Azithromycin

Med Arh, 2004, 58(6), 331 - 4
Chlamydia pneumoniae infection in Slovenian patients with diffuse coronary artery disease; Zorc M et al.; Chlamydia pneumoniae (CP) infection might be involved in the pathogenesis of various forms of coronary artery disease (CAD), but there are no data about diffuse CAD with clinical picture of stable angina pectoris . Authors in a prospective study determined serum CP antibody levels (with MIF test) of 71 patients with coronarographically proven diffuse CAD and compared them to the age matched control group of the healthy Slovenian population . After azithromycin treatment in patients with chronic CP infection or reinfection, the CP antibody levels were determined again . A high percentage of chronic infection with CP was demonstrated (83.1%), and almost half (46.5%) of patients with diffuse CAD had reinfection or reactivation of chronic infection . A significantly higher prevalence of chronic CP infection was found in patients with diffuse CAD than in the healthy population (83.1% vs . 15.9%, p< 0.0001) . After treatment with azithromycin, IgA seronegativity was achieved in 17.3%, in 23.1% the titer was lowered, however, in 57.7% of patients no change of antibody titers was found . In conclusion, a high prevalence of chronic infection with CP was found in patients with diffuse CAD . With azithromycin therapy, the eradication of chronic infection is difficult to achieve as well as to prove.

J Clin Microbiol, 2005 Jan, 43(1), 520 - 2
Acute hemorrhagic pericarditis in a child with pneumonia due to Chlamydophila pneumoniae; Tenenbaum T et al.; Chlamydophila pneumoniae is mainly responsible for respiratory tract infections but has also been associated with endocarditis and myocarditis . We report a case of pneumonia in a child with hemorrhagic pericardial effusion with a positive result by a new C . pneumoniae TaqMan PCR, suggesting a pericardial inflammation directly induced by C . pneumoniae . C . pneumoniae should be suspected in patients with community-acquired pneumonia and concurrent pericarditis . Empirical treatment with azithromycin seems feasible.

Obstet Gynecol Surv, 2005 Jan, 60(1), 16 - 17
Contemporary Management of Preterm Premature Rupture of Membranes: Determinants of Latency and Neonatal Outcome; Gopalani S et al.; Preterm premature rupture of membranes (PPROM) occurs in approximately 3% of all births and accounts for 30% of neonatal morbidity/mortality in premature pregnancies . In the past, a majority of women have delivered within 48 hours of presenting, but recent trials in which women received antibiotics and steroids report that 40% to 50% of them delivered a week after presentation . This retrospective study analyzed outcomes in 134 women seen at 24 to 32 weeks gestation with PPROM . They uniformly received glucocorticoids antenatally (2 12-mg intramuscular doses of betamethasone 24 hours apart or 4 6-mg doses of dexamethasone given intravenously at 12-hour intervals) and antibiotics (usually ampicillin followed by amoxicillin or ampicillin with azithromycin) . The women were monitored by daily nonstress testing and twice-weekly biophysical profiles . Tocolysis was used in nearly 60% of women when regular contractions occurred for 48 hours after admission to ensure fetal exposure to steroids.Forty-three women, 32% of participants, had a latency period exceeding 1 week . On univariate analysis, the only maternal factor significantly associated with short latency was nulliparity . Bacterial vaginosis correlated with a shorter interval to delivery when intermediate, and not only positive, Gram stains were taken into account . Both mean and median latencies increased with declining gestational age . On multivariable linear regression analysis, the amniotic fluid index at admission correlated directly and significantly with latency . Gestational age and the white blood cell count at admission also were independent predictors of latency . There was a trend, although not a significant one, toward increasing intrauterine inflammation with longer latency . Funisitis did occur significantly more often when latency exceeded 1 week . There were no fetal deaths and no significant intraventricular hemorrhage after 28 weeks gestation.The finding that the risk of intrauterine inflammation increases with prolonged latency after PPROM is of concern in view of recent reports relating neonatal infection to long-term neurologic problems.

Clin Infect Dis, 2005 Jan 1, 40(1), 136 - 45 Epub 2004 Dec 06.
Comparison of atovaquone and azithromycin with trimethoprim-sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection; Hughes WT et al.; BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children . Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin . METHODS: A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years . Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP-SMZ daily for >or=2 years . RESULTS: Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs . 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient-years; 95% confidence interval {CI}, -0.22 to 14.12) . Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years) . The results marginally favored atovaquone-azithromycin therapy statistically . Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles . CONCLUSIONS: We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP-SMZ for the prevention of serious bacterial infections and is similarly tolerated.

J Oral Pathol Med, 2005 Jan, 34(1), 13 - 6
Clinical and immunological effects of azithromycin in Behcet's disease; Mumcu G et al.; Background: The aim of this study was to evaluate the effects of azithromycin on mucocutaneous manifestations, oral health and immune response in Behcet's disease (BD) . Methods: Eight BD patients with active mucocutaneous symptoms were treated with azithromycin for 4 weeks . Oral health, clinical manifestations and in vitro interleukin (IL)-12, interferon (IFN)-gamma, IL-10 and monocyte chemotactic protein (MCP)-1 responses were evaluated before and after treatment . Results: The number of folliculitic lesions, healing time of oral ulcers and scores of plaque indexes (PLIs) were lower after azithromycin treatment (P < 0.05) . Scores of PLIs correlated positively with the healing time of oral ulcers (P = 0.02) . Although a trend towards increased stimulated IL-10 responses with azithromycin was observed, no statistically significant difference was found . Stimulated and unstimulated MCP-1, IFN-gamma and IL-12 responses were similar before and after treatment (P > 0.05) . Conclusion: Azithromycin was observed to be effective in decreasing folliculitic lesions and fastening the healing time of oral ulcers in BD . J Oral Pathol Med (2005) 34: 13-6.

J Chromatogr B Analyt Technol Biomed Life Sci, 2005 Jan 5, 814(1), 37 - 42
Quantitative determination of azithromycin in plasma, blood and isolated neutrophils by liquid chromatography using pre-column derivatization with 9-fluorenylmethyloxycarbonyl-chloride and fluorescence detection; Wilms E et al.; In this study, a high-performance liquid chromatographic method with pre-column derivatization and fluorescence detection was optimised and validated for the quantification of azithromycin (AZM) in plasma . Clarithromycin (CLM) was used as an internal standard . Pre-column derivatization was done with 9-fluorenylmethyloxycarbonyl-chloride . Recovery from blood and polymorphonuclear neutrophils (PMNNs) isolated by a gravity separation procedure was also assessed . Analytical separation was carried out using a C18 column as stationary phase and acetonitril-phosphatebuffer as mobile phase . Peak quantification was carried out by excitation at 267nm and detection at 317nm . A lower limit of quantitation of 0.042+/-0.017mg/l in plasma, 0.119+/-0.065mg/l in blood and 0.072+/-0.036 in water was achieved . Linearity was assessed from 0 to 1.5mg/l in plasma and blood and from 0-9mg/l in water . The analytical method proved to be applicable in a pharmacokinetic study of AZM in a Cystic Fibrosis patient.

Pediatr Infect Dis J, 2004 Oct, 23(10), 965 - 6
Recurrent acute interstitial nephritis induced by azithromycin; Soni N et al.; A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis . The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired . Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury.

Am J Cardiol, 2004 Dec 1, 94(11), 1426 - 9
Effect of azithromycin therapy on coronary circulation in patients with coronary artery disease; Hyodo E et al.; This study examined the effect of azithromycin therapy on the coronary microcirculation using measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography in 35 patients with coronary artery disease . CFVR increased significantly after azithromycin therapy (3.0 +/- 0.7 vs 3.5 +/- 0.7, p <0.001) . The changes in CFVR were negatively correlated with changes in high-sensitivity C-reactive protein levels in patients receiving azithromycin.

Respir Care, 2004 Nov, 49(11), 1349 - 53
Bronchioloalveolar carcinoma masquerading as pneumonia; Thompson WH; Bronchioloalveolar carcinoma (BAC) is a relatively rare adenocarcinoma that typically arises in the lung periphery and grows along alveolar walls, without destroying the lung parenchyma . It is often multicentric and may arise from a previously stable scar . Because the parenchyma is preserved and because BAC may arise simultaneously in multiple lobes, the chest radiograph and symptoms (cough, chest pain, and sputum production) may be indistinguishable from pneumonia or other noninfectious inflammatory processes (eg, hypersensitivity pneumonitis or bronchiolitis obliterans) . The clinician should suspect BAC if what otherwise appears to be pneumonia lacks fever or leukocytosis or does not respond to antibiotics . BAC accounts for 2.6-4.3 % of all lung cancers . On a radiograph, BAC often appears as a solitary nodule, but may also appear as a patchy, lobar or multilobar infiltrates, often with air bronchograms indistinguishable from pneumonia . Positron-emission tomography does not help distinguish BAC from pneumonia . Among BAC patients, 62% present without symptoms and with only an abnormal radiograph, whereas 38% present with symptoms of cough, chest pain, and sputum production . Bronchoscopy is usually normal . Preoperative diagnosis with transbronchial biopsy, bronchoscopic cytology examination, or expectorated sputum cytology is more common with the diffuse or multicentric forms . Cure depends on complete resection . A trial of antibiotics and reassessment of clinical findings is a reasonable approach, but biopsy or cytology is the only means of ruling in malignancy and ruling out other etiologies, so biopsy should always be considered when a presumed pneumonia does not respond to antibiotics . I saw a 61-year-old man whose initial diagnosis was pneumonia . He took a 10-day course of oral azithromycin, but his symptoms and chest radiograph were unchanged . A tomogram showed interstitial prominence and peripheral air-space disease in the right upper and lower lobes . Transbronchial biopsy of the right upper lobe showed Clara cells, with substantial atypia and various nuclear-cytoplasmic ratios . The underlying pulmonary architecture was preserved and no invasive component was seen . The diagnosis was changed to nonmucinous BAC . Pneumonectomy was successful and he was cancer-free for about 10 months, after which the cancer returned and from which he eventually died.

Ann Pharmacother, 2005 Jan, 39(1), 86 - 94 Epub 2004 Nov 23.
Use of macrolides and tetracyclines for chronic inflammatory diseases; Voils SA et al.; OBJECTIVE: To review the efficacy of macrolides and tetracyclines in several chronic inflammatory conditions . DATA SOURCES: Searches of MEDLINE (1966-March 2004) and an extensive bibliography search were undertaken . Key terms included acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis, rosacea, and rheumatoid arthritis . STUDY SELECTION AND DATA EXTRACTION: Data were obtained primarily from randomized placebo-controlled trials upon which key recommendations are based . DATA SYNTHESIS: Antibiotics are often prescribed for months or even years for treatment of chronic inflammatory conditions such as acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis, rosacea, and rheumatoid arthritis . Randomized controlled trials have shown that azithromycin is useful in the management of cystic fibrosis and the tetracyclines are beneficial in the management of rheumatoid arthritis, acne, blepharitis, and periodontitis . Several large, randomized controlled trials have failed to show any benefit of macrolides in the secondary prevention of cardiovascular disease . No randomized placebo-controlled clinical trials have been performed to assess the efficacy of macrolides or tetracyclines in patients with rosacea . CONCLUSIONS: The use of tetracyclines and macrolides for rosacea is based primarily on anecdotal reports or open-label trials . Limited clinical trials support the use of tetracyclines or macrolides in acne, blepharitis, periodontitis, rheumatoid arthritis, and cystic fibrosis . Trials to date do not support the use of antibiotics for secondary prevention of cardiovascular disease.

Trans R Soc Trop Med Hyg, 2005 Jan, 99(1), 6 - 12
Simplification and improvement of height-based azithromycin treatment for paediatric trachoma; Basilion EV et al.; Recent data showing that azithromycin is safe at higher dosages than previously documented provide an opportunity to explore several important improvements in the efficiency and effectiveness of height-based treatment of paediatric trachoma . The purpose of this study is to examine the feasibility of a single standardised schedule for application in any trachoma-endemic region . Data for 60813 children from Asia, North and sub-Saharan Africa were analysed . A height schedule maximizing the number of children receiving treatment of 20-40 mg/kg, a conservative estimate of the safe and effective treatment range for paediatric trachoma, was developed . Using the standardised schedule, 97.7% of children aged 6 to 59 months receiving oral suspension and 96.7% of children aged 60 months to 15 years receiving tablets would have received treatment within a dosage range of 20-40 mg/kg . Less than 1% of all children would have received treatment less than 20 mg/kg . These findings suggest that the schedule presented in this paper is likely to yield safe and effective treatment for a broad range of populations vulnerable to trachoma while substantially improving the efficiency of height-based treatment.

Rom J Intern Med, 2003, 41(3), 323 - 8
Multiple myeloma in remission complicated by bone marrow granulomas; Gologan R et al.; BACKGROUND: Granulomas are encountered in 1-2% of biopsies performed in various hematological and non-hematological diseases . Almost 50% of bone marrow granulomas are associated with infections and 25% with hematologic disorders, especially lymphoma and multiple myeloma . Toxoplasmosis is reported to induce granulomas in bone marrow inmunosuppressed patients . On the other side, long-term unexplained remissions after conventional treatment in multiple myeloma were mentioned in up to 10% of cases . CASE REPORT: A 56-years-old female patient was diagnosed with IgG(kappa) multiple myeloma in 1992 . After 5 years, being still in complete remission, frequent bone marrow epithelioid non-caseating granulomas were noticed in biopsy, without clinical symptomatology or modifications of routine paraclinical examinations . The history revealed no treatments with antiarrhythmic, antihypertensive, anticonvulsivants or nonsteroid antiinflammatory drugs . The serologic tests for other infections or systemic diseases known to induce granulomas were negative, except those for toxoplasma gondii IgG . The treatment with azithromycine and pyrimethamine induced the disappearance of granulomas, simultaneously with an important decrease of anti-toxoplasma IgG antibodies titer . CONCLUSIONS: The bone marrow granulomas provide a valuable histologic clue to opportunistic infections and the bone marrow biopsy is useful for their diagnosis . In the specific case of toxoplasmosis, a recently proposed treatment with azithromycin induced the resolution of the granulomas . Due to the usual lack of specificity of the most bone marrow granulomas, a broad and long-term clinical, histopatological and serological follow-up to establish the etiology should be performed.

N Engl J Med, 2004 Nov 4, 351(19), 1962 - 71
Mass treatment with single-dose azithromycin for trachoma; Solomon AW et al.; BACKGROUND: Trachoma, caused by repeated ocular infection with Chlamydia trachomatis, is an important cause of blindness . Current recommended dosing intervals for mass azithromycin treatment for trachoma are based on a mathematical model . METHODS: We collected conjunctival swabs for quantitative polymerase-chain-reaction assay of C . trachomatis before and 2, 6, 12, 18, and 24 months after mass treatment with azithromycin in a Tanzanian community in which trachoma was endemic . For ethical reasons, at 6, 12, and 18 months, we gave tetracycline eye ointment to residents who had clinically active trachoma . RESULTS: At baseline, 956 of 978 residents (97.8 percent) received either one oral dose of azithromycin or (if azithromycin was contraindicated) a course of tetracycline eye ointment . The prevalence of infection fell from 9.5 percent before mass treatment to 2.1 percent at 2 months and 0.1 percent at 24 months . The quantitative burden of ocular C . trachomatis infection in the community was 13.9 percent of the pretreatment level at 2 months and 0.8 percent at 24 months . At each time point after baseline, over 90 percent of the total community burden of C . trachomatis infection was found among subjects who had been positive the previous time they were tested . CONCLUSIONS: The prevalence and intensity of infection fell dramatically and remained low for two years after treatment . One round of very-high-coverage mass treatment with azithromycin, perhaps aided by subsequent periodic use of tetracycline eye ointment for persons with active disease, can interrupt the transmission of ocular C . trachomatis infection .

Pol Merkuriusz Lek, 2004 May, 16 Suppl 1, 96 - 9
{Evaluation of clinical efficacy and direct costs of azithromycin treatment for exacerbation of chronic obstructive pulmonary disease in hospitalized and out-patients}; Faber M et al.; This paper presents the efficacy and cost of therapy with azithromycin for the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) . Two subgroups were investigated: out-patients and hospitalized patients--20 in each group (17 women and 23 men) . Azithromycin 500 mg was administered sequentially once daily . A complete physical examination including temperature, respiratory rate, cough, production and characteristics of sputum so as general aspects of quality of life assessed by COPD exacerbation questionnaire was made in hospitalized patients on a daily base and in a day 10-14 after the end of therapy . Out-patients were assessed in day 1, 3-5 days after the start of study drug treatment and 10-14 days after the end of therapy . Pulmonary function tests were assessed three times during the whole study course . The results of the study suggest similar duration of therapy with azithromycin in both study subgroups, whereas in out-patients decrease and regression of symptoms were statistically significantly quicker with tendency approximately the same in both study subgroups . The cost of therapy with azithromycin was similar in both subgroups but the complete cost of COPD exacerbation treatment was significantly lower in out-patients in comparison to hospitalized patients group (473.71 PLN and 2587.87 respectively).

Am J Manag Care, 2004 Oct, 10(10), 670 - 8
Increasing adherence to a community-based guideline for acute sinusitis through education, physician profiling, and financial incentives; Greene RA et al.; OBJECTIVES: To implement a large-scale multifaceted intervention consisting of physician education, profiling, and a financial incentive, to improve treatment quality for acute sinusitis . STUDY DESIGN: Cohort trial using a historical control of treatment patterns among approximately 500 internists, 200 family practitioners, and 200 pediatricians in a northeastern community-wide individual practice association . PARTICIPANTS AND METHODS: Episode treatment group methods were adapted to identify cases (episodes) and to assess care patterns for acute sinusitis among 420,000 health maintenance organization patients seen between January 1, 1999, and December 31, 2001 . The intervention consisted of care pathway development, physician and patient education, physician profiling, and a financial incentive . RESULTS: A statistical process control chart showed a shift toward recommended treatment patterns after our intervention . The rate of exceptions per episode of acute sinusitis decreased 20%, from 326 exceptions per 1000 episodes between January 1, 1999, and October 31, 2000, to 261 between November 1, 2000, and December 31, 2001 . Decreased use of less effective or inappropriate antibiotics accounted for most of the change (199 to 136 exceptions per 1000 episodes {32% change}) . Azithromycin use decreased 30%, from 97 to 68 prescriptions per 1000 episodes . Firstline antibiotic (amoxicillin and doxycycline) use increased 14%, from 451 to 514 prescriptions per 1000 episodes . Inappropriate radiology use decreased 20%, from 15 to 12 per 1000 episodes . These changes were significant at P < .005 . CONCLUSION: A multifaceted program, including education, physician profiling with actionable recommendations, and a financial incentive, significantly increased physicians' adherence to a community-developed care pathway and was successful at improving adherence to recommended patterns of antibiotic use in acute sinusitis.

J Dermatol, 2004 Aug, 31(8), 682 - 6
Treatment of confluent and reticulated papillomatosis with azithromycin; Atasoy M et al.; Confluent and reticulated papillomatosis (CRP) is a relatively rare disorder of unknown origin, mostly affecting young female adults . We here present the case of a 21-year-old male patient with confluent and reticulated papillomatosis . Skin examination revealed brownish, verrucous, hyperkeratotic, 2 to 5 mm papules, which formed confluent patches and plaques with a reticulate network on the interscapular area . The patient was initially treated with ketoconazole cream for two weeks without improvement . The disease can be rather persistent and resistant to topical therapy . Our case showed a satisfactory response to treatment with azithromycin . Although this treatment is known to be effective in some cases, the action mechanism of azithromycin on CRP is not fully understood.

Am J Ophthalmol, 2004 Oct, 138(4), 547 - 53
Corneal pharmacokinetics of topically applied azithromycin and clarithromycin; Kuehne JJ et al.; PURPOSE: To determine corneal levels of topically administered azithromycin and clarithromycin in a rabbit model . DESIGN: Experimental animal study . METHODS: Corneas of New Zealand albino rabbits were treated with topical azithromycin (2 mg/ml or 4 mg/ml) or clarithromycin (10 mg/ml) . Topical azithromycin was prepared from an intravenous solution and topical clarithromycin from a suspension for oral use . All rabbits received one drop every 2 hours on the right eye . Groups of rabbits were treated for the following intervals: 6, 12, 24, and 48 hours (four rabbits for each combination of time point, drug, and dose) . Corneal tissue was removed 1 hour after the last application . To investigate stability of tissue azithromycin levels, an additional group of four rabbits was treated for 24 hours, but corneal tissue was not removed until 24 hours later . Samples were homogenized, and drug concentrations were measured using high-pressure liquid chromatography (HPLC) analysis and bioactivity assay . RESULTS: Corneal concentrations of azithromycin increased with drug dosage and duration of application . Rabbits treated with azithromycin tolerated the drug well without signs of irritation . Clarithromycin was undetectable in corneal tissue by HPLC and bioactivity assay for all rabbits . Some rabbits treated with clarithromycin had signs of ocular surface irritation . CONCLUSION: Measurable concentrations of azithromycin are achieved in corneal tissue after topical application in a rabbit model, and the drug is well tolerated . Azithromycin may be a useful antibiotic for the topical treatment of human corneal infections, but clarithromycin, in currently available formulations, may not be effective because of poor tissue penetration.

Int J Dermatol, 2004 Oct, 43(10), 766 - 7
Acne treated successfully with azithromycin; Kapadia N et al.; AIM: To study the efficacy, safety, and compliance of 500 mg azithromycin thrice weekly for 12 weeks in acne vulgaris . METHODS: An open-label, noncomparative study was carried out for 12 weeks at the outpatient clinics of Aga Khan University Hospital, Abassi Shaheed Hospital, and Burhani Community Hospital in Karachi, Pakistan . Thirty-five adolescent and postadolescent patients with moderate to severe papulopustular acne vulgaris were enrolled . All patients completed the study . Azithromycin, 500 mg orally thrice weekly for 12 weeks, was used . After the baseline visit, patients were scheduled to return at four-weekly intervals for 12 weeks . Efficacy was gauged by the percentage clearance of papulopustular acne lesions . Safety assessments included the monitoring of adverse events, and compliance was checked at the four-weekly regular visits up to 12 weeks . RESULTS: Twenty-nine patients (82.9%) showed remarkable improvement in the first 4 weeks with 60% reduction of their inflammatory papulopustular lesions . Maximum clearance (80%) was observed at 12 weeks . Residual postinflammatory pigmentation and pitted and linear scarring represented the aftermath of the relapsing pattern of acne . Six patients (17.1%) showed slow clearance with eruptions of new lesions . Adverse events, such as heartburn and nausea, were reported by four patients (11.4%) . All patients completed the 12-week study period . CONCLUSION: Azithromycin, 500 mg thrice weekly for 12 weeks, is a safe and effective treatment of acne vulgaris with excellent patient compliance.

Expert Rev Anti Infect Ther, 2003 Jun, 1(1), 175 - 82
Sulfadiazine and pyrimethamine in the postnatal treatment of congenital toxoplasmosis: what are the options?
Petersen E, Schmidt DR.
Pre- and neonatal screening for congenital toxoplasmosis rests upon the assumption that treatment is beneficial on either acute symptoms or in preventing later reactivation . Postpartum treatment of congenital toxoplasmosis with sulfadiazine and pyrimethamine has remained almost unchanged for 50 years . More recently, sulfadiazine has been substituted by sulfadoxine, which has a much longer half-life and provides a basis for a dose schedule with higher compliance . Newer drugs with potential effects against Toxoplasma gondii, such as azithromycin, atovaquone and clindamycin, require further evaluation in animal models and human studies . No randomized controlled trials have ever been conducted . The available studies are either observational studies of groups of referred patients or observational studies with historical controls accrued over many years, often decades . Pre- and neonatal screening for congenital toxoplasmosis is performed on more than two million pregnant women every year in Europe, North and South America at the estimated cost of more than 500 million annually . The benefit needs to be documented by a prospective, placebo-controlled randomized study, which needs to be organized and financed by the countries performing nationwide, universal screening programs.

Mol Microbiol, 2004 Oct, 54(2), 376 - 85
Peptide-mediated macrolide resistance reveals possible specific interactions in the nascent peptide exit tunnel; Vimberg V et al.; Expression of specific short peptides can render cells resistant to macrolide antibiotics . Peptides conferring resistance to structurally different macrolides including oleandomycin, azithromycin, azaerythromycin, josamycin and a ketolide cethromycin were selected from a random pentapeptide expression library . Analysis of the entire collection of the resistance peptides allowed their classification into five distinct groups according to their sequence similarity and the type of resistance they confer . A strong correlation was observed between the structures of macrolide antibiotics and sequences of the peptides conferring resistance . Such a correlation indicates that sequence-specific interactions between the nascent peptide and the macrolide antibiotic and/or the ribosome can occur in the ribosomal exit tunnel.

Eur J Health Econ, 2004 Jun, 5(2), 129 - 35
Model for simulation of HIV/AIDS and cost-effectiveness of preventing non-tuberculous mycobacterial (MAC)-disease; Hoffmann T et al.; Because most HIV-infected patients die of diseases caused by opportunistic pathogens, the prevention of these infections is an important clinical issue . Cost-containment in the healthcare system is a subject of high priority in public debate . Methods to determine cost-effectiveness of different therapeutic strategies are therefore needed to obtain valid data as the basis for decisions on cost reduction without a decrease in the quality of care . A disease state transition model based on a Markov process was developed to simulate the natural history of HIV infection and the acquired immunodeficiency syndrome (AIDS) . Using this model survival time and treatment costs for every patient can be estimated and the results of alternative medications compared . We determined the cost-effectiveness (per life-year saved, LYS) of different strategies for prevention of Mycobacterium avium complex infections in AIDS patients whose treatment regimens include protease inhibitors . The cost-effectiveness ratios for treatment strategies vary from 13,510 euro to 46,152 euro per LYS without protease inhibitors and from 22,309 euro to 51,336 euro with protease inhibitors . When azithromycin, clarithromycin, and rifabutin were compared, azithromycin was the most cost-effective medication for preventing M . avium complex . The results were stable against a wide range of parameter variations concerning costs and incidence rates.

Pharmacoepidemiol Drug Saf . 2004 Jul 29; {Epub ahead of print}
Effectiveness of amoxicillin, azithromycin, cefprozil and clarithromycin in the treatment of acute otitis media in children: a population-based study; Quach C et al.; Population-based studies may give results different from randomized clinical trials assessing the efficacy of antibiotics.OBJECTIVE: To determine the effectiveness of amoxicillin, azithromycin, cefprozil and clarithromycin in the treatment of acute otitis media (AOM) in children . METHODS: Using Quebec Health Insurance databases (RAMQ), we selected a cohort of children aged </=6 years, with a first episode of AOM between 1999 and 2002 . The index AOM was defined as a medical service claim with a diagnosis of AOM and an antibiotic dispensation in the following 72 hours . Failures were defined as a new antibiotic dispensation, a hospitalization or outpatient visit for complications related to AOM in the 30 days after the index AOM . Data were analyzed using logistic regression . RESULTS: Overall, 12 693 failures occurred among 60 513 first episodes of AOM . Azithromycin was the only antibiotic that was associated with a decreased risk of failure overall, when compared to amoxicillin (OR 0.88, 95%CI: 0.82, 0.94) . However in the first 3 days of treatment (n = 680), azithromycin was more associated with treatment failure (OR 1.6, 95%CI: 1.3, 2.0) . Compared to amoxicillin, post-therapy failures (n = 9387) were more likely to occur with cefprozil (OR 1.2, 95%CI: 1.2, 1.3) but were less with azithromycin (OR 0.8 95%CI: 0.8, 0.9) . CONCLUSIONS: Azithromycin had the lowest risk of failure 30 days after the onset of treatment but an increased risk of failure during the first few days of treatment . Amoxicillin remains an effective first-line drug for treating first AOM episodes .

Exp Parasitol, 2004 Jul-Aug, 107(3-4), 120 - 4
Plasmodium yoelii: activity of azithromycin in combination with pyrimethamine or sulfadoxine against blood and sporozoite induced infections in Swiss mice; Neerja J et al.; The efficacy of pyrimethamine or sulfadoxine administered in combination with azithromycin was examined in a rodent malaria model . Outbred Swiss mice infected with blood stage parasites were treated from day 0 to day 3 and efficacy of different regimens was monitored in terms of the curative response and the delay time to reach 2% parasitaemia (2% DT) . Administration of azithromycin alone at 60 mg/kg/day produced curative response while lower doses showed marginally delayed 2% DT . A marked potentiation in activities of pyrimethamine (100-fold) or sulfadoxine (10-fold) was observed when administered at non-curative doses of 0.1 mg/kg/day in combination with azithromycin (30 mg/kg/day) against blood stage parasites . A combination of 10 mg/kg/day azithromycin with 0.3 mg/kg/day sulfadoxine was also curative . Likewise in the causal prophylactic test, a combination regimen comprising 1/16th and 1/3rd the individual curative doses of pyrimethamine and azithromycin, respectively, prevented the development of patent infection after Plasmodium yoelii sporozoite challenge . Our results suggest that a combination of azithromycin with the second line treatment regimen of fansidar may enhance the therapeutic efficacy of the latter and also provide better prophylaxis against Plasmodium falciparum malaria.

J Trop Pediatr, 2004 Aug, 50(4), 234 - 6
The probiotic effect of Saccharomyces boulardii in a pediatric age group; Erdeve O et al.; The aim of this study was to determine the efficacy of S . boulardii in diarrhea associated with commonly used antibiotics such as sulbactam-ampicillin (SAM) and azithromycin (AZT) . Four hundred and sixty-six patients were assigned to four different groups as follows: group 1:117 patients receiving SAM alone; group 2:117 patients receiving SAM and S . boulardii, group 3:105 patients receiving AZT alone; group 4:127 patients receiving AZT and S . boulardii . Antibiotic-associated diarrhea was seen in 42 of the 222 patients (18.9 per cent) receiving an antibiotic without the probiotic, and in 14 of the 244 patients (5.7 per cent) who received both the probiotic and the antibiotic (p < 0.05) . In the group receiving SAM where S . boulardii use was found to be significant, the use of S . boulardii decreased the diarrhea rate from 32.3 to 11.4 per cent in the 1-5 years age group (p < 0.05) . This is a pioneering study investigating combined antibiotic and probiotic use in pediatric diarrhea patients.

East Mediterr Health J, 2002 Mar-May, 8(2-3), 350 - 3
Prevalence of trachoma in chronic conjunctivitis, Birjand, Islamic Republic of Iran; Yaqubi GH et al.; Between January 1999 and December 2000, 80 consecutive patients with chronic conjunctivitis presenting in the eye clinic of Birjand University of Medical Sciences were assessed for trachoma and chlamydial infection . Direct fluorescent antibody test was used to assess trachoma and Giemsa staining to detect chlamydial infection . Trachoma was detected in 10% of the patients and chlamydial infection detected in 6.3% . The results were similar for both sexes . Although the findings are hospital-based, the prevalence was not so high as to suggest prophylactic use of azithromycin (World Health Organization protocol) for eradication of trachoma in the Birjand population . Further epidemiological studies are recommended.

Lancet Infect Dis, 2004 Sep, 4(9), 557 - 65
Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy; Karakousis PC et al.; Disseminated Mycobacterium avium complex (MAC) infection is a common complication of late-stage HIV-1 infection . Since the advent of highly active antiretroviral therapy (HAART), the rate of MAC infection has declined substantially, but patients with low CD4 cell counts remain at risk . Among patients in the Johns Hopkins cohort with advanced HIV disease, the proportion developing MAC has fallen from 16% before 1996 to 4% after 1996, with a current rate of less than 1% per year . Factors associated with developing MAC include younger age, no use of HAART, and enrollment before 1996 . Prophylaxis with azithromycin or clarithromycin is recommended for all patients with CD4 counts less than 50 cells/mL . Optimum treatment for disseminated MAC includes clarithromycin and ethambutol, and another investigation suggests that the addition of rifabutin might reduce mortality . Both prophylaxis and treatment of disseminated MAC can be discontinued in patients who have responded to HAART, and specific guidelines for withdrawing treatment have been published . Although HAART has altered the frequency and outcome of MAC infection, it remains an important complication of AIDS.

Turk J Gastroenterol, 2004 Jun, 15(2), 90 - 3
Comparison of ranitidine bismuth citrate, tetracycline and metronidazole with ranitidine bismuth citrate and azithromycin for the eradication of Helicobacter pylori in patients resistant to PPI based triple therapy; Altintas E et al.; BACKGROUND/AIMS: Helicobacter pylori is the most common infectious disease all over the world . Ten to twenty percent of the patients remain infected despite treatment with proton pump inhibitors (PPIs), amoxicillin and clarithromycin . We compared PPI, bismuth, tetracycline and metronidazole with ranitidine bismuth citrate, tetracycline and metronidazole in cases resistant to PPIs-based triple therapies . METHODS: The study included 52 patients who underwent a triple therapy with PPI, clarithromycin and amoxicillin for 14 days between September 2001 and December 2002, and were found to be resistant to the therapy . They were randomized to take ranitidine bismuth citrate (Rb) 400 mg twice a day, tetracycline (T) 1 g twice a day and metronidazole (M) 500 mg three times a day for 14 days (RbTM), or ranitidine bismuth citrate (Rb) 400 mg twice a day for 14 days and azithromycin (A) 500 mg once a day for 7 days (RbA) . Four weeks after the treatment, endoscopies were repeated, and patients were assessed with respect to changes in symptoms . When H . pylori was negative on histological analysis and urease test, eradication was achieved . RESULTS: A total of 52 patients, 32 females and 20 males with a mean age of 49+/-12 years, were included in the study . Eradication was achieved in 15 (28%) out of 52 patients in total . There was a significant difference between RbA and RbTM groups (p=0.01) . In fact, H . pylori was eradicated in 3 (12%) out of 25 patients in the RbA group, whereas it was eradicated in 12 (44.4%) out of 27 patients in the RbTM group . Symptom scores significantly improved in both groups after the treatment, though there was not a significant difference between the groups (p=0.705) . CONCLUSIONS: Triple therapy including azithromycin does not seem to be a good choice in cases resistant to the first line therapies; however, a similarly lower rate of eradication was achieved with the quadruple therapy proposed . Therefore, different treatment schemes should be applied in resistant patients, and further studies are needed as well.

Biochim Biophys Acta, 2004 Aug 30, 1664(2), 198 - 205
Real-time imaging of drug-membrane interactions by atomic force microscopy; Berquand A et al.; Understanding drug-biomembrane interactions at high resolution is a key issue in current biophysical and pharmaceutical research . Here we used real-time atomic force microscopy (AFM) imaging to visualize the interaction of the antibiotic azithromycin with lipid domains in model biomembranes . Various supported lipid bilayers were prepared by fusion of unilamellar vesicles on mica and imaged in buffer solution . Phase-separation was observed in the form of domains made of dipalmitoylphosphatidylcholine (DPPC), sphingomyelin (SM), or SM/cholesterol (SM/Chl) surrounded by a fluid matrix of dioleoylphosphatidylcholine (DOPC) . Time-lapse images collected following addition of 1 mM azithromycin revealed progressive erosion and disappearance of DPPC gel domains within 60 min . We attribute this effect to the disruption of the tight molecular packing of the DPPC molecules by the drug, in agreement with earlier biophysical experiments . By contrast, SM and SM-Chl domains were not modified by azithromycin . We suggest that the higher membrane stability of SM-containing domains results from stronger intermolecular interactions between SM molecules . This work provides direct evidence that the perturbation of lipid domains by azithromycin strongly depends on the lipid nature and opens the door for developing new applications in membrane biophysics and pharmacology.

J Vet Intern Med, 2004 Jul-Aug, 18(4), 494 - 8
Efficacy of combined atovaquone and azithromycin for therapy of chronic Babesia gibsoni (Asian genotype) infections in dogs; Birkenheuer AJ et al.; Babesiosis caused by Babesia gibsoni (Asian genotype) is an emerging disease in dogs in the United States . To date, no drugs have been shown to eliminate B . gibsoni (Asian genotype) infections from dogs . Twenty-two dogs that remained persistently infected with B . gibsoni (Asian genotype) after either imidocarb diproprionate and or diminazine aceturate therapy were identified and randomly and evenly distributed into 2 groups . One group was treated with atovaquone and azithromycin combination therapy, and the other group received a placebo . Eight of 10 dogs in the treatment group had no detectable B . gibsoni (Asian genotype) DNA, as determined by a sensitive and specific polymerase chain reaction (PCR) assay, in any of their posttreatment samples . In contrast, B . gibsoni (Asian genotype) DNA was detectable by PCR in the posttreatment samples from 11 of 11 of the placebo-treated dogs . One dog in the treatment group was excluded from the treatment outcome analysis . This dog had 2 consecutive negative PCR assay results and was euthanized because of ongoing degenerative joint disease prior to completion of the study . No adverse effects of treatment were reported in any dog during the study period . A combination of atovaquone and azithromycin is the 1st described treatment that will either eliminate B . gibsoni (Asian genotype) infections or suppress the parasitemia below the limit of detection in the majority of treated dogs.

Chemotherapy, 2004, 50 Suppl 1, 11 - 5
Experience with levofloxacin in a critical pathway for the treatment of community-acquired pneumonia; Marrie TJ; Community-acquired pneumonia (CAP) is associated with considerable morbidity and mortality in both developed and developing countries . Despite research into the optimal management of this condition, there remains great variation in how patients with CAP are treated . A study was performed to assess the results of CAP treatment using a clinical pathway that incorporated admission guidelines, standard treatment orders with oral levofloxacin or cefuroxime axetil plus azithromycin, and an algorithm for oxygen therapy and discharge . The study involved seven centers enrolling 7,734 patients, 55% of whom were treated as outpatients and the remainder were admitted . Overall mortality was 8%, and increasing severity of illness, as assessed by pneumonia severity risk score, was associated with early mortality (within five days of admission) and late mortality (five or more days following admission) . The use of the clinical pathway was associated with a reduction in early mortality . The use of levofloxacin alone or with cefuroxime axetil plus azithromycin was associated with decreased mortality compared with the use of other antibiotics.

J Mol Neurosci, 2004, 24(1), 129 - 36
FDA-preapproved drugs targeted to the translational regulation and processing of the amyloid precursor protein; Morse LJ et al.; The 5' untranslated region (5'UTR) of the transcript encoding the Alzheimer's amyloid precursor protein (APP) is a key regulatory sequence that determines the amount of intracellular APP holoprotein present in brain derived cells . Using neuroblastoma cells (SY5Y) we developed a transfection based screen of a library of FDA drugs to identify compounds that limited APP luciferase reporter expression translated from the APP 5'UTR . Paroxetine (Paxil trade mark ), dimercaptopropanol, phenserine, desferrioxamine, tetrathiolmobdylate, and azithromycin were six leads that were subsequently found to also suppress APP holoprotein levels or to alter APP cleavage (azithromycin) . Since APP holoprotein levels are proportionate to Abeta peptide output in many systems we tested the efficacy of paroxetine and dimercaptopropanol to limit Abeta secretion as measured by ELISA assays . Paroxetine and dimercaptopropanol limited Abeta peptide secretion from lens epithelial cells (B3 cells) . Interestingly, paroxetine changed the steady-state levels of transferrin receptor mRNAs . These data suggested that this serotonin reuptake inhibitor (SSRI) provided extra pharmacological action to chelate interacellular iron or change the intracellular iron distribution . An altered iron distribution would be predicted to indirectly limit APP holoprotein expression and Abeta peptide secretion .

Ann Rheum Dis, 2004 Sep, 63(9), 1113 - 9
Three month treatment of reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study; Kvien TK et al.; OBJECTIVE: To determine the efficacy of weekly treatment with oral azithromycin for 13 weeks on the severity and resolution of reactive arthritis (ReA) . METHODS: 186 patients from 12 countries were enrolled in a randomised, double blind, placebo controlled trial . Inclusion criteria were inflammatory arthritis of < or =6 swollen joints, and disease duration of < or =2 months . All patients received a single azithromycin dose (1 g) as conventional treatment for possible Chlamydia infection, and were then randomly allocated to receive weekly azithromycin or placebo . Clinical assessments were made at 4 week intervals for 24 weeks . RESULTS: 152 patients were analysable (34 failed entry criteria), with a mean (SD) age of 33.8 (9.4) and duration of symptoms 30.7 (17.5) days . Mean C reactive protein (CRP) was 48 mg/l, and approximately 50% of those typed were HLA-B27+, suggesting that the inclusion criteria successfully recruited patients with acute ReA . Treatment and placebo groups were well matched for baseline characteristics . There were no statistical differences for changes in any end point (swollen and tender joint count, joint pain, back pain, heel pain, physician and patient global assessments, and CRP) between the active treatment and placebo groups, analysed on an intention to treat basis or according to protocol completion . The time to resolution of arthritis and other symptoms or signs by life table analyses was also not significantly different . Adverse events were generally mild, but were more commonly reported in the azithromycin group . CONCLUSIONS: This large trial has demonstrated that prolonged treatment with azithromycin is ineffective in ReA.

Pharmacotherapy, 2004 Jul, 24(7), 945 - 9
Azithromycin and warfarin interaction; Shrader SP et al.; A 57-year-old Caucasian woman came to the clinic with symptoms of an upper respiratory tract infection . She was treated with a 5-day course of oral azithromycin 500 mg on day 1, then 250 mg/day for 4 days . During this period, the patient decreased her cigarette smoking from 1 pack/day to 1 pack every 3 days . No additional confounding variables were present . Two days after the completion of therapy, her international normalized ratio (INR) was 8.32 . Six case reports documented in the literature have suggested an azithromycin-warfarin interaction with a resultant increase in INR . Many confounding variables existed in each of these cases, such as hepatic dysfunction, poor appetite, and concomitant drugs that resulted in an increased anticoagulant response . We report a case that involved only one potential confounding variable . Continued documentation of azithromycin-warfarin interactions is valuable considering no mention of this drug interaction exists in most tertiary references and in the package insert for azithromycin, the demonstration that no drug interaction occurred in a retrospective review of 52 cases, and the widespread use of azithromycin in the community . Clinicians should be mindful when prescribing azithromycin in combination with warfarin, and INR values should be monitored.

Chest, 2004 Aug, 126(2), 566 - 81
Mycobacterium avium complex pulmonary disease in patients without HIV infection; Field SK et al.; Mycobacterium avium complex (MAC) is ubiquitous . It is found in various freshwater and saltwater sources around the world, including hot water pipes . Although the organism was identified in the 1890s, its potential to cause human disease was only recognized 50 years later . Only a minority of people exposed to the organism will acquire MAC lung disease, usually those with underlying lung disease or immunosuppression . MAC may, however, cause progressive parenchymal lung disease and bronchiectasis in patients without underlying lung disease, particularly in middle-aged and elderly women . Preliminary data suggest that the interferon-gamma pathways may be deficient in elderly women with MAC lung disease . Other groups of patients who are more likely to harbor MAC in their lungs include patients with a cystic fibrosis or an abnormal alpha(1)-antiproteinase gene and patients with certain chest wall abnormalities . Treatment results continue to be disappointing, and the mortality of patients with MAC lung disease remains high . A PubMed search identified 38 reports of the treatment of MAC lung disease . Apart from the British Thoracic Society study, the only published controlled investigation, the studies published since 1994 have included a macrolide, either clarithromycin or azithromycin, usually in combination with ethambutol and a rifamycin . If success is defined as eradication of the organism without relapse over a period of several years after treatment has been discontinued, the reported treatment success rate with the macrolide containing regimens is approximately 55% . The prolonged treatment period, side effects, and possibly reinfection rather than relapse are responsible for the high failure rate.

Int J Antimicrob Agents, 2004 Aug, 24(2), 181 - 4
Azithromycin versus comparative therapy for the treatment of community acquired pneumonia; Rahav G et al.; A 3-day course of azithromycin was compared with the 10 days of other antibiotics, which general practitioners routinely use as therapy for community acquired pneumonia (CAP) . The study was a prospective open labelled, randomised, multicentre, comparative study from five family clinics . Patients with clinical and radiological evidence of pneumonia were included . The pneumonia resolved in 98.4% (61/62) of patients treated with azithromycin and in 87% (40/46) of patients treated with other antibiotics (P < 0.017) . Restitution of normal function at home (2.3 +/- 1.2 and 4.3 +/- 2.6 days) and return to work (3.4 +/- 2.0 and 5.5 +/- 3.1 days) was more rapid among the group treated with azithromycin ( P < 0.001) . Three days of azithromycin was more convenient and cost effective than the comparators used to treat pneumonia.

Rev Inst Med Trop Sao Paulo, 2004 May-Jun, 46(3), 175 - 7 Epub 2004 Jul 20.
Azithromycin in the treatment of mucosal leishmaniasis; Silva-Vergara ML et al.; This report describes three elderly patients with mucosal form of American tegumentary leishmaniasis associated with chronic cardiopathy . Due to the known toxicity of classical drugs with activity against Leishmania sp., the patients received three oral courses of azithromycin therapy in single 500 mg daily dose during ten days, every other month . All lesions healed after the third series . One of the patients relapsed and a new series of azithromycin was prescribed . Azithromycin may be an alternative drug for the treatment of leishmaniasis in special situations due to its optimal mucosal and intraphagocyte concentration, single daily posology, high tolerance and oral administration . The mechanism of this drug on Leishmania sp . is unknown at present.

J Matern Fetal Neonatal Med, 2004 Jun, 15(6), 418 - 20
Pregnancy in a woman with unilateral lung agenesis; Sicuranza GB et al.; Unilateral lung agenesis is a rare congenital condition of unknown etiology . A 33-year-old nullipara with right lung agenesis and scoliosis was admitted to the hospital at 30 weeks of gestation because of oligohydramnios . At 32 weeks she was treated for an upper respiratory tract infection with azithromycin . She went into premature labor at 34 weeks and was delivered by Cesarean for breech presentation . Both mother and infant did well.

Aliment Pharmacol Ther, 2004 Aug 1, 20(3), 295 - 302
Helicobacter pylori eradication in children and adolescents by a once daily 6-day treatment with or without a proton pump inhibitor in a double-blind randomized trial; Tindberg Y et al.; AIM: To evaluate two simplified Helicobacter pylori eradication treatment alternatives for children and adolescents . METHODS: Study subjects were identified by enzyme-linked immunosorbent assay and immunoblot in a family screening project . Helicobacter pylori infected 10-21 year olds were offered treatment, individuals with abdominal pain underwent upper endoscopy and those with peptic ulcers were excluded . Participants were randomized to either azithromycin 500 mg daily and tinidazole 500 mg two tablets daily in combination with lansoprasole 30 mg daily for 6 days (ATL-group) or with placebo (ATP-group) . Urea Breath Test was performed at inclusion and after a minimum of 6 weeks after end of therapy . RESULTS: In total, 131 individuals were randomized, of whom 31 (24%) had undergone upper endoscopy . Full compliance was achieved in 93% (122 of 131) . The intention-to-treat eradication rate was 67% (44 of 66) and 58% (38 of 65) for the ATL- and the ATP-group, respectively . CONCLUSION: The double-blind randomized clinical trial did not identify a simplified, successful once daily H . pylori treatment for children and adolescents . Thus, twice daily proton pump inhibitor (PPI)-based triple therapies for 7 days remain as the choice of treatment in children . Further, powerful and controlled studies are needed to elucidate the best treatment strategies for H . pylori eradication in this age group.

Int Immunopharmacol, 2004 Sep, 4(9), 1201 - 7
Clarithromycin and azithromycin induce apoptosis of activated lymphocytes via down-regulation of Bcl-xL; Mizunoe S et al.; To evaluate the anti-inflammatory action of macrolide antibiotics, we examined whether macrolide antibiotics could induce apoptosis of activated lymphocytes . The proportion of apoptotic cells was augmented by clarithromycin (CLR) and azithromycin (AZM) compared with control . There was no significant difference in Fas and Fas-ligand expression between the control and macrolide-treated groups . CLR and AZM inhibited the expression of Bcl-xL compared with that of control . Our results suggest that CLR and AZM enhance apoptosis of activated lymphocytes by down-regulation of Bcl-xL.

Ann Dermatol Venereol, 2004 May, 131(5), 461 - 4
{Short treatment of donovanosis with azithromycin}; Clyti E et al.; INTRODUCTION: Azithromycine is recommended in the treatment of donovanosis with a 7-day treatment cycle . We report the efficacy of a single cure of 1 gram in two patients.OBSERVATIONS: Four patients, presenting with donovanosis, were treated with azithromycine according to 2 regimens . The first used 500 mg/d the molecule during 1 week, the second used azithromycine in single cure of 1 gram . The latter led to the complete cure of 2 patients . DISCUSSION: Many antibiotics are used in the treatment of donovanosis . Since 1996, Australian authors have used azithromycine in this indication . A single dose of this molecule appears effective in recent and confined donovanosis.

APMIS, 2004 Apr-May, 112(4-5), 309 - 13
Infection with Cryptosporidium hominis and reinfection with Cryptosporidium parvum in a transplanted ileum; Pozio E et al.; A transplanted ileum was found to be infected with Cryptosporidium hominis 6 days after transplantation . Although the infection resolved, the ileum was later found to be infected with Cryptosporidium parvum . The presence of the parasite was not always correlated with diarrhea . No other gastrointestinal symptom was ever detected . Treatment with azithromycin and paromomycin apparently failed.

Pharmacotherapy, 2004 Jun, 24(6), 727 - 35
Differences in rates of diarrhea in patients with human immunodeficiency virus receiving lopinavir-ritonavir or nelfinavir; Guest JL et al.; STUDY OBJECTIVE: To determine and compare rates of diarrhea in patients receiving an antiretroviral regimen containing lopinavir-ritonavir versus nelfinavir and in patients who received these drugs sequentially . DESIGN: Retrospective cohort analysis . SETTING: Hospital-based human immunodeficiency virus (HIV) clinic . PATIENTS: Four hundred one participants in the HIV Atlanta VA Cohort Study who were prescribed lopinavir-ritonavir or nelfinavir from 1996-2002 . MEASUREMENTS AND MAIN RESULTS: Chart review identified episodes of diarrhea that potentially were associated with an antiretroviral agent . Data collected included antidiarrheal agents dispensed, baseline viral load and CD4+ cell counts, demographic variables, and previous therapy Diarrhea associated with an antiretroviral regimen occurred in 175 (49%) of 354 patients receiving nelfinavir and 17 (17%) of 99 patients receiving lopinavir-ritonavir (p < 0.001) . Treatment for the diarrhea occurred in 118 (33%) of 354 patients receiving nelfinavir and 9 (9%) of 99 receiving lopinavir-ritonavir (p < 0.001) . Patients in the lopinavir-ritonavir group were more likely to have received highly active antiretroviral therapy and azithromycin than patients receiving nelfinavir, and they had lower baseline CD4+ cell counts (p < or = 0.01 for each comparison) . The average number of months/person-year of diarrhea treatment was 2.0 for the nelfinavir group and 0.13 for the lopinavir-ritonavir group . Of the 10 antiretroviral-naive patients who received lopinavir-ritonavir, none needed treatment for diarrhea, whereas 78 (36%) of 217 antiretroviral-naive patients who received nelfinavir required treatment for diarrhea . Of the 52 patients who had been taking nelfinavir and were switched to lopinavir-ritonavir, they were more likely to start antidiarrheal treatment while taking nelfinavir (14 {27%}) than while receiving lopinavir-ritonavir (3 {6%}) (p = 0.004) . CONCLUSIONS: Patients receiving lopinavir-ritonavir were significantly less likely to have diarrhea or to require treatment for diarrhea than patients receiving nelfinavir . The same results occurred when the drugs were given to the same patients sequentially (nelfinavir followed by lopinavir-ritonavir) . The diarrhea associated with lopinavir-ritonavir was less frequent, less severe, and shorter in duration than diarrhea associated with nelfinavir.

Bioelectrochemistry, 2004 Aug, 64(1), 91 - 7
Studies on electrochemical oxidation of azithromycin and its interaction with bovine serum albumin; Wu Y et al.; A novel nanoparticle film modified electrode has been constructed using a glassy carbon electrode (GCE) coated with a carbon nanotube-dihexadecylphosphate (DHP) film . This modified electrode exhibits an enhanced effectiveness for the oxidation of azithromycin . A method is also described for the evaluation of azithromycin-bovine serum albumin (BSA) interaction . The electrochemical behavior of azithromycin as well as its interaction with BSA at this nanoparticle film electrode has been investigated by cyclic voltammetry, linear sweep voltammetry, differential pulse voltammetry and chronocoulometry . The binding number and association constant between azithromycin and bovine serum albumin have been obtained.

Am Heart J, 2004 Jul, 148(1), 72 - 9
Effects of a brief course of azithromycin on soluble cell adhesion molecules and markers of inflammation in survivors of an acute coronary syndrome: A double-blind, randomized, placebo-controlled study; Hillis GS et al.; BACKGROUND: The anti-chlamydial antibiotic, azithromycin, may improve outcome in patients who survive an acute coronary syndrome . The mechanisms are, however, poorly understood . The aims of this study were to define any relationship between Chlamydia pneumoniae seropositivity and levels of specific markers of endothelial activation (soluble cell adhesion molecules) and more general markers of inflammation (C-reactive protein {CRP} and interleukin-6 {IL-6}) and to assess whether azithromycin had any effect on such markers . METHODS: Patients who survived an acute coronary syndrome were randomized to receive treatment with azithromycin (n = 72) or placebo (n = 69) for 5 days . Before therapy, C pneumoniae IgA and IgG titers were checked, with serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, soluble E-selectin (sE-selectin), soluble P-selectin, high-sensitivity CRP, and IL-6 . They were rechecked 3 months later . RESULTS: There were no significant correlations between C pneumoniae titers and levels of CRP, IL-6, or soluble cell adhesion molecules . However, azithromycin treatment significantly reduced mean sICAM-1 levels (P =.006) . This effect was more marked in patients with elevated titers of C pneumoniae IgA and IgG . Soluble E-selectin levels were also reduced in patients who were seropositive, but no effects were seen on other endothelial or inflammatory markers . CONCLUSIONS: After an acute coronary syndrome, a 5-day course of azithromycin reduces levels of sICAM-1, a marker of endothelial cell activation . Although these data suggest a potentially beneficial role for azithromycin, they should be interpreted with caution.

Ann Pharmacother, 2004 Sep, 38(9), 1520 - 4 Epub 2004 Jun 22.
Azithromycin for improving pulmonary function in cystic fibrosis; Carr RR et al.; OBJECTIVE: To review the literature concerning the use of azithromycin in the treatment of patients with cystic fibrosis (CF) . DATA SOURCES: A search of MEDLINE (1966-April 2004), Embase (1980-April 2004), and International Pharmaceutical Abstracts (1971-April 2004) was performed . Search terms included cystic fibrosis, macrolide, and azithromycin . DATA SYNTHESIS: Four studies have been performed in 7-185 patients (children and adults) over a 3- to 6-month period . The azithromycin dosage ranged from 250 mg 3 times weekly to 500 mg daily . The trials reported an improvement in percent predicted forced expiratory volume ranging from 2.95% to 6.2% in patients treated with azithromycin compared with those receiving placebo . CONCLUSIONS: Azithromycin appeared to improve pulmonary function in adults and older children with CF and was well tolerated when administered for 6 months . Further research is needed to determine an optimal dosage regimen, duration of treatment, effects on quality of life, and cost-effectiveness of azithromycin therapy.

Transplantation, 2004 May 15, 77(9), 1465 - 7
Azithromycin therapy for patients with bronchiolitis obliterans syndrome after lung transplantation; Verleden GM et al.; BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the leading cause of late mortality after lung transplantation . METHODS: We added azithromycin (AZI) (250 mg/day for 5 days, followed by 250 mg every other day) to the current immunosuppressive therapy in eight lung transplant recipients (mean age 36 years) with established BOS in an attempt to prevent further decline of the forced expiratory volume in 1 sec (FEV1) . RESULTS: Before the administration of AZI, there was a gradual decline of the FEV1 (-34.4%+/-14.7%) compared with the patients' best postoperative values . Twelve weeks after AZI had been added, there was a significant increase in the FEV1 (+18.3%+/-14.6%, P <0.0001, analysis of variance) with an absolute increase of 328+/-305 mL . This increase persisted in three patients during 9 months of follow-up . CONCLUSIONS: AZI is a promising drug for some patients with BOS after lung transplantation . The exact mechanism of action is unknown at the present time.

Med Arh, 2003, 57(1 Suppl 2), 107 - 10
{Clinical effectiveness of omeprazole, azithromycin and amoxicillin in ulcer healing and eradication of Helicobacter pylori infection}; Gribajcevic M et al.; AIM: Prospective clinical investigation efficacy of omeprazole was proved in combination with two antibiotics (azithromicine and amoxycillin) in H . pylori eradication . Efficacy of omeprazole was also followed in gastric and duodenal ulcer healing . PATIENTS AND METHODS: Patients with dyspepsia and peptic ulcer of stomach and duodenum were examined . Positive H . pylori status was proved by rapid urease test (Pronto dry) . During first 7 days patients were treated with omeprazole (Ulzol caps . 2 x 20 mg), amoxycillin 7 days (Amoxil 2 x 1000 mg), and Azithromicin 3 days (Sumamed 1 x 1000 mg) . After that period patients received omeprazole (Ulzol caps . 1 x 20 mg) in single morning dose next 21 or 28 days in continuation of antisecretory treatment . Control endoscopy revealed rate of ulcer healing and rate of H . pylori infection with same test at least 28 days after initiation of treatment . RESULTS: Complete eradication of H . pylori was in 46/50 (92%) patients (p < 0.001), complete ulcer healing in 48/50 (96%) patients . No patients had complication after omeprazole treatment . Two patients (4%) had worsening of dyspepsia, but without treatment discontinuation . CONCLUSION: Triple treatment with omeprazole, azithromicin and amoxycillin achieved high rate of H . pylori eradication, gastric and duodenal ulcer healing . Treatment was well tolerated, with rapid pain and dyspepsia symptoms relief.

Paediatr Respir Rev, 2004 Jun, 5(2), 116 - 23
Phenotype-specific treatment of difficult asthma in children; Payne D et al.; Most children with asthma can be treated successfully with low-to-moderate doses of inhaled corticosteroid and long-acting beta-2 agonist . Those that fail to respond are a heterogeneous group . We propose that the nature and type of any steroid-resistant inflammation, the extent of any persistent airflow limitation and the extent of bronchial hyper-reactivity should be determined separately to allow a rational treatment approach to these children, rather than the haphazard advice of many current guidelines . Reasons for persistent difficult asthma include persistent eosinophilic inflammation, non-eosinophilic inflammation, airway reactivity without residual inflammation and persistent airflow limitation . We propose a protocol that uses non-invasive and invasive (bronchoscopic) methods to document the response to systemic steroids (depot triamcinolone) . The aim of the protocol is to determine an individualised treatment plan; for example, cyclosporin for persistent eosinophilic inflammation, azithromycin for persistent neutrophilic inflammation and continuous subcutaneous terbutaline if there is airway reactivity without residual inflammation . Multi-centre studies are required to test the utility of this approach.

Int J Dermatol, 2004 Feb, 43(2), 151 - 4
Therapeutic potential of azithromycin in rosacea; Bakar O et al.; BACKGROUND: Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side-effects . Therefore, a need for an effective agent with few side-effects and good patient compliance exists . Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne . We planned a study to evaluate the efficacy and safety of azithromycin in rosacea . METHODS: An open-labeled study was performed in a population of 18 patients, with Plewig-Kligman stage 2 rosacea . Patients were given oral azithromycin for 12 weeks in decreasing doses . RESULTS: Fourteen subjects completed the trial . The treatment produced therapeutic benefits with regard to total scores as well as inflammatory lesion scores . At the end of 12 weeks, there was a 75% decrease in total scores (P < 0.001) and an 89% decrease in inflammatory lesion scores compared with basal values . Improvement continued during the 4 weeks after treatment . Adverse effects were minimal and well tolerated in most patients . CONCLUSION: Azithromycin is a promising agent in the treatment of rosacea with its few side-effects and good patient compliance.

J Periodontol, 2004 Mar, 75(3), 380 - 7
Inhibition of cyclosporin A-induced gingival overgrowth by azithromycin through phagocytosis: an in vivo and in vitro study; Paik JW et al.; BACKGROUND: The objective of the present study was to investigate the effect of cyclosporin A (CsA) and azithromycin (AZI) on collagen metabolism in the gingiva of rats . METHODS: Fifty 6-week-old male Sprague-Dawley (SD) rats (weight 120 to 150 g) were randomly distributed into five groups . All groups received various drugs via gastric feeding for 7 weeks . The first group (Mo group) received mineral oil for 7 weeks as a control; the CsA group received CsA in mineral oil for 7 weeks (dosage 30 mg/kg); the CsA/Mo group received CsA in mineral oil for 6 weeks and mineral oil only for the seventh week; the CsA/AZI group received CsA in mineral oil for 6 weeks and AZI (dosage 10 mg/kg) in mineral oil simultaneously with CsA in the seventh week; and the Mo/AZI group received mineral oil for 6 weeks and AZI in mineral oil for the seventh week . All animals were sacrificed for clinical and histological analyses . Gingival fibroblasts were cultured at the fourth passage, and the amount of collagen was measured . Type I collagen and collagenase mRNA were measured by reverse transcription-polymerase chain reaction . Collagen phagocytosis assay also was performed . RESULTS: Clinically, CsA induced gingival overgrowth in rats, whereas AZI reduced gingival overgrowth . Histological results of the CsA group showed a marked increase of tissue volume compared to the other groups . High collagen amounts were found when gingival overgrowth was induced . However, type I collagen mRNA and collagenase mRNA expressions did not statistically differ among groups . Phagocytosis assay showed that CsA decreased phagocytic activity of gingival fibroblasts, whereas AZI increased the activity . These results suggest that the induction and reduction of CsA-induced gingival overgrowth were closely associated with phagocytic activity . CONCLUSION: Cyclosporin A decreases collagen degradation by lowering phagocytic activity of rat gingival fibroblasts . Azithromycin partially compensates for this lowered phagocytic activity.

Acta Dermatovenerol Croat, 2004, 12(2), 92 - 5
A child with Bartonella henselae osteomyelitis of the right humerus; Ledina D et al.; We present a case of a 22-month-old child with swollen upper part of the right arm and osteolytic lesion of the right humerus, which resembled a neoplastic process . Epidemiological history revealed no scratch marks on the skin or cutaneous papule or pustule . Presumptive diagnosis of hematogenous osteomyelitis was established, but treatment with fusidic acid was unsuccessful . Histological examination of the bioptic specimen of the soft tissue swelling showed a lymph node morphology, with numerous granulomas with central stellate necrosis . Indirect immunofluorescence assay for Bartonella henselae yielded positive results . New treatment included 15 days of trimetoprime and sulfamethoxazole, followed by azithromycin for 5 days . Four months later, swelling resolved and osteolytic lesion almost completely healed with formation of surrounding sclerosis . In conclusion, cat-scratch disease without positive epidemiological history and primary cutaneous papule or pustule may be a serious diagnostic problem, but can be solved by serological and histological examination.

Int J STD AIDS, 2004 Mar, 15(3), 162 - 4
The prevalence of rectal chlamydial infection amongst men who have sex with men attending the genitourinary medicine clinic in Edinburgh; Manavi K et al.; Little is known about the prevalence of rectal chlamydial infection amongst men who have sex with men (MSM) . Previous studies using culture methods reported this to be between 4-6% . The emergence of nucleic acid amplification tests has significantly increased the sensitivity and specificity for chlamydial detection, making it possible to estimate the prevalence of rectal infection more accurately . A prospective cross sectional study involving 443 MSM who were screened for sexually transmitted infections (STIs) between May 1999 and January 2002 . Rectal swabs for chlamydiae were obtained in addition to specimens for routine STI screening . Rectal chlamydiae were detected by ligase chain reaction (LCR) utilizing the Abbott LCX Amplicor with confirmation by COBASE amplicor for the majority of cases . Those with rectal chlamydial infection were treated with azithromycin . The characteristics of men with rectal chlamydial infection were compared with those who were not infected at this site . Rectal chlamydia was detected in 32 (7.2%) of 443 patients . Those with rectal chlamydial infection were more likely to have rectal symptoms (12/32) or having a partner with confirmed chlamydial (2/32) or gonococcal (3/32) urethritis than those MSM without rectal chlamydial infection . They were also more likely to have a history of receptive anal sex (25/32) in the previous three months compared to those MSM without rectal chlamydial infection (263/411) . The most common symptoms of patients with rectal chlamydial infection were pruritus ani and peri-anal pain . Eight (25%) of those with rectal chlamydial infection were known to be HIV seropositive . Rectal chlamydial infection is common amongst MSM and is effectively diagnosed by LCR . The test should be included in the routine STI screening offered to MSM.

Zhonghua Nan Ke Xue, 2004 Feb, 10(2), 122 - 4
{Male urogenital tract mycoplasma infection and drug-resistance evolution}; Guo X et al.; OBJECTIVE: To investigate the male urogenital tract mycoplasma infection and drug-resistance evolution in 2001 and 2003 . METHODS: The results of mycoplasma culture and drug sensitivity tests were explored in 2001 and 2003, and the differences of drug sensitivity between the two years were analysed . RESULTS: Of the 109 mycoplasma positive cases in 2001, 86.2% were infected with Ureaplasma urealyticum (Uu), 3.8% with Mycoplasma hominis (Mh), 10.1% with both Uu and Mh; and of the 134 mycoplasma positive cases in 2003, Uu infection accounted for 79.1%, Mh infection 4.48% and Uu and Mh infection 16.4% . Compared with 2001, the drug-resistance rates to roxithromycin, azithromycin, levofloxacin, ofloxacin and clindamycin rose obviously in 2003; but the drug-resistance rates to josamycin, minomycin and doxycycline did not change significantly . As far as the drug sensitivity rate is concerned, josamycin ranked the first, and doxycycline the second . CONCLUSIONS: Mycoplasma was a high rate of drug-resistance, and the drug sensitivity evolves with the time . Treatment for mycoplasma should be based on the results of drug sensitivity tests . Josamycin can be used as the first choice.

MMWR Morb Mortal Wkly Rep, 2004 Mar 12, 53(9), 197 - 8
Azithromycin treatment failures in syphilis infections--San Francisco, California, 2002-2003; Centers for Disease Control and Prevention (CDC); The San Francisco Department of Public Health (SFDPH) is investigating several clinical failures in syphilis patients treated with the macrolide antibiotic azithromycin . This report describes the use of azithromycin for syphilis treatment, recent treatment failures in San Francisco, and CDC recommendations for syphilis treatment . Clinicians should exercise caution in using azithromycin for treating incubating syphilis or syphilis infection until the risk and mechanism of failure are better understood.

Pediatr Transplant, 2004 Feb, 8(1), 60 - 4
Trial of metronidazole vs . azithromycin for treatment of cyclosporine-induced gingival overgrowth; Chand DH et al.; Gingival overgrowth usually characterized by increased cellular growth of gingival fibroblasts appears to be multifactorial . In patients receiving CyA for more than 3 months, the incidence can approach 70% and can be attributed to pharmaceutical immunosuppression . Case reports have reported regression of overgrowth with both metronidazole and azithromycin . The goal of this study was to determine the efficacy of metronidazole and azithromycin in reducing CyA-induced gingival overgrowth . Twenty-five patients were included in this double-blinded randomized study . All patients were receiving CyA as medically indicated and diagnosed with gingival overgrowth by a dentist . Patients were randomized to receive either 5-days of azithromycin or 7-days of metronidazole given at baseline only . The extent of gingival overgrowth was measured at 0, 2, 4, 6, 12, and 24 wk . Fourteen patients at CCF and 11 patients at CCHMC were studied . Repeated measures anova was performed to assess differences within and between groups . Gingival overgrowth at baseline was not statistically different between groups . The mean degree of gingival overgrowth after treatment was different across all time intervals (p = 0.0049) showing azithromycin to be more effective than metronidazole . Therapy with azithromycin offers an effective alternative to the management of CyA-induced gingival overgrowth .

Nihon Kokyuki Gakkai Zasshi, 2004 Feb, 42(2), 195 - 9
{A case of Q fever infection causing acute exacerbation of chronic respiratory failure}; Abe T et al.; The authors report a case of Q fever infection that caused acute exacerbation of chronic respiratory failure, which had developed as a sequela of pulmonary tuberculosis . This case was found on wide-ranging serological screening for respiratory infection performed in order to investigate the prevalence of Q fever in Japan . A 73-year-old man who had been treated for hypertension and sequelae of pulmonary tuberculosis was admitted to our hospital because of fever, productive cough, and dyspnea on effort . Hypoxia and right heart failure were detected on arterial blood analysis and ultrasonography . The acute exacerbation was triggered by respiratory infection and although the infection improved on azithromycin treatment after admission, respiratory failure continued for the period of admission . Home oxygen therapy was required for the management of chronic respiratory failure on discharge . Paired serum samples were tested for antibodies against Coxiella burnetii by indirect immunofluorescence, showing an elevated antibody titer in the convalescent phase . We believe that Q fever infection caused acute exacerbation of chronic respiratory failure, and that C . burnetii is an agent that might influence the clinical course of chronic respiratory failure.

Antibiot Khimioter, 2003, 48(10), 7 - 10
{Comparative study of azithromycin pharmacokinetics in healthy volunteers in open cross randomized procedure}; Pisarev VV et al.; A method of quantitative determination of azithromycin in HPLC with mass spectrometric detection was developed . The detection limit is 0.5 ng/ml . The method was used in the study of pharmacokinetics and bioequivalence of Zi-Factor (capsules of 250 mg of azithromycin made by Veropharm, Russia) vs . reference-drug . The pharmacokinetic study was performed by the open cross randomized procedure in 18 volunteers . The pharmacokinetic parameters required for estimation of the drug bioequivalence were calculated . The statistical analysis of the pharmacokinetic parameters revealed bioequivalence of Zi-Factor and the reference-drug.

Pharmacotherapy, 2004 Feb, 24(2), 188 - 94
Determination of the lack of a drug interaction between azithromycin and warfarin; McCall KL et al.; STUDY OBJECTIVE: To determine the effect on the international normalized ratio (INR) of adding azithromycin to patients receiving stable dosages of warfarin . DESIGN: Retrospective chart review . SETTING: Outpatient clinic . PATIENTS: Ambulatory patients receiving warfarin and azithromycin concurrently who had a documented therapeutic INR value before the start of azithromycin therapy (pre-INR) and a documented INR value within 30 days after the start of azithromycin therapy (post-INR) . MEASUREMENTS AND MAIN RESULTS: Patients given felodipine during long-term warfarin therapy formed a comparative control group . Patient demographics were similar in both treatment groups . Mean age of the azithromycin group (17 patients) was 59 +/- 13 years and of the control group (20 patients) 65 +/- 12 years . All 17 patients in the azithromycin group and 16 of the controls were women . Mean change from pre-INR to post-INR in the azithromycin and control groups, respectively, was 0.14 +/- 0.64 (pre-INR 2.46, post-INR 2.61) and 0.19 +/- 0.54 (pre-INR 2.46, post-INR 2.66) (p = 0.74) . A post hoc power analysis based on a pooled standard deviation of 0.60 revealed that the study had 68% power to detect a 0.5 change in the INR value . CONCLUSION: No interaction between azithromycin and warfarin was observed in ambulatory patients with therapeutic baseline INR values.

Zhonghua Er Ke Za Zhi, 2004 Jan, 42(1), 23 - 5
{Follow up of 16 cases with congenital toxoplasmosis treated with azithromycin}; Chen GF et al.; OBJECTIVE: To study the therapeutic effects of azithromycin in treatment of congenital toxoplasmosis in children . METHODS: Definite diagnosis of congenital toxoplasmosis was made on the basis of clinical manifestation combined with one or more positive results of the following laboratory tests and excluded other congenital infectious diseases: toxoplasma DNA (TOX-DNA), circulating toxoplasma antigen (TOX-CAG), and toxoplasma IgM antibody (TOX-IgM) . All the patients were given oral azithromycin 10 mg/(kg.d) for 6 days followed by 8 days without medication (one course of treatment), and the regimen was persisted for 2 months and then another 2-month treatment was given at a 1-month interval . The authors continued to provide further treatment according to the state of the illness at one month interval . The patients received 2 to 8 (average 5) courses of treatment . The patients were followed-up for 2.5 to 5 (average 4) years . RESULTS: The treatment was effective in all the patients and the patient's condition was improved . The authors repeated in 12 cases the four tests for toxoplasma (TOX-DNA, TOX-CAG, TOX-IgM, and TOX-IgG) 9 months to one and a half years after treatment . In 10 cases all these tests showed negative results, in 2 cases TOX-IgG was positive and in the other 4 cases symptoms disappeared . CONCLUSION: The results of the study showed that oral azithromycin had significant therapeutic effects with little side effect and was well tolerated . Azithromycin may become an alternative therapy in treatment of congenital Toxoplasma gondii infection in children.

Lancet, 2004 Feb 14, 363(9408), 545 - 56
Sexually transmissible infections other than HIV; Donovan B; Sexually transmitted infections (STIs) are notable for their fastidious requirements for transmission and growth in the laboratory and for their high physical and psychosocial morbidity . The combination of subtle or absent symptoms and stigma preventing the seeking of health care, leaves many infections undiagnosed . The development of nucleic-acid amplification tests heralded a new era in sensitive and robust diagnostic procedures for STIs . Unfortunately, many of these tests are not commercially available or are too expensive for the populations that need them most . Single-dose oral azithromycin has improved the treatment of several bacterial STIs, but quinolones are rapidly becoming ineffective for gonorrhoea . Self-treatment of genital warts with podophyllotoxin or imiquimod preparations is attractive to patients and might be cost effective for health services . The prospect of effective vaccines against genital papillomaviruses in the near future is real . Such vaccines could reduce the global incidence of some anogenital cancers . Episodic treatment of genital herpes is getting easier and cheaper, and suppressive treatment can reduce transmission to regular sexual partners . A vaccine against herpes simplex virus type 2 has shown some limited efficacy . Ultimately, better control of STIs, and reduction of their contribution to the spread of HIV, will require a broad health-sector response with adequate resourcing, and a change in social and political attitudes.

Ann Pharmacother, 2004 Mar, 38(3), 433 - 9 Epub 2004 Jan 23.
Single-dose azithromycin for respiratory tract infections; Law C et al.; OBJECTIVE: To describe the pharmacology, efficacy, and safety data of the use of single-dose azithromycin for respiratory tract infections in children and adults . DATA SOURCES: A MEDLINE search (1990-September 2003) was performed to identify all pertinent studies and review articles . When appropriate information was not available in the literature, data were obtained from the product manufacturers or abstracts from international conferences . STUDY SELECTION AND DATA EXTRACTION: All available studies were reviewed to provide pharmacokinetic, pharmacodynamic, efficacy, and safety data on use of single-dose azithromycin for respiratory tract infections . DATA SYNTHESIS: Several studies have demonstrated that shorter regimens of azithromycin (1500 mg over 3 day vs 5 day or single dose vs 3 day) provide higher serum exposures compared with the longer regimens . This makes it possible to give the same dose over a shorter period of time and achieve the same efficacy with the potential for enhanced adherence . Single-dose azithromycin 30 mg/kg was approved in 2003 for treatment of acute otitis media (AOM) in children . Studies have demonstrated that, when administering azithromycin as a single dose, its efficacy and safety are comparable to that of other standard regimens for AOM . Single-dose regimens for treatment of respiratory tract infections in adults have not been studied widely, with only 2 studies being conducted for treatment of community-acquired pneumonia and one study for treatment of tonsillitis; all demonstrated at least equal efficacy with the single-dose regimen compared with comparators given for longer periods of time . CONCLUSIONS: Available data regarding single-dose azithromycin are promising . Although use of this regimen in children is warranted based on studies to date, additional large-scale trials are needed prior to mainstream use of the regimen in adults.

Infez Med, 1996, 4(1), 7 - 13
{Toxoplasmosis in pregnancy: recent acquisitions and new prospects}; Russo M et al.; Congenital toxoplasmosis may develop after maternal primary infection during pregnancy . The infection is usually asymptomatic in pregnant women but poses a risk of severe effects on the fetus . In Italy the incidence is about 6 per thousand . The infection is transmitted to the fetus in approximately 50 percent of such cases . The risk of transmission rises with growing gestational age at the time of primary infection; on the contrary, the seriousness of the effect on the fetuses becomes less active with more advanced pregnancies . Infants with congenital toxoplasmosis are mostly asymptomatic at birth but long-term studies have indicated that up to 85% of them will develop serious sequelae as severe impairment of vision, mental retardation and deafness during the months or the years after the birth . Preventing congenital toxoplasmosis is fundamental . All seronegative women should be encouraged to observe good dietary and general health regulations until delivery . Today the diagnosis in the mother is more reliable because of the improvements in serological techniques . Moreover, it is possible to identify infected fetuses by prenatal procedures such as ultrasonography, amniocentesis and cordocentesis, of which the last two consent to detect the parasite and/or specific antibodies . Recently a polymerase chain reaction (PCR) assay has been developed for the detection of Toxoplasma in the amniotic fluid . Adequate serological screening of pregnant and prenatal diagnosis can be helpful in reducing the incidence of congenital toxoplasmosis; furthermore abortion should be reserved only to cases with severe toxoplasmosis revealed by ultrasonography . Early recognition of pregnant infection and a specific treatment could reduce the parasitic colonization in the placenta by more than 60% and prevent infection in the fetus . If the fetal infection has already occurred, maternal treatment may modify the fetal disease . Spiramycin as immediate treatment of maternal primary infection is essential in preventing Toxoplasma transmission to the fetus . If the fetus results non-infected, spiramycin should be prolonged until delivery . If the fetus is infected, pyrimethamine-sulphadiazine combination should be given in repeated courses alternated with courses of spiramycin . However, there is an urgent need for more active and safer compounds; it would be useful to evaluate in the pregnant woman other potential therapeutic agents as atovaquone and azithromycin.

Eur J Intern Med, 2003 Dec, 14(8), 470 - 478
Azithromycin therapy in patients with chronic Chlamydia pneumoniae infection and coronary heart disease: immediate and long-term effects on inflammation, coagulation, and lipid status in a double-blind, placebo-controlled study; Gabriel AS et al.; Background: An association between Chlamydia pneumoniae (Cp) infection and coronary heart disease (CHD) has already been reported . We investigated the relationship between Cp infection and other risk factors in CHD patients, as well as the effects of azithromycin treatment . Methods: We studied 38 patients with Cp infection (Cp-pos) and 15 without (Cp-neg) . Cp-pos patients had, both at inclusion and 2 years prior to inclusion, elevated Cp-specific IgA-antibodies, with or without the presence of pharyngeal Cp by polymerase chain reaction (PCR) detection . Blood was analyzed for Cp-antibodies, interleukin-6, interleukin-1 receptor antagonist (IL-1ra), CRP, orosomucoid, fibrinogen, leukocytes, PAI-1, tPA, von Willebrand factor (vWf), platelet count and aggregation, and lipids . Cp-pos patients were randomized to placebo or oral azithromycin, 500 mg on day 1 and then 250 mg/day for 4 days, with repeated therapy after 3 weeks . Blood was taken immediately, as well as 3 months and 2 years after therapy . Results: CRP and IL-1ra levels were higher in Cp-pos than in Cp-neg patients: median, interquartile range 8.5 (3.0-20) vs . 2.0 (1.0-3.8) mg/l, and 316 (165-404) vs . 178 (118-195) ng/l, p=0.0006 and p=0.002, and platelet aggregation was lower: 4.8 (2.9-6.4) vs . 8.1 (4.7-11.4) Omega, p<0.05 . tPA levels increased in azithromycin-treated patients between entry and 3-month follow-up: mean+/-S.D . 3.7+/-4.2 vs . 1.0+/-2.1 microg/l, p<0.05 . Other variables did not differ . Conclusions: Cp infection was associated with increased inflammatory activity and lower platelet aggregability, suggesting that inflammation may be of greater pathophysiological importance than platelet activity in these patients . Although an effect on Cp infection was not shown, azithromycin may have a positive effect on fibrinolysis, as increased levels of tPA were observed in the treatment group.

Pediatr Infect Dis J, 2004 Feb, 23(2 Suppl), S135 - 9
Safety and tolerability of azithromycin in pediatric infectious diseases: 2003 update; Ruuskanen O; Oral azithromycin suspension has been prescribed to >80 million patients . Children find the color and taste of the oral suspension of azithromycin agreeable, and the drug is well-tolerated . On average 9% of patients have treatment-related adverse events, which are most frequently gastrointestinal complaints . The side effects are mild to moderate and very seldom necessitate withdrawal of the treatment . In addition to the conventional 3-day 10-mg/kg/day regimen and the 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5 regimens, single dose 30 mg/kg and 3-day 20-mg/kg/day regimens are well-tolerated, although these new dosages are associated with more adverse effects.

Pediatr Infect Dis J, 2004 Feb, 23(2 Suppl), S102 - 7
Rationale for single and high dose treatment regimens with azithromycin; Gordon EM et al.; The rationale for the use of single dose and shorter course azithromycin treatment regimens is based on the pharmacokinetic properties of azithromycin . The drug has a long elimination half-life (>50 h), which enables short course 1- or 3-day dose regimens to be clinically effective . Azithromycin is concentrated within phagocytic cells and tissues and it achieves targeted delivery by these cells to sites of infection . In vitro and in vivo models have demonstrated that azithromycin is taken up, transported and released at the sites of infection by phagocytic cells such as polymorphonuclear neutrophils and macrophages . Uptake is not saturable; therefore delivery of the total dose of azithromycin as a 1- or 3-day regimen should lead to increased uptake and delivery of the drug to sites of infection.

Am J Kidney Dis, 2004 Feb, 43(2), e25 - 30
Necrotizing glomerulonephritis caused by Bartonella henselae endocarditis; Bookman I et al.; Glomerulonephritis secondary to endocarditis is uncommon and usually associated with valvular infection by blood culture-positive bacteria . We report 3 cases of necrotizing glomerulonephritis associated with culture-negative endocarditis caused by Bartonella henselae . Two of the patients presented with renal abnormalities and were investigated for endocarditis after results of renal biopsy . All 3 patients had an immune complex-mediated necrotizing and crescentic glomerulonephritis with mesangial and capillary wall deposition of immunoglobulin M (IgM), IgG, and C3 . Electron microscopy showed immune-type electron-dense deposits in the mesangium and segmental subendothelial (2 cases) or subepithelial (1 case) deposits . Patients were treated with antibiotics, including azithromycin or doxycycline and ceftriaxone or tobramycin . In addition, 2 patients were administered steroids and 2 patients underwent valve replacement surgery . The 2 patients who underwent cardiac surgery were discharged from the hospital with stable renal function . The third patient died 4 months after hospital admission of renal failure . In conclusion, glomerulonephritis caused by B henselae endocarditis is an immune complex-mediated disease characterized by segmental necrotizing and crescentic glomerular lesions that can respond to aggressive medical and surgical therapy.

Int J Pharm, 2004 Feb 11, 270(1-2), 1 - 8
Pharmacokinetic evaluation of an azithromycin controlled release dosage form in healthy human volunteers: a single dose study; Gandhi R et al.; Azithromycin (AZI) follows a two-compartment model pharmacokinetically . The purpose of this study was to evaluate the in vivo performance of a controlled release (CR) formulation of AZI, which would eliminate the risk of high peak plasma concentrations obtained within 2-3 h after peroral administration of immediate release (IR) products . The study was conducted in twelve healthy male human volunteers to compare an experimental NIPER product (CR tablets) with Vicon (IR tablets) at the same dose level as a single-dose, randomized, one-period, two-treatment, and parallel-study . Concentrations of AZI in serum samples were assessed using the validated HPLC method . From the serum concentration-time profiles various pharmacokinetic parameters (AUC(0-96), AUC(0-inf), C(max) and T(max)) were calculated for both products . Results showed that the high peak concentration obtained by administration of a conventional IR formulation were eliminated with the CR product . A mean dosage form index (DI) of 1.17 with fluctuations of 7.57% was obtained with the CR product at steady state level, indicating reduced fluctuations at the steady state serum concentrations . Elimination of the pronounced peak as well as fluctuations reduced or minimized AZI adverse effects associated with the IR product.

Am J Trop Med Hyg, 2003 Nov, 69(5 Suppl), 29 - 32
Integration of trachoma control into primary health care: the Tanzanian experience; Mecaskey JW et al.; Tanzania was among the first countries to launch a trachoma control program with support from the International Trachoma Initiative (ITI) using surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy with azithromycin . More than one million children less than 10 years of age in Tanzania have active disease and an estimated 54,000 people have trichiasis . Since 2000, Tanzania has implemented major health sector reform that have been carried out in three phases in 114 districts . A key aspect of the reform process is the policy of developing locally distributed essential health packages that then serve as the basis of the comprehensive council health plan . In 2002, the Tanzania Ministry of Health in collaboration with the ITI, the World Bank, and the office of the President embarked on a program of information for districts where trachoma is endemic but where no control program has been launched . Clear goals for the trachoma control program have been reviewed and discussed by the districts and as a result trachoma control was integrated into the comprehensive council health plans for 2003 . This is expected to expand in 2004 and 2005 . This work is presented as a model for the support and integration of disease-specific control efforts into the primary health care system.

Am J Trop Med Hyg, 2003 Nov, 69(5 Suppl), 24 - 8
The global elimination of blinding trachoma: progress and promise; Kumaresan JA et al.; Trachoma is the world's leading cause of preventable blindness . It affects approximately 150 million people living in the world's poorest, rural communities and causes an estimated loss of $2.9 billion in productivity annually . In 1985, the Edna McConnell Clark Foundation joined with the World Health Organization to support studies on trachoma epidemiology and control, resulting in the elaboration of the surgery, antibiotics, facial cleanliness and environmental improvement (SAFE) strategy as the basis for the elimination of this blinding disease . Founded in 1998 by the Clark Foundation and Pfizer, Inc., the International Trachoma Initiative (ITI) is the only organization dedicated to eliminating blinding trachoma through support to national control programs . The availability of donated Zithromax (azithromycin) by Pfizer, Inc . has been paramount to the support of the ITI for implementation of SAFE in 10 country programs . The program has made considerable progress in four years . More than seven million individuals have received treatment, resulting in a cumulative reduction of 50% in active disease rates in children . More than 60,000 have also benefited from lid surgery that has halted progression to blindness . Morocco is expecting to attain the elimination of blinding trachoma by 2005 . However, the challenges facing the goal of global elimination by 2020 involve a vital program expansion, increased financial and technical support, environmental improvement, and continued advocacy efforts.

Am J Trop Med Hyg, 2003 Nov, 69(5 Suppl), 1 - 10
Global burden of trachoma and economics of the disease; Frick KD et al.; Interest in the economics of trachoma is high because of the refinement of a strategy to control trachomatous blindness, an ongoing global effort to eliminate incident blindness from trachoma by 2020, and an azithromycin donation program that is a component of trachoma control programs in several countries . This report comments on the economic distribution of blindness from trachoma and adds insight to published data on the burden of trachoma and the comparative costs and effects of trachoma control . Results suggest that 1) trichiasis without visual impairment may result in an economic burden comparable to trachomatous low vision and blindness so that 2) the monetary burden of trachoma may be 50% higher than conservative, published figures; 3) within some regions more productive economies are associated with less national blindness from trachoma; and 4) the ability to achieve a positive net benefit of trachoma control depends importantly on the cost per dose of antibiotic.

J Infect Dis, 2003 Dec 15, 188(12), 1794 - 803 Epub 2003 Dec 08.
Incomplete immune reconstitution after initiation of highly active antiretroviral therapy in human immunodeficiency virus-infected patients with severe CD4+ cell depletion; Lederman HM et al.; Immune function was observed for 144 weeks in 643 human immunodeficiency virus (HIV)-infected subjects who (1) had nadir CD4+ cell counts of <50 cells/mm3, followed by a sustained increase to > or =100 cells/mm3 after the initiation of HAART, and (2) were enrolled in a randomized trial of continued azithromycin prophylaxis versus withdrawal for prevention of Mycobacterium avium complex disease . The median CD4+ cell count was 226 cells/mm3 at entry and 358 cells/mm3 at week 144 . Anergy (80.2% of patients) and lack of lymphoproliferative response to tetanus toxoid (TT; 73%) after immunization and impaired antibody responses after receipt of hepatitis A (54%) and TT (86%) vaccines were considered to be evidence of impaired immune reconstitution . Receipt of azithromycin did not have an effect on CD4+ cell count but was associated with higher rates of delayed-type hypersensitivity responses to TT (25% of subjects who received azithromycin vs . 15% of those who did not; P=.009) and mumps skin test antigen (29% vs . 17%; P=.001) . Although the subjects had only partial responses to immune function testing, the rate of opportunistic infections was very low, and none of the tests was predictive of risk.

Arch Pediatr, 2003 Sep, 10 Suppl 2, 370s - 375s
{Anti-inflammatory therapy in cystic fibrosis}; Derelle J; Cystic fibrosis lung inflammation is early, sustained and severe and would justify an anti-inflammatory treatment . At present, the inhaled corticosteroid treatment did not give evidence of efficacy, contrary to the oral presentation, but at the cost of side effects . Azithromycin gives more encouraging results with a good tolerance . New molecules are in the process of validation.

Sex Transm Infect, 2003 Dec, 79(6), 453 - 5
Unusual presentation of early lymphogranuloma venereum in an HIV-1 infected patient: effective treatment with 1 g azithromycin; Nieuwenhuis RF et al.; The incidence of lymphogranuloma venereum (LGV) is low in the western world . Early LGV is characterised by bubonic disease following a painless papule or small ulcer . We report a white bisexual male who presented with a painful perianal ulcer, inguinal lymphadenitis, and concomitant infection with human immunodeficiency virus 1 (HIV-1) . Chlamydia trachomatis serovar L2 was identified as the cause after polymerase chain reaction and genotyping the major outer membrane protein by restricted fragment length polymorphism . Treatment with a single dose of 1 g azithromycin was effective . This case illustrates that early LGV may mimic other genital ulcer diseases, such as genital herpes or chancroid, especially in HIV infected patients . In the western world, LGV must still be included in the differential diagnosis of bubonic disease with or without sexually acquired ulcers.

Am J Obstet Gynecol, 2003 Nov, 189(5), 1398 - 400
Treatment of Trichomonas in pregnancy and adverse outcomes of pregnancy: a subanalysis of a randomized trial in Rakai, Uganda; Kigozi GG et al.; OBJECTIVE: The purpose of this study was to assess the association of presumptive Trichomonas vaginalis treatment during pregnancy and birth outcomes . STUDY DESIGN: A community-randomized trial of presumptive sexually transmitted disease treatment during pregnancy was conducted between 1994 and 1999 in Rakai district, Uganda . A subanalysis of a trial of presumptive therapy with azithromycin, cefixime, and metronidazole assessed Trichomonas vaginalis treatment in pregnant women . RESULTS: Children of 94 women with Trichomonas who were treated had increased low birth weight (relative risk, 2.49; 95% CI, 1.12-5.50), preterm birth rate (relative risk, 1.28; 95% CI, 0.81-2.02), and 2-year mortality rate (relative risk, 1.58; 95% CI, 0.99-2.52), compared with children of 112 women with Trichomonas who were not treated . CONCLUSION: Treatment of Trichomonas vaginalis during pregnancy may be deleterious, and we infer that this may be due to metronidazole . This is consistent with a National Institute for Child Health and Human Development trial that found an excess of preterm births in children of women with Trichomonas vaginalis infection who were treated with metronidazole.

J Fr Ophtalmol, 2003 Nov, 26(9), 921 - 7
{Extensive toxoplasmic retinochoroiditis . Diagnostic and therapeutic management}; Theaudin M et al.; INTRODUCTION: To assess the diagnostic and therapeutic management of extensive toxoplasmic retinochoroiditis . PATIENTS AND METHODS: The files of all patients referred between December 1999 and December 2001 for the management of a severe, potentially sight-threatening toxoplasmic retinochoroiditis were retrospectively analyzed . The therapeutic strategy and the progression of intraocular inflammation are reported . RESULTS: Thirteen eyes of seven patients were finally included in the study . The sex ratio (F/M) and the mean age were respectively 4/3 and 44.5 years . Most of the patients were immunocompromised . Both eyes were initially affected in five cases . The diagnosis was confirmed by polymerase chain reaction (PCR) after anterior chamber paracentesis in six cases . Retinal detachment was observed in three cases, initially or during follow-up . All patients were treated with a combination of sulfadiazine and pyrimethamine, but azithromycin was necessary in two cases . Clindamycin was used in two cases of allergy to sulfadiazine . Corticosteroids were associated in five cases . For all patients, infection and inflammation were finally controlled . The visual acuity improved more than two lines in four eyes and remained stable in seven other eyes . DISCUSSION: Clinical diagnosis is still a challenge in severe cases of extensive toxoplasmic retinochoroiditis . PCR is helpful in identifying Toxoplasma gondii DNA . A systemic immunosuppression is frequently associated with a positive PCR . Treatment is based on a standard antiparasitic association and steroids must be discussed for each case according to the intensity of inflammation and the degree of immunosuppression . CONCLUSION: Extensive ocular toxoplasmosis is a serious condition . The final prognosis depends on the location of the necrotic lesions, rapid diagnosis, and efficient treatment.

J Pharm Biomed Anal, 2003 Nov 24, 33(4), 647 - 54
Electrochemical oxidation of azithromycin and its derivatives; Mandic Z et al.; The electrochemical oxidation of azithromycin was investigated in order to elucidate the mechanism for possible oxidative metabolic pathways in humans . Electrochemical studies were carried out by cyclic voltammetry and preparative scale electrolysis at glassy carbon electrodes . It was found that azithromycin undergoes anodic oxidation at one or both amine groups with the rapid follow-up chemistry of intermediate radical cation . Main products of the oxidation were determined by HPLC analysis and were identified as a protonated azithromycin and products obtained by demethylation of the 3'-dimethylamino or macrolactone amino group.

J Can Dent Assoc . 2003 Nov;69(10):660.
Emergency management of acute apical abscesses in the permanent dentition: a systematic review of the literature; Matthews DC et al.; OBJECTIVE: To perform a systematic literature review and meta-analysis on the effectiveness of interventions used in the management of acute apical abscess in the permanent dentition . METHODS: Electronic databases were searched from their inception to March 2002 . These searches, combined with manual searching, yielded 85 citations, of which 35 were relevant . Independent application of inclusion criteria by 3 reviewers yielded 8 eligible randomized controlled studies . Data on population, interventions, outcomes (reduction of pain or swelling or both, as reported by patients or clinicians) and methodological quality were determined by independent triplicate review . Disagreements were resolved by consensus . RESULTS: All papers included in the meta-analysis compared an antibiotic with an active control, a placebo or no pharmacotherapy as an adjunct for patients who had received concomitant therapy (i.e., incision and drainage, endodontic therapy or extraction) . The 8 trials were randomized; in 3 of these, the method of randomization was described and appropriate . Five studies were double-blinded, and 2 of these described the method of blinding . Four trials described withdrawals, but none included an intention-to-treat analysis . Six studies compared 2 antibiotics . For the outcomes "absence of infection"and "absence of pain" the pooled odds ratios (ORs) were not statistically significant; for the outcome "absence of pain and infection," 3 studies showed an equivalent treatment effect in both treatment and control groups . One open-label study (with a quality score of 2) showed a result favouring azithromycin over co-amoxiclav (OR 0.58, 95% confidence interval 0.35-0.96) . Two studies compared adjunctive antibiotic therapy with placebo; no benefit to patients was demonstrated with this intervention . CONCLUSIONS: In the management of localized acute apical abscess in the permanent dentition, the abscess should be drained through a pulpectomy or incision and drainage . This analysis indicated that antibiotics are of no additional benefit . In the event of systemic complications (e.g., fever, lymphadenopathy or cellulitis), or for an immunocompromised patient, antibiotics may be prescribed in addition to drainage of the tooth.

Lancet Infect Dis, 2003 Nov, 3(11), 728 - 34
The possibility of eliminating blinding trachoma; Mecaskey JW et al.; Global elimination of blinding trachoma, the world's leading preventable cause of blindness, now seems possible . The disease, which persists most severely in the poorest parts of Africa and Asia, is already eliminated in North America and Europe . On a scientific basis, the case for elimination was outlined at a WHO global scientific meeting in 1996 . To facilitate action, WHO founded the Alliance for Global Elimination of Trachoma by 2020 (GET 2020) in 1997 . In 1998 a World Health Assembly resolution called for member states to take steps to eliminate blinding trachoma by 2020 using the WHO recommended SAFE strategy (surgery of late stage disease, antibiotics for acute infection, and improved facial hygiene and environmental change-ie, improved access to water and sanitation) . These developments contributed to the decision by Pfizer Inc to donate azithromycin in support of national programmes implementing SAFE and, with the Edna McConnell Clark Foundation, to found the International Trachoma Initiative as a charity dedicated to the elimination of blinding trachoma by 2020 . Reports of the early programme scope and impact are encouraging . In ten national programmes currently underway (constituting about 50% of the global burden) more than 55,000 lid surgeries have halted further corneal damage and prevented blindness, and more than 6 million treatments with azithromycin have been given with reductions in acute infections of around 50% in children . Morocco, one of the first countries to implement SAFE with azithromycin, has achieved remarkable results and expects to eliminate blinding trachoma by 2005 . If political will and public-health support can be mobilised, the goal of eliminating this cause of blindness can become a reality by 2020.

J Neuropathol Exp Neurol, 2003 Oct, 62(10), 990 - 8
Neuropathological and ultrastructural features of amebic encephalitis caused by Sappinia diploidea; Gelman BB et al.; Here we present the neuropathological, ultrastructural, and radiological features of Sappinia diploidea, a newly recognized human pathogen . The patient was a 38-year-old man with visual disturbances, headache, and a seizure . Brain images showed a solitary mass in the posterior left temporal lobe . The mass was composed of necrotizing hemorrhagic inflammation that contained free-living amebae . Immunofluorescence microscopy showed that the organism was not a species of ameba previously known to cause encephalitis . Trophozoites had a highly distinctive double nucleus, and transmission electron microscopy confirmed that they contained 2 nuclei closely apposed along a flattened surface . The 2 nuclei were attached to each other by distinctive connecting perpendicular filaments . This and several other unique structural features led to the diagnosis of S . diploidea encephalitis . The patient was treated postoperatively with a sequential regimen of anti-amebic drugs (azithromycin, pentamidine, itraconazole, and flucytosine) and is alive after 5 years . Guidelines to recognize future cases of S . diploidea encephalitis are as follows . 1) It presented as a tumor-like cerebral mass without an abscess wall . 2) It had central necrotic and hemorrhagic inflammation that contained acute and chronic inflammatory cells without granulomas or eosinophils . 3) It contained trophozoites (40-70 microm diameter) that contained a distinctive double nucleus . 4) Cyst forms in the host were not excluded or definitely evident . 5) Trophozoites engulfed host blood cells and were stained brightly with Giemsa and periodic acid-Schiff . 6) Trophozoites often were present in viable brain parenchyma on the periphery of the mass without inflammatory response . 7) The prognosis after surgical excision and medical treatment was favorable in this instance.

Przegl Lek, 2003, 60(3), 127 - 9
{Azithromycin (Sumamed) administration in empiric treatment of nosocomial pneumonia in upper digestive tract cancer patients}; Szpakowski M et al.; Septic complications are the most frequent and potentially lethal complications among patients treated for tumours . Respiratory tract infection, including pneumonia, is third most frequent of all infections occurring among patients undergoing surgical treatment . Of great clinical and pharmaeconomical importance is rational therapy with antibiotics, which lowers the risk of septic complications and sometimes even saves patients' lives . Azithromycin proved to be effective cure for environmental pneumonia . There has been presented a preliminary research on effectiveness of azithromicin in the treatment of septic pneumonia among patients treated for upper digestive tract cancers.

Zhongguo Zhong Xi Yi Jie He Za Zhi, 2003 Sep, 23(9), 654 - 7
{Controlled clinical study on 49 patients of SARS treated by integrative Chinese and Western medicine}; Zhang RL et al.; OBJECTIVE: To evaluate the efficacy of Integrative Chinese and western medicine (ICWM) in treating SARS . METHODS: By controlled paralled design, 49 patients of SARS were studied, they were divided into the control group (n = 29) and the ICWM group (n = 20) . The former was treated according to the "Recommended Program for Treatment of SARS" provided by Health Ministry, by administering of such drugs as Ribavirin, Levofloxacin, Thymopentin, Azithromycin, etc, the latter was treated with the ICWM protocol for SARS of "Special Technological Action to Prevent and Treat SARS" provided by Science and Technology Ministry . RESULTS: (1) The time for improving symptom in the ICWM group was 5.10 days and that in the control group was 7.62 days, the difference between them was significant (P < 0.05); (2) The days and amount for use hormone before subtract in the two group were similar, with insignificant difference (P > 0.05); (3) The days and amount for use hormone after subtract in the two groups were significantly different (P < 0.05); (4) The time for improving peripheral WBC count and absolute value of lymphocyte, as well as for absorption time of shadow in chest film were not different significantly between the two groups (P > 0.05) . CONCLUSION: In treating SARS, ICWM was superior to the treatment with western medicine alone in aspects of improving clinical symptom, promoting recovery of immune function and absorption of lung inflammation, decreasing the dosage of hormone used and shortening the therapeutic course.

J Eukaryot Microbiol, 2003 Sep-Oct, 50(5), 373 - 8
Isolation of a thermotolerant Paravahlkampfia sp . from lizard intestine: biology and molecular identification; Schuster FL et al.; An amoeba was isolated from the intestines of several moribund pink-tongued skinks (lizards), Hemisphaeriodon gerrardi . Unusual features of this isolate were its ability to grow at temperatures of > or = 37 degrees C, and its inability to use Escherichia coli as a food source or to grow axenically on a variety of enriched culture media suitable for other soil amoeba isolates . Growth was abundant, however, on tissue culture cells, with amoebae clearing cell monolayers in approximately 48 h at 37 degrees C . Trophozoites had a vahlkampfiid-like morphology, moving by means of an anterior eruptive pseudopod . Cysts, round to slightly ovoid and lacking exit pores, were formed in culture . Tests for enflagellation of trophic amoebae were negative . Indirect immunofluorescence staining was negative for Naegleria fowleri and Willaertia sp . The isolate was sensitive to azithromycin, but not to amphotericin B, pentamidine isethionate, fluconazole, 5-fluorocytosine, and sulfadiazine . Phylogenetic analysis based on the PCR-amplified small subunit ribosomal DNA, identified the organism as Paravahlkampfia ustiana, an amoeba not previously isolated from either poikilothermic or homeothermic hosts . No evidence of pathology was seen in stained sections of lizard intestine, suggesting that the ameba was part of the normal fauna of the lizard gut . Its diet in the lizard intestine is unknown and the organism may have unusual growth requirements . Thus, P . ustiana joins other soil amoebae that have been isolated from mammals, amphibia, fish, and reptiles, which have the potential of becoming opportunistic pathogens.

Clin Infect Dis, 2003 Nov 1, 37(9), 1165 - 71 Epub 2003 Sep 30.
Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico; Adachi JA et al.; Increased drug resistance among enteropathogens is an emergent problem in travelers' diarrhea . This randomized, double-blind trial was conducted in Guadalajara, Mexico, during the summers of 1999-2001 to compare azithromycin with levofloxacin for the treatment of travelers' diarrhea . A total of 217 US adults were randomized to receive a single oral dose of azithromycin (1000 mg; 108 persons) or levofloxacin (500 mg; 109 persons), with a follow-up period of 4 days . Three patients in each group dropped out of the study . The median time between initiation of therapy and passage of the last unformed stool (azithromycin group, 22.3 h; levofloxacin group, 21.5 h) and the number of unformed stools passed during the 4-day follow-up period (azithromycin group, 6.5; levofloxacin group, 5.5) were similar . Treatment failure occurred in 10 patients (9.5%) receiving azithromycin and 8 patients (7.5%) receiving levofloxacin . Possible minor, self-limiting adverse events occurred in 57 patients in each treatment group . Azithromycin was found to be a safe and effective alternative to levofloxacin for the treatment of acute travelers' diarrhea in US adult travelers to Mexico.

Chest, 2003 Oct, 124(4), 1482 - 6
Treatment of Mycobacterium avium-intracellulare complex lung disease with a macrolide, ethambutol, and clofazimine; Field SK et al.; BACKGROUND: Mycobacterium avium-intracellulare (MAC) causes progressive lung disease . Recommended treatment regimens include a macrolide and a rifamycin, but drug intolerance and relapse after treatment is completed often limit successful therapy . METHODS: Consecutive individuals referred for treatment of MAC lung disease were treated with a regimen that included either clarithromycin, 500 mg bid, or azithromycin, 250 mg/d, on weekdays; ethambutol, 15 mg/kg/d; and clofazimine, 100 mg/d . The intention was to treat patients for a minimum of 12 months . The diagnosis of MAC lung disease was confirmed by multiple positive sputum culture findings in patients with typical symptoms and radiologic findings . RESULTS: Thirty patients (27 women and 3 men; mean age, 70 +/- 9.4 years {SD}) were treated . A total of 22 of the patients reported adverse effects from clarithromycin or azithromycin . Intolerance of clarithromycin resulted in the withdrawal of four patients before sputum conversion . The remaining patients continued treatment for an average of 10 months, and sputum findings converted to negative in all 26 patients (87%) . One patient died of unrelated causes while still receiving therapy, and five patients (19%) relapsed an average of 17 months after treatment was completed . CONCLUSIONS: Treatment with a macrolide, ethambutol, and clofazimine was successful in 20 of 30 patients (67%) with MAC lung disease and is a reasonable alternative to rifamycin-containing regimens.

Cesk Slov Oftalmol, 2003 Sep, 59(5), 325 - 33
{Chlamydia pneumoniae--the etiologic agent of follicular conjunctivitis followed by keratoconjunctivitis sicca in adult patients}; Krasny J et al.; The authors refer to 21 adult patients at the age of 22 to 87 years, who have suffered from a chronic form of follicular conjunctivitis, found to be caused by Chlamydia pneumoniae as the etiological agent . The observation was made in the period from July 1999 to December 2002 . Chl . pneumoniae was detected by a direct demonstration of the conjunctiva smears and by means of serological examination . The print preparations on glass were examined by the method of indirect immunofluorescence by means of specific monoclonal antibodies (Medac, Germany) . The serological examination included detection of genus-specific IgG, IgA, IgM antibodies, respectively (Medac, Germany) and species-specific anti-Ch . pneumoniae IgG, IgA abd IgM antibodies, respectively (FOCUS Technologies, U.S.A.) . The clinical picture included various long-term subjective complaints (within the range of several months to ten years), particularly a pathological secretion or increased lacrimation, cutting, burning or feeling of a foreign body in the eye . The objective examination revealed chronic changes characterized by a mild edema of bulbar conjunctiva with increased meandering in vessels of irregular caliber and edema in the lower transition plica with follicular structure crossing into the tarsal conjunctiva . In the fornix there was an apparent sticking aqueous or mucinous secretion . The therapy was indicated by the positive smears alone in four patients or positive IgA and/or IgM of genus- or species-specific antibodies in 12 patients . The therapy in the remaining five patients was recommended by the combination of suspect-positive smears in combination with positive genus- or species specific antibody reaction . The therapy made use of systemic administration of a macrolide antibiotic, azithromycin, for the period of 12 to 14 days in a single course of treatment . The pretreatment was always followed by control smears after two weeks and by serological examinations after three and six months . The serological findings remained virtually unchanged during that period of time in all patients under observation . In two of them only the species-specific antibodies anti-Ch . pneumoniae IgA antibodies disappeared six months after the therapy . The clinical findings disappeared slowly, particularly the follicular changes occurred after more than six months after the therapy ended . The subjective complaints, accompanied by a transient hyperemia of conjunctives in particular, remained after the therapy in nine patients older than 45 years, who were found to suffer from kieratoconjnunctivitis sicca . The ocular symptomatology was not accompanied by symptoms of autoimmune disease . The general treatment by antibiotics and the results supportive treatment succeeded in 67% of patients who were completely free of subjective complaints and the pathological process in conjunctives was inhibited.

J Thorac Cardiovasc Surg, 2003 Sep, 126(3), 688 - 93
Atherogenic effects of Chlamydia pneumoniae: refuting the innocent bystander hypothesis; Selzman CH et al.; OBJECTIVE: Serologic evidence of Chlamydia pneumoniae infection and atherosclerosis was first demonstrated in patients with ischemic heart disease in 1988 . Subsequently, the organism has been detected in several cardiovascular lesions . Outside of observational reports, few studies mechanistically link vascular infection with C . pneumoniae and atherogenesis . To better define its pathophysiologic role, we examined the influence of C . pneumoniae infection of human vascular smooth muscle cells on vascular smooth muscle cell proliferation, cell-cycle protein expression, and inflammatory cytokine release . METHODS: Human aortic vascular smooth muscle cells were inoculated with C . pneumoniae in culture . Proliferation was assessed by mitochondrial activity, direct cell counting, and immunohistochemical staining for proliferating cell nuclear antigen . Electromobility gel shift assays probed for the antiproliferative cell-cycle protein p53 . Supernatants were assayed for the mitogens interleukin-6 and interleukin-8 by enzyme-linked immunosorbent assay . RESULTS: After C . pneumoniae inoculation, vascular smooth muscle cell proliferation increased 2-fold by mitochondrial activity and more than 3-fold by cell numbers . C . pneumoniae infection promoted a 3-fold increase in proliferating cell nuclear antigen expression, which was associated with decreased nuclear binding of p53 . Compared with control, C . pneumoniae inoculation resulted in a 2.5-fold increase in released interleukin-6 and interleukin-8 . In each experiment, the influence of C . pneumoniae was abrogated by concomitant treatment with the macrolide antibiotic azithromycin . CONCLUSIONS: C . pneumoniae induced human vascular smooth muscle cell proliferation and proliferating cell nuclear antigen expression, down-regulated p53, and promoted release of prototypical atherogenic cytokines . These in vitro findings indicate that C . pneumoniae is more than an innocent bystander, rather it is a pathophysiologic participant in atherogenesis warranting elimination.

J Mol Neurosci, 2003, 20(3), 267 - 75
Drug discovery targeted to the Alzheimer's APP mRNA 5'-untranslated region: the action of paroxetine and dimercaptopropanol; Payton S et al.; We screened for drugs that specifically interact with the 5'-untranslated region of the mRNA encoding the Alzheimer's amyloid precursor protein (APP) . Our goal was to use newly discovered APP 5' UTR directed compounds to limit amyloid-beta (Abeta)-peptide output in cell culture systems . The APP 5' UTR folds into a stable RNA secondary structure (Gibbs free energy: DeltaG = -54.9 kcal/mol) and is an important regulator of the amount of APP translated in response to IL-1 (Nilsson et al., 1998; Rogers et al., 1999) and iron (Rogers et al., 2002) . Seventeen drug "hits" were identified from a library of 1,200 FDA preapproved drugs (Rogers et al., 2002) . Six of the original 17 compounds were validated for their capacity to suppress reporter gene expression in stable neuroblastoma transfectants expressing the dicistronic reporter construct shown in Fig . 2 . These six leads suppressed APP 5' UTR driven luciferase translation while causing no effect on the translation of dicistronic GFP gene translated from a viral IRES (negative control to ensure specificity during drug screens) . In this report, we show that paroxetine (serotonin reuptake blocker) and dimercaptopropanol (Hg chelator) exerted significant effects on APP expression (steady-state levels of APP), whereas Azithromycin altered APP processing . None of these three compounds altered APLP-1 expression . In the future, we will identify further novel compounds that influence Abeta levels, either via translation inhibition or by changing the activity of proteins coupled between APP translation and APP processing.

JAMA, 2003 Sep 17, 290(11), 1459 - 66
Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial; O'Connor CM et al.; CONTEXT: Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis . OBJECTIVE: To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure . DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more . Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001 . INTERVENTION: The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868) . MAIN OUTCOME MEASURES: The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina . Patients were followed up until 1038 events accrued . RESULTS: After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% {95% confidence interval, -5% to 17%}, P =.23) . Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time . There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%) . Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo . CONCLUSION: Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.

J Pharm Biomed Anal, 2003 Sep 19, 33(2), 211 - 7
LC determination of impurities in azithromycin tablets; Miguel L et al.; A LC method with UV detection for determining azithromycin impurities in tablets as pharmaceutical form has been developed . It is to be employed in routine and stability tests . A linear gradient elution was employed starting with 47% A and 53% B to reach 28% A and 72% B at 48 min . Mobile phase A was KH2PO4 10 mM (H2O) at pH 7.00 . B was a mixture methanol:acetonitrile 1:1 (v/v) . UV detection was performed at 210 nm . The chromatographic column was Phenomenex Synergi MAX-RP 4 microm 250 x 460 mm kept at 50 degrees C . Six impurities were separated and identified and it was possible to quantify five out of the six with reasonable accuracy and precision.

Acta Trop, 2003 Sep, 88(1), 45 - 50
Efficacy of azithromycin in a murine toxoplasmosis model, employing a Toxoplasma gondii strain from Turkey; Degerli K et al.; A murine toxoplasmosis model with Balb/C mice was used to investigate the therapeutic and prophylactic efficacy of azithromycin in a native strain of Toxoplasma gondii . Initially, seven groups--four studies and three controls--were established and 10(3) tachyzoites of this native strain of T . gondii were injected intraperitoneally to the mice in groups 1, 2, 3, 4 and 7 . Azithromycin was given to groups 1-4 at different times of infection orally between 100 and 300 mg/kg/day for 10 days . Azithromycin was found to be effective at 200 mg/kg/day and above in the prophylaxis, at 250 mg/kg/day and above in the treatment of toxoplasmosis . These results suggest that azithromycin is effective in the prophylaxis and early infection of a highly virulent strain of T . gondii, and it doubled the survival time in the late infection . Azithromycin could be an alternative treatment regimen for human toxoplasmosis, if supported by further clinical investigations.

Antimicrob Agents Chemother, 2003 Sep, 47(9), 2770 - 4
Randomized double-blind study comparing 3- and 6-day regimens of azithromycin with a 10-day amoxicillin-clavulanate regimen for treatment of acute bacterial sinusitis; Henry DC et al.; A randomized, double-blind, multicenter study of adults with acute bacterial sinusitis (ABS) compared the efficacy and safety of two azithromycin (AZM) regimens, 500 mg/day once daily for 3 days (AZM-3) or 6 days (AZM-6) to the efficacy and safety of an amoxicillin-clavulanate (AMC) regimen of 500-125 mg three times daily for 10 days . A total of 936 subjects with clinically and radiologically documented ABS were treated (AZM-3, 312; AZM-6, 311; AMC, 313) . Clinical success rates were equivalent among per-protocol subjects at the end of therapy (AZM-3, 88.8%; AZM-6, 89.3%; AMC, 84.9%) and at the end of the study (AZM-3, 71.7%; AZM-6, 73.4%; AMC, 71.3%) . Subjects treated with AMC reported a higher incidence of treatment-related adverse events (AE) (51.1%) than AZM-3 (31.1%, P < 0.001) or AZM-6 (37.6%, P < 0.001) . More AMC subjects discontinued the study (n = 28) than AZM-3 (n = 7) and AZM-6 (n = 11) subjects . Diarrhea was the most frequent treatment-related AE . AZM-3 and AZM-6 were each equivalent in efficacy and better tolerated than AMC for ABS.

Zhonghua Nan Ke Xue, 2003, 9(4), 309 - 11, 315
{Clinical application research of feilinjian peroral liquid in the treatment of chlamydia and mycoplasma infectious prostatitis}; Jiang Y et al.; OBJECTIVES: To evaluate the validity and security of Feilinjian peroral liquid in the treatment of chlamydia trachomatis (CT), mycoplasma hominis (Mh) and Ureaplasma urelyticum (UU) infectious prostatitis . METHODS: Two hundred and three patients of CT, Mh or UU infectious prostatitis diagnosed by strict orientation examination were randomly divided into two groups, one given feilinjian peroral liquid, and the other azithromycin perorally, for one month as treatment period . RESULTS: The analytical results showed that 54 (42.86%) were clinically fully recovered, 32(32.39%) were significantly effective, and 13 (10.31%) were effective in feilinjian peroral liquid group, with total significantly effective rate 68.25% and total effective rate 78.57%, both obviously higher than those in the control group(50.64% and 57.14% respectively) . CONCLUSIONS: Feilinjian peroral liquid is significantly better than azithromycin in ameliorating self-conscious symptoms, symptoms scoring of patients with CT, Mh and UU infection, with little side-effects.

Sex Transm Dis, 2003 May, 30(5), 455 - 69
A comparison of cost-effectiveness of three protocols for diagnosis and treatment of gonococcal and chlamydial infections in women in Africa; Sahin-Hodoglugil NN et al.; BACKGROUND: The cost-effectiveness of different STD diagnosis and treatment approaches has not been evaluated previously . GOALS: The goals of the study were to compare the cost-effectiveness of "gold standard" care (GS), syndromic management (SM), and mass treatment (MT) protocols for the treatment of cervical gonococcal and chlamydial infections in a hypothetical model of 1 million women in Africa . STUDY DESIGN: A decision tree model was constructed for each of the protocols . Sensitivity analyses were conducted and 10,000 Monte Carlo simulations were run to test the robustness of the cost-effectiveness estimates to changes in underlying assumptions . RESULTS: MT with doxycycline for chlamydia was the most cost-effective protocol in terms of cost per cure . SM protocol had the lowest total programmatic costs . For the GS protocol, using azithromycin for chlamydial infections was found to be more cost-effective than using doxycycline . For both the GS and SM protocols, the total cost of the program was most sensitive to the percentage of women seeking STD treatment and the prevalence of non-STD vaginal discharge, whereas the cost of MT was almost exclusively determined by coverage rates . CONCLUSIONS: No single protocol carries with it all the desired conditions of an optimal cost-effective program . The treatment-seeking behavior, STD prevalence, and coverage of each locale must be evaluated to determine the most cost-effective and highest impact program . MT was found to be the most cost-effective protocol in terms of cost per woman treated when compared with the SM and GS protocols for STDs in women.

J Clin Pharm Ther, 2003 Aug, 28(4), 329 - 38
Is oral azithromycin effective for the treatment of cyclosporine-induced gingival hyperplasia in cardiac transplant recipients?
Strachan D, Burton I, Pearson GJ.
Anecdotal evidence suggests that azithromycin is effective for the treatment of cyclosporine-induced gingival hyperplasia in solid-organ transplant recipients . We present the cases of two heart transplant patients who insidiously developed gingival hyperplasia, likely because of immunosuppression with cyclosporine, which was treated with azithromycin . Evidence supporting the efficacy of azithromycin in the treatment of cyclosporine-induced gingival hyperplasia in solid organ transplant recipients was searched for, identified, and then critically assessed . While no data were found specifically evaluating azithromycin in cardiac transplant patients, there were nine pertinent papers identified that evaluated the clinical question of interest in the renal transplant population {Wahlstrom et al . (1995) The New England Journal of Medicine 332, 753; Boran et al . (1996) Transplantation Proceedings 28, 2316; Gomez et al . (1997) Nephrology Dialysis Transplantation 12, 2694; Ljutic (1997) Dialysis & Transplantation 26, 787; Puig et al . (1997) Transplantation Proceedings 29, 2379; Nash et al . (1998) Transplantation 65, 1611; Nowicki et al . (1998) Annals of Transplantation 3, 25; Wirnsberger et al . (1998) Transplantation Proceedings 30, 2117; Citterio et al . (2001) Transplantation Proceedings 33, 2134} . These studies and case reports are summarized . While more evidence is required to support routine use of azithromycin for the treatment of cyclosporine-induced gingival hyperplasia in cardiac transplant recipients, preliminary published evidence from renal transplant patients is certainly favourable.

Sex Transm Infect, 2003 Aug, 79(4), 318 - 9
Tetracycline treatment does not eradicate Mycoplasma genitalium; Falk L et al.; OBJECTIVES: To study the treatment efficacy of tetracyclines and azithromycin in Mycoplasma genitalium positive patients attending an STD clinic . METHODS: All M genitalium positive patients (34 men and 26 women) attending an STD clinic during a 6 month period were treated with antibiotics . All patients known to be partners of M genitalium positive patients and those who were M genitalium positive, but not initially treated, were treated with azithromycin . Patients with urethritis and/or cervicitis were treated with tetracyclines before their M genitalium status was known . RESULTS: 10 of 14 women (71%) and 10 of 16 men (63%) treated with tetracyclines were M genitalium positive at follow up, whereas all patients treated with azithromycin (16 men and 20 women) were M genitalium negative, at the 4 week follow up visit . CONCLUSIONS: These results suggest that tetracyclines are not sufficient to eradicate M genitalium . Randomised controlled treatment trials are urgently needed.

Am J Emerg Med, 2003 Jul, 21(4), 313 - 5
The effect of ED prescription dispensing on patient compliance; Ginde AA et al.; The objective of this study was to evaluate whether dispensing prescriptions in the ED affects patient compliance and return visits to the hospital . Seventy-four patients who were deemed suitable candidates for outpatient therapy with a macrolide antibiotic were identified and prospectively randomized to receive either an entire course of azithromycin from the ED or a prescription for azithromycin to be filled at a local pharmacy free of charge . Pharmacy records and telephone interview were used to measure compliance with patients . Significantly fewer patients filled their prescription in the pharmacy group (74.2%) compared with the ED group, in which all patients received their medication . However, there was no difference in the self-reported compliance of completing the entire course of antibiotics between patients in the ED group (94.3%) and in the pharmacy group (96.8%) . There was no significant difference between groups in return ED visits or hospital admissions . We conclude that delivery of prescriptions in the ED significantly increases the likelihood that the patient will obtain the medication prescribed . Whether the patients actually take the medication as directed is unknown . Patient's self-report did not accurately reflect true compliance and more objective means for measuring compliance is warranted.

J Antimicrob Chemother, 2003 Sep, 52(3), 469 - 72 Epub 2003 Jul 29.
Randomized, double-blind study of the clinical efficacy of 3 days of azithromycin compared with co-amoxiclav for the treatment of acute otitis media; Dunne MW et al.; BACKGROUND: Compared with 5 days of dosing, a 3 day dosing regimen of azithromycin for treatment of acute otitis media (AOM) may improve compliance, will simplify therapy for the caregiver and, by giving the same total dose as the 5 day regimen, provide more drug when the bacterial burden is highest . METHODS: Children of 6 months-12 years were enrolled if they had had symptoms and signs of AOM for <4 weeks and tympanic membrane effusion by acoustic reflectometry . Eligible children were randomized to azithromycin 10 mg/kg/day x 3 days or co-amoxiclav 45 mg/kg/day x 10 days . The primary endpoint was clinical response at day 28 . RESULTS: One hundred and eighty-eight children (mean age 3.5 years) were randomized to azithromycin and 185 to co-amoxiclav . At day 10, the clinical success rate was 153/185 (83%) in children treated with azithromycin and 159/181 (88%) in children treated with co-amoxiclav . At day 28, 134/182 (74%) of the children were cured on azithromycin compared with 124/180 (69%) on co-amoxiclav . Also at day 28, signs of AOM, such as abnormal reflectometry (45% versus 59%; P = 0.017), bulging of the eardrum (10% versus 16%; P = 0.059) and loss of tympanic membrane landmarks (11% versus 22%; P = 0.010) were seen less frequently in azithromycin- than co-amoxiclav-treated children, respectively . Adverse events related to therapy were seen in 11% of azithromycin patients compared with 20% on co-amoxiclav (P = 0.014) . CONCLUSIONS: Azithromycin given over 3 days is as effective as co-amoxiclav for treatment of AOM, may result in more complete resolution of tympanic membrane disease, and is better tolerated.

Arch Intern Med, 2003 Jul 28, 163(14), 1718 - 26
Azithromycin monotherapy for patients hospitalized with community-acquired pneumonia: a 31/2-year experience from a veterans affairs hospital; Feldman RB et al.; BACKGROUND: Current American Thoracic Society (ATS) community-acquired pneumonia treatment guidelines recommend azithromycin monotherapy for a limited subset of hospitalized patients . We evaluated the effectiveness of azithromycin monotherapy in a more generalized population of patients hospitalized with mild-to-moderate community-acquired pneumonia . METHODS: We reviewed medical records from a Veterans Affairs facility for patients admitted with community-acquired pneumonia between December 1, 1997, and June 30, 2001, comparing those receiving azithromycin monotherapy, other ATS-recommended antibiotics, and non-ATS-recommended antibiotics . We excluded patients with immunosuppression, metastatic cancer, or hospital-acquired pneumonia . Outcome measures included times to stability, meeting criteria for change to oral therapy, and eligibility for discharge; length of stay; intensive care unit transfer; and mortality . Outcomes were adjusted for pneumonia severity, skilled nursing facility status, and processes of care . RESULTS: A total of 442 patients were eligible for the study (221 in the azithromycin monotherapy group, 129 in the ATS group, and 92 in the non-ATS group) . Times to clinical stability and to fulfilling early switch criteria were not statistically significantly different among the 3 groups . Mean time to fulfilling early discharge criteria was 2.48 days for patients receiving azithromycin monotherapy vs 2.84 days for those receiving ATS antibiotics (P =.008) and 2.58 days for those receiving non-ATS antibiotics (P =.64) . Overall mean length of stay was shorter in the azithromycin monotherapy group (4.35 days) vs the ATS (5.73 days) (P =.002) and non-ATS (6.21 days) (P<.001) groups . Mortality, intensive care unit transfer, and readmission rates were similar across the groups . CONCLUSION: Azithromycin monotherapy is equally as efficacious as other ATS-recommended regimens for treating hospitalized patients with mild-to-moderate community-acquired pneumonia.

Lancet, 2003 Jul 19, 362(9379), 223 - 9
Trachoma; Mabey DC et al.; Trachoma is the most common infectious cause of blindness . It is caused by ocular serovars of Chlamydia trachomatis . Transmission is favoured in poor communities, where crowding is common and access to water and sanitation inadequate . Repeated reinfection over many years causes dense scarring of the upper eyelid . The resultant inversion of the lashes abrades the eyeball, and the abrasion leads to corneal opacification and visual impairment . The host immune response is probably at least partly the cause of this process . The "SAFE" strategy is used for the control of trachoma: surgery for in-turned lashes, antibiotics for active disease, facial cleanliness, and environmental improvement . The demonstration that a single oral dose of the antibiotic azithromycin is as effective as 6 weeks of topical tetracycline was an important advance in trachoma control . By means of the SAFE strategy, WHO and its partners aim to eliminate trachoma as a public-health problem by the year 2020.

Antimicrob Agents Chemother, 2003 Aug, 47(8), 2450 - 7
Steady-state plasma and bronchopulmonary concentrations of intravenous levofloxacin and azithromycin in healthy adults; Rodvold KA et al.; The purpose of this study was to compare the concentrations of levofloxacin and azithromycin in steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) after intravenous administration . Thirty-six healthy, nonsmoking adult subjects were randomized to either intravenous levofloxacin (500 or 750 mg) or azithromycin (500 mg) once daily for five doses . Venipuncture and bronchoscopy with bronchoalveolar lavage were performed in each subject at either 4, 12, or 24 h after the start of the last antibiotic infusion . The mean concentrations of levofloxacin and azithromycin in plasma were similar to those previously published . The dosing regimens of levofloxacin achieved significantly (P < 0.05) higher concentrations in steady-state plasma than azithromycin during the 24 h after drug administration . The respective mean (+/- standard deviation) concentrations at 4, 12, and 24 h in ELF for 500 mg of levofloxacin were 11.01 +/- 4.52, 2.50 +/- 0.97, and 1.24 +/- 0.55 micro g/ml; those for 750 mg of levofloxacin were 12.94 +/- 1.21, 6.04 +/- 0.39, and 1.73 +/- 0.78 micro g/ml; and those for azithromycin were 1.70 +/- 0.74, 1.27 +/- 0.47, and 2.86 +/- 1.75 micro g/ml . The differences in concentrations in ELF among the two levofloxacin groups and azithromycin were significantly (P < 0.05) higher at the 4- and 12-h sampling times . The respective concentrations in AM for 500 mg of levofloxacin were 83.9 +/- 53.2, 18.3 +/- 6.7, and 5.6 +/- 3.2 micro g/ml; those for 750 mg of levofloxacin were 81.7 +/- 37.0, 78.2 +/- 55.4, and 13.3 +/- 6.5 micro g/ml; and those for azithromycin were 650 +/- 259, 669 +/- 311, and 734 +/- 770 micro g/ml . Azithromycin achieved significantly (P < 0.05) higher concentrations in AM than levofloxacin at all sampling times . The concentrations in ELF and AM following intravenous administration of levofloxacin and azithromycin were higher than concentrations in plasma . Further studies are needed to determine the clinical significance of such high intrapulmonary concentrations in patients with respiratory tract infections.

Minerva Ginecol, 2003 Jun, 55(3 Suppl 1), 1 - 8
{Chlamydia infection}; Lello S et al.; Chlamydial infection of genital tract is the most common sexually transmitted diseases and can have important complications such as pelvic inflammatory disease and ectopic pregnancy . Several diagnostic methods are now available . The treatments of choice are represented by doxycycline and azithromycin.

J Pharm Biomed Anal, 2003 Apr 24, 32(1), 197 - 202
Voltammetric assay of azithromycin in pharmaceutical dosage forms; Nigovic B et al.; The oxidative behaviour of azithromycin was studied at s glassy carbon electrode in different buffer system using cyclic, linear sweep and differential pulse voltammetry . The oxidation process was shown to be irreversible over the entire pH range studied (5-11) and was diffusion-adsorption controlled . Analytical method with adequate precision and accuracy was developed for the determination of azithromycin in phosphate buffer at pH 7 as supporting electrolyte containing 10% methanol and 0.05 M ammonium acetate . The peak current varied linearly with azithromycin concentration in the range 1-15 microg/ml . The procedure was successfully applied for assay of the drug in the pharmaceutical dosage forms . The relative standard deviation (n = 5) of 2.18% was obtained.

Antimicrob Agents Chemother, 2003 Jul, 47(7), 2199 - 203
Tolerability of azithromycin as malaria prophylaxis in adults in northeast papua, indonesia; Taylor WR et al.; Drug tolerability affects compliance . We evaluated the tolerability levels of azithromycin (750-mg loading dose plus 250 mg/day; n = 148 subjects), doxycycline (100 mg/day; n = 75), and placebo (n = 77) as prophylaxis against malaria in Indonesian adults over 20 weeks . Self-reported and elicited symptoms, health perception, hearing, hematology, and biochemistry were assessed . The loading dose was well tolerated . The frequencies (number per person-years {p-yr}) of all daily reported symptoms were similar in the three arms of the study: 40.2/p-yr for azithromycin, 39.7/p-yr for doxycycline, and 38.2/p-yr for placebo . Relative to those who received placebo, azithromycin recipients complained more often of heartburn (rate ratio = 10.5 {95% confidence interval, 2.8 to 88.1}), paresthesia (2.03 {1.08 to 4.24}), and mild (1.55 {1.01 to 2.48}) and severe (11.2 {1.34 to infinity }) itching but less often of fever (0.21 {0.09 to 0.49}) and tinnitus (0.09 {0.04 to 0.21}) . Azithromycin recipients showed no evidence of clinical hearing loss or hematologic, hepatic, or renal toxicity . One azithromycin recipient developed an erythematous rash . Daily azithromycin was well tolerated by these Indonesian adults during 20 weeks of treatment.

Orthopade, 2003 Jun, 32(6), 535 - 40
{Chronic recurrent multifocal osteomyelitis}; Seidl T et al.; Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, inflammatory, skeletal disease of unknown origin, which mainly affects children and adolescents in terms of cleido-spondylo-metaphysal skeletal inflammation . Only 10% of the patients are older than 20 years . To date, only about 200 cases have been reported in the literature . In the course of the disease, the initial radiological signs are osteolysis followed by sclerosis and hyperostosis in the end stage . The histological investigations reveal chronic inflammatory infiltrates with lymphocytes and hyperostosis . Although the prognosis of CRMO, to our current understanding, is self limiting, serious complications have been reported such as pathological fractures and compression fractures of the spine . A recently recommended therapy scheme is based on the administration of azithromycin combined with calcitonin . We present the case of a 25 year old female patient who has suffered from CRMO for 1.5 years with the cervical spine and the manubrium sterni being affected . The current state of diagnosis, therapy, and prognostic outlook of this rare disease are discussed.

Vector Borne Zoonotic Dis, 2003 Spring, 3(1), 45 - 51
Babesiosis diagnosis and treatment; Krause PJ; Human babesiosis due to Babesia microti is an emerging malaria-like infection that is endemic in parts of the northeastern and northcentral United States . The clinical manifestations of babesiosis range from subclinical illness to fulminant disease resulting in death . Prompt and accurate diagnosis is difficult because the signs and symptoms are non-specific . A CBC is a useful screening test since anemia and thrombocytopenia are commonly observed and parasites may be visualized on blood smear . Conclusive diagnosis of this disease generally depends upon microscopic examination of thin blood smears . Babesia frequently are overlooked, however, because parasitemia tends to be sparse, often infecting fewer than 1% of erythrocytes early in the course of the illness . Identification of amplifiable babesial DNA by polymerase chain reaction (PCR) has comparable sensitivity and specificity to microscopic analysis of thin blood smear for detection of babesia in blood . Serologic testing provides useful supplementary evidence of infection because a robust antibody response characterizes human babesial infection, even at the time that parasitemia first becomes detectable . The currently recommended therapy for babesiosis is a 7-10-day course of clindamycin (600 mg every 6 h) and quinine (650 mg every 8 h) . Recently, azithromycin (500-600 mg on day 1, and 250-600 mg on subsequent days) and atovaquone (750 mg every 12 h) was found to be equally effective in treating adults experiencing babesiosis . This combination also was associated with fewer adverse reactions than clindamycin and quinine . Exchange transfusion is a potentially life-saving therapy for patients suffering from severe disease with high parasitemia (>5%), significant hemolysis, or renal or pulmonary compromise . Babesiosis may be prevented by avoiding areas such as tall grass and brush where ticks, deer, and mice are known to thrive.

J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Jul 5, 791(1-2), 45 - 53
Determination of three major components of bitespiramycin and their major active metabolites in rat plasma by liquid chromatography-ion trap mass spectrometry; Zhong D et al.; The rapid, selective and sensitive liquid chromatographic-ion trap mass spectrometric (LC-MS(n)) method was developed and validated for determination of three major components (isovaleryspiramycins, ISV-SPMs) of a novel macrolide antibiotic bitespiramycin and their major active metabolites (spiramycins, SPMs) in rat plasma . The analytes ISV-SPMs, SPMs, internal standard roxithromycin and azithromycin were extracted from plasma samples by liquid-liquid extraction, and chromatographed on a C(18) column using two mobile phase systems . Detection was carried out on an ion trap mass spectrometer by selected reaction monitoring (SRM) mode via electrospray ionization (ESI) . Three components (ISV-SPM I, II, III or SPM I, II, III) could be simultaneously determined within 6.5 min . Linear calibration curves were obtained in the concentration ranges of 4-200 ng/ml for ISV-SPM I and SPM I, 12-600 ng/ml for ISV-SPM II and SPM II, and 18-900 ng/ml for ISV-SPM III and SPM III . The intra- and inter-run precision (RSD), calculated from quality control (QC) samples were less than 8.8 and 10.4% for ISV-SPMs, and 9.3 and 11.2% for SPMs, respectively . The method was applied for the evaluation of the pharmacokinetics of bitespiramycin in rats following peroral/intravenous administration.

J Rheumatol, 2003 Jun, 30(6), 1347 - 50
Whipple's disease with destructive arthritis, abdominal lymphadenopathy, and central nervous system involvement; Dearment MC et al.; We describe a patient with Whipple's disease who had an unusual erosive and destructive polyarthritis, massive abdominal lymphadenopathy, asymptomatic central nervous system involvement, and rare manifestations of orbital pseudotumor and orchitis with epididymitis . Taking oral therapy with trimethoprim-sulfamethoxazole he had recurrent flares of orbital pseudotumor, an episode of orchitis with epididymitis, and persistent polymerase chain reaction T . whipplei-positive cerebrospinal fluid . Resolution was achieved with a one month course of intravenous ceftriaxone and a 6 month course of azithromycin, and no relapse occurred during 24 months of followup.

Am Fam Physician, 2003 May 1, 67(9), 1915 - 22
Update on the prevention and treatment of sexually transmitted diseases; Miller KE et al.; The Centers for Disease Control and Prevention (CDC) recently published updated guidelines that provide new strategies for the prevention and treatment of sexually transmitted diseases (STDs) . Patient education is the first important step in reducing the number of persons who engage in risky sexual behaviors . Information on STD prevention should be individualized on the basis of the patient's stage of development and understanding of sexual issues . Other preventive strategies include administering the hepatitis B vaccine series to unimmunized patients who present for STD evaluation and administering hepatitis A vaccine to illegal drug users and men who have sex with men . The CDC recommends against using any form of nonoxynol 9 for STD prevention . New treatment strategies include avoiding the use of quinolone therapy in patients who contract gonorrhea in California or Hawaii . Testing for cure is not necessary if chlamydial infection is treated with a first-line antibiotic (azithromycin or doxycycline) . However, all women should be retested three to four months after treatment for chlamydial infection, because of the high incidence of reinfection . Testing for herpes simplex virus serotype is advised in patients with genital infection, because recurrent infection is less likely with the type 1 serotype than with the type 2 serotype . The CDC guidelines also include new information on the treatment of diseases characterized by vaginal discharge.

Pharmacol Res, 2003 Jun, 47(6), 549 - 54
Influence of a 3-day regimen of azithromycin on the disposition kinetics of cyclosporine A in stable renal transplant patients; Bachmann K et al.; Some macrolide antibiotics have been shown to produce significant drug-drug interactions through the inhibition of cytochrome P450 (CYP) enzymes . In renal transplant patients these interactions pose potentially serious problems for the safe administration of cyclosporine A (CSA), a substrate of CYP3A4 . The effects of azithromycin on CSA disposition kinetics were evaluated in eight stable renal transplant patients . Patients had been stabilized on individualized doses of CSA which remained unchanged throughout the study . Azithromycin was administered for 3 days . Baseline measurements of CSA disposition kinetics were taken prior to azithromycin treatment (study day 2) and after 3 days (study day 5) of azithromycin treatment (500mg/day, orally) . The key parameters of interest were the area under the CSA blood concentration versus time curve (AUC) measured for 24h after the morning dose of CSA on both days 2 and 5, and the C(max) values of CSA . The geometric mean ratios (GMRs) of those parameters (day 5/day 2) and their 90% confidence intervals (90% CI) were 107 (98,116) and 119 (104,136), respectively . The 7% increase in exposure level and 19% increase in peak plasma concentration are not likely to be clinically significant . It is concluded that azithromycin (500mg/dayx3 days) does not alter the disposition kinetics of CSA in a clinically significant way, and that CSA dosage adjustments are not warranted in renal transplant patients taking these two drugs together.

Pharm Res, 2003 Apr, 20(4), 624 - 31
Cell handling, membrane-binding properties, and membrane-penetration modeling approaches of pivampicillin and phthalimidomethylampicillin, two basic esters of ampicillin, in comparison with chloroquine and azithromycin; Chanteux H et al.; PURPOSE: The purpose of this work was to examine and understand the cellular pharmacokinetics of two basic esters of ampicillin, pivaloyloxymethyl (PIVA) and phthalimidomethyl (PIMA), in comparison with lysosomotropic drugs (chloroquine, azithromycin) . METHODS: Cell culture studies (J774 macrophages) were undertaken to study uptake and release kinetics and to assess the influence of concentration, pH, proton ionophore (monensin), and MRP and P-gp inhibitors (probenecid, gemfibrozil, cyclosporin A, GF 120918) . Equilibrium dialysis with liposomes were performed to directly asses the extent of drug binding to bilayers . Conformational analysis modeling of the drug penetration in bilayers was conducted to rationalize the experimental observations . RESULTS: PIVA and PIMA showed properties in almost complete contrast with those of chloroquine and azithromycin, i.e., fast apparent accumulation and fast release at 4 degrees C as well as at 37 degrees C, saturation of uptake (apparent Kd 40 microM), no influence of monensin, MRP, or P-gp inhibitors; tight binding to liposomes (Kd approx . 40 microM); and sharp increase in calculated free energy when forced in the hydrophobic domain . CONCLUSIONS: Although they are weak organic bases, PIVA and PIMA show none of the properties of lysosomotropic agents . We hypothesize that they remain locked onto the pericellular membrane and may never penetrate cells as such in significant amounts.

J Trop Pediatr, 2003 Apr, 49(2), 128 - 30
Eradication of Cryptosporidium in four children with acute lymphoblastic leukemia; Trad O et al.; Four children on chemotherapy for acute lymphoblastic leukemia presented with severe diarrhea and dehydration . Cryptosporidium was identified in the stools using modified Ziehl-Neelsen stain . Two of them received paromomycin and responded well . One was started on paromomycin for 10 days and although there was clinical improvement, his stools examination continued to be positive for Cryptosporidium . He then received azithromycin for 10 days . He responded well and his stools became negative for Cryptosporidium . The fourth patient received azithromycin from the start and responded well . Cryptosporidium should be considered in all immunocompromised children with severe or prolonged diarrhea, and since it is not seen in a routine ova and parasite examination, the laboratory should be notified for diagnostic confirmation using modified Ziehl-Neelsen stain . Immunocompromised children with Cryptosporidium diarrhea may benefit from paromomycin or azithromycin therapy.

J Infect Dis, 2003 May 15, 187(10), 1669 - 73 Epub 2003 Apr 30.
Does the diagnosis of trachoma adequately identify ocular chlamydial infection in trachoma-endemic areas?
Bird M, Dawson CR, Schachter JS, Miao Y, Shama A, Osman A, Bassem A, Lietman TM.
We evaluated the validity of clinically determined active trachoma as a surrogate for chlamydial eye infection in 1059 children from the Egyptian arm of the Azithromycin in the Control of Trachoma study . Participants were determined to be "clinically active" if they had >or=5 follicles or intense inflammatory infiltration on the tarsal conjunctiva . Conjunctival swabs were tested using ligase chain reaction (LCR) to detect chlamydial DNA . Of clinically active children aged 1-10 years, 31% did not have infection, as determined by LCR . Conversely, 31% of infected children were not clinically active; 78% of clinically active children aged 1-5 years were infected, versus 17% of those aged 11-15 years . The proportion of clinically active children who were infected decreased from 67% before treatment to 10% 14 months after mass azithromycin treatment . Clinically active trachoma is not always a reliable marker of infection, particularly in teenagers and after treatment.

Rev Soc Bras Med Trop, 2003 Jan-Feb, 36(1), 65 - 9 Epub 2003 Apr 22.
Efficacy of azithromycin in the treatment of cutaneous leishmaniasis; Prata A et al.; The present open pilot study was conducted to assess the efficacy of azithromycin for the treatment of patients with cutaneous leishmaniasis in Ara ua and Varzelandia, MG . Twenty-four patients with less of six months of disease evolution were treated after clinical examination, Montenegro test and a biopsy . The treatment schemes consisted of oral doses of 500 mg per day for 3, 5 and 10 days and of 1000 mg for two days . A clinical control was performed monthly and treatment cycles were repeated when necessary until full reepithelialization of the lesions . On the occasion of the final evaluation, 20 patients had completed the study and 17 of them (85%) were cured . The time to obtain a cure was 60 days ifor 6 (30%) patients, 90 days for 7 (35%), and 120 for 4 (20%) . The three patients with treatment failure received a pentavalent antimonial for 20 days . No adverse reactions to the medication were observed and a 14 month follow-up did not show recurrence in any patient . These results suggest that azithromycin can be a good therapeutic option for the treatment of cutaneous leishmaniasis caused by Leishmania Viannia brasiliensis.

Pol Merkuriusz Lek, 2003 Jan, 14(79), 36 - 8
{Comparative analysis of the effectiveness and costs of azithromycin and cefoperazone treatment of patients during COPD exacerbation}; Faber M et al.; The effectiveness and costs of azithromycin and cefoperazone treatment of COPD exacerbation have been analysed in this study . Forty patients at the mean age of 65.9 (+/- 11.5) years were enrolled . The subjects were randomly selected and treated either with cefoperazone 2 x 1.0 g i.v . daily (group I = 20 persons) or with azithromycin 1 x 0.5 g (group II = 20 persons), in sequential method . Body temperature, cough intensity, quality and quantity of expectorated sputum, number of breaths per minute and adverse events were recorded daily . The values of pulmonary function tests and leucocytosis were assessed three times during the study . Statistically significant differences between both groups have been found with respect to the mean time of staying in hospital (9.1 days--group I vs 6.1 days--group II), mean total duration of antibiotic therapy (10.1 days--group I vs . 6.6 days--group II) and duration of intravenous antibiotic therapy only {7.5 days (group I) vs 2.9 days (group II)} (p < 0.05) . Taking into account the duration of hospitalization, it was shown that the mean total costs of treatment of COPD exacerbation with azithromycin was significantly lower than that of treatment with cefoperazone (2375.9 PLN and 1663.7 PLN, respectively) (p < 0.05) . CONCLUSIONS: The effectiveness of treatment with azithromycin in patients with COPD exacerbation was evident . The total costs of treatment of COPD exacerbation with azithromycin is lower than with cefoperazone . Both azithromycin and cefoperazone are safe in the treatment of exacerbation of COPD.

Wien Klin Wochenschr, 2002 Jun 14, 114(10-11), 396 - 9
Is azithromycin treatment associated with prolongation of the Q-Tc interval?
Strle F, Maraspin V.
OBJECTIVES: Prolongation of the corrected Q-T (Q-Tc) interval is associated with a risk of severe and even life-threatening arrythmias . It may occur as an adverse effect of various pharmacological agents including macrolides . We opted to study the influence of the azalide antibiotic azithromycin on the duration of Q-Tc interval as data on this subject are limited . METHODS: A prospective study was performed on 47 patients, 31 females and 16 males, aged 19-77 (median 52) years, treated with azithromycin (total dosage 3 g, divided over 5 days) for typical solitary erythema migrans . The patients were previously healthy and were not receiving any other medication . In all of them ECGs were performed before as well as 7 and 14 days after initiation of the azithromycin therapy . Thus, a total of 141 ECG tracings were analyzed . Q-T intervals were measured manually in a blinded manner and corrected for heart rate according to Bazzet's formula: Q-Tc = measured Q-T (ms)/square root of R-R (s) . RESULTS: Comparison of the Q-Tc intervals before, 7 days, and 14 days after the initiation of azithromycin treatment revealed a mild, but not significant prolongation (median values 406, 412.5 and 419 ms with ranges of 339-488, 352-510, and 346-505 ms, respectively) . Q-Tc intervals exceeding the upper normal value of 440 ms were found in the same proportion of patients prior to as after institution of treatment . None of the ECG tracings showed significant arrhythmias . CONCLUSION: In previously healthy persons, a modest statistically insignificant prolongation of the Q-Tc interval without clinical consequences was observed after completion of a course of 3 g of azithromycin administered over a period of 5 days for solitary erythema migrans.

Infez Med, 2002 Sep, 10(3), 145 - 50
{Macrolides in the treatment of children with Mediterranean spotted fever}; Cascio A et al.; Till now there is not a gold standard therapy for Mediterranean spotted fever (MSF) in children . Standard treatment for MSF is the administration of tetracycline or chloramphenicol, however both these drugs can cause significant adverse effects in children (tetracyclines can cause staining of teeth, chloramphenicol severe hematological adverse events such as aplastic anemia, gray baby syndrome and hemolytic anemia in patients with the Mediterranean form of G6PD deficiency) . We conducted two randomized clinical trials; the first compared clarithromycin versus chloramphenicol: mean time to defervescence was 36.7 +/- 18.1 h in the clarithromycin group and 47.1+/- 21.9 h in the chloramphenicol group (P= 0.047) . The second trial compared clarithromycin versus azithromycin and did not show any statistically significant difference: mean time to defervescence was 46.2 +/- 36.4 h in the clarithromycin group and 39.3 +/- 31.3 h in the azithromycin group (P= 0.34) . On the basis of these studies we think that clarithromycin and azithromycin could constitute an acceptable alternative to chloramphenicol and to tetracyclines for the treatment of MSF in children

Int J Clin Pharmacol Ther, 2002 Nov, 40(11), 507 - 19
Population pharmacokinetic meta-analysis with efavirenz; Barrett JS et al.; A population-based pharmacokinetic (PK) model has been developed for efavirenz based on 16 phase I studies . The combined data set consisted of 334 healthy volunteers, 2,907 efavirenz dose administrations and 9,342 measured plasma concentrations across a range of doses from 100-600 mg . The pharmacokinetic structural model was a 2-compartment model with first-order absorption with differentiation between single- and multiple-dose exposure to account for known hepatic cytochrome P450 induction of efavirenz metabolism . Model-building was performed on the index data set (66% of the total database), as a data-splitting technique was used to validate the final model using NONMEM . The final model confirmed the appropriateness of separate clearance terms for single and multiple dose administration (2.65 versus 10.2 l/h, respectively) . Clearance increased with dose and frequency of administration . A lower clearance was predicted in Asians and Blacks relative to Caucasians . A slightly lower clearance was observed in females relative to males (9.08 compared to 10.2 l/h in males) and interactions on clearance due to co-administration of fluconazole, ritonavir, rifampin, indinavir and azithromycin were identified . The magnitudes of these effects were small and did not suggest dose adjustment in the various subpopulations . With little exception, these results agree with the findings from the non-compartmental analyses . The residual variability was 21% CV and the intersubject variation in CL/F and V/F was 48 and 85%, respectively . The phase I meta-analysis was able to substantiate the pharmacokinetic characteristics of efavirenz derived from the composite of individual well-defined studies . The model was deemed adequate for subsequent evaluation in HIV-infected patients . Covariates and outlier classes identified in this phase I meta-analysis were similarly identified in subsequent analyses of patient data.

Am J Respir Crit Care Med, 2003 Jul 1, 168(1), 121 - 5 Epub 2003 Apr 02.
Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study; Gerhardt SG et al.; Bronchiolitis obliterans syndrome remains the leading cause of morbidity and mortality in the pulmonary transplant population . Previous studies show that macrolide antibiotics may be efficacious in the treatment of panbronchiolitis and cystic fibrosis . In the latter, azithromycin decreases the number of respiratory exacerbations, improves FEV1, and improves quality of life . We hypothesized that oral azithromycin therapy may improve lung function in patients with bronchiolitis obliterans syndrome . To test this hypothesis, we conducted an open-label pilot trial using maintenance azithromycin therapy in six lung transplant recipients (250 mg orally three times per week for a mean of 13.7 weeks) . In this study, five of these six individuals demonstrated significant improvement in pulmonary function, as assessed by FEV1, as compared with their baseline values at the start of azithromycin therapy . The mean increase in the percentage of predicted FEV1 values in these individuals was 17.1% (p </= 0.05) . In addition, the absolute FEV1 increased by 0.50 L (range -0.18 to 1.36 L) . These data suggest a potential role for maintenance macrolide therapy in the treatment of bronchiolitis obliterans syndrome in lung transplant recipients.

J Vet Pharmacol Ther, 2003 Apr, 26(2), 117 - 21
Azithromycin metabolite identification in plasma, bile, and tissues of the ball python (Python regius); Hunter RP et al.; Azithromycin is the first of a class of antibiotics classified as azalides . Six ball pythons (Python regius) were given a single dose of azithromycin at 10 mg/kg p.o . and i.v . in a crossover design . Serial blood samples were collected for unchanged azithromycin and to determine, if possible, the structure and number of circulating azithromycin metabolites . After a 4-month wash-out period, the snakes were given azithromycin p.o . as a single dose of 10 mg/kg for the study of azithromycin metabolism and metabolite tissue distribution . Bile, liver, lung, kidney, and skin samples were analyzed for the metabolites identified from the first experiment . Unchanged azithromycin accounted for 80, 68, and 60% of the total material at 12, 24, and 48 h postadministration in plasma, independent of route of administration . At both 24 and 72 h postadministration, azithromycin accounted for 70% of total azithromycin- associated material in bile . In liver and kidney, unchanged azithromycin accounted for 40% of the total azithromycin-associated material; this doubled in lung and skin . Fifteen metabolites were positively or tentatively identified in plasma, bile, or tissues of all snakes . Four of these possible metabolites: 3'-desamine-3-ene-azithromycin, descladinose dehydroxy-2-ene-azithromycin, 3'-desamine-3-ene descladinose-azithromycin, and 3'-N-nitroso,9a-N-desmethyl-azithromycin are unique to this species . Descladinose-azithromycin, 3'-N-desmethyl,9a-N-desmethyl-azithromycin, and 3'-N-desmethyl, 3'-O-desmethyl-azithromycin were the only metabolites identified in skin . Kidney tissue contained a greater number of metabolites than liver tissue, with 3'-N-didesmethyl-azithromycin being identified only in the kidney . Compared with the dog and cat, a greater number of metabolites were identified in ball python plasma . The percentage of unchanged azithromycin in bile is not different between the three species.

Eur J Obstet Gynecol Reprod Biol, 2003 Apr 25, 107(2), 214 - 6
Mediterranean spotted fever during pregnancy: case presentation and literature review; Bentov Y et al.; Mediterranean spotted fever (MSF) is caused by Rickettsia conorii, an obligate intracellular parasite of eukaryotic cells . Although, usually this disease has a benign course, a rapidly fatal outcome can occur even in young healthy adults . We describe a case of a 40-year-old Bedouin woman gravida 11, para 10, who was admitted at 36 weeks gestation with this rickettsial disease . During pregnancy, the treatment of choice for Mediterranean spotted fever is chloramphenicol, but it seems that Azithromycin could be another possible option .

J Clin Gastroenterol, 2003 Apr, 36(4), 325 - 8
Omeprazole plus azithromycin and either amoxicillin or tinidazole for eradication of Helicobacter pylori infection; Anagnostopoulos GK et al.; GOALS: To establish whether omeprazole plus azithromycin in association with either amoxicillin or tinidazole is effective in curing Helicobacter pylori infection in dyspeptic patients . BACKGROUND: Many antibiotics in combination with antisecretory drugs have been used in an attempt to find the optimal regimen for eradication of H . pylori . Azithromycin is a macrolide that achieves high concentrations in gastric tissue after a single 500-mg oral dose . STUDY: A total of 160 consecutive symptomatic patients with H . pylori received omeprazole 20 mg twice daily for 1 week, azithromycin 500 mg/d for 3 days, and were randomly assigned to either amoxicillin 1 g twice daily (OAzAm group, n = 80) for 1 week or tinidazole 500 mg twice daily for 3 days (OAzT group, n = 80) . H . pylori status was assessed by rapid urease test and histology at entry and by histology and (13)C-urea breath test after the end of the therapy . RESULTS: H . pylori was eradicated in 62.5% of patients in the OAzAm group (intention to treat {ITT} 62.5%) and in 71.2% of patients in the OAzT group (ITT 71.2%) . CONCLUSIONS: Although the compliance was excellent and the side effects negligible, the regimens used were partially effective for the eradication of H . pylori.

Lancet, 2003 Mar 8, 361(9360), 809 - 13
Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial; Cercek B et al.; BACKGROUND: There is serological and epidemiological evidence of an association between Chlamydia pneumoniae infection and coronary artery disease . Results of previous smaller studies have indicated a reduction of recurrent ischaemic events in patients with acute coronary syndrome when given macrolide antibiotics . We aimed to assess whether short-term treatment with the macrolide antibiotic azithromycin reduces recurrent ischaemic events in patients admitted for unstable angina or myocardial infarction . METHODS: We assessed the effect of azithromycin in a multicentre, double-blind randomised trial in 1439 patients with unstable angina or acute myocardial infarction . Patients were randomly allocated to receive 500 mg azithromycin on the first day after randomisation, followed by 250 mg daily for 4 days or placebo . Patients were followed up for 6 months . The primary endpoints were death, recurrent myocardial infarction, or recurrent ischaemia necessitating revascularisation . Analysis was done by intention to treat . FINDINGS: Treatment with azithromycin did not result in reduction of either individual endpoints or any of the primary endpoints . Of the 716 patients in the azithromycin group, 23 (3%) died, 17 (2%) developed myocardial infarction, 65 (9%) had recurrent ischaemia needing revascularisation, and 100 (14%) had one or more of these endpoints . In the placebo group (n=723) the corresponding numbers of patients were 24 (4%), 22 (3%), 59 (8%), and 106 (15%), respectively (p=0.664, 95% CI 0.72-1.24) . 62 (9%) of patients in the azithromycin group and 59 (8%) in the placebo group reached the secondary endpoint of ischaemia or congestive heart failure necessitating admission (difference 0.5%, 95% CI 0.75-1.53; p=0.707) . We recorded few side-effects . INTERPRETATION: Short-term treatment with azithromycin does not reduce development of recurrent events in patients with acute coronary syndrome.

Trans R Soc Trop Med Hyg, 2002 Nov-Dec, 96(6), 691 - 4
Height as a proxy for weight in determining azithromycin treatment for paediatric trachoma; Basilion EV et al.; Azithromycin (Zithromax, Pfizer Inc., New York, NY, USA) is effective in the control of blinding trachoma . Community-based azithromycin treatment is recommended by the World Health Organization as part of a multipronged strategy aimed at the global elimination of binding trachoma by the year 2020 . Paediatric trachoma is treated with azithromycin according to weight at a target dosage of 20 mg/kg . However, conventional weight-based treatment may be problematic in the field due to the logistical difficulties associated with weight scales . We assessed the accuracy of using height as a proxy for weight to determine azithromycin treatment in 4 countries--Viet Nam, Tanzania, Ghana, and Mali--where mass treatment programmes are underway . Population-based data collected from 1988 to 2000 were analysed using least squares regression . Height treatment schedules were developed for each data set . The accuracy of each schedule was evaluated according to the percentage of children receiving treatment within a dosage range of 20-30 mg/kg, a conservative estimate of the safe and effective treatment range for paediatric trachoma . Using height to determine dose, 89-95% of children would receive a dosage of 20-30 mg/kg . In these populations, height-based treatment is a reliable alternative to conventional weight-based treatment . Methods for developing height schedules presented in this analysis could be applied to other regions and therapeutics.

Int J Antimicrob Agents, 2003 Feb, 21(2), 116 - 24
Travellers' diarrhoea; Ericsson CD; Risk of travellers' diarrhoea is about 7% in developed countries and 20-50% in the developing world . Options for prevention include education and chemoprophylaxis . Vaccination is a promising but incomplete option . Achieving behaviour modification of food and water choices among tourists is difficult . Bismuth subsalicylate (BSS)-containing compounds are about 62% effective in the prevention of travellers' diarrhoea . Antibiotics are about 84% effective in preventing travellers' diarrhoea . Routine prophylaxis of travellers' diarrhoea, especially with antibiotics, should be discouraged . Oral rehydration is generally important in the treatment of diarrhoea, but travellers' diarrhoea is only infrequently dehydrating in adults . The addition of oral rehydration solutions confers no additional benefit to loperamide in the treatment of travellers' diarrhoea in adults . Presently, the most active of the antibiotics routinely available for treatment are members of the fluoroquinolone group . Antibiotics that are not absorbed such as aztreonam and a rifampicin-like agent, rifaximin, are both effective . The latter might become a therapy of choice once it is routinely available, due to predictably less adverse reactions with a non-absorbed antibiotic . Preliminary results with azithromycin look very promising . Less severe disease can be treated with a variety of non-antibiotic agents (e.g . BSS-containing compounds, loperamide and a calmodulin inhibitor, zaldaride) . The combination of an antibiotic and loperamide is superior to treatment with either agent alone in a several studies and is arguably the treatment of choice for distressing travellers' diarrhoea.

Am J Vet Res, 2003 Feb, 64(2), 225 - 8
Pharmacokinetics and tissue concentrations of azithromycin in ball pythons (Python regius); Coke RL et al.; OBJECTIVE: To determine pharmacokinetics and tissue concentrations of azithromycin in ball pythons (Python regius) after IV or oral administration of a single dose . ANIMALS: 2 male and 5 female ball pythons . PROCEDURES: Using a crossover design, each snake was given a single dose of azithromycin (10 mg/kg) IV . After a 4-week washout period, each snake was given a single dose of azithromycin (10 mg/kg) orally . Blood samples were collected prior to dose administration and 1, 3, 6, 12, 24, 48, 72, and 96 hours after azithromycin administration . Azithromycin was quantitated by use of liquid chromatography-mass spectrometry . RESULTS: After IV administration, azithromycin had an apparent volume of distribution of 5.69 L/kg and a plasma clearance of 0.19 L/h/kg . Harmonic means for the terminal half-life were 17 hours following IV administration and 51 hours following oral administration . Mean residence times were 37 and 94 hours following IV and oral administration, respectively . Following oral administration, azithromycin had a peak plasma concentration (Cmax) of 1.04 microg/mL, a time to Cmax of 8.4 hours, and a prolonged mean absorption time of 57 hours . Mean oral bioavailability was 77% . Tissue concentrations ranged from 4 to 140 times the corresponding plasma concentration at 24 and 72 hours after azithromycin administration . CONCLUSIONS AND CLINICAL RELEVANCE: Azithromycin is well absorbed and tolerated by ball pythons . On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism.

J Chromatogr Sci, 2003 Jan, 41(1), 10 - 6
Quantitative thin-layer chromatographic method of analysis of azithromycin in pure and capsule forms; Khedr A et al.; A validated stability-indicating thin-layer chromatographic (TLC) method of the analysis of azithromycin (AZT) in bulk and capsule forms is developed . Both AZT potential impurity and degradation products can be selectively and accurately estimated in both raw material and product onto one precoated silica-gel TLC plate 60F254 . The development system used is n-hexane-ethyl acetate-diethylamine (75:25:10, v/v/v) . The separated bands are detected as brown to brownish red spots after spraying with modified Dragendorff's solution . The Rf values of AZT, azaerythromycin A, and the three degradation products are 0.54, 0.35, 0.40, 0.20, and 0.12, respectively . The optical densities of the separated spots are found to be linear in proportion to the amount used . The stress testing of AZT shows that azaerythromycin A is the major impurity and degradation product, accompanied by three other unknown degradation products . The stability of AZT is studied under accelerated conditions in order to provide a rapid indication of differences that might result from a change in the manufacturing process or source of the sample . The forced degradation conditions include the effect of heat, moisture, light, acid-base hydrolysis, sonication, and oxidation . The compatibility of AZT with the excipients used is also studied in the presence and absence of moisture . The amounts of AZT and azaerythromycin A are calculated from the corresponding linear calibration curve; however, the amounts of any other generated or detected unknown impurities are calculated as if it were AZT . This method shows enough selectivity, sensitivity, accuracy, precision, linearity-range, and robustness to satisfy Federal Drug Administration/International Conference of Harmonization regulatory requirements . The method developed can also be used for the purity testing of AZT raw material and capsules, content uniformity testing, dissolution testing, and stability testing of AZT capsules . The potential impurity profiles of both active AZT material and capsule forms are found comparable . The linear range of AZT is between 5 and 30 mcg/spot with a limit of quantitation of 2 mcg/spot . The intraassay relative standard deviation percentage is not more than 0.54%, and the day-to-day variation is not more than 0.86%, calculated on the amounts of AZT RS recovered using different TLC plates.

Acta Med Croatica, 2002, 56(2), 45 - 7
Randomized trial of azithromycin in the prophylaxis of Mediterranean spotted fever; Dzelalija B et al.; A randomized clinical trial was undertaken to compare clinical and serologic parameters of the efficacy of one-dose azithromycin in the prophylaxis of Mediterranean spotted fever (MSF) in 122 persons with a tick bite history . Antibodies to Rickettsia conorii (R . conorii) were detected by indirect immunofluorescence (IFA) assay in 55 (45.1%) of 122 subjects . Positive result was obtained in 19 (31.1%) of 61 subjects with azithromycin prophylaxis and in 36 (59.0%) of 61 subjects without prophylaxis . Clinical signs and symptoms of MSF were recorded in 6 (9.8%) and asymptomatic infection in 30 (49.2%) of 61 subjects without prophylaxis . In subjects with prophylaxis, clinical signs of the disease were not recorded at all, whereas asymptomatic infection was detected in 19 (31.1%) of 61 subjects . Based on the results obtained in our study, we assume that a single dose of azithromycin is promising in MSF prevention.

Scand J Infect Dis, 2002, 34(12), 939 - 41
Azithromycin-induced rash in infectious mononucleosis; Dakdouki GK et al.; Antibiotic-induced skin eruption in the setting of infectious mononucleosis is a common and well-documented clinical scenario . The skin lesions are non-specific and the mechanisms causing them are unclear . Several reports have described this entity with different antibiotic classes, mainly penicillins . Only 1 case of azithromycin-induced skin eruption has previously been described in this setting . Herein, we report the second case.

Cell Biochem Funct, 2003 Mar, 21(1), 93 - 6
Determination of intracellular efficacies of azithromycin against Leishmania major infection in human neutrophils in vitro; Tanyuksel M et al.; Azithromycin is one of a new class of antibiotics known as azalides . Azithromycin has high tissue affinity and this feature is thought to be due to the presence of two basic tertiary amine groups . Leishmania major, one of the causative agents of cutaneous leishmaniosis, is an obligate intracellular parasite . In this in vitro study, the potential anti-leishmanial effect of azithromycin upon intracellular forms namely the amastigote of L . major in mice peritoneal macrophages was investigated . L . major promastigotes were propagated in RPMI-1640 supplemented with 20% fetal calf serum in the log phase . The percentage of phagocytosis and microbiacidal activity of azithromycin on macrophages was assessed in the control and study groups by fluorescence microscopy, using acridine orange . Our results showed that at all the concentrations used (0.05, 0.1, 0.3, 0.6 microg ml(-1)) azithromycin had no inhibitory effect on the phagocytic capacity of mouse peritoneal macrophages . Although no significant difference was observed for leishmaniacidal activity between the study and the control groups at a concentration of 0.05 microg ml(-1) (p>0.05), a significant (p<0.05) increase in leishmaniacidal activity was detected at 0.1, 0.3 and 0.6 microg ml(-1) . As a result, azithromycin does not provide any contribution to the phagocytosis of L . major promastigotes in macrophages in vitro, but it increases the intracellular killing rates of amastigotes . These results suggest that it has a potential anti-leishmanial effect, and may provide a significant advantage in the treatment of the disease .

Jpn J Antibiot, 2000 Jun, 53 Suppl B, 125 - 35
{Clinical safety of azithromycin}; Higa F et al.; The safety of azithromycin has been assessed in the clinical trial in Japan . Among the patients treated with azithromycin, side effects were recorded in 82(4.35%) of 1,886 adults and in 22(3.03%) of 726 children . The most common side effects in both groups were diarrhea, abdominal pain, and other gastrointestinal symptoms . All side effects were classed as mild or moderate . Laboratory abnormalities were recorded in 125(7.75%) of 1,279 adults and 85(19.23%) of 442 children, which included eosinophilia, neutropenia, and increases of GOT and GPT, and so on . All laboratory abnormalities were not severe and transient . Overall, azithromycin was well tolerated and can be safely used to treat bacterial infections in patients of all ages.

Jpn J Antibiot, 2000 Jun, 53 Suppl B, 103 - 10
{The clinical study of azithromycin in otolaryngologic infection}; Naoya M; In this study, we evaluated the efficacy of azithromycin in otolaryngologic infections and tissue penetration . Azithromycin is a new macrolide developed by Pfizer Pharmaceuticals . Azithromycin maintained sustained high tissue levels compared with serum levels following small doses administered over a short period of time . Furthermore, excellent efficacy was achieved with the 3 day regimen of azithromycin, comparable to 10 day regimens of other antibiotics . In summary, azithromycin was demonstrated to be a highly useful antibiotic in infections of ear, nose, and throat.

Jpn J Antibiot, 2000 Jun, 53 Suppl B, 91 - 102
{Summary of the clinical studies with azithromycin in the pediatric fields}; Sunakawa K; The clinical studies with azithromycin fine granules and capsules were conducted during the period from March 1993 to October 1994 . Cmax's in 16 patients who received 10 mg/kg fine granules, were 0.29 +/- 0.24 microgram/ml, T1/2's were 42.0 +/- 11.8 hours, and AUC 0 approximately infinity's were 10.72 +/- 5.00 micrograms.hr/ml . The clinical results for azithromycin fine granule and capsules 10 mg/kg once daily for 3 days are as follows . The efficacy rate of fine granules, combining both "Excellent" and "Good", for pneumoniae where causative pathogenes were identified, was 95.3%, and for those which had failed to respond to previous chemotherapies, was 94.6%, respectively . The efficacy rate of capsules for 3 to 5 days was 100% in 40 cases where causative pathogenes were identified . Adverse reactions were found in 2.5%(fine granules) and in 5.4%(capsules) in cases eligible for evaluation . Abnormal changes in laboratory test were as follows: decrease of WBC by 5.6%(fine granules) and 9.3%(capsules) and increase in eosinophils by 7.1%(fine granules) and 11.4% (capsules) . 59.8% of the patients claimed that the azithromycin 10% fine granules product was "easy to take" . The result of a questionnaire on parents' demand on the improvement of antibiotics, showed that most concern was on the drug frequency(preferably once or twice daily) and the drug administering period(preferably short: 3 days) . With regard to the efficacy, safety and compliance, it can be concluded that Azithromycin is one of the useful therapeutic regimens in the treatment of pediatric infections.

Jpn J Antibiot, 2000 Jun, 53 Suppl B, 72 - 81
{Clinical evaluation of azithromycin for respiratory infectious diseases}; Oizumi K; Azithromycin(AZM), an azalide macrolide with a 15-membered ring, is superior in cell/tissue penetration . Sustained pulmonary tissue concentrations are maintained which are higher than various MICs for major respiratory pathogens . Much research and clinical investigation has been done to evaluate the clinical efficacy of azithromycin abroad . In Japan, an optimal dose-finding pneumonia study was started in January, 1993, and a controlled comparative pneumonia study with clarithromycin was started in December of the same year . Patient compliance was excellent with the 3-day once daily regimen of AZM(500 mg) . Azithromycin has been demonstrated to be highly clinically useful based on high efficacy (including the elderly population) and an established safety profile.

Rapid Commun Mass Spectrom, 2003, 17(4), 342 - 50
Analysis of unknown compounds in azithromycin bulk samples with liquid chromatography coupled to ion trap mass spectrometry; Debremaeker D et al.; A selective reversed-phase liquid chromatography/mass spectrometry (LC/MS(n)) method is described for the identification of azithromycin impurities and related substances in commercial azithromycin samples . Mass spectral data are acquired on an LCQ ion trap mass spectrometer equipped with an atmospheric pressure chemical ionization interface operated in positive ion mode . The LCQ provides on-line LC/MS(n) capability, making it ideally suited for identification purposes . In comparison with UV detection, this hyphenated technique provides as its main advantage efficient identification of novel substances without time-consuming isolation and purification procedures . Using this technique, six novel related substances detected in commercial azithromycin samples have been studied .

Lancet, 2003 Jan 25, 361(9354), 313 - 4
Targeted mass treatment for syphilis with oral azithromycin; Rekart ML et al.; From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver . The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000 . We aimed to eliminate the syphillis outbreak by treating people at risk of infection . In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city . After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001 . Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001<p<0.0044) . This rate rebound and the absence of a sustained effect suggest that targeted mass treatment for syphilis, even though feasible, should not be done routinely.

Pediatr Pulmonol, 2003 Feb, 35(2), 139 - 43
Treatment of cast bronchitis with low-dose oral azithromycin; Schultz KD et al.; Cast or plastic bronchitis is an unusual disorder that is rarely encountered in the pediatric population . It is characterized by the expectoration of large, branching plugs of airway debris . These "casts" conform to the shape of portions of the tracheobronchial tree, and give the disorder its name . Cast bronchitis is typically seen in association with several primary pulmonary disorders and cyanotic congenital heart disease . It can be classified as inflammatory or acellular, based on the histologic characteristics of the casts . The presence of large, obstructive plugs filling the airways of lobes or entire lungs can result in a variety of clinical signs and symptoms, and may ultimately lead to respiratory failure and death . Conventional treatment of cast bronchitis has focused on the clearance of obstructing material from the airways combined with therapy for any underlying cardiopulmonary disease . Unfortunately, this approach has not proven very effective, and patient mortality remains high.We report on a case in which a patient with cast bronchitis was treated with long-term, low-dose oral azithromycin . This therapy resulted in clinical, spirometric, and radiographic improvement of the patient .

Curr Infect Dis Rep, 2003 Feb, 5(1), 53 - 58
Babesiosis: An Update on Epidemiology and Treatment; Gelfand JA et al.; Babesiosis is caused by a tick-borne hemoparasite that, like malaria, can cause fever, hemolysis, and anemia . Typically self-limited, in the asplenic, immunocompromised, or elderly, disease can be severe or deadly . US cases have been primarily due to Babesia microti; WA-1, which may be related to Babesia gibsoni; and MO-1, related to Babesia divergens . European infections are usually due to B . divergens . North American cases are treated either with quinine and clindamycin or with atovaquone and azithromycin . The latter regimen appears less toxic.

J Am Vet Med Assoc, 2003 Jan 1, 222(1), 47 - 51, 35
Detection of Bartonella henselae and Bartonella clarridgeiae DNA in hepatic specimens from two dogs with hepatic disease; Gillespie TN et al.; A 4-year-old Basset Hound and a 6-year-old Doberman Pinscher were referred for diagnostic evaluation following documentation of persistently increased hepatic enzyme activities and hepatic dysfunction . Histologic evaluation of hepatic biopsy specimens from the 2 dogs revealed granulomatous hepatitis in the Basset Hound and lymphocytic hepatitis with fibrosis and copper accumulation in the Doberman Pinscher . No etiologic agents were identified histologically . Bartonella henselae DNA was subsequently amplified from hepatic tissue from the Basset Hound and Bartonella clarridgeiae was amplified from hepatic tissue from the Doberman Pinscher . Amplification was performed with a polymerase chain reaction assay incorporating primers that target a portion of the 16S-23S rRNA intergenic spacer region . Both dogs were treated with azithromycin, in combination with a variety of other medications and herbal treatments, and improved clinically . Identification of Bartonella DNA in these dogs indicates the need for future prospective studies to determine the clinical relevance of Bartonella spp infection in dogs with hepatic disease.

Antibiot Khimioter, 2002, 47(7), 6 - 12
{Mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes}; Hand WI et al.; Azithromycin achieves prolonged, high tissue concentrations in spite of low serum levels and obviously must be effective at tissue sites of infection . These unique features prompted us to evaluate the interactions of azithromycin and human polymorphonuclear leukocytes (PMN) . Uptake of radiolabeled antibiotic by PMN was determined by a velocity-gradient centrifugation technique and expressed as the ratio of cellular to extracellular drug concentration (C/E) . Azithromycin was massively accumulated by human PMN (C/E = 387.2 at 2 h) . Uptake was not influenced by inhibitors of cellular metabolism, but phagocytosis slightly inhibited the entry of azithromycin into PMN . After removal of extracellular drug, the release (efflux) of azithromycin from PMN was extremely slow . Agents which neutralize lysosomal pH, preventing protonation and trapping of azithromycin, markedly increased antibiotic efflux . Active concentration and prolonged retention of azithromycin by phagocytic cells should allow delivery and subsequent release of accumulated drug at sites of infection.

Malar J . 2002 Nov 12;1(1):13.
Triangular test applied to the clinical trial of azithromycin against relapses in Plasmodium vivax infections; Ranque S et al.; BACKGROUND: Sequential analysis enables repeated statistical analyses to be performed throughout a trial recruitment period, while maintaining a pre-specified power and type I error . Thus the trial can be stopped as soon as the information accumulated is considered sufficient to reach a conclusion . Sequential tests are easy to use and their statistical properties are especially suitable to trials with very straightforward objectives such as non-comparative phase II trials . We report on a phase II study based on the triangular test (TT) aiming at assessing the effectiveness of azithromycin in preventing Plasmodium vivax relapses . METHODS: To test whether the P . vivax relapse rate was either <12% or >or= 45% in patients treated with azithromycin, a sequential analysis based on the TT was as used . Patients infected with P . vivax were treated with azithromycin, 1.2 g daily, for 7 days . The onset of a relapse infection was monitored . RESULTS: Five patients presenting with an acute P . vivax infection were included in the study . All the patients were initially cured . Three patients reported mild gastrointestinal adverse effects . When the third patient relapsed, the sample path crossed the upper boundary of the TT, and the trial was stopped . CONCLUSIONS: Using the triangular test, with only a small number of patients, we concluded that azithromycin was not effective enough in preventing P . vivax relapses to warrant further evaluation in phase III . It is suggested that a wider use of sequential analysis in phase II anti-infective drugs trials may have financial and ethical benefits.

Drugs, 2002, 62(18), 2573 - 9
Current trachoma treatment methodologies: focus on advancements in drug therapy; Chiu LM et al.; Currently, there are approximately 6 million people with irreversible blindness as a result of chronic follicular conjunctivitis with subsequent corneal scarring caused by Chlamydia trachomatis, also known as trachoma . On the basis of the clinical studies evaluated, the most widely tested effective pharmacological treatments for trachoma today are topical tetracycline 1% to be applied to both eyes twice daily for 6 weeks or a single oral dose of azithromycin 20 mg/kg (up to 1g) . Although chemotherapy can generate prompt therapeutic response and surgery can reverse the repercussions of these infections, these conditions will persist through reinfections . Implementing proper personal hygiene and environmental improvement measures for the control of infection transmission will be essential in reducing the potentially devastating results of trachoma infections.

J Antimicrob Chemother, 2002 Dec, 50(6), 1075 - 9
Pharmacokinetics of intravenous azithromycin and ceftriaxone when administered alone and concurrently to healthy volunteers; Chiu LM et al.; This study was conducted to identify whether or not a pharmacokinetic interaction existed when azithromycin and ceftriaxone were administered concurrently . This randomized, open-label, three-way crossover study in 12 healthy volunteers characterized the plasma pharmacokinetic parameter profiles of both drugs, as well as the white blood cell uptake and exposure to azithromycin, when the drugs were administered alone and together . The plasma pharmacokinetic parameters for azithromycin and ceftriaxone did not differ significantly either after a single dose or at steady state when the two were co-administered as opposed to being administered alone . Moreover, the neutrophil and monocyte/lymphocyte peak azithromycin concentrations and sampling period exposures also did not differ significantly between the study arm and the control arm . This study confirms that there is no interaction between azithromycin and ceftriaxone when they are administered concurrently.

Pharmacol Res, 2002 Dec, 46(6), 545 - 50
Pharmacokinetics of azithromycin in lung tissue, bronchial washing, and plasma in patients given multiple oral doses of 500 and 1000 mg daily; Di Paolo A et al.; The present study compares the pharmacokinetics of azithromycin in plasma, lung tissue, and bronchial washing after oral administration of 500 mg (standard dose) versus 1000 mg daily for 3 days . Samples were taken during surgery for lung resection at various time points up to 204 h after the last drug dose, and azithromycin levels were analyzed by HPLC method . Azithromycin was widely distributed within the lower respiratory tract; sustained concentrations of the drug were detectable at the last sampling time (204 h) in lung tissue and bronchial washing, with long terminal half-lives of 132.86 and 74.32 h at 500 mg daily and 133.32 and 70.5 h at 1000 mg daily, respectively . Doubling the drug dose resulted in a remarkable increase in lung area under the curve (AUC, 1318 hx microg g(-1) vs 2502 hx microg g(-1)) and peak tissue concentration (9.13+/-0.53 microg g(-1) vs 17.85+/-2.4 microg g(-1)) . In addition to this, enhanced azithromycin penetration from plasma into bronchial secretion and lung tissue was evidenced by the increase in the ratio of AUC(bronchial washing) versus AUC(plasma) (2.96 vs 5.27 at 500 and 1000 mg, respectively) and AUC(lung) versus AUC(plasma) (64.35 vs 97.73 at 500 and 1000 mg, respectively) . In conclusion, the exposure of lung and bronchial washing to azithromycin is increased by doubling the dose, which results in favorable pharmacokinetic profile of the drug in the lower respiratory tract.

Sex Transm Dis, 2002 Nov, 29(11), 703 - 9
Optimal resource allocation for curing Chlamydia trachomatis infection among asymptomatic women at clinics operating on a fixed budget; Tao G et al.; GOAL: The goal was to determine the optimal strategy for screening coverage, test selection, and treatment for infection in asymptomatic women for a given family-planning-program budget . STUDY DESIGN: We developed a resource allocation model to determine the optimal strategy using data from 5078 visits by women universally screened for infection in a publicly funded family planning clinic system in Philadelphia . We maximized the number of infected women cured from the clinic perspective and maximized the cost-savings from the healthcare system perspective . The model incorporated the following age distributions: <20 years (27%), 20 to 24 years (30%), and >24 years (43%), with prevalences of 10.6%, 6.9%, and 2.3%, respectively . We modeled two screening test assays (DNA probe and ligase chain reaction {LCR} for cervical specimens) and two treatments (doxycycline and azithromycin) . The model allowed for different test and treatment choices by age group . RESULTS: At the baseline annual budget of $6 per visit, the strategy that maximized both the number of infected women cured and cost savings would be to screen all women with DNA probe and to treat all women with positive tests with azithromycin . This strategy would result in 183 women cured at a cost-savings of $140,176 . Sensitivity analysis showed that the total budget had a great impact on the optimal strategy, incorporating screening coverage, test selection, and treatment . CONCLUSIONS: Using resource allocation models enables clinic managers operating with a fixed budget to identify a strategy that maximizes the number of asymptomatic women cured and cost savings when the clinic age distribution and age-specific prevalences are known.

Zhonghua Jie He He Hu Xi Za Zhi, 2002 Jul, 25(7), 392 - 5
Intervention by azithromycin on bleomycin-induced lung injury in rats and its mechanisms; Ma J et al.; OBJECTIVE: To study the role of Th1/Th2 balance in the pathogenesis of pulmonary fibrosis and to investigate the therapeutic mechanisms of azithromycin . METHODS: Male wistar rats were randomly divided into three experimental groups: the bleomycin A(5) (BLM) group (BLM group), the azithromycin (AZI) group (AZI group) and the control group . Quantitative analysis of the histopathologic changes was performed by computer gray scan . The expression of IL-10 mRNA and IFN-gamma mRNA was examined by RNase protection assay (RPA) . RESULTS: (1) In the BLM group, up-regulation of IL-10 mRNA was stronger than that of IFN-gamma mRNA, resulting in the inversion of the IL-10/IFN-gamma mRNA ratio, a shift from the Th1-like response of IFN-gamma predominance in the control group to the Th2-like response of IL-10 predominance in the BLM group . (2) The oral administration of AZI inhibited the expression of IL-10 and IFN-gamma mRNA; reversed the Th2-like response in the BLM group to the Th1-like response on day 7; and decreased the exudation of inflammatory cells as well as the degree of fibrosis . CONCLUSIONS: (1) At the early stage of fibrosing alveolitis, Th2 domination and the lack of IFN-gamma in the presence of alveolar epithelial and basement membrane injury may promote the development of fibrosis . (2) Azithromycin can inhibit the expression of IL-10 and IFN-gamma, and reverse the Th2-like response in the BLM group to a Th1-like response, and as a result, decrease the inflammatory injury as well as the degree of BLM-induced lung injury in rats.

J Chromatogr Sci, 2002 Oct, 40(9), 529 - 33
Isocratic liquid chromatographic method for the analysis of azithromycin and its structurally related substances in bulk samples; Kamau FN et al.; An isocratic liquid chromatographic method with UV detection at 215 nm, which is suitable for the analysis of azithromycin (AZT) in bulk samples, is described . AZT is separated from its synthesis intermediates and a degradation product as well as from six unknown impurities on an XTerra RP18 column at 70 degrees C using a mobile phase consisting of acetonitrile-pH 6.5 0.2M K2HPO4-water (35:10:55, v/v/v) at 1.0 mL/min . The XTerra stationary phase contains methyl groups that are incorporated in the bulk structure of the material . This allows for special selectivities . Robustness is evaluated by a full factorial design experiment . The method shows good selectivity, repeatability, linearity, and sensitivity.

J Postgrad Med, 2002 Jul-Sep, 48(3), 179 - 81
Azithromycin as treatment for cryptosporidiosis in human immunodeficiency virus disease; Kadappu KK et al.; BACKGROUND: Cryptosporidiosis caused by the protozoa Cryptosporidium, is the common cause of diarrhoea in Acquired Immune Deficiency Syndrome (AIDS) . AIM: To study the efficacy of short-term azithromycin in the management of cryptosporidiosis . SETTINGS AND DESIGN: Randomised, controlled trial . MATERIAL AND METHODS: All consecutive patients infected with Human Immunodeficiency Virus (HIV), who were positive for cryptosporidial oocysts were taken for this prospective randomised study . RESULT: Short-term azithromycin treatment for cryptosporidial diarrhoea in AIDS patients was associated with good clinical improvement but parasitological benefit was doubtful . All 13 patients, who had symptoms of cryptosporidiosis, symptomatically improved with 5 days of treatment with azithromycin and became asymptomatic after 7 days of antibiotic, but stool sample was positive for cryptosporidium even after 7 days of therapy . After 14 days of treatment with azithromycin in 13 patients, in five patients stool was free of cryptosporidial oocyst . The drug was well tolerated in all the patients . CONCLUSION: Short-term azithromycin can be used as a safe and effective treatment for symptomatic Cryptosporidiosis but not effective in eradicating Cryptosporidial infection.

Int J Antimicrob Agents, 2002 Nov, 20(5), 348 - 60
Disposition and intracellular activity of azithromycin in human THP-1 acute monocytes; Hall IH et al.; Uptake of {14C}-azithromycin into THP-1 human monocytes was determined at pH 7.4, 6.8 or 5.5 over 4-log antibiotic concentrations for 24 h under a number of conditions . Stimulation of cells was with bacteria, latex beads, lipopolysaccharide (LPS), or zymogen A . Subcellular organelle disposition was determined after isolation by ultracentrifugation or sucrose gradients . Hydrolytic enzyme activities and mediators of intracellular inflammation (IL-1, IL-6, IL-8, and TNFalpha) were assessed . Azithromycin uptake into human THP-1 monocytes was initially linear achieving approximately 2% of the extracellular concentration . At pH 7.4, uptake was both passive- and carrier-mediated, but as the pH became more acidic, the uptake was exclusively passive . The intracellular concentration was not pH-dependent over 24 h . Uptake was dependent upon temperature but not the presence of foetal calf serum . Intracellular disposition in zymogen A-stimulated and unstimulated cells was throughout all compartments of the cell, but was higher in the nucleus and cell sap . Phagosomes of stimulated cells contained higher level of the antibiotic . Efflux from THP-1 monocytes was complete between 3 and 4 h . After 1 h treatment with zymogen A, THP-1 monocytes demonstrated an increase in intracellular acidity, protein kinase C, SOD and NAG activities, and NO, H(2)O(2), TNFalpha and IL-1 release over the 1st h . After 2-4 h the pH became alkaline, activities of NADPH reductase, NAG and cathepsin were reduced, and the release of NO, H(2)O(2), TNFalpha and IL-6 were suppressed . Protein synthesis and killing of the bacteria was evident in bacteria kept in monocyte-free medium and those phagocytized by the THP-1 monocytes moderately at 2 h, but more significantly at 24 h . The early killing of the bacteria appears to be a cidal mechanism whereas later, a standard bacteriostatic mechanism was evident . Nevertheless, suppression of these chemical mediators and hydrolytic enzyme activities would reduce the infection and the spread to adjacent areas.

Braz J Med Biol Res, 2002 Oct, 35(10), 1153 - 7 Epub 2002 Oct 13.
Trachoma among the Yanomami Indians; Paula JS et al.; The Yanomami are one of the last primitive groups of Indians living in Brazil . They have almost no contact with other cultures . The epidemiology of eye disease among Yanomami is virtually unknown . For the first time, a trachoma survey was conducted among Yanomami Indians in the State of Amazonas near the Venezuelan border of the Brazilian rain forest . Ophthalmic examination was carried out on a total of 613 individuals (338 males and 275 females) from eight Yanomami villages along the Maraui River located in the upper Rio Negro Basin . Age was classified into three categories (children, adults, and elderly) and trachoma was classified into five grades: follicular, inflammatory intense, cicatricial, trichiasis, and corneal opacity . Trachoma was endemic in all villages visited . Overall, 30.3% of the subjects had trachoma . Females were significantly more affected (37.4%) than males (23.9%) . The inflammatory trachoma rate reached 24.9% in children and the cicatricial form increased with age, reaching 13.9% among adults and 35.21% among the elderly . Trichiasis or corneal opacities were not detected and treatment of the entire population was initiated with 1 g azithromycin . The detection of endemic trachoma among the Yanomami is relevant for the understanding of the epidemiology of this disease in the Brazilian rain forest and underscores the necessity for a program of trachoma control in this region.

J Vasc Surg, 2002 Nov, 36(5), 1011 - 7
Chlamydia pneumoniae antigens facilitate experimental aortic dilatation: prevention with azithromycin; Tambiah J et al.; OBJECTIVE: The purpose of this study was to investigate whether Chlamydia pneumoniae (live, antigens, or polysaccharide) cause abdominal aortic aneurysm in a susceptible animal host with appropriate drug reversal . METHODS: At laparotomy, preparations of C pneumoniae (live, formalin-inactivated, and heat-inactivated) in calcium chloride were applied to the adventitial surface of the abdominal aorta of rabbits fed a cholesterol-enriched diet . Aortic diameter was measured with ultrasonography . After 3 weeks, immunohistochemistry was used to detect aortic C pneumoniae and macrophages . Presence of C pneumoniae DNA also was assessed . RESULTS: At high doses (5 x 10(7) organisms) periaortic application of both live and formalin-inactivated preparations resulted in doubling of aortic diameter after 3 weeks, from 2.0 +/- 0.5 mm to 4.3 +/- 1.3 mm (P <.02) . C pneumoniae DNA and antigens, together with a heavy macrophage infiltrate, were detected in the dilated aorta . In contrast, periaortic application of heat-inactivated preparations resulted in minimal macrophage influx and aortic dilatation . Treatment of rabbits with azithromycin or carprofen for 10 days after laparotomy abolished the effects of formalin-inactivated C pneumoniae on aortic dilatation . Azithromycin reduced the number of macrophages in the aortic wall more effectively than carprofen . CONCLUSION: Because membrane antigenicity is retained in formalin-inactivated but not heat-inactivated organisms, in this experimental model, chlamydial membrane antigens (rather than live organisms) appear to cause the aneurysmal dilatation and associated macrophage recruitment . Azithromycin is likely to reverse these effects with an antiinflammatory mechanism.

Ann Intern Med, 2002 Nov 5, 137(9), 734 - 7
Successful discontinuation of therapy for disseminated Mycobacterium avium complex infection after effective antiretroviral therapy; Shafran SD et al.; BACKGROUND: Highly active antiretroviral therapy (HAART) is associated with improvement or resolution of several HIV-associated opportunistic infections . Although prophylaxis against disseminated Mycobacterium avium complex infection may be successfully discontinued after a favorable response to HAART, the 1999 guidelines from the U.S . Public Health Service/Infectious Diseases Society of America recommend continuing therapy for disseminated M . avium complex infection, regardless of the response to HAART . OBJECTIVE: To examine the outcome among patients with disseminated M . avium complex infection whose antimycobacterial therapy was discontinued after a favorable response to HAART . DESIGN: Retrospective chart review between May 2000 and May 2001 . SETTING: 13 Canadian HIV clinics . PATIENTS: 52 HIV-infected adults (43 men; mean age, 37.3 years) in whom successful antimycobacterial therapy for disseminated M . avium complex infection was discontinued after a favorable virologic response to HAART . MEASUREMENTS: Survival, survival free of disseminated M . avium complex infection, and CD4(+) cell count responses . RESULTS: At the time of diagnosis of disseminated M . avium complex infection, the median CD4(+) cell count was 0.016 x 10(9) cells/L, and the median plasma HIV RNA level was 90 000 copies/mL (plasma HIV RNA levels were available for only 21 patients) . The patients received a median of 32 months of antimycobacterial therapy that included ethambutol plus either clarithromycin or azithromycin . When antimycobacterial therapy was discontinued, the median CD4(+) cell count was 0.23 x 10(9) cells/L and the median plasma HIV RNA level was less than 50 copies/mL . A median of 20 months after discontinuation of antimycobacterial therapy, only 1 patient had developed recurrent M . avium complex disease (37 months after stopping antimycobacterial therapy) . This patient had stopped HAART 2 months earlier because of uncontrolled HIV viremia . Twenty months after stopping antimycobacterial therapy, the other 51 patients had a median CD4(+) cell count of 0.288 x 10(9) cells/L; 34 (67%) had undetectable plasma HIV RNA levels, and 8 (15%) had plasma HIV RNA levels of 50 to 1000 copies/mL . CONCLUSIONS: Discontinuation of successful disseminated M . avium complex therapy after a successful response to HAART is safe and reduces patients' pill burdens, potential drug adverse effects, drug interactions, and costs of therapy.

Am J Trop Med Hyg, 2002 Sep, 67(3), 273 - 7
Activity of azithromycin against Leishmania major in vitro and in vivo; Krolewiecki A et al.; Azithromycin, an azalide antibiotic of the macrolide family, concentrates in the tissues and especially in macrophages . Because Leishmania parasites reside in these cells, we tested this antibiotic for a possible antileishmanial activity in vitro and in vivo . Azithromycin decreased the Leishmania major promastigote count in cell-free cultures at log phase approximately 50-fold . In macrophage cultures infected with L . major amastigotes, azithromycin caused a significant decrease in parasite levels with an ED50 of 12 microg/ml . The activity in vivo was evaluated after infection of the footpads of susceptible BALB/cByJ mice and resistant C57BL/6J mice with L . major . Treatment of BALB/cByJ mice with azithromycin, 100 to 200 mg/kg/d, resulted in a significant decrease in lesion size and in the number of parasites per lesion, whereas no effect was seen in the treated C57BL/6J mice . Azithromycin has activity against L . major in vitro and in vivo . Given the severity of the disease and the limitations of the available therapeutic agents, azithromycin may have a significant role in the treatment of this group of diseases.

Pediatr Pathol Mol Med, 2002 Sep-Oct, 21(5), 477 - 84
Pathological case of the month: sudden death in a child as a result of pancreatitis during valproic acid therapy; Mileusnic D et al.; Valproic acid is a widely used drug in the treatment of epilepsy and, compared to other anticonvulsant drugs, is considered safe . The most common side effects of valproic acid ingestion or therapy are transient nausea, vomiting, abdominal cramps, and diarrhea . Most of these complaints are mild . However, more serious adverse reactions can occur such as hepatotoxicity and pancreatitis . It has been proposed that, whenever possible, valproic acid not be used in the younger child, the child with a severe seizure disorder or other neurological disorders, mental retardation, developmental delay, organic brain disease, congenital abnormalities, or the child who is taking multiple anticonvulsant drugs, as these factors may increase the likelihood of hepatotoxicity and/or pancreatitis . In the present report, we describe a fatal case of acute hemorrhagic pancreatitis in a four and a half-year-old Hispanic female child who was receiving valproic acid in combination with another anticonvulsant drug for control of focal seizures . The patient also received the macrolide antibiotic azithromycin . For pediatricians and forensic pathologists valproic acid-induced pancreatitis can be a challenging diagnosis which must not be mistaken for abdominal trauma . We discuss the workup of the patient and differential diagnosis.

Am J Gastroenterol, 2002 Oct, 97(10), 2536 - 9
Comparison of azithromycin and clarithromycin in triple therapy regimens for the eradication of Helicobacter pylori; Sullivan B et al.; OBJECTIVE: We sought to compare an azithromycin-based regimen with an already established clarithromycin-based regimen in the eradication of Helicobacter pylori infection . METHODS: A prospective, randomized, blinded comparative analysis was performed on 56 patients with upper GI symptoms who presented to the Gastroenterology Department at the Naval Medical Center Portsmouth . All patients had documented H . pylori infection on endoscopy via rapid urease test and histopathology . Patients were randomized to a treatment arm, which consisted of bismuth, clarithromycin, amoxicillin, and lansoprazole (B-LAC) or one consisting of bismuth, azithromycin, amoxicillin, and lansoprazole (B-LAA) . To assess eradication, patients then received repeat endoscopy at 8 wk from entrance into the study . Rapid urease test and histopathology were again used to evaluate infection . Patients recorded all side effects . Comparison between the two groups was made using the chi2 method . RESULTS: Of the 56 patients included in the study, 27 went on to receive B-LAC, whereas 29 received B-LAA . The per protocol eradication rate was 84.6% with B-LAC and 55.5% with B-LAA (p = 0.021) . Under intention to treat analysis, the eradication rates for B-LAC and B-LAA were 81% and 52%, respectively (p = 0.019) . There was a significant difference between the two groups in number of subjects using nonsteroidal anti-inflammatory drugs (NSAIDs) (p = 0.013) and a trend toward a difference in histamine-2 (H2) blocker use (p = 0.066) . Taking these two variables into account, a logistical regression was performed and continued to show a significant superiority in the B-LAC regimen (p = 0.03) . CONCLUSIONS: The results of our study suggest that B-LAC is superior to B-LAA in the eradication of Helicobacter pylori . Our results also suggest that B-LAA is not a suitable regimen in the treatment of H . pylori because of its substandard eradication rate.

Lancet, 2002 Sep 28, 360(9338), 978 - 84
Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial; Equi A et al.; BACKGROUND: The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis . Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial . METHODS: 41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial . They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months . After 2 months of washout, the treatments were crossed over . The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods . Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures . Side-effects were assessed by pure tone audiometry and liver function tests . Analysis was by intention-to-treat . FINDINGS: Median relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5) . 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059) . Forced vital capacity and mid-expiratory flow did not significantly change overall . 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005) . Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change . There were no noticeable side-effects . INTERPRETATION: A 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment . The mechanism of action remains unknown.

World J Gastroenterol, 2002 Oct, 8(5), 879 - 82
Azithromycin in a triple therapy for H.pylori eradication in active duodenal ulcer; Ivashkin VT et al.; AIM: To assess and compare the efficacy and safety of two triple regimes: A) metronidazole, amoxicillin and omeprazole, which is still widely used in Russia, and B) azithromycin, amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication . METHODS: 100 patients with active duodenal ulcer were included in the open, multicentre, randomized study with comparative groups . Patients were randomly assigned to one of the following one-week triple regimes: A) metronidazole 500 mg bid, amoxicillin 1 g bid and omeprazole 20 mg bid (OAM, n=50) and B) azithromycin 1 g od for the first 3 days (total dose 3 g), amoxicillin 1 g bid and omeprazole 20 mg bid (OAA, n=50) . Omeprazole 20 mg od was given after the eradication course as a monotherapy for three weeks . The control endoscopy was performed 8 weeks after the entry . H.pylori infection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test . RESULTS: 97 patients completed the study according to the protocol (1 patient of the OAM group did not come to the control endoscopy, 2 patients of the OAA group stopped the treatment because of mild allergic urticaria) . Duodenal ulcers were healed in 48 patients of the OAM group (96 %; CI 90.5-100 %) and in 46 patients of the OAA group (92 %; CI 89.5-94.5 %) (p=ns) . H.pylori infection was eradicated in 15 out of 50 patients with OAM (30 %; CI 17-43 %) and in 36 out of 50 patients treated with OAA (72 %; CI 59-85 %) (P<0.001)- ITT analysis . CONCLUSION: The triple therapy with omeprazole, amoxicillin and metronidazole failed to eradicate H.pylori in the majority of patients, which is an essential argument to withdraw this regimen out of the national recommendations . Macrolide with amoxicillin are preferable to achieve higher eradication rates . Azithromycin (1 g od for the first 3 days) can be considered as a successful component of the triple PPI-based regimen.

Antibiot Khimioter, 2002, 47(5), 12 - 5
{Combined treatment of persisting urogenital chlamydia infection with sumamed and interferon alfa}; Gomberg MA; The results of complex treatment of 235 patients with persisting urogenital chlamidial infection are presented . The treatment regime included immunotropic agent interferone alfa-alpha 2b and antibiotic azithromycin (Sumamed, "Pliva", Croatia) 1 g per day 3 times every 7 days . Chlamidial persistence diagnosis was performed by culture method (determination of small cytoplasmic inclusions), by the method of immune fluorescence and PCR . The treatment provided positive influence on immune status (amount of CD4+; HLA-DR+ cell and IgA level normalized after the treatment) . In 3 months after the treatment only 2 cases of Chlamydia trachomatis infection recurrence were registered . Treatment efficacy achieves 94.8 per cent.

Contracept Technol Update, 1998 Aug, 19(8), 102 - 3
Low risk of infection from IUD use shown; Improved tonsillar disposition of azithromycin following a 3-day oral treatment with 20 mg kg(-1) in paediatric patients; Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, ItalyThe present study was performed in order to compare azithromycin concentrations in tonsils of paediatric patients treated with different dose regimens of this antibiotic . Sixty-four children, scheduled to undergo surgical removal of tonsils, were treated with azithromycin 10 or 20 mgkg(-1) daily as oral suspension for 3 days . Samples of blood and tonsil were collected during surgery at days 0.5, 2.5, 4.5, 6.5 or 8.5 after the last dose . Azithromycin concentrations were measured by reversed phase high-performance liquid chromatography . In patients treated with 10 mgkg(-1), the highest concentrations of azithromycin were detected in plasma and tonsils at day 0.5 and 2.5, respectively . Consistent drug levels could be measured in tonsils up to 8.5 days . After administration of 20 mgkg(-1), azithromycin tonsillar concentrations were higher than those obtained with 10 mgkg(-1) up to day 6.5, whereas plasma levels did not differ significantly . The present results indicate that an improved tonsillar distribution of azithromycin can be achieved when this antibiotic is administered for 3 days at doses higher than 10 mgkg(-1) daily . These findings give pharmacokinetic support to the suggestion that increments of azithromycin dosing might ensure enhanced therapeutic levels at infective sites of the upper respiratory tract.

Rev Hosp Clin Fac Med Sao Paulo, 2002 Jan-Feb, 57(1), 9 - 14
Low efficacy of an ultra-short term, once-daily dose triple therapy with omeprazole, azithromycin, and secnidazole for Helicobacter pylori eradication in peptic ulcer; Silva FM et al.; PURPOSE: To determine the eradication rate of an ultra-short treatment schedule for Helicobacter pylori infection in a population with peptic ulcers, using omeprazole, secnidazole, and azithromycin in a once-daily dose for 3 days . METHODS: Thirty patients with peptic ulcer diagnosed by upper endoscopy and for Helicobacter pylori infection by rapid urease test and histologic examination received omeprazole 40 mg, secnidazole 1000 mg, and azithromycin 500 mg, administered once daily for 3 days . A follow-up exam was performed 12 weeks after the end of the treatment . Patients who were negative for Helicobacter pylori infection by rapid urease test and histologic examination were considered cured . RESULTS: Patients were predominantly female, and the mean age was 50 years . Duodenal peptic ulcer was found in 73% of the patients . Eradication was achieved in 9 of the 28 (32%) patients as determined from the follow-up endoscopic exam . The eradication rate by intention to treat was 30% . Side effects were present in 3% of the patients, and compliance to treatment was total . CONCLUSIONS: In spite of the low rate of side effects and good compliance, the eradication index was low . A possible drawback of this therapy is that it reduces the efficacy of macrolide and nitroimidazole compounds in subsequent treatments.

Clin Rev Allergy Immunol, 2002 Aug, 23(1), 29 - 39
Use of modulators of airways inflammation in patients with CF; Ren CL; One of the hallmarks of cystic fibrosis (CF) lung disease is the presence of intense, neutrophil-dominated airway inflammation, and many researchers have focused on developing therapies to reduce inflammation in CF lung disease . Systemic corticosteroids can delay progression of lung disease, but at the cost of unacceptable side effects . Inhaled corticosteroids are widely used, but their efficacy has yet to be demonstrated in a controlled fashion . Ibuprofen has also been shown to delay disease progression, but its use has been limited by the need to obtain individual pharmacokinetics and concern about side effects . Other treatments with potential anti-inflammatory effects include pentoxifylline, leukotriene antagonists, docosahexaenoic acid, and azithromycin . Few, if any, large clinical studies of these therapies have been published, but several are presently underway . Because neutrophil elastase appears to be a key mediator of tissue damage in CF lung disease, anti-elastase compounds have also been studied, including alpha-1-protease inhibitor, secretory leukocyte protease inhibitor, and small molecule inhibitors . There have been no large-scale controlled trials of these therapies in CF . More recently, investigators have focused on cytokine modulation, using either interleukin-10 or interferon gamma . Some complementary and alternative medicine therapies may also have anti-inflammatory effects, although their clinical value has yet to be demonstrated in a rigorously-controlled fashion . In summary, numerous anti-inflammatory therapies have been applied to CF lung disease, but more large, well-controlled studies will need to be performed to determine their true clinical usefulness.

Expert Opin Pharmacother, 2002 Aug, 3(8), 1109 - 15
Babesiosis in humans: a treatment review; Weiss LM; Human infections with Babesia species, in particular Babesia microti, are tick-borne illnesses that are being recognised with increased frequency . Coinfection with ehrlichiosis and Lyme disease is also being recognised as an important feature of these tick-borne illnesses . Despite the superficial resemblance of Babesia to malaria, these piroplasms do not respond to chloroquine or other similar drugs . However, the treatment of babesiosis using a clindamycin-quinine combination has been successful . Data in animal models and case-reports in humans have suggested that an atovaquone-azithromycin combination is also effective . This was confirmed in a recent prospective, open, randomised trial of clindamycin-quinine versus azithromycin-atovaquone . This paper reviews the literature on the treatment of human babesiosis and the animal models of these human pathogens.

Eur J Pharm Sci, 2002 Aug, 16(3), 175 - 84
Characterization of azithromycin hydrates; Gandhi R et al.; Azithromycin (AZI) is a macrolide antibiotic with an expanded spectrum of activity that is commercially available as a dihydrate . This study was carried out to characterize hydrates of azithromycin . A commercial dihydrate sample was used to prepare monohydrate from water/ethanol (1:1) mixture . Hydrates were characterized using DSC, TGA, KFT, XRD, HSM, SEM and FT-IR . TGA showed that the commercial samples are dihydrate and the sample prepared from water/ethanol (1:1) was a monohydrate . Solubility studies revealed that monohydrate converted to dihydrate during solubility studies and as a result there was no significant difference in the equilibrium solubility of MH and DH . Thermal analysis under various conditions revealed that dehydration and melting took place simultaneously . Anhydrous AZI was found to be hygroscopic and converted to DH on storing at room temperature . Molecular modeling studies revealed the probable sites of attachment of water molecules to AZI.

Acta Pharmacol Sin, 2002 Jul, 23(7), 591 - 6
Effects of various principles from Chinese herbal medicine on rhodamine123 accumulation in brain capillary endothelial cells; He L et al.; AIM: To search for novel effective P-glycoprotein (P-gp) reversal agents in the blood-brain barrier (BBB) . METHODS: Using rhodamine123 (Rh123) to examine the functional activity of P-gp in cultured bovine brain capillary endothelial cells (BCEC) and screen various principles on P-gp modulation in BBB . RESULTS: All of tested compounds (1-10 micromol/L) increased the intracellular accumulation of Rh123 in a concentration-dependent manner . The rank order of these agents in increasing Rh123 accumulation in BCEC was: cyclosporin A (CsA) > tetrandrine (Tet) > vincrinstine (VCR) approximate, equals flunarizine (Flu) > dl-tetrahydropalmatine (dl-THP) > dauricine (DRC) > azithromycin (Azi) > verapamil (Ver) approximate, equals berbamine (BBM) > daurisoline (DRS) > berberine (BBR) approximate, equals doxorubicin (Dox) > l-tetrahydropalmatine (l-THP) > tetramethylpyrazine (TMP) . These agents at concentration of 10 micromol/L increased Rh123 accumulation by 346 %, 203 %, 136 %, 129 %, 115 %, 103 %, 92 %, 87 %, 81 %, 75 %, 67 %, 67 %, 63 %, and 54 %, respectively . The effects of CsA, Tet, Ver, Flu, Azi, and dl-THP on cellular accumulation of Rh123 in BCEC were reversible . When CsA, Tet, Ver, Flu, Azi, or dl-THP-pretreated BCEC were examined at 48, 36, 24, 36, 36, or 12 h, respectively, after removing the agent, the amount of cellular Rh123 accumulation in BCEC returned to control levels (no drug treatment) . CONCLUSION: The functional activity of P-gp on the blood-brain barrier could be modulated by various MDR-reversing agents and some principles with low toxicity extracted from medicinal herbs, such as some isoquinoline alkaloids without permanent modifying effects on the intrinsic level of P-gp function.

Am J Ophthalmol, 2002 Jul, 134(1), 34 - 40
A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis; Bosch-Driessen LH et al.; OBJECTIVE: To compare the effects of two treatment regimens, one of which included azithromycin, for the treatment of sight-threatening (near optic disk or fovea) ocular toxoplasmosis . DESIGN: Prospective, randomized open-labeled multicenter study, masked in part with regard to evaluation . METHODS:PARTICIPANTS TOTAL ENROLLMENT: 46 patients with sight-threatening ocular toxoplasmosis; pyrimethamine and azithromycin group: 24 patients; pyrimethamine and sulfadiazine group: 22 patients . INTERVENTION: Patients were randomized into two treatment regimens . Group 1 was treated with pyrimethamine and azithromycin complemented with folinic acid and the addition of prednisone from day 3 . Group 2 was treated with pyrimethamine and sulfadiazine complemented with folinic acid and the addition of prednisone from day 3 . Patients used study medications daily for 4 weeks . Ocular and laboratory examinations were performed at least weekly during the observation period . The study was masked in part with regard to evaluation . MAIN OUTCOME MEASURES: An assessment was made of the time to resolution of the intraocular inflammatory activity, the size of the retinochoroidal lesion, and visual acuity before and after the treatment as well as all adverse effects of treatments . RESULTS: Adverse effects were more frequent in the pyrimethamine/sulfadiazine group (P <.04), and three patients in this group had to discontinue treatment . The time to resolution of inflammatory activity, decrease in size of retinochoroidal lesions, and optimal visual acuity did not differ between the two treatment groups . The number of patients who developed recurrences during the first year after treatment was similar for both groups . CONCLUSIONS: The efficacy of the multidrug regimen with pyrimethamine and azithromycin was similar to the standard treatment with pyrimethamine and sulfadiazine . However, the frequency and severity of adverse effects was significantly lower with a regimen containing pyrimethamine and azithromycin . Multidrug therapy with the combination of pyrimethamine and azithromycin appears to be an acceptable alternative for treatment of sight-threatening ocular toxoplasmosis.

Peptides, 2002 May, 23(5), 1015 - 8
In vitro effect of short-term exposure to two synthetic peptides, alone or in combination with clarithromycin or rifabutin, on Cryptosporidium parvum infectivity; Giacometti A et al.; The viability of Cryptosporidium parvum after exposure to peptide antibiotics was studied by two different methods, a cell culture system and a double fluorogenic staining . The peptides KFFKFFKFF and IKFLKFLKFL exerted high cytotoxic effects on sporozoites, as demonstrated by cell cultures (complete inhibition after 60 min at 100 microg/ml) and flow cytometry (30% after 20 min at 100 microg/ml), but did not affect consistently the oocysts . Clarithromycin and rifabutin demonstrated less activity against sporozoites but higher activity against oocysts (30% after 180 min at 10 microg/ml) . The combination between peptides and azithromycin or rifabutin exerted the highest activities.

Sex Transm Infect, 2002 Apr, 78 Suppl 1, i164 - 9
Heterosexual outbreak of infectious syphilis: epidemiological and ethnographic analysis and implications for control; Patrick DM et al.; This study describes the epidemiology and ethnography of an outbreak of infectious syphilis in Vancouver, British Columbia . Between 1996 and 1999, British Columbias's rate of infectious syphilis rose from 0.5 to 3.4 per 100,000, with a dense concentration of cases among sex trade workers, their clients, and street-involved people in the downtown eastside area of Vancouver . Sexual networks were imported cases with secondary spread (dyads and triads), large densely connected dendritic networks of sex trade workers and clients, or occasional starburst networks among gay men . Only 232 of 429 partners were documented as having been treated (54% of those named, or 0.9 per case) . The geographical and demographic concentration of this outbreak led to consideration of a programme of focused mass treatment with single dose azithromycin.

Am J Med, 2002 Jun 15, 112(9), 730 - 2
Cases from the medical grand rounds of the Osler Medical Service at Johns Hopkins University; Seo P; A 77-year-old man was in good health until he complained of fatigue 3 weeks before presentation . Two weeks before admission, he developed gradually worsening shortness of breath . One week before admission, he developed a cough that initially was nonproductive but later was associated with hemoptysis.His past medical history was remarkable for a history of colon cancer (Dukes' stage III), for which he underwent a hemicolectomy and treatment with adjuvant chemotherapy in 1993 . He had a myocardial infarction in 1986 and underwent coronary artery bypass surgery in 1999 . He also had a history of hypertension, type 2 diabetes, and gout . He smoked in the past but had stopped more than 30 years ago.He was initially evaluated by his primary care physician, who noted that he complained of diaphoresis but denied fevers, chills, or contact with others who were ill . His physical examination was remarkable for bilateral crackles that were more pronounced on the right . A chest radiograph demonstrated bilateral pulmonary infiltrates (Figure 1) . He was treated with amoxicillin . The next day, however, his physician noted that his dyspnea had worsened and that his oxygen saturation on room air was poor . He was therefore admitted for further evaluation.The amoxicillin was discontinued, and he was treated with levofloxacin, followed by ceftriaxone and azithromycin as his pulmonary status continued to deteriorate . He received intravenous diuretic agents, which failed to improve his respiratory status.During the initial phase of hospitalization, he was anemic, with a hematocrit of 21.3% . His serum creatinine level, which had been 1.0 mg/dL in 1999, was now 2.5 mg/dL . Urinalysis was remarkable for the presence of numerous red blood cells . His oxygen requirement increased, and he eventually required a 100% nonrebreather mask . A computed tomographic scan of the chest demonstrated prominent alveolar opacities throughout the right upper, middle, and lower lobes, with similar opacities in the left upper and left lower lobes (Figure 2) . An echocardiogram showed an ejection fraction of 50%, as well as mild mitral regurgitation . Serologies were remarkable for an antinuclear antibody titer of 1:320 and a P-antineutrophil cytoplasmic antibody (P-ANCA) titer of greater than 1:320 . C-ANCA was negative . Anti-glomerular basement membrane and anti-human immunodeficiency virus antibodies were undetectable.

Southeast Asian J Trop Med Public Health, 2001 Dec, 32(4), 770 - 5
Intestinal parasitic infections among human immunodeficiency virus-infected and -uninfected children hospitalized with diarrhea in Bangkok, Thailand; Chokephaibulkit K et al.; A prospective observational study was conducted to determine the prevalence and the clinical impact of intestinal parasitic infections in diarrheal illness among HIV-infected and HIV-uninfected children hospitalized with diarrhea in Bangkok, Thailand . Stool samples were examined for intestinal parasites using a simple smear method, a formalin-ether concentration method, a modified acid-fast stain and a modified trichrome stain . Intestinal parasites (IP) were identified in the stool specimens of 27 of 82 (33%) HIV-infected and 12 of 80 (15%) HIV-uninfected children (p=0.01) . Microsporidia and Cryptosporidium were the most common IP found . Eighty-two percent of HIV-infected and 97% of HIV-uninfected groups presented with acute diarrhea and 76% of each group had watery diarrhea . Pneumonia was the most common concurrent illness, found in 22% . Clinical findings were unable to differentiate children infected with IP . Sixty-three percent of HIV-infected and 83% of HIV-uninfected children who had IP made a satisfactory recovery without specific anti-parasitic therapy . However, 9 children (7 HIV-infected and 2 HIV-uninfected) with persistent diarrhea who also had cryptosporidiosis and/or microsporidiosis did not respond to azithromycin and/or albendazole respectively . HIV-infected children with cryptosporidiosis were older and had more advanced HIV infection than those with microsporidiosis . Routine stool examination for IP should be considered due to the absence of clinical markers . The lack of effective therapy for the major IP found underscores the importance of preventive measures.

Lancet, 2002 May 11, 359(9318), 1648 - 54
Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial; Evans AT et al.; BACKGROUND: The value of azithromycin for treatment of acute bronchitis is unknown, even though this drug is commonly prescribed . We have investigated this question in a randomised, double-blind, controlled trial . METHODS: Adults diagnosed with acute bronchitis, without evidence of underlying lung disease, were randomly assigned azithromycin (n=112) or vitamin C (n=108) for 5 days (total dose for each 1.5 g) . All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer . The primary outcome was improvement in health-related quality of life at 7 days; an important difference was defined as 0.5 or greater . Analysis was by intention to treat . FINDINGS: The study was stopped by the data-monitoring and safety committee when 220 patients had been recruited . On day 7, the adjusted difference in health-related quality of life was small and not significant (difference 0.03 {95% CI -0.20 to 0.26}, p=0.8) . 86 (89%) of 97 patients in the azithromycin group and 82 (89%) of 92 in the vitamin C group had returned to their usual activities by day 7 (difference 0.5% {-10% to 9%}, p>0.9) . There were no differences in the frequency of adverse effects; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects, compared with none in the azithromycin group . Most patients (81%) reported benefit from the albuterol inhaler . INTERPRETATION: Azithromycin is no better than low-dose vitamin C for acute bronchitis . Further studies are needed to identify the best treatment for this disorder.

J Asthma, 2002 Apr, 39(2), 181 - 5
Effect of azithromycin on the severity of bronchial hyperresponsiveness in patients with mild asthma; Ekici A et al.; The effect of azithromycin on bronchial hyperresponsiveness was measured in a group of 11 patients with mild asthma . Azithromycin 250 mg orally was administered intermittently to all the patients twice a week for eight weeks . The only other treatment was inhaled beta2 agonist, when required . A histamine inhalation test was performed at the beginning and at the fourth and the eighth week of the study . The mean PC20 values increased significantly over the initial value at the eighth week after the administration of azithromycin (p < 0.05) but mean values for FEV1 and FEV1 percent predicted did not differ significantly . These results suggested that eight weeks of intermittent, low-dose administration of azithromycin in patients with mild asthma might reduce the severity of bronchial hyperresponsiveness.

Med Clin North Am, 2002 Mar, 86(2), 361 - 73
Babesiosis; Krause PJ; Babesiosis is an emerging infection caused by protozoal parasites and transmitted by the same tick that transmits Lyme disease . Babesiosis is found throughout the world, but most cases have been described from the northeastern and northern midwestern United States . Patients experience a flulike illness that usually lasts for 1 or 2 weeks but may require hospital admission . Those at greatest risk of fatal disease include individuals older than age 50 years; asplenic individuals; and immunocompromised individuals as a result of immunosuppressive drugs, malignancy, or HIV infection . Specific diagnosis is made through examination of a Giemsa-stained thin blood smear, DNA amplification using polymerase chain reaction, or detection of specific antibody . Treatment consists of clindamycin and quinine or atovaquone and azithromycin and, in severe cases, exchange transfusion.

Acta Pharmacol Sin, 2002 May, 23(5), 471 - 6
In vitro metabolic characteristics of cytochrome P-450 2A6 in Chinese liver microsomes; Xia XY et al.; AIM: To investigate the metabolic characteristics of cytochrome P-450 C YP2A6 in human liver microsomes . METHODS: Cytochrome P-450 enzyme activities were measured by biochemical assays . Xenobiotics were employed to observe their effects on CYP2A6 in vitro . The kinetics of coumarin 7-hydroxylase was determined, and the correlation between CYP2A6 and UDP-glucuronosyltransferase (UGT) was analyzed . RESULTS: CYP2A6 activities of human liver microsomes were from 0.47 to 4.14 micromol . min-1 . g-1, with a 8.8-fold variation . The Km and Vmax of CYP2A6 ranged from 0.25 to 1.56 micromol/L and 1.41 to 8.70 micromol . min-1 . g-1, respectively . CYP2A6 activity was markedly inhibited (> 50 %) by pilocarpine, diethyldithio carbamic (DDC), and rifampicin, the IC50 was 5.31 micromol/L, 156.35 micromol/L, and 38.81 micromol/L, respectively . alpha-Naphthoflavone, sulfaphenazole, troleandomycin (TAO), ketoconazole, phenobarbital, prednisolone, and azithromycin had little or no effects on coumarin 7-hydroxylation . A significant correlation was observed between CYP2A6 and UGT2 (r = 0.9453, P < 0.05) . CONCLUSION: CYP2A6 activity and kinetics exhibited a considerable variation in human liver microsomes in vitro, and a significant correlation was existed between CYP2A6 and phase II enzyme UGT2 . Not only pilocarpine, CYP2A6 specific inhibitor, but also rifampicin and DDC inhibited CYP2A6 activity selectively.

Antimicrob Agents Chemother, 2002 May, 46(5), 1594 - 6
Distribution of azithromycin in plasma and tonsil tissue after repeated oral administration of 10 or 20 milligrams per kilogram in pediatric patients; Blandizzi C et al.; Azithromycin concentrations in the tonsils of 56 pediatric patients, treated with 10 or 20 mg of the drug per kg of body weight for 3 days, were compared . Azithromycin levels in plasma and tonsil samples were determined up to 8.5 days after the last dose . The 20-mg/kg regimen resulted in an improved tonsillar distribution of azithromycin, suggesting the achievement of enhanced therapeutic concentrations at infective sites of the upper respiratory tract.

J HIV Ther, 2002 Feb, 7(1), 13 - 6
Mycobacterial diseases and HIV; Pozniak A; This article focuses on tuberculosis (TB) and Mycobacterium avium complex (MAC), as these are the most important of the mycobacterioses in HIV-infected patients . It is estimated that in 1999, HIV-related TB reached 1000000 cases and caused 30% of the 2500000 AIDS-related deaths . In HIV-infected patients, TB may have unusual clinical features and can cause diagnostic difficulties . Despite the effectiveness of modern short-course treatment, mortality due to HIV-related TB remains high both during and after treatment . While highly effective therapy exists for both HIV and TB, concomitant administration is fraught with difficulties and many physicians delay HAART for 2 or more months to minimise the risk of toxic side effects . Patients with CD4 counts <50 cells/micro l should receive MAC prophylaxis . Clarithromycin or azithromycin are the preferred agents.

J Clin Pharmacol, 2002 Apr, 42(4), 444 - 9
A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers; Amsden GW et al.; Atorvastatin is a common option among the HMG-CoA reductase inhibitors for the treatment of lipid disorders because of its excellent lipid-lowering efficacy and overall safety profile . Although these agents can rarely cause rhabdomyolysis by themselves, macrolides, among other agents, have been demonstrated to increase the likelihood of this via inhibition of CYP metabolism of the lipid agent . This study investigated the potential for azithromycin and clarithromycin to inhibit the metabolism of atorvastatin . Although there was no interaction between azithromycin and atorvastatin, clarithromycin did have a significant effect on atorvastatin pharmacokinetic parameters . When coadministered, clarithromycin raised subject exposure (AUC24) by 82% and peak plasma concentrations by 56% . These data suggest that while azithromycin appears to be safe to coadminister with atorvastatin, clarithromycin should be avoided in patients taking this and similarly metabolized HMG-CoA inhibitors.

Int J Antimicrob Agents, 2002 Mar, 19(3), 189 - 94
The safety of azithromycin in the treatment of adults with community-acquired respiratory tract infections; Treadway G et al.; The comparative safety of azithromycin was assessed in adult patients (> or =12 years) with community-acquired respiratory tract infections . Of 3229 patients evaluated, 1616 received azithromycin 500 mg once daily for 3 days and 1613 received standard regimens of amoxycillin, amoxycillin/clavulanic acid, cefaclor, clarithromycin, or roxithromycin . A similar incidence of treatment-related adverse events occurred with azithromycin (10.3%) and comparators (11.5%) . Significantly fewer patients were withdrawn from azithromycin than comparator treatment (0.4 versus 2.1%; P=0.0001) . Most adverse events were mild/moderate in intensity and affected the gastrointestinal system . Azithromycin was as well tolerated as other antibiotics commonly used for bacterial infections in adults.

Nihon Kokyuki Gakkai Zasshi, 2002 Jan, 40(1), 17 - 25
{Cost-effectiveness analysis of ambulatory treatment for adult patients with community-acquired pneumonia: according to Japanese Respiratory Society guidelines}; Morimoto T et al.; The Japanese Respiratory Society has recently formulated practice guidelines for the management of adult patients with community-acquired pneumonia . The guidelines recommend the use of various oral antibiotics at individual physicians' discretion . We compared the cost-effectiveness of amoxicillin/clavulanate (AMPC/CVA), azithromycin (AZM), clarithromycin (CAM), cefdinir (CFDN), levofloxacin (LVFX), and minocycline (MINO), when used on an ambulatory basis . We performed a formal cost-effectiveness analysis from the perspective of direct cost payers in the framework of the Japanese medical system . Outcomes considered were quality-adjusted life days (QALD), costs per patient, and incremental costs per quality-adjusted life year (QALY) gained . Under baseline conditions, the effectiveness of MINO, AZM, CAM, and LVFX were on a par and higher than that of AMPC/CVA or CFDN by 125-290.5 QALD . The least expensive antibiotic was MINO (55,070 to 59,208 yen), followed by AZM (56,049 to 60,188 yen), CAM (56,171 to 60,309 yen), LVFX (61,988 to 66,127 yen) . AMPC/CVA (122,432 to 133,797 yen), and CFDN (123,375 to 134,649 yen) . Thus, MINO, AZM, and CAM were cost-effective antibiotics for adults with community-acquired pneumonia . Sensitivity analyses revealed that the initial success rate of each antibiotic was crucial in determining cost-effectiveness . When the number of times antibiotics are taken in a day and the period of therapy were taken into account, AZM was most beneficial with 917,179-1,152,694 yen (US$ 7,643-9,606) per additional QALY over MINO in patients without comorbidity . This result, however, was not applicable to patients with chronic lung disease . MINO was the least expensive and the most cost-effective in empirically treating adult patients with community-acquired pneumonia on an ambulatory basis . AZM provides a higher quality of life for adults without comorbidity with generally acceptable marginal cost.

Transplantation, 2002 Mar 27, 73(6), 1002 - 5
Chlamydia pneumoniae respiratory infection after allogeneic stem cell transplantation; Geisler WM et al.; Chlamydia pneumoniae is a common cause of upper and lower respiratory tract infections in immunocompetent patients; however, its role as a respiratory pathogen in immunocompromised hosts has been infrequently recognized . We describe C . pneumoniae lower respiratory tract infection in a 19-year-old male after allogeneic stem cell transplantation . The patient developed fever on day +14, and a subsequent computed tomography scan of the chest revealed a right lateral pleural-based opacity, which was then resected during thoracoscopy . Diagnosis was made by culture and staining of the resected tissue with C . pneumoniae-specific monoclonal antibodies, and azithromycin was administered . To the best of our knowledge, this is the first report of C . pneumoniae respiratory infection after stem cell or marrow transplantation . C . pneumoniae often coexists with other etiologic agents of pneumonia in immunocompromised patients . Considering the infrequency of infections from this organism in this clinical setting, one must still rule out other more likely respiratory pathogens.

Infect Dis Obstet Gynecol, 2001, 9(4), 197 - 202
A randomized trial of azithromycin versus amoxicillin for the treatment of Chlamydia trachomatis in pregnancy; Kacmar J et al.; OBJECTIVE: To compare the compliance, side effects and efficacy of amoxicillin and azithromycin for the treatment of Chlamydia trachomatis infection in pregnancy . METHODS: This is a randomized single-blind trial of women diagnosed with C . trachomatis before 33 weeks gestation . Women were randomlyassigned either 500 mg amoxicillin orally three times per dayfor 7 days or a single dose of 1 g azithromycin orally . Patients were interviewed by telephone approximately 3-7 days following therapy to assess compliance and side effects . Test of cure was performed at a follow-up visit 4-6 weeks following completion of therapy . RESULTS: Thirty-nine patients were randomized with 19 receiving amoxicillin and 20 receiving azithromycin . There were no differences in baseline data between the two groups, and there were no statistically significant differences in side effects, compliance or efficacy . In the amoxicillin group 84% of women took all pills, while 100% completed the single 1 g dose of azithromycin . Side effects were common in both groups (38% overall), with 40% of the azithromycin group reporting moderate to severe gastrointestinal side effects compared to 17% in the amoxicillin group (p = 0.11) . Of patients who returned for follow-up test of cure, 3 of 15 (20%) in the amoxicillin group were positive compared with 1 of 19 (5%) in the azithromycin group (p = 0.3) . CONCLUSIONS: Side effects of therapy for C . trachomatis in pregnancy are common . Amoxicillin was slightly better tolerated than azithromycin . Compliance and cure rates with both regimens was high.

J Clin Psychopharmacol, 2002 Apr, 22(2), 162 - 8
In vitro inhibition of pimozide N-dealkylation by selective serotonin reuptake inhibitors and azithromycin; Desta Z et al.; Pimozide is often coprescribed with serotonin reuptake inhibitor (SSRI) antidepressants to treat depression in patients with Tourette's syndrome . In human liver microsomes (HLMs), the inhibition of the primary route of pimozide metabolism, N-dealkylation to 1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one (DHPBI), by four SSRIs (fluoxetine, sertraline, paroxetine, and fluvoxamine) and azithromycin was tested . Inhibition constants (K(i) values) were estimated from Dixon plots (three HLMs for each inhibitor) using the appropriate enzyme inhibition model by nonlinear regression . At 10 microM paroxetine, sertraline, fluoxetine, or fluvoxamine, the formation of DHPBI from pimozide (10 microM) in HLMs was inhibited by an average (three HLMs) of 7%, 7.7%, 8%, and 16%, respectively, whereas this inhibition did not exceed 55% at the maximum concentrations (100 microM) of the SSRIs tested . Azithromycin had negligible effect on pimozide (10 microM) N-dealkylation (19% at 100 microM azithromycin) . These inhibition data were compared with ketoconazole, which was included as a positive control of CYP3A inhibition . At 0.1 microM and 0.5 microM ketoconazole, the formation of DHPBI from 10 microM pimozide was inhibited by 32% and 62%, respectively . The K(i) values (+/- SD) of ketoconazole, sertraline, fluvoxamine, azithromycin, fluoxetine, and paroxetine were 0.07 microM, 89 +/- 44 microM, 89 +/- 24 microM, 103 +/- 52 microM, 117 +/- 27 microM, and 129 +/- 33 microM, respectively . These values are least 100-fold higher than the expected plasma concentrations after the usual daily doses of the SSRIs and azithromycin, suggesting that coadministration of SSRIs and azithromycin are unlikely to markedly diminish the elimination of pimozide in patients . However, in vivo predictions from in vitro data are not always perfect . In vivo, the SSRIs or azithromycin may concentrate in the liver relative to plasma . In addition, the possibility that these drugs could alter pimozide disposition through effects on transport proteins or via promoter repression cannot be ruled out.

Infect Control Hosp Epidemiol, 2001 Dec, 22(12), 781 - 3
Azithromycin prophylaxis during a hospitalwide outbreak of a pertussis-like illness; Martinez SM et al.; A questionnaire regarding tolerability and adherence was administered for 5 days to hospital employees who received azithromycin prophylaxis during a hospitalwide outbreak of a pertussis-like illness . Analysis of the 239 responses from those having received prophylactic azithromycin determined that it was well tolerated and accounted for a minimal loss of days worked; 81.5% were fully adherent with the regimen.

Thorax, 2002 Mar, 57(3), 212 - 6
Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial; Wolter J et al.; BACKGROUND: Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF) . While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial, their use is limited by side effects . Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis, a condition with features in common with the lung disease of CF . METHODS: To determine if azithromycin (AZM) improves clinical parameters and reduces inflammation in patients with CF, a 3 month prospective randomised double blind, placebo controlled study of AZM (250 mg/day) was undertaken in adults with CF . Monthly assessment included lung function, weight, and quality of life (QOL) . Blood and sputum collection assessed systemic inflammation and changes in bacterial flora . Respiratory exacerbations were treated according to the policy of the CF Unit . RESULTS: Sixty patients were recruited (29 men) of mean (SD) age 27.9 (6.5) years and initial forced expiratory volume in 1 second (FEV1) 56.6 (22.3)% predicted . FEV1% and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean (SE) decline of -3.62 (1.78)% (p=0.047) and -5.73 (1.66)% (p=0.001), respectively . Fewer courses of intravenous antibiotics were used in patients on AZM (0.37 v 1.13, p=0.016) . Median C reactive protein (CRP) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group (p<0.001) . QOL improved over time in patients on AZM and remained unchanged in those on placebo (p=0.035) . CONCLUSION: AZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function . Long term AZM may have a significant impact on morbidity and mortality in patients with CF . Further studies are required to define frequency of dosing and duration of benefit.

Int J STD AIDS, 2002 Mar, 13(3), 145 - 51
Mycoplasma genitalium -- an up-date; Taylor-Robinson D; Mycoplasma genitalium was first isolated from men with non-gonococcal urethritis (NGU) more than 20 years ago . Use of polymerase chain reaction technology has shown it to be a cause of acute NGU and probably chronic NGU, almost independently of Chlamydia trachomatis, but there is no substantial evidence that it causes acute or chronic prostatitis . In women, M . genitalium is not associated with bacterial vaginosis, but it is strongly associated with cervicitis and endometritis and serologically with salpingitis and tubal factor infertility . Further studies may show M . genitalium to be associated, perhaps causally, with epididymoorchitis, neonatal disease and reactive arthritis . Furthermore, its potential for enhancing HIV transmission needs to be explored . M . genitalium is susceptible to various broad-spectrum antibiotics, but M . genitalium-associated diseases are probably best treated with azithromycin.

J Pharm Biomed Anal, 2002 Feb 1, 27(5), 833 - 6
A new HPLC method for azithromycin quantitation; Zubata P et al.; A simple liquid chromatographic method was developed for the estimation of azithromycin raw material and in pharmaceutical forms . The sample was chromatographed on a reverse phase C18 column and eluants monitored at a wavelength of 215 nm . The method was accurate, precise and sufficiently selective . It is applicable for its quantitation, stability and dissolution tests.

Acta Otolaryngol, 2001 Dec, 121(8), 925 - 9
A comparative study of azithromycin and pseudoephedrine hydrochloride for otitis media with effusion in children; Safak MA et al.; We compared the outcomes of two different regimens--azithromycin and pseudoephedrine hydrochloride (PHCl)--for the treatment of otitis media with effusion (OME) in children . In a double-blind randomized clinical study, a total of 90 children aged between 2 and 13 years with persistent OME were randomly assigned to one of 3 treatment groups . The first group received azithromycin at a dose of 10 mg/kg once daily for 3 days and this regimen was repeated weekly for up to 12 weeks according to the results of tympanometry and pneumatic otoscopy . The second group received azithromycin at a dose of 10 mg/kg once daily for 3 days for the first week, and this regimen was repeated for 1 day a week for the following 11 weeks . The third group received PHCl, 4 mg/kg, 3 times daily for up to 12 weeks . Each patient underwent pneumatic otoscopic and tympanometric investigations at baseline and at Weeks 4, 8 and 12 . The outcomes in the azithromycin-treated groups were superior to that in the decongestant group . However, the difference between the outcomes in the azithromycin groups according to the treatment protocol was not statistically significant . Azithromycin therapy, particularly a once-weekly regimen, helps patients to comply with treatment and also helps us to achieve good results with minimal therapy.

Zhonghua Nei Ke Za Zhi, 1999 Oct, 38(10), 677 - 80
{An experimental study on the effect of azithromycin treatment in bleomycin-induced pulmonary fibrosis of rats}; Chen J et al.; OBJECTIVE: To evaluate the therapeutic effects and mechanism of azithromycin treatment in bleomycin-induced pulmonary fibrosis of rats . METHODS: Animal model of bleomycin-A5-induced pulmonary fibrosis was established in rats.36 animal models were divided into two groups: a bleomycin-induced pulmonary fibrosis group and a azithromycin group in which the animal models were treated with azithromycin (80 mg/kg once a day for three continuous days in a week) . The animals of the two groups were killed at the first,second and fourth week respectively.Another six rats constituted a normal control group, instillated withsaline intratracheally and killed at the first week . Pathological changes activity of nuclear factor kappaB (NF-kappaB) of alveolar macrophage, cytokine tumor necrosis factor (TNF) alpha, transforming growth factor-beta (TGF-beta) mRNA expression and protein levels of alveolar macrophage and lung tissue were studied or measured . RESULTS: Amelioration of alveolitis and lung fibrosis after treatment with azithromycin was shown in pathological section (P < 0.05) . The activity of NF-kappaB was significantly higher in one-week pulmonary fibrosis model than that in normal control and its level in alveolar macrophage reduced (67.2%) after treatment with azithromycin . The level of protein and mRNA of TNFalpha, TGF-beta in lung tissue and alveolar macrophage was increased in the early stage of pulmonary fibrosis and reduced after treatment with azithromycin (P < 0.05) . CONCLUSION: It is suggested that azithromycin might be a therapeutic drug for pulmonary fibrosis in the future . Azithromycin reduced the degree of alveolitis and fibrosis through inhibition of the activity of NF-kappaB and the expression of TNFalpha, TGF-beta mRNA and lowering the level of protein in alveolar macrophage and lung tissue in the early stage of pulmonary fibrosis . This might be one of the mechanisms of azithromycin treatment in pulmonary fibrosis.

Clin Infect Dis, 2002 Feb 1, 34(3), 371 - 8 Epub 2001 Dec 14.
Azithromycin prophylaxis for Mycobacterium avium complex during the era of highly active antiretroviral therapy: evaluation of a provincial program; Phillips P et al.; Mycobacterium avium complex (MAC) disease was evaluated in a provincial program of azithromycin prophylaxis . Highly active antiretroviral therapy (HAART) was prescribed to 383 (65%) of 587 patients eligible for MAC prophylaxis (CD4 <75 cells/mm3) . By use of an intent-to-treat analysis, MAC disease was observed in 21 of 271 patients who did not receive prophylaxis (incidence rate, 8 events per 100 person-years) . MAC events occurred in 10 of 316 patients who received azithromycin (2.37 events per 100 person-years) . Localized lymphadenitis compatible with immune reconstitution disease accounted for 23% of all MAC events, in contrast to studies in the pre-HAART era, where almost all cases were disseminated . None of the MAC isolates from the 10 prophylaxis failures were resistant to azithromycin . Azithromycin appeared to be protective against disseminated MAC in patients who were either unresponsive or nonadherent to HAART, but it did not prevent the development of immune reconstitution disease due to MAC.

Presse Med, 2001 Dec 1, 30(36), 1792 - 801
{The relationship between Chlamydia pneumoniae and atherosclerosis}; Gayet A et al.; BACKGROUND: Risk factors for arthrosclerosis have been well identified . More than ten years ago, an infectious process was incriminated, particularly the pathogenic effect of Chlamydia pneumoniae in the development of atheromatous lesions responsible for ischemic cardiovascular diseases . DATA BASES: Several approaches have been used to assess the presence of a relationship between C . pneumoniae and the development of cardiovascular disease . Serological, histopathological (study of the atheromatous plaque), pathophysiological, and finally animal studies using models reproducing the human disease have generally favored an association . Therapeutic trials, especially those testing roxithromycin or azithromycin have demonstrated the action of secondary prevention of ischemic heart disease (unstable angina, myocardial infarction) . CONCLUSION: The notion of an association between these two factors is biologically plausible . Several points remain to be clarified, particularly the need to develop a reliable diagnostic method for C . pneumoniae infections . It would also be useful to prove the viability of the pathogen within atheromatous plaques and finally to design studies of immune response to C . pneumoniae infections . Prospective therapeutic trials for primary prevention of cardiovascular disease would be most informative but would be most difficult to conduct.

J Eur Acad Dermatol Venereol, 2001 Sep, 15(5), 405 - 9
Electron microscopic evidence of persistent chlamydial infection following treatment; Bragina EY et al.; Chlamydia trachomatis infections of the female and male genital tracts are often asymptomatic and, thus, tend to become persistent . In the persistent state the typical Chlamydia life cycle is arrested and standard antibiotic regimens do not always eradicate this infection . We sought to relate treatment failures in men and women with persistent chlamydial genital tract infections to electron microscopic evidence of chlamydial persistence and with atypical morphological forms of the organism . Of 16 patients with chlamydial persistence following azithromycin treatment, morphological variants of this organism were observed by electron microscopy from one endocervical sample and one male urethral sample . We document the presence of intracellular inclusions containing only reticulate bodies, extracellular monomembrane and polymembrane phagosomes containing elementary bodies and reticulate bodies with abnormal outer membranes in the process of dividing extracellularly . These observations parallel previous in vitro studies of chlamydial persistence under adverse conditions . This capacity of C . trachomatis to undergo atypical morphological alterations in vivo may contribute to its persistence and relative resistance to antibiotics.

Biopharm Drug Dispos, 2001 Jan, 22(1), 15 - 21
Bioequivalence assessment of Azomycin (Julphar, UAE) as compared to Zithromax (Pfizer, USA)--two brands of azithromycin--in healthy human volunteers; Najib NM et al.; Two studies have been performed to assess the relative bioavailability of Azomycin (Julphar, UAE) as compared with Zithromax (Pfizer, USA) at the International Pharmaceutical Research Center (IPRC), Amman, Jordan . One study involved Azomycin capsules and the other Azomycin suspension . Each study enrolled 24 volunteers and in both studies, after an overnight fasting, the two brands of azithromycin were administered as single dose on two treatment days separated by a 2 weeks washout period . After dosing, serial blood samples were collected for a period of 192 h . Plasma harvested from blood, was analysed for azithromycin by HPLC coupled with electrochemical detection . Various pharmacokinetic parameters including AUC(0-t,) AUC(0-infinity,) C(max), T(max), T(1/2) and K(elm) were determined from plasma concentrations for both formulations and found to be in good agreement with the reported values . AUC(0-t), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data . No significant difference was found based on ANOVA; 90% confidence intervals for the test/reference ratios of these parameters were found within the bioequivalence acceptance range of 80-125% . Based on these statistical inferences it was concluded that Azomycin capsule is bioequivalent to Zithromax capsule and Azomycin suspension is bioequivalent to Zithromax suspension .

Clin Infect Dis, 2002 Jan 15, 34(2), 154 - 8 Epub 2001 Dec 04.
Clarithromycin versus azithromycin in the treatment of Mediterranean spotted fever in children: a randomized controlled trial; Cascio A et al.; We conducted an open-label randomized controlled trial to compare the efficacy and safety of clarithromycin (15/mg/kg/day in 2 divided doses for 7 days) with those of azithromycin (10 mg/kg/day in 1 dose for 3 days) in the treatment of children with Mediterranean spotted fever . Until now, there has not been a gold-standard therapy for this rickettsial disease in children . Eighty-seven children were randomized to receive 1 of the 2 drugs . The mean time to defervescence (+/- standard deviation) was 46.2+/-36.4 h in the clarithromycin group and 39.3+/-31.3 h in the azithromycin group . These differences were not statistically significant and both drugs were equally well-tolerated . Clarithromycin and azithromycin could be acceptable therapeutic alternatives to chloramphenicol and tetracyclines for children aged < or =8 years with Mediterranean spotted fever . Azithromycin, because it has a long half-life, offers the advantages of administration in a single daily dose and a shorter duration of therapy, which could increase compliance in children.

Hautarzt, 2001 Oct, 52(10 Pt 2), 947 - 9
{Confluent and reticulate papillomatosis . Successful therapy with azithromycin}; Weigl LB et al.; Confluent and reticulated papillomatosis is a fairly rare dermatosis of still unknown origin affecting mostly female young adults . The lesions are mainly localized in the midline of the trunk . Systemic treatment is the treatment of choice because the disease is resistant to topical therapy and recurrences are often seen . In recent publications retinoids and minocycline have been reported as the favourite therapeutic approaches . We successfully treated a 19-year-old-girl with azithromycin resulting in a complete healing of all skin lesions . The patient has been free of disease for five months . Based on our own case and data in literature, azithromycin is an effective, reasonable and safe therapeutic alternative.

Pharmacotherapy, 2001 Nov, 21(11), 1436 - 43
Possible interaction between intravenous azithromycin and oral cyclosporine; Page RL 2nd et al.; A 42-year-old man who had received a cadaveric kidney transplant 9 years earlier was admitted to the hospital with pneumonia . His oral cyclosporine dosage for the past 2 years was stabilized at 100 mg twice/day; his cyclosporine whole blood trough levels 15 days earlier and on the day he was admitted were both 178 ng/ml . The patient was treated with intravenous ceftriaxone and intravenous azithromycin and continued to receive the same dosage of oral cyclosporine . On hospital day 3, his cyclosporine trough level rose to 400 ng/ml and his dosage was reduced by 50% . Trough levels were 181 ng/ml and 175 ng/ml on hospital days 6 and 9, respectively On hospital day 9, the patient stopped receiving azithromycin . On hospital day 14, his cyclosporine trough level dropped to 76 ng/ml, and his cyclosporine dosage was increased back to 100 mg twice/day . The dosage produced trough levels consistent with those before he had been admitted . The patient was discharged on day 20, and a follow-up cyclosporine trough level determined 3 weeks later was 175 ng/ml . Administration of azithromycin may have caused the increased cyclosporine concentrations in this patient through p-glycoprotein inhibition and/or competition for biliary excretion . Azithromycin's interference may be inferred by the increase in cyclosporine levels after administration of this drug and the decrease in cyclosporine levels after its discontinuation-both consistent with the pharmacokinetic properties of cyclosporine . Ceftriaxone and acute-phase reactant activation during infection, however, also may have interfered with the patient's cyclosporine elimination . Azithromycin generally is considered unlikely to interact with cyclosporine . Nonetheless, practitioners should be aware of this possibility and should monitor cyclosporine levels closely, especially in critically ill patients who have other complications.

Int J Antimicrob Agents, 2001 Nov, 18(5), 419 - 25
Characteristics and mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes; Hand WL et al.; Azithromycin achieves prolonged, high tissue concentrations in spite of low serum levels and obviously must be active at tissue sites of infection to be effective . These unique features prompted us to evaluate the interactions of azithromycin and human polymorphonuclear leukocytes (PMN) . Uptake of radiolabeled antibiotic by PMN was determined by a velocity-gradient centrifugation technique and expressed as the ratio of cellular to extracellular drug concentration (C/E) . Azithromycin was massively accumulated by human PMN (C/E=387.2 at 2 h) . Uptake was not influenced by inhibitors of cellular metabolism, but phagocytosis slightly inhibited the entry of azithromycin into PMN . After removal of extracellular drug, the release (efflux) of azithromycin from PMN was extremely slow . Agents which neutralize lysosomal pH, preventing protonation and trapping of azithromycin, markedly increased antibiotic efflux . Active concentration and prolonged retention of azithromycin by phagocytic cells should allow delivery and subsequent release of accumulated drug at sites of infection.

Pacing Clin Electrophysiol, 2001 Oct, 24(10), 1572 - 4
QT prolongation associated with azithromycin/amiodarone combination; Samarendra P et al.; Administration of oral azithromycin, in addition to previously well-tolerated long-term amiodarone therapy, was associated with a marked prolongation of QT interval and increased QT dispersion, both substrates for life-threatening ventricular tachyarrhythmia and torsades de pointes . This is a report of QT prolongation and increased QT dispersion associated with the use of azithromycin . The report assumes an added significance, in view of widespread empirical use of this antibiotic for the treatment of lower respiratory infections and belief of its safety in patients with cardiac diseases . Based on the authors' experience, they would like to emphasize that the combination of azithromycin with other drugs known to prolong QT or causing torsades de pointes be used with caution until the question of the proarrhythmic effect of azithromycin is resolved by further studies.

Aliment Pharmacol Ther, 2001 Nov, 15(11), 1787 - 93
A randomized comparison of four omeprazole-based triple therapy regimens for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia; Laurent J et al.; BACKGROUND: Helicobacter pylori eradication rates in France after therapy with omeprazole, amoxicillin and clarithromycin are among the lowest in Europe . This study evaluated alternative eradication regimens . METHODS: Helicobacter pylori-positive patients (n=323) with non-ulcer dyspepsia were randomized to receive one of four 1-week regimens consisting of omeprazole, 20 mg b.d., plus either: amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d . (OAC); bacampicillin, 1200 mg b.d., and clarithromycin, 500 mg b.d . (OBC); clarithromycin, 250 mg b.d., and metronidazole, 500 mg b.d . (OCM); or amoxicillin, 1000 mg b.d, and azithromycin, 500 mg on day 1 and 250 mg on days 2-5 (OAAz) . Eradication was confirmed by urea breath test 4-6 weeks after treatment . Susceptibility testing was performed in the case of eradication failure . RESULTS: The eradication rate with OAAz was 38% (95% CI, 25.6-49.4) on intention-to-treat analysis, which was lower (P < 0.05) than with the other regimens {OCM, 61% (50.0-72.8); OBC, 65% (54.0-76.5); OAC, 72% (61.8-81.8)} . Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant . CONCLUSIONS: OAC remains the reference treatment for H . pylori eradication in France, although bacampicillin offers a useful alternative to amoxicillin . Susceptibility testing should be considered after unsuccessful eradication therapy.

Am J Health Syst Pharm, 2001 Oct 1, 58(19), 1819 - 23
Ultrashort regimen of lansoprazole-amoxicillin-azithromycin for eradicating Helicobacter pylori; Chahine C et al.; The efficacy and safety of two ultrashort azithromycin-containing regimens for Helicobacter pylori infection were studied . Patients positive for H . pylori infection were assigned to receive either a three-day drug regimen (group A) or a five-day regimen (group B) . In both groups, patients received lansoprazole 30 mg p.o . twice daily on day 1 and, on days 2 and 3, lansoprazole 30 mg p.o . twice daily, amoxicillin 1 g (of anhydrous amoxicillin) p.o . twice daily, and azithromycin 500 mg (of anhydrous azithromycin) p.o . twice daily . Group B patients received lansoprazole 30 mg p.o . twice daily and amoxicillin 1 g p.o . twice daily for two additional days . Gastric biopsy specimens were subjected to culture and susceptibility testing . A minimum of four weeks after the completion of therapy, the patients underwent a 14C-urea breath test to determine whether H . pylori had been eradicated . A total of 28 patients were enrolled (15 in group A and 13 in group B) . Treatment was well tolerated . H . pylori was eradicated in 4 (36%) of 11 patients in group A and 2 (22%) of 9 group B patients (26.6% and 15.4%, respectively, in intention-to-treat analysis) . None of the isolates of H . pylori showed resistance to amoxicillin or clarithromycin . Regimens consisting of lansoprazole plus two or four days of azithromycin and amoxicillin therapy eradicated H . pylori in 36% and 22% of patients, respectively.

Med Trop (Mars), 2001, 61(1), 48 - 50
Development of new drugs for chemoprophylaxis of malaria; Milhous WK; When U.S . troops first encountered drug resistant malaria during the Vietnam war, the United States Army responded by establishing a malaria drug research program . In 1988, the Walter Reed Army Institute of Research developed mefloquine (WR 149240) and halofantrine (WR 171669) . Actually, in association with SmithKline Beecham, the WRAIR is developing tafenoquine (WR 238605), an analog of primaquine, which is expected to be effective in both preventing and treating malaria in deployed military personnel . Final phase III studies leading to U.S . Food and Drug Administration approval are planned for 2000 . Applied research is also carried out with the association atovaquone-proguanil (Malarone) or with azithromycin, but also with primaquine, the associations paludrine-dapsone or lapudrine-dapsone, analogs of floxacrine (WR 243251), and a guanylhydrazone (WR 182393) . The future scientific directions must focus on basic and applied research for a better understanding of the modes of action and mechanisms of resistance to standard and developmental drugs . Using new techniques, the design and synthesis of new drugs would hopefully result in the development of drugs that circumvent the malaria parasites elusive mechanisms of drug resistance.

Rev Esp Quimioter, 2000 Dec, 13(4), 379 - 83
{Prospective, comparative study (1994-1998) of the influence of short-term prophylactic treatment with azithromycin on patients with advanced COPD}; Gomez J et al.; Despite the advances in therapy, chronic obstructive pulmonary disease (COPD) requires frequent hospital admissions due to acute exacerbations . We carried out a prospective randomized study of two groups of patients with COPD, one (n = 54) treated with azithromycin (500 mg/day) for three days every 21 days during the winter months, and a control group (n = 40) without treatment . A statistically significant reduction in the number of acute infectious episodes (187) and hospital admissions (22) was observed in the treated group versus the control group (249 and 45, respectively) . A short prophylactic treatment course with azithromycin is a good alternative in the management of patients with severe, advanced COPD, and could lead to an improvement in social and healthcare costs

Bull World Health Organ, 2001, 79(7), 632 - 40
Efficacy of oral azithromycin versus topical tetracycline in mass treatment of endemic trachoma; Fraser-Hurt N et al.; OBJECTIVE: To compare the impact of mass treatment with oral azithromycin and topical tetracycline on the prevalence of active trachoma . METHODS: A total of 1803 inhabitants from 106 households of eight Gambian villages were randomized, in pairs, to receive either three doses of azithromycin at weekly intervals, or daily topical tetracycline over 6 weeks . Ocular examinations were conducted before treatment, and 2, 6 and 12 months after treatment . FINDINGS: Prior to treatment, 16% of the study participants had active trachoma . Two months after treatment, the prevalence of trachoma was 4.6% and 5.1% in the azithromycin and the tetracycline groups, respectively (adjusted odds ratio (OR) = 1.09; 95% confidence interval (CI) = 0.53, 2.02) . Subsequently, the prevalence rose to 16% in the tetracycline group, while remaining at 7.7% in the azithromycin group (adjusted OR at 12 months = 0.52; 95% CI = 0.34, 0.80) . At 12 months post-treatment, there were fewer new prevalent cases in the azithromycin group, and trachoma resolution was significantly better for this group (adjusted OR = 2.02; 95% CI = 1.42, 3.50) . CONCLUSION: Oral azithromycin therefore appears to offer a means for controlling blinding trachoma . It is easy to administer and higher coverages may be possible than have been achieved hitherto.

Sex Transm Infect, 2001 Aug, 77(4), 271 - 5
Sexually transmitted infections and vaginal douching in a population of female sex workers in Nairobi, Kenya; Fonck K et al.; OBJECTIVE: To assess the association between vaginal douching and sexually transmitted infections (STI) among a group of female sex workers (FSWs) in Nairobi, Kenya . METHODS: This study was part of a randomised, placebo controlled trial of monthly prophylaxis with 1 g of azithromycin to prevent STIs and HIV infection in a cohort of Nairobi FSWs . Consenting women were administered a questionnaire and screened for STIs . RESULTS: The seroprevalence of HIV-1 among 543 FSWs screened was 30% . HIV infection was significantly associated with bacterial vaginosis (BV), trichomoniasis, gonorrhoea, and the presence of a genital ulcer . Regular douching was reported by 72% of the women, of whom the majority inserted fluids in the vagina, generally after each sexual intercourse . Water with soap was the fluid most often used (81%), followed by salty water (18%), water alone (9%), and a commercial antiseptic (5%) . Douching in general and douching with soap and water were significantly associated with bacterial vaginosis (p = 0.05 and p = 0.04 respectively) . There was a significant trend for increased frequency of douching and higher prevalence of BV . There was no direct relation observed between douching and risk for HIV infection or other STIs . CONCLUSION: The widespread habit of douching among African female sex workers was confirmed . The association between vaginal douching and BV is of concern, given the increased risk of HIV infection with BV, which has now been shown in several studies . It is unclear why we could not demonstrate a direct association between douching and HIV infection . Further research is required to better understand the complex relation between douching, risk for bacterial vaginosis, and risk for HIV and other STIs.

Southeast Asian J Trop Med Public Health, 2000 Dec, 31(4), 801 - 7
A randomized clinical trial of combinations of artesunate and azithromycin for treatment of uncomplicated Plasmodium falciparum malaria in Thailand; Krudsood S et al.; Recently, a combination of artesunate and mefloquine has proved effective, although is contraindicated in early pregnancy and young children . Azithromycin, a widely used antibiotic and has antimalarial effects, replace mefloquine as a new alternative antimalarial regimen . Two hundred and two uncomplicated falciparum malaria patients were randomly assigned to 1 of 3 regimens . Patients in group I (n = 68) received artesunate 200 mg once daily for 3 days, group II (n = 67) received artesunate 200 mg together with mefloquine 10 mg/kg on the first 2 days and artesunate 200 mg together with mefloquine 5 mg/kg on the third day, and group III (n = 67) received artesunate 200 mg together with azithromycin 50 mg once daily for 3 days . The 28 day cure rates were 44, 98 and 56%, respectively . The median time to recrudescence was significantly longer in group III . In conclusion, a combination of artesunate and azithromycin might be useful in treating children in whom bacterial and malarial infections may be concomitant . However, further work is required in order to enhance its clinical efficacy.

Am J Obstet Gynecol, 2001 Jun, 184(7), 1352 - 4; discussion 1354-6
A randomized controlled trial comparing amoxicillin and azithromycin for the treatment of Chlamydia trachomatis in pregnancy; Jacobson GF et al.; OBJECTIVE: Our goal was to compare the efficacy of azithromycin with that of amoxicillin for the treatment of Chlamydia trachomatis infection during pregnancy . STUDY DESIGN: A randomized controlled trial of pregnant women with cervical C trachomatis infection receiving care at two inner-city, university-based prenatal clinics . Pregnant women were randomly assigned to receive either oral amoxicillin, 500 mg, three times daily for 7 days, or oral azithromycin, 1 g, in a single dose . Partners were referred for treatment . Tests of cure were scheduled 4 weeks after initiation of treatment . Statistical analysis was performed by using the Student t test and chi2 analysis . RESULTS: One hundred twenty-nine pregnant women were enrolled, and 110 (85%) completed the protocol . There was similar treatment efficacy between amoxicillin and azithromycin (58% vs 64%, respectively,P =.56) . In the amoxicillin group 3 women (5.5%) were intolerant, compared with 6 (10.9%) in the azithromycin group (P =.31) . CONCLUSION: Amoxicillin and azithromycin are equally efficacious in the treatment of cervical C trachomatis during pregnancy.

Rev Soc Bras Med Trop, 2001 Mar-Apr, 34(2), 203 - 5
{Experimental infection in mice by Plasmodium berghei: an evidence of antiparasitic action of azithromycin}; Gakiya E et al.; Infections of Plasmodium berghei in mice was stopped by azithromycin which was administered orally in dosages of 100mg/kg, for 28 days . This antibiotic was given since the same day that the animals were infected . The outcome suggests the necessity of more investigations on this antiparasitic activity.

Am Fam Physician, 2001 May 15, 63(10), 1969 - 74
When to suspect and how to monitor babesiosis; Mylonakis E; In the past decade, cases of babesiosis in humans have been reported with increasing frequency, especially in the northeastern United States . Babesia microti (in the United States) and bovine strains (in Europe) cause most infections in humans . Most cases are tick-borne, although cases of transfusion-associated and transplacental/perinatal transmission have also been reported . Factors associated with more severe disease include advanced age, previous splenectomy and immunodeficient states . Symptoms include high fever, chills, diaphoresis, weakness, anorexia and headache . Later in the course of the illness, the patient may develop jaundice . Congestive heart failure, renal failure and acute respiratory distress syndrome are the most common complications . Therapy using the combination of quinine sulfate and clindamycin was the most commonly used treatment; however, atovaquone suspension plus azithromycin was recently reported an equally effective and less toxic therapy . Exchange transfusion, together with antibabesial chemotherapy, may be necessary in critically ill patients.

Treatmentupdate, 1998 Jul, 10(5), 3 - 4
Azithro once a week for MAC; NTZ for cryptosporidiosis: larger expanded access; buyers' club/FDA conflict . Food and Drug Administration; AIDS: The experimental drug nitazoxanide (NTZ) appears effective in treating cryptosporidiosis, which causes severe diarrhea and death in many HIV-positive patients . The PWA Health Group, a buyers' club in New York, has been trying to make the drug available to AIDS patients, but has had a shipment seized by U.S . Customs . The PWA Health Group alleges that this action was politically motivated . Unimed Pharmaceuticals plans to make the drug available in an open label trial, but people with intestinal CMV, MAC, or KS will be excluded, along with those taking azithromycin or clarithromycin . Activists accuse Unimed of withholding the drug from patients in need by refusing to make it available on a compassionate use basis .

PI Perspect, 1996 Nov, (No 20), 16 - 7
MAC management; Opportunistic infections update; AIDS: An update is presented on some of the treatment developments for opportunistic infections (OIs) associated with HIV infection . Treatments discussed include clarithromycin and clofazimine for treatment of mycobacterium avium complex (MAC), azithromycin for prevention of MAC, fluconazole for prevention of fungal infections, MSL109 for treatment of cytomegalovirus retinitis, and two new approaches for the treatment of Kaposi's sarcoma . Azithromycin's positive role in preventing PCP provides evidence of new directions in multiple OI prevention approaches .

AIDS Alert . 1996 Oct;11(10):120.
Azithromycin effective in preventing MAC; Opportunistic infections in Vancouver; AIDS: Participants at the XI International Conference on AIDS in Vancouver appeared impressed by the improvements being made in the diagnosis, treatment, and prophylaxis of AIDS-related opportunistic infections . Improvements in the following areas are discussed: cytomegalovirus infection prophylaxis and maintenance with oral ganciclovir, prophylactic effects of azithromycin against Mycobacterium avium complex infection and its potential for preventing Pneumocystis carinii pneumonia, and the use of doxil versus bleomycin plus vincristine in treating Kaposi's sarcoma . Developments in the use of cyclodextrin (itraconazole) for treating oral candidiasis showed it may be a more suitable option than fluconazole given fluconazole's high price, drug interactions, and potential to cause resistance .

AIDS Alert, 1996 Sep, 11(9), 101 - 3
Antivirals key to MAC prevention regimen; MAC prophylaxis revisited; AIDS: Mycobacterium avium complex (MAC) infection occurs in 18 to 40 percent of people with AIDS, and most commonly in those with CD4 counts under 50 . MAC is a difficult infection to diagnose, as its symptoms mimic many other infections and tumors . MAC infections can occur in the respiratory system or gastrointestinal tract, and the infection may spread through the bloodstream . Clinical trials for MAC prophylaxis include clarithromycin, rifabutin, or a combination of both . The individual drugs and the combination both may cause side effects that would require discontinuation of treatment . Azithromycin administered weekly, compared to rifabutin, or a combination of both, also had some significant adverse effects . The azithromycin/rifabutin combination resulted in the lowest rate of MAC breakthrough . Drug resistance and cross resistance to these drugs exist .

AIDS Alert, 1996 Aug, 11(8), 94 - 5
Old drug approved for MAC prevention; Progress report: prophylaxis and therapy for MAC; AIDS: Study efforts are showing progress in the prevention and therapy of Mycobacterium avium complex (MAC) infection . A review of recent study developments highlights clinical findings on prophylactic use of rifabutin, clarithromycin, and azithromycin, used both as monotherapies and as combination therapies . Three tables highlight study results from MAC prophylaxis studies, MAC treatment studies, and candidate regimens for MAC prophylaxis in AIDS . Treatment of disseminated MAC is also addressed . The combination of clarithromycin and clofazimine should not be used as initial therapy . Clofazimine's role in initial therapy is uncertain, and combinations of clarithromycin and ethambutol, with or without rifabutin, appear to be the best current treatment options .

Notes Undergr . 1996 Apr;(no 32):6.
Hold the big MAC; Young A; AIDS: The Retrovirus Conference provided information on two studies that examine the prevention of Mycobacterium avium complex (MAC) . People with an active infection run fevers, lose weight, and have no appetite . Rifabutin is currently the only drug with Food and Drug Administration (FDA) approval for the prevention of MAC . It was found to be most effective in combination with azithromycin, but because the two drugs are chemically similar, resistance to both is a threat . Thirty percent of the people taking clarithromycin developed resistance . A related antibiotic, roxithromycin, works both as a prevention for MAC and as a treatment for cryptosporidiosis .

Notes Undergr . 1996 Jan;(no 31):4.
Speaking of the runs.
What's in the water?
AIDS: Cryptosporidiosis is a protozoal infection that can come from water, or be spread from person to person . Individual protozoa are very resistant to the environment and disinfectants . How cryptosporidium causes infection is unknown, but it is known that large adult animals that commonly become infected do not get sick; small animals such as mice do not get symptomatic infection so there are no disease models to study in the lab . It is not known how many people are carrying the organism, however, in people with AIDS, 10 to 20 percent appear to be infected and testing for cryptosporidiosis is nearly impossible . It is also unknown what the immune system responds to in order to make antibodies to cryptosporidium . There have been outbreaks of cryptosporidiosis in the water supply of cities with public water filtering systems, such as Milwaukee in 1993 . Boiling water for at least 1 minute kills the cryptosporidial oocysts if any exist, and while some bottled water claims to be cryptosporidium free, no data exist to prove it . No really good treatment exists for cryptosporidiosis, but Azithromycin is better absorbed than other drugs studied; it can be obtained directly from Pfizer through their compassionate use program . A new study using IGX is being conducted using chicken immunoglobulins which fight cryptosporidiosis . Participants drink irradiated eggnog five times per day . Participants must be HIV positive, have cryptosporidiosis, and not have other intestinal infection . The Network can be contacted for more information on this study .

Am J Vet Res, 2001 May, 62(5), 687 - 91
Inoculation of two genotypes of Hemobartonella felis (California and Ohio variants) to induce infection in cats and the response to treatment with azithromycin; Westfall DS et al.; OBJECTIVES: To describe clinical and laboratory findings associated with cats experimentally infected by inoculation with the 2 recognized genotypes of Hemobartonella felis (small variant, Hfsm; large variant, Hflg) and to determine the response of cats to treatment with azithromycin . ANIMALS: 18 young adult domestic shorthair cats of both sexes . PROCEDURES: Cats were inoculated with H felis and monitored weekly, using CBC counts and a polymerase chain reaction (PCR) designed to detect both genetic variants of H felis . Beginning 26 days after inoculation, 11 cats were administered azithromycin (15 mg/kg of body weight, PO, q 12 h, for 7 days) . RESULTS: Inoculation resulted in coinfection with Hflg and Hfsm, and both variants were detected by PCR . Clinical abnormalities and anemia were most severe in Hflg- and dual-infected cats . Results of PCR and CBC were positive for H felis in 112/112 (100%) and 42/112 (37.5%), respectively, samples collected after inoculation . Administration of azithromycin had little effect on clinical variables, including anemia . All cats, regardless of treatment with azithromycin, had positive results for the PCR at the end of the study period . CONCLUSIONS AND CLINICAL RELEVANCE: In these cats, Hflg was more pathogenic than Hfsm, and coinfection with both variants was detected . Results of the PCR were superior to results of CBC for detecting infection with H felis . Azithromycin administered at the dose and duration reported here was not efficacious for the treatment of cats with hemobartonellosis.

Clin Infect Dis, 2001 Jun 1, 32(11), 1562 - 6 Epub 2001 Apr 30.
Persistently positive culture results in a patient with community-acquired pneumonia due to Legionella pneumophila; Tan JS et al.; We describe a patient with community-acquired pneumonia due to Legionella pneumophila serogroup 6 . This patient was found to have bronchoalveolar carcinoma of the lung by means of cytologic testing in 1 of 2 bronchoalveolar lavage samples, but no lesions were visible on bronchoscopy . Despite intravenous administration of azithromycin to the patient, repeat culture and polymerase chain reaction showed persistence of Legionella; the isolates remained susceptible to azithromycin . The patient did not respond to 14 doses of daily intravenously administered azithromycin . The poor outcome may have been partially due to the suspected underlying lung malignancy, as shown by cytologic examination, and by a delay in seeking medical attention.

Clin Infect Dis, 2001 Jun 1, 32(11), 1547 - 53 Epub 2001 May 04.
Azithromycin-containing regimens for treatment of Mycobacterium avium complex lung disease; Griffith DE et al.; Ninety-two patients were assessable in 3 consecutive, open, noncomparative, prospective, controlled, single-center trials of the use of multidrug regimens that contain azithromycin for treating pulmonary Mycobacterium avium complex (MAC) disease . Azithromycin was provided at a dose of 300-600 mg per day with oral companion drugs administered daily (regimen A, 29 patients); 600 mg 3 times weekly (t.i.w.), with oral companion drugs administered daily (regimen B, 20 patients); and 600 mg (t.i.w.), with oral companion drugs administered t.i.w . (regimen C, 43 patients) . All regimens included rifabutin (or rifampin) and ethambutol as companion drugs as well as initial streptomycin . Treatment success was defined as 12 months of negative cultures while on therapy . Treatment failure was defined as sputum culture positivity after at least 6 months of therapy . Of the patients in each regimen who reached study end points, 17 of 29 (59%) were in regimen A, 11 of 20 (55%) were in regimen B, and 28 of 43 (65%) were in regimen C met the treatment success criterion . There were no statistically significant differences in outcome between the 3 regimens . These studies demonstrate the effectiveness of daily and t.i.w . regimens containing azithromycin for treatment of MAC lung disease.

Clin Ther, 2001 Mar, 23(3), 451 - 66
Pharmacokinetic and safety profile of desloratadine and fexofenadine when coadministered with azithromycin: a randomized, placebo-controlled, parallel-group study; Gupta S et al.; BACKGROUND: Significant cardiac toxicity has been associated with some older antihistamines (eg, terfenadine and astemizole) when their plasma concentrations are increased . There is thus a need for a thorough assessment of the cardiac safety of newer antihistamine compounds . OBJECTIVE: This study was undertaken to assess the effects of coadministration of desloratadine or fexofenadine with azithromycin on pharmacokinetic parameters, tolerability, and electrocardiographic (ECG) findings . METHODS: Healthy volunteers aged 19 to 46 years participated in this randomized, placebo-controlled, parallel-group, third-party-blind, multiple-dose study . Subjects received desloratadine 5 mg once daily, fexofenadine 60 mg twice daily, or placebo for 7 days . An azithromycin loading dose (500 mg) followed by azithromycin 250 mg once daily for 4 days was administered concomitantly starting on day 3 . Group 1 received desloratadine and azithromycin, group 2 received desloratadine and placebo, group 3 received placebo and azithromycin, group 4 received fexofenadine and azithromycin, and group 5 received fexofenadine and placebo . RESULTS: The results of the pharmacokinetic analysis revealed little change in mean maximum concentration (Cmax) and area under the concentration-time curve (AUC) values for desloratadine with concomitant administration of azithromycin: Cmax ratio, 115% (90% CI, 92-144); AUC, ratio 105% (90% CI, 82-134) . The corresponding ratios for 3-hydroxydesloratadine were 115% (90% CI, 98-136) and 104% (90% CI, 88-122), respectively . A substantial increase was observed in mean Cmax and AUC values for fexofenadine when administered with azithromycin: Cmax, ratio, 169% (90% CI, 120-237); AUC ratio, 167% (90% CI, 122-229) . Compared with the group receiving desloratadine and azithromycin, subjects receiving fexofenadine and azithromycin also displayed greater variability in pharmacokinetic parameters for the antihistamine . Mean Cmax and AUC values of azithromycin were slightly higher when administered with desloratadine (Cmax ratio, 131% {90% CI, 92-187}; AUC ratio, 112% {90% CI, 83-153}) but were lower when given in combination with fexofenadine (Cmax ratio, 87% {90% CI, 61-124}; AUC ratio, 88% {90% CI, 65-1201) . The most common adverse event for all regimens was headache, reported in 20 (22%) subjects . All combinations of desloratadine or fexofenadine with and without azithromycin were well tolerated, and no statistically significant changes in PR, QT, or QT, interval, QRS complex, or ventricular rate were observed . CONCLUSIONS: Small increases (<15%) in mean pharmacokinetics of desloratadine were observed with coadministration of azithromycin . By contrast, peak fexofenadine concentrations were increased by 69% and the AUC was increased by 67% in the presence of the azalide antibiotic . Based on the reported adverse-events profile and the absence of changes in ECG parameters, the combination of desloratadine and azithromycin was well tolerated . This study suggests that desloratadine has a more favorable drug-interaction potential than does fexofenadine.

AIDS, 2001 Mar 30, 15(5), 583 - 9
Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS; Jacobson JM et al.; OBJECTIVE: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS . DESIGN: A phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine . SETTING: Eight clinical sites in the United States . PATIENTS: Forty-two adult HIV-infected patients with confirmed or presumed acute TE . METHODS: Patients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy . The induction period was 6 weeks followed by 24 weeks of maintenance therapy . MAIN OUTCOME MEASURES: Patient response was evaluated clinically and radiologically . RESULTS: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period . Ten experienced disease progression . Of the 15 patients who received maintenance therapy, seven (47%) relapsed . Six patients discontinued treatment during the induction period as a result of reversible toxicities . Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose . CONCLUSION: The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate . The combination was safe, but low-grade adverse events were common.

Antimicrob Agents Chemother, 2001 May, 45(5), 1572 - 7
Tolerance and pharmacokinetic interactions of rifabutin and azithromycin; Hafner R et al.; This multicenter study evaluated the tolerance and potential pharmacokinetic interactions between azithromycin and rifabutin in volunteers with or without human immunodeficiency virus infection . Daily dosing with the combination of azithromycin and rifabutin was poorly tolerated, primarily because of gastrointestinal symptoms and neutropenia . No significant pharmacokinetic interactions were found between these drugs.

Jpn J Antibiot, 2001 Feb, 54 Suppl A, 70 - 6
Azithromycin: a new 15-membered macrolide; Treadway G; Azithromycin is the sole member of the macrolide sub-class, the azalides . Due to its altered chemical structure, azithromycin is characterized by a broader spectrum of activity, lower incidence of adverse events and drug interactions and a pharmacokinetic profile, that is in contrast to existing macrolides . Because of its high and prolonged cellular and tissue concentrations, patients are able to complete a course of azithromycin within a shorter timeframe as compared to other antibiotics . Azithromycin is widely used in the treatment of adult and pediatric respiratory tract infections . Continued research into azithromycin's utility has resulted in indication development for several devastating infections such as trachoma . Large-scale studies of its activity against Chlamydia pneumoniae related atherosclerosis are underway.

J Heart Lung Transplant, 2001 Apr, 20(4), 486 - 9
Mycobacterium marinum infection in a lung transplant recipient; Torres F et al.; We report a case of Mycobacterium marinum infection in a lung transplant recipient who presented with nodules on the hand and forearm following exposure to fish-tank water of a superficial hand burn . Skin biopsy revealed granulomatous inflammation and fibrosis . Tissue culture grew Mycobacterium marinum . The patient underwent surgical excision of the lesions and treatment with ethambutol and azithromycin for 12 months and experienced complete resolution of the infection . Transplant recipients who receive immunosuppressive therapy are at increased risk for opportunistic infections . For a patient with nodular lesions on the extremities, exposure to fish, fish-tank water, or swimming should suggest infection with Mycobacterium marinum.

Bull World Health Organ, 2001, 79(3), 201 - 7 Epub 2003 Jul 07.
Cost-effectiveness of trachoma control measures: comparing targeted household treatment and mass treatment of children; Frick KD et al.; OBJECTIVE: The present study compares the cost-effectiveness of targeted household treatment and mass treatment of children in the most westerly part of Nepal . METHODS: Effectiveness was measured as the percentage point change in the prevalence of trachoma . Resource measures included personnel time required for treatment, transportation, the time that study subjects had to wait to receive treatment, and the quantity of azithromycin used . The costs of the programme were calculated from the perspectives of the public health programme sponsor, the study subjects, and the society as a whole . FINDINGS: Previous studies have indicated no statistically significant differences in effectiveness, and the present work showed no significant differences in total personnel and transportation costs per child aged 1-10 years, the total time that adults spent waiting, or the quantity of azithromycin per child . However, the mass treatment of children was slightly more effective and used less of each resource per child aged 1-10 years than the targeted treatment of households . CONCLUSION: From all perspectives, the mass treatment of children is at least as effective and no more expensive than targeted household treatment, notwithstanding the absence of statistically significant differences . Less expensive targeting methods are required in order to make targeted household treatment more cost-effective.

Clin Infect Dis, 2001 Apr 15, 32(8), 1117 - 25 Epub 2001 Mar 26.
Severe babesiosis in Long Island: review of 34 cases and their complications; Hatcher JC et al.; Thirty-four consecutive patients were hospitalized with diagnosis of severe Babesia infection over the course of 13 years . The average time from onset of symptoms to diagnosis was 15 days . When compared with uninfected febrile control patients, affected patients complained significantly more often of malaise, arthralgias and myalgias, and shortness of breath (P<.05), and they more often had thrombocytopenia and abnormal liver function (P<.05) . Forty-one percent of patients with Babesia developed complications such as acute respiratory failure, disseminated intravascular coagulation, congestive heart failure, and renal failure . Analysis of data revealed that complicated babesiosis was more commonly associated with the presence of severe anemia (hemoglobin level <10 g/dL; P=.01) and higher parasitemia levels (>10%; P=.08) . Patients were treated with a combination of drugs that included clindamycin, quinine, atovaquone, or azithromycin . Despite treatment, parasitemia persisted for an average of 8.5 days (range, 3--21 days) . Exchange transfusion was performed for 7 patients, and it effectively reduced the high levels of parasitemia . Three patients died . Improved outcomes may result with prompt recognition and treatment of babesiosis.

J Dermatol, 2001 Jan, 28(1), 1 - 4
Azithromycin monthly pulse vs daily doxycycline in the treatment of acne vulgaris; Parsad D et al.; Acne vulgaris is a common skin disease seen primarily in adolescent and young adults . As the treatment involves long term therapy with antibiotics, an agent with a long half life can be very useful in increasing the compliance . To evaluate the role of a monthly dose of azithromycin and compare it with daily doxycycline, we conducted this randomized comparative study . Sixty patients with moderate to severe acne were randomly assigned to two treatment groups, A & B . Patients in group A received 100 mg doxycycline daily in addition to topical 0.05% tretinoin cream, whereas patients in group B were given 500 mg azithromycin once a day for four days per month along with 0.05% topical tretinoin for a total of 12 weeks . Of the 60 patients, 22 in group A and 28 in group B were evaluated . The monthly dose of azithromycin was found to be as effective as daily doxycycline on a pure protocol basis and statistically significantly better than doxycycline by intention to treat analysis.

J Assoc Physicians India, 2000 Jul, 48(7), 746 - 7
Bleeding complication during coumarin therapy due to amiodarone and azithromycin; Bharat V et al.; A patient with mechanical heart valves developed bleeding, after the introduction of amiodarone and azithromycin . Though the anticoagulant effect could be neutralized, the patient succumbed to heart failure . Any new drug prescribed to patients on anticoagulant must be assessed for its potential for interaction and warrants frequent prothrombin time testing.

J Antimicrob Chemother, 2001 Apr, 47(4), 441 - 6
Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections; Ferwerda A et al.; To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study . The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI . Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days . Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav . The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav . This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55) . Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group . This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints . A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses) . The azithromycin group had fewer adverse events . We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI . An additional advantage is the easy administration and short duration of therapy.

J Antimicrob Chemother, 2001 Apr, 47(4), 417 - 20
Treatment alternatives for Mycobacterium kansasii; Graybill JR et al.; Mycobacterium kansasii was administered intravenously to congenitally athymic (nude) mice . Beginning 1 week later, rifapentine, azithromycin, ethambutol or combined therapy was initiated orally . All three drugs were highly active individually . Although there was no evidence of antagonism, combined therapy was not more effective than either component used alone.

Int J Pediatr Otorhinolaryngol, 2001 Apr 6, 58(1), 47 - 51
Comparison of amoxicillin and azithromycin in the prevention of recurrent acute otitis media; De Diego JI et al.; OBJECTIVE: To compare the outcome of patients with recurrent acute otitis media (AOM) treated either with amoxicillin or with azithromycin . METHODS: This prospective, controlled, and randomized study, compares the outcome of 71 patients with recurrent AOM treated with azithromycin (31 patients) or amoxicillin (40 patients) for the prevention of AOM . azithromycin was given at a dose of 10 mg/kg once a week, whereas amoxicillin was administered daily as a single intake of one third of the therapeutic dosage (20 mg/kg per day) . All treatments were prescribed for 3 months . Both groups were homogeneous with regard to the currently accepted predisposing factors of recurrent AOM . Mean age of children was 35.3 months, and average follow-up was 11.5 months . The treatment was considered effective when the number of episodes of AOM dropped to less than 50% after the prophylaxis . RESULTS: Patients in the azithromycin group had a clinical response to prophylaxis (80.6%) comparable to those treated with amoxicillin (89.5%) (P=0.300) . The incidence of adverse effects was similar in both groups . CONCLUSION: According to these results, a prophylaxis with azithromycin is as useful as amoxicillin to prevent recurrent AOM.

J Infect Dis, 2001 Mar 15, 183(6), 907 - 12 Epub 2001 Feb 21.
Azithromycin prophylaxis during a hospital outbreak of Mycoplasma pneumoniae pneumonia; Hyde TB et al.; Outbreaks of Mycoplasma pneumoniae (MP) in closed communities can have a high attack rate and can last several months . Azithromycin chemoprophylaxis has not been evaluated as a means of limiting transmission . This randomized, double-blinded placebo-controlled trial of azithromycin was conducted among asymptomatic hospital employees during an MP outbreak . Oropharyngeal swabs were obtained for detection of MP by polymerase chain reaction, and questionnaires were administered to assess clinical illness . Of the 147 employees who were enrolled, 73 received azithromycin and 74 received placebo . Carriage was similar within and between groups at weeks 1 and 6 (9.6% vs . 6.7% and 10.3% vs . 13.2%, respectively) . Four episodes of clinically significant respiratory illness occurred in the azithromycin group versus 16 episodes in the placebo group (protective efficacy, 75%; 95% confidence interval, 28%-91%) . Use of azithromycin prophylaxis in asymptomatic persons during an MP outbreak in a closed setting may be of value in reducing clinical illness.

Panminerva Med, 2000 Sep, 42(3), 197 - 9
Azithromycin in the treatment of Plasmodium falciparum gametocytes . Preliminary observation; Bregani ER et al.; BACKGROUND: Treatment of malaria represents a problem as antimalarial drugs are relatively few, and because of the increasing widespread resistance of Plasmodium falciparum to most of these drugs . A partial efficacy of azithromycin against Pl . falciparum hepatic stage and against trophozoytes in the erythrocytic stages of the disease has been demonstrated . No data concerning the activity against gametocytes are available, and primaquine stands as the only therapy against Pl . falciparum gametocytes . Primaquine causes haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, so primaquine therapy is usually avoided . A better tolerated therapy against gametocytes would be useful to reduce malaria transmission . We present the results of a study concerning the efficacy of azithromycin in the treatment of P . falciparum gametocytes . METHODS: A prospective study was performed: 4 patients with Pl . falciparum gametocytes (3 children, 1 adult) were treated with azithromycin for concomitant bacterial infections; in the meantime two children with gametocytes were taken as control . Azithromycin was administered as recommended . RESULTS: Gametocytes were detectable in children thick blood smears after 8, 5 and 6 days respectively after the beginning of azithromycin therapy, while they were undetectable in the adult thick blood smear 5 days after the beginning of the therapy . The gametocytes spontaneously disappeared in the two controls 4 to 6 days after the beginning of observation . CONCLUSIONS: These data suggest that azithromycin seems ineffective against Pl . falciparum gametocytes . Further studies are needed in order to determine whether azithromycin treated gametocytes are infective to mosquitoes or not, and to confirm this first observation.

Bull World Health Organ, 2001, 79(1), 8 - 14 Epub 2003 Nov 05.
Pilot study of the use of community volunteers to distribute azithromycin for trachoma control in Ghana; Solomon AW et al.; OBJECTIVE: To assess the skills of community health volunteers in diagnosing active trachoma and distributing azithromycin in the Northern Region of Ghana . METHODS: Six community health volunteers from Daboya were trained to diagnose trachoma and to treat the disease using azithromycin . They were also informed of the drug's possible side-effects . Under supervision, each volunteer then examined, and if necessary treated, 15 households . The dose of azithromycin was determined by weight; height was also measured . Tablets were given in preference to suspension when possible . RESULTS: The volunteers' diagnostic sensitivity for active trachoma was 63%; their specificity was 96% . At the household level, their "decision to treat" was correct in 83% of households . In 344 treatment episodes, volunteers planned a dose of azithromycin outside the range 15-30 mg/kg on only seven occasions (2.0% of all planned treatments) . The volunteers' drug management skills were good, the response of the community was excellent, and adverse reactions were infrequent . Diagnosis of active trachoma, record-keeping skills, and knowledge of side-effects were found to need greater emphasis in any future education programme . Most people aged four years or older were able to swallow tablets . For those taking tablets, the correlation between the data gathered for height and weight shows that calculating azithromycin doses by height is a valid alternative to calculating it by weight . CONCLUSION: Trained community health volunteers have a potential role in identifying active trachoma and distributing azithromycin . To simplify training and logistics, it may be better to base dosage schedules on height rather than weight for those taking tablets, which included most people aged four years or more in the population studied.

Z Orthop Ihre Grenzgeb, 2000 Nov-Dec, 138(6), 530 - 9
{Chronic recurrent multifocal osteomyelitis}; Schilling F et al.; The aim of this paper is to give a detailed description of the so-called "chronic recurrent multifocal osteomyelitis" (CRMO) . The clinical, radiological and histopathological results of an analysis of 29 cases (15 children/adolescents and 14 adults) are presented and correlated to current data from the literature . We could delinate the following points: 1 . CRMO is a systemic aseptic inflammation of the bone marrow (Osteitis), it can occur polytopically and association with pustulous dermatologic symptoms is possible . 2 . It is not a rare disease 3 . Osteomyelitis is probably "reactive" and a plasma-cell sclerotic process with ist own characteristic histologic three-phase course . 4 . We could observe 5 specific types of localization which can be documented by X-ray or bone scan . 5 . Accompanying arthritis os often present, especially "sympathetic coxitis" . 6 . The use of drugs in treatment of CRMO (i.e . azithromycin, calcitonin, and bisphosphonates) is discussed . In conclusion we want to point out, that 1 . 99mTC bone scan should always be performed when there is suspicion for CRMO to reveal the pattern of affection, 2 . the rheumatologist and dermatologist should be contacted, 3 . operation is normally not necessary for treatment of the mostly self-limitin disease, and 4 . the term "SAPHO syndrome" should be avoided, further differentiation of the diagnosis is necessary.

Int J Antimicrob Agents, 2000 Sep, 16(1), 37 - 43
Comparison of azithromycin leukocyte disposition in healthy volunteers and volunteers with AIDS; McNabb J et al.; Azithromycin, has been proved to be effective in the treatment and prophylaxis of a wide variety of infections . While the penetration of azithromycin into a number of types of mammalian cells has been well characterized, the influence of HIV infection on the intracellular disposition of this agent has not been studied . We therefore studied the disposition of azithromycin in polymorphonuclear (PMN) and mononuclear (MONO) leukocytes from six healthy volunteers and six volunteers with AIDS . After oral administration of a single 1200-mg dose of azithromycin (two 600-mg tablets), blood samples were collected over 6 days and intracellular azithromycin concentrations in MONOs and PMNs were measured . Analysis of the intracellular pharmacokinetics revealed an apparent difference in the MONO and PMN profile; this profile was similar for both groups . Intracellular concentrations of azithromycin remained high throughout the study period . Furthermore, no statistically significant differences in the intracellular area under the curve (11309+/-2543 vs . 16650+/-6254 for PMN; 14180+/-3802 vs . 21211+/-10001 for MONO) were observed between the healthy and AIDS populations, respectively . Our data confirm the extensive uptake of azithromycin by white blood cells both in healthy volunteers and in AIDS patients.

Clin Infect Dis, 2001 Feb 1, 32(3), 506 - 9 Epub 2001 Jan 24.
Azithromycin and gentamicin therapy for the treatment of humans with brucellosis; Solera J et al.; Ten patients with brucellosis were treated with azithromycin and gentamicin to assess the treatment's safety and efficacy . Seven patients had an excellent therapeutic response at the end of therapy; however, relapse was noted in 3 . When relapse was considered in combination with an initial lack of efficacy, 5 patients (50%; 95% confidence interval, 18.7%-81.3%) did not respond to therapy; these results do not favor the use of azithromycin to treat brucellosis in humans.

J Antimicrob Chemother, 2001 Jan, 47(1), 97 - 9
Activity of buforin II alone and in combination with azithromycin and minocycline against Cryptosporidium parvum in cell culture; Giacometti A et al.; The in vitro anti-cryptosporidial activity of buforin II alone and in combination with azithromycin and minocycline was investigated . Buforin II showed moderate activity, which increased with increasing concentration to 55.7% suppression of growth at 20 microM . Moreover, its activity was enhanced when it was combined with either azithromycin or minocycline with >90% parasite reduction at the highest concentration tested . Buforin II may be active in inhibiting Cryptosporidium parvum growth in vitro upon combination with either azithromycin or minocycline.

J Antimicrob Chemother, 2001 Jan, 47(1), 61 - 6
Serum and WBC pharmacokinetics of 1500 mg of azithromycin when given either as a single dose or over a 3 day period in healthy volunteers; Amsden GW et al.; Owing to azithromycin's prolonged half-life, shorter and shorter dosage regimens are being studied for treatment of respiratory tract infections . Previous studies have concluded that the 3 and 5 day (1.5 g total) regimens not only provide at least equal serum and WBC exposures but also equal efficacy rates . An earlier clinical study using the entire 1.5 g dose at once or the current 3 day regimen in patients with atypical pneumonia noted equal efficacy . Similar trials are currently underway in both adult and paediatric populations . The goal of the present study was to investigate whether there were equal serum and WBC exposures when azithromycin was dosed as the current 3 day regimen or as a single large dose . Equal exposures would help validate future clinical trials of single dose regimens . Twelve healthy volunteers received both azithromycin regimens (1.5 g single dose and 500 mg/day for 3 days) in random order . Serum and WBC samples were collected at baseline and repeatedly for 10 days following the first dose of each regimen . Serum samples were assayed via HPLC (CV% < 10) and WBC samples via liquid chromatography/mass spectrometry (CV% < 10) . Data were modelled using noncompartmental methods . Statistics were via ANOVA with significance defined as P < 0.05 . All subjects completed both regimens with minimal incidence of adverse effects . Serum data {mean (range)} demonstrated no significant difference in exposure between the two regimens {single 13.1 (3.02-20.6) mg x h/L versus 3 day 11.2 (2.98-24.5) mg x h/L: P = 0.12}, although it favoured the shorter regimen . WBC results demonstrated much higher exposures than seen with serum, but no significant difference between the two regimens was identified . These results suggest that a single oral 1.5 g regimen of azithromycin for respiratory tract infections should provide exposure at least equal to currently approved treatment regimens.

Pediatr Infect Dis J, 2000 Dec, 19(12 Suppl), S174 - 80
Comparison of the palatability of the oral suspension of cefdinir vs . amoxicillin/clavulanate potassium, cefprozil and azithromycin in pediatric patients; Powers JL et al.; BACKGROUND: Patient adherence to therapeutic regimens is extremely important to successful treatment of acute otitis media . Among pediatric patients medication palatability, particularly that of oral suspensions, is essential for patient acceptance, therapeutic compliance and successful outcome . METHODS: A series of six randomized, single blind, crossover trials were conducted, each comparing cefdinir oral suspension with one of the following antibiotic oral suspensions: amoxicillin/clavulanate potassium; cefprozil; or azithromycin . Each medication comparison was evaluated in a single center and multicenter study . Subjects 4 to 8 years of age were asked to taste and smell each medication and assign preference using a visual "smile-face" scale . Ratings were converted to a numeric score ranging from 5 ("really good") to 1 ("really bad") . RESULTS: Among the 715 subjects 85% rated the taste of cefdinir as good or really good, the highest possible ratings; 63% of subjects assigned the same ratings to amoxicillin/clavulanate potassium, cefprozil or azithromycin . Seventy-one percent rated the smell of cefdinir as good or really good; 64% assigned the same ratings to the comparators . CONCLUSIONS: Based on the findings from these trials, children 4 to 8 years of age preferred the taste and smell of cefdinir oral suspension to that of the comparator agents.

Aliment Pharmacol Ther, 2000 Dec, 14(12), 1613 - 7
Pantoprazole, azithromycin and tinidazole: short duration triple therapy for eradication of Helicobacter pylori infection; Calabrese C et al.; BACKGROUND: Azithromycin is an acid-stable macrolide that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a period of 5-days, after a single 500 mg oral dose . AIM: To evaluate and compare the efficacy, safety, and tolerability of two eradicating regimens of pantoprazole, azithromycin and tinidazole . METHODS: A total of 100 consecutive symptomatic H . pylori-positive patients received pantoprazole 40 mg b.d . for 1 week, and were randomly assigned to either azithromycin 500 mg o.m . and tinidazole 500 mg b.d . during the first 3 days (early group, n=50) or during the last 3 days of therapy with pantoprazole (late group, n=50) . H . pylori status was assessed by histology and rapid urease test at entry and by histology and 13C-urea breath test 1 month after the end of the therapy . RESULTS: Ninety-nine patients completed the study . H . pylori was eradicated in 86% of patients in the early group (intention-to-treat 86%) and in 88% of patients in the late group (intention-to-treat 88%) . CONCLUSIONS: This short triple therapy is effective for H . pylori eradication . The compliance was excellent and side-effects negligible . Moreover, the pantoprazole pre-treatment did not modify the efficacy of the therapy.

Rev Esp Quimioter, 2000 Sep, 13(3), 297 - 305
{Pharmacovigilance study of azithromycin tablets (500 mg) in the treatment of adult patients with respiratory tract infections}; Alvarez MP et al.; Our aim was to study a new form of azithromycin (500 mg tablets) in order to evaluate the tolerability and the influence of the ingestion of food on tolerability, the efficacy and treatment compliance in a large number of patients with respiratory tract infections . We carried out an open, non-comparative, multicenter, observational and prospective pharmacovigilance study of 3223 outpatients with respiratory tract infections randomly assigned to receive a daily dose of azithromycin for three months taken either during or outside meals . Patients were evaluated during an initial visit and two later ones in order to record the adverse events and establish the clinical efficacy . The diagnostics were as follows: pharyngotonsillitis (1200), acute otitis media (394), acute bronchitis (1134), exacerbation of chronic bronchitis (436), and community-acquired pneumonia (53) . The overall therapeutic efficacy was satisfactory (cure or improvement) in 96% to 97% at the second visit and in 93% to 94% in the third (pharyngotonsillitis, 93%; acute otitis media, 91%; acute bronchitis, 94%; exacerbation of chronic bronchitis, 94%; and community-acquired pneumonia, 96%) . A total of 170 adverse events were reported in 141 patients (4.4%); 12 were severe yet not related to the study medication . Eighty-eight patients showed adverse events presumed to be related to azithromycin; most were in the digestive tract . No differences in tolerability were observed in relation to food intake . Treatment compliance was high (97%) . The elevated clinical efficacy, adequate compliance and the excellent tolerability profile of azithromycin tablets make them a safe and effective alternative in the treatment of respiratory tract infections.

N Engl J Med, 2000 Nov 16, 343(20), 1454 - 8
Atovaquone and azithromycin for the treatment of babesiosis; Krause PJ et al.; BACKGROUND: Babesiosis is a tick-borne, malaria-like illness known to be enzootic in southern New England . A course of clindamycin and quinine is the standard treatment, but this regimen frequently causes adverse reactions and occasionally fails . A promising alternative treatment is atovaquone plus azithromycin . METHODS: We conducted a prospective, nonblinded, randomized trial of the two regimens in 58 subjects with non-life-threatening babesiosis on Nantucket, on Block Island, and in southern Connecticut . The subjects were assigned to receive either atovaquone (750 mg every 12 hours) and azithromycin (500 mg on day 1 and 250 mg per day thereafter) for seven days (40 subjects) or clindamycin (600 mg every 8 hours) and quinine (650 mg every 8 hours) for seven days (18 subjects) . RESULTS: Adverse effects were reported by 15 percent of the subjects who received atovaquone and azithromycin, as compared with 72 percent of those who received clindamycin and quinine (P<0.001) . The most common adverse effects with atovaquone and azithromycin were diarrhea and rash (each in 8 percent of the subjects); with clindamycin and quinine the most common adverse effects were tinnitus (39 percent), diarrhea (33 percent), and decreased hearing (28 percent) . Symptoms had resolved three months after the start of therapy in 65 percent of those who received atovaquone and azithromycin and 73 percent of those who received clindamycin and quinine (P=0.66), and after six months no patient in either group had symptoms . Three months after the completion of the assigned regimen, no parasites could be seen on microscopy, and no Babesia microti DNA was detected in the blood of any subject . CONCLUSIONS: For the treatment of babesiosis, a regimen of atovaquone and azithromycin is as effective as a regimen of clindamycin and quinine and is associated with fewer adverse reactions.

J Cardiovasc Pharmacol, 2000 Oct, 36(4), 533 - 7
The effect of chronic azithromycin therapy on soluble endothelium-derived adhesion molecules in patients with coronary artery disease; Semaan HB et al.; In patients with coronary artery disease (CAD), azithromycin therapy is associated with decreased cytokine levels and overall reduction of inflammation . Chlamydia pneumoniae (C.Pn) is a common pathogen that may be an important factor in the development and progression of atherosclerosis . Cell-adhesion molecules have an important role in recruitment of inflammatory cells during plaque development and are expressed by endothelial cells on activation . We sought to define the effect of treatment with azithromycin on circulating levels of soluble vascular cell-adhesion molecule (VCAM-I), intercellular adhesion molecule (ICAM-1), and E-selectin in patients with CAD . Plasma concentrations of VCAM-1, ICAM-1, and E-selectin were measured in 40 patients with documented CAD and a positive (> or = 1:16) immunoglobulin G (IgG) titer against C.Pn, 20 subjects with normal coronary arteries, and 14 healthy volunteers . Patients were assigned randomly to receive either 500 mg/wk of azithromycin or placebo for 3 months . Serum samples were obtained at baseline, at 3 months, and during the follow-up visit at 6 months . Patients with documented CAD exhibited elevation of VCAM-1 (535 +/- 227 ng/ ml; p = 0.0001) and E-selectin (69 +/- 29 ng/ml; p = 0.006), but not ICAM-1 (321 +/- 65 ng/ml) concentrations as compared with the patients with angiographically proven normal coronary arteries (252 +/- 80; 50 +/- 22; and 311 +/- 40 ng/ml) and healthy controls (110 +/- 18; 29 +/- 2; and 238 +/- 47 ng/ml, respectively) . Prolonged treatment with azithromycin did not significantly affect the plasma levels of soluble VCAM-1, ICAM-1, and E-selectin . Soluble markers of endothelial activation are markedly increased in patients with documented CAD as compared with those with normal coronary arteries and healthy controls . Despite substantial heterogeneity in plasma E-selectin, ICAM-1, and VCAM-1 levels, long-term azithromycin treatment did not affect plasma levels of these adhesion molecules, indicative of endothelial activation, over a period of 6 months.

Pacing Clin Electrophysiol, 2000 Sep, 23(9), 1433 - 5
Potentially fatal interaction between azithromycin and disopyramide; Granowitz EV et al.; A patient on disopyramide developed disopyramide toxicity when treated concurrently with azithromycin . Evidence of toxicity included an elevated serum disopyramide level and ventricular tachycardia requiring cardioversion . The azalide antibiotic presumably inhibited dealkylation of disopyramide to its major metabolite, mono-N-dealkyldisopyramide . Physicians should avoid using azithromycin in patients on disopyramide . If this drug combination is unavoidable, disopyramide levels must be closely monitored.

Prim, Care Update Ob Gyns . 2000 Sep 1, 7(5), 173 - 176
Mycoplasma pneumoniae in women; Tebes S et al.; Mycoplasma pneumoniae (primary atypical or Eatons' agent) is a common cause of walking or atypical pneumonia in young adults . It is responsible for approximately 43% of the cases of community-acquired pneumonia in patients between the ages of 17 and 44 . Patients with Mycoplasma pneumonia typically present with the gradual onset of a nonproductive cough, sore throat, fever, and pulmonary infiltrates on chest x-ray . The diagnosis is based on symptomatology and on radiographic findings such as interstitial infiltrates, patchy infiltrates, plate-like atelectasis, nodular infiltration, or hilar adenopathy . The primary treatment for Mycoplasma pneumoniae is a macrolide antibiotic, preferably azithromycin: 500 mg initially and then 250 mg daily for 4 days.

Circulation, 2000 Oct 10, 102(15), 1755 - 60
Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study; Muhlestein JB et al.; BACKGROUND: Chlamydia pneumoniae is associated with coronary artery disease (CAD), although its causal role is uncertain . A small preliminary study reported a >50% reduction in ischemic events by azithromycin, an antibiotic effective against C pneumoniae, in seropositive CAD patients . We tested this prospectively in a larger, randomized, double-blind study . METHODS AND RESULTS: CAD patients (n=302) seropositive to C pneumoniae (IgG titers >/=1:16) were randomized to placebo or azithromycin 500 mg/d for 3 days and then 500 mg/wk for 3 months . The primary clinical end point included cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction (MI), stroke, unstable angina, and unplanned coronary revascularization at 2 years . Treatment groups were balanced, and azithromycin was generally well tolerated . During the trial, 47 first primary events occurred (cardiovascular death, 9; resuscitated cardiac arrest, 1; MI, 11; stroke, 3; unstable angina, 4; and unplanned coronary revascularization, 19), with 22 events in the azithromycin group and 25 in the placebo group . There was no significant difference in the 1 primary end point between the 2 groups (hazard ratio for azithromycin, 0.89; 95% CI, 0.51 to 1.61; P:=0.74) . Events included 9 versus 7 occurring within 6 months and 13 versus 18 between 6 and 24 months in the azithromycin and placebo groups, respectively . CONCLUSIONS: This study suggests that antibiotic therapy with azithromycin is not associated with marked early reductions (>/=50%) in ischemic events as suggested by an initial published report . However, a clinically worthwhile benefit (ie, 20% to 30%) is still possible, although it may be delayed . Larger (several thousand patient), longer-term (>/=3 to 5 years) antibiotic studies are therefore indicated.

Am J Cardiol, 2000 Oct 1, 86(7), 789 - 91, A9
In vivo uptake of azithromycin in human coronary plaques; Schneider CA et al.; Ten patients with symptomatic coronary artery disease received oral azithromycin for 3 days and underwent directional atherectomy on the third day . Azithromycin was found in all plaque samples with a median concentration of 284 ng/ml (95% confidence interval 163 to 517 ng/ml).

Ann Intern Med, 2000 Oct 3, 133(7), 493 - 503
Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count . A randomized, double-blind, placebo-controlled trial . AIDS Clinical Trials Group 362 Study Team; Currier JS et al.; BACKGROUND: Patients infected with HIV who experience increases in CD4(+) cell counts are at reduced risk for opportunistic infections . However, the safety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain . OBJECTIVE: To compare the rate of M . avium complex infection in patients with increased CD4(+) cell counts who receive azithromycin and those receiving placebo . DESIGN: Randomized, double-blind, placebo-controlled trial . SETTING: 29 university-based clinical centers in the United States . PARTICIPANTS: 643 HIV-1-infected patients with a previous CD4(+) cell count less than 0.05 x 10(9) cells/L and a sustained increase to greater than 0.10 x 10(9) cells/L during antiretroviral therapy . INTERVENTION: Azithromycin, 1200 mg once weekly (n = 321), or matching placebo (n = 322) . MEASUREMENTS: Mycobacterium avium complex cultures, CD4(+) cell counts, and clinical evaluations for AIDS-defining illnesses and bacterial infections were done every 8 weeks . Plasma HIV-1 RNA levels were measured at 16-week intervals . RESULTS: During follow-up (median, 16 months), 2 cases of M . avium complex infection were reported among the 321 patients assigned to placebo (incidence rate, 0.5 event per 100 person-years {95% CI, 0.06 to 1.83 events per 100 person-years}) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a treatment difference of 0.5 event per 100 person-years (CI, -0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin . Both cases were atypical in that M . avium complex was localized to the vertebral spine . Patients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs . 2%; hazard ratio, 0.24 {CI, 0.10 to 0.57}) . CONCLUSIONS: Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4(+) cell count while receiving antiretroviral therapy.

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