Efficacy of a 1-week regimen of ranitidine bismuth citrate in combination with metronidazole and clarithromycin for Helicobacter pylori eradication.
(17/1145)
BACKGROUND: In order to improve the efficacy and simplicity of the FDA-approved regimen of ranitidine bismuth citrate (RBC) and clarithromycin dual therapy, we added an inexpensive antibiotic (metronidazole), changed the dosage scheme to twice daily dosing, and decreased the duration of therapy to 1 week. METHODS: This was an open label study in which subjects with previously untreated Helicobacter pylori infection documented by serology or endoscopy and confirmed by the 13C-urea breath test received a 1-week course of RBC 400 mg b.d., metronidazole 500 mg b.d. and clarithromycin 500 mg b.d. A repeat breath test was performed 4-6 weeks after completing therapy. RESULTS: Forty-seven out of 50 subjects completed the protocol. Intention-to-treat and per protocol cure rates were 86% and 91%, respectively. The regimen was well tolerated. Study drugs were stopped in two patients due to side-effects. The most common side-effect was self-limited diarrhoea. CONCLUSION: Twice daily RBC-based triple therapy with metronidazole and clarithromycin for 1 week is well tolerated and effective in eradicating H. pylori infection. (+info)
Antimicrobial activities of benzoxazinorifamycin (KRM-1648) and clarithromycin against Mycobacterium avium-intracellulare complex within murine peritoneal macrophages, human macrophage-like cells and human alveolar epithelial cells.
(18/1145)
Profiles of the in-vitro antimicrobial effects of KRM-1648 and clarithromycin against Mycobacterium avium-intracellulare complex (MAC) within murine peritoneal macrophages, the THP-1 human macrophage cell line and the A-549 type II alveolar epithelial cell line were determined. MAC organisms grew more rapidly in A-549 and THP-1 cells than in murine peritoneal macrophages. Peritoneal macrophages produced significant amounts of reactive nitrogen intermediates in response to MAC infection, but A-549 and THP-1 cells did not. KRM-1648 progressively killed M. intracellulare residing in macrophages, but did not completely eliminate M. intracellulare from A-549 and THP-1 cells. Moreover, in the case of M. intracellulare-infected A-549 and THP-1 cells, bacterial regrowth was observed during the middle to late phase of cultivation. Clarithromycin exhibited moderate levels of microbicidal activity against M. intracellulare residing in peritoneal macrophages, THP-1 cells and A-549 cells. The profiles of clarithromycin-mediated killing or inhibition of the intracellular organisms in A-549 and THP-1 cells were similar to those observed for organisms within peritoneal macrophages. (+info)
Lack of effect of zafirlukast on the pharmacokinetics of azithromycin, clarithromycin, and 14-hydroxyclarithromycin in healthy volunteers.
(19/1145)
This randomized, open-label, crossover study was conducted to investigate whether the coadministration of zafirlukast would affect the pharmacokinetics of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC). Twelve healthy subjects (six males and six females) received single 500-mg doses of azithromycin and clarithromycin with and without zafirlukast given to a steady-state concentration. Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose, respectively. Serum was assayed for azithromycin, clarithromycin, and 14-OHC concentrations by validated high-performance liquid chromatography assay systems. Data analyses were done by noncompartmental and nonparametric methods. Analysis of the patients indicated that the addition of steady-state concentrations of zafirlukast did not significantly alter the pharmacokinetic parameters of or overall exposure (based on the area under the concentration-time curve) to azithromycin, clarithromycin, and 14-OHC. While zafirlukast is a known inhibitor of CYP3A4, it does not appear to exert a clinically or statistically significant pharmacokinetic effect on azithromycin, clarithromycin, or 14-OHC. (+info)
Pharmacokinetics of a clarithromycin suspension administered via nasogastric tube to seriously ill patients.
(20/1145)
The pharmacokinetics of clarithromycin and its 14-(R)-hydroxylated metabolite were studied on two separate occasions after nasogastric administration of 500 mg of a clarithromycin suspension to 16 seriously ill adults in an intensive care unit. The clarithromycin suspension appeared to be adequately absorbed, and the pharmacokinetics of neither clarithromycin nor 14-(R)-hydroxyclarithromycin differed significantly between the two dosing periods. No substantial differences in pharmacokinetics were observed compared to previously published studies of other adult populations. Minimal intrapatient variability of pharmacokinetic parameters was observed in these seriously ill patients. (+info)
Antimicrobial activities and postantibiotic effects of clarithromycin, 14-hydroxy-clarithromycin, and azithromycin in epithelial cell lining fluid against clinical isolates of haemophilus influenzae and Streptococcus pneumoniae.
(21/1145)
The antimicrobial activity of concentrations of selected macrolides found in epithelial cell lining fluid was investigated. Clarithromycin demonstrated greater potency and a significantly longer postantibiotic effect (PAE) than azithromycin against Streptococcus pneumoniae. Azithromycin displayed greater potency, faster killing, and a longer PAE than clarithromycin against Haemophilus influenzae. Drug concentrations in epithelial cell lining fluid similar to those found in tissue did not improve the synergistic potential of 14-hydroxy-clarithromycin and indicate that a maximal PAE may exist despite increasing concentrations of drug. (+info)
Randomized controlled comparison of nitroimidazoles for the eradication of Helicobacter pylori and relief of ulcer-associated and non-ulcer dyspepsia.
(22/1145)
BACKGROUND: A combination of omeprazole, clarithromycin and either metronidazole or tinidazole is commonly used for Helicobacter pylori eradication. Metronidazole is considerably cheaper than tinidazole but the two have not previously been compared in a randomized trial. METHODS: One hundred and twenty dyspeptic H. pylori-positive patients with endoscopically defined peptic ulcer [DU (n = 65), GU (n = 12)] or non-ulcer dyspepsia (NUD, n = 43) were randomized to receive a 1-week course of twice daily omeprazole 20 mg, clarithromycin 250 mg and either metronidazole 400 mg (OCM) or tinidazole 500 mg (OCT) in a double-blind fashion. Eradication of H. pylori, safety and side-effects of treatment, dyspeptic symptom score and consumption of antisecretory drugs were assessed at 6 weeks and 1 year after treatment. RESULTS: H. pylori eradication was successfully achieved in 57/60 (95%, ITT analysis) of patients receiving OCT and 58/60 (97%, ITT analysis) receiving OCM. Both regimens had similar side-effect profiles, which accounted for only one patient withdrawal. All patients remained uninfected (as assessed by 14C-urea breath test) at 1-year follow-up, but major symptom improvements and decreased antisecretory drug use were only seen in patients with DU (P<0.0001). CONCLUSIONS: Treatment with OCM is as effective as the more expensive OCT at eradicating H. pylori. H. pylori eradication results in long-term relief of dyspeptic symptoms and reduced antisecretory consumption only in patients with DU, and not in those with NUD. (+info)
The effect of antibiotic resistance on the outcome of three 1-week triple therapies against Helicobacter pylori.
(23/1145)
BACKGROUND: Resistance of Helicobacter pylori to antibiotics may be a major reason for treatment failure. AIM: To evaluate the effect of primary H. pylori resistance to antibiotics on the cure rates of three anti-H. pylori 1-week triple therapies. METHODS: One hundred and sixteen consecutive patients diagnosed H. pylori-positive by gastric histology, rapid urease test and culture were enrolled. Activity of tested antibiotics was determined by means of the E-test. Patients were treated for 7 days with: (i) pantoprazole 40 mg o.d. plus amoxycillin 1 g b.d. and metronidazole 250 mg q.d.s. (PAM); (ii) pantoprazole 40 mg o.d. plus clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s. (PCM); or (iii) pantoprazole 40 mg o.d. plus amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (PAC). Two months after completion of therapy, endoscopy and gastric biopsies were repeated. RESULTS: Primary resistance rates to metronidazole, clarithromycin and amoxycillin were 17.2, 6.9 and 0%, respectively. Overall H. pylori cure rates expressed as intention-to-treat and per protocol analyses were, respectively, 79% and 86% with PAM, 82% and 89% with PCM, and 85% and 85% with PAC. Significantly lower cure rates were observed in metronidazole-resistant patients treated with PAM (56% vs. 96%, P = 0.01) or PCM (50% vs. 97%, P = 0.01). A trend towards lower H. pylori cure rates was observed in clarithromycin-resistant patients treated with PCM (67% vs. 91%, P = 0.74) or PAC (50% vs. 87%, P = 0.68). CONCLUSION: Primary resistance to metronidazole influences the H. pylori cure rate of anti-H. pylori proton pump inhibitor-based triple therapies which include this antibiotic. A similar trend exists for primary clarithromycin resistance. (+info)
Multisite reproducibility of results obtained by the broth microdilution method for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum.
(24/1145)
A multicenter study was conducted to assess the interlaboratory reproducibility of broth microdilution testing of the more common rapidly growing pathogenic mycobacteria. Ten isolates (four Mycobacterium fortuitum group, three Mycobacterium abscessus, and three Mycobacterium chelonae isolates) were tested against amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem, sulfamethoxazole, and tobramycin (M. chelonae only) in four laboratories. At each site, isolates were tested three times on each of three separate days (nine testing events per isolate) with a common lot of microdilution trays. Agreement among MICs (i.e., mode +/- 1 twofold dilution) varied considerably for the different drug-isolate combinations and overall was best for cefoxitin (91.7 and 97.2% for one isolate each and 100% for all others), followed by doxycycline, amikacin, and ciprofloxacin. Agreement based on the interpretive category, using currently suggested breakpoints, also varied and overall was best for doxycycline (97.2% for one isolate and 100% for the rest), followed by ciprofloxacin and clarithromycin. Reproducibility among MICs and agreement by interpretive category was most variable for imipenem. Based on results reported from the individual sites, it appears that inexperience contributed significantly to the wide range of MICs of several drugs, especially clarithromycin, ciprofloxacin, and sulfamethoxazole. New interpretive guidelines are presented for the testing of M. fortuitum against clarithromycin; M. abscessus and M. chelonae against the aminoglycosides; and all three species against cefoxitin, doxycycline, and imipenem. (+info)