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PubMed2003

Electrochemical oxidation of azithromycin and its derivatives.

The electrochemical oxidation of azithromycin was investigated in order to elucidate the mechanism for possible oxidative metabolic pathways in humans. Electrochemical studies were carried out by cyclic voltammetry and preparative scale electrolysis at glassy carbon electrodes. It was found that azithromycin undergoes anodic oxidation at one or both amine groups with the rapid follow-up chemistry of intermediate radical cation. Main products of the oxidation were determined by HPLC analysis and were identified as a protonated azithromycin and products obtained by demethylation of the 3'-dimethylamino or macrolactone amino group.

Azithromycin↗
PubMed2001

Comparative serum bactericidal activity of clarithromycin and azithromycin against macrolide-sensitive and resistant strains of Streptococcus pneumoniae.

The serum pharmacodynamics of clarithromycin and azithromycin were studied against isolates of S. pneumoniae, including efflux resistant (M. phenotype) strains, by analyzing their serum bactericidal activity (SBA) over time. Normal healthy subjects were given a single 500 mg oral dose of these macrolides and serum samples were collected over 12 hrs. Paired isolates with MICs ranging from 0.25 ug/ml to 8.0 ug/ml were analyzed. Prolonged (at least 6 hrs) SBA was observed with clarithromycin for strains with MICs < or = 2.0 ug/ml. No SBA was observed in strains with MICs >or = 4.0 ug/ml. Azithromycin exhibited SBA for at least 6 hrs for strains up to a MIC = 0.5 ug/ml. No SBA was observed for isolates with MICs > or = 1.0 ug/ml. In contrast to azithromycin, clarithromycin exhibited SBA for at least one-half of its normal dosing interval against S. pneumoniae strains well above its current susceptibility breakpoint concentration of 0.25 microg/ml. These findings may have relevance to the ongoing debate as to the appropriate susceptibility breakpoints for the newer macrolides.

Administration, Oral↗
PubMed2002

Azithromycin treatment failure in community-acquired pneumonia caused by Streptococcus pneumoniae resistant to macrolides by a 23S rRNA mutation.

In this report, we describe an azithromycin treatment failure in community-acquired pneumonia. During the first three days of azithromycin, the patient's symptoms worsened, and she was subsequently admitted to the hospital. Blood cultures were positive for a penicillin-susceptible, macrolide-resistant S. pneumoniae. DNA sequencing revealed an A2059G mutation in domain V of the 23S rRNA. To our knowledge, this is the first clinical report of an azithromycin failure in the treatment of S. pneumoniae resistant to macrolides by this mechanism.

Anti-Bacterial Agents↗
PubMed1997

Susceptibility of twenty penicillin-susceptible and -resistant pneumococci to levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin by MIC and time-kill.

This study uses MIC and time-kill methodology to examine the antipneumococcal activity of levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Ten strains had levofloxacin MICs of 1.0 microgram/ml, and ten levofloxacin MICs of 2.0 micrograms/ml. Five strains in each group were macrolide susceptible, and five were macrolide resistant. MICs for ciprofloxacin and ofloxacin ranged from 0.5 to 4.0 micrograms/ml and 1.0 to 8.0 micrograms/ml, respectively. MICs of erythromycin, azithromycin, and clarithromycin were similar for macrolide susceptible strains, ranging between 0.004 to 0.06 microgram/ml, and were > or = 128.0 micrograms/ml for macrolide resistant strains. The three quinolones were bactericidal (99.9% killing) for all macrolide-susceptible strains at 2 x MIC at 24 h. The three quinolones yielded 99% killing of all strains after 12 h at 2 x MIC, and 90% killing of all strains after 6 h at the MIC of levofloxacin and ciprofloxacin and 2 x MIC for ofloxacin. Levofloxacin yielded 90% killing of all strains after 4 h at 2 x MIC and ofloxacin at 4 x MIC. For macrolide-susceptible strains, erythromycin and clarithromycin were bactericidal for 9 of 10 strains after 24 h at 4 x and 2 x MIC, respectively, and azithromycin was bactericidal after 24 h at 2 x MIC for 8 of 10 strains. All three macrolides were bactericidal after 12 h only, while 90% killing occurred in 9 of 10 strains at 8 x MIC after 6 h. Quinolone kill kinetics were similar for the 10 macrolide-resistant strains. For macrolide-resistant strains, at 64 to 128.0 micrograms/ml, virtually no decrease in count was seen, with no bactericidal effect.

Anti-Bacterial Agents↗
PubMed1998

Comparison of bactericidal activity after multidose administration of clarithromycin, azithromycin, and ceruroxime axetil against Streptococcus pneumoniae.

The objective of this study was to compare the duration of serum bactericidal activity (SBA) for clarithromycin, azithromycin, and cefuroxime axetil in 12 young healthy volunteers after 5 days of therapy (dosed to steady-state) against two strains each of penicillin (PCN)-susceptible, -intermediate, and -resistant Streptococcus pneumoniae. This was a randomized, 3-way crossover study. All isolates were susceptible to clarithromycin (MICs 0.125 mg/l) and azithromycin (MICs 0.25-0.5 mg/l), while cefuroxime axetil susceptibilities correlated with PCN. Results showed that SBA was maintained for 100% of the dosing interval for clarithromycin and 50-100% for azithromycin regardless of PCN susceptibility when standard doses were employed. Cefuroxime axetil was active only against the PCN-susceptible isolate for 50% of the dosing interval, indicating that it should only be used for PCN-susceptible S. pneumoniae.

Anti-Bacterial Agents↗
PubMed2005

Blood schizontocidal activity of azithromycin and its combination with alpha/beta arteether against multi-drug resistant Plasmodium yoelii nigeriensis, a novel MDR parasite model for antimalarial screening.

Many different drug-resistant lines of rodent malaria are available as screening models. It is obligatory to screen new compounds for antimalarial activity against a series of resistant lines in order to identify a compound with potential for the treatment of multi-drug resistant (MDR) malaria infections. Instead of using a battery of resistant lines, a single MDR Plasmodium yoelii nigeriensis strain that shows a wide spectrum of drug resistance to high doses of chloroquine, mepacrine, amodiaquine, mefloquine, quinine, quinidine, halofantrine as well as tetracyclines, fluoroquinolines and erythromycin, was used to assess the blood schizontocidal efficacy of a new macrolide azithromycin and other antibiotics. The present study shows that only azithromycin has the potential to control an MDR P. y. nigeriensis infection in Swiss mice, provided the treatment with a dose of 50-100 mg/kg/day by oral route is continued for a period of 7 days. Tetracycline, oxytetracycline, doxycyline, erythromycin, ciprofloxacin and norfloxacin, although active in vitro, failed to protect the mice. Tetracycline, ciprofloxacin and norfloxacin combinations with chloroquine did not control the infection. Additionally, the antimalarial efficacy of azithromycin can be potentiated with the addition of arteether, which is an ethyl ether derivative of artemisinin. A total (100%) curative effect has been obtained with a shorter regimen of 4 days only.

Animals↗
PubMed2002

Azithromycin-induced intrahepatic cholestasis.

Azithromycin (Zithromax), an erythromycin derivative that belongs to a subgroup of the macrolides known as azolides, has generally been considered to be a very safe medication. Hepatic side effects are uncommon but may include jaundice, fever, and right upper quadrant pain. Herein we describe a patient who developed azithromycin-induced cholestatic hepatitis that resolved upon discontinuation of the drug. Lack of other known causes for liver disease, the temporal relationship with this drug, and the typical changes of liver histology have established the diagnosis. Clinicians should be aware of this side effect of azithromycin, which is widely prescribed.

Aged↗
PubMed1998

Azithromycin impact on neutrophil oxidative metabolism depends on exposure time.

Several antimicrobial agents have already been investigated relating to their influence on neutrophil ROS generation. Azithromycin provides, a dose-related anti-oxidant effect, after 15 min incubation, with the stimulating agent FMLP, as well with PMA or S. aureus. This finding was however obtained with concentrations not considered in therapeutics. Since short incubation times are not representative of the physiological situation, and since azithromycin is characterized by prolonged high concentrations within phagocytes, the same experiments were performed over 2 and 4 h exposures. A time-dependent anti-oxidant effect was then reported. The maximum effect was obtained with PMA (IC50 were 856 and 30 micrograms/ml for 15 min and 4 h incubation times respectively). Time-dependent modifications of neutrophil oxidative metabolism seem to be correlated with intracellular concentrations. Depressed oxidative metabolism might be related neither to azithromycin cellular toxicity, nor to superoxide scavenging properties. By increasing exposure periods, therapeutic concentrations could therefore lead to an anti-inflammatory effect, potentially of clinical interest since associated with bacteriostatic activity.

Anti-Bacterial Agents↗
PubMed2000

Pantoprazole, amoxycillin and either azithromycin or clarithromycin for eradication of Helicobacter pylori in duodenal ulcer.

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

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Pantoprazole, azithromycin and tinidazole: short duration triple therapy for eradication of Helicobacter pylori infection.

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

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Azithromycin for the treatment of acne.

BACKGROUND: Acne affects a large number of young adults, including women, who often present with facial as well as truncal involvement. Systemic antimicrobial agents currently used for the reduction of inflammatory papules and cysts require frequent administration and are sometimes associated with uncomfortable side-effects contributing to a decrease in compliance. METHODS: Ninety-nine episodes of inflammatory acne in 79 patients treated with oral antimicrobial agents were studied retrospectively over a period of 46 weeks. Patients were treated with tetracycline, erythromycin, minocycline, and doxycycline, the most commonly prescribed oral antimicrobials used to treat acne. Individuals that were unable to tolerate this therapy or had failed conventional therapy were treated with the azalide antibiotic azithromycin, given in a single oral 250-mg dose three times a week. The other agents were administered daily in divided doses as is current practice. Patients were also on topical care. RESULTS: The efficacy and reported side-effects were examined for all agents. Significant improvement was noted in 4 weeks. All agents were effective in reducing inflammatory lesions and improving acne. Azithromycin produced a slightly higher percentage of patients with a greater than 80% reduction in their inflammatory acne lesions (85.7%) vs. an average of 77.1% for all other agents. All differences observed were not statistically significant. CONCLUSIONS: The results show that azithromycin is a safe and effective alternative in the treatment of inflammatory acne with few side-effects and good compliance, and suggest the need for further investigation with a clinical trial that will compare the long-term efficacy and tolerability.

Acne Vulgaris↗
PubMed2002

Erythromycin susceptibility of viridans streptococci from the normal throat flora of patients treated with azithromycin or clarithromycin.

OBJECTIVE: To study the emergence of macrolide resistance in throat flora following treatment with clarithromycin or azithromycin. METHODS: Throat samples were collected before and after treatment and plated as a lawn on Columbia blood agar with an erythromycin E test strip. Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin and azithromycin were determined against isolates of distinct morphology with erythromycin E test MIC results equal to or greater than 2 mg/L. Polymerase chain reaction techniques were used to determine the genetic mechanisms of resistance. RESULTS: There were 749 resistant isolates of which 474 (63%) were streptococci. Only a quarter of the patients had no resistant streptococci before treatment started. There were increases in the numbers of resistant isolates and in the number of patients carrying a resistant flora during and after treatment. The most common genes identified were mefA/E in isolates with low-level resistance and ermA/M in isolates with high-level resistance. CONCLUSIONS: There is a pool of streptococci carrying genes associated with macrolide resistance in the normal respiratory flora of generally healthy adults. Differences between the patients treated with clarithromycin and those treated with azithromycin were difficult to assess because of the large number of patients in each group with macrolide-resistant streptococci before treatment. Although there were some differences these were not statistically significant.

Anti-Bacterial Agents↗
PubMed1999

High dose omeprazole plus amoxicillin and azithromycin in eradication of Helicobacter pylori in duodenal ulcers.

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

Adult↗
PubMed2002

Chlamydia pneumoniae antigens facilitate experimental aortic dilatation: prevention with azithromycin.

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

Animals↗
PubMed2002

No advantage of treating acute respiratory tract infections with azithromycin in a placebo-controlled study.

Acute respiratory tract infection (ARTI) is the commonest reason for which antibiotics are prescribed, despite the fact that ARTI is mostly of viral origin. The effectiveness of antibiotics in these illnesses is, at best, questionable. Jordan is a developing country where bacterial infections are thought to be more common than in developed countries and initially viral illnesses are frequently superimposed by bacterial infections. The present study represents an attempt to assess whether routine antibiotic treatment of ARTI has any beneficial effect on the course of the illness. The study was conducted in northern Jordan between 1 June and December 14, 2000. Patients > or =8 y of age visiting either of 2 health centers and diagnosed by the physician with ARTI above the level of the bronchioles were assigned on an alternating basis to receive either azithromycin or placebo. Patients were assessed at their initial visit and were subsequently followed up after 3 d, 1 week and 2 weeks. A total of 185 patients were included in the study. Patients administered azithromycin or placebo did similarly in terms of the proportions improved or cured and the duration of illness. We conclude that routine use of antibiotics (azithromycin) in ARTI is unlikely to alter the course of the illness.

Acute Disease↗
PubMed1993

Clinical efficacy of azithromycin in lower respiratory tract infections.

A total of 51 patients with acute exacerbation of chronic bronchitis and pneumonia were enrolled: 27 treated with azithromycin (500 mg once a day for 3 days), and 24 with roxithromycin (150 mg every 12 hours for 7 days). The two regimens were equally effective, with clinical cure in 80% and 72% of patients respectively. Bacteriological eradication on day 19-23 was obtained in 7/11 cases (64%) and in 6/13 cases (46%) in the two groups, respectively. No side effects occurred in patients treated with azithromycin, while they occurred in the roxithromycin group (2 vomiting and 1 gastritis). Clinical and bacteriological efficacy, excellent tolerability, simplified dosage (single daily dose) and short-course (3 days) therapeutic regimen make azithromycin, in our experience, efficacious for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia.

Adolescent↗
PubMed2000

Description and status of the azithromycin and coronary events study (ACES).

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

Adult↗
PubMed2000

Effect of azithromycin on murine arteriosclerosis exacerbated by Chlamydia pneumoniae.

Chlamydia pneumoniae infection can exacerbate atherosclerosis in animals. To test the hypothesis that antibiotic therapy inhibits the atherogenic effects of C. pneumoniae infection, 10-week-old apolipoprotein E (ApoE) null mice were infected with C. pneumoniae or placebo, were treated for 2 weeks after infection with azithromycin or placebo, and were killed at 20 weeks of age. Infection did not affect the size of the aortic lesion, and antibiotic treatment had no effect. Another group of mice, 12-week-old ApoE mice, were infected with C. pneumoniae or placebo, were treated for 2 weeks after infection with azithromycin or placebo, and were killed at 26 weeks of age. C. pneumoniae infection increased the size of the lesion in infected mice, but azithromycin did not reduce the size of the aortic lesion in infected mice. Therefore, immediate therapy of acute infection may be necessary to prevent the proatherogenic effects of C. pneumoniae infection.

Animals↗