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PubMed1998

Treatment of disseminated Mycobacterium genavense infection in a murine model with ciprofloxacin, amikacin, ethambutol, clarithromycin and rifabutin.

Mycobacterium genavense is a recently described agent which can induce disseminated infections in patients with AIDS. Up to now, no standard approach to treatment has been defined and patients have been treated empirically with antibiotics used for treating infections caused by other nontuberculous mycobacteria. In this study, we compared the effectiveness of ciprofloxacin, amikacin, ethambutol, clarithromycin and rifabutin in the treatment of an animal model of M. genavense infection in C57BL/6 mice. Antimycobacterial treatment was started 4 weeks after an intravenous bacterial challenge and was continued for 30 days. Treated and control mice were killed at days 15 and 30 of treatment and the number of viable bacteria in their spleens was counted. Treatment with clarithromycin (50 mg/kg/day sc) and rifabutin (20 mg/kg/day po) was found to decrease the bacterial counts in the spleens significantly as early as 15 days after the onset of treatment (P < 0.01). The effect of treatment was more pronounced after 30 days of treatment (P < 0.001). Amikacin (25 mg/kg/day sc) and ethambutol (50 mg/kg/day sc) were found to decrease significantly the cfu in the spleens only after 30 days of treatment (P < 0.01). Ciprofloxacin (25 mg/kg/day sc) was ineffective in the experimental conditions used here.

Amikacin↗
PubMed1999

Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxycillin, tetracycline and trovafloxacin in The Netherlands.

Successful treatment of Helicobacter pylori infection is becoming compromised by emerging resistance. We report the prevalence rates of H. pylori resistance to metronidazole, clarithromycin, amoxycillin, tetracycline and trovafloxacin in The Netherlands. A total of 231 H. pylori clinical isolates were collected throughout the country over a period of 6 months during 1997-1998. The MICs of the above-mentioned antibiotics were determined in a single laboratory. The overall percentage of resistance for clarithromycin and metronidazole was 1.7% and 21.2%, respectively. None of the strains was resistant to amoxycillin or tetracycline. The primary resistance rate of trovafloxacin was as high as 4.7%. Since trovafloxacin has not yet been introduced on to the Dutch market, the resistance is probably induced by the use of other quinolones. Our data indicate that treatment outcome would benefit from susceptibility testing before starting therapy, especially when prescribing metronidazole.

Amoxicillin↗
PubMed2000

Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors.

Subinhibitory concentrations of bacitracin, vancomycin and other inhibitors of cell wall synthesis reversed to varying extents the intrinsic resistance of Mycobacterium tuberculosis to clarithromycin. Ethambutol reversed clarithromycin resistance in all of the M. tuberculosis strains studied regardless of their susceptibility to this drug.

Anti-Bacterial Agents↗
PubMed2000

Inhibition of growth of Pneumocystis carinii by lactoferrins alone and in combination with pyrimethamine, clarithromycin and minocycline.

The in vitro activity of lactoferrins alone and in combination with clarithromycin, minocycline and pyrimethamine was investigated against three clinical isolates of Pneumocystis carinii. Susceptibility was tested by inoculating isolates on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with serial dilutions of each agent. At 20 mg/L, bovine lactoferrin, the most active agent, suppressed the growth of cystic and trophic forms by >60%. Human lactoferrin, at the same concentration, suppressed the growth of cystic and trophic forms by >50%. Lactoferrins at 20 mg/L combined with clarithromycin 4 mg/L had high anti-P. carinii activity, with a >90% decrease in cystic and trophic form counts. Our study suggests that lactoferrins may inhibit P. carinii growth in vitro and act synergically with other clinically used compounds. These findings lend experimental support to the use of iron-chelating agents in the therapy of pneumocystis infections.

Animals↗
PubMed2001

Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea.

Antibiotic resistance in Helicobacter pylori varies according to geographical region. We studied the primary resistance rates among 652 H. pylori isolated from Korea in relation to collection date, disease presentation, age and gender. Resistance rates were 40.6% (metronidazole), 5.9% (clarithromycin), 5.3% (tetracycline), 0% (amoxycillin), 1.5% (furazolidone) and 1.5% (nitrofurantoin). Resistance to metronidazole and clarithromycin increased from 1994 to 1999 (from 33.3 to 47.7% and 4.8 to 7.7%, respectively), but the differences only reached significance when rates of metronidazole resistance in women were compared with those in men (48.6 versus 36.9%).

Adolescent↗
PubMed2001

A 9 year study of clarithromycin and metronidazole resistance in Helicobacter pylori from Spanish children.

The evolution of clarithromycin, metronidazole and amoxycillin resistance in 246 Spanish Helicobacter pylori clinical isolates, obtained from paediatric patients during a 9 year period, was determined by an agar dilution technique. Clarithromycin resistance (MIC 1 mg/L) was 2.27% (IC95 0.05-12.02) in 1991-1993, 20.98% (IC95 12.72-31.46) in 1994-1996 and 28.33% (IC95 20.48-37.28) in 1997-1999 (P < 0.01). Metronidazole resistance (MIC 8 mg/L) was 7.14% (IC95 1.49-19.48) in 1991-1993, 20.25% (IC95 12.04-30.79) in 1994-1996 and 43.90% (IC95 32.95-55.30) in 1997-1999 (P < 0.01). Amoxycillin resistance was not found (all strains showed MICs < 2 mg/L).

Anti-Bacterial Agents↗
PubMed2001

Localization of [14C]amoxicillin in rat gastric tissue when administered with lansoprazole and clarithromycin.

The gastric mucosal distribution of [14C]amoxicillin when administered to rats with or without lansoprazole and clarithromycin was investigated. After oral administration, the amount found in the gastric mucosa was higher than after iv administration. Co-administration of lansoprazole and clarithromycin had no apparent effect on the distribution pattern of [14C]amoxicillin within the deeper stomach layers. About 50-60% of the radioactivity in the gastric tissue was present in the mucosal layer, irrespective of the route of administration. Microautoradiograms of the gastric mucosa indicated that [14C]amoxicillin was distributed in both the mucous layer and surface epithelial cells following oral administration. [14C]amoxicillin was secreted mainly by surface epithelial cells after iv administration, although only in small quantities.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

Comparison of phenotypic and genotypic methods for the detection of clarithromycin resistance in Mycobacterium avium.

The MICs of clarithromycin for 10 clinical isolates of Mycobacterium avium were determined using three methods: Bactec 460-TB, broth microdilution and Etest. The results were compared with the presence of resistance mutations in the 23S rRNA gene. Isolates were obtained from five AIDS patients who were treated with clarithromycin. Five isolates were recovered before and five during treatment. MICs were reproducible and comparable between the three methods. They were < or = 4 mg/L for pre-treatment isolates and > or = 128 mg/L for strains recovered during treatment. An MIC > or = 128 mg/L was associated with the presence of mutations in the 23S rRNA gene that were absent in the isolates exhibiting MIC < ro = 4 mg/L.

Anti-Bacterial Agents↗
PubMed2002

Effect of clarithromycin on chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation in an experimental murine model.

Fourteen-membered macrolides (e.g. clarithromycin and erythromycin), but not 16-membered macrolides (e.g. josamycin), are effective in diffuse panbronchiolitis. However, there are no studies that have compared the effects of 14- and 16-membered macrolide antibiotics on biofilm formation. Treatment with high-dose clarithromycin (100 mg/kg) resulted in a significant decrease in the number of viable bacteria in an experimental murine model. Josamycin at a dose of up to 100 mg/kg had no effect on the number of viable bacteria in the lung. Our results may explain, at least in part, the clinical efficacy of 14-membered macrolide antibiotics in patients with chronic pneumonia caused by Pseudomonas aeruginosa.

Animals↗
PubMed2002

In vitro transfer of clarithromycin and amoxicillin across the epithelial barrier: effect of Helicobacter pylori.

The mode of absorption of amoxicillin and clarithromycin, two antibiotics used in the treatment of Helicobacter pylori infection, has not been completely elucidated. The aims of this study were to investigate the passage of these antibiotics across normal and infected epithelium and to measure their accumulation in HT29-19A or Caco2 epithelial cell monolayers. In non-infected cultures, basal-to-apical fluxes were significantly higher than apical-to-basal fluxes for both antibiotics, but this difference disappeared in monolayers infected with H. pylori. In 24 h studies, clarithromycin, but not amoxicillin, showed rapid intracellular accumulation. No difference was found between the transepithelial passage of amoxicillin across the HT29-19A and Caco2 monolayers.

Amoxicillin↗
PubMed2005

In vitro activity of linezolid, clarithromycin and moxifloxacin against clinical isolates of Mycobacterium kansasii.

OBJECTIVES: To compare the activity of linezolid with a range of drugs used in the treatment of Mycobacterium kansasii infections. RESULTS: The percentages of resistant isolates against isoniazid, rifampicin and ethambutol were 2.9%, 1.9% and 2.9%, respectively. All isolates were susceptible to clarithromycin and moxifloxacin both with MIC(90) values of 0.125 mg/L. Linezolid was active against all isolates with MIC(50) and MIC(90) values of 0.5 and 1 mg/L, respectively, both below the susceptibility breakpoint established for mycobacteria. CONCLUSION: Linezolid, clarithromycin or moxifloxacin, could be used as alternative drugs for treatment of infections due to rifampicin-resistant isolates as well as short-course or intermittent therapy of M. kansasii lung disease.

Acetamides↗
PubMed1997

Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection.

OBJECTIVE: To compare the efficacy of two- and three-drug regimens for treating Mycobacterium avium complex (MAC) bacteremia in patients with AIDS. DESIGN: Randomized open-label clinical trial. SETTING: Outpatient HIV specialty centers' clinics. PATIENTS: A total of 106 adults with AIDS and MAC bacteremia. INTERVENTIONS: Patients were treated with clarithromycin 500 mg twice daily and ethambutol 800-1,000 mg daily and were randomized to receive clofazimine 100 mg daily or no clofazimine. MAIN OUTCOME MEASURES: Quantitative blood MAC cultures, symptoms, adverse reactions and survival. RESULTS: Patients randomly assigned to three drugs had significantly higher baseline colony counts of MAC in blood than patients receiving two drugs. The proportion of patients becoming culture-negative was 65% in the two-drug group and 54% in the three-drug group. The median time to negative culture was 58 days for patients in the two-drug and 63 days for the three-drug group. At the last visit during treatment, the mean reduction in colony forming units/ml of MAC in blood was 1.8 log10 for the two-drug group and 2.3 log10 for the three-drug group. Improvement in fever and night sweats was reported by 87 and 89% of the two-drug patients and 84 and 86% of the three-drug patients. During the study, 38% of two-drug patients and 61% of three-drug patients died (P = 0.032), and time to death was shorter in patients treated with three drugs (P = 0.012). In a multivariate analysis, both assignment to clofazimine and high baseline colony counts of MAC bacteremia were significantly associated with death (P < 0.05). CONCLUSION: The addition of clofazimine to a regimen of clarithromycin and ethambutol for MAC bacteremia in AIDS patients does not contribute to clinical response and is associated with higher mortality.

AIDS-Related Opportunistic Infections↗
PubMed2004

Nontuberculous mycobacteria-induced parotid lymphadenitis successfully limited with clarithromycin and rifabutin.

OBJECTIVES/HYPOTHESIS: Nontuberculous mycobacterial adenitis of the parotid gland is often difficult to diagnose. The rarity of these infections in the parotid region and the lack of specific guidelines pose a treatment challenge to the clinician. Three cases of nontuberculous mycobacterial adenitis are presented, with clinical response to antibiotics before surgery. STUDY DESIGN: Retrospective chart review was made of children up to 18 years of age presenting with a parotid mass diagnosed as nontuberculous mycobacterial infection. METHODS: Three patients (age range, 15 to 30 mo) with nontuberculous mycobacteria-induced parotid lymphadenitis were treated with a combination antibiotic regimen of clarithromycin and rifabutin or with clarithromycin alone. RESULTS: All three patients responded clinically to the antibiotic treatment as evidenced by a smaller mass size and resolution of the overlying discoloration. Subsequent parotidectomy or biopsy appeared to be easier to perform because of decreased inflammation and edema and a more readily dissectible facial nerve. CONCLUSION: Children with nontuberculous mycobacteria-induced parotid lymphadenitis should be started on a trial of antibiotic treatment before surgery. Although surgery remains the definitive treatment modality, a larger study of preoperative antibiotic use against nontuberculous mycobacterial adenitis of the parotid in children is necessary.

Anti-Bacterial Agents↗
PubMed2002

Relation between alcohol consumption and the success of Helicobacter pylori eradication therapy using omeprazole, clarithromycin and amoxicillin for 1 week.

OBJECTIVE: To study the relationship between daily alcohol consumption and the result of eradication therapy for Helicobacter pylori using omeprazole, clarithromycin and amoxicillin for 1 week. DESIGN: Clinical trial. SETTING: Urban health centre, general medicine section. PARTICIPANTS: One hundred and fifty-six patients with a diagnosis of peptic ulcus or chronic gastritis. Helicobacter pylori infection was confirmed by the urease test, the 14C-urea breath test, IgG serology or biopsy. INTERVENTIONS: A combination of omeprazole, 20 mg twice daily, clarithromycin, 500 mg twice daily, and amoxicillin, 1000 mg twice daily was administered for 1 week. No other drugs were given. Four to 8 weeks later a 14C-urea breath test was carried out to confirm eradication. MAIN OUTCOME MEASURES: Logistic regression was used to assess the relationship between eradication and daily alcohol consumption (main covariable), age, sex, smoking, length of illness, pathology studied (ulcus or gastritis) and therapeutic compliance. RESULTS: Eradication (intention to treat analysis) was successful in 118 patients (75.6%; 95% CI, 68.9-82.4). The only variable significantly associated with the result of the therapy was daily alcohol consumption, with a higher probability of failure in non-consumers (29.9%) than in consumers (12.2%), adjusted OR 3.24 (95% CI, 1.12-9.20; P = 0.03). Eradication was dose dependent: 70.1% in abstemious patients (n = 107), rising to 79.3% in users of 4-16 g of pure ethanol a day (n = 29) and to 100% in users of 18-60 g daily (n = 20) with a P value of 0.005 for the trend. CONCLUSIONS: Daily alcohol consumption appears to have an additive effect in this eradication therapy.

Adult↗
PubMed2000

Clarithromycin-induced alterations in vaginal flora.

Many antibiotics have been shown to alter both the bacterial and the fungal flora of the vagina, in some cases potentially increasing a woman's propensity toward urinary tract infections and vaginal candidiasis. The effects of some of the newer macrolide antibiotics on women's vaginal flora have not been previously studied, and almost none of the previous studies specifically cultured for effects on vaginal lactobacillus. Young women (ages 18-45 years) who were about to go onto therapy with clarithromycin, who did not have any conditions known to affect the vaginal flora (eg, diabetes mellitus, spermicide use, menopausal status without hormone replacement therapy), and who agreed to participate in the study were cultured with aerobic and anaerobic and fungal vaginal cultures before starting the antibiotic. These same women were then retested about 4 to 6 weeks after the start of their antibiotic course, and the results of their preantibiotic and postantibiotic cultures were compared. Lactobacillus was present in 33% of patients by vaginal culture before treatment, but this decreased to 0% after treatment. Escherichia coli was present in only 8% of patients before treatment, but this increased to 17% of patients after treatment. Enterococcus was present in 25% of patients before treatment but in only 8% of patients after treatment. The incidence of Gardnerella vaginalis was not affected by the treatment. Candida species incidence increased from 17% to 33% with treatment. The overall effects of clarithromycin on the vaginal flora are similar to other older antibiotics that have been tested.

Adult↗
PubMed2005

Comparison of clarithromycin and ciprofloxacin therapy for Bacillus anthracis Sterne infection in mice with or without (60)Co gamma-photon irradiation.

Biological agents and ionizing radiation lead to more severe clinical outcomes than either insult alone. This study investigated the survival of non-irradiated and (60)Co-gamma-irradiated mice given therapy for inhalation anthrax with ciprofloxacin (CIP) or a clinically relevant mixture of clarithromycin (CLR) and its major human microbiologically important metabolite 14-hydroxy clarithromycin (14-OH CLR). All B6D2F1/J 10-week-old female mice were inoculated intratracheally with 3 x 10(8) c.f.u. of Bacillus anthracis Sterne spores 4 days after the non-lethal 7 Gy dose of (60)Co gamma radiation. Twenty-one days of treatment with CLR/14-OH CLR, 150 mg kg(-1) twice daily, or CIP, 16.5 mg kg(-1) twice daily, began 24 h after inoculation. Pharmacokinetics indicate that the area under the curve (AUC) for 14-OH CLR on the concentration-versus-time graph was slightly higher in gamma-irradiated than non-irradiated animals. Neither drug was able to increase survival in gamma-irradiated animals. CIP and CLR/14-OH CLR therapies in non-irradiated animals increased survival from 49 % (17/35 mice) in buffer-treated animals to 94 % (33/35) and 100 %, respectively (P < 0.001). B. anthracis Sterne only was isolated from 25-50 % of treated mice with or without irradiation. Mixed infections with B. anthracis Sterne were present in 50-71 % of gamma-irradiated mice but only in 5-10 % of mice without irradiation.

Animals↗
PubMed1996

A seven-day Helicobacter pylori treatment regimen using clarithromycin, omeprazole and tripotassium dicitrato bismuthate.

AIM: To evaluate clarithromycin 500 mg t.d.s., tripotassium dicitrato bismuthate 240 mg b.d. and omeprazole 20 mg b.d. for 7 days as a Helicobacter pylori treatment regimen. METHODS: The H. pylori status of dyspeptic patients undergoing endoscopy was assessed by histology, culture and rapid urease testing of biopsies and by 13C-urea breath test. Fifty patients who were H. pylori-positive were treated with the above treatment regimen for 7 days. Those patients with active duodenal ulcers present at endoscopy were given omeprazole 20 mg nocte for a further 21 days. Not less than 28 days after completing treatment, all tests were repeated to reassess H. pylori status. Bacterial sensitivity of H. pylori cultures was determined and patients recorded any side-effects. RESULTS: On an intention-to-treat basis, H. pylori infection was cured in 90% (95% CI: 78-96%) of patients. Taste disturbance was experienced by 35% patients. Compliance was excellent, with 96% patients taking more than 95% of tablets. Metronidazole resistance was 41% but all cultures were sensitive to clarithromycin. CONCLUSIONS: This 7-day treatment achieved a high level of cure of H. pylori infection with relatively minor side-effects. It may have a role to play, particularly where there is a high level of metronidazole resistance.

Adult↗
PubMed2004

Effect of cyclo-oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin.

BACKGROUND: We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole. AIM: To determine the effects of a cyclo-oxygenase (COX)-2-specific inhibitor, SC-236, and a non-selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori. METHODS: Three H. pylori reference strains, and 18 clinical isolates were treated with SC-236 or indometacin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E-test respectively. RESULTS: SC-236 and indometacin inhibited H. pylori growth in a dose-dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC-236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC-236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC-236 or 0.1 mm indometacin (all P < 0.001). CONCLUSION: Both SC-236 and indometacin suppressed the growth and urease activity of H. pylori in a dose-dependent manner, and increased its susceptibility to the antibiotics.

Anti-Bacterial Agents↗