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PubMed1992

Comparative in vitro activity of clarithromycin. Spanish Collaborative Group.

The activity in vitro of clarithromycin, a new macrolide, was compared to that of various antibiotics in tests using 3,880 clinical isolates. Clarithromycin was two times more active than erythromycin against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, streptococci of groups C, G and F, Brucella melitensis, Legionella pneumophila and Mycoplasma spp., 16 times more active against Ureaplasma urealyticum and 2 to 4 times less active against Campylobacter spp. In general, clarithromycin showed intrinsic activity 2 to 4 times higher than that of roxithromycin and 4 to 8 times higher than that of miocamycin. Cross-resistance was found between the macrolides. Clarithromycin was bactericidal against Streptococcus spp. and Haemophilus influenzae.

Clarithromycin↗
PubMed1995

Helicobacter pylori gastritis therapy with omeprazole and clarithromycin increases serum carbamazepine levels.

An antibiotic combination that includes a proton pump inhibitor such as omeprazole and an antibiotic such as clarithromycin is likely to become the new standard regimen for treatment of Helicobacter pylori gastritis because this combination is extremely effective and very well tolerated. The current report highlights a potentially significant pharmakokinetic drug interaction between clarithromycin and carbamazepine in two patients with long-standing epilepsy who were given such therapy for Helicobacter pylori gastritis. In both cases, clarithromycin therapy was temporally related to an increase in serum carbamazepine levels, which returned to the therapeutic range following cessation of clarithromycin therapy. The potential implications of this newly recognized drug interaction are discussed.

Adult↗
PubMedDate not supplied

A survey of the quality of generic clarithromycin products manufactured in Slovenia and Israel.

This study evaluated the quality of 11 generic clarithromycin products obtained in Poland, Slovakia, Slovenia, or Israel and manufactured in Slovenia or Israel. The generic products were examined visually, assayed by high-pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories. Fifty-five percent of generic products fell short of the specifications for the innovator product. Ten percent of the generic products did not contain the amount of clarithromycin claimed in the label; 18% released less drug than did the branded tablets in the standard dissolution assay. In light of these results, it is not possible to conclude that all generic tablets are of the same quality as the innovator product; clinical trial results achieved with branded clarithromycin should not be extrapolated to generic products.

Anti-Bacterial Agents↗
PubMed1999

CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin.

OBJECTIVES: Omeprazole is metabolized mainly by CYP2C19 which has two major mutations (CYP2C19*2 in exon5 and CYP2C19*3 in exon4) associated with the poor metabolizer (PM) phenotype. The aim of this study was to examine the relationship between genetic polymorphism of CYP2C19 and metabolism of omeprazole administrated as a single dose or as repeated-doses, which were in both cases co-administered with clarithromycin. METHODS: Twelve healthy Japanese subjects were typed for CYP2C19 polymorphism. In the single-dose study, plasma levels of omeprazole and its metabolites were measured for 24 h after administration of 20 mg omeprazole and 400 mg clarithromycin to six healthy Japanese subjects. In the repeated-dose study, plasma levels of omeprazole and its metabolites were measured after repeated oral administration of 20 mg omeprazole and 400 mg clarithromycin twice daily for 6 days and then after 20 mg omeprazole and 400 mg clarithromycin once on the 7th day to the other 6 healthy Japanese subjects. RESULTS: In the single-dose study, the areas under the plasma concentration-versus-time curve (AUCs) of omeprazole of homozygotes for the wild-type allele (*1/*1 n = 2), heterozygotes (n = 3) for the CYP2C19*2 (*1/ *2) or for the CYP2C19*3 (*1/*3) and heterozygote (n = 1) for the two defects (*2/*3) were on average 450, 1007 and 6710 ng x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5-hydroxyomeprazole for *1/*1, *1/*2 or *1/*3 and *2/*3 were 1, 2 and 30, respectively. In the repeated-dose study, the AUCs of omeprazole for * 1/ *1, *1/*2 or *1/*3 and *2/*3 were 4041 (n = 2), 3149 (n = 3) and 6684 (n = 1) ng x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5-hydroxyomeprazole for *1/*1, * 1/*2 or * 1/*3 and *2/*3 were7, 11 and 30, respectively. In the repeated-dose study, the AUC of omeprazole of * 1/*1 genotypes was nine-fold higher, that of *1/*2 and *1/*3 genotypes was three-fold higher, and the Cmax value of omeprazole was three-fold higher compared with subjects with the same genotype in the single-dose study. However, there were few differences in the AUC and Cmax of omeprazole between the *2/*3 genotype in the single-dose study and the homozygote for the CYP2C19*2 (*2/*2) in the repeated-dose study. CONCLUSION: Subjects with *1/*1, *1/*2 and *1/*3 genotypes in the repeated-dose study had lower CYP2C19 activity than subjects of the same genotype in the single-dose study. The difference in omeprazole metabolism between subjects with different genotypes observed on day 1 seemed to disappear after 7 days of repeated-dose administration.

Adult↗
PubMed2002

Double-blind, placebo-controlled study comparing the effect of azithromycin with clarithromycin on oropharyngeal and bowel microflora in volunteers.

The purpose of this double-blind study was to assess the effect of azithromycin and clarithromycin on oral and fecal microflora. Bacterial species from fecal samples and throat washes from healthy volunteers were identified and quantified before, during and after receipt of either placebo ( n=6), azithromycin (500 mg once daily for 3 days; n=6) or clarithromycin (500 mg twice daily for 7 days; n=6). In both antibiotic groups, the changes in oropharyngeal aerobic microflora following antibiotic administration were minor. Antibiotics neither changed the bacterial load of Streptococcus spp. compared with placebo, nor did macrolide-resistant streptococci emerge. In the fecal aerobic microflora, the number of organisms of the family Enterobacteriaceae decreased slightly after antibiotic administration in both the clarithromycin and the azithromycin groups, but levels normalized by day 21 after therapy. No colonization with nonfermenters or Clostridium difficile was seen, and the total number of anaerobic bacteria was not affected in any study group. In conclusion, there were no significant differences between azithromycin and clarithromycin in their effect on human oropharyngeal and intestinal microflora, nor was the use of these antibiotics associated with colonization by resistant, gram-positive organisms or overgrowth of opportunistic microorganisms.

Adolescent↗
PubMed2007

Safety and tolerability of clarithromycin administered to children at higher-than-recommended doses.

A tendency among pediatricians in Greece to use higher-than-recommended doses of clarithromycin was noted over several years, prompting this study of the safety and tolerability of this macrolide in 343 children over a period of 9 months. The study group comprised nonhospitalized patients of 29 pediatricians practicing in Athens. All were prescribed clarithromycin for upper respiratory (n = 257) or lower respiratory tract infection (n = 78). Overall, 77.8% were treated with doses that exceeded the recommended dose of 15 mg/kg/day, and 26% received doses of > or = 30 mg/kg/day (median dose, 20 mg/kg/day). The tolerability of clarithromycin was judged as "very good" in 75% of the children, as "good" in 16%, and as "moderate" in 5%, whereas intolerability was observed in 4% of the cases. Adverse reactions, mainly gastrointestinal in nature, were reported in 17.5% of the cases. With regard to both tolerability and adverse events recorded, there were no statistically significant differences between the group of patients who received the recommended dose and the group who received higher doses. Clarithromycin continues to present a safe and well-tolerated profile for the treatment of common pediatric infections, even when administered at higher-than-recommended doses. Whether it is more efficacious in this setting is a matter for further study.

Adolescent↗
PubMed2005

Antimicrobial effects of antioxidants with and without clarithromycin on Helicobacter pylori.

Increasing resistance to currently used antimicrobials has resulted in the evaluation of other agents that have antimicrobial activity against Helicobacter pylori. H. pylori American Type Culture Collection (ATCC) strain 49503 (a toxin-producing strain known to be associated with gastric cancer) was grown, a cell suspension prepared in 2 mL PBS and diluted 10-fold. One hundred microL of this cell suspension was added to vitamin C 0.5%, vitamin E 0.5%, garcinol 100 microg/mL, Protykin (containing 50% trans-resveratrol) 100 microg/mL and garcinol + Protykin 100 microg/mL in Lennox broth, and incubated for 16 h under microaerophilic conditions. Three replicates of 10 microL from each 10(-7) dilution tube were plated, colonies were counted after 16 h, and growth of H. pylori was confirmed by the CLO test. These colony counts were compared to control cultures without the addition of any antioxidants. The experiments were then repeated with the addition of 15 microg/mL of clarithromycin to experimental and control samples. Enhanced killing of H. pylori by 37.6% was noted when vitamin C was added, which increased to 66% when clarithromycin was added, compared to controls (p < 0.05). With garcinol and Protykin alone there was 91.4 and 87% killing of H. pylori, respectively, while a combination of garcinol + Protykin resulted in 90.8% killing compared to controls (p < 0.05). When clarithromycin was added, there was 76.3% increased killing with garcinol alone, 55.3% with Protykin alone, and 73.7% with garcinol + Protykin compared to controls (containing clarithromycin) (p < 0.05). Vitamin E had no effect on H. pylori growth compared to controls. We conclude from this study that some antioxidants such as vitamin C, garcinol and Protykin, but not vitamin E, may have potential as antimicrobial agents against H. pylori.

Anti-Bacterial Agents↗
PubMedDate not supplied

Drug intolerance to high-dose clarithromycin among elderly patients.

We treated 13 elderly patients with chronic mycobacterial lung disease with clarithromycin using 1000 mg b.i.d. as monotherapy. Patients had a mean age of 70 years, and 12 of 13 had creatinine clearances of 31-71 ml/min. Adverse events were seen in 100% of patients, with the most common being bitter taste (92%), nausea (92%), vomiting (54%) and central nervous system symptoms (54%). Elevated liver enzymes developed in five (38%) of 13 patients at weeks 1-6 of therapy. Mean serum levels of clarithromycin plus its 14-OH metabolite were 12.9 +/- 3.6 micrograms/ml (SD). There were 11 patients (85%) who discontinued the high dose within 3 months because of side effects. Serum drug levels of clarithromycin plus its 14-OH metabolite consistently exceeded 12 micrograms/ml in six of six patients who discontinued drug (10 of 10 values) compared with neither of two patients who tolerated the high dose (0 of 6 values). A dose reduction to 500 mg b.i.d. was well tolerated (nine of 10 patients). Future trials with clarithromycin in this population should use lower doses with attention to body mass and renal function to minimize side effects.

Aged↗
PubMed2006

Clarithromycin reduces recurrent cardiovascular events in subjects without periodontitis.

Inflammation leading to acute coronary syndrome may be triggered by bacteria causing periodontal infection. We investigated if recurrence of cardiovascular events in unstable coronary patients are associated with periodontitis or microbiological/serological markers of it. Periodontitis-related parameters of 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months, were adjusted to the occurrence of a recurrent cardiovascular event during a follow-up period (average 519 days). In the age group under 65 years the patients with periodontitis had a univariate odds ratios (OR) 95% confidence intervals (95% CI) of 5.0 (1.02-24.55) for a recurrent cardiovascular event in comparison with patients without periodontitis. Dental status correlated positively with serum lipopolysaccharide concentrations and combined IgG antibody response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. The end point frequency did not differ between clarithromycin and placebo groups in bacterium-positive, seropositive, or periodontitis patients. Fewer end points in clarithromycin group were seen in bacterium-negative, seronegative, edentulous, and non-periodontitis patients. Periodontitis and edentulousness are associated with recurrent cardiovascular events, especially in younger patients. Long-term clarithromycin therapy seems to be beneficial in prevention of recurrent cardiovascular events in non-periodontitis but not in periodontitis patients.

Adult↗
PubMed2004

The effect of clarithromycin, fluconazole, and rifabutin on sulfamethoxazole hydroxylamine formation in individuals with human immunodeficiency virus infection (AACTG 283).

BACKGROUND: Sulfamethoxazole hydroxylamine formation, in combination with long-term oxidative stress, is thought to be the cause of high rates of adverse drug reactions to sulfamethoxazole in human immunodeficiency virus (HIV)-infected subjects. Therefore the goal of this study was to determine the effect of fluconazole, clarithromycin, and rifabutin on sulfamethoxazole hydroxylamine formation in individuals with HIV-1 infection. METHODS: HIV-1-infected subjects (CD4 + count >/=200 cells/mm 3 ) were enrolled in a 2-part (A and B), open-label drug interaction study (Adult AIDS Clinical Trial Group [AACTG] 283). In part A (n = 9), subjects received cotrimoxazole (1 tablet of 800 mg sulfamethoxazole/160 mg trimethoprim daily) alone for 2 weeks and then, in a randomly assigned order, cotrimoxazole plus either fluconazole (200 mg daily), rifabutin (300 mg daily), or fluconazole plus rifabutin, each for a 2-week period. Part B (n = 12) was identical to part A except that clarithromycin (500 mg twice daily) was substituted for rifabutin. RESULTS: In part A, fluconazole decreased the area under the plasma concentration-time curve (AUC), percent of dose excreted in 24-hour urine, and formation clearance (CL f ) of the hydroxylamine by 37%, 53%, and 61%, respectively (paired t test, P < .05). Rifabutin increased the AUC, percent excreted, and CL f of the hydroxylamine by 55%, 45%, and 53%, respectively ( P < .05). Fluconazole plus rifabutin decreased the AUC, percent excreted, and CL f of the hydroxylamine by 21%, 37%, and 46%, respectively ( P < .05). In part B the fluconazole data were similar to those of part A. Overall, clarithromycin had no effect on hydroxylamine production. CONCLUSIONS: If the exposure (AUC) to sulfamethoxazole hydroxylamine is predictive of sulfamethoxazole toxicity, then rifabutin will increase and clarithromycin plus fluconazole or rifabutin plus fluconazole will decrease the rates of adverse reactions to sulfamethoxazole in HIV-infected subjects.

Adult↗
PubMed2004

High levels of dual resistance to clarithromycin and metronidazole and in vitro activity of levofloxacin against Helicobacter pylori isolates from patients after failure of therapy.

Current treatment for Helicobacter pylori infections generally includes two or more antimicrobials (amoxicillin, clarithromycin, nitroimidazoles, tetracycline, etc.), but treatment fails in 10-20% of all cases, often because of drug resistance. Levofloxacin has been proposed as an alternative for these refractory infections. We examined 67 H. pylori isolates from patients unsuccessfully treated with amoxicillin, clarithromycin, metronidazole and levofloxacin. Minimum inhibitory concentrations determined with the epsilometer test revealed clarithromycin and metronidazole resistance in 91 and 82.1% of the isolates, respectively; 52 (77.6%) were resistant to both drugs. All 67 isolates were susceptible to amoxicillin and tetracycline. Fifty-two isolates had levofloxacin MICs of 0.01-2 mg/l; the remaining 15 (22.4%), all clarithromycin- and metronidazole-resistant, had MICs >/= 8 mg/l. Levofloxacin may be an option for refractory H. pylori infections, but the choice should be based on in vitro susceptibility data, and physicians should consider local resistance patterns when treating these infections empirically.

Clarithromycin↗
PubMed2005

Comparative pharmacodynamics of telithromycin and clarithromycin with Streptococcus pneumoniae and Staphylococcus aureus in an in vitro dynamic model: focus on clinically achievable antibiotic concentrations.

To compare the pharmacodynamics of telithromycin and clarithromycin, killing kinetics of differentially susceptible Streptococcus pneumoniae and Staphylococcus aureus exposed to clinical doses of telithromycin and clarithromycin were studied in an in vitro dynamic model that simulates human pharmacokinetics. With S. pneumoniae, a bacterial strain-independent and antibiotic-independent relationship was delineated for the area between the control growth curve and the time-kill curve (ABBC) and the simulated ratio of the area under the curve (AUC) to minimum inhibitory concentration (MIC). Based on the ABBC-AUC/MIC relationship, a greater anti-pneumococcal effect of 800mg telithromycin compared with 2x500 mg clarithromycin was predicted for a hypothetical strain with MICs equal to the respective MIC50 values. Although telithromycin was less efficient against S. aureus, treatment for 3 days with telithromycin was not accompanied by a loss in susceptibility, whereas the enrichment of resistant staphylococci occurred with one of the two clarithromycin-treated strains.

Anti-Bacterial Agents↗
PubMed2006

Open-label study of clarithromycin in patients with undifferentiated connective tissue disease.

OBJECTIVE: The macrolide family of antibiotics (erythromycin, clarithromycin, and others), have both antimicrobial and immunomodulatory effects. This study explored the effect of clarithromycin on the clinical course of patients with undifferentiated connective tissue disease (UCTD) in a 12-week open-label study. METHODS: The diagnosis of UCTD was based on symptoms/signs of connective tissue disease, and the presence of 1 or more positive autoimmune disease tests, but with insufficient criteria to make a definitive diagnosis. Screening and monthly follow-up visits over 12 weeks included the following: history and physical examination; concurrent medications; the 68/66 tender/swollen joint count; visual analog scores 0 to 100 mm for patient and physician global assessment of disease activity, and patient pain; antinuclear antibody panel, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, and blood chemistry. RESULTS: Seven patients with rheumatic disease were treated with clarithromycin; 6 of 7 had symptomatic relief. Two subjects treated empirically before the decision to perform an open-label study responded favorably. Four of 5 patients who completed the prospective open-label study had mean maximal improvements from baseline of 78, 75, and 79% in patient pain, patient global, and investigator global assessments, respectively. Pain relief occurred as early as 1 week. Drug withdrawal with rechallenge in 2 patients resulted in flare followed by recapture of symptomatic relief. CONCLUSIONS: Clarithromycin, a macrolide antibiotic, led to clinical improvement in patients with UCTD. Efficacy and safety data support further investigation of macrolide antibiotic use as a primary or adjunctive treatment in various connective tissue diseases.

Adult↗
PubMed2000

Effect of clarithromycin on experimental rhinovirus-16 colds: a randomized, double-blind, controlled trial.

PURPOSE: Macrolide antibiotics are frequently prescribed to patients with symptoms of a common cold. Despite their lack of proven antiviral activity, macrolide antibiotics may have anti-inflammatory actions, such as inhibition of mucus secretion and production of interleukins 6 and 8 by epithelial cells. Because the symptoms of rhinovirus colds are attributed to the inflammatory response to infection, we studied the effects of treatment with clarithromycin on the symptomatic and inflammatory response to nasal inoculation with rhinovirus. SUBJECTS AND METHODS: We performed a prospective, double-blind, controlled trial in 24 healthy subjects who were seronegative for antibodies to rhinovirus-16. Subjects were randomly assigned to receive either clarithromycin (500 mg) or trimethoprim-sulfamethoxazole (800/160 mg, as a control antibiotic) twice a day for 8 days, beginning 24 hours before inoculation with rhinovirus-16. RESULTS: All 12 subjects in each group were infected and developed symptomatic colds. The groups did not differ in the intensity of cold symptoms (median [25th to 75th percentile] score in the clarithromycin group of 25 [5 to 33] versus 21 [11 to 26] in the trimethoprim-sulfamethoxazole group, P = 0.86), weight of nasal secretions (25 g [8 to 56 g] versus 12 g [5 to 28 g], P = 0.27), or decline in nasal peak flow during the 8 days following viral inoculation. In both groups, similar and significant increases from baseline were observed in the numbers of total cells and neutrophils, and in the concentrations of interleukins 6 and 8, in nasal lavage fluid during the cold. The changes that we observed did not differ from those in an untreated historical control group. CONCLUSIONS: We conclude that clarithromycin treatment has little or no effect on the severity of cold symptoms or the intensity of neutrophilic nasal inflammation in experimental rhinovirus-16 colds.

Adult↗
PubMed2000

Phase III, randomized, double-blind study of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis.

BACKGROUND: Clarithromycin has an established efficacy and safety profile in the treatment of respiratory tract infections. OBJECTIVE: The purpose of this study was to compare the clinical and bacteriologic efficacy and tolerability of clarithromycin extended-release and immediate-release formulations in patients with acute exacerbation of chronic bronchitis (AECB). METHODS: In a phase III, randomized, double-blind, parallel-group, multicenter study. patients aged > or =12 years with signs and symptoms of AECB and a productive cough with purulent sputum received treatment with extended-release (two 500-mg tablets once daily) or immediate-release (one 500-mg tablet twice daily) clarithromycin for 7 days. Assessments were performed before treatment, within 48 hours after treatment, and at the test-of-cure visit (study days 19-21). Patients who took > or =1 dose of study drug were included in the safety analysis. RESULTS: Of 620 patients randomized and treated, 182 were clinically and bacteriologically assessable (100 in the extended-release group and 82 in the immediate-release group). Treatment groups were well matched with respect to demographic characteristics and medical and social history. At the test-of-cure visit, 83% (83/100) of patients in the extended-release and 82% (67/82) of patients in the immediate-release group achieved clinical cure; 86% (85/99) and 85% (70/82), respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were 86% (100/116) in the extended-release group and 88% (86/98) in the immediate-release group. The most frequently reported adverse events were diarrhea (6% in extended-release group vs 4% in immediate-release group; no significant difference), taste alterations (4% in each group), and nausea (3% in each group); no clinically meaningful changes in laboratory values or vital signs, as assessed by the investigator, were observed. CONCLUSION: This study suggests that clarithromycin extended-release and immediate-release formulations have equivalent clinical and bacteriologic efficacy and tolerability in patients with AECB.

Acute Disease↗
PubMedDate not supplied

Immediate reaction to clarithromycin.

We present the case of bronchospastic reaction to clarithromycin had during a drug challenge test. Personal allergic history was negative for respiratory allergies and positive for adverse drug reactions to general and regional anesthesia and to ceftriaxone. After the administration of 1/4 of therapeutic dose of clarithromycin the patient showed dyspnea, cough and bronchospasm in all the lung fields. The positivity of the test was confirmed by the negativity to the administration of placebo. The quickness and the clinical characteristic of the adverse reaction suggest a pathogenic mechanism of immediate-type hypersensitivity. On reviewing the literature we have found no reports of bronchospastic reaction to clarithromycin. Macrolides are a class of antibiotics mainly used in the last years in place of beta-lactams because of a broad spectrum of action and a low allergic power. In fact, there are few reports on allergic reactions to these molecules. Clarithromycin is one of the latest macrolides, characterised by the presence of a 14-carbon-atom lactone ring as erythromycin, active on a wide spectrum of pathogens.

Adult↗
PubMed2003

Efficacies of cyclodextrin-complexed and liposome-encapsulated clarithromycin against Mycobacterium avium complex infection in human macrophages.

Cyclodextrins and liposomes have been used in recent years as drug delivery vehicles, improving the bioavailability and therapeutic efficacy of many poorly water-soluble drugs. In this study, we used two approaches to enhance the availability of the poorly water-soluble antibiotic, clarithromycin, by inclusion complex formation and by liposome-encapsulation. We examined the efficacies of these formulations against Mycobacterium avium complex (MAC) in human peripheral blood monocyte-derived macrophages. The water solubility of clarithromycin was enhanced by about 700-fold by complexation with cyclodextrin. The use of a rapid radiometric (BACTEC) method for the detection of MAC growth and susceptibility showed identical MICs against MAC for both the free and complexed drug. The anti-MAC efficacy of the cyclodextrin complex of clarithromycin in macrophages was slightly lower than the free drug, probably due to the high stability of the inclusion complex. At higher drug concentrations, Liposome-encapsulated clarithromycin was slightly more effective against intracellular MAC growth than the free drug.

Clarithromycin↗
PubMed2001

Comparison of the Etest and the NCCLS-approved agar dilution method to detect metronidazole and clarithromycin resistant Helicobacter pylori.

Although the NCCLS has approved the agar dilution method as the test of choice for antimicrobial susceptibility testing of Helicobacter pylori, a critical evaluation of this method in clinical trials to detect antibiotic resistance has not been performed. This study compares the Etest and agar dilution methods for detection of metronidazole and clarithromycin resistance in clinical isolates of H. pylori. MIC data were gathered from US-based clinical trials. The Etest was performed on Mueller-Hinton sheep blood agar plates following incubation for 4 days under 12% CO(2). The agar dilution test was performed according to the recently approved NCCLS methodology using aged sheep blood in a Mueller-Hinton agar base. Metronidazole resistance as determined by Etest was significantly higher than that determined by agar dilution (39%; 690/1768 vs. 25. 1%; 367/1465)(P<0.01). Clarithromycin resistance as determined by Etest was higher than that determined by agar dilution, but was not significantly different (12.5%; 209/1671 vs. 10.6%; 150/1414)(P>0.5). Inter-patient metronidazole resistance showed that the MIC values for identical isolates tested by both methods were equivalent in 58% (109/188). Of the 42% with a >2log(2) difference in MIC values, 17. 6% had a change in susceptibility pattern. For clarithromycin, 71.4% (237/332) of the MIC values for identical isolates tested by both methods had equivalent MIC values. Of the MIC values with a >2log(2) difference in MIC values, only 3% showed a change in susceptibility pattern. Intra-patient variability, i.e. paired isolates from the same patient, was assessed only for metronidazole. Of the 1393 paired isolates tested by Etest, 38.8% were shown to be resistant. Almost 69% of the Etest MIC determinations were deemed equivalent and 16.7% had a change in susceptibility pattern. Of the 639 paired isolates tested by agar dilution, 23.9% were resistant to metronidazole. Almost 72% of the agar dilution MIC values were equivalent and 11.3% of the determinations had a change in susceptibility pattern. Clarithromycin resistance rates are similar, when determined by either test method. The Etest yields a significantly higher prevalence of metronidazole resistance among H. pylori compared with the agar dilution method and both methods yield discordant results, when isolates from different parts of the same stomach are compared. Neither method is reliable in determining metronidazole resistance in H. pylori.

Anti-Bacterial Agents↗