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