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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
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