophylaxis (PEP) between April 1998 and November 1999 at San Francisco General Hospital . The total cost of PEP medications was also computed . Overall, it is noted that one-third of the 367 sexual assault survivors chose to initiate PEP . Men who were anally raped are at the highest risk for HIV transmission and were most likely to initiate PEP . Among women, on the other hand, those who were non-White and homeless were less likely to accept PEP . In the context of cost, the total per-person cost of medication dispensed during the study period (US$65 per person offered PEP) is comparable to other medications offered routinely following sexual assault, such as azithromycin for chlamydia prophylaxis (US$43 per treatment) . However, there is no definitive evidence that PEP is effective in preventing HIV seroconversion after sexual assault . It is suggested that in developing rational policy recommendation offering HIV PEP after sexual assault, further studies are needed to better delineate the rates of HIV seroprevalence among sexual assailants, the efficacy of PEP after sexual exposure, and the psychological benefits or harm incurred by the sexually assaulted patients .

Pharmacotherapy, 2000 Sep, 20(9), 1055 - 9
Retrospective evaluation of a potential interaction between azithromycine and warfarin in patients stabilized on warfarin; Beckey NP et al.; STUDY OBJECTIVE: To investigate a potential interaction between azithromycin and warfarin . DESIGN: Retrospective case-control study . SETTING: Veterans Affairs medical center . PATIENTS: Fifty-two patients stable on anticoagulation therapy . INTERVENTION: Patients who received a prescription for azithromycin and warfarin at any time since the hospital was opened, June 1, 1995, to July 22, 1999, were identified through a computerized report generated from the pharmacy prescription package . MEASUREMENTS AND MAIN RESULTS: Patients having a stable international normalized ratio (INR; defined as a therapeutic INR +/- 0.2) for at least two consecutive visits before receiving an azithromycin prescription were reviewed . Changes in INR from before and after addition of azithromycin were compared with changes in a control group . Controls were identified from a computer-generated report of patients who received a prescription for terazosin and warfarin at any time since the hospital was opened to July 22, 1999 (terazosin was chosen as it has no known interaction with warfarin) . These patients also had a stable INR for at least two consecutive visits before receiving the terazosin prescription . In patients with INRs on record within 14 days after starting azithromycin or terazosin (9 patients/group), the average change in INR was 0.18 +/- 0.48 in the azithromycin group and 0.07 +/- 0.49 in the terazosin group (p=0.60) . For patients with an INR on record within 30 days after starting azithromycin or terazosin (26 patients/group), the average change in INR was 0.25 +/- 0.67 in the azithromycin group and 0.05 +/- 0.55 in the terazosin group (p=0.18) . CONCLUSION: An interaction between azithromycin and warfarin was not observed in this retrospective review of patients with a stable INR receiving the combination.

J Int Med Res, 2000 May-Jun, 28(3), 101 - 10
Azithromycin versus pivampicillin in the treatment of acute exacerbations of chronic bronchitis: a single-blind, double-dummy, multicentre study; Schouenborg P et al.; This single-blind, double-dummy, multicentre study compared oral azithromycin, administered as tablets, 500 mg once daily for 3 days, versus oral pivampicillin, 700 mg twice daily for 10 days, in adults with acute exacerbations of chronic bronchitis (not needing parenteral antibiotic therapy, hospitalization or oxygen support) . Clinical success (cure + improvement) rates were similar for both groups at the end of treatment (day 10; azithromycin, 124 of 133 {93%}; pivampicillin, 79 of 92 {86%}) and at follow-up (day 52; 98 of 126 {78%} versus 66 of 81 {81%}) . The treatments produced similar levels of pathogen eradication at the end of treatment (49 of 54 {91%} versus 32 of 37 {86%}) . Azithromycin-treated patients had significantly reduced chest discomfort at the end of treatment, and a trend towards improved lung function . The two groups were similar with respect to improvements in other clinical symptoms and patient well-being, and to the incidences of adverse events and treatment discontinuations . This oral azithromycin regime is an effective treatment for acute exacerbations of chronic bronchitis, similar in efficacy to the longer pivampicillin regime and may offer superior patient compliance.

J Paediatr Child Health, 2000 Aug, 36(4), 378 - 81
A randomized controlled trial of azithromycin and amoxycillin/clavulanate in the management of subacute childhood rhinosinusitis; Ng DK et al.; OBJECTIVE: Subacute childhood rhinosinusitis is a disorder commonly seen in children with allergic rhinitis . Antibiotics have been recommended as a major component of the treatment regime . The objective of the present study was to compare the effectiveness of a 3-day course of azithromycin and a 2-week course of amoxycillin/clavulanate in the treatment of subacute childhood rhinosinusitis . METHODOLOGY: A randomized single-blinded control study of subacute rhinosinusitis was conducted, comparing a 3-day course of azithromycin and a 2-week course of amoxycillin/clavulanate . Inclusion criteria were children aged between 5 and 16 years, duration of nasal blockage or discharge between 30 and 120 days, and abnormal sinus radiographs . All enrolled children were prescribed budesonide nasal spray (Rhinocort Aqua Nasal Spray, Astra Pharmaceuticals, Sodertalje, Sweden) as adjuvant treatment . RESULTS: Forty-two children were recruited into the study and one defaulted on follow-up . Failure occurred in 6 of 20 for the azithromycin group and 5 of 21 for the amoxycillin/clavulanate group . The odds ratio was 1.46 (95%CI 0.37-5 . 80, P = 0.73) . No relapse occurred in azithromycin group and 5 of 21 in amoxycillin/clavulanate group . The odds ratio was 0.16 (95%CI 0 . 017-1.51, P = 0.18) . Both antibiotics were well tolerated, however, two children, one from each group, complained of mild transient epigastric discomfort . CONCLUSIONS: This small study did not provide evidence of a difference between 14 days of amoxycillin/clavulanate and 3 days of azithromycin . Larger studies will be needed to determine which, if any, antibiotic regimen should be used in treating subacute childhood rhinosinusitis.

Ann Pharmacother, 2000 Mar, 34(3), 330 - 4
Severe thrombocytopenia associated with alatrofloxacin; Gales BJ et al.; OBJECTIVE: To report the development of severe thrombocytopenia during alatrofloxacin therapy . CASE SUMMARY: A 54-year-old Native American woman was admitted for pneumonia after completing a 10-day course of loracarbef 200 mg po bid . On admission, the woman was hypoxic (PO2 56 mm Hg) and had a platelet count of 408 x 10(3)/mm3 . Alatrofloxacin 300 mg iv piggyback qd was initiated in the emergency department . The patient's condition gradually improved during the next three days . While preparing for discharge on hospital day 4, the patient developed epistaxis that lasted approximately three hours . Laboratory testing revealed a platelet count of 7 x 10(3)/mm3; stable red blood cell count, hemoglobin, and hematocrit values; and a normal white blood cell count . Alatrofloxacin therapy was discontinued and azithromycin was initiated on hospital day 4 . Methylprednisolone 125 mg iv piggyback every 12 hours was initiated on hospital day 5 . The platelet count fell to 2 x 10(3)/mm3 on hospital day 5 and then began to rise, reaching 60 x 10(3)/mm3 when the patient was discharged on hospital day 8 . DISCUSSION: Numerous infectious, disease-related, environmental, and pharmacologic factors may cause thrombocytopenia . Drug-induced thrombocytopenia usually develops during the first two weeks of therapy and resolves within one week of drug discontinuation . Thrombocytopenia occurred in <1% of more than 7000 patients receiving alatrofloxacin or trovafloxacin during clinical trials . CONCLUSIONS: The time course of this patient's development of and recovery from thrombocytopenia suggests that it was induced by alatrofloxacin . Clinicians should monitor patients receiving alatrofloxacin or trovafloxacin for signs and symptoms of bleeding and thrombocytopenia.

J Reprod Med, 2000 Jun, 45(6), 490 - 2
Medical management of interstitial pregnancy with a retained IUD . A case report; McBroom JW; BACKGROUND: Systemic methotrexate therapy for interstitial pregnancy has an increased failure rate as compared to other ectopic locations . No case of interstitial pregnancy with a retained intrauterine device (IUD) has been reported on before . CASE: An asymptomatic, 21-year-old woman presented with a positive pregnancy test and a retained IUD . Vaginal ultrasound revealed a left interstitial pregnancy . Diagnostic laparoscopy was followed by a single dose of methotrexate (50 mg/m2) . Five days later, a marked increase in the human chorionic gonadotropin level was followed by a second course (four doses) of methotrexate, 1 mg/kg, alternating with 0.1 mg/kg of leucovorin . Concomitant Chlamydia was treated with azithromycin, and the IUD was expelled spontaneously . CONCLUSION: Medical management of interstitial pregnancy may prevent surgery that limits future fertility, but the evidence suggests that more than one dose of methotrexate may be required.

Am J Rhinol, 2000 May-Jun, 14(3), 143 - 8
Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal lavage; Yamada T et al.; Recently, epidemiologic and experimental studies have been reported that long-term macrolides are effective for the treatment of chronic airway inflammatory diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic fibrosis (Jaffe A, Francis J, Rosenthal M, et al . Long-term azithromycin may improve lung function in children with cystic fibrosis . Lancet 351:420, 1998), and that macrolides can directly reduce the production of IL-8 by nasal epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al . Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells . Laryngoscope 107:1661-1666, 1997) . In this study we administered macrolides with 14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for at least 3 months and measured the IL-8 level in nasal lavage from those patients . The IL-8 levels in nasal lavage from patients with nasal polyps were reduced during macrolide treatment . There was significant correlation between decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on the size of the nasal polyps . In the group whose polyps were reduced in size, the IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and were significantly higher before macrolide treatment than those in the group whose polyps showed no change (p < 0.005) . This reduction in IL-8 may be an important aspect of the effect of macrolide treatment on nasal polyps in chronic rhinosinusitis.

Infection, 2000 May-Jun, 28(3), 153 - 6
Comparison of azithromycin and doxycycline in the treatment of erythema migrans; Barsic B et al.; BACKGROUND: A randomized, multicenter, open clinical trial was undertaken in order to compare the efficacies of azithromycin and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans . PATIENTS AND METHODS: A total of 48 patients was treated orally with azithromycin, 500 mg bid on the 1st day, followed by 500 mg once daily for the next 4 days or doxycycline (40 patients) 100 mg bid for 14 days . RESULTS: Intention-to-treat analysis of clinical efficacy showed no difference between the two treatment regimens . Clinical success was observed in 46 (95.8%) azithromycin- and 33 (82.5%) doxycycline-treated patients, (p = 0.0731) . Minor symptoms persisted or appeared in the posttreatment period in two of 47 azithromycin- and three of 35 doxycycline-treated patients (p = 0.646) . Major manifestations appeared only in two patients in the doxycycline group (p = 0.179) . There was no difference in the tolerability of both drugs . CONCLUSION: Azithromycin (a total dose of 3 g) is equally effective as standard doxycycline treatment for erythema migrans in adult patients.

J Chemother, 2000 Jun, 12(3), 240 - 3
Treatment of early syphilis with azithromycin; Gruber F et al.; An open, noncomparative study was performed to establish the efficacy of azithromycin in the treatment of early syphilis . Sixteen patients were treated with oral azithromycin: 1g the first day and then 500 mg for the following 8 days . Two patients were excluded from the study, leaving 14 patients for the evaluation of the efficacy . Venereal Disease Research Laboratory (VDRL) negativity was observed in 3 out of 6 patients treated for primary syphilis after 3 months and in all patients after 6 months . Two of 8 patients treated for manifest or early latent secondary syphilis had VDRL negativity after 3 months and 4 patients after 6 months . This study demonstrates that azithromycin is effective in the treatment of early syphilis . Two patients experienced gastrointestinal side effects which did not require treatment interruption.

Int J Technol Assess Health Care, 1999 Summer, 15(3), 531 - 47
The cost-effectiveness of prophylaxis for Mycobacterium avium complex in AIDS; Scharfstein JA et al.; OBJECTIVE: To develop a simulation model to project costs, life expectancy, and cost-effectiveness in discounted dollars per quality-adjusted life-year (QALY) saved for clinical strategies to prevent Mycobacterium avium complex (MAC) in patients with AIDS . METHODS: We used natural history data from the Multicenter AIDS Cohort Study, efficacy and toxicity data from randomized clinical trials, and cost data from the AIDS Cost and Services Utilization Survey . The model permits timing of prophylaxis to be stratified by CD4 count (201-300, 101-200, 51-100, and < or = 50/mm3), and allows combinations of prophylaxis, crossover to second- and third-line agents for toxicity, and consideration of adherence, resistance, and quality of life . RESULTS: The model projects that the average HIV-infected patient with a beginning CD4 count between 201 and 300/mm3 has total lifetime costs of approximately $43,150 and a quality-adjusted life expectancy of 42.35 months . If azithromycin prophylaxis for M . avium complex is begun after the CD4 declines to 50/mm3, costs and quality-adjusted survival increase to approximately $44,040 and 42.78 months, respectively, for an incremental cost-effectiveness ratio of $25,000/QALY compared with no M . avium complex prophylaxis . Other prophylaxis options (i.e., rifabutin, clarithromycin, and combination therapies) either cost more but offer shorter survival, or have cost-effectiveness ratios above $260,000/QALY . Sensitivity analysis reveals that, for reasonable assumptions about quality of life, risk of infection, prophylaxis cost, adherence, and resistance, azithromycin remains the most cost-effective prophylaxis option . CONCLUSIONS: Azithromycin prophylaxis, begun after the CD4 count has declined to 50/mm3, is the most cost-effective M . avium complex prophylaxis strategy . Consistent with new United States Public Health Service guidelines, it should be the first-line prophylaxis option.

Eur Respir J, 2000 May, 15(5), 856 - 62
Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release; Criqui GI et al.; Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid . Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis . A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently . In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo . Sputum induction conducted 74 h pre- and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8 . There were significant (p<0.05) pre- to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms . However, no significant differences were found between azithromycin and placebo conditions in the post- minus pre-exposure value for these variables . The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables.

Pharmacotherapy, 2000 Jun, 20(6), 657 - 61
Comparison of the serum and intracellular pharmacokinetics of azithromycin in healthy and diabetic volunteers; Ernst EJ et al.; STUDY OBJECTIVE: To compare serum and intracellular pharmacokinetics of azithromycin in healthy volunteers and patients with diabetes . DESIGN: Open-label, parallel study . SETTING: Clinical research center . SUBJECTS: Twelve patients with diabetes and 12 healthy volunteers . INTERVENTIONS: Subjects were given a single 500-mg dose of azithromycin followed by 250 mg/day for 2 days . Blood samples were obtained just before and after the third dose for up to 24 hours for serum and 168 hours for intracellular measurement of azithromycin . MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters were calculated by noncompartmental methods and compared with a t test . The groups did not differ in maximum concentration, time to maximum concentration, or area under the concentration-time curve in serum or polymorphonuclear cells (PMNs) . Differences in the PMN:serum ratio were observed at the 24-hour time point (healthy 1209 +/- 432, diabetic 859 +/- 286, p=0.051) . CONCLUSION: In general, the pharmacokinetics of azithromycin are comparable in diabetics and healthy volunteers . Accumulation of drug in macrophages was slightly lower in patients.

J Infect Dis, 2000 Jun, 181 Suppl 3, S579 - 81
Description and status of the azithromycin and coronary events study (ACES); Jackson LA; The Azithromycin and Coronary Events Study is a randomized, double-blind, placebo controlled trial of azithromycin among adults with stable coronary artery disease . The study is based on the hypothesis that infection with Chlamydia pneumoniae may be causally associated with cardiovascular disease and therefore that treatment directed against this organism may reduce the risk of subsequent coronary events . Participants randomized to treatment will receive 600 mg of azithromycin orally once a week for 1 year and will be followed a mean of 4 years for the composite primary outcome of coronary heart disease death, nonfatal myocardial infarction, hospitalization for unstable angina, and coronary revascularization . Secondary objectives include those related to a better understanding of the relationship between antibody titer and inflammatory markers with treatment status and outcome; therefore, all participants will have blood specimens obtained at enrollment and a random 25% will have additional specimens collected periodically during follow-up.

J Infect Dis, 2000 Jun, 181 Suppl 3, S569 - 71
The ACADEMIC study in perspective (Azithromycin in coronary artery disease: elimination of myocardial infection with Chlamydia); Anderson JL et al.; Chlamydia pneumoniae, a common cause of respiratory infection, is vasotropic and frequently found in human atheromas . Whether it plays a causal role in coronary artery disease (CAD) is uncertain . The effects of 3 months of azithromycin treatment or placebo were tested in 302 patients with chronic CAD seropositive to C . pneumoniae at 3-6 months . Azithromycin reduced a global rank sum score of 4 inflammatory markers (C-reactive protein {CRP}, interleukin {IL}-1, IL-6, tumor necrosis factor-alpha; P=.011) and a global rank sum change score (+/-SD) (from 535+/-201 to 587+/-190; P=.027) at 6 (but not 3) months . Change scores for CRP and IL-6 and median IL-1 levels were lower . C . pneumoniae IgG and IgA antibody titers were unchanged . Clinical cardiovascular events at 6 months did not differ between groups (azithromycin, 9; placebo, 7) . Infections were reduced and drug was well tolerated . Thus, azithromycin caused modest but significant reductions in markers of inflammation, but differences in clinical events were not evident at 6 months . However, power was limited and conclusions should await results of the 2-year evaluation and larger studies.

J Infect Dis, 2000 Jun, 181 Suppl 3, S505 - 7
Chlamydia pneumoniae-induced atherosclerosis in a rabbit model; Muhlestein JB; In order to establish a causative relationship between Chlamydia pneumoniae and atherosclerosis, animal models have been proposed . In a rabbit model, arterial intimal thickening has been induced by direct intravascular and intranasal inoculation with C . pneumoniae . C . pneumoniae infection can induce significant acceleration of atherosclerosis in a mildly hyperlipidemic rabbit model but is prevented by treatment with azithromycin . Together these preliminary rabbit experiments suggest that C . pneumoniae may play a causative role in atherosclerosis . More animal studies are underway that are designed to address further mechanistic and therapeutic questions regarding the association between C . pneumoniae and atherosclerosis.

Vet Res Commun, 2000 Apr, 24(3), 169 - 77
Evaluation of the efficacy of atovaquone alone or in combination with azithromycin against acute murine toxoplasmosis; Moshkani SK et al.; Mice were infected intraperitoneally with 10,000 tachyzoites of Toxoplasma gondii (RH) strain and, 24 h later, were treated orally for 10 days with atovaquone and azithromycin, either alone or in combination . Evaluation of the efficacy of the drugs was performed by microscopic examination of smears prepared from the organs of the mice, and by subinoculation of visceral and brain suspensions from surviving mice into healthy mice at the end of the experiments . It was found that 58%, 83% and 100% of the mice survived after administration of 75, 150 or 200 mg/kg per day of azithromycin, respectively . Moreover, 8%, 17% and 25% of the mice survived after treatment with atovaquone at 20, 50 or 100 mg/kg per day, respectively . No synergistic or additive effects of combinations of atovaquone and azithromycin were observed . However, azithromycin did not eradicate the parasite from the brain and viscera of the infected mice, whereas atovaquone at 20, 50 and 100 mg/kg per day removed the parasite from viscera and at 100 mg/kg per day eradicated the parasite from the brain of infected mice . The combinations of atovaquone and azithromycin failed to completely eradicate the parasite from the brain and viscera of infected mice.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1761 - 4
Effect of azithromycin plus rifampin versus amoxicillin alone on eradication and inflammation in the chronic course of Chlamydia pneumoniae pneumonitis in mice; Bin XX et al.; The effects of treatment with azithromycin plus rifampin (A+R), amoxicillin (A), or placebo (P) on the chronic course of experimental Chlamydia pneumoniae pneumonitis in mice were assessed by culture, PCR, and immunocytochemistry as well as by degree of inflammation in lung tissue . Eradication of the pathogen was significantly more frequent and inflammation in tissue was significantly reduced after treatment with A+R compared to after treatment with A or P . Combination therapy with azithromycin plus rifampin showed favorable effects in the chronic course of C . pneumoniae pneumonitis.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1737 - 8
Failure of azithromycin in treatment of Brill-Zinsser disease; Turcinov D et al.; Two patients suffering from Brill-Zinsser disease were treated with azithromycin, which did not prove effective . Rickettsia prowazekii, the agent causing Brill-Zinsser disease, cannot be treated with azithromycin . Both patients had epidemiological features consistent with and a clinical course typical of the disease . The diagnosis of Brill-Zinsser disease was serologically confirmed.

J Surg Res, 2000 May 1, 90(1), 76 - 81
Chlamydia pneumoniae activates nuclear factor kappaB and activator protein 1 in human vascular smooth muscle and induces cellular proliferation; Miller SA et al.; BACKGROUND: Observational data strongly suggest an association between Chlamydia pneumoniae and atherosclerotic cardiovascular disease . However, few studies have mechanistically linked C . pneumoniae to vascular remodeling . The purpose of the present study was to examine the mechanistic relationship between C . pneumoniae and human vascular smooth muscle cell (VSMC) physiology . We sought to determine the influence of human VSMC infection by C . pneumoniae on (1) VSMC proliferation and (2) activation of the proinflammatory and proliferative transcription factors nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) . MATERIALS AND METHODS: C . pneumoniae was grown and isolated from Hep 2 cells . Human aortic VSMCs were inoculated with C . pneumoniae in the presence and absence of the azalide antibiotic azithromycin . Cell proliferation was assayed by direct cell counting 48 h following infection . Two hours following infection, nuclear extracts were isolated, and activation of both NF-kappaB and AP-1 was assessed by electrophoretic mobility shift assay . RESULTS: Compared with control, C . pneumoniae infection stimulated VSMC proliferation (P < 0.05) and induced both NF-kappaB and AP-1 DNA binding activity . These effects were eliminated by concurrent treatment with azithromycin . CONCLUSIONS: VSMC infection with C . pneumoniae activates proliferative intracellular signals and stimulates cell growth . These data implicate C . pneumoniae as a pathogenic mediator and a potential therapeutic target in the prevention of atherosclerotic disease .

Ann Otol Rhinol Laryngol, 2000 Apr, 109(4), 435 - 7
Irreversible sensorineural hearing loss as a result of azithromycin ototoxicity . A case report; Ress BD et al.; Azithromycin, an azalide antibiotic, rarely causes ototoxicity . According to the few reports in existence, azithromycin-induced ototoxicity occurred following prolonged high-dose therapy in patients with acquired immunodeficiency syndrome and resulted in a reversible sensorineural hearing loss . We present a case of irreversible sensorineural hearing loss due to azithromycin ototoxicity in an otherwise healthy woman following low-dose exposure to azithromycin.

Med J Aust, 2000 Feb 21, 172(4), 163 - 6
A targeted, single-dose azithromycin strategy for trachoma; Laming AC et al.; OBJECTIVE: To evaluate the impact of treating children with acute trachoma and their contacts with oral azithromycin . DESIGN: Open, uncontrolled, prospective evaluation of a community-based treatment strategy . SETTING: Central Australian semi-desert Aboriginal community (1995-1996) . PARTICIPANTS: 216 school- and pre-schoolchildren aged 6 months and up to 15 years . INTERVENTION: All children with acute trachoma and their contacts (co-resident siblings aged between 6 months and 15 years) received single-dose oral azithromycin suspension (20 mg/kg, to a maximum of 1000 mg) . MAIN OUTCOME MEASURE: Prevalence of acute trachoma (World Health Organization trachoma diagnostic criteria) . RESULTS: Trachoma prevalence at baseline was 42% (71/169) and 55% (18/33) for schoolchildren and pre-schoolchildren, respectively: 103 schoolchildren and 21 pre-schoolchildren, comprising 77 with follicular trachoma and their 47 contacts, were treated with azithromycin over an 8-week period . Acute trachoma prevalence in schoolchildren fell to 22% at 6-8 months (P < 0.0001) and was 31% at 12 months (P < 0.05 compared with baseline) . Pre-schoolchildren were followed up for 6 months after treatment, and their trachoma prevalence fell from 55% to 25% (P < 0.05) . Further treatment was given to children with trachoma at 12 months, and the point prevalence of trachoma for schoolchildren at 24 months was 34% . CONCLUSIONS: In contrast to mass-treatment strategies, significant reductions in trachoma prevalence at 6 months were achieved by screening 35% of community members (216) and treating 20% (124) . The subsequent prevalence increases support the need for more comprehensive treatment programs, including health promotion and efforts to improve living conditions.

Antimicrob Agents Chemother, 2000 May, 44(5), 1333 - 6
Efficacy of SCH27899 in an animal model of Legionnaires' disease using immunocompromised A/J mice; Brieland JK et al.; The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease . A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L . pneumophila serogroup 1 (10(5) CFU per mouse) . At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg {MPK} intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L . pneumophila were assessed . In the absence of SCH27899, there was 100% mortality in L . pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria . In contrast, administration of SCH27899 at a dose of > or =30 MPK resulted in > or =90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L . pneumophila . In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI) . Administration of SCH27899, OFX, or AZI at a dose of > or =30 MPK once daily for 5 days resulted in > or =85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria . However, L . pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics . These studies demonstrate that SCH27899 effectively prevents fatal replicative L . pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria . However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic.

N Engl J Med, 2000 Apr 13, 342(15), 1085 - 92
Discontinuation of prophylaxis for Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy . Terry Beirn Community Programs for Clinical Research on AIDS; El-Sadr WM et al.; BACKGROUND: Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection . However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy . METHODS: We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy . The primary end point was M . avium complex disease or bacterial pneumonia . RESULTS: A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter . In 48 percent of the patients, the HIV RNA value was below the level of quantification . The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness . During follow-up over a median period of 12 months, there were no episodes of confirmed M . avium complex disease in either group (95 percent confidence interval for the rate of disease in each group, 0 to 1.5 episodes per 100 person-years) . Three patients in the azithromycin group (1.2 percent) and five in the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50; P=0.48) . Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups . Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; relative risk, 6.6; P=0.002) . CONCLUSIONS: Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy.

J Antimicrob Chemother, 2000 Apr, 45(4), 453 - 6
Activity of nitazoxanide alone and in combination with azithromycin and rifabutin against Cryptosporidium parvum in cell culture; Giacometti A et al.; The in vitro activity of nitazoxanide alone and in combination with azithromycin and rifabutin was investigated against four clinical isolates of Cryptosporidium parvum . The susceptibility tests were performed by inoculation of the isolates on toe cell monolayers and determination of the parasite count after 48 h incubation at 37 degrees C . The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of each agent . Antibiotic-free plates were used as controls . Experiments were performed in triplicate . Nitazoxanide showed moderate anticryptosporidial activity: it suppressed the growth of parasites by >50% at 8 mg/L . A parasite reduction of 79.8-83.9% was observed when nitazoxanide 8 mg/L was combined with azithromycin 8 mg/L and rifabutin 8 mg/L . The study suggests that nitazoxanide may be active in inhibiting C . parvum growth in vitro upon combination with azithromycin or rifabutin.

J Antimicrob Chemother, 2000 Mar, 45(3), 375 - 7
Anticryptosporidial activity of ranalexin, lasalocid and azithromycin alone and in combination in cell lines; Giacometti A et al.; The in vitro anticryptosporidial activities of ranalexin, lasalocid and azithromycin alone and in combination were investigated against four clinical isolates of Cryptosporidium parvum . Susceptibility was tested by inoculating the isolates on to cell monolayers and determining the parasite count after 48 h incubation at 37 degrees C . The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of the above-mentioned compounds . Ranalexin showed moderate anticryptosporidial activity: at a concentration of 64 mg/L it reduced parasite counts by 33.8% . Azithromycin at a concentration of 8 mg/L gave inhibition comparable to that observed with the highest concentration of ranalexin . Lasalocid showed the highest activity, with a 70.3% reduction in parasite counts at 2 mg/L . The combination of ranalexin 64 mg/L and lasalocid 2 mg/L completely suppressed parasite growth without harming the monolayer.

Clin Infect Dis, 2000 Feb, 30(2), 288 - 92
Early results (at 6 months) with intermittent clarithromycin-including regimens for lung disease due to Mycobacterium avium complex; Griffith DE et al.; We initiated a prospective noncomparative trial of treatment for lung disease due to Mycobacterium avium complex (MAC) in human immunodeficiency virus-negative patients, with a regimen of clarithromycin (1000 mg), rifabutin (300-600 mg), and ethambutol (25 mg/kg) administered 3 times per week . Fifty-nine patients were enrolled . Twelve (20%) were lost to follow-up, and 6 (10%) developed clarithromycin intolerance . The remaining 41 patients (69%) completed the initial 6 months of therapy . The sputum of 32 of these patients (78%) converted to negative . When results were compared with the sputum response rates at 6 months in previous studies with a regimen including daily clarithromycin and regimens including intermittent (3 times per week) azithromycin with the same companion drugs, no differences in treatment responses were evident . Adverse reactions related to rifabutin were a major problem, and for 24 (41%) of 59 patients the dosage was decreased or the drug was withdrawn . Intermittent (3 times per week) administration of clarithromycin appears to be as effective as daily administration in effecting sputum conversion in pulmonary MAC disease.

Am Fam Physician, 2000 Jan 15, 61(2), 379 - 86
Update on the prevention and treatment of sexually transmitted diseases; Miller KE et al.; The Centers for Disease Control and Prevention updated its guidelines for the treatment of sexually transmitted diseases . The guidelines include the following information: recommendations for hepatitis A immunization and expanded indications for hepatitis B vaccination; updated diagnostic criteria for pelvic inflammatory disease and parenteral treatment regimens; information on two additional antiviral agents for the treatment of genital herpes; a recommendation for use of a single 1-g dose of azithromycin (Zithromax) to treat urethritis and chlamydial cervicitis; information on the use of quinolones in the treatment of gonococcal infections; information on podofilox and imiquimod, which are both patient-applied medications, in the treatment of noncervical human papillomavirus infection; updated guidelines for the prevention and detection of congenital syphilis; and information on how to prevent the spread of sexually transmitted diseases by educating patients about the importance of changing their sexual behaviors . To have a significant impact on the current rate of transmission of sexually transmitted diseases, family physicians should develop a plan to integrate the guidelines into their practices.

Wien Klin Wochenschr, 1999 Dec 10, 111(22-23), 923 - 32
Erythema migrans in the immunocompromised host; Maraspin V et al.; From 1990 to 1996 a total of 67 adult patients with typical erythema migrans (EM) and a previously identified immunocompromised condition were investigated at the University Medical Centre, Department of Infectious Diseases, Ljubljana, Slovenia . The course and outcome of borrelial infection were compared with 67 previously healthy age and sex-matched individuals with EM who were examined at our institution in the same year . Clinical characteristics of Lyme borreliosis before treatment and the duration of EM after the institution of therapy with antibiotics including amoxicillin, azithromycin, cefuroxime-axetil, doxycycline, and ceftriaxone were comparable in both groups . The occurrence of early disseminated borrelial infection before treatment and the frequency of treatment failure (defined as the onset of severe minor or major manifestations of Lyme borreliosis, persistence of B . burgdorferi sensu lato in the skin and/or persistence of EM after treatment) were found significantly more often in immunocompromised patients than in the control group (16/67 versus 6/67, respectively; p = 0.0358) . Re-treatment was required in 13 (19.4%) patients of the immunocompromised group and only in five (7.5%) patients of the control group (p = 0.0762) . However, in spite of the more severe course and the more frequent need for re-treatment among patients whose immune system was impaired, the outcome of borrelial infection after one year was favourable in both groups.

Aliment Pharmacol Ther, 2000 Jan, 14(1), 69 - 72
Pantoprazole, amoxycillin and either azithromycin or clarithromycin for eradication of Helicobacter pylori in duodenal ulcer; Vcev A et al.; BACKGROUND: Studies have shown that 1-week triple therapy consisting of a proton pump inhibitor, amoxycillin and clarithromycin may cure Helicobacter pylori infection in the majority of patients . AIM: To establish whether pantoprazole plus amoxycillin in association with either azithromycin or clarithromycin is useful in curing H . pylori infection in patients with a duodenal ulcer . METHODS: One hundred and ten patients with active duodenal ulcers and H . pylori infection were treated with pantoprazole (days 1-7, 40 mg b.d.; days 8-28 40 mg o.d.) plus amoxycillin 1 g b.d . for the first 7 days . Patients were randomly assigned to receive either azithromycin 500 mg o.d . for the first 6 days (PAAz group; n=55) or clarithromycin 500 mg b.d . for the first 7 days of treatment (PAC group; n=55) . H . pylori status was determined by urease test and histology before the treatment, and again 4 weeks after cessation of any medication . RESULTS: One hundred and three patients completed the study . H . pylori infection was eradicated in 78% (39/50) of patients in the PAAz group (ITT analysis: 71%, 95% CI: 61-83%) vs . 81% (43/53) of patients in the PAC group (ITT analysis: 78%, 95% CI: 69-90%) (N.S.) . All ulcers had healed . CONCLUSION: Our study shows that 1-week triple therapy with pantoprazole, amoxycillin and either azithromycin or clarithromycin is not satisfactory (<80% ITT H . pylori eradication rate).

J Antimicrob Chemother, 1999 Dec, 44(6), 811 - 7
Cost-effectiveness of azithromycin for preventing Mycobacterium avium complex infection in HIV-positive patients in the era of highly active antiretroviral therapy.The Swiss HIV Cohort Study; Sendi PP et al.; We conducted a cost-effectiveness analysis to determine the clinical and economic consequences of Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in a health care system with access unrestricted by financial barriers . The analysis was performed from a health care perspective and compared azithromycin (1200 mg/week) with no prophylaxis over a period of 10 years based on data from the Swiss HIV Cohort Study (SHCS) and randomized controlled trials . The main outcome measures were: expected survival; average health care costs; and cost-effectiveness in 1997 Swiss francs ( pound1 corresponds to about 2.3 CHF) per life-year saved . In patients with an initial CD4 count <50 cells/mm(3) and no AIDS, azithromycin increased expected survival by 4 months . In patients with AIDS, HAART durability had a major impact on expected survival and costs . Incremental survival increased from 2 to 4 months if we assumed a 10 year, instead of a 3 year, HAART effect . The cost-effectiveness of azithromycin relative to no prophylaxis in patients without AIDS was between 47,000 CHF (3-year HAART effect) and 60,000 CHF (10-year HAART effect) per life-year saved . The cost-effectiveness ratio increased to 118,000 CHF per life-year saved in patients with symptomatic AIDS . In conclusion, in the era of HAART, MAC prophylaxis with azithromycin increases expected survival and reduces health care costs substantially . Starting MAC prophylaxis in patients without AIDS is more effective and cost-effective than in patients with AIDS.

Hum Reprod Update, 1999 Sep-Oct, 5(5), 433 - 47
Chlamydia trachomatis: impact on human reproduction; Paavonen J et al.; Chlamydia trachomatis infections are the most prevalent bacterial sexually transmitted infections (STI) recognized throughout the world . Worldwide, the magnitude of morbidity associated with sexually transmitted chlamydial infections is enormous . C.trachomatis is a common cause of urethritis and cervicitis, and sequelae include pelvic inflammatory disease (PID), ectopic pregnancy, tubal factor infertility, epididymitis, proctitis and reactive arthritis . The sharp worldwide increase in the incidence of PID during the past two decades has led to the secondary epidemics of tubal factor infertility and ectopic pregnancy . Chlamydial PID is the most important preventable cause of infertility and adverse pregnancy outcome . Chlamydial infections, like STI in general, are primarily a woman's health care issue since the manifestations and consequences are more damaging to the reproductive health in women than in men . Based on the available evidence, approximately 20% of women with chlamydial lower genital tract infection will develop PID, approximately 4% develop chronic pelvic pain, 3% infertility, and 2% adverse pregnancy outcome . However, these estimates are based on relatively weak evidence . Research on the link between C.trachomatis and male aspects of infertility has been much more limited . Currently recommended treatment regimens include azithromycin in a single dose or doxycycline for 7 days . These therapies are highly efficacious . Timely management of sex partners is essential for decreasing the risk for re-infection . Immunopathogenesis of C.trachomatis infection is one of the main focal points of current research into Chlamydia . Chlamydial infection fills the general prerequisites for disease prevention by screening, i.e . chlamydial infections are highly prevalent, usually asymptomatic, are associated with significant morbidity, can be reliably diagnosed, and are treatable . Screening programmes for C.trachomatis will be of paramount importance in the prevention of long-term sequelae . The cost of screening is only a fraction of the health care costs incurred due to complications resulting from undiagnosed and untreated chlamydial infections . Current strategies to control C.trachomatis still largely depend on clinic-based screening of symptomatic patients, and have not been successful . The development of highly sensitive and specific nucleic acid amplification tests for the diagnosis of chlamydial infections has been an important advance in the ability to conduct population-based screening programmes to prevent complications . Thus, the case for screening is clearly made, but much detail remains to be worked out.

Pediatr Infect Dis J, 1999 Nov, 18(11), 955 - 8
Impact of community-based mass treatment for trachoma with oral azithromycin on general morbidity in Gambian children; Whitty CJ et al.; BACKGROUND: The World Health Organization has recently targeted the elimination of trachoma as a public health problem by the year 2020 . Community-based treatment with antibiotics, including oral azithromycin, is recommended for severely affected communities . The incidence of adverse effects after azithromycin treatment is not known in trachoma endemic communities . METHODS: We compared the effects of azithromycin with those of topical tetracycline given as mass treatment for trachoma on childhood morbidity in eight rural Gambian villages . The entire population of four villages received oral azithromycin suspension (Zithromax, Pfizer) in doses of 20 mg/kg on Days 1, 8 and 15; the other four villages received topical tetracycline eye ointment for 42 days . Morbidity surveys of subjects 3 months to 14 years old were conducted on Days 0, 7, 14, 21 and 28 . RESULTS: Of the 804 subjects recruited complete follow-up data were available on 791 (412 azithromycin, 379 tetracycline) . Fever and headache were the most common complaints . Apart from cough other symptoms were equally prevalent in both groups at baseline . The azithromycin group had 20% fewer illness, fever and headache episodes and 40% fewer diarrhea and vomiting episodes at follow-up than did the tetracycline group . CONCLUSIONS: Azithromycin treatment for trachoma had favorable short term effects on childhood morbidity in rural Gambian villages, particularly in the high malaria transmission season, and adverse effects were not a problem.

Clin Exp Metastasis, 1999 Jun, 17(4), 361 - 7
Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells; Yatsunami J et al.; We examined the effects of macrolide antibiotics on tumor angiogenesis, tumor growth and metastasis in the B 16BL6 mouse melanoma and C57BL mouse system . Two 14-membered ring macrolide antibiotics, roxithromycin and clarithromycin, significantly reduced the dense capillary network area in a mouse dorsal air sac angiogenesis model, whereas a 15-membered ring macrolide, azithromycin, and a 16-membered ring macrolide, josamycin, did not show any inhibitory effect on angiogenesis at the same dose . Intraperitoneal administration of roxithromycin and clarithromycin at 50 mg/kg/day reduced the tumor size of B 16BL6 melanoma to about 41% and 56%, respectively, of that of the control, and significantly suppressed pulmonary metastasis of B16BL6 cells in a spontaneous system . Azithromycin and josamycin, on the other hand, did not inhibit tumor growth or pulmonary metastasis of B16BL6 cells . Immunohistochemistry revealed that roxithromycin and clarithromycin reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo . These results suggest that 14-membered ring macrolides have antiangiogenic and antitumor effects and might have possible therapeutic applications.

Am Heart J, 1999 Nov, 138(5 Pt 2), S512 - 3
Value of animal models for Chlamydia pneumoniae-related atherosclerosis; Fong IW; Chlamydia pneumoniae is strongly implicated in the pathogenesis of atherosclerosis in human beings . Animal models are important to help establish causality, to understand the mechanism of infection induced atherogenesis, to examine interaction of other factors or variables, to explore treatment regimens and their efficacy, and to help develop a vaccine for prevention . To date, the rabbit model is the only animal model shown to develop de novo atherosclerotic changes with C pneumoniae infection . However, the mouse model may be useful to show enhancement with other factors such as hypercholesterolemia and to explore pathogenic mechanisms . In our studies, we have shown that C pneumoniae respiratory infection in the rabbit results in early atherosclerotic changes in 26% with single inoculation and in 35% after triple inoculation, but sham infection or infection with Mycoplasma pneumoniae does not result in similar changes . Early treatment (5 days after inoculation) with 30 mg/kg per day azithromycin once every 6 days was 87% effective in preventing atherosclerotic changes, but delayed treatment (6 weeks after inoculation) was ineffective . Further studies are needed with longer or more aggressive regimens or possible combination of agents to determine whether it is possible to reverse preformed lesions . An effective vaccine for prevention of C pneumoniae -induced pneumonia and possibly atherosclerotic lesions in human beings would have tremendous application and would circumvent the shortcomings of antibiotic therapy.

J Antimicrob Chemother, 1999 Sep, 44(3), 411 - 4
Safety and effect on anti-Chlamydia pneumoniae antibody titres of a 1 month course of daily azithromycin in adults with coronary artery disease; Jackson LA et al.; A pilot study of azithromycin treatment following percutaneous coronary revascularization procedures was performed to assess safety and the effect of azithromycin treatment on anti-Chlamydia pneumoniae antibody titres . Patients were randomized to a 1 month course of azithromycin (total dose of 8.0 g) or placebo . Safety and compliance were assessed at 2 and 4 weeks and serological testing was performed on samples obtained at enrolment and at 6 months post-enrolment . Azithromycin was well tolerated at this dose . No effect of treatment on antibody titres was demonstrated . These results support further clinical trials to assess the effect of azithromycin treatment on cardiovascular disease outcomes.

Rev Soc Bras Med Trop, 1999 Jul-Aug, 32(4), 401 - 3
{The evaluation of the efficacy of azithromycin and pyrimethamine used alone or in combination in the treatment of an experimental infection in mice by Toxoplasma gondii}; Braz LM et al.; The efficacy of azithromycin and pyrimethamine in experimental infection of mice with Toxoplasma gondii was tested . Daily dosages of 200 mg/kg and 12.5 mg/kg, respectively, were given orally over a period of ten days . The medications were administered in combination or separately . The combined use of the drugs yielded better results, and a similar investigation using a cystogenic strain of the parasite will be conducted in a future study.

Lancet, 1999 Sep 11, 354(9182), 891 - 5
Efficacy of azithromycin in prevention of Pneumocystis carinii pneumonia: a randomised trial . California Collaborative Treatment Group; Dunne MW et al.; BACKGROUND: Azithromycin in combination with sulphonamides is active against Pneumocystis carinii pneumonia (PCP) in animals . We assessed the clinical efficacy of azithromycin for PCP prophylaxis in human beings . METHODS: We identified HIV-1-infected patients with PCP during a prospective randomised trial comparing azithromycin, rifabutin, and the two drugs in combination for prevention of disseminated Mycobacterim avium infection . Patients had CD4-cell counts less than 100/microL at entry and received PCP prophylaxis according to the standard practice of their clinician . Analysis was by intention to treat . FINDINGS: Patients receiving azithromycin, either alone (n=233) or in combination with rifabutin (n=224), had a 45% lower risk of developing PCP than those receiving rifabutin alone (n=236; p=0.008) . Compared with rifabutin alone, hazard ratio for azithromycin was 0.54 (95% CI 0.32-0.94), for azithromycin plus rifabutin was 0.55 (0.32-0.94), and for regimens containing azithromycin was 0.55 (0.35-0.86) . The most common side-effects involved the gastrointestinal tract with dose-limiting toxicities, and were mainly seen in patients receiving combination therapy . INTERPRETATION: Azithromycin as prophylaxis for M . avium complex disease provides additional protection against P . carinii over and above that of standard PCP prophylaxis . Use of azithromycin is beneficial only as primary prophylaxis.

Med Clin (Barc), 1999 Jul 3, 113(4), 124 - 8
{A randomized comparative study of 3 days of azithromycin treatment and 10 days of cefuroxime treatment in exacerbations in patients with chronic obstructive pulmonary disease}; Alvarez Gutierrez FJ et al.; BACKGROUND: The aim of this study was to prospectively evaluate the clinical and gasometric evolution and the side effects of two treatment schedules in the exacerbations of patients with chronic obstructive pulmonary disease (COPD): 500 mg/24 h of azithromycin (AZM) for three days versus 500 mg/12 h of acetyl cefuroxime (ACF) for 10 days . PATIENTS AND METHODS: Patients were randomized included into each therapeutic schedule . The patients were seen three times (days 1 and 4, and at 15-21 days) to evaluate clinical symptoms scores . Forced spirometry and arterial gasometry were performed the first and the last time the patients were seen . The number of patients requiring admission during follow up and the secondary effects of each antibiotic were quantified . RESULTS: A total de 50 patients were treated with AZM and 51 with ACF . The evolution of the symptoms was similar although with a trend to greater improvement in those treated with AZM . This improvement was significant for the characteristics of expectoration (p < 0.05) . Functional and gasometric evolution was similar in the two schedules . Three patients treated with AZM required hospital admission, as did 5 treated with ACF . A greater number of secondary effects were observed in patients treated with ACF (18%) than in those receiving AZM (10%), with gastrointestinal side effects being the most commonly observed . CONCLUSIONS: Treatment with short schedule of AZM may have the same activity as longer schedule of ACF, with fewer secondary effects thereby suggesting that AZM may be an effective alternative in the treatment of exacerbations in patients with COPD.

Antimicrob Agents Chemother, 1999 Sep, 43(9), 2302 - 4
Mononuclear and polymorphonuclear leukocyte dispositions of clarithromycin and azithromycin in AIDS patients requiring Mycobacterium avium complex prophylaxis; Bui KQ et al.; The intracellular dispositions of clarithromycin and azithromycin in AIDS patients requiring Mycobacterium avium complex (MAC) prophylaxis were studied . The dispositions of both drugs in mononuclear and polymorphonuclear leukocytes were markedly different . Our data support the proven efficacy of these agents for MAC prophylaxis since clarithromycin and azithromycin displayed sustained intracellular concentrations which exceeded their MICs for MAC throughout the dosing periods.

Antimicrob Agents Chemother, 1999 Sep, 43(9), 2268 - 72
In vitro activities of azithromycin and ofloxacin against Chlamydia pneumoniae in a continuous-infection model; Kutlin A et al.; Chlamydia pneumoniae is a well-established cause of community-acquired pneumonia and bronchitis in adults and children . Chronic infections with C . pneumoniae have been implicated in the development of atherosclerosis and other diseases in humans . Methods currently used for the culture and propagation of C . pneumoniae are not analogous to the infection as it occurs in vivo . We have established a model of continuous C . pneumoniae infection in vitro . HEp-2 cells inoculated with CM-1 and TW-183 strains have been persistently infected for periods of over 1.5 and 2 years, respectively . The cultures were maintained without centrifugation or the addition of cycloheximide, fresh host cells, or chlamydia . We observed cycles of host cell lysis, detachment, and regrowth with both strains of C . pneumoniae . Continuous C . pneumoniae infections may more closely resemble the actual events as they occur in vivo and, therefore, may be a better model for the in vitro study of C . pneumoniae infection . When we used continuously infected cells to determine the effects of azithromycin and ofloxacin on C . pneumoniae propagation in vitro, we found that both drugs reduced but did not completely eliminate the organism . This may be an important observation, as the failure of antibiotic therapy against C . pneumoniae infection in humans has been described.

Lancet, 1999 Aug 21, 354(9179), 630 - 5
Azithromycin in control of trachoma; Schachter J et al.; BACKGROUND: Trachoma is the leading cause of preventable blindness . Programmes to prevent blindness due to trachoma are based on community-wide treatment with topical tetracycline . We assessed the potential of community-wide azithromycin treatment for trachoma control . METHODS: Pairs of villages in trachoma endemic areas of Egypt, The Gambia, and Tanzania were matched on trachoma rates in 1-10-year-old children . Villages were randomly assigned community-wide oral azithromycin treatment (three doses with intervals of 1 week) or treatment with 1% topical tetracycline (once daily for 6 weeks) . Clinical examinations were done at baseline, 2-4.5 months, and 12-14 months after treatment . Chlamydia trachomatitis was identified by ligase chain reaction (LCR) . Analyses were by intention to treat . Univariate comparisons and multivariate analyses were used to compare outcomes . FINDINGS: LCR positivity was correlated with clinical severity, but about 30% of Egyptian and Gambian villagers with no active disease were LCR positive . Village-wide LCR positivity ranged from 16.5% (Tanzania) to 43.6% (Egypt) . Treatment compliance was over 90% except in the tetracycline treatment village in Egypt . Of the participants initially LCR positive, 866 (95%) of 924 who received at least one azithromycin dose and 482 (82%) of 587 who received 28 days or more topical tetracycline, were negative at follow-up . At 1 year, village-wide LCR positivity rates were substantially lower than at baseline with both treatments; the decreases were greater with azithromycin than with tetracycline (93% vs 77% in Egypt, 78 vs 66% in The Gambia, 64 vs 55% in Tanzania) . Similarly, greater reduction in clinical activity occurred after azithromycin . In multivariate analyses, factors associated with being LCR positive at 1 year were: not receiving azithromycin; age under 10 years; and LCR positivity at baseline . INTERPRETATION: Community-wide treatment with oral azithromycin markedly reduces C . trachomatis infection and clinical trachoma in endemic areas and may be an important approach to control of trachoma.

J Eval Clin Pract, 1999 Aug, 5(3), 283 - 95
Systematic validation of disease models for pharmacoeconomic evaluations . Swiss HIV Cohort Study; Sendi PP et al.; Pharmacoeconomic evaluations are often based on computer models which simulate the course of disease with and without medical interventions . The purpose of this study is to propose and illustrate a rigorous approach for validating such disease models . For illustrative purposes, we applied this approach to a computer-based model we developed to mimic the history of HIV-infected subjects at the greatest risk for Mycobacterium avium complex (MAC) infection in Switzerland . The drugs included as a prophylactic intervention against MAC infection were azithromycin and clarithromycin . We used a homogenous Markov chain to describe the progression of an HIV-infected patient through six MAC-free states, one MAC state, and death . Probability estimates were extracted from the Swiss HIV Cohort Study database (1993-95) and randomized controlled trials . The model was validated testing for (1) technical validity (2) predictive validity (3) face validity and (4) modelling process validity . Sensitivity analysis and independent model implementation in DATA (PPS) and self-written Fortran 90 code (BAC) assured technical validity . Agreement between modelled and observed MAC incidence confirmed predictive validity . Modelled MAC prophylaxis at different starting conditions affirmed face validity . Published articles by other authors supported modelling process validity . The proposed validation procedure is a useful approach to improve the validity of the model.

Drug Saf, 1999 Aug, 21(2), 137 - 52
Risk-benefit assessment of therapies for Mycobacterium avium complex infections; Griffith DE; Mycobacterium avium complex (MAC) is an important pathogen that can cause chronic lung disease in immunocompetent patients and disseminated disease in patients with the acquired immunodeficiency syndrome (AIDS) . Treatment of MAC with antituberculosis drugs was unsatisfactory, but the introduction of the newer macrolides, clarithromycin and azithromycin, and of rifabutin has greatly improved the outcome of treatment regimens for MAC . However, these agents are also associated with many new treatment-related adverse effects and potential drug-drug interactions . Rifamycins {rifampicin (rifampin) more than rifabutin} induce cytochrome P450 enzymes and accelerate the metabolism of clarithromycin and HIV protease inhibitors . Conversely, clarithromycin inhibits these enzymes, resulting in increased rifabutin toxicity . The net results are treatment regimens that may be extremely difficult to tolerate, especially for elderly or debilitated patients . Clarithromycin and azithromycin must be administered in combination with other agents such as ethambutol to prevent the emergence of macrolide resistance . Unfortunately, not all patients respond to the combination of a macrolide, rifabutin and ethambutol, and many have significant adverse effects (mostly gastrointestinal) with this regimen . For some patients the treatment is worse than the disease . The same 3-drug regimen is also effective therapy for disseminated MAC in AIDS patients, in whom the additional problem of a rifamycin/protease inhibitor interaction may be present . Fortunately, as opposed to pulmonary MAC disease in immunocompetent patients, disseminated MAC disease is a diminishing problem because of effective prophylactic regimens for MAC and improved antiretroviral therapy for HIV . Significant progress has been made in the treatment of MAC disease with the introduction of the newer macrolides . It is to be hoped that even better drugs that are more active against MAC and are associated with less toxicity and drug-drug interactions will be introduced in the future.

J Clin Pharmacol, 1999 Aug, 39(8), 842 - 6
The effect of azithromycin on the pharmacokinetics of indinavir; Foulds G et al.; This study was performed to examine the effect of the coadministration of azithromycin on the pharmacokinetics of the protease inhibitor indinavir (Crixivan) . In an open-label, parallel-design study, 32 healthy male and female volunteers were given indinavir (800 mg tid) for 5 days . One hour prior to the first dose of indinavir on day 5, 18 subjects received 1200 mg azithromycin (Zithromax), and 14 subjects received matching placebo . Serial samples of plasma were obtained for 8 hours following the morning dose of indinavir on days 4 and 5 and assayed for indinavir by HPLC/UV . Twenty-seven subjects completed the study . Following coadministration of azithromycin with indinavir, there was no significant change between day 5 and day 4 in AUC (20.7 mg.hr/ml and 23.1 mg.hr/ml; 90% CI on the ratio 81%-100%) or Cmax (9.88 mg/ml and 10.3 mg/ml; 90% CI 86%-108%) . The day 5 to day 4 difference in indinavir concentrations following coadministration with azithromycin was not significantly different from the day 5 to day 4 difference with placebo (AUC p = 0.68; Cmax p = 0.074) . Therefore, azithromycin does not significantly alter the kinetics of indinavir.

Pharmacotherapy, 1999 Jul, 19(7), 902 - 8
Potential interaction between azithromycin and warfarin; Foster DR et al.; Azithromycin is considered unlikely to interact with warfarin . Unlike other macrolide antibiotics, it is not hepatically metabolized and did not produce an interaction with warfarin in a single-dose study . A 71-year-old woman with a prosthetic heart valve, stabilized with warfarin, had international normalized ratios (INRs) maintained between 2.5 and 3.5 . Six days after she received a prescription for a 5-day course of azithromycin, her INR was 15.16 . Phytonadione 10 mg was administered subcutaneously, and warfarin was held for 3 days until her INR fell to 2.10 . She then was restabilized with warfarin . Until more information is known about the safety of warfarin and azithromycin, caution is advised when the agents are given together . Close monitoring of INR is recommended, and warfarin dosage adjustment may be necessary.

Am J Vet Res, 1999 Jul, 60(7), 880 - 3
Use of a urea breath test to evaluate short-term treatments for cats naturally infected with Helicobacter heilmannii; Neiger R et al.; OBJECTIVE: To evaluate efficacy of 3 short-term treatments in cats naturally infected with Helicobacter heilmannii . ANIMALS: 29 cats infected with H heilmannii that had positive results for a urea breath test, rapid urease test, and Helicobacter species-specific polymerase chain reaction test . PROCEDURES: Cats anesthetized for routine surgical procedures were randomly allocated to 4 groups: group 1, control cats; group 2, cats treated with azithromycin, tinidazole, ranitidine, and bismuth once daily for 4 days; group 3, cats treated with clarithromycin, metronidazole, ranitidine, and bismuth twice daily for 4 days; and group 4, cats treated with clarithromycin, metronidazole, ranitidine, and bismuth twice daily for 7 days . Efficacy was determined on the basis of results of a urea breath test performed 10 and 42 days after end of treatment . RESULTS: Ten days after treatment, 0 of 4, 4 of 6, 11 of 11, and 8 of 8 cats in groups 1 to 4, respectively, had a negative result for a urea breath test . Forty-two days after treatment, 0 of 4, 3 of 6, 7 of 11, and 4 of 8 cats in groups 1 to 4, respectively, still had a negative result . CONCLUSIONS AND CLINICAL RELEVANCE: Treatments used in this study regularly suppressed breath 13CO2 production . However, although 23 of 25 (92%) cats had negative results for a urea breath test 10 days after treatment, only 14 of 25 (56%) cats still had negative results 42 days after treatment . It is difficult to achieve a definitive long-term cure in cats naturally infected with H heilmannii.

Infection, 1999 May-Jun, 27(3), 198 - 202
Azithromycin: single 1.5 g dose in the treatment of patients with atypical pneumonia syndrome--a randomized study; Schonwald S et al.; An open comparative study was undertaken in order to assess the efficacy and safety of a single dose of azithromycin in the treatment of community-acquired atypical pneumonia . A total of 100 adult patients with atypical pneumonia syndrome were randomized to receive 1.5 g of azithromycin as a single dose, or 500 mg once daily for 3 days . The presence of Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, and Legionella pneumophila infection was diagnosed by serological tests . Control clinical examinations were performed 72 h, 10-12 days and 4 weeks after treatment initiation . Among 96 patients (48 in each group) who were evaluable for clinical efficacy M . pneumoniae infection was confirmed in 24, C . pneumoniae in nine, C . psittaci in five, C . burnetii in six, and L . pneumophila in five . Forty-seven patients (97.9%) in each group were cured . Side effects were observed in two patients in the single-dose group, and one patient in the 3-day group . In conclusion, a single 1.5 g dose of azithromycin may be an alternative to the standard 3-day azithromycin regimen in the treatment of outpatients with atypical pneumonia syndrome.

Ann Pharmacother, 1999 May, 33(5), 615 - 22
Chlamydia pneumoniae and coronary heart disease; Carlisle SS et al.; OBJECTIVE: To review the potential association between Chlamydia pneumoniae (CP) infection and coronary artery disease (CAD), and to describe possible therapeutic interventions . DATA SOURCES: A MEDLINE search of literature (January 1966-January 1998) pertaining to CP infection associated with heart disease was performed . Additional literature was obtained from review of journals and reference lists of pertinent articles identified through the search . STUDY SELECTION AND DATA EXTRACTION: All articles involving CP and CAD were considered for possible inclusion in this review . Other selected articles involved possible links between infection and the atherosclerotic process, inflammation and inflammatory mediators in the atherosclerotic process, and isolation of CP from human tissue . DATA SYNTHESIS: Numerous reports have suggested an association between chronic CP and CAD . CP has been seroepidemiologically linked to CAD . The organism has also been isolated from atherosclerotic lesions . Two reports in humans and one report in animals have shown that macrolide therapy (azithromycin or roxithromycin) may decrease the risk of adverse cardiovascular events . CONCLUSIONS: Evidence seems to support an association between CP infection and an increased incidence of CAD . Additional and larger seroepidemiologic studies of this association need to be performed to establish a causal relationship between infection and CAD . Determination of the actual role of CP in CAD may decide the role of specific antichlamydial therapy in the management of this condition.

Ann Pharmacother, 1999 May, 33(5), 607 - 14
Antiinfectives update: focus on treatment and prevention of viral and associated infections; McNicholl IR et al.; OBJECTIVE: To review the clinically significant antiinfectives approved by the Food and Drug Administration (FDA) since 1996, with an emphasis on agents used for treatment, prevention, or suppression of infection in immunocompromised individuals . DATA SOURCES: A MEDLINE search covering November 1994 to March 1998 was conducted to identify all antiinfectives (new medications and old medications with new indications) and the pertinent literature for review . The search was updated in August 1998 and supplemented with an FDA listing of approved drugs to enhance completeness . STUDY SELECTION: Clinically relevant studies were selected to highlight specific points about each medication . Preclinical publications were used when sufficient information was not available from clinical trials and this information was needed for clinical practice . CONCLUSIONS: Several new and promising antiretroviral agents (stavudine, lamivudine, saquinavir soft-gel capsules, nelfinavir, efavirenz) have been approved, which may allow more options to control HIV viremia . New options for treatment, prevention, and suppression of infections in immunocompromised individuals include azithromycin, cidofovir, famciclovir, valacyclovir, and itraconazole suspension . Liposomal-based amphotericin products may be associated with less toxicity than conventional amphotericin B; however, superior efficacy has not been proven.

J Infect Dis, 1999 Jul, 180(1), 229 - 33
Killing of Mycobacterium avium by neutrophils and monocytes from AIDS patients treated with recombinant granulocyte-macrophage colony-stimulating factor; Cinti S et al.; In this study, 30 AIDS patients without Mycobacterium avium infection were randomized to receive treatment with azithromycin (1200 mg), granulocyte-monocyte colony-stimulating factor (GM-CSF; 250 microg/m2/day for 5 days), or both agents . The M . avium killing capacity of neutrophils and monocytes harvested from each patient before intervention and during (day 4), and after therapy (day 8) was assessed . The mean virus load change in the groups receiving GM-CSF was +0.14 log human immunodeficiency virus RNA . After GM-CSF therapy, neither neutrophils nor monocytes could significantly reduce M . avium growth (P=.96 and.31, respectively) . Bone pain, myalgia, presyncope, or fever occurred in 55% of patients receiving GM-CSF . Thus, the GM-CSF regimen used in this study did not affect virus load, frequently caused adverse reactions, and did not improve the M . avium killing capacity of neutrophils and monocytes . Future studies using a different GM-CSF regimen are indicated.

Helicobacter, 1999 Mar, 4(1), 54 - 7
High dose omeprazole plus amoxicillin and azithromycin in eradication of Helicobacter pylori in duodenal ulcers; Vcev A et al.; BACKGROUND: The aim of our study was to establish whether one-week triple therapy regimen (omeprazole, amoxicillin, azithromycin) with low dose (2 x 20 mg/day) or high dose omeprazole (2 x 40 mg/day) is more effective in curing H . pylori infection in patients with active duodenal ulcer disease . METHODS: One hundred and twenty patients with duodenal ulcer and H . pylori infection were treated with amoxicillin 2 x 1000 mg/day for the first 7 days plus azithromycin 500 mg/day for the first 6 days . Patients were randomly assigned to receive either omeprazole 2 x 20 mg/day for the first 7 days (group A; n = 60) or omeprazole 2 x 40 mg/day for the first 7 days (group B; n = 60) . After 7 days all patients in both groups continued treatment with omeprazole (40 mg/day (days 8-14) and 20 mg/day (days 15-28)) . H . pylori status was determined by urease test and histology before the treatment and 4 weeks after cessation of any medication . RESULTS: One hundred and thirteen patients completed the study . H . pylori infection was eradicated in 73.2% {41/56} of patients in group A (intention-to-treat {ITT} analysis: 68.3%; 95% CI: 58.6-80.4%) vs . 82.5% {47/57} of patients in group B (ITT analysis: 78.3%; 95% CI: 67.8-87.9%; NS) . All ulcers had healed after 4 weeks of omeprazole treatment . Side effects, usually minor, were recorded in 12.5% (group A) and in 14% (group B) of patients (NS), but therapy was discontinued for only one patient in group B (NS) . CONCLUSION: There was no statistically significant difference between one-week triple therapy regimen (omeprazole, amoxicillin, azithromycin) with high dose omeprazole (2 x 40 mg/day) and regimen with low dose omeprazole (2 x 20 mg/day) in curing H . pylori infection in patients with active duodenal ulcer disease.

Antimicrob Agents Chemother, 1999 Jun, 43(6), 1516 - 9
Pharmacokinetics of azithromycin administered alone and with atovaquone in human immunodeficiency virus-infected children . The ACTG 254 Team; Ngo LY et al.; To evaluate if atovaquone (ATQ) interacts pharmacokinetically with azithromycin (AZ) in human immunodeficiency virus-infected children, 10 subjects (ages, 4 to 13 years) were randomized in a crossover study to receive AZ (5 mg/kg/day) alone (ALONE) or AZ (5 mg/kg/day) and ATQ (30 mg/kg/day) simultaneously (SIM) prior to receiving AZ and ATQ staggered by 12 h . Despite a lack of significant difference in the mean AZ pharmacokinetic parameters, the steady-state values of AZ's area under the concentration-time curve from 0 to 24 h and maximum concentration in serum were consistently lower (n = 7 of 7) for the SIM regimen than they were for the ALONE regimen . A larger study will be required to determine if ATQ affects AZ pharmacokinetics and efficacy in a clinically significant manner.

Antimicrob Agents Chemother, 1999 Jun, 43(6), 1491 - 3
Effect of azithromycin plus rifampin versus that of azithromycin alone on the eradication of Chlamydia pneumoniae from lung tissue in experimental pneumonitis; Wolf K et al.; Azithromycin, doxycycline, and rifampin, alone or in combination, were tested in vitro against Chlamydia pneumoniae AR-39 . The combination of azithromycin plus rifampin showed the strongest activity and produced higher rates of eradication of C . pneumoniae from lung tissues than azithromycin alone in experimental mouse pneumonitis.

Pharmacotherapy, 1999 May, 19(5), 648 - 54
Economic evaluation of three methods of treating urogenital chlamydial infections in the emergency department; Petitta A et al.; We attempted to determine the economic impact of three alternatives for the treatment of chlamydial infections in the emergency department: a written prescription for 7 days of doxycycline therapy (D-RX); a prepacked 7-day supply of doxycycline (D-ED); or a single 1-g dose of azithromycin (AZI) . Data inputs for the model were obtained from both patient experience and literature sources . Primary health outcomes of the model were number of infection relapses . Economic outcomes were costs for initial treatment, treatment of relapses, and treatment of complications of relapse . For every 1000 patients, D-ED and AZI resulted in 21.6 (-10 to -41) and 36.2 (-25 to -63) fewer relapses than D-RX, respectively; AZI resulted in 14.6 (-35 to -4) fewer relapses than D-ED . Total costs were decreased for D-ED and AZI versus D-RX by $18,879 (-$39,000 to -$8000) and $24,039 (-$59,000 to -$10,000), respectively, and AZI resulted in a total cost decrease of $5160 (-$35,000 to +$6000) versus D-ED . Both D-ER and AZI decreased infection relapses and overall health care costs compared with D-RX . Also, AZI resulted in additional decreases in relapses versus D-ED, although the incremental impact on cost was inconclusive.

Am Fam Physician, 1999 May 1, 59(9), 2523 - 30, 2535-6
Malaria prevention in travelers; Juckett G; The prevention of malaria in travelers is becoming a more challenging clinical and public health problem because of the global development of drug-resistant Plasmodium strains of malaria and the increasing popularity of travel to exotic locales . Travelers can reduce their risk of acquiring malaria by using bed netting, wearing proper clothing and applying an insect repellent that contains N,N-diethyl-meta-toluamide . Chloroquine, once the standard agent for weekly malaria prophylaxis, is no longer reliably effective outside the Middle East and Central America because of the emergence of resistant Plasmodium falciparum strains . Mefloquine is now the most effective and most recommended antimalarial agent on the U.S . market; however, the side effects of this agent have begun to limit its acceptance . Doxycycline is effective for malaria prophylaxis in travelers who are unable to take mefloquine . Daily proguanil taken in conjunction with weekly chloroquine is an option for pregnant patients traveling to sub-Saharan Africa . Terminal prophylaxis with two weeks of primaquine phosphate can eliminate an asymptomatic carrier state and the later development of malaria in newly returned long-term travelers with probable exposure to Plasmodium vivax or Plasmodium ovale . Travelers who elect not to take an antimalarial agent or who are at high risk for malaria and are more than 24 hours from medical care can use self-treatment regimens such as those featuring pyrimethamine-sulfadoxine . Conventional agents may be contraindicated in certain travelers, especially pregnant women and small children, and several prophylactic agents are not available in the United States . Azithromycin and a number of malaria vaccines are currently under investigation.

Ann Transplant, 1998, 3(3), 25 - 7
Partial regression of advanced cyclosporin-induced gingival hyperplasia after treatment with azithromycin . A case report; Nowicki M et al.; Gingival hyperplasia is a well recognised complication of cyclosporin A therapy . Although its pathogenesis is still debated in several recent reports a second generation macrolide antibiotic-azithromycin induced partial or even complete regression of hyperplasia . We present a patient after kidney transplantation treated with cyclosporin who developed very advanced gigival overgrowth (stage 3+) . The patient received a 3-day treatment with azithromycin which was repeated after 3 months . The first course of the drug caused a partial regression of gingival hyperplasia during following months but the repeated treatment did not provide a further regression of the changes.

Antimicrob Agents Chemother, 1999 May, 43(5), 1152 - 5
Lack of effect of zafirlukast on the pharmacokinetics of azithromycin, clarithromycin, and 14-hydroxyclarithromycin in healthy volunteers; Garey KW et al.; This randomized, open-label, crossover study was conducted to investigate whether the coadministration of zafirlukast would affect the pharmacokinetics of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC) . Twelve healthy subjects (six males and six females) received single 500-mg doses of azithromycin and clarithromycin with and without zafirlukast given to a steady-state concentration . Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose, respectively . Serum was assayed for azithromycin, clarithromycin, and 14-OHC concentrations by validated high-performance liquid chromatography assay systems . Data analyses were done by noncompartmental and nonparametric methods . Analysis of the patients indicated that the addition of steady-state concentrations of zafirlukast did not significantly alter the pharmacokinetic parameters of or overall exposure (based on the area under the concentration-time curve) to azithromycin, clarithromycin, and 14-OHC . While zafirlukast is a known inhibitor of CYP3A4, it does not appear to exert a clinically or statistically significant pharmacokinetic effect on azithromycin, clarithromycin, or 14-OHC.

Int J Antimicrob Agents, 1999 Feb, 11(2), 121 - 32
Effect of clarithromycin and azithromycin on production of cytokines by human monocytes; Khan AA et al.; We examined the in vitro effect of clarithromycin and azithromycin on cytokine production by LPS and Pansorbin stimulated human monocytes . At concentrations that are physiologically achievable, both antibiotics affected in vitro production of IL-1alpha, IL-1beta, IL-6, IL-10, GM-CSF and TNF-alpha to varying degrees . Of those individuals in whom a significant increase or decrease in cytokine production was noted, clarithromycin treatment resulted in a significant suppression of production of each cytokine in 71% and a significant increase in 29% of the individuals . Similar results were noted with azithromycin . The results with IL-6 and TNF-alpha in the clarithromycin studies were most striking . A significant decrease was noted in 60% of individuals for IL-6 and 86% for TNF-alpha . For azithromycin, the most interesting results were for IL-1alpha (decrease in 100% of individuals) and for TNF-alpha (decrease in 100% of individuals) . These results show that both clarithromycin and azithromycin alter cytokine production in human monocytes and thus possess immunomodulatory activity.

Int J Antimicrob Agents, 1999 Mar, 11 Suppl 1, S7 - 14; discussion S31-2
Pharmacological considerations in the emergence of resistance; Amsden GW; Resistance to macrolides in vitro is increasingly being reported . However, there has been no corresponding increase in clinical failures noted . Lack of clinical failures due to resistance is most likely the result of the high intracellular concentrations that these drugs achieve in phagocytes . In the case of clarithromycin, concentrations in both monocytes and granulocytes fluctuate between peaks of approximately 22-25 mg/l and troughs of approximately 5 mg/l during a standard dosing interval . In contrast, azithromycin attains concentrations of over 60 mg/l in granulocytes and at least 100 mg/l in monocytes . After 7 days, azithromycin concentrations of >32 mg/l are still observed . These data also imply that against pathogens with increasing minimum inhibitory concentrations (MICs), macrolides with relatively lower or less sustained intracellular concentrations will become ineffective clinically much sooner than compounds, such as azithromycin, that concentrate to a high degree and are retained in white blood cells for prolonged periods.

Am J Gastroenterol, 1999 Apr, 94(4), 962 - 6
Once-daily therapy for H . pylori infection: a randomized comparison of four regimens; Laine L et al.; OBJECTIVE: We sought to determine the efficacy and tolerability of novel, once-daily therapies in the treatment of Helicobacter pylori infection . METHODS: One hundred sixty subjects with H . pylori infection documented by endoscopic biopsy or serology plus 13C-urea breath test were randomly assigned to omeprazole 80 mg q.d . and metronidazole extended-release formulation 750 mg q.d . for 10 days (OM); OM plus amoxicillin 1.5 g q.d . for 10 days (OMAm); OM plus azithromycin 500 mg q.d . for 7 days (OMAz); or OM plus clarithromycin 1 g q.d . for 10 days (OMCI) . A repeat breath test was done 6 wk after the completion of therapy . Subjects were considered compliant if they took > or = 80% of each study medication as prescribed . RESULTS: Intent-to-treat eradication rates were OM = 8% (95% confidence interval {CI}, 2-20%), OMAm = 35% (95% CI, 21-52%), OMAz = 65% (95% CI, 48-79%), and OMCI = 78% (95% CI, 62-89%) . Lack of compliance was seen in 5% of subjects given OM, 8% given OMAm, 3% given OMAz, and 15% given OMCI . CONCLUSIONS: This pilot study demonstrated that once-daily triple therapy with high-dose omeprazole, metronidazole extended-release formulation, and clarithromycin achieved an eradication rate approaching 80% . Further study may permit development of optimal once-daily dosing and enhance eradication rates.

Antimicrob Agents Chemother, 1999 Apr, 43(4), 813 - 21
Efficacy of doxycycline, azithromycin, or trovafloxacin for treatment of experimental Rocky Mountain spotted fever in dogs; Breitschwerdt EB et al.; Dogs were experimentally inoculated with Rickettsia rickettsii (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever . Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups . Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography . Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio . Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group . As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point . As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration.

Circulation, 1999 Mar 30, 99(12), 1540 - 7
Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study; Anderson JL et al.; BACKGROUND: Chlamydia pneumoniae commonly causes respiratory infection, is vasotropic, causes atherosclerosis in animal models, and has been found in human atheromas . Whether it plays a causal role in clinical coronary artery disease (CAD) and is amenable to antibiotic therapy is uncertain . METHODS AND RESULTS: CAD patients (n=302) who had a seropositive reaction to C pneumoniae (IgG titers >/=1:16) were randomized to receive placebo or azithromycin, 500 mg/d for 3 days, then 500 mg/wk for 3 months . Circulating markers of inflammation (C-reactive protein {CRP}, interleukin {IL}-1, IL-6, and tumor necrosis factor {TNF}-alpha), C pneumoniae antibody titers, and cardiovascular events were assessed at 3 and 6 months . Treatment groups were balanced, with age averaging 64 (SD=10) years; 89% of the patients were male . Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 (but not 3) months (P=0 . 011) as well as the mean global rank sum change score: 531 (SD=201) for active drug and 587 (SD=190) for placebo (P=0.027) . Specifically, change-score ranks were significantly lower for CRP (P=0.011) and IL-6 (P=0.043) . Antibody titers were unchanged, and number of clinical cardiovascular events at 6 months did not differ by therapy (9 for active drug, 7 for placebo) . Azithromycin decreased infections requiring antibiotics (1 versus 12 at 3 months, P=0.002) but caused more mild, primarily gastrointestinal, adverse effects (36 versus 17, P=0.003) . CONCLUSIONS: In CAD patients positive for C pneumoniae antibodies, global tests of 4 markers of inflammation improved at 6 months with azithromycin . However, unlike another smaller study, no differences in antibody titers and clinical events were observed . Longer-term and larger studies of antichlamydial therapy are indicated.

J Antimicrob Chemother, 1998 Dec, 42(6), 761 - 7
Lysosomal alterations induced in cultured rat fibroblasts by long-term exposure to low concentrations of azithromycin; Van Bambeke F et al.; Computer-aided simulations suggest that the doses and schedules of administration of azithromycin proposed in treatment and prophylaxis of Mycobacterium avium complex (MAC) in AIDS patients will result in drug concentrations in serum and extracellular fluids remaining for sustained periods of time in the 0.03-0.1 mg/L range . We exposed cultured rat embryo fibroblasts to these concentrations (and multiples up to 20 mg/L) for up to 16 days . Electron microscopy showed that after 7 days' incubation in 0.03 mg/L azithromycin, there was conspicuous accumulation of osmiophilic, lamellar structures (myeloid bodies) in lysosomes, suggesting the onset of a phospholipidosis . Assay of total cell phospholipids and cholesterol showed significant increases in cells exposed to > or = 1 to 5 mg/L of azithromycin in association with hyperactivity of the lysosomal enzyme cathepsin B . The data suggest that azithromycin, at extracellular concentrations pertinent to its use for MAC treatment, and perhaps also prophylaxis, causes limited morphological alterations of the lysosomes in cultured cells which are of the same nature as those developing rapidly and extensively at higher concentrations.

J Matern Fetal Med, 1999 Jan-Feb, 8(1), 12 - 6
Efficacy of azithromycin in reducing lower genital Ureaplasma urealyticum colonization in women at risk for preterm delivery; Ogasawara KK et al.; OBJECTIVE: The purpose of this study was to determine if azithromycin is effective in reducing lower genital colonization of Ureaplasma urealyticum in women with preterm labor or preterm premature rupture of membranes (PROM) . METHODS: A randomized, double-blinded, placebo-controlled prospective study of 60 pregnancies was carried out between 22 and 34 weeks . Genital mycoplasma cultures were performed at the time of admission . Patients were randomized to receive either a single dose of azithromycin (four 250 mg capsules) or a placebo in addition to prophylactic intravenous ampicillin . Repeat cultures were done on undelivered patients 7 days after enrollment . The study had power to detect a 50% decrease in colonization . RESULTS: Overall, lower genital colonization was 47/59 (79.7%) for U . urealyticum . Seven days after enrollment, U . urealyticum was isolated in 14/15 (93.3%) of the azithromycin-treated cases and in 11/14 (78.6%) of the controls (RR = 1.19, 95% CI = 0.88-1.61) . Vertical transmission of U . urealyticum was 3/15 (20%) in the azithromycin-treated cases and 5/10 (50%) for the controls (RR = 0.40, 95%, CI = 0.12-1.31) . CONCLUSION: These data suggests that a single 1 g dose of azithromycin is ineffective in reducing lower genital colonization with U . urealyticum.

Eur J Clin Microbiol Infect Dis, 1998 Dec, 17(12), 828 - 33
Randomized, multicentre study of the efficacy and tolerance of azithromycin versus clarithromycin in the treatment of adults with mild to moderate community-acquired pneumonia . Azithromycin Study Group; O'Doherty B et al.; Adults with mild to moderate community-acquired pneumonia were treated with azithromycin (500 mg once daily for 3 days) or clarithromycin (250 mg twice daily for 10 days) and clinically assessed between days 3 and 7 and days 12 and 16 . Patients classified as improved at the day 12-16 visit were also evaluated between days 19 and 23 . Two hundred three patients were treated (101 with azithromycin, 102 with clarithromycin) . A satisfactory clinical response was recorded at the end of therapy in 83 of 88 (94%) evaluable azithromycin-treated and 84 of 88 (95%) evaluable clarithromycin-treated patients (P=0.518) . At day 19-23, only one patient in each treatment group had relapsed . Thirty-one of 32 (97%) pathogens isolated from patients in the azithromycin group were eradicated, compared with 32 of 35 (91%) isolated from clarithromycin patients . In all patients with atypical pneumonia, the clinical response was satisfactory at follow-up . Incidences of treatment-related adverse events were similar for the two groups (P=0.815) . Two (2%) clarithromycin patients discontinued therapy due to severe treatment-related adverse events; none in the azithromycin group did . This study shows that a 3-day, once-daily course of azithromycin is as clinically effective and well tolerated as a 10-day, twice-daily course of clarithromycin in the treatment of mild to moderate community-acquired pneumonia.

Pharmacotherapy, 1999 Feb, 19(2), 245 - 8
Intravenous azithromycin-induced ototoxicity; Bizjak ED et al.; Intravenous azithromycin is increasingly administered for treatment of hospitalized patients with community-acquired pneumonia . Macrolide antibiotics cause ototoxicity, which occurs most frequently when high serum concentrations are achieved . Current dosing guidelines for intravenous azithromycin can result in much higher serum concentrations than is seen with oral administration . We describe a 47-year-old woman who developed complete deafness after receiving 8 days of intravenous azithromycin.

Acta Med Croatica, 1998, 52(4-5), 209 - 14
Omeprazole, azithromycin and amoxicillin or amoxicillin plus clavulanic acid in eradication of Helicobacter pylori in duodenal ulcer disease; Vcev A et al.; Treatment with omeprazole (OME), azithromycin (AZI) and amoxicillin (AMO) resulted in encouraging Helicobacter pylori cure rates in pilot and control studies . The aim of this study was to establish whether OME + AZI in combination with either AMO or ACA (amoxicillin plus clavulanic acid) are effective in curing H . pylori infection . A hundred patients with active duodenal ulcer and H . pylori infection were treated with OME (day 1-10: 2 x 40 mg/day, day 11-24: 40 mg/day, day 25-42: 20 mg/day) plus AZI 500 mg/day for the first 6 days . Patients were randomly assigned to either AMO 2 x 1000 mg/day (group A, n = 50) or ACA 2 x 1250 mg/day (group B, n = 50) during the first 10 days of treatment . H . pylori status was determined by urease test and histology before and 6 weeks after completion of therapy . Ninety-five patients completed the study . H . pylori infection was eradicated in 85.4% (41/48) patients from group A (intention-to-treat (ITT) analysis: 82%) versus 91.5% (43/47) patients from group B (ITT) analysis: 86%) (NS) . All ulcer had healed after 42 days of omeprazole treatment . Side effects, usually minor, were recorded in 12.5% (group A) and 14.9% (group B) of patients (NS) . Therapy had to be discontinued in two patients (one in group A and one group B) only . Ten-days treatment with OME and AZI (for the first 6 days) with AMO or ACA are simple and highly effective regimens to cure H . pylori infection in patients with duodenal ulcer disease.

J Int Med Res, 1998 Oct-Nov, 26(5), 257 - 65
Comparison of the efficacy, safety and tolerability of azithromycin and co-amoxiclav in the treatment of acute periapical abscesses; Adriaenssen CF; The activity, safety and tolerability of the azalide azithromycin were compared with those of co-amoxiclav in the treatment of acute periapical abscesses in adults in an open, randomized, multicentre comparative study . Patients of either sex, recruited from 106 dental practices in Belgium, were aged between 18 and 75 years and had acute periapical abscesses not requiring drainage, confirmed by radiology . Azithromycin was administered as a 500-mg tablet orally once daily for 3 days (n = 150) and co-amoxiclav as a 625-mg capsule three times daily, for 5-10 days (n = 153) . Both before and after treatment, masticatory pain, percussion pain, headache, and oedema and redness of soft tissue were graded on a four-point scale . Overall clinical success (cure plus improvement) was seen in 131/144 (91%) evaluable patients receiving azithromycin and in 142/148 (96%) receiving co-amoxiclav (difference not significant) . There was no significant difference between the two groups in the incidence or severity of adverse events or in the number of discontinuations because of adverse events.

Br J Ophthalmol, 1998 Nov, 82(11), 1306 - 8
Azithromycin for ocular toxoplasmosis; Rothova A et al.; AIMS: To investigate the efficacy of azithromycin in patients with ocular toxoplasmosis . METHODS: 11 immunocompetent patients with ocular toxoplasmosis were treated with azithromycin (500 mg the first day, followed by 250 mg/day for 5 weeks) . Ocular and systemic examinations were performed during active retinitis episodes and all patients were followed for at least 1 year . RESULTS: The intraocular inflammation disappeared within 4 weeks in seven patients, including two cases with progressive retinitis despite previous treatment with pyrimethamine, sulphadiazine, and folinic acid . Recurrence of retinitis occurred in three patients (27%) within the first year of follow up . No systemic side effects of azithromycin were encountered . CONCLUSION: These results indicate that although azithromycin cannot prevent recurrent disease it may be an effective alternative for patients with ocular toxoplasmosis who cannot tolerate standard therapies.

Aliment Pharmacol Ther, 1998 Dec, 12(12), 1269 - 72
Evaluation of a new ultrashort triple therapy for Helicobacter pylori disease; Trevisani L et al.; BACKGROUND: 1-week proton pump inhibitor-based triple therapies are considered the most effective and convenient drug combinations for curing Helicobacter pylori infection . Short therapies, lasting less than 1 week have been investigated rarely . AIM: To assess the efficacy and tolerability of a 3-day lansoprazole triple therapy after 1 day of lansoprazole pre-treatment . METHODS: Seventy H . pylori-positive (rapid urease test and histology) patients received LAzT3 regimen (lanzoprazole 30 mg b.d . and azithromycin 500 mg o.m . for 3 days; tinidazole 2000 mg o.m . on day 1 and 1000 mg o.m . on days 2-3) after 1 day of lansoprazole pretreatment . Patients with active ulcer received lansoprazole 30 mg o.m . for an additional 4 weeks . Follow-up gastroscopy was carried out 4-6 weeks after completion of therapy . Eradication was defined as negative histology and rapid urease test . RESULTS: Four patients failed to attend the follow-up endoscopy . One patient complained of minor side-effects . H . pylori was eradicated in 57 of 66 patients suitable for evaluation, with a per-protocol cure rate of 86.3% (95%CI: 76-94%), and an intention-to-treat cure rate of 81.4% (95%CI: 70-90%) . CONCLUSIONS: This new ultrashort triple therapy including lansoprazole, azithromycin and tinidazole seems to be effective in eradicating H . pylori . It is safe and well-tolerated, and may be taken into consideration as a valid alternative to the better known and widely used 1-week proton pump inhibitor-based triple therapies.

Aliment Pharmacol Ther, 1998 Dec, 12(12), 1263 - 7
Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection; Chey WD et al.; BACKGROUND: We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection . METHODS: From March 1997 to March 1998, patients infected with H . pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m . for 3 days: or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m . for 3 days . H . pylori eradication was established by a urea breath test at least 4 weeks after therapy . Side-effects and compliance were assessed using a diary . RESULTS: Sixty-eight patients were enrolled . Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease . Treatment 1 cured H . pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively . The corresponding eradication rates for Treatment 2 were 79% and 75% . Two patients taking Treatment 2 dropped out of the study because of side-effects . CONCLUSIONS: With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H . pylori infection than azithromycin 500 mg/day for 3 days.

J Chemother, 1998 Dec, 10(6), 474 - 5
Long term treatment with clarithromycin for cryptosporidiosis and emergence of drug resistant disseminated infection due to Mycobacterium avium: case report; Matteelli A et al.; Macrolide resistance in disseminated Mycobacterium avium infection is of major concern in AIDS patients as these drugs represent the main component of combination therapy . Clarithromycin and azithromycin should not be used alone for the treatment and prophylaxis of the disease because of the risk of selecting resistant strains . We report the case of a clarithromycin resistant disseminated M . avium infection in an AIDS patient, acquired after long term monotherapy with clarithromycin for the treatment of cryptosporidiosis.

J Chemother, 1998 Dec, 10(6), 469 - 73
Azithromycin compared with minocycline in the treatment of acne comedonica and papulo-pustulosa; Gruber F et al.; This open study was conducted in 72 outpatients with acne vulgaris, to compare the clinical efficacy and tolerability of azithromycin and minocycline . Azithromycin was administered as a single oral dose (500 mg/day) for 4 days in four cycles every 10 days and minocycline was administered 100 mg daily for 6 weeks . Improvement was assessed 6 weeks after initiation of treatment with a four-graded scale . A satisfactory clinical response was observed in 75.8% of the patients treated with azithromycin and in 70.5% of those treated with minocycline . There were no significant differences between these two acne treatments in terms of reduction of the number of lesions (p> 0.05) . Both agents were well tolerated and mild side effects were reported in 10.3% of azithromycin and 11.7% of minocycline treated patients . We conclude that azithromycin is at least as clinically effective and well tolerated as minocycline as treatment of facial comedonic and papulopustular acne.

Antimicrob Agents Chemother, 1999 Jan, 43(1), 163 - 5
Pharmacokinetics in serum and leukocyte exposures of oral azithromycin, 1,500 milligrams, given over a 3- or 5-day period in healthy subjects; Amsden GW et al.; The pharmacokinetics in serum and leukocyte (WBC) exposures of 1,500 mg of oral azithromycin administered as 3-day (500 mg/day, days 1 to 3) and 5-day (500 mg on day 1 and 250 mg/day on days 2 to 5) regimens were compared in 12 healthy volunteers . Serum, polymorphonuclear leukocytes, and mononuclear leukocytes were collected over a 12-day period from the start of each regimen . Results of the study indicate that the exposures of serum and both types of WBCs were similar with both regimens . Drug concentrations in day 12 WBCs were well above the MICs for all relevant community-acquired respiratory tract pathogens . Terminal half-lives in serum obtained by both regimens were essentially equal at 66 h and consistent with past reports . These results indicate that the standard 1,500-mg dose of oral azithromycin can be administered over either 5 or 3 days.

Enferm Infecc Microbiol Clin, 1998, 16 Suppl 1, 45 - 51
{Cerebral toxoplasmosis}; Ribera Pascuet E et al.; Toxoplasmic encephalitis is associated with high mortality and morbidity and still presents a notable incidence in our setting . Neither the clinical symptoms nor radiological features are diagnostic of this disease; however, because of its frequency and clinical importance, specific treatment is begun whenever toxoplasmosis is suspected . In patients with negative serology, or who are receiving adequate prophylaxis, or who do not respond to 2 weeks of treatment, or who present radiological lesions suggestive of another illness, diagnosis should not be delayed, and brain biopsy should be considered as soon as possible . In these cases, SPECT with 201TI (sensitivity and specificity over 90-95% for lymphoma) and/or the PCR technique to detect T . gondii (sensitivity 50-65% and specificity 95-100%) or Epstein-Barr virus (sensitivity 70-80% and specificity 95% for lymphoma) can be very useful . The treatment of choice is pyrimethamine (100 mg the first day followed by 50 mg/day) and sulphadiazine (1-1.5 g/6 h) during 6-8 weeks . If the patient is allergic to sulfadiazine and cannot be desensitized the regimen of choice is pyrimethamine and clindamycin (600 mg/6 h), with similar efficacy . Clinical experience with other therapeutic alternatives is limited . Pyrimethamine can be associated with clarithromycin (0.5-1 g/12 h), azithromycin (1-1.5 g/day) atovaquone (750 mg/6 h), dapsone (100 mg/day) or doxycyclin (200 mg/12 h) . Cotrimoxazole or clindamycin can be administered intravenously to patients who cannot receive enteral treatment . The toxicity of these therapeutic regimens is significant and treatment has to be suspended in 10-40% of cases . The interactions that can be produced with other drugs used to treat HIV-infected patients are generally of little clinical relevance.

Ther Drug Monit, 1998 Dec, 20(6), 680 - 4
Simultaneous high-performance liquid chromatography analysis of azithromycin and two of its metabolites in human tears and plasma; Raines DA et al.; This article describes a high-performance liquid chromatographic (HPLC) method for the measurement of azithromycin (AZI) and two of its metabolites, 9a-N-desmethylazithromycin (ADES) and N-desmethylazithromycin (NDES), in human tears and plasma . The drug, metabolites, and internal standard (n-propylazithromycin {IS}) were detected electrochemically after injection of the extracted sample into the HPLC system . The peak height ratio (AZI, ADES, or NDES to IS) varied linearly, with concentrations in the ranges of 0.1 mg/L to 2.0 mg/L (tears) and 0.01 mg/L to 2.0 mg/L (plasma) of AZI, ADES, and NDES; the correlation coefficient (r) was more than 0.994 mg/L for all of the compounds (n=6) . The analysis of tear samples collected at different intervals within 12 hours to 144 hours after a dose of 20 mg/kg of AZI from a trachoma patient yielded concentrations ranging from 1.52 mg/L to 0.34 mg/L for AZI, 0.79 mg/L to 0.27 mg/L for ADES, and 1.99 mg/L to less than 0.20 mg/L for NDES . The concentration of AZI in plasma ranged from 0.15 mg/L to 0.01 mg/L, whereas ADES and NDES were undetectable.

Int J Infect Dis, 1998 Jul-Sep, 3(1), 39 - 47
Prevention and treatment of disseminated Mycobacterium avium complex infection in human immunodeficiency virus-infected individuals; Shafran SD; Disseminated Mycobacterium avium complex (DMAC) infection is a common complication of advanced HIV disease, and is an independent predictor of mortality . The clinical features of DMAC infection are fever, weight loss, abdominal pain, anemia, elevated serum alkaline phosphatase, and elevated serum lactate dehydrogenase . The diagnosis is made by blood cultures; clinical diagnosis is unreliable . Chemoprophylaxis of DMAC infection with azithromycin is recommended when the CD4 lymphocyte count is below 50 cells/mm3 . Established DMAC infection is treated with clarithromycin plus ethambutol, unless the isolate is macrolide-resistant, in which case the optimal therapy is uncertain . Highly active antiretroviral therapy is important in both prevention and treatment of DMAC infection.

J Travel Med, 1997 Mar 1, 4(1), 44 - 45
An Open Trial of Trimethoprim Alone against Cyclospora Infections; Shlim DR et al.; Cyclospora is a coccidian parasite that infects the upper intestine and causes a prolonged illness consisting of fatigue, anorexia, and diarrhea . Untreated infections can last for several weeks.1 Trimethoprim-sulfamethoxazole (co-trimoxazole) was found to be an effective treatment for Cyclospora infections in a 1994 study performed in Nepal.2 However, people with known allergies to sulfa drugs cannot take co-trimoxazole . A number of antibiotics have been tried against Cyclospora infections without success, including norfloxacin, tinidazole, diloxanide furoate, and quinacrine hydrochloride . Azithromycin was not successful in a small open trial in 1993.3 Trimethoprim is not chemically related to sulfa, and allergy to co-trimoxazole is usually attributed to the sulfamethoxazole component . In order to find a treatment for people infected with Cyclospora who are allergic to sulfa drugs, we undertook an open trial of trimethoprim alone, in a dose of 200 mg twice a day for 7 days.

J Travel Med, 1995 Mar 1, 2(1), 4 - 5
Arguments against Chemoprophylaxis in Areas at Low Risk for Chloroquine-Resistant Plasmodium falciparum; Armengaud M; Chemoprophylaxis of malaria prevents the disease not the infection (suppressive chemoprophylaxis) with "high levels of confusion and low levels of compliance." The magnitude of danger of contracting malaria for travelers varies in several endemic zones . In West Africa, without prophylaxis, malaria is estimated to have an incidence of 1.4% per person per month . In South and Central America, the incidence is 0.05 and 0.01% per month, respectively . In Asia, the transmission and percentage of infection due to Plasmodium falciparum is much lower . The dangers of chemoprophylaxis in an area at low risk for chloroquine resistant P . falciparum are a reality . Incompletely active drugs change clinical manifestations, and changes in clinical manifestations delay the establishment of a correct diagnosis . The rate of adverse events is 15-20%, and hospitalization due to side effects of prophylaxis occurs in one in 10,000 travelers . Neuropsychiatric side effects have been reported with both mefloquine and chloroquine . A false sense of security can hinder a physician practicing in a nonendemic area from thinking of malaria when a traveler returns with fever . To complicate the picture, in many countries, there is an emerging drug resistance in P . falciparum as well as an emerging chloroquine resistance in P . vivax strains (20% in New Guinea and Irian Jaya) . In short, no available chemoprophylaxis is free from toxicity, and its efficacy is never 100% . Alternatives to conventional chemoprophylaxis are encouraged in areas of low morbidity of malaria . In areas where P . vivax occurs primarily, and when the risk of serious side effects from chemoprophylaxis outweighs the risk of life threatening P . falciparum infection, there are four alternative strategies.2,3 The first strategy is that the traveler avoid mosquito bites . With a compulsive attitude, a high degree of protection can be realized with the proper use of pyrethrum-impregnated mosquito netting, topical DEET-containing insect repellents and impregnated protective clothing . Secondly, when the stay in malaria-endemic areas is less than 1 week, the disease will appear after returning home . No chemoprophylaxis is needed during the journey . With the onset of fever, diagnosis and therapy are performed without delay at home . This strategy assumes the participation of an informed physician . A third strategy is standby treatment, which is defined by the World Health Organization (WHO) as the use of antimalarial drugs carried for self administration when fever occurs and prompt medical attention is not available . Standby treatment is a safe option for an informed tourist traveling to areas at low risk of malaria or in areas where chemoprophylaxis may not be effective . Likewise, self therapy might be preferred for travelers who make frequent journeys characterized by brief and successive visits to malarious and nonmalarious areas, and for long-term travelers, and expatriots . Standby treatment minimizes drug overuse, demands early investigation of any febrile illness, and insists that effective treatment is given rapidly for P . falciparum malaria that occurs in nonimmune persons . This strategy is the responsibility assumed by teaching physicians and appears to be more advantageous than classic long-term chemoprophylaxis . A fourth strategy is systematic curative treatment carried out under supervision upon a traveler's return home . The administration of halofantrine after departure from endemic areas was studied for the prevention of P . falciparum malaria after short-term exposure,4 but the adverse cardiac effects of this drug obviates the usefulness of this "radical cure" . Possibly the administration of doxycycline or azithromycin after departure from malarious areas could prevent P . falciparum malaria after short-term exposure and with less deleterious side effects . This approach requires more research, and again this will be the responsibility of physicians.

Kansenshogaku Zasshi, 1998 Sep, 72(9), 918 - 23
{A mechanism of clarithromycin resistance in Helicobacter pylori}; Saika T et al.; The aim of this study was to elucidate the mechanism of clarithromycin (CAM) resistance in laboratory strains and clinical isolates of Helicobacter pylori . The CAM resistance in laboratory strains was induced in vitro by CAM exposure . The majority of CAM-resistant strains were highly resistant to CAM (MICs > 100 micrograms/ml) . These CAM-resistant strains also showed cross resistance to azithromycin, rokitamycin and clindamycin . The sites of point mutations in these resistant strains were identified as follows; the conserved domain V of genes encoding 23S rRNA were amplified first by PCR and this PCR products (1.4 kb) were subsequently digested with BsaI and MboII and RFLP patterns were analyzed . 1.4 kb amplicons of CAM-susceptible strains yielded two DNA bands of 1000 bp and 400 bp when digested with BsaI but no digestion product was seen by MboII digestion . In contrast to this, two types of RFLP patterns were observed for the resistant strains induced in vitro by CAM; one was the formation of three bands (700 bp, 400 bp and 300 bp) after BsaI digestion, and the other was the formation of two bands (approximately 700 bp) by MboII digestion . RFLP patterns of CAM-susceptible and CAM-resistant clinical isolates obtained from patients before and after CAM medication were similar to those observed for the CAM-susceptible strains and CAM-resistant strains developed in the laboratory . These results strongly suggest that the CAM resistance of H . pylori was caused by point mutation of 23S rRNA.

P N G Med J, 1996 Sep, 39(3), 252 - 60
Issues in the management of sexually transmitted diseases in Papua New Guinea; Passey M; This paper outlines three important issues in the clinical management of sexually transmitted diseases (STDs) in Papua New Guinea which have, until now, gone unrecognized or been neglected . Suggestions for possible solutions are made . The high prevalence of both chlamydial and trichomonal infections in women cannot be ignored . Both of these infections have been shown to increase the transmission of HIV . The current algorithm for the treatment of vaginal discharges does not include treatment for trichomonal infection in the first instance, yet trichomoniasis has been shown to be the most common STD in community studies both here and elsewhere . Trichomoniasis is usually asymptomatic in men, but still increases the risk of HIV transmission; furthermore, it causes illness in their female partners and thus needs to be treated . The current recommended regimens for the treatment of gonococcal and chlamydial infection are complex due to the number of drugs recommended for gonorrhoea to combat the problem of drug resistance, and the length of therapy for chlamydia . Compliance with such a regimen is likely to be poor, particularly in asymptomatic partners . We need to consider the relative advantages provided by a drug which could be given as a single oral dose for chlamydia, and perhaps for both infections . Azithromycin is one possibility, as it has been shown to be effective for chlamydial infection in numerous studies, and has been found satisfactory for gonorrhoea where local isolates were susceptible . Testing of a small number of isolates from Papua New Guinea has shown that azithromycin may be suitable for use here, but further susceptibility testing needs to be performed . Utilization of services for STDs, particularly by women, is extremely low . This is due to a combination of factors involving limited knowledge of symptomatology and its significance, the asymptomatic nature of many infections, the structure of the services, health worker behaviour, and social attitudes . To address these issues we must make modifications to STD service provision, as well as provide widespread information about the potentially serious consequences of contracting STDs, including both infertility and AIDS . Possible modifications to the services are discussed, and include making routine screening available for women through currently existing services such as family planning and antenatal clinics and considering the possibility of establishing Women's Health Clinics which would provide all primary reproductive health services in an integrated mannerPIP: This paper summarizes three relevant issues in the clinical management of STDs in Papua New Guinea which have gone unrecognized or been neglected until now . First, the issue of chlamydial and trichomonal infections, which have been shown to increase HIV transmission, is discussed . Although trichomonal infections generally display less pathology than chlamydial infections, they are nonetheless a serious problem . Both types of infections are also more prevalent in Asaro Valley as compared with gonorrhoea and syphilis . The second discussion focuses on the treatment regimen for gonococcal and chlamydial infections . The current treatment, which involves the intake of different tablets and extends for a week, seems to be unappealing and unrealistic for most patients . Thus, a more cost-effective drug has been introduced: azithromycin, which has been proven effective against chlamydial infection and has also been found satisfactory for gonorrhea treatment where local isolates were susceptible . The final topic is that of the barriers to the use of STD treatment services . This study revealed that the low utilization of these services, particularly by women, is due to 1) the limited knowledge of symptomatology and its significance, 2) to the asymptomatic nature of some infections, 3) to factors concerning the structure of services, 4) to health worker behavior, and 5) to social attitudes . Additionally, potential modifications to the existing services are discussed, including the possibility of establishing women's health clinics, which would provide all primary reproductive health services in an integrated manner .

Am J Trop Med Hyg, 1998 Oct, 59(4), 509 - 12
Ability of azithromycin in combination with quinine for the elimination of babesial infection in humans; Shih CM et al.; We report the ability of azithromycin in combination with quinine to eliminate the Babesia infection in a native Taiwanese woman . Failure of elimination of the babesial infection was observed two weeks after treating with standard regimen of oral quinine plus intravenous clindamycin for a 10-day course of therapy . Azithromycin in place of clindamycin was administered for another 10-day course of therapy two months following initial treatment . Clearance of Babesia parasites was observed and verified by hamster inoculation . These results suggest that azithromycin plus quinine should be considered as an alternative therapy for human babesiosis, especially in the failure of treatment with standard regimens.

J Clin Pharmacol, 1998 Sep, 38(9), 830 - 5
Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers; Apseloff G et al.; A 14-day, randomized, open, phase I clinical trial was designed to examine possible pharmacokinetic interactions between rifabutin and two other antibiotics, azithromycin and clarithromycin, used in the treatment of Mycobacterium avium complex infections . Thirty healthy male and female volunteers were divided into five groups of six participants each: 18 received 300 mg/day of rifabutin, 12 in combination with therapeutic doses of either azithromycin or clarithromycin; the remaining 12 received azithromycin or clarithromycin alone . On day 10 the study was terminated because of adverse events, including severe neutropenia . Fourteen participants who received rifabutin developed neutropenia, including all 12 participants who received azithromycin or clarithromycin concomitantly . Analyses of serum revealed no apparent pharmacokinetic interaction between azithromycin and rifabutin . However, the mean concentrations of rifabutin and 25-O-desacetyl-rifabutin (an active metabolite) in participants who received clarithromycin and rifabutin concomitantly were more than 400% and 3,700%, respectively, of concentrations in those who received rifabutin alone . Physicians should be aware that recommended prophylactic doses of rifabutin may be associated with severe neutropenia within 2 weeks after initiation of therapy, and all patients receiving rifabutin, especially with clarithromycin, should be monitored carefully for neutropenia.

J Infect Dis, 1998 Sep, 178(3), 900 - 3
Combination drug therapy for cryptosporidiosis in AIDS; Smith NH et al.; Aside from effective antiretroviral therapy, there is no consistently effective antiparasitic therapy for cryptosporidiosis in AIDS . The purpose of this study was to assess safety, efficacy, and durability of combination therapy with paromomycin and azithromycin for chronic cryptosporidiosis . Patients with AIDS, chronic cryptosporidiosis, and < 100 CD4 cells/microL were treated with open-label paromomycin (1.0 g twice a day) plus azithromycin (600 mg once a day) for 4 weeks, followed by paromomycin alone for 8 weeks . In 11 patients, median stool frequency decreased from 6.5/day (baseline) to 4.9/day (week 4) and 3.0/day (week 12) . Median reductions in 24-h oocyst excretion were 84%, 95%, and >99% at 2, 4, and 12 weeks, respectively . None of the responses were attributable to antiretrovirals . Of 5 survivors at 12-30 months of follow-up, 3 remain asymptomatic off medications, and 2 have chronic, mild diarrhea . Treatment of cryptosporidiosis with azithromycin and paromomycin was associated with significant reduction in oocyst excretion and some clinical improvement.

AIDS, 1998 Aug 20, 12(12), 1503 - 12
Preventing Mycobacterium avium complex in patients who are using protease inhibitors: a cost-effectiveness analysis; Bayoumi AM et al.; BACKGROUND: Practice guidelines recommending Mycobacterium avium complex (MAC) prophylaxis for patients with HIV disease were based on clinical trials in which individuals did not receive protease inhibitors . OBJECTIVE: To estimate the cost-effectiveness of strategies for MAC prophylaxis in patients whose treatment regimen includes protease inhibitors . DESIGN: Decision analysis with Markov modelling of the natural history of advanced HIV disease . Five strategies were evaluated: no prophylaxis, azithromycin, rifabutin, clarithromycin and a combination of azithromycin plus rifabutin . MAIN OUTCOME MEASURES: Survival, quality of life, quality-adjusted survival, health care costs and marginal cost-effectiveness ratios . RESULTS: Compared with no prophylaxis, rifabutin increased life expectancy from 78 to 80 months, increased quality-adjusted life expectancy from 50 to 52 quality-adjusted months and increased health care costs from $233000 to $239800 . Ignoring time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $44300 per life year . Adjusting for time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $41500 per quality-adjusted life year (QALY) . In comparison with rifabutin, azithromycin was associated with increased survival, increased costs and an incremental cost-effectiveness ratio of $54300 per QALY . In sensitivity analyses, prophylaxis remained economically attractive unless the lifetime chance of being diagnosed with MAC was less than 20%, the rate of CD4 count decline was less than 10 x 10(6) cells/l per year, or the CD4 count was greater than 50 x 10(6) cells/l . CONCLUSION: MAC prophylaxis increases quality-adjusted survival at a reasonable cost, even in patients using protease inhibitors . When not contraindicated, starting azithromycin or rifabutin when the patient's CD4 count is between 50 and 75 x 10(6) cells/l is the most cost-effective strategy . The main determinants of cost-effectiveness are CD4 count, viral load, place of residence and patient preference.

Eur J Clin Microbiol Infect Dis, 1998 May, 17(5), 309 - 12
Azithromycin versus placebo in acute infectious rhinitis with clinical symptoms but without radiological signs of maxillary sinusitis; Haye R et al.; In this double-blind, parallel-group, multicenter study, 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema (pus) were randomly assigned to receive either 500 mg azithromycin once daily for 3 days (87 patients) or placebo daily for 3 days (82 patients) . Nasal secretion, maxillary tenderness and pain, nasal obstruction, general malaise, and hyposmia were assessed at the start of the study and on days 4, 11, and 25 of treatment . After 11 days 58% of the patients in the azithromycin group were cured versus 31% in the placebo group; after 25 days the cure rate was 79% versus 67%, respectively . When both cure and improvement were considered, the corresponding figures after day 25 were 90% and 88%, respectively . Adverse events, predominantly gastrointestinal, occurred in 24 (27%) of the azithromycin-treated patients and in 15 (18%) of those treated with placebo, but the difference was not statistically significant . There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema (pus) . Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms, as the results after 25 days for both improvement and cure are equal . In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema, treatment with azithromycin seems to result in a better cure rate after 10-12 days when compared with placebo.

Acta Otorrinolaringol Esp, 1998 May, 49(4), 306 - 12
{Comparison of azithromycin, amoxicillin/clavulanic acid and cefaclor in the treatment of acute ENT infections}; Garcia Callejo FJ et al.; A comparison was made of the clinical effectiveness of azithromycin (once daily for three days at a dose of 10 mg/kg in children or 500 mg/day in adults) and amoxicillin/clavulanic acid and cefaclor (standard doses for 7 to 14 days) in acute ear, nose and throat infections in an open randomized study . The group with azithromycin included 37 otitis media, 24 pharyngotonsillitis and 6 maxillary sinusitis (n = 67) . The amoxicillin/clavulanic acid group, 22 otitis media, 19 pharyngotonsillitis and 6 maxillary sinusitis (n = 47) and the cefaclor group, 15 otitis media, 12 pharyngotonsillitis and 4 maxillary sinusitis (n = 31) . Fifteen days after beginning treatment, 97% (65/67) of the patients who received azithromycin had improved or cured, compared with 85% (40/47) of those who received amoxicillin/clavulanic acid and 84% (26/31), cefaclor (p < 0.02) . Pathogens were not eradicated in 3% (2/58) of the patients who received azithromycin, compared with 13% (4/28) who received amoxicillin/clavulanic acid and 15% (4/28) cefaclor . Patients with azithromycin showed an earlier clinical improvement and more rapid normalization of the leukocyte count, erythrocyte sedimentation rate and acute phase proteins . No patient with azithromycin had adverse effects, versus 15% (7/47) for patients with amoxicillin/clavulanic acid and 16% (5/31) for cefaclor . Treatment compliance was 100, 83 (39/47) and 84% (26/31), respectively (p < 0.01) . We conclude that azithromycin treatment for three days is faster and more effective clinically and analytically than standard treatment with amoxicillin/clavulanic acid or cefaclor in acute infections of the ear, nose and throat.

Postgrad Med J, 1998 Apr, 74(870), 237 - 9
Fever, hepatosplenomegaly and pancytopenia in a patient living in the Mediterranean region; Buyukasik Y et al.; A 24 year old woman living in the Mediterranean region of Turkey present with a three-month history of weight loss and irregular fever that was peaking at 40 degrees C with shivering . No definite aetiology could be identified in a local hospital . A bacterial infection had been suspected, but antibiotic therapy, at first with sulbactam-ampicillin and later with azithromycin, had no influence on the fever . Physical examination revealed an emaciated patient with fever (39 degrees C), pallor, and hepatosplenomegaly (spleen 9 cm and liver 5 cm palpable below the costal margin) . No peripheral lymphadenopathy was present . The laboratory examinations are summarised in the table . Notably, a prominent increase of macrophages containing intracellular micro-organisms (figures 1 and 2) was seen in the bone marrow smears . The same micro-organisms were also identified within the Kupffer cells in liver biopsy.

Eur J Contracept Reprod Health Care, 1997 Dec, 2(4), 263 - 7
Hormonal contraception and pelvic inflammatory disease; Henry-Suchet J; Estrogen-progestogen contraception (OC) is significantly associated with a high prevalence of Chlamydia trachomatis in the lower genital tracts of young women . In contrast, pelvic inflammatory disease is less frequent and is associated with milder pelvic lesions in OC users than in non-users . A recent study suggests that OC use can be associated with silent endometritis and salpingitis . The usual clinical, biological and laparoscopic signs of acute and chronic pelvic inflammatory disease are described . As shown tby several cost-benefit analyses, C . trachomatis detection in family planning centers is cost-effective and the eradication of bacteria is obtained in 90% of cases by a new treatment: azithromycin (1 g for 1 day) . Although the data clearly show that C . trachomatis screening is cost-effective, selection of the diagnostic laboratory tests used in such screening programs should be carefully evaluated relative to cost, feasibility, specificity and sensitivity, and should be adapted to the presumed prevalence in screened populations . A systematic screening is indicated in populations susceptible to a prevalence of 5% or more.

Transplantation, 1998 Jun 27, 65(12), 1611 - 5
Efficacy of azithromycin in the treatment of cyclosporine-induced gingival hyperplasia in renal transplant recipients; Nash MM et al.; BACKGROUND: Gingival hyperplasia (GH) is a common side effect of cyclosporine . Azithromycin (Zithromax; AZI) is a macrolide antibiotic reported in case studies to reduce cyclosporine-induced gingival hyperplasia (CIGH) in renal transplant recipients (RTR) . METHODS: The efficacy of AZI to treat CIGH in RTR was examined in a double-blind, randomized crossover trial . Patients (n=17) with CIGH were randomized to receive AZI and a matching placebo in alternate order for 5 days, separated by a 2-week washout period . Follow-up visits were conducted at week 6 and week 12 . Changes in GH were evaluated by measuring the clinical gingival sulcus depths, tooth length, and the length of the interdental papillae to the cementum-enamel junction of two teeth in each of the four quadrants . RESULTS: Significant improvements were observed in all three types of periodontal measurements, representing reductions of gingival tissue above the medial aspect of the tooth, of the gingival sulcus depth, and of the length of the interdental papillae . Patients reported an improvement in gum bleeding . AZI was well tolerated, and 67% of the patients reported that the treatment was at least somewhat useful . CONCLUSIONS: AZI should be considered for RTR with CIGH.

Med Klin (Munich), 1998 Jun 15, 93(6), 360 - 4
{Disseminated infection with Mycobacterium avium complex (MAC) in HIV infection}; Fatkenheuer G et al.; EPIDEMIOLOGY: Disseminated MAC-infection is one of the most frequent opportunistic infections occurring in HIV-infected patients . Severely immunocompromised patients with CD4-counts < 50/microliter are at greatest risk for the disease . Survival of untreated infection is very poor (5 to 6 months) . With therapy survival is prolonged by about 4 months . CLINICAL PRESENTATION AND DIAGNOSTIC PROCEDURES: The leading symptom of MAC-infection is fever eventually accompanied by weight lost, night sweats, enlarged lymph nodes, hepatosplenomegaly, abdominal pain and anemia . Blood cultures are very sensitive and the most appropriate examination . Other diagnostic procedures include bone marrow cultures, biopsies of the gastrointestinal tract, lymph nodes and the liver . Detection of MAC in sputum and stool samples only proves colonisation but not dissemination . However, colonisation of the gastrointestinal tract frequently precedes disseminated disease . THERAPY: Combination of clarithromycin, rifabutin and ethambutol has proven to be the most efficacious therapy and therefore has to be considered as standard therapy for disseminted MAC-infection . Problems most frequently encountered with this medication include uveitis (rifabutin) gastrointestinal disturbances (clarithromycin) and leucopenia (rifabutin) as well as drug interactions with protease-inhibitors (rifabutin) . PROPHYLAXIS: Clarithromycin, rifabutin and azithromycin given as primary prophylaxis can diminish the risk of disseminated MAC-infection . Although a survival benefit has been seen with clarithromycin, primary prophylaxis of MAC-infection is not standard care in many centers . Reasons to withhold MAC-prophylaxis include lower incidence rates in some countries as well as possible side effects and drug interactions . CONCLUSION: Disseminated MAC-infection is a frequent opportunistic disease in HIV-infected persons who are severely immunocompromised . Antibiotic combination therapy with clarithromycin, rifabutin and ethambutol improves clinical symptoms and survival . Primary prophylaxis with different regimens is efficacious but the specific epidemiologic situation in each country has to be considered.

Pediatr Infect Dis J, 1998 Jun, 17(6), 447 - 52
Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease; Bass JW et al.; OBJECTIVE: To determine the efficacy of azithromycin in the treatment of patients with typical cat-scratch disease . DESIGN: Prospective, randomized, double blind, placebo-controlled clinical trial . SETTING: Large military medical center and its referring clinics . PATIENTS: Active duty military members and their dependents with laboratory-confirmed, clinically typical cat-scratch disease . INTERVENTION: Study participants assigned by randomization to treatment with oral azithromycin or placebo for 5 days . OUTCOME MEASURES: Lymph node volume was calculated using three dimensional ultrasonography at entry and at weekly intervals . The ultrasonographer was blinded to the treatment groups . Endpoint evaluations were predetermined as time in days to 80% resolution of the initial total lymph node volume . RESULTS: Demographic and clinical data showed that the azithromycin and placebo treatment groups were comparable at entry although the placebo group tended to be older . Eighty percent decrease of initial lymph node volume was documented in 7 of 14 azithromycin-treated patients compared with 1 of 15 placebo-treated controls during the first 30 days of observation (P = 0.026) . After 30 days there was no significant difference in rate or degree of resolution between the two groups . CONCLUSIONS: Treatment of patients with typical cat-scratch disease with oral azithromycin for five days affords significant clinical benefit as measured by total decrease in lymph node volume within the first month of treatment.

J Infect Dis, 1998 Jul, 178(1), 121 - 6
Initial (6-month) results of three-times-weekly azithromycin in treatment regimens for Mycobacterium avium complex lung disease in human immunodeficiency virus-negative patients; Griffith DE et al.; Two consecutive, open, prospective trials of intermittent azithromycin (600 mg), usually given Monday, Wednesday, and Friday (TIW) for Mycobacterium avium complex (MAC) lung disease were initiated in human immunodeficiency virus-negative patients . Regimen A consisted of TIW azithromycin and daily ethambutol (15 mg/kg/day), daily rifabutin (300 mg/day), and initial twice weekly (BIW) streptomycin . Regimen B consisted of TIW azithromycin, TIW ethambutol (25 mg/kg/dose), TIW rifabutin (600 mg/dose), and initial BIW streptomycin . Of 19 patients enrolled in regimen A who completed at least 6 months of therapy, 14 (74%) had sputum samples become culture-negative . Of 39 patients enrolled in regimen B who completed at least 6 months of therapy, 24 (62%) had sputum conversion . These sputum conversion rates are comparable to previous rates at 6 months in patients receiving daily clarithromycin- or azithromycin-containing regimens . No resistance to azithromycin emerged with either regimen . This is the first study to demonstrate the efficacy of intermittent administration of medication for MAC lung disease.

Herz, 1998 May, 23(3), 185 - 92
{Arteriosclerosis as a sequela of chronic Chlamydia pneumoniae infection}; Stille W et al.; In the last years several new data allow a controversial but convincing interpretation of the pathogenesis of atherosclerosis (arteriosclerosis) . Atherosclerosis can be apparently the result of ultrachronic persistent infection by Chlamydia pneumoniae and not the result of different risk factors . The main arguments for the chlamydial genesis are: 1 . Correlation of coronary heart disease and other atherosclerotic disease with antibodies against C . pneumoniae . 2 . C . pneumoniae could be detected with different techniques (PCR, immunohistology, electromicroscopy, culture) in a high percentage in atheromas from different sites . 3 . Three international studies with macrolides in coronary heart disease were successful . 4 . The target cells of atherosclerosis (endothelia, macrophages, muscle cells) can be infected by C . pneumoniae in vitro . 5 . Positive animal experiments . The Koch-Henle criteria for the proof of the etiology are largely fulfilled--even if there are doubts about the validity of these criteria in chronic local infections . A number of unexplainable aspect of atherosclerosis can be seen in a new light . The higher incidence of coronary heart disease in young males has a parallel in the remarkable androtropism of many bacterial diseases (pneumococcal pneumonia, tuberculosis) . The reduction of incidence of atherosclerotic diseases since 1965 can be explained by the much higher intake of doxycyclin and macrolides . The low incidence of coronary heart disease in France--sometimes regarded as an effect of red wine--can be explained as a result of a much higher use of antichlamydial antibiotics . The increase of inflammatory parameters (C-reactive protein, fibrinogen, leucocytes) before acute coronary infarction are not risk factors but signs of an active chronic infection . The interpretation is possible, that atherogenic changes in lipids like increase of LDL and decrease of HDL are not risk factors but consequence of chronic arterial infection by chlamydia . The low incidence of atherosclerosis in the tropics--despite high frequency of chlamydial infection--is difficult to explain . Vascular infection can be related with the age of the patient at the primary infection . With low hygiene, intestinal primary infections in early childhood can be possible . Arterial infection would be thus a result of a primary infection in adolescence ("yet another poliomyelitis story") . There are good arguments for the thesis that C . pneumoniae is the primary cause of atherosclerosis and not a secondary invader . The consequence, nevertheless, is similar: Antibiotics get a key role . The macrolides roxithromycin, azithromycin, clarithromycin and the tetracyclin doxycyclin fulfill the criteria as potential antichlamydial agents . In general a longer treatment (6 to 8 to 12 weeks) seems advisable . It is necessary to start international studies with antibiotics in coronary infarction and other clinical manifestations of atherosclerosis . The relevant antibiotics licensed for chlamydial infections are cheap and safe . Despite of the urgent need for controlled studies, it seems already justified to treat high-risk patients with antibiotics . Meticulous protocols and long-term control of patients are necessary to evaluate the therapeutic effects . Preventive studies in patients without clinical manifestation of atherosclerosis are urgently needed . The risks of resistance or side effects are neglectable, but the organisation of such studies would be very difficult.

Sante, 1998 Mar-Apr, 8(2), 150 - 6
{Strategies to control trachoma}; Schemann JF et al.; Epidemiological data for trachoma in Mali have suggested a number of ways in which blindness caused by trachoma could be prevented or cured: improvements in domestic and urban environments (e.g . sanitation), the provision of household water supplies, improvements in personal hygiene (through health education to promote the washing of children's faces), mass administration of local (tetracycline) or general (azithromycin) antibiotics and eyelid surgery using the method of Trabut . A cost-benefit analysis was performed for antibiotic distribution and eyelid surgery . Such a study is required to assess the value of environmental improvements and the provision of water supplies . Improvements in personal hygiene and environment are the only effective ways to reduce the incidence of trachoma, but eyelid surgery should be developed to prevent the blindness caused by trachoma.

J Clin Pathol, 1998 Feb, 51(2), 138 - 42
Chronic cryptosporidiosis in patients with AIDS: stable remission and possible eradication after long-term, low dose azithromycin; Dionisio D et al.; AIMS: To investigate the effectiveness of long term, low dose azithromycin treatment for chronic cryptosporidiosis in patients with AIDS . METHODS: Azithromycin was administered as initial daily treatment to 13 patients with AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received 1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days . Nine of the 13 patients were also given low dose maintenance treatment with different schedules of azithromycin for 30 to 360 days (mean 129) . Patients were monitored, during and after treatment, for parasite shedding in stool and for daily stool frequency and body weight . All but one patient had severe immunodeficiency . RESULTS: Long term, low dose maintenance treatment was associated with major clinical and parasitological benefits: there was probable eradication of infection in 2 patients, and 7 patients showed a complete response with persistent high decrease (5 patients) or clearance (2 patients) of parasite in stool . The drug was well tolerated, and there was no relapse either during treatment or during follow up (up to 21 months) . These results were more impressive than those observed after the short term initial course of azithromycin, which was unable at any tested dose to achieve parasite clearance in stool (except in the patient with less advanced immunodeficiency) or to prevent relapse in 3 patients who discontinued treatment . Reversible side effects occurred with the 1500 mg daily dose . CONCLUSIONS: Long term, low dose azithromycin is well tolerated and may induce stable remission of chronic cryptosporidiosis in patients with AIDS . It may lead to probable eradication of the infection in some patients, even those with severe immunodeficiency.

Am J Trop Med Hyg, 1998 Mar, 58(3), 335 - 7
A case study of cytokine profiles in acute human babesiosis; Shaio MF et al.; The immune response in a patient with acute babesiosis was determined by measurements of lymphocyte subpopulations, serum levels of cytokines, and adhesion molecules . The ratio of CD4+:CD8+ lymphocytes was reduced early in the infection, but returned to a normal value after treatment with azithromycin and quinine . Natural killer (NK) cells markedly increased in the acute phase but progressively decreased and to the normal range in the convalescent phase . Serum levels of tumor necrosis factor-alpha, interferon-gamma, interleukin-2 (IL-2), IL-6, E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 were highly elevated in the acute phase while normal levels of these mediators were observed one month after treatment . These results suggest that CD8+ T cells and NK cells may be involved in the host defense mechanisms against acute babesiosis.

Lijec Vjesn, 1997 Nov, 119(10), 270 - 2
{Azithromycin in the prevention of Mediterranean spotted fever}; Dzelalija B et al.; Antibodies to Rickettsia conorii were detected by the indirect immunofluorescence (IFA) assay in 64 (51.6%) out of 124 examinees living in North Dalmatia (Croatia) who had a history of recent tick bites during 1994 and 1995 . Positive titers of IFA antibodies to R . conorii were detected in 12 (31.5%) out of 38 examinees with carried out prophylaxis by azithromycin . The usual clinical signs of Mediterranean spotted fever were registered in 22 (25.6%) and asymptomatic infection in 30 (34.8%) out of 86 examinees without prophylaxis . Clinical signs of the disease were not registered in examinees with prophylaxis.

J Chemother, 1998 Feb, 10(1), 64 - 8
Treatment of atypical pneumonia with azithromycin: comparison of a 5-day and a 3-day course; Socan M; The efficacy of a 5-day regimen consisting of 500 mg in a single dose on the first day followed by 250 mg once daily for 4 consecutive days was compared with that of a 3-day course of azithromycin given in single daily doses of 500 mg for treatment of atypical pneumonia . Adult patients hospitalized with atypical pneumonia in the years 1990 to 1993 were studied retrospectively . For each patient, the medical history, laboratory data, the results of serological tests, chest radiographs and treatment outcome were reviewed . Out of 148 patients with atypical pneumonia, 40 were treated with azithromycin for 5 days (Group 1) and 41 for 3 days (Group 2) . The success rate in Group 1 was 80% (32 patients) . Eight patients did not respond to treatment: 5 had significant complement fixing antibody titers to adenovirus and in 3 the etiology was unknown . The success rate in Group 2 was 88% (36 patients) . Azithromycin was ineffective in all 3 patients with adenoviral pneumonia, in 1 patient with Q fever, and in 1 patient with no identified pathogen . Azithromycin is equally effective as treatment of atypical pneumonia in adult patients if given for 3 or 5 days at the same total dose.

Clin Infect Dis, 1998 Mar, 26(3), 611 - 9
Once weekly azithromycin therapy for prevention of Mycobacterium avium complex infection in patients with AIDS: a randomized, double-blind, placebo-controlled multicenter trial; Oldfield EC 3rd et al.; We conducted a randomized, double-blind, placebo-controlled multicenter trial of azithromycin (1,200 mg once weekly) for the prevention of Mycobacterium avium complex (MAC) infection in patients with AIDS and a CD4 cell count of < 100/mm3 . In an intent-to-treat analysis through the end of therapy plus 30 days, nine (10.6%) of 85 azithromycin recipients and 22 (24.7%) of 89 placebo recipients developed MAC infection (hazard ratio, 0.34; P = .004) . There was no difference in the ranges of minimal inhibitory concentrations of either clarithromycin or azithromycin for the five breakthrough (first) MAC isolates from the azithromycin group and the 18 breakthrough MAC isolates from the placebo group . Of the 76 patients who died during the study, four (10.5%) of 38 azithromycin recipients and 12 (31.6%) of 38 placebo recipients had a MAC infection followed by death (P = .025) . For deaths due to all causes, there was no difference in time to death or number of deaths between the two groups . Episodes of non-MAC bacterial infection per 100 patient years occurred in 43 azithromycin recipients and 88 placebo recipients (relative risk, 0.49; 95% confidence interval, 0.33-0.73) . The most common toxic effect noted during the study was gastrointestinal, reported by 78.9% of azithromycin recipients and 27.5% of placebo recipients . Azithromycin given once weekly is safe and effective in preventing disseminated MAC infection, death due to MAC infection, and respiratory tract infections in patients with AIDS and CD4 cell counts of < 100/mm3.

Am J Gastroenterol, 1998 Mar, 93(3), 390 - 3
A four-day low dose triple therapy regimen for the treatment of Helicobacter pylori infection; Trevisani L et al.; OBJECTIVE: The current guidelines recommend 1-wk triple therapy regimens for eradicating H . pylori infection . Until now, shorter regimens have scarcely been investigated . Azithromycin is a new generation macrolide antibiotic with unusual and favorable pharmacokinetics, and seems to be a very promising agent for innovative anti-H . pylori regimens . We assessed the efficacy and tolerability of a new 4-day low dose triple therapy in comparison with a well established 1-wk triple therapy in the treatment of Helicobacter pylori infection . METHODS: One hundred-sixty consecutive patients with biopsy-proven H . pylori infection were randomized to receive lansoprazole 30 mg b.i.d . on days 1-4, azithromycin 500 mg u.i.d . on days 2-4, and tinidazole 2000 mg u.i.d . on day 3 (LAT group), or 7 days of triple therapy of omeprazole 20 mg u.i.d., clarithromycin 250 mg b.i.d., and tinidazole 500 mg b.i.d . (OCT group) . Patients with gastric or duodenal active ulcer received proton pump inhibitors for an additional 4 wk . H . pylori eradication was defined as negative of both rapid urease test and histology on biopsies taken from the gastric body and antrum at least 1 month after the end of treatment . RESULTS: Seven patients in the LAT group and four in the OCT group were lost to follow-up . No significant difference in either efficacy or tolerability was observed between the two regimens . Active ulcers healed in 97.8% of cases with LAT and in 100% of cases with OCT . The eradication rate was 80.8% in the LAT group and 85.5% in the OCT group, considering the per-protocol results, and 73.3% and 81.2%, respectively, considering the intention-to-treat results . Side effects occurred in one LAzT patient and in two OCT patients; they were mild and did not interfere with compliance . CONCLUSION: The new proposed ultrashort triple therapy, including lansoprazole, low dose azithromycin for 3 days, and a single dose of tinidazole, appears to be a very effective anti-H . pylori regimen, a simpler, cheaper, well-tolerated, and equally effective alternative to 1-wk triple therapy.

Circulation, 1998 Feb 24, 97(7), 633 - 6
Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model; Muhlestein JB et al.; BACKGROUND: Chlamydia pneumoniae infection has been associated with atherosclerosis by serological studies and detection of bacterial antigen within plaque . We sought to evaluate a possible causal role in an animal model . METHODS AND RESULTS: Thirty New Zealand White rabbits were given three separate intranasal inoculations of either C pneumoniae (n = 20) or saline (n = 10) at 3-week intervals and fed chow enriched with a small amount (0.25%) of cholesterol . Immediately after the final inoculation, infected and control rabbits were randomized and begun on a 7-week course of azithromycin or no therapy . Three months after the final inoculation, rabbits were euthanatized and sections of thoracic aortas were blindly evaluated microscopically for maximal intimal thickness (MIT), percentage of luminal circumference involved (PLCI), and plaque area index (PAI) of atherosclerosis . Vascular chlamydial antigen was assessed by direct immunofluorescence . MIT differed among treatment groups (P=.009), showing an increase in infected rabbits (0.55 mm; SE = 0.15 mm) compared with uninfected controls (0.16 mm; SE = 0.06 mm) and with infected rabbits receiving antibiotics (0.20 mm; SE = 0.03 mm) (both P<.025), whereas MIT in infected/treated versus control rabbits did not differ . PLCI also tended to differ (P<.1) and PAI differed significantly (P<.01) among groups with a similar pattern . Chlamydial antigen was detected in 2 untreated, 3 treated, and 0 control animals . CONCLUSIONS: Intranasal C pneumoniae infection accelerates intimal thickening in rabbits given a modestly cholesterol-enhanced diet . In addition, weekly treatment with azithromycin after infectious exposure prevents accelerated intimal thickening . These findings strengthen the etiologic link between C pneumoniae and atherosclerosis and should stimulate additional animal and human studies, including clinical antibiotic trials.

Dtsch Med Wochenschr, 1998 Jan 30, 123(5), 103 - 8; discussion 109
{Short-term (6 days) eradication of Helicobacter pylori infection in the practice of a health insurance physician}; Seelis RE et al.; OBJECTIVE: To obtain epidemiological data concerning Helicobacter pylori (H.p.) infections and peptic ulcer in patients with upper abdominal pain in a routine non-hospital based health-insurance practice, as well as to test the efficacy of H.p . eradication, especially with a new shortterm treatment scheme in this setting . PATIENTS AND METHODS: H.p . status and possible peptic ulceration (urease test, biopsies of gastric antrum and body) were determined in 1242 consecutive patients with upper abdominal pain examined gastroscopically . Patients who were H.p . positive and had a peptic ulcer or recurrent gastritis with erosions were given dual or triple medication (lansoprazole or pantoprazole with one or two antibiotics: amoxycillin, clarithromycin, azithromycin, tinidazole), under conditions of controlled compliance . RESULTS: The H.p . infection rate was 45.9% for the whole group (mean age: 49.9 years) . An acute ulceration was found in 10.4% of the whole group, i.e . 20.1% of the 129 H.p . positive patients . 194 patients were given an eradication treatment . In 62 of them, put on a new 6-day eradication regimen (azithromycin, 1 x 500 mg daily; tinidazole, 1 x 2000 mg/d; and pantoprazole, 2 x 40 mg/d), an eradication rate of 93% (under protocol) or 92% (intention to treat) was achieved . INTERPRETATION: In routine non-hospital practice a 6-day modified triple-medication treatment with azithromycin, tinidazole and pantoprazole proved efficacious in eradicating H.p . infection . It not only caused few side effects and was cheap, but also achieved high patient compliance.

J Pediatr Hematol Oncol, 1998 Jan-Feb, 20(1), 83 - 5
Eradication of Cryptosporidium in a child undergoing maintenance chemotherapy for leukemia using high dose azithromycin therapy; Russell TS et al.; PURPOSE: To describe a case of severe diarrhea caused by Cryptosporidium in a patient undergoing maintenance chemotherapy . Important aspects of disease caused by Cryptosporidium, including diagnosis and treatment, are also reviewed . METHODS AND RESULTS: A 4-year-old boy with acute lymphoblastic anemia in remission had a prolonged course of diarrhea and wasting . C . parvum was identified in the gastrointestinal tract by biopsy and in the stool using modified acid fast staining . Improvement in the stool consistency was noted after 3 days of therapy with azithromycin, and, after 14 days of therapy, Cryptosporidium oocysts could no longer be identified in the stool . CONCLUSIONS: C . parvum should be considered in all immunocompromised patients with severe or prolonged diarrhea, especially if there is no blood or leukocytes in the stool . Because Cryptosporidium is not always tested for in a routine ova and parasite examination, the lab should be notified if it is in the differential diagnosis . Azithromycin therapy may prove beneficial in the treatment of intestinal Cryptosporidium in immunocompromised individuals.

Lijec Vjesn, 1997 Jul, 119(7), 210 - 3
{Omeprazole and azithromycin with and without metronidazole in the eradication of Helicobacter pylori in duodenal ulcer disease}; Vcev A et al.; This prospective, single blind, randomized study was designed to compare the efficacy and tolerance of two therapeutic schedules for eradication of H . pylori in patients with duodenal ulcer . Patients were randomized into two groups . Group 1 (n = 25) was treated with omeprazole 20 mg each morning for 28 days, azithromycin 500 mg/day for 5 days and metronidazole 3 x 500 mg/day for 5 days . Group 2 (n = 25) was treated with omeprazole 20 mg/day for 28 days and azithromycin 500 mg/day for 5 days . H . pylori status was determined by rapid urease test and histology before and 1, 6 and 12 months after the therapy . After 4 weeks of treatment ulcers healed in 96% (24/25) of patients in the first group and in 92% (23/25) of patients in the second group . One and 12 months after the treatment, eradication of Helicobacter pylori was achieved in 72% (18/25) of patients in the first group and in 64% (16/25) of patients in the second group . In 12 months after the treatment ulcer recurred in 43.7% (7/16) of patients in whom H . pylori was not eradicated and in 2.9% (1/34) of patients with eradicated H . pylori . The side effects were minor and/or transitory and did not require discontinuation of the treatment.

JAMA, 1998 Feb 4, 279(5), 384 - 6
Possible effectiveness of clarithromycin and rifabutin for cryptosporidiosis chemoprophylaxis in HIV disease . HIV Outpatient Study (HOPS) Investigators; Holmberg SD et al.; CONTEXT: Cryptosporidium parvum infection, a common cause of diarrhea in persons infected with the human immunodeficiency virus (HIV), is difficult to treat or prevent . OBJECTIVE: To evaluate relative rates of cryptosporidiosis in HIV-infected patients who were either receiving or not receiving chemoprophylaxis or treatment for Mycobacterium avium complex . DESIGN: Analysis of prospectively collected data from HIV-infected patients' visits to their physicians since 1992 . SETTING: Ten (8 private, 2 publicly funded) HIV clinics in 9 US cities . PATIENTS: A total of 1019 HIV-infected patients with CD4+ cell counts less than 0.075 x 10(9)/L . MAIN OUTCOME MEASURES: Incidence of clinical cryptosporidiosis during treatment with clarithromycin, rifabutin, and azithromycin . RESULTS: Five of the 312 patients reportedly taking clarithromycin developed cryptosporidiosis vs 30 of the 707 patients not taking clarithromycin (relative hazard {RH}, 0.25 {95% confidence interval (CI), 0.10-0.67}; P=.004) . Two of the 214 patients taking rifabutin developed cryptosporidiosis vs 33 of the 805 not taking rifabutin (RH, 0.15 {95% CI, 0.04-0.62}; P=.01) . Prophylactic efficacy of either drug was 75% or greater . No protective effect was seen in the 54 patients reportedly taking azithromycin (RH, 1.48 {95% CI, 0.44-5.04}; P=.46) . CONCLUSIONS: Clarithromycin and rifabutin were highly protective against development of cryptosporidiosis in immune-suppressed HIV-infected persons in this analysis; further study is warranted.

Nephrol Dial Transplant, 1997 Dec, 12(12), 2694 - 7
Treatment of cyclosporin-induced gingival hyperplasia with azithromycin; Gomez E et al.; BACKGROUND: Gingival hyperplasia is a known complication of cyclosporin therapy . Although plaque control has been shown to be of benefit, gingival surgery is occasionally necessary . The aim of this study was to review the effect of a short-course therapy with azithromycin in renal transplant patients with cyclosporin-induced gingival hyperplasia . METHODS: Thirty-eight patients received 500 mg/day of azithromycin for 3 consecutive days . The degree of gingival hyperplasia was classified as: 0, no gingival overgrowth; 1, mild overgrowth; 2, moderate overgrowth, and 3, severe overgrowth . Gingival bleeding and evolution of gingival hyperplasia were determined at 0 (pretreatment), 7, 30, 90 and 180 days . Cyclosporin, serum creatinine and ALT levels were simultaneously determined on the same days . RESULTS: Seven patients were excluded, leaving a total of 31 included in the trial . Eleven had a score of 3, 17 a score of 2, and 3 a score of 1 . The degree of gingival hyperplasia was unrelated to the dose and levels of cyclosporin . Gingival hyperplasia improved in all patients (P < 0.001, Friedman test) . The degree of improvement was better when the degree of hyperplasia was lower . In 27 patients gingival hyperplasia remained absent 6 months later, 3 patients required a second course of treatment, and another required gingival surgery . Gingival bleeding, present in 28 patients when diagnosed, disappeared in all cases in 2.2 +/- 1.2 (1-7) days . No adverse effects were observed . Cyclosporin, serum creatinine, and ALT levels were not affected by treatment . CONCLUSIONS: Azithromycin improves cyclosporin-associated gingival hyperplasia, especially when administered early in the process.

Dtsch Med Wochenschr, 1997 Sep 26, 122(39), 1178 - 80
{Meningitis after acute Borrelia burgdorferi infection in HIV infection}; Dudle G et al.; HISTORY AND CLINICAL FINDINGS: A 39-year-old HIV positive patient developed myalgia, headache and cough 4 weeks after a tick bite . His temperature was 37.4 degrees C and a circular pale erythema was noted over the left lower leg . INVESTIGATIONS: C-reactive protein was raised to 120 mg/l, white blood cell count was 5860/microliter, CD4-lymphocyte count 250/microliter . The chest radiogram showed pneumonitic infiltration in the left lower lobe . There were IgM antibodies against Borrelia burgdorferi . TREATMENT AND COURSE: Left lower lobe pneumonia and chronic erythema migrans were diagnosed and he was given oral azithromycin (500 mg on the first day and 250 mg for 4 days) . The pneumonia cleared up, but 2 weeks later he developed symptoms of meningitis (496 cells per microliter, 87% lymphocytes, positive Borrelia burgdorferi antibody titer), which quickly and lastingly responded to ceftriaxon (2 g daily by brief infusion for 14 days) . CONCLUSION: This immune-compromised HIV-infected patient developed disseminated borreliosis with CNS involvement 2 weeks after the occurrence of chronic erythema migrans . The initial treatment of the latter with azithromycin was unable to prevent the meningitis . It is unlikely that there was a causal connection between the borreliosis and the pneumonia.

Clin Infect Dis, 1998 Jan, 26(1), 146 - 50
Successful double-blinded, randomized, placebo-controlled field trial of azithromycin and doxycycline as prophylaxis for malaria in western Kenya; Andersen SL et al.; Azithromycin prevents malaria in animal models and early clinical trials . We determined the prophylactic efficacy of three antibiotic regimens given for 10 weeks (azithromycin, 250 mg daily; azithromycin, 1,000 mg weekly; and doxycycline, 100 mg daily) relative to that of placebo for 232 adult volunteers residing in an area of intense malaria transmission . Any confirmed parasitemia during the study was considered a prophylactic failure . Two hundred thirteen volunteers (92%) completed the study . The prophylactic efficacies were as follows: daily azithromycin, 82.7% (95% confidence interval {CI}, 68.5%-91.1%); weekly azithromycin, 64.2% (95% CI, 47.1%-77.1%); and daily doxycycline, 92.6% (95% CI, 79.9%-97.5%) . All regimens were well tolerated . We concluded that both 100 mg of doxycycline and 250 mg of azithromycin, given daily, were effective as prophylaxis for malaria in this setting . If studies with nonimmune volunteers confirm these results for semi-immune volunteers, a daily azithromycin regimen may have special utility for individuals with contraindications to treatment with doxycycline or other antimalarial agents.

JAMA, 1998 Jan 14, 279(2), 130 - 6
The cost-effectiveness of preventing AIDS-related opportunistic infections; Freedberg KA et al.; CONTEXT: Multiple options are now available for prophylaxis of opportunistic infections related to the acquired immunodeficiency syndrome (AIDS) . However, because of differences in incidence rates as well as drug efficacy, toxicity, and costs, the role of different types of prophylaxis remains uncertain . OBJECTIVE: To determine the clinical impact, cost, and cost-effectiveness of strategies for preventing opportunistic infections in patients with advanced human immunodeficiency virus (HIV) disease . DESIGN: We developed a Markov simulation model to compare different strategies for prophylaxis of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) infection, fungal infections, and cytomegalovirus (CMV) disease in HIV-infected patients . Data for the model were derived from the Multicenter AIDS Cohort Study, randomized controlled trials, and the national AIDS Cost and Services Utilization Survey . MAIN OUTCOME MEASURES: Projected life expectancy, quality-adjusted life expectancy, total lifetime direct medical costs, and cost-effectiveness in dollars per quality-adjusted life-year (QALY) saved . RESULTS: For patients with CD4 cell counts of 0.200 to 0.300 x 10(9)/L (200-300/microL) who receive no prophylaxis, we projected a quality-adjusted life expectancy of 39.08 months and average total lifetime costs of $40288 . Prophylaxis for PCP and toxoplasmosis with trimethoprim-sulfamethoxazole for patients with CD4 cell counts of 0.200 x 10(9)/L (200/microL) or less increased quality-adjusted life expectancy to 42.56 months, implying an incremental cost of $16000 per QALY saved . Prophylaxis for MAC for patients with CD4 cell counts of 0.050 x 10(9)/L (50/microL) or less produced smaller gains in quality-adjusted life expectancy; incremental cost-effectiveness ratios were $35000 per QALY saved for azithromycin and $74000 per QALY saved for rifabutin . Oral ganciclovir for the prevention of CMV infection was the least cost-effective prophylaxis ($314000 per QALY saved) . Results were most sensitive to the risk of developing an opportunistic infection, the impact of opportunistic infection history on long-term survival, and the cost of prophylaxis . CONCLUSIONS: The cost-effectiveness of prophylaxis against HIV-related opportunistic infections varies widely, but prophylaxis against PCP or toxoplasmosis and against MAC delivers the greatest comparative value . In an era of limited resources, these results can be used to set priorities and explore new alternatives for improving HIV patient care.

Sex Transm Dis, 1998 Jan, 25(1), 5 - 11
Doxycycline and azithromycin for prevention of chlamydial persistence or recurrence one month after treatment in women . A use-effectiveness study in public health settings; Hillis SD et al.; BACKGROUND: To treat chlamydial infection, the Centers for Disease Control and Prevention recommends either a single dose of azithromycin or a 7-day course of doxycycline . Cost is a concern with the single-dose regimen; compliance is a concern with the multidose regimen . GOAL: To compare the use-effectiveness of azithromycin and doxycycline for preventing persistence or recurrence of Chlamydia trachomatis infection in women and to evaluate associated risk behaviors . STUDY DESIGN: One hundred and ninety-six chlamydia-infected women and their sex partners were recruited into a randomized controlled trial of single-dose versus multidose regimens in seven public health clinics, with no incentives for enrollment, compliance, or follow-up . The outcome, measure was a positive test for C . trachomatis by polymerase chain reaction testing at 1 month after treatment . RESULTS: C . trachomatis positivity at 1 month was similar for women receiving single-dose (5.1%, 5/98) and multidose therapy (4.1%, 4/98) . Reported compliance among 73 women taking multidose therapy was 94.5% . A twofold to threefold increased risk of chlamydial persistence or recurrence was observed among women who were < or = 24 and white or who reported: a recent new partner, multiple partners, or a partner who may have had multiple partners at the time of enrollment or that not all partners were treated during the 1-month follow-up period after initiation of treatment . CONCLUSIONS: The use-effectiveness of single-dose and multidose therapy was comparably high . Observed rates of persistence or recurrence were consistent with reported rates of pharmacological treatment failure . However, all women with C . trachomatis detected at 1 month had behavioral risk factors that may have contributed to reinfection.

J Antimicrob Chemother, 1997 Nov, 40(5), 713 - 6
A new semi-solid agar dilution method for determining amoxycillin, clarithromycin and azithromycin MICs for Helicobacter pylori isolates; Kobayashi I et al.; The MICs of amoxycillin, clarithromycin and azithromycin for 26 strains of Helicobacter pylori were determined using Mueller-Hinton semi-solid agar (SSA) without CO2 incubation, as in the conventional agar dilution method . The tested H . pylori strains grew satisfactorily in the SSA method within 48 h of incubation . Reasonable values of MICs of three antibiotics for these strains were obtained by this method, avoiding the inactivation of macrolides due to acidification of the medium . By this method, the MICs of the antibiotics for the reference strains were within the acceptable NCCLS ranges for quality control.

Ann Pharmacother, 1997 Nov, 31(11), 1308 - 10
Symptomatic syndrome of inappropriate antidiuretic hormone secretion associated with azithromycin; Cadle RM et al.; OBJECTIVE: To report a case of symptomatic syndrome of inappropriate antidiuretic hormone (SIADH) secretion associated with azithromycin and review the literature related to this adverse drug reaction . DATA SOURCES: Review articles identified by a computerized (MEDLINE) (1966-April 1996) and manual (Index Medicus) search . DATA SYNTHESIS: Azithromycin is a well-tolerated broad-spectrum macrolide antibiotic . We report a symptomatic case of SIADH secretion associated with azithromycin . The patient received two doses of azithromycin before the development of sudden mental status changes associated with severe hyponatremia . All other potential causes were ruled out . No previous reports exist in the literature . CONCLUSIONS: Azithromycin may be associated with symptomatic SIADH secretion . Awareness and attention are required if patients develop mental status changes or hyponatremia while receiving azithromycin so that appropriate diagnostic and therapeutic actions can be implemented.

J Int Med Res, 1997 Sep-Oct, 25(5), 285 - 95
An open, multicentre, comparative study of the efficacy and safety of azithromycin and co-amoxiclav in the treatment of upper and lower respiratory tract infections in children . The Paediatric Azithromycin Study Group; Lauvau DV et al.; An open prospective, multicentre, comparative, randomized (2:1) study was conducted in 481 children diagnosed as having mild-to-moderate lower respiratory tract infections . The efficacy and safety of azithromycin suspension (10 mg/kg), dosed orally once daily for 3 days, was compared with that of co-amoxiclav (10 mg/kg in a 4:1 ratio), dosed orally three times daily for 5-10 days . The proportion of evaluable patients (n = 472) showing a cure or improvement was significantly higher in the azithromycin group (96.8%) than in the co-amoxiclav group (91%, P = 0.0199) . There were six relapses in both groups, giving an overall response rate of 95% for azithromycin versus 87.1% for co-amoxiclav (P = 0.0025) . Adverse events were reported in 10% of the patients treated with azithromycin, and 11.3% of co-amoxiclav patients . Reported and counted compliance was significantly better in the azithromycin group . A 3-day regimen of azithromycin was as effective and as safe as a 5-10 day regimen of co-amoxiclav in the treatment of respiratory tract infections in children, and compliance was improved.

Drugs, 1997, 54 Suppl 2, 8 - 15; discussion 28-9
Prevention strategies for Mycobacterium avium-intracellulare complex (MAC) infection . A review of recent studies in patients with AIDS; Cohn DL; In patients with AIDS, disseminated Mycobacterium avium-intracellulare complex (MAC) infection is a common bacterial infection and is associated with considerable morbidity and mortality . In placebo-controlled studies, rifabutin, clarithromycin and azithromycin (administered as single agents) have been shown to prevent the development of MAC bacteraemia in patients with advanced HIV disease . Clarithromycin also conferred a survival benefit over placebo, but this was not initially observed with either rifabutin or azithromycin . Subsequently, the efficacy of single agent therapy was compared with that of combination treatment as prophylaxis against the development of disseminated MAC . In the AIDS Clinical Trials Group (ACTG) 196/Community Programs for Clinical Research on AIDS (CPCRA) 009 study, clarithromycin monotherapy and clarithromycin and rifabutin combination therapy regimens were both more effective than rifabutin monotherapy in reducing the incidence of MAC bacteraemia . However, the combination regimen was generally not well tolerated . In the California Consortium Treatment Group (CCTG)/Multiple Opportunistic Prevention Prophylactic Strategy (MOPPS) study, azithromycin plus rifabutin was significantly more effective than either agent administered alone, and azithromycin was more effective than rifabutin . However, azithromycin (alone or in combination with rifabutin) caused frequent gastrointestinal adverse events . Emergence of resistance in those failing prophylaxis appeared to be higher with clarithromycin than with azithromycin or rifabutin . The use of the combination regimen of clarithromycin plus rifabutin did not reduce the selection of clarithromycin-resistant isolates . Several issues need to be considered in the choice of MAC prophylaxis for the individual patient . On the basis of efficacy and potential drug interactions with protease inhibitors, clarithromycin or azithromycin is preferred to rifabutin . However, rifabutin is less likely to result in the emergence of resistance than the macrolides, and is likely to prevent tuberculosis, whereas azithromycin and clarithromycin will prevent some bacterial infections . Combination therapy for prophylaxis is not indicated in most situations.

Enferm Infecc Microbiol Clin, 1997 Apr, 15(4), 196 - 9
{Penetration of azithromycin into human neutrophils: effect of hydrogen peroxide production}; Rodriguez-Bano J et al.; BACKGROUND: The aim of this study was to evaluate the uptake of azythromycin at therapeutic concentrations by human polymorphonuclear leukocytes (PMN), as well as the effect of environmental temperature, pH, and cell viability on this uptake . The effect of azythromycin and other macrolides on hydrogen peroxide production by PMN was also assessed . METHODS: Uptake of radiolabeled azythromycin by PMN was determined by a radiometric technique . Hydrogen peroxide production by PMN was measured by the phenol red method . RESULTS: The intracellular concentrations achieved by azythromycin in PMN were 20 to 60 fold the extracellular ones, even at extracellular concentration of 0.125 mg/l . The uptake was significantly affected by low temperature, acid pH, and cell viability . Hydrogen peroxide production was not affected by the macrolides studied . CONCLUSIONS: Azythromycin at therapeutical concentrations achieves high intracellular accumulation in human PMN . The effect of environmental temperature, pH and cell viability on uptake points out that a passive diffusion, with lysosome trapping, is the essential mechanism of azythromycin uptake by phagocytic cells . In spite of the high intracellular concentrations achieved by macrolides, hydrogen peroxide production by PMN is not affected by these compounds.

Ann Pharmacother, 1997 Sep, 31(9), 965 - 9
Toleration of intravenous azithromycin; Luke DR et al.; OBJECTIVE: To study the toleration of various infusate concentrations of single intravenous doses of azithromycin . DESIGN: Randomized, double-blind, two-treatment, two-period, crossover . SETTING: Clinical pharmacology unit . PARTICIPANTS: Twenty-four healthy men aged 19-41 years . STUDY DESIGN: All subjects were initially randomized to receive single 1-hour intravenous infusions of azithromycin 1 g at infusate concentrations of 1, 2, or 5 mg/mL (n = 6 each) compared with placebo (n = 6) . Subjects who were randomized to receive 1 mg/mL concentrations were subsequently administered 5 mg/mL concentrations at least 2 weeks later, those given 2 mg/mL were crossed over to 4 mg/mL, and those in the 5-mg/mL group were crossed over to 1 mg/mL concentrations . MAIN OUTCOME MEASURES: Subjects recorded intravenous infusion toleration using visual analog scales ranging from 0 (no signs or symptoms) to 10 (poor toleration) for erythema, pain, swelling, and tenderness . Vascular Doppler recordings were obtained during and after infusion cephalad to the infusion site . RESULTS: Infusion site reactions increased in incidence and severity with infusion concentrations of 4 and 5 mg/mL; the most frequent reactions were tenderness and erythema . There were no apparent trends in Doppler readings . CONCLUSIONS: Single doses of azithromycin 1 g at infusate concentrations up to 2 mg/mL were well tolerated when administered over 1 hour to healthy men.

J Pharm Sci, 1997 Sep, 86(9), 1030 - 3
Study of 7,7',8,8'-tetracyanoquinodimethane charge transfer complexes with some lone-pair-donating drugs; Bebawy LI et al.; The interaction between 7,7',8,8'-tetracyanoquinodimethane (TCNQ) and oxamniquine (I), azithromycin (II), omeprazole (III), pantoprazole (IV), and benzydamine hydrochloride (V) was investigated . The reaction conditions were optimized to obtain typical charge transfer complexes (CTC) . The nature of the formed complexes was proved by thorough study of the thermodynamic parameters namely delta G (free energy), delta H (enthalpy), and delta S (entropy) . The association constant KcAD and the molar absorptivity xi lambda AD of the formed complexes were determined using the Benesi-Hildbrand equation . The effect of temperature on these constants gave evidence of CTC formation . The reaction of TCNQ with I-V was found to be in 1:1; as being determined by the Foster method . Spectrophotometric measurements of the formed CTC were used for the quantitative determination of the studied drugs in both pure or pharmaceutical formulation . The mean percentage recoveries were 99.17 +/- 0.34, 99.75 +/- 0.12, 100.52 +/- 0.41, 98.75 +/- 0.63, and 99.23 +/- 62 for I, II, III, IV, and V, respectively . There was no significant difference observed when the method was statistically compared with the official and reference methods used to determine these drugs.

J Acquir Immune Defic Syndr Hum Retrovirol, 1997 Aug 1, 15(4), 275 - 82
Prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS: a cost-effectiveness analysis; Freedberg KA et al.; OBJECTIVE: To determine the effectiveness and costs of prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS . DESIGN: A decision analysis model was constructed to compare rifabutin (300 mg/day), azithromycin (1200 mg/week), and clarithromycin (500 mg twice per day) with no prophylaxis . Sensitivity analysis was done on all model parameters, including initial CD4 count for beginning prophylaxis . SETTING: The setting was hypothetical for the cost-effectiveness model . Clinical data were taken from published prospective randomized controlled trials . MAIN OUTCOME MEASURES: Outcomes were measured in terms of projected life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness in U.S . dollars per quality-adjusted life-year saved ($/QALY) . RESULTS: For patients with AIDS and those having CD4 counts <75 cells/mm3, azithromycin, clarithromycin, and rifabutin prophylaxis increased lifetime per person MAC-related costs by $994, $2,117, and $2,185 U.S., respectively . Quality-adjusted life expectancy increased from 1.6068 QALYs to between 1.6186 and 1.6255 QALYs . The cost-effectiveness ratios were $58,200, $116,000, and $179,100/QALY saved for azithromycin, clarithromycin, and rifabutin prophylaxis, respectively, each compared with no prophylaxis . Results were most dependent on the annual cost of prophylaxis, the initial CD4 count when starting prophylaxis, and any survival benefit with prophylaxis . For each type of prophylaxis, strategies beginning with CD4 counts <25 or 50 cells/mm3 were substantially more cost-effective than those beginning in patients with higher CD4 counts . CONCLUSIONS: MAC prophylaxis is likely to cost society an additional $99 to $219 million U.S . per 100,000 patients treated . In the context of Centers for Disease Control and Prevention (CDC) recommendations to use prophylaxis in patients with CD4 counts <75 cells/mm3, azithromycin represents the best value and is most cost-effective when used in patients with CD4 counts <25 cells/mm3.

Circulation, 1997 Jul 15, 96(2), 404 - 7
Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction; Gupta S et al.; BACKGROUND: The clinical significance of the association between elevated anti-Chlamydia pneumoniae (Cp) antibody titres and coronary heart disease (CHD) is unclear . We explored the relationship between antibodies against Cp and future cardiovascular events in male survivors of myocardial infarction (MI) . The effect of azithromycin antibiotic therapy was assessed in a subgroup of post-MI patients . METHODS AND RESULTS: We screened 220 consecutive male survivors of MI for anti-Cp antibodies . Of these, 213 patients were stratified into three groups: group Cp-ve (n=59), no detectable Cp antibodies; group Cp-I (n=74), intermediate titres of 1/8 to 1/32 dilution; and group Cp+ve (n=80), seropositive at > or = 1/64 dilution . Patients with persisting seropositivity of > or = 1/64 were randomized to either oral azithromycin (Cp+ve-A, 500 mg/d for 3 days {n=28} or 500 mg/d for 6 days {n=12}) or placebo (Cp+ve-P, n=20) . Cp+ve-NR (n=20) represented patients not recruited into the antibiotic trial . The incidence of adverse cardiovascular events (over a mean follow-up period of 18+/-4 months) was recorded and shown to increase with increasing anti-Cp titre: Cp-ve, n=4 (7%); Cp-I, n=11 (15%); Cp+ve-NR, n=6 (30%); and Cp+ve-P, n=5 (25%) . Cp+ve-NR and Cp+ve-P groups had a fourfold-increased risk for adverse cardiovascular events compared with the Cp-ve group (odds ratio {OR}, 4.2; 95% confidence interval {CI}, 1.2 to 15.5; P=.03) . In contrast, the OR for cardiovascular events in patients receiving azithromycin (Cp+ve-A, single or double course) was the same as in the Cp-ve group (OR, 0.9; 95% CI, 0.2 to 4.6, P=NS) . Patients receiving azithromycin were more likely to experience a decrease in IgG anti-Cp titres than were those in the placebo group (P=.02) . CONCLUSIONS: An increased anti-Cp antibody titre may be a predictor for further adverse cardiovascular events in post-MI patients . Taking a short course of azithromycin may lower this risk, possibly by acting against Cp.

J Med Assoc Thai, 1997 Jul, 80(7), 440 - 5
Azithromycin in non-gonococcal urethritis; Charoenwatanachokchai A et al.; The efficacy and safety of a single 1 g oral dose of azithromycin was evaluated in 100 male patients with non-gonococcal urethritis (NGU) . Enrolled were men with > or = 5 polymorphonuclear leukocytes (PMNL)/high power field (HPF) (x 1000 magnification) in a Gram-stained smear of urethral discharge with or without symptoms and signs of NGU . Of the 66 evaluable patients, Chlamydia trachomatis was isolated from 18 cases (27.3%) and Ureaplasma urealyticum from 12 cases (18.2%) . After treatment, signs and symptoms disappeared from 59 cases (89.4%) . Forty-four cases (66.7%) showed reduced PMNL/HPF . C . trachomatis was eradicated in 18 cases (100%) and U . urealyticum in 12 cases (83.3%) . One patient complained of mild dizziness, moderate nausea, and palpitations . Single 1 g oral dose of azithromycin appears to be effective and safe for treating chlamydial, non-chlamydial, and ureaplasmal NGU . In addition, its ease of use encourages patient compliance.

Arzneimittelforschung, 1997 Jul, 47(7), 866 - 8
Intracellular activity of azithromycin against Mycobacterium avium complex in human macrophages; Wildfeuer A et al.; In the concentration range examined (0.5-16 micrograms/ml) the azalide antibiotic azithromycin (CAS 83905-01-5, Zithromax) inhibited the growth of mycobacteria in macrophages over 7 days . The higher concentrations of azithromycin, 8 and 16 micrograms/ml, reduced the number of phagocytized bacteria in macrophages by at least 1 log unit within 4 days . The system used, macrophages from healthy volunteers, is suitable for testing the intracellular activity of drugs against the Mycobacterium avium complex.

Pharmacotherapy, 1997 Jul-Aug, 17(4), 827 - 9
Reduced serum theophylline concentrations after discontinuation of azithromycin: evidence for an unusual interaction; Pollak PT et al.; A 68-year-old man receiving long-term therapy with oral sustained-release theophylline 450 mg twice/day was admitted to the hospital after failing treatment with azithromycin for an acute exacerbation of obstructive lung disease . Peak serum theophylline concentration was 20 microg/ml (normal 10-20 microg/ml) . Azithromycin was discontinued and the theophylline dosage reduced by 33% . The subsequent 80% decrease in serum theophylline to 4.6 microg/ml was unexpectedly large . Two rechallenges produced similar transient depressions of serum theophylline concentrations after withdrawal of azithromycin, suggesting an interaction . Withdrawal of azithromycin may leave an increased number of active enzyme sites available as the drug is cleared from the system . In some circumstances, it may be useful for pharmacokinetic interaction studies to continue measuring concentrations after the suspected interacting agent is stopped.

Drugs, 1997 Jul, 54(1), 69 - 80
The role of advanced generation macrolides in the prophylaxis and treatment of Mycobacterium avium complex (MAC) infections; Amsden GW et al.; Since the start of the acquired immunodeficiency syndrome (AIDS) epidemic, the role of Mycobacterium avium complex (MAC) as an opportunistic pathogen in advanced AIDS patients has become more and more clear . Once identified in an advanced AIDS patient it is possible to find evidence that the MAC organism and infection is not only present in the pulmonary tree, but has also disseminated to a wide variety of body organs . Treatment of MAC or disseminated MAC (DMAC) infections has historically been very difficult due to the inherent resistance of the MAC pathogen to most standard antimycobacterial agents . This has resulted in the development of new agents for the prevention of DMAC infection as well as combinations of both new and standard agents for its treatment . Three drugs are currently approved for single-agent DMAC prophylaxis, including rifabutin, azithromycin and clarithromycin . Combinations of agents for DMAC treatment are highly variable in content but most experts agree that all combinations should contain one of the advanced generation macrolides (azithromycin or clarithromycin) . Both of these agents have favourable intracellular pharmacokinetics and pharmacodynamics which maximise their effects against this mostly intracellular pathogen . Due to the paucity of comparative data, no one macrolide can be recommended over the other . However, the expected increase in compliance, lower weekly and annual costs, and lack of any drug interactions may make azithromycin a preferable choice, but this should be decided on a case-by-case basis.

J Med Assoc Thai, 1997 Jun, 80(6), 343 - 7
Azithromycin in the treatment of chlamydial cervicitis and eradication of Ureaplasma urealyticum in female lower genital tract; Charoenwatanachokchai A et al.; From May 1995 to May 1996, thirty-six females with chlamydial cervicitis were enrolled at Bangrak Hospital's Venereal Disease Clinic in an open study to assess the efficacy and safety of a single, 1-gram oral dose of azithromycin . Thirty-five had positive C . trachomatis and one had a positive Gen-probe test . Twenty-two returned for their first and second follow-ups and 18 came back for their final follow-up (visit 4) . Eradication rate was 100 per cent on all visits . Fourteen patients were excluded from the final analysis- three had dropped out from the beginning, ten had sexual intercourse without a condom and one had a positive Gen-probe test but negative C . trachomatis culture . U . urealyticum was isolated from the vaginal wall of 15 of the 36 cases and eradication rate was 0 per cent at visit 2 and visit 4 . In conclusion, this study shows that a single, 1-gram oral dose of azithromycin is an effective and well-tolerated alternative therapy for chlamydial cervicitis.

Clin Pharmacol Ther, 1997 Jun, 61(6), 641 - 8
Disposition of oral azithromycin in humans; Luke DR et al.; BACKGROUND: The oral bioavailability of azithromycin is approximately 37% in healthy subjects; little is known about the disposition of the remaining 63% of the dose . This study attempted to describe the fate of azithromycin before absorption . METHODS: Twelve subjects with ileostomies in place for > 1 month were studied in this open-label, randomized, three-center, two-period, two-treatment crossover study . Subjects randomly received single 500 mg intravenous infusion (over 1 hour) or two 250 mg oral capsules after a fast for > 12 hours . Blood and ileostomy samples were collected serially after each administration and analyzed for azithromycin and two metabolites (descladinose and 9a-N-desmethyl metabolites) by HPLC with electrochemical detection . RESULTS: Mean +/- SD peak concentration values after oral and intravenous administration were 0.21 +/- 0.08 and 3.40 +/- 1.12 microgram/ml . Mean values for area under the serum concentration versus time curve were 1.27 +/- 0.65 and 7.14 +/- 1.34 micrograms x hr/ml, respectively . The absolute bioavailability of 16.2% was approximately one-half the value observed previously in healthy subjects . Recovery in ileostomy fluid (percent of dose in 24 hours) or azithromycin, descladinose, and 9a-N-desmethyl metabolites were 13%, 0.5%, and 1% (total, 15%) after intravenous dosing and 47%, 13%, and 2% (total, 62%) after oral dosing . Total and ileal clearances were 776 +/- 126 and 158 +/- 63 ml/min after intravenous dosing . CONCLUSION: Because more descladinose metabolite was detected after oral dosing, acid degradation of azithromycin before absorption contributed to some loss in oral bioavailability . Further, ileal clearance (biliary plus intestinal excretion clearance) in this population represented 21% of total clearance . Taken together, these data suggest that the cause of low oral bioavailability of azithromycin is the result of incomplete absorption rather than acid degradation or extensive first-pass metabolism.

Bone Marrow Transplant, 1997 Jun, 19(12), 1261 - 3
Cryptosporidiosis after CD34-selected autologous peripheral blood stem cell transplantation (PBSCT) . Treatment with paromomycin, azithromycin and recombinant human interleukin-2; Nachbaur D et al.; We report two cases of cryptosporidiosis after CD34-selected PBSCT for lymphoma . While the first patient died of pulmonary cryptosporidiosis, treatment with paromomycin, azithromycin and subcutaneous low-dose rhIL-2 to improve numerical and functional T lymphocyte defects completely eliminated infection in the second patient . We conclude, that the removal of mature T lymphocytes by positive selection of CD34+ cells bears the risk of a delayed immune reconstitution resulting in an increased incidence of severe and sometimes fatal opportunistic infections . IL-2 might be useful in this situation by accelerating immune reconstitution and reducing the danger of opportunistic infections.

Antimicrob Agents Chemother, 1997 Jun, 41(6), 1399 - 402
Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers; Rodvold KA et al.; The steady-state concentrations of clarithromycin and azithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers . Mean plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin concentrations were similar to those previously reported . Clarithromycin was extensively concentrated in ELF (range of mean +/- standard deviation concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h) and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h) . The concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22 +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h to 41.7 +/- 12.1 microg/ml at 24 h . The concentrations of 14-(R)-hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to 31.3 +/- 17.7 microg/ml at 24 h . During the period of 24 h after drug administration, azithromycin and clarithromycin achieved mean concentrations in ELF and AM higher than the concomitant concentrations in plasma.

J Antimicrob Chemother, 1997 May, 39(5), 623 - 30
Delivery of azithromycin to Chlamydia trachomatis-infected polarized human endometrial epithelial cells by polymorphonuclear leucocytes; Paul TR et al.; An in-vitro model was designed to evaluate whether polymorphonuclear leucocytes (PMN) loaded with azithromycin could migrate and deliver the antibiotic in a bioactive form to chlamydia inclusions in polarized human endometrial epithelial (HEC-1B) cells infected with Chlamydia trachomatis . PMN chemotaxis through the extracellular matrix and between infected epithelial cells was readily observed if the HEC-1B cells had been infected with chlamydiae for 36 or 48 h . Inclusions in infected epithelial cells exposed to PMN loaded with azithromycin were initially distinguished by deformed reticulate bodies and an excessive amount of chlamydial outer membrane vesicles . As the amount of PMN-delivered antibiotic increased, chlamydial inclusions were filled with large cell envelope 'ghosts' which were the remnants of lysed reticulate bodies . The lethal effect of azithromycin was confirmed by a reduction in the viability of infectious progeny . Our results demonstrate that the damage to chlamydiae was due to transport and delivery of azithromycin by PMN to infected genital epithelial cells . When infected HEC-1B cells were exposed to PMN not loaded with the antibiotic, chlamydial morphology was not obviously affected yet few viable progeny could be recovered . In this case, PMN-induced damage to host epithelial cells probably interrupted chlamydial nutrient acquisition and subsequent maturation and formation of infectious progeny.

Clin Pharmacol Ther, 1997 May, 61(5), 554 - 62
Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents; Iatsimirskaia E et al.; Biotransformation of rifabutin, an antibiotic used for treatment of tuberculosis in patients infected with the human immunodeficiency virus (HIV), and its interactions with some macrolide and antifungal agents were studied in human intestinal and liver microsomes . Both liver and enterocyte microsomes metabolized rifabutin to 25-O-deacetylrifabutin, 27-O-demethylrifabutin, and 20-, 31-, and 32-hydroxyrifabutin . The same products (except 25-O-deacetylrifabutin) were formed by microsomes from lymphoblastoid cells that contained expressed CYP3A4 . The apparent Michaelis-Menten constant (Km); approximately 10 to 12 mumol/L) and maximal velocity (Vmax; approximately 100 pmol/min/mg of protein) values for CYP-mediated metabolism were similar in liver and enterocyte microsomes . Deacetylation of rifabutin (Km approximately 16 to 20 mumol/L and Vmax approximately 50 to 100 pmol/min/mg of protein) was catalyzed by microsomal cholinesterase . Clarithromycin, ketoconazole, and fluconazole inhibited CYP-mediated metabolism of rifabutin in enterocyte microsomes equally or more potently than in liver microsomes but had no effect on cholinesterase activity . Azithromycin did not inhibit in vitro metabolism of rifabutin . This study provides evidence that CYP3A4 and cholinesterase are major enzymes that biotransform rifabutin in humans and that intestinal CYP3A4 contributes significantly to rifabutin presystemic first-pass metabolism and drug interactions with macrolide and antifungal agents.

Clin Infect Dis, 1997 May, 24(5), 958 - 64
Relationship of adverse events to serum drug levels in patients receiving high-dose azithromycin for mycobacterial lung disease; Brown BA et al.; We treated 39 elderly human immunodeficiency virus-noninfected patients with Mycobacterium avium complex and/or Mycobacterium abscessus lung disease with azithromycin (600 mg daily), given initially as monotherapy . Adverse events occurred in 33 of 39 patients (85%) receiving azithromycin alone, most commonly gastrointestinal (GI) symptoms (32 of 39, or 82%) and hearing impairment (10 of 39, or 26%) . Twenty-four of 39 patients (62%) required a lower dose or withdrawal of the drug . The mean serum level in patients who required a dose reduction because of hearing impairment was 0.8 +/- 0.4 microg/mL, and that in patients whose reduction was necessitated by GI symptoms was 0.7 +/- 0.4 microg/mL; in comparison, the mean serum level was 0.3 +/- 0.16 microg/mL in patients with no adverse events (P = .004 and .003, respectively) . Decreasing the daily dose to 300 mg resulted in resolution of most adverse events . Serum levels with monotherapy were comparable to levels after the addition of other antituberculous drugs that included rifampin or rifabutin . Thus, a 300-mg rather than 600-mg daily dose of azithromycin is better tolerated by elderly patients, and serum levels appear unaffected by other antituberculous agents, including rifampin.

Curr Opin Pulm Med, 1997 Mar, 3(2), 139 - 45
Nontuberculous mycobacteria; Griffith DE; The nontuberculous mycobacteria (NTM), especially Mycobacterium avium complex, are being recognized with increasing frequency as clinical pathogens, not only as a cause of disseminated disease in patients with AIDS but also as a cause of chronic lung disease in patients without AIDS . These infections have traditionally been difficult and frustrating to treat; however, the introduction of new agents, such as clarithromycin, azithromycin, and rifabutin, has significantly improved outcome for patients with some NTM infections . The new therapeutic regimens can be associated with severe toxicities and drug interactions that dictate the need for careful monitoring of patients undergoing treatment for M . avium complex disease . Clinicians will be called on with increasing frequency to determine the significance of NTM isolated from their patients . This determination will require knowledge about the pathogenicity and the appropriate therapy of a variety of NTM species.

Minerva Med, 1997 Mar, 88(3), 117 - 9
{Azithromycin combined with pyrimethamine in the treatment of neurotoxoplasmosis, in an AIDS patient}; Trotta M et al.; We report one case of successful treatment of cerebral toxoplasmosis in acquired immunodeficiency syndrome (AIDS) with azithromycin combined with pyrimethamine . Toxoplasmic encephalitis had been diagnosed on the basis of multiple lesions exhibiting ring like contrast enhancement on double contrast Computed Tomographic (CT) scan of the brain . Thereby our patient had been treated with pyrimethamine 25 mg/die, after an attack dose of 100 mg in the first day, and clindamycin 2400 mg/die, because of sulfa-drug allergy, but clindamycin had to be discontinued because of rash development . At this point azithromycin, at a dose of 1000 mg/die for 21 days and 1500 mg a week for the following 50 days of follow-up, was added to pyrimethamine . Follow-up CT scan after 20 days of treatment (10 with clindamycin+pyrimethamine and 10 with azithromycin+pyrimethamine) revealed partial resolution of the brain lesions and subsequently (after 50 and 80 days of treatment) complete resolution.

Clin Infect Dis, 1997 Mar, 24(3), 363 - 8
A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the treatment of trachoma in children; Dawson CR et al.; Trachoma, an infectious keratoconjunctivitis caused by Chlamydia trachomatis, is a leading cause of preventable blindness in developing countries . In this study we compared oral azithromycin with oxytetracycline/polymyxin eye ointment (once daily for 5 days every 4 weeks; total of six treatment cycles) for the treatment of active endemic trachoma in 168 rural Egyptian children . A suspension of azithromycin was administered to children as a dose of 20 mg/kg by one of three schedules: a single dose, one dose a week for 3 weeks, and one dose every 4 weeks for a total of six doses . The children's clinical status and chlamydial infection rates were evaluated for 1 year . The clinical cure rates were 35% 2 months after initial treatment, 16% at 8 months (during the annual autumn epidemic of purulent conjunctivitis), and 47% at 1 year . The pretreatment chlamydial infection rate of 33% (determined by direct immunofluorescence) decreased to 5% at 2 months and was 9% at 12 months . There were no significant clinical or laboratory differences among the four treatment groups . Thus, 1-6 doses of azithromycin were equivalent to 30 days of topical oxytetracycline/polymyxin ointment and may offer an effective alternative means of controlling endemic trachoma.

Med Clin North Am, 1997 Mar, 81(2), 361 - 79
Nontuberculous mycobacterial infections; French AL et al.; The acquired immunodeficiency syndrome (AIDS) pandemic has led to greater understanding and respect for the pathogenic potential of non-tuberculous mycobacteria . Mycobacterium avium complex (MAC) has emerged as the most common systemic bacterial infection in AIDS, causing debilitating disseminated disease in late-stage HIV-infected patients . With the release of the macrolide antibiotics, clarithromycin and azithromycin, effective and well-tolerated therapeutic regimens for MAC have been developed which prolong survival and increase quality of life . The macrolides and rifabutin are also effective as preventive therapy for MAC in patients with AIDS . Mycobacterium kansasii, which causes pulmonary disease similar to tuberculosis as well as disseminated disease in AIDS, is treatable with isoniazid, rifampin and ethambutol . Clinical syndromes and therapeutic options for other non-tuberculous mycobacteria in AIDS are also reviewed.

Int J STD AIDS, 1997 Feb, 8(2), 124 - 9
Pilot studies of azithromycin, letrazuril and paromomycin in the treatment of cryptosporidiosis; Blanshard C et al.; Pilot studies of the safety and efficacy of 3 drugs thought to have anticryptosporidial activity were carried out to determine whether any of them are suitable for large-scale clinical trials . Open studies of the use of azithromycin, letrazuril and paromomycin in patients with acquired immunodeficiency syndrome (AIDS) and confirmed cryptosporidial diarrhoea for at least a month . Azithromycin 500 mg daily was ineffective . Letrazuril 150-200 mg daily was associated with an improvement in symptoms in 40% of patients treated and cessation of excretion of cryptosporidial oocysts in the stool in 70%; however biopsies remained positive . Paromomycin therapy was associated with a complete resolution of diarrhoea in 60% of patients treated and some improvement in symptoms in a further 5% but it did not eliminate the infection . None of the drugs had any major toxicities . Dose escalation studies of azithromycin should be performed . Letrazuril should be further investigated for efficacy in double-blind placebo-controlled trials . Paromomycin appears to result in prolonged symptomatic remission of cryptosporidial diarrhoea, but has no effect on cryptosporidial cholangitis.

Ann Med Interne (Paris), 1997, 148(2), 167 - 71
{Current status in the prevention of Mycobacterium avium complex infections in patients with HIV infection}; Doco-Lecompte T et al.; Mycobacterium avium complex (MAC) infections in AIDS are increasingly common and contribute to the mortality in severe immunocompromised patients . In this paper, we review the published studies on the prevention of the MAC infections . Rifabutin and the new macrolides (clarithromycin, azithromycin) are shown to be effective in the primary prevention . However, they can fail and are difficult to manage with the antiretroviral treatment, specially antiproteases and prevention of the other opportunistic infections . For the prevention of the relapse of the MAC infections, it is necessary to give a prolonged treatment with a bio-therapy associating at least a new macrolide with rifabutin or ethambutol, which is also difficult to manage with the other treatments.

J Antimicrob Chemother, 1997 Jan, 39(1), 45 - 51
In-vitro activity of atovaquone, sulphamethoxazole and dapsone alone and combined with inhibitors of dihydrofolate reductase and macrolides against Pneumocystis carinii; Cirioni O et al.; The anti-Pneumocystis carinii activity of atovaquone, dapsone and sulphamethoxazole alone and combined with dihydrofolate reductase (DHFR) inhibitors and macrolides was investigated against five clinical isolates of P . carinii . The susceptibility tests were performed by inoculation of the organisms on to cell monolayer and parasite count after 72 h incubation at 37 degrees C . Culture plates were added to Dulbecco's modified Eagle's medium containing serial dilutions of atovaquone, dapsone and sulphamethoxazole alone or in combination with diaveridine, pyrimethamine, trimethoprim, azithromycin, clarithromycin and roxithromycin . Atovaquone, dapsone and sulphamethoxazole were found to be effective at levels well below the concentrations that could be achieved clinically, while DHFR inhibitors were shown to combine effectively with dapsone and sulphamethoxazole . No synergy could be demonstrated between atovaquone and DHFR inhibitors or macrolides . A mild synergic effect was noted when macrolides were combined with dapsone and sulphamethoxazole . Pyrimethamine (0.5 mg/L) combined with dapsone and trimethoprim (0.5 mg/L) combined with sulphamethoxazole exerted the strongest inhibitory effect.

Eur J Gastroenterol Hepatol, 1997 Jan, 9(1), 45 - 8
Short-term low-dose triple therapy with azithromycin, metronidazole and lansoprazole appears highly effective for the eradication of Helicobacter pylori; Caselli M et al.; BACKGROUND: Although the OCN (omeprazole, clarithromycin and nitroimidazoles) short-term low-dose regimens are regarded as 'the standard' in the treatment of Helicobacter pylori infection, azithromycin is a new-generation, acid-stable macrolide which may prove particularly useful for a new short-term low-dose triple therapy regimen . OBJECTIVE: To further improve OCN eradication treatments by reducing both the number of pills and the total cost . METHODS: A new short-term low-dose triple therapy (LAM) using lansoprazole 30 mg once a day for 1 week, azithromycin 500 mg once a day for 3 days, and metronidazole 250 mg twice a day for the same 3 days, was administrated to 60 patients presenting with H . pylori-positive gastritis with or without peptic ulcer, and compared with the classic 'Bazzoli regimen' (OCT: omeprazole, clarithromycin, tinidazole) in 60 matched patients . H . pylori infection before and after therapy was evaluated by a rapid urease test, conventional histology and toluidine-stained semi-thin sections . Three biopsies from the corpus and three from the antrum were taken during endoscopical examination before and 7-8 weeks after discontinuation of the treatment . Patient compliance, drug tolerance and drug costs were also taken into consideration . RESULTS: H . pylori infection was eradicated 7-8 weeks after treatment in 56 of the 60 patients in the LAM group (93.3%), and in 52 of the 57 patients in the OCT group who completed the treatment (91.2%), with no statistical difference . When gastric or duodenal ulceration was present, ulcer healing was observed in all cases . CONCLUSION: The new proposed short-term low-dose triple therapy (LAM) appears to be as effective as the OCT for the eradication of H . pylori infection . The new treatment, however, seems to have advantages in terms of drug tolerance, patient compliance and therapy cost.

BMJ . 1996 Dec 7;313(7070):1428.
Who steps up efforts against trachoma; Kmietowicz Z; PIP: The World Health Organization (WHO) has developed a strategy, SAFE, to eradicate trachoma globally: it includes surgery for trichiasis, antibiotics, facial cleanliness, and environmental improvement . Goals of the alliance of governments, international organizations, and nongovernmental organizations assembled by WHO include: 1) to identify countries where trachoma is epidemic; 2) to map the disease; 3) to initiate community-based hygiene programs; and 4) to make surgery widely available . 15% of the world's blindness is due to trachoma; about 6 million people have been irreversibly blinded, and an estimated 146 million require treatment to avoid blindness . David Mabey, professor of communicable diseases at the London School of Hygiene and Tropical Medicine, describes trachoma, which is spreading in Africa, as "the forgotten disease of the poorest people in the world." The disease, which is caused by Chlamydia trachomatis, is associated with overcrowding, poor hygiene, and limited access to water and sanitation . Contact with the eye discharge of an infected person, or with flies that seek eyes, transmits the disease . Treatment with tetracycline requires daily doses of eye ointment for 6 weeks . Azithromycin, which is expensive, can be given in 1 dose, and is currently being tested . Since people are reinfected quickly, whole communities are being treated in studies in Gambia and Tanzania . A vaccine is being developed .

Semin Respir Infect, 1996 Dec, 11(4), 301 - 10
New developments in the treatment of nontuberculous mycobacterial (NTM) disease; Griffith DE et al.; Until recently, therapy for most Nontuberculous Mycobacterial (NTM) disease, especially disease caused by Mycobacterium avium-complex (MAC), has been difficult and frustrating . The introduction of the newer macrolides (clarithromycin and azithromycin) has significantly added to the efficacy of regimens for both disseminated and pulmonary MAC disease . Clinical activity of these agents is lost when a MAC isolate develops in-vitro resistance that is facilitated by use of the macrolides as single agents . These valuable drugs should, therefore, never be used as single agents for the treatment of disseminated or pulmonary MAC disease . The newer macrolides also show promise for the treatment of other NTM infections such as those caused by M . abscessus, M . fortuitum, M . chelonae, M . xenopi, M . marinum, M . haemophilum, and M . genavense . Rifabutin, a derivative of rifamycin S, is an effective agent for prophylaxis against disseminated MAC and may have utility for treatment of pulmonary and disseminated MAC disease . Interactions between clarithromycin and rifamycin may alter efficacy of the macrolide and enhance toxicity of rifabutin . Although therapy of many NTM infections remains difficult with somewhat unpredictable results, the introduction of newer drugs, particularly the macrolides, has appreciably improved a previously dismal outlook for successful therapy.

Aliment Pharmacol Ther, 1996 Dec, 10(6), 1021 - 7
Cure of Helicobacter pylori infection in the elderly: effects of eradication on gastritis and serological markers; Pilotto A et al.; BACKGROUND: Specific data on anti-H . pylori treatments in elderly people are very scarce . The aim of the study was to evaluate in the elderly the efficacy of different anti-H . pylori therapies and the behaviour of serum anti-H . pylori antibodies, pepsinogen A and C, and PGA/PGC ratio induced by the anti-H . pylori treatment . METHODS: One hundred and twenty-one dyspeptic patients aged > 60 years (mean age, 73 years; range, 61-89 years) with H . pylori-positive gastric ulcers (17 patients), duodenal ulcers (33 patients) or chronic gastritis (71 patients) were treated with one of the following anti-H . pylori treatments: (A) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days; (B) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 mg q.d.s . for 7 days; (C) omeprazole 40 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 q.d.s . for 7 days; (D) omeprazole 20 mg/day plus clarithromycin 250 b.d . for 7 days; (E) omeprazole 20 mg/day plus clarithromycin 250 b.d . for 7 days plus metronidazole 250 q.d.s . for 7 days; and (F) omeprazole 40 mg/day plus clarithromycin 250 mg b.d . for 7 days plus metronidazole 250 mg q.d.s . for 7 days . At the baseline and 2 months after therapy, endoscopy and serum anti-H . pylori antibodies, pepsinogen A and C, and PGA/PGC ratio were measured . RESULTS: Ten patients (8.2%) dropped out of the study . Six patients (4.9%) reported side-effects . The eradication rates of the six regimens, expressed using intention-to-treat and per protocol analysis, were, respectively: (A) 39% and 44%; (B) 50% and 56%; (C) 65% and 77%; (D) 47% and 50%; (E) 85% and 90%; and (F) 83% and 87% . The triple therapy for regimens E and F was significantly more effective than dual therapies (regimens A and D; intention-to-treat = P < 0.007, per protocol = P < 0.001) or the triple therapy for regimens B and C (intention-to-treat = P < 0.009, per protocol = P < 0.03) . Patients cured of H . pylori infection showed a significant decrease in the activity of gastritis (P < 0.0001), a significant drop in IgG anti-H . pylori (P = 0.0004) and pepsinogen C (P < 0.0001), and an increase in PGA/PGC ratio (P < 0.001), while patients remaining H . pylori-positive showed no changes in the serum parameters . CONCLUSIONS: In the elderly, triple therapy with omeprazole+metronidazole+clarithromycin for 1 week is well tolerated and highly effective; anti-H . pylori antibody and PGC serum levels decrease soon after anti-H . pylori therapy only in patients cured of H . pylori infection.

Aliment Pharmacol Ther, 1996 Dec, 10(6), 997 - 1000
Helicobacter pylori eradication using one-week low-dose lansoprazole plus amoxycillin and either clarithromycin or azithromycin; Cammarota G et al.; AIM: To evaluate and compare two 1-week low-dose triple therapies based on lansoprazole, amoxycillin and a macrolide in eradicating Helicobacter pylori . METHODS: Seventy consecutive patients, suffering from dyspeptic symptoms with H . pylori infection, were randomly allocated to one of two treatment groups: (A) (LAC; n = 35) lansoprazole 30 mg once daily, amoxycillin 1000 mg b.d., clarithromycin 250 mg b.d., all for 7 days; and (B) (LAA; n = 35) lansoprazole 30 mg once daily and amoxycillin 1000 mg b.d., both for 7 days, plus azithromycin 500 mg once daily for only 3 days . The H . pylori status was evaluated by means of histology and rapid urease test at entry and 8 weeks after treatment . RESULTS: Three patients did not complete the treatment: one in the LAC group was withdrawn owing to severe side-effects; two patients in the LAA group stopped the treatment prematurely . H . pylori eradication was obtained in 28 of 34 (82%; 95% CI = 66-93%) patients in the LAC group and in 20 of 33 (61%; 95% CI = 42-77%) patients in the LAA group . The difference is significant (P < 0.029) . On intention-to-treat analysis, the rates of eradication were (28 of 35 patients, 80% in the LAC group and 20 of 35 patients, 57% in the LAA group . Side-effects occurred in nine (26%) and six (18%) patients in the LAC and LAA groups, respectively . CONCLUSIONS: Low-dose lansoprazole plus amoxycillin and clarithromycin is more effective than low-dose lansoprazole plus amoxycillin and azithromycin, but it gave a greater incidence of side-effects.

Chemotherapy, 1996 Nov-Dec, 42(6), 402 - 9
A linear model for the pharmacokinetics of azithromycin in healthy volunteers; Ripa S et al.; The pharmacokinetic profile of azithromycin, after oral ingestion of 500 mg, was determined in 10 healthy volunteers . Statistical and biochemical reason seemed to indicate a zero-order absorption of the drug . The disposition of azithromycin was described by a two-compartment model (plasma compartment and extravascular compartment) with elimination from the plasma compartment . The absorption process ends abruptly after a time T = 2.3 +/- 0.49 h, from the administration . The transfer rate constant from the plasma compartment to the extravascular compartment (k12 = 0.12 +/- 0.04 h-1) and the mean residence time of the drug in the extravascular compartment (MRT2 = 43.53 +/- 13.80 h) indicate a rapid and extensive distribution of azithromycin from the serum into the extravascular fluids . The results confirmed the efficacy of a single daily dose of 500 mg per os for clinical use.

J Infect, 1996 Nov, 33(3), 227 - 9
Response to oral and intravenous azithromycin in a patient with toxoplasma encephalitis and AIDS; Wiselka MJ et al.; We present a patient with AIDS and toxoplasma encephalitis who was unable to tolerate established therapy with sulphadiazine or clindamycin but responded to oral azithromycin and pyrimethamine . The patient was maintained on oral azithromycin but subsequently relapsed after 8 months . The recurrence was successfully treated with intravenous azithromycin . The case illustrates that azithromycin can be used to treat patients with toxoplasma encephalitis who are unable to tolerate or fail to respond to other therapeutic agents . Failure of oral azithromycin may be due to inadequate tissue concentrations and patients may further benefit from intravenous administration.

Antimicrob Agents Chemother, 1996 Nov, 40(11), 2582 - 5
Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses; Olsen KM et al.; The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses . Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered . Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high-performance liquid chromatography . Azithromycin was extensively concentrated in cells and ELF . Drug concentrations in AMs (peak mean +/- standard deviation, 464 +/- 65 micrograms/ml) exceeded 80 micrograms/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 +/- 28 micrograms/ml) exceeded 20 micrograms/ml up to 340 h (14 days) . Azithromycin concentrations in ELF peaked at 124 h (3.12 +/- 0.93 micrograms/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations . Although the clinical significance of antibiotic concentrations in these compartments is nuclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.

Antimicrob Agents Chemother, 1996 Nov, 40(11), 2577 - 81
Safety, toleration, and pharmacokinetics of intravenous azithromycin; Luke DR et al.; To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described . In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects . Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 {good} to 10 {poor}), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion . Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated . Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate . There were no consistent trends in endogenous motilin levels throughout the study . The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related . The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg . The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug . Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

Eur J Pharmacol, 1996 Oct 24, 314(1-2), 215 - 27
Interaction of the macrolide azithromycin with phospholipids . II . Biophysical and computer-aided conformational studies; Montenez JP et al.; In a comparison paper, we show the azithromycin causes a lysosomal phospholipidosis in cultured cells, binds in vitro to negatively charged bilayers without causing aggregation or fusion, and inhibits lysosomal phospholipase A1 . In this paper, we show that azithromycin decreases the mobility of the phospholipids in negatively charged liposomes (using 31P nuclear magnetic resonance) and that it increases the fluidity of the acyl chains close to the hydrophilic/hydrophobic interface, but not deeper into the hydrophobic domain (assessed by measuring the fluorescence polarization of trimethylammonium-diphenylhexatriene and diphenyhexatriene, respectively) . Computer-aided conformational analysis of mixed monolayers of azithromycin and phosphatidylinositol shows that the drug can be positioned largely in the hydrophobic domain, but close to the interface, with the macrocycle facing the C1 of the fatty acids (allowing the N9a endocyclic tertiary amine to interact with the phospho-groups), the cladinose located on the hydrophobic side of the lipid/water interface and the desosamine projected into the hydrophobic domain . This position is consistent with the experimental data . Analysis of virtual molecules shows that this unanticipated behavior to the shielding of the ionizable N3' amino-group in the desosamine by methyl-groups, and to the wide dispersion of hydrophobic domains all over the molecule . The interaction of azithromycin with phospholipids may account for some of its unusual pharmacokinetic properties and for its potential to cause lysosomal phospholipidosis.

Eur J Pharmacol, 1996 Oct 24, 314(1-2), 203 - 14
Interaction of the macrolide azithromycin with phospholipids . I . Inhibition of lysosomal phospholipase A1 activity; Van Bambeke F et al.; Azithromycin, the first clinically developed dicationic macrolide antibiotic, displays an exceptional accumulation in lysosomes of cultured cells . In fibroblasts incubated with 50 mg/l (66.6 microM), it induces a distinct phospholipidosis as evidenced by biochemical and ultrastructural criteria, which strikingly resembles alterations described previously with gentamicin, a pentacationic aminoglycoside antibiotic which inhibits the lysosomal catabolism of phospholipids . We show that both drugs inhibit, in an equimolar manner, the activity of phospholipase A1 (assayed for phosphatidylcholine, included in negatively charged liposomes), in a way consistent with the model of 'charge neutralization' proposed already for gentamicin (Mingeot-Leclercq et al., 1988, Biochem . Pharmacol . 37, 591) . Both drugs bind to negatively charged liposomes . Yet, in spite of this binding, azithromycin does not induce aggregation or fusion of negatively charged vesicles, under conditions in which gentamicin (or spermine, a fully hydrophilic polycation) causes a massive aggregation, and bis(beta-diethylaminoethylether)hexestrol (a dicationic amphiphile) causes fusion . The molecular interactions of azithromycin with acidic phospholipids are further examined in a companion paper.

Enferm Infecc Microbiol Clin, 1996 Oct, 14(8), 466 - 9
{Coinfection by mycobacteria in HIV-positive patients}; von Wichmann MA et al.; BACKGROUND: The aim of this study was to describe the clinical characteristics and therapeutic management of coinfection by mycobacteria in the authors hospital . METHODS: Two cases of coinfection detected in mixed cultures in agar 7H11 or simultaneous positive cultures in several evaluable clinical samples (blood cultures for MAI and M . kansasii and sputum or stools for M . tuberculosis) . RESULTS: One coinfection by MAI and M . tuberculosis and another by MAI and M . kansasii in two severely immunosuppressed HIV positive patients with less than 0.010 CD4 lymphocytes/10(9)/l . The clinical manifestations were unspecific, with fever and deterioration of the general state predominating over the 30-45 days of evolution . One of the patients improved with treatment which, in both cases, included a macrolide . Survival was very short and death was by intercurrent causes . CONCLUSIONS: For the diagnostic of coinfection in severely immunosuppressed patients multiple organic samples should be taken and appropriately processed to detect the mixed cultures or the presence of different mycobacteria in different samples from the same patients . Although the diagnosis of the species is fundamental, the empiric treatment of a disease by mycobacteria in severely immunosuppressed patients should include at least: ethambutol and clarithromycin or azithromycin in addition to other first line tuberculostatic drugs until definitive identification.

Jpn J Antibiot, 1996 Oct, 49(10), 932 - 8
{Therapy with azithromycin in pediatric infections}; Kuroda Y et al.; Azithromycin (AZM) was orally administered to 12 pediatric patients with the following bacterial infections: pharyngitis in four cases, tonsillitis in one, pharyngo-bronchitis in two, and mycoplasmal pneumonia in five . In eleven of the twelve cases (91.7%) was the drug found effective . Neither abnormal clinical findings nor abnormal laboratory test results changes were observed . Eleven of the twelve pediatric patients claimed that the formulation of the drug is easy to take . The above results suggest that AZM is a useful antibiotic drug in the treatment of pediatric patients with bacterial infections.

J Antimicrob Chemother, 1996 Oct, 38(4), 727 - 31
The in-vitro anti-rickettsial activity of macrolides; Keysary A et al.; The anti-rickettsial activity of azithromycin and clarithromycin was studied in Vero cells . The rate of rickettsial inhibition-growth caused by both macrolides was determined using rickettsial counts and ELISA . Both macrolides inhibited > 50% the growth of Rickettsia conorii and Rickettsia typhi at concentrations of 1.0 and 0.1 mg/L, respectively . The growth of Coxiella burnetii was inhibited to a rate of > or = 50% at the concentrations of 0.01 and 1.0 mg/L of azithromycin and clarithromycin, respectively.

Pharm Res, 1996 Oct, 13(10), 1507 - 13
Predicting injection site muscle damage . I: Evaluation of immediate release parenteral formulations in animal models; Sutton SC et al.; PURPOSE: The current animal model generally accepted by the pharmaceutical industry and the FDA for assessment of muscle damage following intramuscular injection (IM) is the rabbit lesion volume model (RbLV) . However, this model is resource intensive . The goal of this study was to find a resource sparing alternative to the rabbit lesion model for assessing injection site toleration in IM formulation screening . METHODS: Short term animal model alternatives to RbLV for evaluating IM formulations were examined . In addition to RbLV, myeloperoxidase (MPO), p-nitrophenyl N-acetyl-beta-glucosaminide (NA beta G) and/or plasma creatine phosphokinase (CK) activities were determined in rabbits (Rb) and rats (Rt) after injection of formulations (digoxin, azithromycin and danofloxacin) . The edema from these formulations 24 hr after subcutaneous injection into the rat footpad (RFE) was also determined . RESULTS: MPO and NA beta G were not considered very useful as biochemical predictors of muscle damage for these formulations . Histology generally correlated with RbLV values . Compared to saline, RbLV was marked for all formulations within 1-3 days of injection . After day 3, lesions quickly resolved, and no significant differences were found . For these formulations, all CK animal models and RFE were generally predictive of RbLV . A formulation with RtCK > 1000 U/L or RbCK > 3000 U/L, was predicted to be poorly, tolerated . CONCLUSIONS: Due to ease, number of animals, time and intrinsic mechanism, we concluded that for most formulations, 2 and 4 hr RtCK data alone should be reasonably predictive of muscle damage.

Antimicrob Agents Chemother, 1996 Oct, 40(10), 2375 - 9
Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin; Patel KB et al.; The bronchopulmonary and plasma pharmacokinetics of clarithromycin (CLA; 500 mg given twice daily for nine doses) or azithromycin (AZ; 500 mg for the first dose and then 250 mg once daily for four doses) were assessed in 41 healthy nonsmokers . Bronchoalveolar lavage was performed at 4, 8, 12, or 24 h after administration of the last dose . The concentrations (mean +/- standard deviation) of CLA, 14-hydroxyclarithromycin, and AZ were measured in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) cells by high-performance liquid chromatography assay . The concentrations of CLA achieved in ELF were 34.02 +/- 5.16 micrograms/ml at 4 h, 20.63 +/- 4.49 micrograms/ml at 8 h, 23.01 +/- 11.9 micrograms/ml at 12 h, and 4.17 +/- 0.29 microgram/ml at 24 h, whereas at the same time points AZ concentrations remained below the limit of assay sensitivity (0.01 microgram/ml) for all but two subjects . The concentrations of CLA in the AM cells were significantly higher than those of AZ at 8 h (703 +/- 235 and 388 +/- 53 micrograms/ml, respectively) . However, the ratio of the concentration in AM cells/concentration in plasma was significantly higher for AZ than for CLA for all time points because of the lower concentration of AZ in plasma . These results indicate that while AZ has higher tissue concentration to plasma ratios, as shown by other investigators, the absolute concentrations of CLA in AM cells and ELF are higher for up to 8 and 12 h, respectively, after administration of the last dose.

Southeast Asian J Trop Med Public Health, 1996 Sep, 27(3), 522 - 5
Activity of artemether-azithromycin versus artemether-doxycycline in the treatment of multiple drug resistant falciparum malaria; Na-Bangchang K et al.; The efficacy of the combination of artemether with doxycycline or azithromycin was evaluated in 60 patients with acute uncomplicated falciparum malaria who attended malaria clinic in Mae Sot, Tak Province (Thai-Myanmar border) . Patients (30 each) were randomized to receive (a) 300 mg artemether together with 100 mg doxycycline as initial doses, followed by 100 mg artemether plus 100 mg doxycycline at 12 hours later, then 100 mg doxycycline every 12 hours for another 4 days, or (b) 300 mg artemether together with 500 mg azithromycin, followed by 250 mg azithromycin at 24 and 48 hours . The follow-up period was 28 days . Patients in either group had a rapid initial response to treatment with comparable PCT and FCT . The cure rate of artemether-azithromycin regimen was significantly lower than that of artemether-doxycycline regimen (14.8 vs 53.3%) . Low cure rate from artemether-azithromycin combination in this study was likely to be due to inadequate azithromycin dosage . However, with the low incidence of gastrointestinal adverse effects, the once daily dose of azithromycin could still be increased in order to enhance its clinical efficacy . The simplicity of drug administration and lesser incidence of adverse effects make azithromycin a more proper partner of artemether than doxycycline . Further dose-finding and pharmacokinetic study with the artemether-azithromycin combination is encouraging.

Panminerva Med, 1996 Sep, 38(3), 145 - 9
Evaluation of the efficacy and tolerability of four different therapeutic regimens for the Helicobacter pylori eradication; Tursi A et al.; The aim of our study is to evaluate the efficacy and tolerability of four different therapeutic regimens for Helicobacter pylori eradication . One-hundred and thirty-two consecutive patients suffering from either peptic ulcer or non-ulcer dyspepsia, with Helicobacter pylori infection, were allocated to one of the following 4 groups with different therapeutic regimens: A) omeprazole 20 mg bid for 14 days/amoxycillin 1000 mg bid for 14 days/tinidazole 500 mg bid for 14 days (30 patients, 13 with peptic ulcer); B) omeprazole 20 mg bid for 14 days/amoxycillin 1000 mg bid for 14 days (41 patients, 23 with peptic ulcer); C) omeprazole 20 mg bid for 14 days/azithromycin 500 mg/day for 3 days for 2 consecutive weeks (25 patients, 12 with peptic ulcer); D) omeprazole 20 mg/day for 7 days/clarithromycin 250 mg bid for 7 days/tinidazole 500 mg bid for 7 days/ (36 patients, 14 with peptic ulcer) . The Helicobacter pylori status was evaluated by means of histology, culture and urease test, at entry and 8 weeks after treatment . 2 group A, B and D patients, 1 D patient didn't complete the treatment . In evaluable patients, the Helicobacter pylori eradication was obtained in 24 patients of group A (85.71%), in 24 of group B (58.98%), in 11 of group C (45.83%) and in 24 of group D (70.58%) . On intention-to-treat analysis, Helicobacter pylori eradication was 80% in group A, 56.09% in group B, 44% in group D and 66.67% in group D . Sideeffects occurred in 6 patients of group A (20.68%), in 5 of group B (12.5%), in 3 group D (8.82%) and none of group C . In conclusion, triple therapy with omeprazole/clarithro-mycin/tinidazole is better for cost/benefit ratio; omeprazole/amoxycillin/tinidazole is more effective than others regimens in the Helicobacter pylori eradication, but causes more side effects; double therapy with omeprazole/azithromycin is the most tolerable and the least efficacy for Helicobacter pylori eradication.

J Int Med Res, 1996 Sep-Oct, 24(5), 407 - 18
Comparison of azithromycin and co-amoxiclav in the treatment of acute tracheobronchitis and acute infectious exacerbations of chronic bronchitis in adults . Azithromycin Study Group; Biebuyck XA; Azithromycin, a broad-spectrum azalide, and co-amoxiclav were compared in a randomized, multicentre, open-label trial in 759 patients treated for acute tracheobronchitis (n = 620) or acute infectious exacerbations of chronic bronchitis (n = 139) . Patients were randomized (2:1) to a 3-day regimen of two azithromycin 250 mg capsules once daily or a 5-10-day regimen of co-amoxiclav, one 625 mg tablet three times daily . Azithromycin produced a significantly higher cure rate (70.6% versus 61.1%) than co-amoxiclav (P = 0.011) and there were fewer failures (7.8% versus 13.6%) and relapses in the azithromycin-treated group, giving a higher overall response rate for azithromycin (89.7% versus 80.2%, P = 0.0003) . With azithromycin, compliance was better than with co-amoxiclav and there was a significantly shorter time to improvement or cure . A higher incidence of adverse events, mostly gastrointestinal, was reported by patients taking co-amoxiclav (21.3% versus 14%, P = 0.0097), causing more patients in this group to discontinue therapy (7% versus 1.2%, P = 0.00004).

Antimicrob Agents Chemother, 1996 Sep, 40(9), 2039 - 42
Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry; Wenisch C et al.; Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg) . Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration . Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria . Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly . Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median {range}, 62% {27 to 91%} of the control values; P < 0.01) and generate reactive oxygen products (75% {34 to 26%} of the control values; P < 0.01) . Clarithromycin resulted in reduced phagocytosis (82% {75 to 98%} of control values; P < 0.01) but did not alter reactive oxygen production (84% {63 to 113%} of the control values; P > 0.05) . Roxithromycin treatment did not affect granulocyte phagocytosis (92% {62 to 118%} of the control values; P > 0.05) or reactive oxygen production (94% {66 to 128%} of the control value; P > 0.05) . No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons) . These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.

Pediatr Infect Dis J, 1996 Sep, 15(9 Suppl), S24 - 9
A multicenter, randomized, open label comparison of azithromycin and amoxicillin/clavulanate in acute otitis media among children attending day care or school; Khurana CM; OBJECTIVE: This multicenter, randomized, open label study compared the efficacy and safety of azithromycin and amoxicillin/clavulanate for the treatment of acute otitis media among children who were attending a day-care facility or school . METHODS: Eligible children with acute otitis media from 21 US centers were randomized to treatment with 10 mg/kg of azithromycin oral suspension on Day 1, followed by 5 mg/kg once daily for the next 4 days or approximately 40 mg/kg/day of amoxicillin/clavulanate suspension in 3 divided doses for 10 days . Clinical efficacy was evaluated on Days 14, 30 and 45 . Acceptance and convenience of the medications were assessed on Day 14 by parent interviews with a standardized questionnaire . RESULTS: Of the 263 children enrolled in the study, 233 were evaluable at the primary evaluation 45 days after the start of treatment . Satisfactory clinical response rates (cure, delayed cure and improvement) were 60.5% in patients treated with azithromycin and 64.9% in patients treated with amoxicillin/clavulanate . Satisfactory clinical response rates at secondary evaluations were also comparable: 92.2% vs . 90.0% at Day 14 and 66.7% vs . 72.7% at Day 30 in patients treated with azithromycin and amoxicillin/clavulanate, respectively . No significant differences in treatment failures, relapses or recurrences were noted with either medication . Azithromycin was significantly better tolerated and caused fewer treatment-related adverse events (7.2%) than amoxicillin/clavulanate (17.1%) (P < 0.001) . In response to the interview and questionnaire, parents of children treated with azithromycin noted less need for special arrangements to give medication (2.0% vs . 14.9%) . Children liked the taste of azithromycin (89.2%) and did not have to be forced to take the medication (2.4%) . Parents of children receiving amoxicillin/clavulanate noted that 61.8% liked the medication and 19.4% of children had to be forced to take it . CONCLUSIONS: This study demonstrates that azithromycin was comparable to amoxicillin/clavulanate in achieving satisfactory clinical response rates in children with acute otitis media attending day care or school . Azithromycin was significantly better tolerated than amoxicillin/ clavulanate . Parents considered azithromycin to be significantly more convenient to administer and more acceptable to children.

Pediatr Infect Dis J, 1996 Sep, 15(9 Suppl), S20 - 3
A multicenter, double blind comparison of azithromycin and amoxicillin/ clavulanate for the treatment of acute otitis media in children; McLinn S; OBJECTIVE: To compare the efficacy and safety of azithromycin and amoxicillin/clavulanate in pediatric acute otitis media . METHODS: Investigators from 12 US centers recruited 677 children . In a randomized, double blind, double dummy fashion, participants received either azithromycin suspension (n = 341) once daily for 5 days or amoxicillin/clavulanate suspension (n = 336) in three divided doses daily for 10 days . RESULTS: Among evaluable patients satisfactory clinical response rates (cured and improved) measured 11 days after therapy began were 87.5% in the azithromycin group and 87.9% in the amoxicillin/clavulanate group; corresponding rates at 30 days were 73.5% in the azithromycin and 71.2% in the amoxicillin/clavulanate groups . Relapse rates were comparable for the treatment groups . Treatment-related side effects, primarily gastrointestinal, were reported significantly less frequently with azithromycin (8.8%) than with amoxicillin/clavulanate (30.8%) (P < 0.0001) . Two (0.6%) azithromycin patients and 12 (3.6%) amoxicillin/ clavulanate patients discontinued therapy because of treatment-related side effects (P < 0.006 between groups) . CONCLUSIONS: In these children with acute otitis media, azithromycin given once daily for 5 days and amoxicillin/clavulanate given three times daily for 10 days had similar efficacy; however, azithromycin was significantly better tolerated.

N Engl J Med, 1996 Aug 8, 335(6), 392 - 8
Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both . California Collaborative Treatment Group; Havlir DV et al.; BACKGROUND: Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection . Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing . METHODS: We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter . The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs . They were monitored monthly with blood cultures for M . avium complex . RESULTS: In an intention-to-treat analysis, the incidence of disseminated M . avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs . The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, 0.53; P = 0.008) . The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, 0.28; P<0.001) or azithromycin alone (hazard ratio, 0.53; P = 0.03) . Among the patients in whom azithromycin prophylaxis was not successful, 11 percent of M . avium complex isolates were resistant to azithromycin . Dose-limiting toxic effects were more common with the two-drug combination than with azithromycin alone (hazard ratio, 1.67; P=0.03) . Survival was similar in all three groups . CONCLUSIONS: For protection against disseminated M . avium complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates . Rifabutin plus azithromycin is even more effective but is not as well tolerated.

Am J Trop Med Hyg, 1996 Aug, 55(2), 219 - 22
Atovaquone in the treatment of Babesia microti infections in hamsters; Wittner M et al.; The traditional therapy for the treatment of human Babesia microti infections has been the combination of clindamycin and quinine . However, in recent years, it has become apparent that some patients have not responded to this regimen . We became involved in the treatment of several cases of babesiosis in which atovaquone was used to treat this infection . Therefore, using the hamster model, we determined the efficacy of atovaquone alone as well as atovaquone plus azithromycin for the treatment of experimental babesiosis . Atovaquone (100 mg/kg/day) and atovaquone (100 mg/kg/day) with azithromycin (150 mg/kg/day) were effective agents for the treatment of experimental babesiosis in hamsters . When atovaquone was used as monotherapy recrudescences occurred . Organisms obtained from recrudescent animals, when inoculated into uninfected animals, proved to be unresponsive to atovaquone therapy, suggesting the emergence of drug resistance . Resistant organisms did not emerge in hamsters treated with the combination of atovaquone and azithromycin . Atovaquone should be considered in the therapeutic regimen of patients with babesiosis who have either failed standard therapy or have become intolerant to such therapy.

J Pediatr, 1996 Aug, 129(2), 297 - 300
Azithromycin therapy for Cryptosporidium parvum infection in four children infected with human immunodeficiency virus; Hicks P et al.; Cryptosporidium parvum intestinal infection in immunodeficient patients can cause severe intestinal fluid losses with severe dehydration or chronic diarrhea with malnutrition . Therapies tried in human beings and animals include paromomycin, clarithromycin, azithromycin, octreotide, hyperimmune bovine colostrum, and bovine transfer factor . No specific therapy has been found to be consistently beneficial to children . We report azithromycin treatment of four children with acquired immunodeficiency syndrome who had severe diarrheal illnesses in which Cryptosporidium parvum was the sole pathogen detected . Three of these children had a marked decrease in stool volume and frequency within 36 hours of initiating therapy and resolution of diarrhea within 5 days; Cryptosporidium organisms became undetectable on examination of stool or colonic biopsy or by both after therapy was discontinued . A fourth patient required prolonged therapy with azithromycin to achieve clearance . Azithromycin therapy should be considered for immunocompromised patients with intestinal Cryptosporidium infection.

J Antimicrob Chemother, 1996 Jun, 37 Suppl C, 125 - 31
A comparative study of the efficacy, safety and tolerability of azithromycin and cefaclor in the treatment of children with acute skin and/or soft tissue infections; Montero L; An open, multicentre study was carried out in 200 paediatric patients between 6 months and 12 years of age with skin and/or soft tissue infections (mild-to-moderate dermatological conditions and abscesses) to compare the efficacy and safety of azithromycin and cefaclor oral suspensions . Patients were randomly assigned to receive either azithromycin (10 mg/kg once daily for 3 days) or cefaclor (20 mg/kg/day in three divided doses for 10 days) . The clinical efficacy of both treatments was comparable: 92/98 (94%) of the evaluable azithromycin patients were cured or improved as were 93/98 (95%) of those treated with cefaclor . Before treatment, 74 pathogens were isolated from 60 of the azithromycin- and 80 pathogens from 66 of the cefaclor-treated patients . In the azithromycin group, 70/74 (95%) pathogens were eradicated, as were 79/80 (99%) pathogens in the cefaclor group . All 200 patients were evaluable for safety analyses . Both drugs were well tolerated, with a low incidence of side-effects: 3/100 (3%) in the azithromycin group and 2/100 (2%) in the cefaclor group . No patient in either treatment group withdrew from the study because of adverse events . In conclusion, azithromycin is as effective and as well tolerated as cefaclor in the treatment of children with skin and/or soft tissue infections.

J Antimicrob Chemother, 1996 Jun, 37 Suppl C, 63 - 9
An open study to compare azithromycin with cefaclor in the treatment of children with acute otitis media; Rodriguez AF; An open, multicentre study involving 259 children between 6 months and 13 years of age was performed to assess the efficacy and safety of azithromycin and to compare it with cefaclor as treatment of acute otitis media . Patients were randomized to receive either azithromycin 10 mg/kg once daily for 3 days or cefaclor 40 mg/kg daily in divided doses every 8 h for 10 days . Cure or improvement in signs and symptoms was observed in 112/114 (98%) evaluable azithromycin-treated patients and 116/120 (97%) evaluable cefaclor-treated patients on days 11-15 . In contrast to cefaclor, however, azithromycin was associated with a significantly (P = 0.033) higher cure rate 1 month after completion of treatment . In those patients who were followed up to days 25-30, the response was satisfactory (cure or improvement) in 31/32 (97%) patients who had received azithromycin and in 31/36 (86%) to whom cefaclor had been administered . Patients tolerated both treatments well and no severe adverse events related to therapy were recorded in either group . The results of this study show that a 3-day, once-daily regimen of azithromycin has comparable clinical efficacy and tolerability to a thrice-daily course of cefaclor administered for 10 days, but the azithromycin is associated with a lower incidence of relapse.

J Antimicrob Chemother, 1996 Jun, 37 Suppl C, 53 - 61
Penetration of azithromycin into middle ear effusions in acute and secretory otitis media in children; Pukander J et al.; In an open-label study, the concentrations of azithromycin in middle ear effusions and plasma were determined in 29 children between 1 and 8 years of age with a diagnosis of either secretory otitis media of at least 1 month's duration or acute otitis media . Azithromycin (10 mg/kg) was administered as a single dose 12, 24 or 48 h before the insertion of tympanostomy tubes to 17 children with secretory otitis media and once daily for 5 days (10 mg/kg on day 1, 5 mg/kg on days 2-5) to 12 children with acute otitis media . In the 16 evaluable patients with secretory otitis media, azithromycin penetrated middle ear effusions, with group mean concentrations approximately two orders of magnitude greater than the concurrent plasma concentrations 12, 24 and 48 h after administration . Similar plasma:effusion ratios were found 24 and 48 h after starting once-daily therapy in 10 evaluable patients with acute otitis media.

J Antimicrob Chemother, 1996 Jun, 37 Suppl C, 45 - 51
Concentrations of azithromycin in tonsilar and/or adenoid tissue from paediatric patients; Vaudaux BP et al.; Azithromycin levels in tonsillar and/or adenoid tissue were determined in children (1.6-7.5 years old) who were scheduled for surgical removal of their tonsils and/or adenoids . The children received azithromycin oral suspension 10 mg/kg once daily for 3 days . Tissue samples were obtained during surgery 1 (n = 4), 2 (n = 5), 4 (n = 6), or 8 (n = 5) days after the last dose of azithromycin . Serum samples were also obtained from four children in each of these groups at the time of surgery . Mean tissue concentrations of azithromycin were 10.33 +/- 3.01, 7.21 +/- 4.04, 9.30 +/- 3.74 and 1.49 +/- 0.48 mg/kg, respectively, 1, 2, 4 and 8 days after the last dose . At the corresponding times, serum concentrations were markedly lower: 47.25 +/- 19 . 19, 14.00 +/- 8.45, 8.00 +/- 2.16 and < 4 micrograms/L, respectively . The mean tissue:serum concentration ratios were, 227 +/- 54, 547 +/- 184 and 956 +/- 355, respectively, 1, 2 and 4 days after treatment . No adverse events attributable to azithromycin were observed in any of the 23 children who had received at least one dose of azithromycin . The study shows that levels of azithromycin in tonsillar and adenoid tissue were consistently higher than in serum and remained elevated up to 8 days after the end of dosing, supporting the use of a short-course (3-day), once-daily regimen of azithromycin in the treatment of upper respiratory tract infections.

J Antimicrob Chemother, 1996 Jun, 37 Suppl C, 37 - 44
The absence of an effect of food on the bioavailability of azithromycin administered as tablets, sachet or suspension; Foulds G et al.; Present product labelling indicates that azithromycin capsules should not be taken with food . However, three recent studies demonstrated that food does not significantly decrease the bioavilabilities of three new formulations of azithromycin (250 mg tablets, 1000 mg sachet, 500 mg paediatric suspension) . With a 500 mg dosage, the mean relative bioavailability of azithromycin following ingestion of a standard high-fat breakfast was 96% when administered as two 250 mg tablets and 113% when administered as a suspension . The mean relative bioavailability of a 1000 mg sachet was 112% . The absolute bioavailability of the sachet formulation, relative to a 1 h iv infusion of 1000 mg, was 44% . Thus, azithromycin tablets, suspension and sachet may be given without regard to meals, further enhancing the convenience of once-daily, short-duration dosing regimens.

J Am Geriatr Soc, 1996 Jun, 44(6), 665 - 70
The clinical usefulness of serum pepsinogens, specific IgG anti-HP antibodies and gastrin for monitoring Helicobacter pylori treatment in older people; Pilotto A et al.; OBJECTIVE: To evaluate the clinical usefulness of Pepsinogen A (PGA) and C (PGC), PGA/PGC ratio, gastrin, and specific IgG anti-HP antibodies (anti-HP Ab) in monitoring the effect of cure for Helicobacter pylori (HP) infection in older people . DESIGN: We studied the changes in serum parameters (PGA, PGC, PGA/PGC ratio, gastrin and anti-HP Ab) in older patients before and 2 months after stopping therapy for the cure of HP infection . PATIENTS: Eighty-eight older patients (M = 43, F = 45, mean age = 73.3, range = 60-89) with chronic gastritis (42), gastric ulcer (14) or duodenal ulcer (32) were found HP-positive by histology of gastric antral and body biopsies and the rapid urease test . INTERVENTIONS: Two different associations of antibiotics and antiulcer drugs (omeprazole, metronidazole, azithromycin, or clarithromycin) for 2-4 weeks . MEASUREMENTS: At the beginning of the study and 2 months after treatment withdrawal, the subjects were studied by upper G.I . endoscopy with at least two antral and two body gastric biopsies (Giemsa stain and rapid urease test for HP); serum PGA (RIA method, microgram/mL), PGC (RIA method, microgram/mL), PGA/PGC ratio, gastrin (RIA method, picogr/mL), and anti-HP Ab (ELISA method, Biolife, MU/mL) were also determined . Statistical analysis was based on either the Wilcoxon test, for paired data, the chi-square test, the Kruskal Wallis test, or the Mann-Whitney test for unpaired data . The choice of the best cut-off value in the different parameters was performed by receiver operating characteristics curves (ROC) and by Youden index . The correlation between HP density in the gastric mucosa and gastritis activity was verified by Spearman rank correlation test . RESULTS: After therapy, 56/88 patients proved HP-negative (HP-eradicated: M = 30, F = 26, mean age = 73.0, range = 60-87 years), whereas 32/88 were not cured (HP-persistent: M = 13, F = 19, mean age = 73.0, range = 60-89 years) . After therapy, in HP-eradicated cases, a statistically significant change was found in anti-HP Ab (75.23 +/- 8.94 vs 47.32 +/- 5.26, P < .001), PGC (21.58 +/- 1.97 vs 14.34 +/- 1.75, P < .001), and PGA/PGC ratio (8.46 +/- 0.68 vs 11.54 +/- 0.89, P < .001), but not in PGA and gastrin . On the other hand, in HP-persistent cases, anti-HP Ab, PGA, PGC, PGA/ PGC ratio and gastrin did not change after therapy . The sensitivity and specificity were, respectively, 0.62 and 0.56 for anti-HP Ab and 0.75 and 0.56 for the PGA/PGC ratio, which demonstrated the best diagnostic accuracy (68%) . CONCLUSIONS: The eradication of HP from the stomach of older patients induces a rapid and significant decrease in serum levels of IgG anti-HP antibodies and PGC, with an increase in PGA/PGC ratio but not in gastrin . Unchanged serum levels of IgG anti-HP antibodies, PGC, and PGA/PGC ratio 2 months after completing HP eradication therapy are indicative of ongoing HP infection . The PGA/PGC ratio showed the best diagnostic accuracy among serum measures tested.

Clin Infect Dis, 1996 May, 22(5), 809 - 12
Babesiosis in patients with AIDS: a chronic infection presenting as fever of unknown origin; Falagas ME et al.; Babesiosis is a malaria-like, tick-transmitted zoonosis caused by protozoa of the family Piroplasmorida, which includes Babesia and Theileria species . In the United States, the infection is endemic in the Northeast and upper Midwest, although cases have recently been described in Northern California and Washington State . We report a case of babesiosis in a patient infected with HIV who presented with a prolonged fever of unknown origin; the patient had not undergone splenectomy . Parasitemia persisted despite initial clinical improvement after treatment with quinine and clindamycin . Babesiosis was controlled with a maintenance regimen consisting of clindamycin, doxycycline, and high-dose azithromycin, but the infection was not eradicated . Babesiosis should be considered in the differential diagnosis of HIV-infected patients with fevers and/or anemia in areas where the infection is endemic . HIV-infected patients who are severely immunosuppressed, even those without a history of splenectomy, may present with severe manifestations of babesiosis and develop a chronic infection, which may require therapy to prevent relapse of disease.

Ophthalmology, 1996 May, 103(5), 842 - 6
Single-dose azithromycin in the treatment of trachoma . A randomized, controlled study; Tabbara KF et al.; PURPOSE: To compare the safety and efficacy of single oral-dose azithromycin with a 7-week topical tetracycline ointment course in the treatment of active trachoma . METHODS: A total of 64 patients with active trachoma were selected randomly to receive azithromycin (20 mg/kg) in a single dose or topical tetracycline eye ointment for 6 weeks . Clinical assessments were made before and at 4, 8, 12, and 24 weeks after treatment . Conjunctival scrapings were obtained before and after 24 weeks after treatment and fixed for Giemsa and direct immunofluorescence staining . RESULTS: Trachoma resolved in 17 (63.3%) patients who received azithromycin compared with 19 (65.4%) who were treated with tetracycline ointment . There were no significant differences in treatment effect or baseline characteristics between the treatment groups . Both treatments were well tolerated, and no adverse events were noted . CONCLUSION: Single-dose azithromycin is as effective as a 6-week course of topical tetracycline ointment in the treatment of active trachoma . The findings may help establish high compliance in treating trachoma and could contribute to the control of trachoma worldwide.

Ann Intern Med, 1996 May 1, 124(9), 785 - 91
Azithromycin compared with amoxicillin in the treatment of erythema migrans . A double-blind, randomized, controlled trial; Luft BJ et al.; OBJECTIVE: To determine whether azithromycin or amoxicillin is more efficacious for the treatment of erythema migrans skin lesions, which are characteristic of Lyme disease . DESIGN: Randomized, double-blind, double-dummy, multicenter study . Acute manifestations and sequelae were assessed using a standardized format . Baseline clinical characteristics and response were correlated with serologic results . Patients were followed for 180 days . SETTING: 12 outpatient centers in eight states . PATIENTS: 246 adult patients with erythema migrans lesions at least 5 cm in diameter were enrolled and were stratified by the presence of flu-like symptoms (such as fever, chills, headache, malaise, fatigue, arthralgias, and myalgias) before randomization . INTERVENTION: Oral treatment with either amoxicillin, 500 mg three times daily for 20 days, or azithromycin, 500 mg once daily for 7 days . Patients who received azithromycin also received a dummy placebo so that the dosing schedules were identical . RESULTS: Of 217 evaluable patients, those treated with amoxicillin were significantly more likely than those treated with azithromycin to achieve complete resolution of disease at day 20, the end of therapy (88% compared with 76%; P=0.024) . More azithromycin recipients (16%) than amoxicillin recipients (4%) had relapse (P=0.005) . A partial response at day 20 was highly predictive of relapse (27% of partial responders had relapse compared with 6% of complete responders; P<0.001) . For patients treated with azithromycin, development of an antibody response increased the possibility of achieving a complete response (81% of seropositive patients achieved a complete response compared with 60% of seronegative patients; P=0.043) . Patients with multiple erythema migrans lesions were more likely than patients with single erythema migrans lesions (P<0.001) to have a positive antibody titer at baseline (63% compared with 17% for IgM; 39% compared with 16% for IgG) . Fifty-seven percent of patients who had relapse were seronegative at the time of relapse . CONCLUSIONS: A 20-day course of amoxicillin was found to be an effective regimen for erythema migrans . Most patients were seronegative for Borrelia burgdorferi at the time of presentation with erythema migrans (65%) and at the time of relapse (57%).

Antimicrob Agents Chemother, 1996 Mar, 40(3), 825 - 6
Distribution of azithromycin into brain tissue, cerebrospinal fluid, and aqueous humor of the eye; Jaruratanasirikul S et al.; To measure the concentrations of azithromycin in the central nervous system, 20 patients with brain tumors (group I) received a single 500-mg oral dose of azithromycin either 24, 48, 72, or 96 h prior to the tumor removal operation and 10 patients with cataracts undergoing surgery (group II) and 7 patients scheduled to undergo lumbar puncture (group III) received the same dose of azithromycin 24 h prior to the operation or procedure . Serum from all patients, brain tissue from group I, aqueous humor from group II, and cerebrospinal fluid from group III were assayed for azithromycin concentration . The mean concentrations of azithromycin in brain tissue 24, 48, 72, and 96 h after administration were 2.63 +/- 2.58, 3.64 +/- 3.81, 0.74 +/- 0.37, and 0.41 micrograms/g, respectively . In contrast, the concentrations of azithromycin in cerebrospinal fluid and aqueous humor of the eye were very low or undetectable . Therefore, these data show that azithromycin appears to be widely distributed into brain tissue but not into cerebrospinal fluid or aqueous humor of the eye.

Ann Intern Med, 1996 Feb 15, 124(4), 389 - 99
Doxycycline compared with azithromycin for treating women with genital Chlamydia trachomatis infections: an incremental cost-effectiveness analysis; Magid D et al.; OBJECTIVE: To compare the economic consequences of doxycycline therapy with those of azithromycin therapy for women with uncomplicated cervical chlamydial infections . DESIGN: Decision analysis in which the health outcomes, costs, and cost-effectiveness of two provider-administered treatment strategies for women with uncomplicated cervical chlamydial infections were compared: 1) initial therapy with doxycycline, 100 mg orally twice daily for 7 days (estimated cost, $5.51) and 2) initial therapy with azithromycin, 1 g orally administered as a single dose (estimated cost, $18.75) . RESULTS: Under baseline assumptions, the azithromycin strategy incurred fewer major and minor complications and was less expensive overall than the doxycycline strategy despite a higher initial cost for acquiring antibiotic agents . In univariate sensitivity analyses, the azithromycin strategy prevented more major complications but was more expensive than the doxycycline strategy when doxycycline effectiveness was greater than 0.93 . In a multivariate sensitivity analysis combining 11 parameter estimates selected so that the cost-effectiveness of the doxycycline strategy would be maximized relative to that of the azithromycin strategy, the azithromycin strategy resulted in fewer complications but was more costly . The incremental cost-effectiveness was $521 per additional major complication prevented . However, if the difference in the cost of azithromycin and doxycycline decreased to $9.80, the azithromycin strategy was less expensive and more effective, even under these extreme conditions . CONCLUSIONS: On the basis of the best available data as derived from the literature and experts, the azithromycin strategy was more cost-effective than the doxycycline strategy for women with uncomplicated cervical chlamydial infections . Despite the dominance of the azithromycin strategy over the doxycycline strategy, the adoption of the azithromycin strategy may be limited by the practical financial constraints of our currently fragmented health care system, in which the costs and benefits of preventing chlamydia sequelae are often incurred by different components of the system.

Antibiot Khimioter, 1996 Feb, 41(2), 9 - 13
{Clinico-laboratory evaluation of the effectiveness of azithromycin in the treatment of patients with Chlamydia and mixed Chlamydia-gonorrhea infections}; Vasil'ev MM et al.; One hundred and fifteen females with nonsevere inflammatory diseases of the urogenital tracts were examined . Mixed chlamydial and gonorrheal infection was stated in 35 patients . In 38 patients chlamydial infection was diagnosed . To develop an optimal procedure for the treatment, the pharmacokinetics of azithromycin was studied . The results showed that the optimal primary dose of the drug was 1000 mg . Two regimens were recommended for the treatment of the patients . According to the first regimen azithromycin was administered in a single dose of 1000 mg . The efficacy amounted to 82.4 per cent in the cases with the mixed infection and to 89.9 per cent in the cases with chlamydiosis . According to the second regimen azithromycin was administered in a course dose of 3000 mg, the duration of the course being 9 days . The efficacy of the therapy amounted to 89.9 and 95 per cent respectively.

J Chemother, 1996 Feb, 8(1), 55 - 8
Inadequate azithromycin activity against Brucella melitensis in mice with acute or chronic infections; Domingo S et al.; The activities of therapeutic regimens with azithromycin (AZI) and doxycycline combined with streptomycin (DOX-SM) were compared in Brucella melitensis infected mice . In a chronic model, AZI given over 10, 14 or 21 consecutive days (50 mg/kg/24 h) significantly reduced the infection (1.3-1.6 logs, day 48 post-infection) . However, the effectiveness of DOX (21 days, 50 mg/kg/12 h) was higher than AZI (3.4 logs of reduction, day 48 post-infection) . Besides, when DOX was administered for 45 days, it "cured" all the animals from day 78 . Similar results were obtained in an acute model infection . One single dose of DOX or DOX-SM, starting one day after lethal challenge, was able to protect 83% of the mice . In contrast, only 25% of the mice treated with AZI (50-200 mg/Kg) survived the challenge . Our findings demonstrate that AZI, in contrast to DOX-SM, does not cure experimental brucellosis.

Am J Gastroenterol, 1996 Feb, 91(2), 258 - 63
Triple therapy with azithromycin, omeprazole, and amoxicillin is highly effective in the eradication of Helicobacter pylori: a controlled trial versus omeprazole plus amoxicillin; Bertoni G et al.; BACKGROUND: Azithromycin is a new-generation, acid-stable macrolide antibiotic that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a 5-day period after a single 500-mg oral dose . METHODS: We evaluated a new metronidazole-free triple therapy with omeprazole 20 mg b.i.d . plus amoxicillin 1 g b.i.d . (both for 14 days) and azithromycin 500 mg mane (for the first 3 days only) (group I) versus double therapy with omeprazole 20 mg b.i.d . plus amoxicillin 1 g t.i.d., both for 14 days (group II) . H . pylori status was determined by urease test and histology before and 6 wk after completion of therapy . RESULTS: Ninety-two patients with peptic ulcer disease or nonulcer dyspepsia completed the study . H . pylori infection was eradicated in 44 (91.6%) of 48 patients randomized to receive triple therapy versus 26 (59.1%) of 44 who received double therapy (p < 0.001) . Smoking, but not omeprazole pretreatment, proved to be a risk factor for treatment failure only in the double-therapy group (p = 0.05) . All ulcers healed by the time of the 8-wk endoscopic control . Side effects, usually minor, were recorded in 12.5% and 9.1% of patients, respectively (NS), but therapy had to be discontinued in one patient in group I and in three in group II (NS) . CONCLUSIONS: Two-week triple therapy with omeprazole, amoxicillin, and (for the first 3 days) low-dose azithromycin is highly effective in eradicating H . pylori . This regimen is safe and well-tolerated, and we recommend that it be used as first-line treatment, as an alternative to less-effective omeprazole-amoxicillin double therapy . Moreover, azithromycin appears to be a new, promising antibiotic for future innovative anti-H . pylori combinations.

Int J Clin Pharmacol Res, 1996, 16(4-5), 103 - 7
Azithromycin in the treatment of pneumonias caused by Chlamydia spp: a retrospective study; Kuzman I et al.; A retrospective study was undertaken in order to compare the efficacy and safety of azithromycin and doxycycline in the treatment of pneumonias caused by Chlamydia spp . Patients with radiologically confirmed pneumonia and positive complement fixation test for chlamydial infection who were hospitalized in the University Hospital of Infectious Diseases, Zagreb during the years 1989-1992 were reviewed . Among them, 83 were treated with azithromycin, given in a total dose of 1.5 g over 5 days (500 mg once daily at day 1 followed by 250 mg at days 2-5, 60 patients) or 3 days (500 mg once daily, 23 patients) . Twenty-two patients were treated with doxycycline (100 mg b.i.d . for 10 days) . Treatment groups were comparable with respect to age, sex, and severity of signs and symptoms of illness . All the patients were cured . There were no differences in duration of fever after treatment initiation between patients treated with azithromycin (whether pretreated with beta-lactam antibiotics or not) and doxycycline (p > 0.05) . In addition, 3- and 5-day azithromycin courses were equally effective (p > 0.05) . Both drugs were well tolerated, and only two patients treated with azithromycin reported nausea . It may be concluded that in the treatment of pneumonias caused by Chlamydia spp . azithromycin is as effective and well tolerated as doxycycline.

Int J STD AIDS, 1996, 7 Suppl 1, 5 - 8
Azithromycin in the management of Chlamydia trachomatis infections; Ridgway GL; The unique pharmacological profile of the azalide macrolide azithromycin, coupled with its in vitro activity against both Chlamydia trachomatis and the ureaplasmas, suggested that genital infections caused by these bacteria could be successfully treated with a single dose of the antibiotic . This has now been confirmed in worldwide clinical studies . A single oral dose of azithromycin 1 g eradicates C . trachomatis in almost 100% of cases of non-gonococcal urethritis and cervicitis . Unfortunately, there are no specific clinical signs for genital chlamydial infection . It is therefore necessary to use therapy effective against known and unknown pathogens for treating lower genital tract infection . Clinical cure rates for both chlamydial and non-chlamydial, non-gonococcal infections compare favourably with standard 7-day doxycycline therapy, being in excess of 85% . Side effects are few (< 20%) and essentially minor.

Int J STD AIDS, 1996, 7 Suppl 1, 34 - 7
Azithromycin in the prophylaxis of opportunistic infections in AIDS; McCutchan JA; Prevention of opportunistic infections contributes to improved quality of life and survival in individuals with acquired immunodeficiency syndrome (AIDS) . Agents which are more effective and convenient, less costly, and better tolerated are needed for multiple organism primary prophylaxis . Azithromycin, azalide with high and prolonged intracellular levels, promise to provide to protection against Mycobacterium avium complex (MAC) disease in those with advanced AIDS when given weekly . A large trail comparing rifabutin (300 mg daily), a currently approved primary prophylactic agent for MAC, with azithromycin (1200 mg weekly) has been completed and is under analysis . If weekly azithromycin provides equivalent or better protection from disseminated MAC, the cost effectiveness and convenience of MAC prophylaxis may be improved.

Int J STD AIDS, 1996, 7 Suppl 1, 18 - 22
The potential role of azithromycin in the treatment of prophylaxis of toxoplasmosis; Chang HR; Infection with Toxoplasma gondii is the most common parasitic infection worldwide with an estimated prevalence of 1-2 billion people . The risk of developing severe toxoplasmosis is higher for immunocompromised individuals and fetuses of mothers who have acquired a primo-infection . The current therapy of choice for toxoplasmosis is the synergistic combination of pyrimethamine and sulphadiazine . This therapy is highly effective but its use is complicated in immuno-compromised individuals due to adverse secondary effects . In addition, since pyrimethamine is potentially teratogenic, its use is not recommended during early pregnancy . Clindamycin, a lincosaminide, in combination with pyrimethamine has been shown to be an acceptable therapeutic alternative in patients who are unable to tolerate pyrimethamine plus sulphadiazine . In the search for new, effective compounds with less adverse or toxic effects, recent efforts have focused on the new macrolides and the azalides . Here, the results of the investigations and, in particular, the theoretical considerations for the potential use of azithromycin in the therapy of toxoplasmosis in immunocompromised individuals are reviewed.

Ann Intern Med, 1996 Jan 1, 124(1 Pt 1), 1 - 7
A cost-effectiveness analysis of screening and treatment for Chlamydia trachomatis infection in asymptomatic women; Genc M et al.; OBJECTIVE: To assess the cost-effectiveness of identifying and treating asymptomatic female carriers of Chlamydia trachomatis . DESIGN: Cost-effectiveness analysis based on previously reported cohort analytic studies and average salaries and costs of medical care in Sweden . SETTING: Women attending youth, family planning, and gynecology clinics . PARTICIPANTS: 1000 women and their male sex partners . INTERVENTION: Screening with tissue cell culture, confirmed enzyme immunoassay, and DNA amplification assays based on either polymerase chain reaction or ligase chain reaction was compared with no screening (no treatment and no tracing of sexual contacts) . The effect of antibiotic regimens on the outcome of the screening strategies was also evaluated . RESULTS: When the prevalence of chlamydial infection exceeded 6%, screening of women with DNA amplification assay and treatment of positive patients with a single oral dose of azithromycin given under supervision in the clinic was the most cost-effective intervention strategy . At greater prevalences, screening with enzyme immunoassay also generated savings and improved the cure rates compared with no screening, but such screening was less cost-effective than screening with a DNA amplification assay . Compared with no intervention, tissue cell culture is cost-effective only when the prevalence of infection is greater than 14% . Compared with the azithromycin regimen, the standard 7-day, twice-daily doxycycline regimen resulted in significantly lower cure rates because of patients' poor compliance with this regimen . CONCLUSION: For asymptomatic female carriers of C . trachomatis, screening with a DNA amplification assay combined with the single-dose azithromycin treatment of positive patients is the most cost-effective strategy when the prevalence is 6% . When the prevalence is lower than 6%, the decision to choose a competing strategy depends on the physician's view of the value of preventing an illness caused by untreated chlamydial infection.

J Antimicrob Chemother, 1995 Dec, 36(6), 951 - 9
The activity of azithromycin on the infectivity of Chlamydia trachomatis in human amniotic cells; Patton DL et al.; The effects of azithromycin on the infectivity and growth of Chlamydia trachomatis were investigated in primary human amniotic epithelial cells . Infection was prevented when cultures were exposed to the drug 6 h after inoculation and growth was completely inhibited when the drug was added to cultures 24, 48, 72 h or 7 days after infection . The same inhibition was observed at 0.5, 1.0 and 5.0 mg/L . Ultrastructural observations depicted interruption in the growth cycle of the chlamydia and ghost-like envelopes were present in the near empty inclusions . Azithromycin is effective in inhibiting chlamydial growth no matter when treatment is initiated after infection.

Antimicrob Agents Chemother, 1995 Dec, 39(12), 2801 - 2
Levels of azithromycin and alpha-1 acid glycoprotein in serum in patients with community-acquired pneumonia; Bohte R et al.; After an oral dose of 500 mg of azithromycin in patients with community-acquired pneumonia, their serum concentrations ranged between 0.06 and 0.25 mg/liter during the first 12 hours; the calculated percentages of unbound drug varied between 45 and 86% . This study shows that in these patients, the total levels of azithromycin in serum are lower than those expected and that the percentage of bound drug is clinically irrelevant.

Antimicrob Agents Chemother, 1995 Dec, 39(12), 2625 - 30
Genetic basis of macrolide resistance in Mycobacterium avium isolated from patients with disseminated disease; Nash KA et al.; Clarithromycin (CLM) and azithromycin (AZM) are important agents in the treatment of disseminated Mycobacterium avium complex disease; however, monotherapy with these macrolides often leads to clinically significant resistance . The underlying resistance mechanism was investigated by comparing 23S rRNA gene sequences in the domain V region of 10 CLM-susceptible strains included in this study . The only differences in the domain V sequences associated with CLM resistance were at position 2274 of the complete M . avium 23S rRNA gene (GenBank accession no . X74494) . All the CLM-susceptible strains had an A residue at this site, whereas seven of the eight CLM-resistant strains had either a C, G, or T . Four of these seven CLM-resistant strains emerged during monotherapy with CLM and two emerged during AZM monotherapy, showing that resistance selected by either macrolide was associated with mutation of the 23S rRNA gene . Thermodynamic analysis of secondary rRNA structure suggests that the observed mutations cause an alteration in free energy associated with rRNA folding, which may result in a localized conformation change in assembled ribosomes . Such a shift may be important in the resistance of ribosomes to the effects of macrolides . This study therefore establishes a link between mutations within the 23S rRNA gene and clinically significant macrolide resistance in M . avium and also identifies a possible molecular mechanism of resistance at the level of the ribosome.

Ann Intern Med, 1995 Nov 15, 123(10), 771 - 3
Prophylaxis of Plasmodium falciparum malaria with azithromycin administered to volunteers; Anderson SL et al.; OBJECTIVE: To determine whether azithromycin, 250 mg/d, is effective prophylaxis for liver infection or for both liver and subsequent blood infection with Plasmodium falciparum . DESIGN: Controlled phase II trial with two cohorts entered sequentially . SETTING: Clinical trials center of Walter Reed Army Institute of Research, Washington, D.C . PATIENTS: Each of the two cohorts consisted of 12 normal adult volunteers who had not had malaria during the previous 2 years: 10 who received azithromycin prophylaxis and 2 controls who did not received treatment . INTERVENTION: For cohort 1, prophylactic efficacy against liver infection alone during the initial 7 days of the infection was determined by loading participants with azithromycin before challenge with P . falciparum-infected mosquitoes on day 0 and by then giving the drug for 7 days after the challenge . The regimen was 500 mg on day 14 before the challenge, followed by 250 mg/d from day 13 before the challenge through day 7 after the challenge . For cohort 2, prophylactic efficacy against both the liver infection and the subsequent blood infection was determined by continuing drug administration for 28 days after the challenge . MEASUREMENTS: Plasmodium falciparum infection was diagnosed through peripheral blood smears obtained up to 70 days after challenge . Malarial symptoms and adverse drug reactions were also monitored . RESULTS: In cohort 1, 4 of 10 volunteers who received azithromycin prophylaxis (40%) did not develop parasitemia . In cohort 2, none of the 10 volunteers receiving azithromycin prophylaxis (100%) developed parasitemia . For each cohort, both control volunteers became parasitemic on days 9 through 13 after the challenge . Adverse drug reactions were few and mild . CONCLUSIONS: In this model, prophylaxis with azithromycin (250 mg/d) was partially effective against liver parasites and completely successful against the combination of liver and blood parasites . These data suggest that azithromycin has the potential to be an effective, well-tolerated clinical prophylactic agent for P . falciparum malaria.

J Int Med Res, 1995 Nov-Dec, 23(6), 413 - 22
Azithromycin compared with clarithromycin in the treatment of adult patients with acute purulent tracheobronchitis: a cost of illness study; Sternon J et al.; Adult, professionally active patients with acute purulent tracheobronchitis were treated with azithromycin (3 or 5 days; n = 62) or clarithromycin (7 to 10 days; n = 69) in an open, randomized study . Bronchitis-related costs and treatment efficacy were assessed at day 5-6 and day 14-21 . Both antibiotics were of equal clinical efficacy, although the median time to improvement of symptoms was significantly shorter for azithromycin patients than for clarithromycin patients . Some 77% of azithromycin patients and 78% of clarithromycin patients were unable to work for at least 1 day . The total time when patients were unable to work was shorter for azithromycin patients than for clarithromycin patients, but this difference did not remain significant when weekends and holidays were taken into account . Further studies are needed to assess the impact of azithromycin on time to clinical improvement, on lost working days, and on the associated costs.

Plast Reconstr Surg, 1995 Nov, 96(6), 1378 - 83
A prospective, double-blind, placebo-controlled trial of a single dose of azithromycin on postoperative wound infections in plastic surgery; Amland PF et al.; Over a 9-month period from September of 1991 to May of 1992, 339 patients were included in a randomized, double-blind, placebo-controlled study using azithromycin as the prophylactic agent to determine whether it effects a clinically meaningful reduction in postoperative surgical infections in plastic surgery . Azithromycin was given as prophylaxis in 171 patients and placebo in 168 patients . The study medication was a single oral dose taken at 8 P.M . the day before surgery . The patients were followed up for a minimum of 4 weeks after surgery . The patients who received wound infection prophylaxis had 5.1 percent infections compared with 20.5 percent in the placebo group (p = 0.00009) . Eighty percent of all wound infections were first seen after discharge, explaining why plastic surgeons might overlook their infectious complications . There was a significant reduction in postoperative complications (p = 0.04) and in the additional use of antibiotics postoperatively (p = 0.007) in the prophylaxis group . Subgroup analysis showed a significant reduction in surgical infections in breast surgery (p < 0.05) and reconstructive surgery with flaps (p < 0.05) . No effect of the prophylactic regime was demonstrated in patients undergoing secondary surgery for cleft lip and palate disease.

Ann Pharmacother, 1995 Oct, 29(10), 991 - 3
Treatment of non-HIV cryptosporidial diarrhea with azithromycin; Bessette RE et al.; OBJECTIVE: To report a patient with non-HIV-related cryptosporidial diarrhea who was treated effectively with a regimen of high-dose azithromycin therapy . CASE SUMMARY: A 42-year-old immunocompetent man contracted cryptosporidiosis from an ailing calf that he had purchased . He finally was admitted to the hospital because of excessive weight loss and profuse diarrhea . The patient was started on a course of high-dose azithromycin therapy and symptoms resolved within 48 hours . Follow-up stool cultures were negative for the parasite . DISCUSSION: Although usually associated with immunocompromised patients, cryptosporidiosis occurs in immunocompetent hosts in a significant portion of the reported cases each year . Although self-limiting in most cases in this population, the disease can be severe at times and require treatment . Paromomycin therapy has been used in the past with good results . Although macrolides have had erratic effects against this parasite in the past, azithromycin (an azalide) demonstrated good efficacy in this patient . CONCLUSIONS: Azithromycin has demonstrated that it may be an effective option for the treatment of cryptosporidiosis in immunocompromised patients . Studies involving its use in immunocompromised patients are currently underway.

J Antimicrob Chemother, 1995 Oct, 36(4), 641 - 6
Efficacy of azithromycin and rifabutin in preventing infection by Mycobacterium avium complex in beige mice; Bermudez LE et al.; We investigated the potential of the azalide, azithromycin, and rifabutin in preventing disseminated infection due to Mycobacterium avium complex (MAC) in beige mice . Azithromycin 200 mg/kg, rifabutin (30 mg/kg or 60 mg/kg) were administered by gavage 6 days before mice were challenged orally with 10(8) cfu MAC and daily for 10 days thereafter during which time the mice were again challenged with the same inoculum on alternate days (days +1, +3, +5, +7, and +9) . Sixty-four days later, the presence of bacteria in the blood and the number of viable bacteria in liver, spleen and appendix were estimated . Treatment with azithromycin and 60 mg/kg/day rifabutin but not 30 mg/kg/day, significantly decreased the incidence of bacteraemia and the number of bacteria in the appendix . The administration of azithromycin resulted in significantly fewer MAC in the liver and spleen but not in the appendix whereas the converse was true of 60 mg/kg rifabutin . Our results indicate that both azithromycin and rifabutin can prevent MAC disseminated infection, but that the azalide is more effective than the rifamycin in reducing the burden of infection.

Am Fam Physician, 1995 Oct, 52(5), 1455 - 62
Chlamydia trachomatis infection update; Heath CB et al.; Chlamydia trachomatis has become the most common sexually transmitted infection in the United States . Aggressive screening of sexually active young adults is needed, as well as prompt and reliable treatment of infected partners, to mitigate the effects of this disease . Tests using enzyme immunoassay and DNA probe have increased the efficiency of diagnosis through rapid detection, although culture remains the most reliable test . Treatment with single-dose azithromycin is a successful alternative to the definitive treatment, seven days of doxycycline therapy.

Lancet, 1995 Sep 30, 346(8979), 881 - 2
Effects of azithromycin on malariometric indices in The Gambia; Sadiq ST et al.; Azithromycin (a macrolide-like antibiotic) has antimalarial effects in vitro and in animal models . In the course of a randomised trial of trachoma control we examined the effects of azithromycin on parasite and spleen rates in the population aged 5-14 years from eight villages in the Farafenni study area in The Gambia, West Africa . The entire population of four treatment villages received three doses of azithromycin 20 mg/kg weekly (days 1, 8, and 15) and four control villages received daily tetracycline eye ointment topically (days 1-42) . Among 226 children studied before treatment and at day 28, azithromycin reduced the proportions with Plasmodium falciparum parasites (rate ratio 0.56, 95% confidence interval 0.44-0.71; p < 0.0001), with palpable spleens (RR 0.50, 95% CI 0.36-0.70; p < 0.0001), with febrile parasitaemia (RR 0.45, 95% CI 0.27-0.75; p < 0.01), and with P malariae infection (p < 0.001) . This effect was related more to resolution of parasitaemia than to prevention of new infections.

Clin Infect Dis, 1995 Sep, 21(3), 594 - 8
Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease; Griffith DE et al.; We initiated a multidrug trial that included high-dose rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease . Twenty-six patients received rifabutin (600 mg/d) in combination with ethambutol, streptomycin, and either clarithromycin (500 mg b.i.d.; 15 patients) or azithromycin (600 mg/d; 11 patients) . Rifabutin-related adverse events occurred in 77% of patients . Fifty-eight percent of patients required a dosage adjustment or discontinuance of rifabutin therapy . The most common adverse event was a reduction in the mean total white blood cell (WBC) count, which decreased from 8,600 +/- 2,800/mm3 before treatment to 4,500 +/- 2,100/mm3 during treatment (P = .0001) . Although all patients had some decrease in WBC count, only three patients (12%) required a dosage adjustment for this reason . Other common adverse events included gastrointestinal symptoms (nausea, vomiting, or diarrhea; 42%) and abnormal liver enzyme levels (12%) . Eight of 11 patients (73%) with gastrointestinal symptoms, including one patient with abnormal liver enzyme levels, required a rifabutin-dosage adjustment . The most severe adverse events, always requiring an adjustment of therapy, were a diffuse polyarthralgia syndrome (19%) and anterior uveitis (8%) . The latter toxicity has previously been reported to occur only in patients with AIDS and was seen only in patients who also were receiving clarithromycin . On the basis of the current findings, we recommend that rifabutin be used at a dose of 300 mg/d in multidrug regimens that include a macrolide for treatment of MAC lung disease.

J Infect Dis, 1995 Sep, 172(3), 810 - 6
Activities of clarithromycin, azithromycin, and ofloxacin in combination with liposomal or unencapsulated granulocyte-macrophage colony-stimulating factor against intramacrophage Mycobacterium avium-Mycobacterium intracellulare; Onyeji CO et al.; The effects of ofloxacin, clarithromycin, and azithromycin in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) against Mycobacterium avium-Mycobacterium intracellulare (MAI) were evaluated in an in vitro human macrophage infection model . Treatment of MAI-infected macrophages with GM-CSF alone induced a maximal killing effect at 1000 U/mL, and the potency was increased 100-fold by encapsulating the cytokine within liposomes . Antibiotics were applied at concentrations close to their clinically achievable serum trough and peak levels . Addition of GM-CSF to azithromycin and therapeutic trough concentrations of ofloxacin and clarithromycin was associated with significant (P < .01) augmentation of antimycobacterial activity compared with the effects of the agents alone . However, the enhancement effect by GM-CSF was not seen with therapeutic peak concentrations of ofloxacin and clarithromycin . Thus, GM-CSF may be a useful adjunct in the treatment of MAI infections with azithromycin, clarithromycin, and ofloxacin.

Clin Pharmacol Ther, 1995 Sep, 58(3), 310 - 5
Azithromycin and terfenadine: lack of drug interaction; Harris S et al.; A double-blind placebo-controlled study was conducted in healthy men to determine the effect of coadministration of azithromycin on the pharmacodynamics and pharmacokinetics of terfenadine . Administration of 500 mg azithromycin for 1 day and 250 mg on 4 subsequent days did not affect the pharmacokinetics of the pharmacologically active terfenadine carboxylate metabolite when 60 mg terfenadine was given twice daily for 12 days, starting 7 days before azithromycin administration . Terfenadine alone resulted in a 0.010 msec increase in the rate-corrected QT interval (QTc), but the incremental effects of azithromycin and placebo on QTc in volunteers receiving terfenadine were not statistically different . It is concluded that the potentially life-threatening disorders that have been attributed to a pharmacokinetic interaction between macrolide antibiotics and terfenadine are unlikely to take place in patients treated simultaneously with azithromycin and terfenadine.

Sex Transm Dis, 1995 Sep-Oct, 22(5), 274 - 80
The cost effectiveness of azithromycin for Chlamydia trachomatis infections in women; Haddix AC et al.; BACKGROUND AND OBJECTIVES: Azithromycin, an approved single-dose therapy for cervical chlamydia infections, costs four times as much as doxycycline, the standard multidose theapy . GOAL OF THIS STUDY: This study examined whether azithromycin is cost effective for treating cervical chlamydia infections . STUDY DESIGN: Two diagnostic strategies were compared: 1) laboratory confirmation of chlamydia, and 2) presumptive diagnosis from the perspective of the healthcare system and the publicly funded clinic . RESULTS: From the healthcare perspective, the cost per case of pelvic inflammatory disease prevented with azithromycin ranges from a savings of $3,502 for laboratory confirmation to a cost of $792 for presumptive diagnosis . From the publicly funded clinic perspective, the cost per case of pelvic inflammatory disease prevented ranges from $709 for lab-confirmed diagnosis to $3,969 for presumptive treatment . CONCLUSION: For the healthcare system, azithromycin is a cost-effective alternative to doxycycline . However, the cost of azithromycin must decrease markedly for it to be less costly to the publicly funded clinic.

Eur J Clin Microbiol Infect Dis, 1995 Aug, 14(8), 669 - 76
Multicentre comparative study of the efficacy and safety of azithromycin compared with amoxicillin/clavulanic acid in the treatment of paediatric patients with otitis media; Principi N; An open multicentre study was conducted in 484 children between the ages of 6 months and 12 years with otitis media to compare the efficacy, the safety and the tolerance of once-daily azithromycin given for three days versus thrice-daily amoxicillin/clavulanic acid (CA) given for ten days . A satisfactory response (cure plus improvement) was noted 10 to 14 days after the start of treatment in 199 of 215 (92.6%) azithromycin-treated children and in 186 of 198 (93.9%) amoxicillin/CA-treated children . The relationship between treatment and clinical response was independent of chronicity of infection and the presence or absence of a perforated eardrum . Improvement in signs and symptoms of otitis media occurred significantly more rapidly in the children treated with azithromycin . Treatment-related or possibly treatment-related adverse events were recorded in 11 of 243 (4.5%) azithromycin-treated patients and in 20 of 240 (8.3%) treated with amoxicillin/CA . No patients in the azithromycin treatment group were withdrawn from treatment, but six amoxicillin/CA patients, including two < 2 years of age, discontinued treatment prematurely because of adverse events; the difference between treatment groups was statistically significant (p = 0.0146) . It is concluded that azithromycin given as an oral suspension once daily for three days is as safe and effective as amoxicillin/CA given thrice daily for ten days in the treatment of children with otitis media.

Antimicrob Agents Chemother, 1995 Aug, 39(8), 1875 - 7
Pharmacokinetics of azithromycin in pediatric patients with acute otitis media; Nahata MC et al.; The objective of our study was to characterize the pharmacokinetics of azithromycin after the oral administration of multiple doses in suspension to children with acute otitis media . Thirteen children (ranging in age from 7.5 months to 5 years) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5 . Each child fasted overnight before receiving the final dose on day 5 . Multiple blood samples were collected after the last dose . Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method . The means and standard deviations for the maximum concentration of azithromycin in serum, the time to maximum concentration of azithromycin in serum, the area under the concentration-time curve (from 0 to 24 h), and the elimination half-life were 224 +/- 120 ng/ml, 1.8 +/- 0.4 h, 1,841 +/- 651 ng.h/ml, and 31.6 +/- 6.6 h, respectively . Concentrations in serum (means +/- standard deviations) at 0 h (predose) and at 24, 48, and 72 h after the final dose were 51 +/- 26, 47 +/- 21, 27 +/- 17, and 17 +/- 13 ng/ml, respectively . Thus, the once-daily administration of azithromycin resulted in sustained systemic exposure to the drug . The drug dosage regimen used in this study should lead to tissue drug concentrations exceeding the MICs for common pathogens.

Ann Acad Med Singapore, 1995 Jul, 24(4), 547 - 9
An open non-comparative pilot study with azithromycin in the treatment of non-gonococcal urethritis in the sexually transmitted disease clinics in Hong Kong; Lo KK et al.; The aim of this study is to find out the efficacy and safety of azithromycin in the treatment of males with uncomplicated non-gonococcal urethritis . It is an open, non-comparative study carried out in the major sexually transmitted disease clinics in Hong Kong . The subjects were 45 male outpatients with clinical symptoms and signs of acute non-gonococcal urethritis . Patients presenting with acute urethritis were examined and non-gonococcal urethritis were examined and non-gonococcal urethritis was daignosed by the positive urethral smear for white blood cells but negative for gonococcus . They were given a single 1 gram oral dose of azithromycin at the clinic . Follow-ups after one and two weeks to examine for cure and adverse events were made . The result showed that 35 out of 42 evaluable patients were cleared of urethritis . Only 2 out of 22 chlamydial antigen positive patients still remained positive at the last visit . Adverse events were not uncommon but all were only mild . We concluded that 1 gram single dose of azithromycin was effective and well tolerated in the treatment of non-gonococcal urethritis in male patients.

Clin Ther, 1995 Jul-Aug, 17(4), 701 - 7
An open-label, noncomparative study to evaluate the efficacy, safety, and tolerability of azithromycin in the treatment of patients with acute sinusitis; Amin NM et al.; The efficacy, safety, and tolerability of a 5-day, once-daily course of azithromycin were assessed in patients with acute sinusitis . Patients received two 250-mg capsules of azithromycin on day 1 and one 250-mg capsule on days 2 through 5 . Of 102 clinically assessable patients, 27 (26.5%) were cured and 69 (67.6%) were improved on days 5 to 7 . At days 12 to 16, 88 (86.3%) had a favorable clinical response . A total of 64 patients experienced adverse events; in all but two patients, adverse events were of mild or moderate severity . Thus azithromycin given once daily for 5 days was an effective treatment for patients with acute sinusitis.

Ann Pharmacother, 1995 Jul-Aug, 29(7-8), 760 - 8
Therapeutic approaches for AIDS-related toxoplasmosis; Behbahani R et al.; OBJECTIVE: To summarize current knowledge of prophylaxis and treatment of AIDS-related toxoplasmosis . DATA SOURCES: A MEDLINE search (1985-1994) was used to identify pertinent literature, including reviews . STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review . Pertinent information, as judged by the authors, was selected for discussion . DATA SYNTHESIS: Trimethoprim/sulfamethoxazole (TMP/SMX) appears to be useful for prophylaxis against toxoplasmosis in patients with AIDS . The most effective TMP/SMX dose for prevention of toxoplasmosis needs to be determined . Dapsone in combination with pyrimethamine therapy may be an effective alternative for toxoplasmosis prophylaxis . The most effective regimen for the treatment of AIDS-related toxoplasmosis is the combination therapy of pyrimethamine/sulfadiazine . In patients who cannot tolerate sulfadiazine therapy because of adverse effects or allergy, pyrimethamine with clindamycin therapy may be considered as a second-line alternative . Lifelong suppressive therapy is required after either treatment regimen to prevent relapse . Other newer agents such as azithromycin, clarithromycin, atovaquone, or timetrexate-leucovorin need further studies to confirm their true effectiveness in the treatment of toxoplasmosis . CONCLUSIONS: TMP/SMX remains a useful agent in prophylaxis against toxoplasmosis . Pyrimethamine/sulfadiazine is the most effective combination in the treatment of acute toxoplasmosis.

Med Clin North Am, 1995 Jul, 79(4), 803 - 15
Azithromycin and clarithromycin; Schlossberg D; Azithromycin and clarithromycin are alternatives to conventional macrolides in the routine treatment of many dermatologic, upper respiratory, and lower respiratory tract infections . In this role as alternative therapy, they are better tolerated, less toxic, and more convenient to take, although at a greater cost to the patient . This dosing convenience is an important consideration for the clinician; as shown by Nelson, patient compliance ranges from 95% with once-daily dosing to 58% with four-times-a-day dosing . Thus, less frequent dosing with both drugs as well as the shorter course of therapy possible with azithromycin may be therapeutically advantageous . In addition to their role as alternatives to conventional macrolide therapy, azithromycin and clarithromycin extend the spectrum of macrolides and offer new therapeutic options for H . influenzae, MAC in AIDS, MOTT, and leprosy . Finally, experimental therapy may extend their use for additional opportunistic infections, such as toxoplasmosis and cryptosporidiosis.

Antimicrob Agents Chemother, 1995 Jul, 39(7), 1530 - 7
In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii; Fichera ME et al.; In order to characterize the delayed effect of clindamycin and macrolide antibiotics against Toxoplasma gondii tachyzoites (E . R . Pfefferkorn and S . E . Borotz, Antimicrob . Agents Chemother . 38:31-37, 1994), we have carefully examined the replication of parasites as a function of time after drug addition . Intracellular tachyzoites treated with up to 20 microM clindamycin (> 1,000 times the 50% inhibitory concentration) exhibit doubling times indistinguishable from those of controls (approximately 7 h) . Drug-treated parasites emerge from infected cells and establish parasitophorous vacuoles inside new host cells as efficiently as untreated controls, but replication within the second vacuole is dramatically slowed . Growth inhibition in the second vacuole does not require continued presence of drug, but it is dependent solely on the concentration and duration of drug treatment in the first (previous) vacuole . The susceptibility of intracellular parasites to nanomolar concentrations of clindamycin contrasts with that of extracellular tachyzoites, which are completely resistant to treatment, even through several cycles of subsequent intracellular replication . This peculiar phenotype, in which drug effects are observed only in the second infectious cycle, also characterizes azithromycin and chloramphenicol treatment, but not treatment with cycloheximide, tetracycline, or anisomycin . These findings provide new insights into the mode of clindamycin and macrolide action against T . gondii, although the relevant target for their action remains unknown.

Pathol Biol (Paris), 1995 Jun, 43(6), 561 - 4
{New pathogens and mode of action of azithromycin: Toxoplasma gondii}; Derouin F; Azithromycin can inhibit the growth of Toxoplasma gondii tachyzoites in vitro, but the effect is only observed with prolonged incubation with the drug, reflecting the delayed mode of action of this macrolide on the parasite . Azithromycin is probably acting by inhibition of protein synthesis but the site of action and fixation in the parasite has not been demonstrated . Azithromycin is also effective against intracystic bradyzoites in vitro, but long term administration of azithromycin to chronically infected mice failed to reduce the mean number of brain cysts . In models of acute toxoplasmosis, azithromycin was found to have a limited effect on brain infection, whereas parasites were cleared from blood and lungs of infected mice, resulting in a significant protection of treated mice comparatively to untreated controls . When azithromycin is combined with pyrimethamine or sulfadiazine, an additive effect is observed in vitro, and a remarkable synergistic effect is observed in vivo in the treatment of acute toxoplasmosis . Together, these results are in favor of the use of azithromycin in combined therapies for the treatment and/or prophylaxis of toxoplasmosis.

Pathol Biol (Paris), 1995 Jun, 43(6), 512 - 4
Azithromycin drug interactions; Felstead S; Pre clinical work in vivo and in vitro have suggested that azithromycin has a low potential for significant drug interactions . Clinical studies conducted thus far have generated results in accordance with the preclinical science {6} . Direct comparisons with the most modern macrolides have been published and evidence suggests that azithromycin is likely to be associated with fewer significant drug interactions . However, as a final point, I wish to point out that proof of an absolute negative is not possible and therefore in any patient, on multiple medication with adverse findings, a drug interaction should be considered as part of the differential diagnosis.

Ann Allergy Asthma Immunol, 1995 Jun, 74(6), 491 - 4
Cerebral toxoplasmosis in childhood and adult HIV infection treated with 1-4 hydroxynaphthoquinone and rapid desensitization with pyrimethamine; Bouboulis DA et al.; BACKGROUND: We describe a child and an adult infected with the human immunodeficiency virus (HIV) who developed cerebral lesions consistent with toxoplasmosis . A biopsy in the child and IgG ELISA in both patients confirmed the diagnosis of Toxoplasma gondii . The patients were initially treated with pyrimethamine, however, computerized tomography studies (CT scan) revealed progression of a left frontal and temporoparietal lesion . Therapy in the child was changed to pyrimethamine, clindamycin, and azithromycin . Repeat CT scan showed further disease progression and therapy was changed to high-dose pyrimethamine (3 mg/kg/d) and azithromycin . A subsequent CT scan disclosed further radiologic progression with increasing edema . The adult patient developed a maculopapular rash during attempted treatment with pyrimethamine . METHODS: Introduction of 2 (trans-4{4 chlorophenol} cyclohexy{3-hydroxy-1, 4 naphthoquinone} (HNPQ) an experimental antiparasitic compound previously used only in adult HIV clinical trials, was instituted in the child and rapid oral desensitization to pyrimethamine was initiated in the adult patient . RESULTS: HNPQ resulted in resolution of the cerebral lesion in the child and rapid oral desensitization to pyrimethamine produced an excellent clinical response in the adult . To our knowledge, these are the first cases of childhood and adult cerebral toxoplasmosis treated successfully with HNPQ and rapid oral desensitization to pyrimethamine . CONCLUSION: HNPQ and pyrimethamine desensitization should be considered as alternate modes of therapy in patients who become intolerant or fail to respond to traditional therapy for toxoplasmosis.

Int J Clin Pharmacol Ther, 1995 Jun, 33(6), 356 - 9
Azithromycin does not increase plasma concentrations of oral midazolam; Backman JT et al.; Interaction between azithromycin and midazolam was investigated in a double-blind, randomized crossover study of 2 phases . Ten healthy volunteers were given azithromycin (500 mg on day 1 and 250 mg on days 2-5) or placebo pretreatments . On day 5 they ingested 15 mg midazolam . Plasma samples were collected and psychomotor performance measured for 17 h . Azithromycin treatment increased the median (range) concentration peak time of midazolam from 1.0 (0.5-2) h to 1.25 (0.5-5) h and decreased plasma concentrations of midazolam during initial 3 hours after the intake of midazolam (p < 0.05) . Mean +/- SE mean peak concentration of midazolam was decreased from 86 +/- 17 ng ml-1 to 57 +/- 9 ng ml-1 (p < 0.05) . Azithromycin did neither increase the total area under concentration-time curve nor change the elimination half-life of midazolam . In Maddox wing test the maximum effects of midazolam were reached later during azithromycin phase, but no other changes were observed in pharmacodynamics of midazolam . Azithromycin may delay the absorption of midazolam, which can postpone the onset of action of midazolam.

Clin Infect Dis, 1995 Apr, 20 Suppl 1, S66 - 71
New treatments for Chlamydia trachomatis genital infection; Weber JT et al.; To provide information for the formulation of treatment guidelines, we review recently published articles and abstracts on advances in the treatment of Chlamydia trachomatis genital infection . We ask specific questions about new treatments that are answered on the basis of the results of clinical trials and efficacy studies . New, potentially effective treatments for C . trachomatis genital infection include azithromycin and ofloxacin . Clinical studies indicate that the efficacy of these agents is equivalent to that of the current recommended agent doxycycline . Both azithromycin and ofloxacin are substantially more expensive than doxycycline . Azithromycin has the advantage of being given as a single dose, while doxycycline and ofloxacin are administered for 1 week . Issues of compliance, cost, and toxicity for specific patients should be considered when deciding whether to treat C . trachomatis genital infections with these agents.

Antimicrob Agents Chemother, 1995 Apr, 39(4), 806 - 11
Effect of atovaquone and atovaquone drug combinations on prophylaxis of Pneumocystis carinii pneumonia in SCID mice; Comley JC et al.; The prophylactic efficacies of atovaquone (ATQ) alone and in combination with azithromycin, clarithromycin, rifabutin, proguanil, PS-15, trimethoprim, co-trimoxazole, or dapsone were investigated in a SCID mouse model of Pneumocystis carinii pneumonia (PCP) . ATQ alone was shown to have a significant dose-related effect, and at 200 mg/kg of body weight per day administered orally, the efficacy of ATQ was comparable to that of Septrin (co-trimoxazole) . Of the drugs investigated orally in combination with ATQ, only dapsone (25 mg/kg/day) and to a lesser extent PS-15 (5 mg/kg/day) had any noteworthy antipneumocystis activity (at the doses examined) when administered alone . ATQ drug combinations affected the prophylactic efficacy of a subcurative dosage of ATQ (50 mg/kg/day given orally) in the following ways: dapsone (25 mg/kg/day) or co-trimoxazole (25 mg of sulfamethoxazole plus 5 mg of trimethoprim per kg/day) had no significant effect on ATQ, azithromycin (200 mg/kg/day) or clarithromycin (200 mg/kg/day) had a slight additive effect with ATQ, trimethoprim (100 mg/kg/day) or PS-15 (5 mg/kg/day) had an additive effect with ATQ, and proguanil (25 mg/kg/day) or rifabutin (200 mg/kg/day) had a marked synergistic effect on ATQ . The last result was particularly noteworthy as neither proguanil nor rifabutin was effective against PCP when administered alone . None of the drugs examined antagonized the prophylactic activity of ATQ in experimental PCP in SCID mice . The results suggest that clinical trials of ATQ with synergistic drug combinations may now be justified, particularly if such drug combinations improve ATQ's efficacy and broaden its spectrum of activity.

Bratisl Lek Listy, 1995 Mar, 96(3), 165 - 7
{Treatment of chlamydia infections and a brief review of the problems}; Pec J et al.; The authors treated 35 patients (17 males, 18 females) with chlamydial infection of the urogenital system by means of azithromycin dosed 1.0 g for the first day, 500 mg from the second till the fifth day of treatment with 82.9% effectivity.

Am J Trop Med Hyg, 1995 Feb, 52(2), 159 - 61
Activity of azithromycin as a blood schizonticide against rodent and human plasmodia in vivo; Andersen SL et al.; We compared the efficacy of azithromycin to the clinical antimalarial doxycycline in Plasmodium berghei-infected mice and in P . falciparum-infected Aotus monkeys . When mice were administered drug orally twice a day for three days, the minimum total dose of azithromycin that cured all mice was 768 mg/kg . Doxycycline at a dose of 1,536 mg/kg cured no mice . The efficacy of fast-acting blood schizonticides (quinine, halofantrine, artemisinin) against P . berghei was augmented by azithromycin . In monkey experiments in which there were two animals per experimental group, azithromycin (100 mg/kg/day for seven days) eliminated parasitemia; azithromycin (30 mg/kg/day) initially cleared 99.8-100% of the parasites with recrudescence in the one completely cleared case . Doxycycline (30 mg/kg/day) cleared 100% of the parasites with recrudescence in both cleared cases . Since azithromycin can be clinically administered at a somewhat higher daily dosage than doxycycline, the data suggest that it may be possible to replace drugs of the tetracycline class with azithromycin in combination with fast-acting blood schizonticides for the treatment of P . falciparum infection.

J Vet Pharmacol Ther, 1995 Feb, 18(1), 38 - 46
Pharmacokinetics, oral bioavailability and tissue distribution of azithromycin in cats; Hunter RP et al.; Azithromycin is the first of a class of antibiotics classified as azalides . In an initial experiment four cats were given a single dose of azithromycin 5 mg/kg orally (p.o.), followed 2 weeks later by a single intravenous bolus (i.v.) dose of 5 mg/kg . Subsequently, six cats were given {14C}azithromycin p.o . in a single dose of 5.4 mg/kg for the study of tissue distribution and metabolism . In both experiments, serial blood samples were collected and the plasma assayed for unchanged azithromycin to determine various pharmacokinetic parameters . After p.o . administration, bioavailability was 58% and absorption rapid with a tmax of 0.85 +/- 0.72 h and a Cmax of 0.97 +/- 0.65 microgram/mL . The harmonic mean terminal t1/2 after i.v . administration was 35 h . Tissue half-lives varied from 13 h in fat to 72 h in cardiac muscle . Three metabolites were identified in bile . Unchanged azithromycin accounted for 100% of the total radioactivity in lung and skin tissues when assayed . In comparison with other species, the bioavailability in cats is higher than in humans but lower than in dogs . As in the dog, > 50% of the azithromycin-related material in feline bile was unchanged azithromycin.

Scand J Infect Dis, 1995, 27(5), 503 - 5
Azithromycin for treatment of community acquired pneumonia caused by Legionella pneumophila: a retrospective study; Kuzman I et al.; A clinical, retrospective and non-comparative study was undertaken to assess the clinical efficacy and tolerability of azithromycin in the treatment of community-acquired pneumonia caused by Legionella pneumophila . A total of 16 patients with a serologically confirmed diagnosis of Legionnaires' diseases were included . Azithromycin was administered orally at a total dose of 1.5 g for either 3 or 5 days . All patients were no side-effects requiring discontinuation of the treatment . Further increase of abnormal baseline liver function was recorded in 2 patients and in 1 patient mild, transient eosinophilia . Equal clinical efficacy and tolerability were observed with the 3- and 5-day dosage regimen . These results indicate that azithromycin given at a standard dose of 1.5 g is effective and well tolerated in the treatment of Legionnaires' disease.

Infection, 1995, 23 Suppl 1, S5 - 9
Pharmacokinetics of macrolides . Comparison of plasma, tissue and free concentrations with special reference to roxithromycin; Nilsen OG; When macrolide antibiotics are administered according to the standard therapeutic regimens, the highest plasma concentrations of total drug, both during the first dosage interval and at steady state, are obtained with roxithromycin, followed by clarithromycin and azithromycin . The corresponding free plasma concentrations, calculated from published data on plasma protein binding for the three macrolides, are of the same order of magnitude and the highest values are again those of roxithromycin . With the use of improved analytical methodology, a stable and prolonged total elimination half-life of roxithromycin of about 19 h was demonstrated at steady state in healthy adults with a 300 mg once daily dosage regimen . Intra-group subject variations (adults, children, the elderly etc.) were smaller than anticipated . Roxithromycin is found in high and similar concentrations both in plasma and tissue, demonstrating a balanced pharmacokinetic behaviour.

Infection, 1995, 23 Suppl 1, S28 - 32
Potential role of roxithromycin against the Mycobacterium avium complex; Young LS et al.; Until the recent experience with azithromycin and clarithromycin, macrolides were not considered to be important agents against mycobacteria . Clinical evidence is now growing that the newer 14 and 15 membered macrolide compounds have therapeutic activity against Mycobacterium avium, Mycobacterium chelonae and Mycobacterium leprae . Several years ago, when evaluating the activity of roxithromycin using one of the more virulent M . avium in our collection, the authors found that roxithromycin exerted a bacteriostatic effect in cultured human macrophages . However, in combination with tumour necrosis factor, which induces macrophage activation, roxithromycin caused enhanced intracellular killing . The significance of this finding is that tumour necrosis factor can be elaborated by activated macrophages during the course of infection . The roxithromycin doses that were chosen for these studies were less than achievable blood levels . More recently, the in vitro effect of roxithromycin against a panel of isolates from AIDS patients has been assessed and it was found that some (but not all) of the inhibitory concentrations, by the T-100 method of Inderlied, are within achievable serum levels . This, however, may not be the basis for anticipating in vivo activity since macrolide compounds are known to be concentrated within cells and particularly within phagolysosomes . Demonstration of effect in an in vitro test system is encouraging, but should be considered only as a preliminary step to careful assessments in experimental animals, such as the beige mouse, and studies in humans.

J Antimicrob Chemother, 1994 Dec, 34(6), 989 - 99
The effect of a single oral dose of azithromycin on chlamydial infertility and oviduct ultrastructure in mice; Tuffrey M et al.; Azithromycin has been recommended for the treatment of human chlamydial genital tract infections because of the sustained, chlamydicidal levels of the antibiotic which can be achieved after a single dose . The effect of single dose azithromycin on the prevention or reversal of chlamydial-induced damage to the oviduct or to fertility was assessed in a mouse model of chlamydial salpingitis which closely mimics the human disease . C3H mice were treated with progesterone and then inoculated under the ovarian bursa with a human genital tract isolate of Chlamydia trachomatis, serovar F . Azithromycin at doses from 135-250 mg/kg was administered by oral intubation . Morphological damage to the oviduct lumen was assessed by scanning electron microscopy, while fertility was assessed by breeding experiments . Treatment of mice two or seven days after infection with 135 mg/kg azithromycin completely reversed chlamydial-induced ultrastructural changes and infertility . Treatment 12 or more days after infection, at doses as high as 250 mg/kg, failed to prevent infertility . The onset of fertility correlated with the loss of ciliated epithelia from the oviduct . However, the regeneration of ciliated epithelia following azithromycin treatment did not necessarily restore tubal patency . These results, if true for women also, indicate the need for rapid, effective antibiotic therapy for chlamydial salpingitis to prevent infertility and other sequelae of tubal damage.

J Infect Dis, 1994 Oct, 170(4), 934 - 8
A comparison of anticryptosporidial activity of paromomycin with that of other aminoglycosides and azithromycin in immunosuppressed rats; Rehg JE; Of six evaluated aminoglycosides, paromomycin was the only one that showed activity against Cryptosporidium parvum in immunosuppressed rats . Oral dosages > or = 200 mg/kg/day reduced the severity of ileal infections; however, paromomycin was ineffective against cecal and biliary tract infections at 400 mg/kg/day orally and 50 mg/kg/day intraperitoneally . Oral paromomycin (400 mg/kg/day) was also less effective than azithromycin (400 mg/kg/day) against Cryptosporidium infection involving the ileum, cecum, or biliary tract of immunosuppressed rats . The data suggest that paromomycin may be an effective treatment for acute cryptosporidiosis of the small intestine but is probably ineffective against large intestine or biliary tract infections in the immunosuppressed host.

Ann Ital Med Int, 1994 Oct-Dec, 9(4), 249 - 54
{Treatment and prevention of Mycobacterium avium complex infection in AIDS}; Famularo G et al.; Since Mycobacterium avium complex (MAC) infects most, if not all, HIV-positive patients, effective regimens for its treatment and prophylaxis are a necessity . We review here the available literature in an attempt to establish clear-cut criteria for the administration of antibiotics and immunotherapy and for the prophylactic treatment of MAC infections . Several antibiotics, chiefly in combination regimens, are active against MAC . Recent data indicate rifabutin as a first-line antibiotic for the treatment of MAC infections . However, since this antibiotic accelerates hepatic metabolism of many drugs (zidovudine in particular), it has the potential to reduce their serum concentrations and hence limit their antiviral activity . Moreover, rifabutin is active against retroviruses only at extremely high concentrations which are not reached in vivo at normally-prescribed dosages . The recent demonstration that the cytokine interferon-gamma (IFN-gamma) in combination with conventional antibiotic therapy may be effective for disseminated MAC infections indicates that immunotherapy could play a pivotal role in the treatment of MAC infections . Lifetime prophylaxis with rifabutin (300 mg/die) is advised for all patients with HIV infection and fewer than 100 CD4 T lymphocytes/mm3 in the peripheral blood: this antibiotic regimen significantly reduces the frequency of disseminated MAC infections . Further studies are required to evaluate the effectiveness of other prophylactic regimens such as azithromycin and clarithromycin . We conclude that rifabutin and immunotherapy with IFN-gamma will play a key role in the treatment of MAC infections.

Antimicrob Agents Chemother, 1994 Oct, 38(10), 2449 - 51
Intracellular and extracellular penetration of azithromycin into inflammatory and noninflammatory blister fluid; Freeman CD et al.; The penetration of azithromycin into the blister fluids of six volunteers was analyzed after a 5-day regimen (total of 1.5 g) . Differences in drug concentrations in a paper disk and serum and in the mass of azithromycin from inflammatory blister chamber leukocytes and noninflammatory blister chamber leukocytes were significant (P < 0.05).

Clin Infect Dis, 1994 Sep, 19(3), 486 - 8
Pilot study of azithromycin for treatment of primary and secondary syphilis; Verdon MS et al.; Azithromycin has in vitro activity against Treponema pallidum and is effective against experimental syphilis in rabbits . We undertook an open, noncomparative pilot study of oral azithromycin (500 mg once daily for 10 days) to treat 16 patients with primary or secondary syphilis who were seronegative for human immunodeficiency virus . Cure was documented for 11 of 13 patients observed > or = 3 months; three patients were lost to follow-up . The serological response of one patient with secondary syphilis was indeterminate, and one patient with primary syphilis had either relapse or reinfection . Four patients had mild gastrointestinal side effects, and another patient had an episode of nausea and vomiting; all side effects occurred in the first 3 days and resolved spontaneously as treatment continued . Azithromycin shows promise as an alternative agent for treatment of early syphilis; controlled trials and assessment of other dosage regimens are indicated.

Antimicrob Agents Chemother, 1994 Sep, 38(9), 1937 - 43
Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin; Beale AS et al.; Following intravaginal inoculation of progesterone-treated outbred mice with Chlamydia trachomatis MoPn, 4 to 6 log10 inclusion-forming units were recovered in vaginal swabs for 21 days but all animals were culture negative after 28 days . Serum antibody titers were elevated and remained high for at least 70 days . Between 28 and 70 days, upper tract infection (inflammation and distension of the uterine horns, occlusion of oviducts with inflammatory exudate, pyosalpinx, and hydrosalpinx) was seen in > 80% of the animals . Mice were dosed orally, commencing at 7 days after infection, with minocycline, doxycycline, or amoxicillin-clavulanate . Further groups received azithromycin either as a single high dose or as lower once-daily doses . In addition, minocycline and amoxicillin-clavulanate were administered at 24 h after infection, and this early treatment prevented elevation of antibody titers whereas delayed therapy did not . Vaginal swabs from mice in all treatment regimens were culture negative except for 25% of mice receiving either early amoxicillin-clavulanate or low-dose azithromycin, which yielded low numbers (20 to 70 inclusion-forming units) of chlamydiae . Numbers of fertile mice in the early treatment regimens and their litter sizes were similar to those of noninfected controls, although 25% of amoxicillin-clavulanate-treated mice had unilateral hydrosalpinges . In comparison, 88% of untreated mice developed hydrosalpinges and only 25% conceived . Delayed dosing did not affect the outcome of amoxicillin-clavulanate therapy but did diminish the protective efficacy of minocycline such that 50% of treated mice had either unilateral hydrosalpinges or ovarian abscesses . Doxycycline and azithromycin were highly effective in restoring fertility . This model makes possible the study of both short- and long-term outcomes of chlamydial infection.

Antibiot Khimioter, 1994 Sep-Oct, 39(9-10), 3 - 5
{Interactions in the system of copper ion-azalide (azithromycin)}; Sher AA et al.; Interactions in the bio-inorganic systems of the copper ions and azalide (azithromycin) were analyzed by spectroscopic methods (atom-absorption spectroscopy, IR and UV spectrometry in the visible spectrum) and electrochemical methods (potentiometry) . The system samples within molar ratios of the metal ion and ligand of 10:1 to 1:10 and wide pH ranges were tested . Formation of a compound consisting of the metal ion and ligand at a ratio of 1:1 was detected . The experimental data showed that the product of the compound solubility equaled 9.8.10(-14) (pH 7.0, 0.1 KNO3).

Antimicrob Agents Chemother, 1994 Aug, 38(8), 1862 - 3
Efficacy of azithromycin as a causal prophylactic agent against murine malaria; Andersen SL et al.; The efficacy of the newly marketed azalide azithromycin was compared with that of the clinical agent doxycycline in a murine model of sporozoite-induced malaria . Drug was administered once; Plasmodium yoelii sporozoites were administered 2 h later; survival at day 60 was determined . For parenterally administered drug, 160 mg of azithromycin or doxycycline per kg of body weight was 100% effective; 40 mg of azithromycin per kg was 80% effective, but 40 mg of doxycycline per kg was 40% effective . Orally administered azithromycin was somewhat less effective than parenterally administered drug, consistent with the 37% clinical oral bioavailability of this agent . For orally administered azithromycin, 160 mg/kg was 100% effective and 40 mg/kg was 40% effective . The efficacy of azithromycin in comparison with that of doxycycline and the known prolonged levels of azithromycin in the livers of humans suggest that azithromycin has potential as a clinical causal prophylactic agent for malaria.

Antimicrob Agents Chemother, 1994 Aug, 38(8), 1721 - 5
Intermittent azithromycin for treatment of Mycobacterium avium infection in beige mice; Klemens SP et al.; The activity of azithromycin (AZI) was evaluated in the beige mouse model of disseminated Mycobacterium avium infection . Mice were infected intravenously with approximately 10(7) viable avium ATCC 49601 . AZI at 50, 100, or 200 mg/kg of body weight or clarithromycin (CLA) at 200 mg/kg was given by gavage 5 days per week for 4 weeks . Groups of treated mice were compared with untreated control animals . A dose-related reduction in cell counts in organs was observed with AZI treatment . AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in spleens . The activities of these two agents at 200 mg/kg were comparable against organisms in lungs . In a second study, AZI at 200 mg/kg was given daily for 5 days; this was followed by intermittent AZI treatment for the next 3 weeks . The activities of AZI given on a three-times- and five-times-per-week basis in the continuation phase were comparable . AZI given on a once-weekly basis was less active . The regimen of AZI given in combination with rifapentine on a once-weekly basis for 8 weeks showed promising activity . Clinical evaluation of AZI and rifapentine will help to define the roles of these agents in the treatment of disseminated M . avium complex infection.

Drugs, 1994 Aug, 48(2), 179 - 88
Management of toxoplasmosis; Georgiev VS; Toxoplasma gondii, an intracellular coccidian protozoan, is the causative agent of toxoplasmosis, a widespread infection affecting various birds and mammals including humans . In immunocompetent hosts, the infection is usually asymptomatic and benign . Toxoplasmosis is either congenital or acquired . In general, prenatal therapy of congenital toxoplasmosis is beneficial in reducing the frequency of infant infection . Therapies are based primarily on spiramycin because of the relative lack of toxicity and high concentrations achieved in the placenta . Clindamycin is the standard drug for chemoprophylaxis in newborn infants, and is directed at preventing the occurrence of retinochoroiditis as a late sequel to congenital infection . The standard treatment for acquired toxoplasmosis in both immunocompetent and immunodeficient patients is the synergistic combination of pyrimethamine and sulphonamides . Toxoplasmic encephalitis is the most common manifestation of acquired toxoplasmosis in immunocompromised patients and if not treated is fatal . However, because of toxicity, the therapeutic efficacy of pyrimethamine-sulphonamide combinations may be seriously limited in immunodeficient patients . A number of novel and less toxic agents are being currently studied in clinical settings, including macrolide antibiotics (clindamycin, clarithromycin and azithromycin) and atovaquone, as well as some older anti-infective drugs such as cotrimoxazole (trimethoprim/sulfamethoxazole) . Maintenance or prophylactic therapy is essential in many patients with acquired immunodeficiency syndrome (AIDS) where toxoplasmosis is most often the result of a pre-existent latent infection.

Chemotherapy, 1994 Jul-Aug, 40(4), 252 - 5
Therapeutic effects of roxithromycin and azithromycin in experimental murine brucellosis; Lang R et al.; Mice infected with Brucella melitensis were treated with azithromycin or roxithromycin at a dose of 50 mg/kg/day i.p . alone and in combination with streptomycin 75 mg/kg/day for 14 days . Streptomycin at this dose was previously documented to be ineffective against murine brucellosis . Azithromycin- and azithromycin/streptomycin-treated animals demonstrated a significantly better cure rate than controls . Therapy failure was observed in all mice treated with roxithromycin 50 mg/kg/day i.p . alone or in combination with streptomycin 75 mg/kg/day . Our findings demonstrate that azithromycin cures experimental murine brucellosis and may be an effective alternative in the therapy of human brucellosis.

Antimicrob Agents Chemother, 1994 Jul, 38(7), 1455 - 9
Activities of azithromycin and clarithromycin against nontuberculous mycobacteria in beige mice; Klemens SP et al.; The comparative activities of azithromycin (AZI) and clarithromycin (CLA) were evaluated against nontuberculous mycobacteria in a murine model of disseminated infection . Four-week-old beige mice (C57BL/6J bgj/bgj) were infected intravenously with approximately 10(7) viable Mycobacterium kansasii, M . xenopi, M . simiae, or M . malmoense . Treatment with AZI at 200 mg/kg, CLA at 200 mg/kg, ethambutol at 125 mg/kg, rifampin at 20 mg/kg, or clofazimine at 20 mg/kg of body weight was started 7 days postinfection, and the treatments were administered 5 days per week for 4 weeks . Control groups were sacrificed at the start and end of the treatments . Spleens and lungs were homogenized, and viable cell counts were determined by serial dilution and plating onto 7H10 agar . AZI and CLA had activities comparable to or better than that of rifampin, ethamutol, or clofazimine against these nontuberculous mycobacteria in the beige mouse test system . AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in the spleens for M . xenopi and M . malmoense . The activities of AZI and CLA were comparable against organisms in the spleens for M . kansasii and M . simiae . The activities of these two agents were comparable against organisms in the lungs for all four nontuberculous mycobacterial species . AZI or CLA in combination with other agents may be useful for the therapy of nontuberculous mycobacterial infections in humans.

Antimicrob Agents Chemother, 1994 Jul, 38(7), 1452 - 4
Comparative activities of azithromycin and clarithromycin against Mycobacterium avium infection in beige mice; Cynamon MH et al.; The comparative activities of azithromycin (AZI) and clarithromycin (CLA) against eight Mycobacterium avium complex (MAC) isolates were evaluated in the beige mouse model of disseminated infection . Mice were infected intravenously with approximately 10(7) viable MAC isolate . AZI at 100 or 200 mg/kg of body weight or CLA at 200 mg/kg of body weight was given by gavage daily for 10 days starting at 7 days postinfection . In each study, groups of treated mice were compared with untreated control animals . A dose-related reduction in organism cell counts in the spleens between the groups receiving AZI at 100 and 200 mg/kg was observed . AZI at 200 mg/kg was more active than CLA at 200 mg/kg against six of eight MAC isolates in the spleens . CLA at 200 mg/kg was more active than AZI at 200 mg/kg against three of eight MAC isolates in the lungs . The difference between AZI at 200 mg/kg and CLA at 200 mg/kg against organisms in the lungs was not significant for the remaining five isolates . Clinical trials comparing the activities of AZI and CLA in combination with other agents in patients with disseminated MAC infection are necessary to ascertain any clinically significant differences in the efficacies of these agents.

J Antimicrob Chemother, 1994 Jul, 34(1), 111 - 8
Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis; Dumas JL et al.; The efficacy of prolonged administration of azithromycin was evaluated in a murine model of lethal chronic toxoplasmosis . Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group . All 26 animals given azithromycin 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001) . Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithromycin regimen but viable cysts were identified in the brain tissue of these animals when they were killed . Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin was associated with a reduction in brain inflammation . The concentrations of azithromycin in the brains of five animals ranged from 0.7 to 2.3 micrograms/g; there was no evidence of accumulation even after 100 doses . Azithromycin merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complication.

Clin Ter, 1994 Jul, 145(7), 35 - 9
{Evaluation of the clinical efficacy of azithromycin in acute respiratory infections in children}; Bottaro G et al.; Azithromycin activity in vivo has been studied in a group of children with acute respiratory tract infections in order to test the efficacy and tolerability of this antibiotic . The study involved 135 children treated with a single daily 10 mg/kg dose of azithromycin for three consecutive days . Ten days after this treatment 100% of children with otitis media, tracheobronchitis, or rhinosinusitis and 95.9% of children with pharyngo-tonsillitis were cured . Recurrences were never observed . Azithromycin proved remarkably effective for treatment of acute respiratory infections and otitis media in children . Tolerability and therapeutic compliance were excellent.

Lancet, 1994 Jun 4, 343(8910), 1396 - 7
Azithromycin prophylaxis against a chloroquine-resistant strain of Plasmodium falciparum; Kuschner RA et al.; Azithromycin has antimalarial activity and favourable pharmacokinetic properties for a prophylactic antimalarial agent . We investigated the ability of azithromycin to prevent malaria in volunteers infected with a chloroquine-resistant strain of Plasmodium falciparum . 4 volunteers received oral azithromycin 500 mg followed by 250 mg daily for 7 further days . Subjects were infected on the third day of azithromycin . 3 subjects were protected compared with none of 15 controls . The volunteer not protected by azithromycin had unquantifiable plasma levels of azithromycin, probably because of poor absorption . Azithromycin could be a promising prophylactic agent for P falciparum malaria.

Am J Obstet Gynecol, 1994 May, 170(5 Pt 1), 1375 - 6
Presence of azithromycin breast milk concentrations: a case report; Kelsey JJ et al.; We describe a case of breast milk concentrations of azithromycin, an azalide antibiotic, in a woman with postpartum bilateral tubal ligation incisional cellulitis . Azithromycin appears to demonstrate a time-dependent versus time-accumulation profile in breast milk.

Aliment Pharmacol Ther, 1994 Apr, 8(2), 187 - 92
Activity of metronidazole, azithromycin and three benzimidazoles on Giardia lamblia growth and attachment to a human intestinal cell line; Katelaris PH et al.; BACKGROUND: Attachment of Giardia lamblia trophozoites to enterocytes is essential for colonization of the small intestine and is considered a prerequisite for Giardia-induced enterocyte damage . Inhibition of attachment may therefore have therapeutic potential . METHODS: Enterocyte-like differentiated Caco-2 cells were used as a biologically appropriate attachment surface to determine the effect of three benzimidazole compounds (albendazole, mebendazole and thiabendazole), azithromycin and metronidazole on Giardia attachment . The results were compared with the ability for each drug to inhibit Giardia growth, measured using {3H}-thymidine uptake . RESULTS: The benzimidazoles inhibited Giardia attachment at much lower concentrations than did metronidazole . However, metronidazole was a much more potent inhibitor of growth than any of the benzimidazoles . Azithromycin did not significantly impair Giardia attachment or growth . The benzimidazoles decrease attachment but are less giardiacidal than metronidazole . CONCLUSION: This model appears useful for testing potential antigiardial compounds and investigating mechanisms of drug action.

Minerva Gastroenterol Dietol, 1994 Mar, 40(1), 47 - 9
{Azithromycin-omeprazole . Treatment for the eradication of Helicobacter pylori}; Marchi M et al.; AIM . To evaluate the benefit of 4-week regimen including azithromycin+omeprazole (vs omeprazole alone) for eradication of Helicobacter pylori . METHODS . Twenty HP positive patients with an ulcer dyspepsia (NUD) were included in this study . They were given either omeprazole 40 mg for 4 weeks alone or in combination with azithromycin 1 g/die for 1 week . Endoscopy was performed before 4 weeks after and 4 months after treatment . The presence of HP was assessed in antral and corporeal biopsies by urease test and histology . RESULTS . HP eradication was observed in 9/10 (90%) patients in the omeprazole+azithromycin group and 0/10 patients in the omeprazole alone group . CONCLUSION . Omeprazole 40 mg for 4 weeks in combination with azithromycin 1 g die for 1 week eradicates HP in 90% of these patients . The good eradication percentage and absence of collateral effect make us extend patients' number to test.

Clin Ter, 1994 Jan, 144(1), 27 - 30
{Effectiveness of and tolerance to azithromycin versus roxithromycin in the treatment of patients with acute infections of the upper respiratory tract}; Bosatra A et al.; A multicenter open prospective comparative study was carried out during two years enrolling 60 patients with upper respiratory infections . Thirty were treated with single daily 500 mg doses of azithromycin for three days, and 30 received two daily doses of roxithromycin of 150 mg each for seven days . Both treatments were equally well tolerated, and there was no substantial difference concerning clinical recovery . However, azithromycin treatment was more practical and of shorter duration.

Antimicrob Agents Chemother, 1994 Jan, 38(1), 31 - 7
Comparison of mutants of Toxoplasma gondii selected for resistance to azithromycin, spiramycin, or clindamycin; Pfefferkorn ER et al.; Azithromycin and spiramycin markedly inhibited the growth of Toxoplasma gondii in cultured human fibroblasts . However, 3 days of treatment were required to reveal their full antitoxoplasma activity . This delayed onset of inhibition was similar to that previously reported for clindamycin . Mutants of T . gondii resistant to azithromycin (AziR-1) and spiramycin (SprR-1) were isolated and compared with a previously described mutant resistant to clindamycin (ClnR-2) . Mutant ClnR-2 was cross-resistant to all three antibiotics, while AziR-1 was cross-resistant only to spiramycin and SprR-1 was cross-resistant only to azithromycin . In short-term studies of protein synthesis by freshly prepared extracellular parasites, clindamycin and azithromycin were effective only at concentrations much greater than their 50% inhibitory concentrations in infected cultures and the resistant mutants did not differ from the wild type in antibiotic sensitivity . Thus, protein synthesis on cytoplasmic ribosomes of the parasite did not seem to be the target of these antibiotics . To determine whether mitochondrial protein synthesis in T . gondii was inhibited by clindamycin or azithromycin, wild-type parasites were grown in cultured cells in the presence of antibiotic concentrations well above the 50% inhibitory concentrations . Mitochondrial function, measured by oxygen uptake per purified extracellular parasite, did not decrease substantially, after the parasites had multiplied 11-fold in the presence of antibiotic . Thus, mitochondrial protein synthesis did not seem to be the target of clindamycin or azithromycin . An alternative target is protein synthesis in the putative apicomplexan organelle that has a 35-kb genome.

Drugs Exp Clin Res, 1994, 20(3), 121 - 6
Comparison of the effects of midecamycin acetate and azithromycin on gastrointestinal motility in man; Sifrim D et al.; The gastrointestinal motor effects of the macrolide antibiotic, azithromycin, were compared with those of midecamycin acetate . The method of investigation consisted of intraluminal pressure measurements in the gastric antrum and upper small intestine by means of a low compliance perfused catheter system . Eleven healthy volunteers participated in the single blind, placebo-controlled study of both interdigestive and postprandial gastrointestinal motility . Azithromycin was administered by mouth in a single 500 mg dose or in two daily doses of 250 mg; midecamycin acetate was given in a dose of 600 mg b.i.d . The effect of midecamycin acetate on gastric antral and jejunal motility was not significantly different from that of placebo . This was true for both the interdigestive and the postprandial phases of gastrointestinal motility . Peroral treatment with azithromycin resulted in a statistically significant increase in the postprandial antral motility index as compared to placebo . This increase was observed in the distal antrum as well as in the proximal antrum . In addition, the gastric contractions were found to originate higher up in the stomach after azithromycin as compared to placebo or midecamycin acetate.

Scand J Infect Dis, 1994, 26(6), 706 - 10
Three-day azithromycin compared with ten-day roxithromycin treatment of atypical pneumonia; Schonwald S et al.; An open, randomized, multicentre study compared the efficacy and safety of 3-day azithromycin with 10-day roxithromycin for the treatment of atypical pneumonia . Azithromycin was administered 500 mg once daily to 90 and roxithromycin 150 mg bid to 60 patients . Causative pathogens were identified by serological methods . In the azithromycin treatment group, Mycoplasma pneumoniae was identified in 65, Chlamydia spp . in 9 and Coxiella burnetti in 1 patient . In the roxithromycin treatment group, M . pneumoniae was identified in 39, Chlamydia spp . in 9 and C . burnetti in 3 patients . 89 azithromycin and 53 roxithromycin patients were eligible for efficacy analysis . Clinical cure rate was 98.9% in the azithromycin and 94.3% in the roxithromycin treatment group . Adverse events were observed in 3 patients in each group . Azithromycin appears to be as effective as roxithromycin for the treatment of atypical pneumonia . The 3-day azithromycin regimen may offer an additional advantage over 10-day roxithromycin by virtue of its more convenient administration.

J Ocul Pharmacol, 1994 Winter, 10(4), 633 - 41
Ocular pharmacokinetics of orally administered azithromycin in rabbits; O'Day DM et al.; Azithromycin was orally administered to Dutch-belted rabbits following extracapsular lens extraction in one eye . At various times the animals were sacrificed, and serum and ocular tissues were obtained for drug level determination by HPLC-EC . Following a single dose, peak levels of drug in ocular tissues were measured within 8 hours (cornea > 0.5 micrograms/g {15mg/kg}; > 1.5 micrograms/g {3Omg/kg}) . Highest levels were obtained in iris and ciliary body ( > 15 micrograms) . Measurable tissue levels persisted for at least 120 hours . Trough levels increased proportionately during drug multiple dose administration . Five days following five daily 15mg/kg doses, corneal levels exceeded 0.5 micrograms/g, and iris and ciliary levels were higher than 15 micrograms/g . Aqueous humor and serum levels were equivalent . Vitreous humor levels, though higher than aqueous humor, were consistently < 1 microgram/ml . Extracapsular cataract extraction did not significantly affect drug uptake.

Int J Tissue React, 1994, 16(5-6), 211 - 20
Accumulation, release and subcellular localization of azithromycin in phagocytic and non-phagocytic cells in culture; Carlier MB et al.; The authors have examined the pharmacokinetic parameters of azithromycin in phagocytic (J774 macrophages) and non-phagocytic (rat embryo fibroblasts and NRK-cells) cultured cells . Azithromycin demonstrates an exceptionally large accumulation in all the cell types tested (perhaps in two functionally and structurally distinct compartments) and a slow release of the cell-associated drug . Azithromycin probably accumulates in cells by a non-specific transport process following the model of diffusion/segregation . The cell-associated drug distributes mostly in the lysosomal compartment (50-70%) and the remaining part is freely soluble in the cytosol . In fibroblasts, and to a lesser extent in NRK-cells, azithromycin (10mg/l) induces a decrease of the buoyant density of the lysosomes which may be brought about by the drug itself together with osmotically-bound water and/or by the accumulation of low-density materials within these organelles . These observations open important questions with respect to the potential toxicity of azithromycin . The significance of such alterations and of their biological consequences are at present under investigation.

Clin Pharmacokinet, 1993 Nov, 25(5), 370 - 4
Azithromycin clinical pharmacokinetics; Lalak NJ et al.; Azalide antibiotics, of which azithromycin is the first demonstrated, have different pharmacokinetics from other antibiotics currently used . The bioavailability of the drug is approximately 37% . Extensive and rapid distribution from serum into the intracellular compartments is followed by rapid distribution to the tissues . Tissue concentrations exceed serum concentrations by up to 100-fold following a single azithromycin 500mg dose . Concentration of the drug within phagocytes aids in its ability to combat infections . High concentrations of azithromycin are found in the tonsil, lung, prostate, lymph nodes and liver, with only small concentrations found in fat and muscle . A 500mg dose on day 1, followed by 250mg daily on days 2 to 5, has been demonstrated to maintain azithromycin concentrations at sites of infection and continues to be effective for several days after administration has ceased . The pharmacokinetics of azithromycin make it a drug with diverse therapeutic applications.

Eur J Clin Microbiol Infect Dis, 1993 Nov, 12(11), 853 - 6
Pyrimethamine plus azithromycin for treatment of acute toxoplasmic encephalitis in patients with AIDS; Saba J et al.; A prospective study was conducted to evaluate azithromycin in combination with pyrimethamine for treatment of acute Toxoplasma encephalitis in patients with AIDS . Of the 14 patients given 75 mg pyrimethamine and 500 mg azithromycin daily for four weeks, eight were evaluable for clinical response . Five responded favorably, one had an intermediate response and two an unfavorable response . Of the nine patients evaluable for radiological response, six responded favorably, and three had an intermediate response . Eleven adverse events occurred in nine patients: rash (n = 5), abnormal liver function (n = 2), vomiting (n = 3) and hypoacousia (n = 1) . This pilot study suggests that the combination of pyrimethamine and azithromycin may be further investigated and that the optimal dosage of azithromycin has yet to be determined.

Antimicrob Agents Chemother, 1993 Sep, 37(9), 1993 - 6
In vitro evaluation of the activities of azithromycin alone and combined with pyrimethamine against Toxoplasma gondii; Cantin L et al.; By using an in vitro microassay to assess drug interaction, azithromycin combined to pyrimethamine was found more active than pyrimethamine alone against Toxoplasma gondii, and additivity between those drugs was demonstrated . Our results show that the combination of azithromycin and pyrimethamine may lead to a more rapid control of T . gondii.

Antimicrob Agents Chemother, 1993 Sep, 37(9), 1786 - 9
In vivo administration of azithromycin affects lymphocyte activity in vitro; Tomazic J et al.; A therapeutic dose of azithromycin was administered to test subjects and then the following lymphocyte functions were examined in vitro: proliferative lymphocyte response to stimulation with pokeweed mitogen, levels of immunoglobulins G, A, and M in serum, and the amount of the soluble interleukin 2 receptors in supernatants of mononuclear cell cultures stimulated with phytohemagglutinin and phorbol myristate acetate . The study was performed as a controlled clinical trial comparing an azithromycin-treated group (n = 21) and a placebo-treated control group (n = 10) . Healthy female volunteers were placed into one of the two groups, and the study was performed as a double-blind trial . Although the findings of the present study showed that azithromycin significantly increased the proliferative lymphocyte response to pokeweed mitogen, the results could have been due to experimental variation . However, impairment of the lymphocyte function was not observed, which could represent valuable information . Likewise, no effect of azithromycin on levels of the immunoglobulins in serum was observed . The most marked effect of azithromycin on the lymphocyte function was demonstrated by an elevation in the amount of soluble interleukin 2 receptor production in mononuclear cell cultures . The lack of impairment or, perhaps, even a beneficial influence on the immunodefense system may be an important property of azithromycin, especially in immunocompromised individuals.

Clin Infect Dis, 1993 Aug, 17(2), 264 - 6
Rapid response of AIDS-related bacillary angiomatosis to azithromycin; Guerra LG et al.; A 28-year-old male with AIDS and a CD4 cell count of 100/mm3 presented with fever, hepatosplenomegaly, weight loss, and multiple, polypoid, angiomatous lesions on his face . It was determined by means of biopsy that the lesions were due to bacillary angiomatosis . The patient was treated with oral azithromycin (1 g daily as a single dose) . Rapid resolution of the skin lesions was noted . After 1 week of therapy, diminution in the size of the liver and spleen was noted . The only significant side effect noted was diarrhea, which was controlled with symptomatic therapy.

Antimicrob Agents Chemother, 1993 Aug, 37(8), 1701 - 3
Inhibition of Toxoplasma gondii protein synthesis by azithromycin; Blais J et al.; Azithromycin was shown to specifically inhibit the protein synthesis of Toxoplasma gondii in experimental systems by using free tachyzoites and T . gondii-infected mouse macrophages . RNA synthesis of the parasite was not affected by azithromycin . Inhibition of protein synthesis was also proportional to the relative anti-Toxoplasma activity of three macrolides.

J Pediatr, 1993 Jul, 123(1), 154 - 6
Azithromycin for treatment of severe Cryptosporidium diarrhea in two children with cancer; Vargas SL et al.; Two children with cancer received azithromycin for Cryptosporidium-associated diarrhea that was unresponsive to supportive care . One child had choleriform diarrhea requiring daily fluid replacement of up to 65% of his total body weight; the other had protracted diarrhea and wasting . In both cases, administration of azithromycin was followed by prompt clinical improvementPublication Types:

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