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PubMed2000

Comparison of clarithromycin-sensitive and clarithromycin-resistant Mycobacterium avium strains isolated from AIDS patients during therapy regimens including clarithromycin.

OBJECTIVES: Sixteen Mycobacterium avium strains were isolated from the blood of eight AIDS patients over a period of months. All the patients were on combination therapies including clarithromycin, and all had treatment failure and relapses of M.avium bacteremia. Paired clarithromycin-sensitive and resistant M.avium strains isolated at the beginning of treatment and at the first relapse of bacteremia were compared. METHODS: The M.avium isolates were identified after hybridization with DNA probes specific for M.avium rRNA and typed epidemiologically with random amplified polymorphic DNA analyses using three arbitrary primers. The rate of intracellular cell entry or the tumour necrosis factor alpha induction by the M.avium isolates were studied in human monocytes and J774 cells. RESULTS: When the M.avium isolates were hybridized with the rRNA probes, we obtained lower hybridization values with clarithromycin-resistant isolates than with clarithromycin-sensitive isolates. This appeared to be due to smaller amounts of rRNA available for hybridization than to mutation of the 23S rRNA sequences in clarithromycin-resistant strains. The RAPD analyses showed that the clarithromycin-resistant isolates were clonally related to the clarithromycin-sensitive strains in six of the eight patients. The other two patients had a RAPD profile, suggesting a re-infection and/or polyclonal infection. The M.avium isolates obtained on day 0 and after the emergence of resistance to clarithromycin did not differ in terms of their intracellular entry rate, or in terms of tumour necrosis factor alpha induction. CONCLUSIONS: We infer that M.avium strains isolated during bacteraemic relapses on combination therapies including clarithromycin are epidemiologically related to the initial strain and do not show changes in the rate of intracellular cell entry and in terms of tumour necrosis factor alpha induction. Re-infections and/or polyclonal infections however, although less frequent, can also occur.

AIDS-Related Opportunistic Infections↗
PubMed1998

The bactericidal activity of clarithromycin versus ampicillin alone and in combination with omeprazole and/or bismuth against clarithromycin-susceptible and clarithromycin-resistant strains of Helicobacter pylori.

We evaluated the in vitro bactericidal effect of clarithromycin versus ampicillin alone and in combination against clarithromycin-sensitive and clarithromycin-resistant strains of Helicobacter pylori. No combination containing clarithromycin achieved complete bactericidal effect against clarithromycin-resistant strains. Complete bactericidal effect was achieved for all strains by triple-agent combinations that contained bismuth, omeprazole, and relatively high concentrations of ampicillin. These in vitro results demonstrate the additive bactericidal activity provided by a combination of agents for the eradication of H. pylori. Bismuth may play a particularly important role in the bactericidal effect.

Ampicillin↗
PubMed1992

Activities of WIN-57273, minocycline, clarithromycin, and 14-hydroxy-clarithromycin against Mycobacterium avium complex in human macrophages.

The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacterium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 micrograms of WIN-57273 per ml (MICs for the two strains, 1 microgram/ml), 4 microgram of 14-OH clarithromycin per ml (MICs, 8 and 2 micrograms/ml, respectively, at pH 7.4), 4 micrograms of minocycline per ml (MICs, 64 and 32 micrograms/ml, respectively), and 4 micrograms of clarithromycin per ml (MICs, 2 and 0.5 micrograms/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P less than 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P less than 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P less than 0.02), clarithromycin (P less than 0.02), 14-OH clarithromycin plus clarithromycin (P less than 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH clarithromycin (P less than 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P less than 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P less than 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.

Anti-Infective Agents↗
PubMed2001

Comparative efficacy of clarithromycin modified-release and clarithromycin immediate-release formulations in the treatment of lower respiratory tract infection.

BACKGROUND: A modified-release (MR) formulation of clarithromycin, distinct from the extended-release formulation, has recently been developed and has efficacy and tolerability similar to standard immediate-release (IR) clarithromycin, with the advantage of once-daily dosing. OBJECTIVE: The purpose of this study was to compare the efficacy (as measured by relief of clinical symptoms and eradication of specific pathogens) and tolerability of clarithromycin MR 500 mg administered once daily versus clarithromycin IR 250 mg administered twice daily for 5 days. METHODS: In this randomized, double-blind (with matching placebo), parallel-group. multicenter, controlled trial, patients with lower respiratory tract infection were randomized to 1 of 2 treatment regimens: clarithromycin MR 500 mg once daily plus clarithromycin IR 250 mg placebo twice daily or clarithromycin IR 250 mg BID plus clarithromycin MR 500 mg placebo once daily. RESULTS: Statistically equivalent clinical cure and success rates, overall symptomatic improvement, and bacteriologic responses were achieved with both treatments. In the clarithromycin MR group, the clinical cure rate was 72.5% (87/120), and the clinical success rate (cure plus symptomatic improvement) was 97.5% (117/120). Of the 124 patients treated with clarithromycin IR 250 mg BID, 98 (79.0%) achieved a clinical cure, and 120 (96.8%) achieved clinical success. There were no statistically significant between-group differences in clinical cure or success rates. More than 85% of patients in both study groups experienced improvement in dyspnea, cough, wheezing, chest discomfort, fatigue, and fever, and the visual appearance of sputum: these symptoms resolved completely in the majority of patients. Bacteriologic response (efficacy against specific pathogens), which was assessed as an objective efficacy criterion, was assessable for 40 patients treated with clarithromycin MR and 49 patients treated with clarithromycin IR. Bacteriologic eradication of the pretreatment target pathogen was achieved in 95.0% (38/40) of assessable patients treated with clarithromycin MR 500 mg once daily and 91.8% (45/49) of patients treated with clarithromycin IR 250 mg BID. Treatment-related adverse events were mild to moderate in all cases. Nausea (n = 9), diarrhea (n = 6), abdominal pain (n = 5), and gastric pain (n = 3) were the only study drug-related adverse events reported by > or = 1 patient in each treatment arm. Diarrhea was reported only in the clarithromycin IR group (n = 6) (P = 0.029 vs clarithromycin MR). CONCLUSIONS: Clarithromycin MR 500 mg administered once daily for 5 days is as effective and well tolerated as the IR formulation, with the advantage of once-daily dosing and fewer episodes of diarrhea.

Adolescent↗
PubMed1992

Individual efficacy of clarithromycin (A-56268) and its major human metabolite 14-hydroxy clarithromycin (A-62671) in experimental pneumococcal pneumonia in the mouse.

In man, clarithromycin (A-56268) is metabolized to a 14-hydroxy derivative (14-OH clarithromycin, A-62671); this metabolite is absent in mice. An experimental mouse model was used to compare the efficacy of clarithromycin versus 14-OH clarithromycin in pneumococcal pneumonia by treatment with either the parent drug or its 14-OH metabolite alone. Four groups of 15 mice were infected intra-tracheally with a virulent strain of Streptococcus pneumoniae serotype 3 (approximately 10(5) cfu/mouse). Treatment was begun 18 h post infection, with clarithromycin or erythromycin 50 mg/kg subcutaneously (sc) bd, 14-OH clarithromycin 25 mg/kg sc bd or antibiotic free saline sc bd for 24 or 48 h. Survival rates ten days after one day of treatment with clarithromycin, 14-OH clarithromycin, erythromycin, or saline were 53%, 60%, 27% and 0% respectively. After two days treatment the rates were 100%, 100%, 53% (P less than 0.01) and 0% respectively. Thirty-six h after two doses, 14-OH clarithromycin demonstrated superior intra-pulmonary killing activity to erythromycin (2.7 +/- 0.4 vs 6.6 +/- 0.8 log10 cfu/mL lung homogenate) (P less than 0.001) and comparable activity to clarithromycin (3.6 +/- 1.3 log10 cfu/mL). These results show that clarithromycin (50 mg/kg sc) and 14-OH clarithromycin (25 mg/kg sc) have similar in vivo efficacy in a mouse model, in which the 14-OH metabolite is not produced from clarithromycin. This suggests that in man, the clinical efficacy of clarithromycin is not impaired by metabolism to 14-OH clarithromycin, which achieves serum concentrations in man of approximately 1 mg/L after multiple doses of clarithromycin 500 mg po.

Animals↗
PubMed1999

The importance of clarithromycin dose in the management of Helicobacter pylori infection: a meta-analysis of triple therapies with a proton pump inhibitor, clarithromycin and amoxycillin or metronidazole.

BACKGROUND: It is not clear which dose of clarithromycin (500 mg b.d. or 250 mg b.d.) is more effective for Helicobacter pylori eradication in proton pump inhibitor-based triple therapies. METHODS: We undertook a meta-analysis of the effect of 7-day triple therapies consisting of a proton pump inhibitor (P), and clarithromycin (C) and amoxycillin (A) or metronidazole (M). A meta-analysis of all clinical trials performed in an adult population and published in English up to March 1998 was undertaken. Studies with doses of clarithromycin 500 mg b.d. or 250 mg b.d. only were included. RESULTS: A total of 82 studies (31 papers and 51 abstracts) involving 110 treatment arms and 6123 patients were analysed that met the predetermined inclusion and exclusion criteria. In the PAC combination, the pooled eradication rate in patients treated with clarithromycin 500 mg b.d. was 89.5% (95% CI: 86.9-92. 0%) by per protocol analysis and 86.6% (95% CI: 81.0-89.3%) by intention-to-treat analysis. These rates are significantly higher than those achieved with clarithromycin 250 mg b.d. (83.3% by per protocol and 78.2% by intention-to-treat analysis, both P < 0.0001). This difference was confirmed in head-to-head comparative studies. In the PMC regimen, clarithromycin 500 mg b.d. eradicated 90.8% (95% CI: 87.0-94.5%) of the infections compared to 88.5% (95% CI: 85.5-91. 5%) in patients treated with clarithromycin 250 mg b.d. by per protocol analysis (P = 0.082). The corresponding rates by intention-to-treat analysis for clarithromycin 500 mg b.d. and 250 mg b.d. was 88.3% and 86.7%, respectively (P = 0.259). CONCLUSIONS: Seven-day triple therapies with a proton pump inhibitor, clarithromycin and amoxycillin or metronidazole are highly effective treatments for the eradication of H. pylori. Clarithromycin 500 mg b. d. should be used in these combinations to achieve the best first treatment results, which can minimize the subsequent development of bacterial resistance to clarithromycin and metronidazole.

Adult↗
PubMed2001

The activity of 14-hydroxy clarithromycin, alone and in combination with clarithromycin, against penicillin- and erythromycin-resistant Streptococcus pneumoniae.

There are no data regarding the activity of clarithromycin's active metabolite, 14-hydroxy clarithromycin, against penicillin-intermediate, penicillin-resistant or erythromycin-resistant Streptococcus pneumoniae. Agar dilution MICs were determined for clarithromycin, 14-hydroxy clarithromycin (henceforth called 'metabolite'), azithromycin, erythromycin and clarithromycin/metabolite (2:1 and 1:1 ratio) against 24 penicillin-intermediate and 14 penicillin-resistant strains, including 13 erythromycin-resistant clinical strains and one ATCC strain of S. pneumoniae. The interaction between clarithromycin and its metabolite was determined using an agar chequerboard assay against all isolates, and time-kill tests were performed against five penicillin-intermediate (macrolide-susceptible) and five penicillin-resistant (two macrolide-resistant) strains of S. pneumoniae using all antibiotics alone at simulated peak serum concentrations, and clarithromycin/metabolite in a 2:1 ratio (physiological). MICs were as follows: clarithromycin, 0.008-->64 mg/L; metabolite, 0.015-->64 mg/L; erythromycin, 0.015-->64 mg/L; azithromycin, 0.125-->64 mg/L; clarithromycin/metabolite (1:1 and 2:1 combinations), 0.001-->64 mg/L. The MIC of the clarithromycin/metabolite combination was one or more tube dilution lower than the MIC of clarithromycin in 28 of the isolates tested. In chequerboard testing, 13 strains (seven erythromycin susceptible and six erythromycin resistant) demonstrated synergy, 18 additivity and seven indifference. In time-kill testing, bacterial eradication below detection limits occurred with clarithromycin and metabolite in seven of 10 organisms. The combination of parent and metabolite was more rapidly bactericidal than clarithromycin alone in six of the seven isolates (P = 0.026). The metabolite has potent activity against S. pneumoniae and enhances the activity of the parent compound against this organism. The metabolite's activity must be considered in evaluating clarithromycin in vitro to avoid underestimation of clarithromycin's activity against the pneumococcus.

Anti-Bacterial Agents↗
PubMed1990

Enhancement of the in vitro and in vivo activities of clarithromycin against Haemophilus influenzae by 14-hydroxy-clarithromycin, its major metabolite in humans.

MICs of clarithromycin and its major human metabolite, 14-hydroxy-clarithromycin, for Haemophilus influenzae in combination were reduced two- to fourfold compared with the MICs of each compound alone. Serum reduced the MICs of the parent compound and metabolite two- to fourfold compared with the MICs in medium without serum. In serum spiked with clinically relevant concentrations of clarithromycin and 14-hydroxy-clarithromycin at a fixed ratio of 4:1, 15 of 16 strains (94%) were inhibited and killed by combinations containing 1.2 and 0.3 micrograms/ml, respectively. In time kill experiments, the combination of parent compound and metabolite at one-fourth and one-half of their individual MICs, respectively, reduced bacterial counts by greater than 5 log CFU. The postantibiotic effect of clarithromycin combined with 14-hydroxy-clarithromycin was twice that of clarithromycin when tested alone. When orally administered to gerbils with H. influenzae otitis media, the 14-hydroxy metabolite was significantly more active than clarithromycin in reducing bacterial counts from the middle ear. The in vivo activity of the two compounds in combination was synergistic or additive, depending on the level of H. influenzae present at the time treatment was initiated. Significant reductions in bacterial counts and increases in cure rates were observed when clarithromycin at 50 or 100 mg/kg of body weight was combined with 14-hydroxy-clarithromycin at 12 mg/kg or higher. Results from in vitro and in vivo combinations suggest that routine susceptibility tests and animal efficacy studies with clarithromycin alone may underestimate its potential efficacy against H. influenzae.

Animals↗
PubMed2002

Fluorescence in situ hybridization vs. epsilometer test for detection of clarithromycin-susceptible and clarithromycin-resistant Helicobacter pylori strains in gastric biopsies from children.

AIM: To compare the results of culture and epsilometer test with fluorescence in situ hybridization for the detection of Helicobacter pylori and the presence of clarithromycin-susceptible and clarithromycin-resistant strains in antral biopsies from children. METHODS: Antral biopsies from 149 unselected children were investigated prospectively; 15 had previously received anti-H. pylori therapy. H. pylori status was defined by histology, rapid urease test and 13C-urea breath test. Fluorescence in situ hybridization was applied on fresh tissue with probes specific for the clarithromycin-susceptible wild type and three clarithromycin-resistant mutants. Susceptibility to clarithromycin was tested by epsilometer test in two laboratories. RESULTS: Culture and fluorescence in situ hybridization gave negative results in all 66 H. pylori-negative children (specificity, 100%). Of 83 infected children, cultures were successful in 75 (90%), epsilometer test in 71 (86%) and fluorescence in situ hybridization in 77 (93%). Eleven children (13%) showed discrepant results between the applied methods, indicating mixed infection. Clarithromycin-resistant isolates were identified in 16 of 73 previously untreated children. CONCLUSIONS: Primary resistance to clarithromycin is common (22%) in H. pylori isolates from children living in Germany. Fluorescence in situ hybridization is an excellent, fast method for the detection of H. pylori and clarithromycin-resistant mutants in gastric biopsies. Multiple biopsies identify mixed infections, indicating that clarithromycin-resistant and clarithromycin- susceptible strains are not evenly distributed within the stomach.

Adolescent↗
PubMed2006

Update on clarithromycin resistance in Helicobacter pylori in Hong Kong and its effect on clarithromycin-based triple therapy.

AIM: To determine the antibiotic susceptibility of Helicobacter pylori and evaluate the efficacy of a clarithromycin-based triple therapy in relation to antibiotic resistance. METHODS: Consecutive patients referred for upper endoscopy due to dyspeptic symptoms were recruited. Gastric biopsies were obtained for the CLO test, histology and culture. Antibiotic susceptibility was assessed by the E-test. Patients with H. pylori infection received rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily for 7 days. RESULTS: Of 234 patients recruited, 124 were H. pylori-positive and culture was successful in 102 patients. The updated prevalences of resistance to clarithromycin, amoxicillin and metronidazole were 7.8, 0 and 39.2%, respectively. A total of 86 patients received 1-week triple therapy with rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily, and 81 patients attended the follow-up test. Eradication rates by per-protocol and intention-to-treat analysis were 92.6 and 87.2%, respectively. The eradication rate by per protocol was significantly higher in patients with clarithromycin-susceptible strains than in those with clarithromycin-resistant strains (98.6 vs. 28.6%, p < 0.001). CONCLUSION: Clarithromycin resistance reduces the clinical efficacy of clarithromycin-based triple therapy. However, due to the low prevalence of clarithromycin resistance, clarithromycin-based therapy is still the first choice for clinical use.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

In vitro activity of clarithromycin alone and in combination with ciprofloxacin or levofloxacin against Legionella spp.: enhanced effect by the addition of the metabolite 14-hydroxy clarithromycin.

Clarithromycin is metabolized to an active metabolite, 14-hydroxy clarithromycin. These compounds have demonstrated excellent in vitro activity against Legionella species, with both agents having significantly lower MICs than erythromycin. Using a checkerboard assay, the activity of clarithromycin and its hydroxy metabolite, alone and in combination, was examined against 41 Legionella organisms. The activity of clarithromycin and 14-hydroxy clarithromycin, in a 2:1 ratio, plus ciprofloxacin or levofloxacin was also determined. Activity of the antibiotic combinations was determined by calculating the fractional inhibitory concentration index. An agar dilution method using buffered charcoal yeast extract media was used for susceptibility and synergy testing. An inoculum of 10(4) CFU/spot was used, with all plates incubated at 35 degrees C for 48 h. The MIC90 for clarithromycin or 14-hydroxy clarithromycin alone was 0.5, versus 0.25 microgram/mL for the combination. Additive effects were observed with clarithromycin and its hydroxy metabolite for 61% of the Legionella species, with fractional inhibitory concentration indices ranging from 0.63 to 1.25. The 14-hydroxy metabolite significantly increased the activity of both fluoroquinolone/clarithromycin combinations. Based on these data, in vitro susceptibility testing of agents such as clarithromycin should be reevaluated to account for the activity of active metabolites.

Anti-Bacterial Agents↗
PubMed2002

An open-label, randomized, multicenter, comparative study of the efficacy and safety of 7 days of treatment with clarithromycin extended-release tablets versus clarithromycin immediate-release tablets for the treatment of patients with acute bacterial exacerbation of chronic bronchitis.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of clarithromycin extended-release (ER) tablets and immediate-release (IR) tablets. METHODS: This was a Phase III, open-label, randomized, multicenter, comparative study in ambulatory patients with a diagnosis of acute exacerbation of chronic bronchitis (AECB). Eligible patients were randomized 1:1 to receive either 1 clarithromycin ER 500-mg tablet QD for 7 days or 1 clarithromycin IR 250-mg tablet BID for 7 days. Clinical and bacteriologic responses were assessed within 48 hours after the last dose of study drug and at a test-of-cure visit 21 +/- 2 days posttreatment. RESULTS: Of 233 patients randomized, 162 (86/117 [73.5%] in the ER group and 76/115 [66.1%] in the IR group) completed the study protocol. Compliance did not differ significantly between the treatment groups; however, significantly fewer patients in the ER group reported missing doses of study medication than in the IR group (7/118 [5.9%] vs 16/115 [13.9%]; P = 0.04). The clinical cure rates for the clarithromycin ER and IR groups were 81.0% (68/84) and 82.1% (64/78) and the clinical success (clinical cure plus clinical improvement) rates were 94.0% [79/84] and 89.7% [70/78], respectively. There were insufficient data for analysis of bacteriologic efficacy. However, bacteria were eradicated or presumed eradicated in 71.4% (10/14) and 79.2% (19/24) of patients in the ER and IR groups, respectively. The number of adverse events (AEs) considered to be possibly or probably related to study drug (23.4% [52/222] of patients receiving clarithromycin ER and 24.4% [43/176] of patients receiving clarithromycin IR) was similar between groups, as was the severity of these events (94.2% [49/52] in the ER group classified as mild or moderate vs 93.0% [40/43] in the IR group). Overall, the most commonly reported AEs were diarrhea, nausea, abdominal pain, headache, and taste disturbance. CONCLUSION: Clarithromycin ER 500-mg tablets QD for 7 days were as effective and well tolerated as clarithromycin IR 250-mg tablets BID for 7 days in treating adults with AECB.

Adult↗
PubMed2001

Clarithromycin resistance of Helicobacter pylori has a major impact on the efficacy of the omeprazole-amoxicillin-clarithromycin therapy.

Clarithromycin resistance of Helicobacter pylori is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (PPI-AC) therapy, which is the first-line regimen in our country. We determined the respective effects of clarithromycin primary and secondary resistances on efficacy of the PPI-AC regimen and examined whether failures were associated with persistence of the same strain or with emergence of a new one. Hundred and twenty three H. pylori-infected patients were treated for seven days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. MICs of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA. The pre-treatment and post-treatment prevalences of clarithromycin resistance were 18.7% (23/123) and 69.2% (9/13), respectively. The rates of eradication were 67.6% (69/102), 78.8% (67/85), and 11.8% (2/17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection; resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other. In conclusion, in our hospital, failures of the PPI-AC therapy are related to both clarithromycin primary and secondary resistances but emergence of secondary resistance does not explain all failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.

Adolescent↗
PubMed1998

One-week triple therapy using omeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia: influence of dosage of omeprazole and clarithromycin.

BACKGROUND: Triple therapy based upon omeprazole, amoxycillin and clarithromycin for 7 days is the reference treatment used in France for the eradication of Helicobacter pylori. However, optimal dosages of omeprazole and clarithromycin have not been determined. AIMS: To compare four eradication regimens using this treatment in patients with non-ulcer dyspepsia. METHODS: Two hundred and seventy-four patients with symptoms of dyspepsia, normal upper GI endoscopy and a positive urease test were included in the study. A 13C-urea breath test (UBT) was obtained before and 6 weeks after treatment. Patients were randomized to one of the following 7-day regimens: 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O20AC500) or 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O20AC1000) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O40AC500) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O40AC1000). Compliance was assessed by returned tablet counts. Eradication was defined as conversion from positive 13C-UBT at entry to negative 13C-UBT 6 weeks after cessation of therapy. RESULTS: Two hundred and fifty-eight patients were included in the intention-to-treat (ITT) analysis. From the least to the most effective regimen, eradication rates were: O20AC1000: 60.0% (95% CI: 47.6-72.4), O20AC500: 64.1% (52.3-75.8), O40AC1000: 64.2% (52.7-75.7), O40AC500: 74.6% (64.2-85.0) (N.S.). Overall compliance was good in 92% of patients. The most frequent adverse events were diarrhoea and taste impairment, occurring mainly in the high-dose clarithromycin groups. CONCLUSIONS: Eradication rates obtained in this study were lower than those expected on the basis of previously reported studies. This study supports the use of a double dose of omeprazole, although the difference between groups was non-significant, but provides no argument in favour of a high dose of clarithromycin.

Amoxicillin↗
PubMed1999

Impact of clarithromycin resistance on the effectiveness of a regimen for Helicobacter pylori: a prospective study of 1-week lansoprazole, amoxycillin and clarithromycin in active peptic ulcer.

BACKGROUND: Clarithromycin is a key antimicrobial in the combinations used to cure Helicobacter pylori infections, so there is a need to define the impact of in vitro resistance on in vivo results. METHODS: A prospective trial was designed to study the effectiveness of the 1-week combination of lansoprazole, clarithromycin and amoxycillin in 102 consecutive patients with active peptic ulcer. The pre-treatment and post-treatment sensitivity to amoxycillin, metronidazole and clarithromycin were studied by E-test, and H. pylori status was defined by histology, culture and urease test at diagnosis and one month after treatment, and by urea-breath test 2 months after treatment. RESULTS: The eradication rate (intention-to-treat analysis) was 77% (95% CI: 69-86). No clinical factor was found to be different between eradicated and non-eradicated patients. Clarithromycin-resistant strains were found in 10 (10%; CI: 5-17) patients. The eradication rate was 20% (CI: 3-56) in these patients vs. 83% (CI: 75-91) in patients harbouring clarithromycin-sensitive strains (P < 0.001). A logistic-regression analysis confirmed clarithromycin resistance as the only factor associated with treatment failure. CONCLUSIONS: Clarithromycin resistance significatively impairs the effectiveness of the combination of lansoprazole, amoxycillin, and clarithromycin. The 80% efficacy goal will be difficult to reach in areas with high (>10%) primary clarithromyicin resistance, if currently recommended proton pump inhibitor-triple therapies are used.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Impact of Helicobacter pylori resistance to clarithromycin on the efficacy of the omeprazole-amoxicillin-clarithromycin therapy.

BACKGROUND: Helicobacter pylori resistance to clarithromycin is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (proton pump inhibitor-AC) therapy, which is the first-line regimen in France. AIM: To determine the respective effects of clarithromycin primary and secondary resistances on efficacy of the proton pump inhibitor-AC regimen and to determine whether failures are associated with persistence of the same strain or with emergence of a new one. METHODS: A total of 123 H. pylori-infected patients were treated for 7 days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. Minimal inhibitory concentrations of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA. RESULTS: The pre-treatment and post-treatment prevalences of clarithromycin resistance were 19% (23 out of 123) and 69% (nine out of 13), respectively. The rates of eradication were 68% (69 out of 102), 79% (67 out of 85), and 12% (two out of 17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection. Resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other. CONCLUSIONS: In our hospital, failures of the proton pump inhibitor-AC therapy are related to both clarithromycin primary and secondary resistances, but the emergence of secondary resistance does not explain all of the failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.

Administration, Oral↗
PubMed2002

Eradication rates of clarithromycin-resistant Helicobacter pylori using either rabeprazole or lansoprazole plus amoxicillin and clarithromycin.

BACKGROUND: The resistance of Helicobacter pylori to clarithromycin has become one of the primary reasons for eradication failure. AIM: To compare the eradication rates of triple therapy using amoxicillin (A), clarithromycin (C) and rabeprazole (R) or lansoprazole (L) against clarithromycin-sensitive and clarithromycin-resistant strains. METHODS: Two hundred and ninety-five patients were randomly divided into four groups and treated for 1 week: 147 cases were treated with RAC, i.e. 49 cases with R20C400 (10 mg R + 750 mg A + 200 mg C, twice daily), 48 cases with R40C400 (20 mg R + 750 mg A + 200 mg C, twice daily) and 50 cases with R40C800 (20 mg R + 750 mg A + 400 mg C, twice daily); 148 cases with treated with LAC (30 mg L + 750 mg A + 200 mg C, twice daily). RESULTS: According to intention-to-treat and per protocol analyses, the eradication rates were 88% and 91% with RAC and 78% and 81% with LAC; the eradication rates with R20C400, R40C400 and R40C800 were 94%, 81% and 86%, respectively, in the intention-to-treat analysis. In addition, the eradication rates for clarithromycin-sensitive strains with RAC and LAC were 98% and 89%, respectively, and for clarithromycin-resistant strains with RAC and LAC were 8.1% and 0%, respectively. CONCLUSIONS: The eradication rate was significantly higher with RAC than LAC. The eradication rate for clarithromycin-resistant strains was low in both groups, and an improved eradication rate could not be achieved by changing the dose of clarithromycin or proton pump inhibitor.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Postantibiotic effects and bactericidal activities of clarithromycin-14-hydroxy-clarithromycin, versus those of amoxicillin-clavulanate, against anaerobes.

The bactericidal activities and postantibiotic effects (PAE) of clarithromycin-14-hydroxy-clarithromycin and amoxicillin-clavulanate against Bacteroides fragilis and Peptostreptococcus anaerobius were determined. A concentration of twice the MIC resulted in bactericidal activity against four of four and three of four organisms at 24 h with clarithromycin-14-hydroxy-clarithromycin and amoxicillin-clavulanate, respectively. The PAE of clarithromycin-14-hydroxy-clarithromycin was 1.44 to 3.20 h, compared to the less than 1 h of amoxicillin-clavulanate. Clarithromycin-14-hydroxy-clarithromycin possesses good activity against susceptible anaerobes.

Amoxicillin-Potassium Clavulanate Combination↗