Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Clarithromycin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2005

Once-daily azithromycin for 3 days compared with clarithromycin for 10 days for acute exacerbation of chronic bronchitis: a multicenter, double-blind, randomized study.

STUDY OBJECTIVES: To compare the efficacy and safety of oral azithromycin 500 mg once daily for 3 days with those of oral clarithromycin 500 mg twice daily for 10 days. DESIGN: Randomized, double-blind, double-dummy, multicenter study. SETTING: Seventy-six study centers in eight countries (Argentina, Brazil, Canada, Chile, Costa Rica, India, South Africa, and USA). PATIENTS: Three hundred and twenty-two adult outpatients with acute exacerbation of chronic bronchitis (AECB) as documented by increased cough or sputum production, worsening dyspnea, and purulent sputum production. INTERVENTIONS: Randomization 1 : 1 to azithromycin 500 mg once daily for 3 days or clarithromycin 500 mg twice daily for 10 days. RESULTS: The primary efficacy endpoint was clinical response at day 21-24, or test of cure (TOC) visit in the modified intent-to-treat (MITT) analysis (n = 318 patients). The TOC clinical cure rates in the MITT population were equivalent in the two treatment groups at 85% with azithromycin and 82% with clarithromycin (95% CI -5.9%, 12.0%). Clinical success rates on day 10-12 were also equivalent at 93% with azithromycin and 94% with clarithromycin (95% CI -7.9%, 4.4%). Clinical cure rates at TOC by pathogen were equivalent for the two treatment groups for Haemophilus influenzae (azithromycin, 85.7%; clarithromycin, 87.5%), Moraxella catarrhalis (91.7% and 80.0%, respectively) and Streptococcus pneumoniae (90.6% and 77.8%, respectively). Bacteriologic success rates were also equivalent between the azithromycin and clarithromycin treatment groups at TOC for S. pneumoniae (90.6% and 85.2%, respectively), H. influenzae (71.4% and 81.3%, respectively) and M. catarrhalis (100% and 86.7%, respectively). The overall incidence of treatment-related adverse events was similar in the azithromycin and clarithromycin groups (20.9% and 26.8%, respectively), with the most common being abdominal pain (6.3% and 6.1%, respectively), diarrhea (4.4% and 5.5%, respectively), and nausea (4.4% and 3.7%, respectively). CONCLUSIONS: Three-day treatment with azithromycin 500 mg once daily is equivalent to a 10-day treatment with clarithromycin 500 mg twice daily in adult patients with AECB.

Acute Disease↗
PubMed2005

Interactions between clarithromycin and digoxin in patients with end-stage renal disease.

OBJECTIVE: To report a significant increase in the serum levels of digoxin associated with the use of clarithromycin in six patients undergoing renal replacement therapy. CASE SUMMARY: All six patients were males with end-stage renal disease and in need of renal replacement therapy. Four patients were anuric. The mean age was 78.8 +/- 5.8 (66-83) years. All patients except one, who was treated by hemofiltration, were treated by hemodialysis. All patients except one, who had been treated with metildigoxin (0.35 mg/week), were also taking digoxin (0.375 mg/week). Clarithromycin was administered at a dose of 200-400 mg/day for the treatment of bronchitis in all patients. The concomitant administration of clarithromycin increased serum digoxin levels from 1.8-4.0-fold in all cases. In two of six cases, a high probability of digoxin intoxication and suspicion of digoxin intoxication was evident. In three of six cases, serum digoxin levels increased within 12 days after the co-administration of clarithromycin, while in the other three cases, serum digoxin levels were increased 53-190 days after the administration of clarithromycin. CONCLUSION: The simultaneous administration of clarithromycin caused an increase in digoxin levels in six patients undergoing renal replacement therapy. The increase in the serum digoxin can be attributed to the inhibition of P-glycoprotein in the intestine and/or bile capillary rather than the kidney by clarithromycin since renal function was dramatically impaired, and four of the patients were anuric. The issue of why serum digoxin levels were increased so late in three patients undergoing renal replacement is unclear. However, this interaction seemed to be clinically significant even in ESRD patients, whose renal function was highly impaired. The simultaneous use of digoxin and clarithromycin should be avoided even in patients undergoing renal replacement therapy whose renal function is impaired, since digoxin levels may increase unexpectedly.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

[The prevalence and mechanism of Helicobacter pylori resistance to clarithromycin in Beijing].

OBJECTIVE: (1) To determine the prevalence of Helicobacter pylori strains resistant to clarithromycin in Peking. (2) To determine the genetic mutation in relation to clarithromycin resistance. METHODS: Helicobacter pylori were cultured from gastric biopsies obtained from 89 patients during upper endoscopy. Minimal inhibitory concentrations of clarithromycin were determined by Etest method. Genomic DNA was prepared by the hexadecyltrimethylammonium bromide (CTAB)-phenol extraction method. Mutations in clarithromycin-resistant strains were identified by polymerase chain reaction and restrictions analysis. RESULTS: (1) The prevalence of Helicobacter pylori strains resistant to clarithromycin was 13.5% in Beijing. (2) All twelve clarithromycin-resistant strains had the new BsaI site which is characteristic of the A2143G point mutation in 23S rRNA gene, none of the tested twenty-four susceptible strains had the A2142G or A2143G mutation. CONCLUSION: The prevalence of clarithromycin-resistant strains was not rare in Beijing. Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori.

Anti-Bacterial Agents↗
PubMed2003

[Meta-analysis of clarithromycin compared to other antibiotics for the treatment of lower respiratory tract infections].

Clarithromycin is a macrolide antibiotic commonly used for the treatment of respiratory infections. The aim of this study was to assess its effectiveness for the treatment of lower respiratory tract infections. A number of meta-analyses of clinical trials comparing clarithromycin to the antibiotics most frequently used in the treatment of lower respiratory tract infections, such as cephalosporins, amoxicillin-clavulanic acid, erythromycin and azithromycin, have been performed. Clarithromycin's effectiveness for the treatment of lower respiratory tract infections was better than that for cephalosporins (OR = 1.43; 95% CI = 1.09-1.86) and, although not to the same extent, that for amoxicillin-clavulanic acid (OR = 1.58; 95% CI = 0.92-2.70); however, the efficacy was only similar to that shown for azithromycin (OR = 0.57; 95% CI = 0.19-1.68). The fourth meta-analysis compared the effectiveness of clarithromycin to that of erythromycin for the treatment of pneumonia and showed a superior odds ratio in favor of clarithromycin (OR = 1.46; 95% CI = 0.97-2.2). Meta-analyses comparing clarithromycin's safety to that of the same drugs in the same conditions used in the assessment of effectiveness showed a similar incidence of adverse events compared to amoxicillin-clavulanic acid, and azithromycin, a slightly lower incidence compared to erythromycin, and a slightly higher incidence compared to cephalosporins. In conclusion, these meta-analyses show that clarithromycin is an effective and safe antibiotic for the treatment of lower respiratory tract infections. Furthermore, a new once-daily dose formulation with a positive impact on therapeutic compliance is currently available, making clarithromycin a first-line treatment for lower respiratory tract infections.

Anti-Bacterial Agents↗
PubMed1994

Treatment of experimental Toxoplasma gondii infection by clarithromycin-based combination therapy with minocycline or pyrimethamine.

The efficacy of clarithromycin combined with either pyrimethamine or minocycline for treatment of experimental Toxoplasma gondii infection was investigated. Mice were infected intraperitoneally with 2 x 10(3) to 2 x 10(4) T. gondii strain RH or TS4 tachyzoites. Mortality was recorded for 35 days postinfection. Latency was evaluated by inoculation of brain homogenates from surviving mice into naive untreated mice. The combination of clarithromycin and pyrimethamine therapy caused a significantly greater reduction in mortality than did either drug alone. Similar synergy was observed between clarithromycin and minocycline. A 100% cure rate of active and latent infection was achieved in mice treated with the clarithromycin based combinations. Clarithromycin in combination with either pyrimethamine or minocycline produced efficacy comparable to combined therapy of pyrimethamine with sulfamethoxazole. The in vitro potency of clarithromycin, pyrimethamine, or minocycline against T. gondii on a mouse macrophage monolayer was not predictive of the in vivo efficacy in mice. Clarithromycin combined with minocycline or pyrimethamine could allow greater flexability for treatment of patients predisposed to the toxicity associated with standard pyrimethamine-sulfonamide or pyrimethamine-nonsulfonamide therapy. This therapy could be especially useful since clarithromycin-based therapy provides safe and effective treatment against Mycobacterium avium complex infections associated with AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

A multicenter, investigator-blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis.

A multicenter, investigator-blinded, randomized, parallel-group study was conducted to compare oral levofloxacin 500 mg once/day for 14 days with clarithromycin 500 mg twice/day for 14 days in the treatment of acute bacterial sinusitis. Of 216 adult outpatients randomized to treatment, 190 were evaluable for efficacy. The primary efficacy measure was clinical response, based on resolution of signs and symptoms 2-5 days after therapy. A secondary efficacy measure was relapse rate 1 month after therapy. Among evaluable patients, clinical success rates (cured or improved) were 96.0% and 93.3% for levofloxacin (L) and clarithromycin (C), respectively (95% CI -9.2%, 3.7%). The confidence interval (CI) for treatment difference (C-L) included zero and its upper limit was less than 15%, indicating that levofloxacin was as effective as clarithromycin. In all, 4.1% of patients receiving levofloxacin and 7.2% receiving clarithromycin had a relapse of symptoms 1 month after therapy (95% CI-12.2%, 3.2%). Long-term success (initial success, absence of relapse at 1 month, no further antibacterial therapy 2-5 days after therapy) was 79.2% in the levofloxacin group and 76.4% in the clarithromycin group (95% CI -14.7%, 9.0%). Based on investigator-assessed treatment-emergent adverse events, overall tolerability of the drugs was similar, except for a higher frequency of taste perversion and diarrhea in the clarithromycin group. Levofloxacin had an advantage over clarithromycin based on two quality-of-life (QOL) parameters: number of times taking other drugs for targeted medical conditions and mean total cost of these drugs. No statistical significance was found in other QOL variables. These findings suggest that the efficacy and tolerability of levofloxacin 500 mg once/day are comparable with those of clarithromycin 500 mg twice/day in the treatment of acute bacterial sinusitis.

Abdominal Pain↗
PubMed2001

Pattern of primary resistance of Helicobacter pylori to metronidazole or clarithromycin in the United States.

BACKGROUND: Therapy for Helicobacter pylori is generally empiric despite the fact that resistance to metronidazole and clarithromycin compromise therapeutic efficacy. The aim of this study was to aid clinicians in choosing a course of therapy for H pylori infection in the United States. METHODS: The frequency of primary clarithromycin and metronidazole resistance among H pylori isolated from patients enrolled in US-based clinical trials between 1993 and 1999 was reviewed in relation to patient age, sex, region of the United States, and test method (Etest and 2 agar dilution procedures). RESULTS: Clarithromycin and metronidazole resistance rates were based on the results of 3439 pretreatment Etest determinations and 3193 agar dilution determinations. Sex and age were available on 900 and 823 individuals, respectively. Metronidazole resistance was 39% by Etest and 21.6% by agar dilution (P<.001). Clarithromycin resistance was 12% by Etest and 10.6% by agar dilution. Amoxicillin or tetracycline resistance was rare. Metronidazole and clarithromycin resistance was more common in women than men (eg, 34.7% vs 22.6% for metronidazole and 14.1% vs 9.7% for clarithromycin (P =.01 and P =.06, respectively). Antibiotic resistance increased gradually up to age 70 years, then declined significantly (P<.05) regardless of test method. Regional differences in antimicrobial resistance did not occur. CONCLUSIONS: While age and sex had significant effects on resistance rates, regional differences were not present. The high prevalence of resistance to metronidazole and clarithromycin may soon require the performance of antimicrobial susceptibility testing of H pylori isolates prior to initiating treatment.

Adult↗
PubMed2004

Pharmacokinetics of clarithromycin in rats with acute renal failure induced by uranyl nitrate.

In rats pretreated with dexamethasone (an inducer of CYP3A1/2 in rats) and troleandomycin (an inhibitor of CYP3A1/2 in rats), the area under the plasma concentration-time curve from time zero to time infinity (AUC) values of clarithromycin were significantly smaller (365 compared with 600 micro g min/ml) and greater (1410 compared with 581 micro g min/ml), respectively, than those in control rats. This indicated that clarithromycin was metabolized via CYP3A1/2 in rats. The expression of CYP3A1(23) increased in rats with acute renal failure induced by uranyl nitrate (rats with U-ARF). Hence, it could be expected that AUC of clarithromycin could be smaller in rats with U-ARF. However, after intravenous administration of clarithromycin at a dose of 20mg/kg, the AUC and time-averaged total body (Cl) and nonrenal (Cl(nr)) clearance values were comparable between the two groups of rats. The 9000 x g supernatant fraction of liver homogenates in rats with U-ARF had comparable metabolic activities for clarithromycin compared with those in control rats, suggesting that the CYP3A isozyme responsible for metabolism of clarithromycin seemed not to be expressed considerably in the rats. This could explain the comparable AUC, Cl and Cl(nr) values of clarithromycin between the two groups of rats.

Acute Kidney Injury↗
PubMed1993

Single- and multiple-dose pharmacokinetics of clarithromycin, a new macrolide antimicrobial.

The pharmacokinetics of clarithromycin and its active 14(R)-hydroxy metabolite were evaluated after single and multiple oral doses of 250 and 500 mg of clarithromycin. Multiple-dose regimens used 12-hour dosing intervals for 7 doses. Plasma and urine concentrations were measured using high-performance liquid chromatography. Appearance of clarithromycin and its metabolite in plasma were rapid, as reflected by mean times to maximum plasma concentration ranging from 1.8 to 2.6 and 1.8 to 2.9 hours, respectively. The rises in clarithromycin peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) were disproportionate to increase in dose, suggesting nonlinearity in parent compound pharmacokinetics. Clarithromycin terminal disposition half-life (t1/2) also exhibited dose dependency, ranging from harmonic means of 2.7 to 4.8 hours. In contrast, based on Cmax AUC, and predicted/observed accumulation ratios, nonlinearity in metabolite pharmacokinetics was not observed. Plasma accumulation of metabolite occurred to a much lesser degree than that of the parent compound despite a substantially longer t1/2 for the metabolite (metabolite accumulation ratios based on AUC dose 7/AUC dose 1:250-mg regimen = 1.03 +/- 0.33, 500-mg regimen = 0.81 +/- 0.29, parent accumulation ratios: 250-mg regimen = 1.64 +/- 0.47, 500-mg regimen = 1.65 +/- 0.69). This would suggest that formation of this metabolite is capacity-limited and that this may in part account for the nonlinearity observed in clarithromycin pharmacokinetics. Urinary excretion constituted a relatively important route of elimination of clarithromycin, with renal clearance accounting for 17 to 31% of apparent total body clearance.

Administration, Oral↗
PubMedDate not supplied

Effectiveness of the macrolide clarithromycin in the treatment of Mycobacterium avium complex infection in HIV-infected patients.

In a randomized double-blind study, nine mycobacteremic patients with AIDS-related disseminated Mycobacterium avium complex (MAC) infection received clarithromycin or placebo in addition to a basic regimen that included isoniazid, ethambutol and clofazimine. All four patients receiving clarithromycin showed blood culture conversion and clinical response. Of the five patients treated without clarithromycin, two showed resolution of mycobacteremia and clinical response, while another two died without having shown response. The remaining patient deteriorated until a switch from placebo to clarithromycin led to blood culture conversion and rapid clinical improvement. After finishing six weeks of intensive treatment, clarithromycin was given in an open maintenance phase to all patients, initially in combination with rifabutin for 24 weeks and then alone. One patient had a relapse of MAC infection while receiving clarithromycin alone. The relapse was associated with acquired resistance to the drug. Clarithromycin appears to be a promising component of multi-drug therapy for patients with MAC infection. Monotherapy can lead to drug resistance.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

A comparative study of clarithromycin and amoxycillin suspensions in the treatment of pediatric patients with acute otitis media.

This phase III, single-blind, randomized, multicentre clinical trial compared the safety and efficacy of clarithromycin and amoxycillin in the treatment of otitis media in pediatric patients. Two hundred and fifty-nine patients aged 1-12 were prescribed suspensions of clarithromycin (132 patients) or amoxycillin (127 patients). Both suspensions were prescribed at a dose of 125 mg for children weighing less that 25 kg or at 250 mg for children weighing more than 25 kg, but three doses of amoxycillin per day were given, while only two doses clarithromycin per day were required. Each drug was administered for approximately 5 days. Clinical evaluations were performed pre-treatment (Study Day 1), at the end of treatment (Study Days 6-9), and post-treatment (Study Days 28-32). At the end of treatment, 91 out of 114 evaluable patients (80%) had clinical cures with clarithromycin, while 71 out of 105 evaluable patients (68%) had clinical cures with amoxycillin (p = 0.057). Clinical success rates were 96% for both treatments (110/114, clarithromycin; 101/105 amoxycillin). Adverse events related to the study medications occurred in four of 132 patients receiving clarithromycin (3%) and eight out of 127 subjects receiving amoxycillin (6%). Three patients discontinued treatment due to adverse events, all three receiving amoxycillin. At the doses administered, clarithromycin given twice-daily was as safe and effective as given three-times-daily in the treatment of acute otitis media in pediatric patients.

Acute Disease↗
PubMedDate not supplied

Serum and cellular pharmacokinetics of clarithromycin 500 mg q.d. and 250 mg b.i.d. in volunteers.

In an open-label, randomized, crossover study 12 healthy volunteers were given clarithromycin orally 250 mg twice daily (b.i.d.) and 500 mg once a day (q.d.). Blood and saliva samples were collected on study days 1 and 5 to determine the pharmacokinetics of clarithromycin and its 14-hydroxy metabolite in plasma and saliva, and to measure concentrations of clarithromycin in mononuclear cells (MNCs) and polymorphonuclear leucocytes (PMNs). The mean peak levels of clarithromycin on day 5 of therapy in serum (2.3 vs. 1.2 mg/l), saliva (1.1 vs. 0.3 mg/l) and blood cells 60 vs. 26 mg/l in MNCs and 29 vs. 14 mg/l in PMNs) were at least doubled, the trough levels were lower with 500 mg q.d. vs. 250 mg b.i.d. (0.09 vs. 0.28 mg/l in serum; 0.06 vs. 0.13 mg/l in saliva; < 1 vs. 6.8 mg/l in MNCs; 0.8 vs. 2.8 mg/l in PMNs). The mean relative peak serum concentrations of the 14-hydroxy metabolite were somewhat lower with the 500 mg dosage (0.78 vs. 0.46 mg/l). The peak concentrations of clarithromycin and its 14-hydroxy metabolite in saliva were 25-40% and 50-80% of the maximum serum concentrations with both dosage regimens. Clarithromycin exhibits good and rapid penetration into intracellular as well as into extravasal extracellular body compartments. Clarithromycin 500 mg q.d. compares favourably with 250 mg b.i.d., as far as peak serum levels and bioavailability are concerned, but trough levels are lower at the end of the 24-hour dosing interval.

Administration, Oral↗
PubMed1991

Comparative study of clarithromycin and penicillin V in the treatment of streptococcal pharyngitis.

This study evaluated the safety and efficacy of clarithromycin in the treatment of patients with Group A beta-hemolytic streptococcal pharyngitis. Subjects were treated with either 250 mg clarithromycin twice daily or 250 mg penicillin V four times a day for 10 days and followed for approximately three weeks post-treatment. At the completion of therapy, 96% (45/47) of patients treated with clarithromycin and 89% (43/48) of patients treated with penicillin V were clinically cured or improved. Recurrence of symptoms occurred in 7 and 5 patients who were treated with clarithromycin and penicillin V respectively. Initial bacteriologic eradication was observed in all but one patient. Recurrence of Streptococcus pyogenes occurred in 5 (11%) patients who received clarithromycin and 7 (15%) patients who received penicillin V. The majority of adverse events reported during this study were mild and involved the gastrointestinal tract. Diarrhea was more frequent in patients who received clarithromycin. In this multicenter, randomized, double-blind trial, clarithromycin was as safe and effective as penicillin V in the treatment of Streptococcus pyogenes throat infections.

Adolescent↗
PubMedDate not supplied

Clarithromycin suspension vs penicillin V suspension in children with streptococcal pharyngitis.

Clarithromycin, an advanced-generation macrolide antibiotic, has demonstrated excellent in vitro activity against group A beta-hemolytic streptococcus (GABHS). Potent activity against Streptococcus pyogenes and a favorable pharmacokinetic profile have made it a reasonable alternative for treatment of patients with streptococcal pharyngitis. The safety and efficacy of clarithromycin and penicillin V were compared in a randomized, investigator-blind study. Children 6 months to 12 years of age received 5 days of clarithromycin suspension 7.5 mg/kg twice daily (n = 268) or 10 days of penicillin V suspension 13.3 mg/kg three times daily (n = 260). Patients were evaluated for signs and symptoms of pharyngitis, and throat swabs for culture were obtained prior to therapy, at the end of therapy, and at follow-up. Clarithromycin and penicillin V produced comparable rates of clinical success (cure + improvement) at the posttreatment (97% and 94%) and follow-up (81% and 82%) evaluations. The GABHS eradication rate, however, was significantly higher with clarithromycin (94% vs 78%, P < .001). Both drugs were well tolerated; gastrointestinal complaints were similar and mild. Resistance did not occur with the short course of clarithromycin or the standard regimen of penicillin V. Five days' treatment with clarithromycin was superior to 10 days of penicillin in eradicating S. pyogenes.

Analysis of Variance↗
PubMed2004

Comparison of the efficacy of 250 mg and 500 mg clarithromycin used with lansoprazole and amoxicillin in eradication regimens for Helicobacter pylori infection.

AIMS AND METHODS: The aim of this study was to compare the efficacy of 250 mg and 500 mg clarithromycin used with lansoprazole and amoxicillin in eradication of H. pylori infection. 235 patients with H. pylori infections and non-ulcer dyspepsia were randomly assigned to one of the following regimens: lansoprazole 30 mg, amoxicillin 1000 mg, clarithromycin 250 mg (LAC250) and lansoprazole 30 mg, amoxicillin 1000 mg, clarithromycin 500 mg (LAC500). All drugs were given twice daily for 7 days. The patients were assessed for prevalence of H. pylori with the CLO test. Gastric biopsy samples obtained during upper gastrointestinal endoscopy before randomization and 4-6 weeks after completion of therapy were used for histology and culture. Bacterial sensitivity to clarithromycin and amoxicillin was determined with the E-test. RESULTS: 101 patients in the LAC250 mg group and 102 in the LAC500 group completed the study. On intention-to-treat analysis, eradication rates were 81% with LAC250 and 82% with LAC500 (p=0.88). On per-protocol analysis, eradication rates were 92% with LAC250 and 96% with LAC500 (p=0.23). Among the 203 patients (86% of the entire study group) for whom H. pylori antibiotic-sensitivity testing was technically feasible, primary resistance to clarithromycin was found in 9% and to amoxicillin in 0%. Eradication of clarithromycin sensitive/resistant strains was 94%/38% for LAC250 (p < 0.001) and 93%/40% for LAC500 (p < 0.001). CONCLUSIONS: The cure rates for the two regimens were similar, although adverse effects were more frequent with the LAC500 regimen, suggesting that 250 mg of clarithromycin b.d. may be sufficient in our patient population.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Alarming trend of clarithromycin-resistant Streptococcus pyogenes in Japan (1998-2002).

We investigated annual changes in clarithromycin resistance and resistance genes in 579 strains of Streptococcus pyogenes isolated from patients with symptomatic respiratory tract infections who visited primary medical institutions during the 5-year period from 1998 to 2002. The minimum inhibitory concentrations (MICs) of clarithromycin for S. pyogenes were measured using the standard broth microdilution method according to the National Committee for Clinical Laboratory Standards (NCCLS) guidelines, and strains showing MICs of 1 microg/ml or greater were regarded as being resistant to clarithromycin, according to the resistance standard specified by the NCCLS. The rates of S. pyogenes resistance to clarithromycin were 7.3% overall, 5.8% in 1998, 4.9% in 1999, 7.7% in 2000, 6.4% in 2001, and 11.1% in 2002. While the annual rates fluctuated slightly each year, an overall tendency to increase was observed during the 5-year period. Regarding the macrolide-resistance genes in the macrolide-resistant strains, mefA/E (+)/ ermB(-) was the most common genotype detected in these strains, while the ermB (+)/ mefA/E (-) and mef A/E (-)/ ermB (-) genotypes were detected at about the same rate. The MICs of clarithromycin for the ermB (+) strains tended to be higher than those of the mefA/E (+) strains, but some mefA/E (-) / ermB (-) strains also exhibited high MICs of clarithromycin, similar to those of the ermB (+) strains. The above results indicate that the number of clarithromycin-resistant strains of S. pyogenes is gradually increasing and that the resistance is becoming stronger; thus, special attention must be paid to the appearance of macrolide-resistant strains of S. pyogenes.

Anti-Bacterial Agents↗
PubMed2005

The effect of oral clarithromycin on health status and sputum bacteriology in stable COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation, poor health status and recurrent infective exacerbations. Macrolide antibiotics have been shown to improve symptoms and exacerbation rate in chronic lung disease, particularly cystic fibrosis (CF) and diffuse pan-bronchiolitis. The effect of long-term oral clarithromycin on health status, sputum bacterial numbers and exacerbation rate in subjects with clinically stable COPD is undetermined. METHODS: Subjects with moderate-to-severe COPD were recruited into a prospective, double-blind, randomised-controlled trial of 3-months oral clarithromycin (Klaricid XL) or placebo once-daily. The effect of clarithromycin on health status (St. George respiratory and Short Form-36 questionnaires), sputum quantitative bacterial numbers and exacerbation rate were investigated. RESULTS: Sixty-seven subjects (46 males) were recruited; 31 and 36 subjects received clarithromycin and placebo, respectively. There were 7(10%) withdrawals. Compared to placebo, clarithromycin did not significantly improve health status, sputum bacterial numbers, or exacerbation rate. CONCLUSIONS: Three months of oral clarithromycin given to subjects with stable COPD does not improve health status, sputum bacterial numbers or exacerbation rate. Treatment of COPD with clarithromycin during the clinical stable state yields no clinical advantages and therefore cannot be recommended as means of eliminating sputum bacteria or preventing infective exacerbations.

Administration, Oral↗
PubMed1998

The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin.

OBJECTIVE: To assess the relative contribution of intestinal and hepatic CYP3A inhibition to the interaction between the prototypic CYP3A substrates midazolam and clarithromycin. METHODS: On day 1, 16 volunteers (eight men and eight women; age range, 20 to 40 years; weight range, 45 to 100 kg) received simultaneous doses of midazolam intravenously (0.05 mg/kg over 30 minutes) and orally (4 mg of a stable isotope, 15N3-midazolam). Starting on day 2, 500 mg clarithromycin was administered orally twice daily for 7 days. On day 8, intravenous and oral doses of midazolam were administered 2 hours after the final clarithromycin dose. Blood and urine samples were assayed for midazolam, 15N3-midazolam, and metabolites by gas chromatography-mass spectrometry. RESULTS: There was no significant (p > 0.05) difference in the urinary excretion of 1'-hydroxymidazolam after intravenous and oral dosing on day 1 or day 8, indicating that the oral dose was completely absorbed into the gut wall. The oral clearance of midazolam was found to be significantly greater in female subjects (1.9 +/- 1.0 versus 1.0 +/- 0.3 L/hr/kg; p < 0.05) than in male subjects but not systemic clearance (0.35 +/- 0.1 versus 0.44 +/- 0.1 L/hr/kg). For women not receiving oral contraceptives (n = 6) a significant gender-related difference was observed for systemic and oral clearance and for area under the curve and elimination half-life after oral administration. A significant (p < 0.05) reduction in the systemic clearance of midazolam from 28 +/- 9 L/hr to 10 +/- 3 L/hr occurred after clarithromycin administration. Oral midazolam availability was significantly increased from 0.31 +/- 0.1 to 0.75 +/- 0.2 after clarithromycin dosing. Likewise, intestinal and oral availability were significantly increased from 0.42 +/- 0.2 to 0.83 +/- 0.2 and from 0.74 +/- 0.1 to 0.90 +/- 0.04, respectively. A significant correlation was observed between intestinal and oral availability (n = 32, r = 0.98, p < 0.05). After clarithromycin administration, a significant correlation was observed between the initial hepatic or intestinal availability and the relative increase in hepatic or intestinal availability, respectively. Female subjects exhibited a greater extent of interaction after oral and intravenous dosing than male subjects (p < 0.05). CONCLUSION: These data indicate that in addition to the liver, the intestine is a major site of the interaction between oral midazolam and clarithromycin. Interindividual variability in first-pass extraction of high-affinity CYP3A substrates such as midazolam is primarily a function of intestinal enzyme activity.

Adult↗