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 91 records · Page 5Linked to original sources
PubMed2003

Effect of clarithromycin on steady-state digoxin concentrations.

OBJECTIVE: To evaluate the magnitude and dose-relatedness of the effect of clarithromycin on the pharmacokinetics of digoxin, and to compare the effects of clarithromycin with those of P-glycoprotein inhibitors. METHODS: Eight Japanese inpatients with congestive heart failure participated in this study. Each patient received oral digoxin therapy for at least 7 days and were coadministered oral clarithromycin to prevent or treat pneumonia. To evaluate the effects of clarithromycin on the pharmacokinetics of digoxin, digoxin concentrations were compared before and after coadministration of clarithromycin. RESULTS: Digoxin concentrations were higher after coadministration of clarithromycin in all patients (before, 0.838 +/- 0.329 ng/mL; after, 1.36 +/- 0.619 ng/mL); (p < 0.005). A significant correlation was observed between the dose of clarithromycin and the percentage of increase in the digoxin concentration. CONCLUSIONS: Digoxin concentrations increased during concomitant administration of clarithromycin, and this effect was dose-dependent on clarithromycin. The percentage increase in digoxin concentrations after the usual oral dose of clarithromycin (400 mg/d) is approximately 70%. Therefore, digoxin concentrations must be monitored carefully after coadministration of clarithromycin, and the doses of digoxin may need readjustment in patients who are concomitantly receiving clarithromycin.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Ranitidine bismuth citrate and clarithromycin, alone or in combination, for eradication of Helicobacter mustelae infection in ferrets.

OBJECTIVE: To determine whether ranitidine bismuth citrate, clarithromycin, or a combination of ranitidine bismuth citrate and clarithromycin would be efficacious in eradication of Helicobacter mustelae infection in ferrets. ANIMALS: 60 seven-month-old ferrets. PROCEDURE: To determine dosages of clarithromycin and ranitidine bismuth citrate that would suppress growth of, but not eradicate infection with, H mustelae, ferrets (n = 6/group) were treated p.o. with clarithromycin or ranitidine bismuth citrate at various dosages. Efficacy of treatment was then determined by treating ferrets with clarithromycin alone, ranitidine bismuth citrate alone, or clarithromycin and ranitidine bismuth citrate. Gastric biopsy specimens were obtained before, during, and at various times after treatment and submitted for quantitative bacterial culture and histologic evaluation. Minimum concentrations of clarithromycin that inhibited 90% of the growth of isolates obtained before and after treatment were determined. RESULTS: Dosages of clarithromycin and ranitidine bismuth citrate that suppressed growth of H mustelae were 12.5 and 24 mg/kg of body weight, p.o., every 8 hours, respectively. Infection was not eradicated in ferrets treated with ranitidine bismuth citrate alone but was eradicated in all 6 ferrets treated with clarithromycin and ranitidine bismuth citrate and in 4 of 6 treated with clarithromycin alone. A decrease in susceptibility to clarithromycin was detected for H mustelae isolates obtained after treatment. Mild or moderate antral gastritis was observed even in ferrets from which infection was eradicated. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of ranitidine bismuth citrate and clarithromycin was efficacious in eradicating H mustelae infection from ferrets.

Animals↗
PubMed1998

Pharmacokinetic interaction between ritonavir and clarithromycin.

BACKGROUND: Because ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, and clarithromycin, a macrolide antibiotic used in the treatment of disseminated infection caused by Mycobacterium avium complex, are likely to be administered concurrently for treatment of patients with HIV and acquired immunodeficiency syndrome (AIDS), the drug interaction potential of these 2 agents was evaluated. Both clarithromycin and ritonavir are metabolized to a significant extent through cytochrome P450-mediated biotransformation and are potential inhibitors of these enzymes. OBJECTIVE: To evaluate the pharmacokinetic effects of concomitant administration of multiple doses of ritonavir and clarithromycin. METHODS: This was an open-label, randomized, 3-period crossover study. Ritonavir alone (200 mg every 8 hours), clarithromycin alone (500 mg every 12 hours), and ritonavir and clarithromycin in combination were administered to 22 healthy volunteers. Blood samples were collected on day 4 for determination of ritonavir, clarithromycin, and its metabolite 14-(R)-hydroxyclarithromycin. RESULTS: Ritonavir practically completely inhibited the formation of 14-(R)-hydroxyclarithromycin. The mean area under the plasma concentration-time curve (AUC) for clarithromycin increased by 77% with concomitant ritonavir, and the harmonic mean terminal half-life increased from 5 hours to 14 hours. Statistically significant increases in peak plasma concentration (31%) and minimum plasma concentration (182%) were also observed. The effect of concomitant clarithromycin administration on ritonavir pharmacokinetics was statistically significant but small, with a 12.5% increase in mean AUC and a 15.3% increase in peak plasma concentration. The terminal half-life increased from 3.47 to 3.87 hours with concomitant clarithromycin. CONCLUSIONS: No adjustment of the ritonavir dose is necessary when administered with clarithromycin. In addition, no changes in clarithromycin dose are warranted in patients with normal renal function.

AIDS-Related Opportunistic Infections↗
PubMed1999

Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans.

BACKGROUND AND PURPOSE: A triple therapy with omeprazole, amoxicillin (INN, amoxicilline), and clarithromycin is widely used for the eradication of Helicobacter pylori. Omeprazole and clarithromycin are metabolized by CYP2C19 and CYP3A4. This study aimed to elucidate whether clarithromycin affects the metabolism of omeprazole. METHODS: After administration of placebo or 400 mg clarithromycin twice a day for 3 days, 20 mg omeprazole and placebo or 400 mg clarithromycin were administered to 21 healthy volunteers. Plasma concentrations of omeprazole and clarithromycin and their metabolites were determined before and 1, 2, 3, 5, 7, 10, and 24 hours after dosing. CYP2C19 genotype status was determined by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Subjects were classified into three groups on the basis of PCR-RFLP analyses for CYP2C19: homozygous extensive metabolizer group (n = 6), heterozygous extensive metabolizer group (n = 11), and poor metabolizer group (n = 4). Mean area under the plasma concentration-time curves from 0 to 24 hours (AUC) of omeprazole in the homozygous extensive metabolizer, heterozygous extensive metabolizer, and poor metabolizer groups were significantly increased by clarithromycin from 383.9 to 813.1, from 1001.9 to 2110.4, and from 5589.7 to 13098.6 ng x h/mL, respectively. There were significant differences in the mean AUC values of clarithromycin among the three groups. CONCLUSION: Clarithromycin inhibits the metabolism of omeprazole. Drug interaction between clarithromycin and omeprazole may underlie high eradication rates achieved by triple therapy with omeprazole, amoxicillin, and clarithromycin.

Adult↗
PubMed1997

Influence of pH on the antimicrobial activity of clarithromycin and 14-hydroxyclarithromycin against Haemophilus influenzae using an in vitro pharmacodynamic model.

Clarithromycin activity can be influenced by the pH of the surrounding environment. Evidence supports a reduced pH of middle ear fluid (MEF) and lung tissues in patients with otitis media and pneumonia, respectively. To evaluate the influence of pH on clarithromycin activity, an in vitro pharmacodynamic chamber model (PDCM) was used to generate bacterial time-kill curves for clarithromycin and a 2:1 ratio of clarithromycin and 14-hydroxyclarithromycin (HC) against Haemophilus influenzae at three different pH values: 7.2, 6.8, 6.4. Concentrations observed in MEF and lung tissues were simulated for clarithromycin alone and clarithromycin plus HC. Differences in activity at each pH were identified by comparing initial kill curve slopes and total log reduction. Experiments with amoxicillin-clavulanate were conducted as a reference. In simulated MEF regimens at pH 7.2, activity of clarithromycin alone improved by adding HC (additional 2 log10 reduction at 8 h); however, at pH values of 6.8 and 6.4, kill curves resembled growth controls. In simulated lung regimens, differences between clarithromycin alone and clarithromycin plus HC were insignificant; both produced a 2 log10 reduction at pH 7.2, and activity dramatically dropped to < 0.4 log10 as pH declined. In contrast, amoxicillin-clavulanate consistently produced a 3 log10 reduction over each pH value with more rapid initial kill relative to all clarithromycin regimens. These findings suggest the activity of clarithromycin against H. influenzae may be significantly compromised in respiratory tract infections involving a reduced pH. Trials with emphasis on clinical outcomes analysis will assist further in determining the significance of these experimental findings.

Clarithromycin↗
PubMed2001

Clarithromycin potentiates glucocorticoid responsiveness in patients with asthma: results of a pilot study.

BACKGROUND: Selected macrolide antibiotics have steroid-sparing effects in patients with steroid-dependent asthma. In addition to inhibiting methylprednisolone clearance, macrolides may also display anti-inflammatory effects. OBJECTIVE: To determine whether clarithromycin, by virtue of its anti-inflammatory effects, enhances glucocorticoid sensitivity. DESIGN: Open-label, pilot study in a paired design (pre- and posttreatment). PARTICIPANTS: Seven patients, mean age 27 (range 15 to 42 years), with mild to moderate asthma under good control. METHODS: Clarithromycin (500 mg) was administered twice daily for 10 days with blood drawn for lymphocyte stimulation assays at baseline, and again upon completion of therapy. Lymphocytes were stimulated with phytohemagglutinin in the presence and absence of increasing concentrations of clarithromycin and dexamethasone (DEX). RESULTS: At baseline, clarithromycin alone did not cause a significant degree of suppression of T-lymphocyte activation, yet clarithromycin significantly enhanced the sensitivity of lymphocytes to suppression by DEX as measured by a shift in the DEX dose-response curve by at least 6-fold (P = 0.04). In addition, a 10-day course of clarithromycin resulted in: 1) a significant decrease in the inhibitory concentration which results in a 50% reduction in proliferation for DEX alone, thereby increasing glucocorticoid sensitivity (P = 0.04); 2) heightened inhibitory effect of clarithromycin alone (P = 0.03); and 3) a sustained suppressive effect with the combination of clarithromycin and DEX on the inhibition of lymphocyte stimulation (P = 0.01). CONCLUSIONS: Clarithromycin acts synergistically with DEX in suppressing lymphocyte activation. In addition, a 10-day course resulted in a significant treatment effect as evidenced by lower inhibitory concentration which results in a 50% reduction in proliferation value for DEX, a heightened response to clarithromycin alone, and a consistent degree of suppression of lymphocyte stimulation when clarithromycin and DEX were used together.

Adolescent↗
PubMed2003

Quantification of clarithromycin, its 14-hydroxy and decladinose metabolites in rat plasma, gastric juice and gastric tissue using high-performance liquid chromatography with electrochemical detection.

A rapid, selective and sensitive HPLC assay has been developed for the simultaneous analysis of clarithromycin, its 14-hydroxy-clarithromycin metabolite, and its decladinose acid degradation product, in small volumes of rat gastric juice aspirate, plasma and gastric tissue. Sample were extracted with n-hexane/2-butanol (4:1) and the internal standard was roxithromycin. A Kromasil ODS 5 micrometer(75x4.6 mm I.D.) column was used with a mobile phase consisting of acetonitrile/aqueous phosphate buffer (pH 7, 0.086 M) (45:55 v/v). The column temperature was 30 degrees C and coulometric detection was used at 850 mV using a screen voltage of 600 mV. The analysis time was less than 8 min. The limits of quantitation for clarithromycin, 14-OH clarithromycin and decladinose clarithromycin were 0.15 microgram ml(-1) or lower in plasma (0.05 ml); 0.16 microgram ml(-1) or lower in gastric juice (0.2 ml); and 0.51 microgram g(-1) or lower for gastric tissue (0.25 g). The method was linear up to at least 20.3, 15.4 and 12.5 microgram ml(-1) for clarithromycin, 14-OH-clarithromycin and decladinose, respectively, in gastric juice aspirate and plasma and up to 40.6, 30.9 and 25.0 microgram g(-1) in gastric tissue. The assay was applied to the measurement of clarithromycin, 14-OH-clarithromycin and, for the first time, decladinose clarithromycin in pharmacokinetic studies of gastric transfer of clarithromycin in individual rats.

Animals↗
PubMed1999

Gastroprotective effect of intragastric clarithromycin against damage induced by ethanol in rats.

Intragastric administration of clarithromycin, a macrolide antibiotic, macroscopically protected the rat gastric mucosa from 96% ethanol-induced lesions. This protective effect was dose-dependent, the reduction being 92.3, 81.4, 52.2, and 5.4% at doses of 400, 200, 100, and 50 mg/kg, respectively. Clarithromycin protection was not significantly modified by pretreatment with either subcutaneous indomethacin (5 mg/kg), a selective cyclooxygenase inhibitor, or iodoacetamide (100 mg/kg), a specific sulfhydryl blocker. Gastric motor activity, measured by the balloon method, was inhibited by clarithromycin in a dose-dependent fashion. The inhibited gastric motor activity induced by clarithromycin was not modified by pretreatment with either indomethacin or iodoacetamide. Ethanol (1 ml/rat, gavage needle) induced hemorrhagic bandlike lesions in the mucosa of the glandular stomach along the long axis of the greater curvature with the occurrence of a complete inhibition of gastric motor activity. This inhibition was not modified by pretreatment with clarithromycin, indomethacin, or iodoacetamide. There was an increase in the fluid volume for clarithromycin at 100, 200, and 400 mg/kg at 30 min and in the mucus volume only for clarithromycin at 400 mg/kg at 30 min. Gastric mucosal blood flow was absent in the ethanol-induced lesions but in the nonlesion areas was the same in clarithromycin-pretreated and vehicle-pretreated rats as in control (no ethanol) rats. Clarithromycin protection was significantly diminished, although not completely abolished by subcutaneous yohimbine (5 mg/kg), a selective alpha2-adrenoceptor antagonist. Yohimbine also significantly reduced both basal and clarithromycin-stimulated gastric mucus secretion. Our data support the conclusion that the protective effect of intragastric clarithromycin was not mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, or changes in the gastric contractile patterns. The protection may be the result of an increase in both the fluid volume and the mucus volume retained in the gastric lumen. alpha2-Adrenoceptors possibly are involved by the mucus-dependent mechanism.

Adrenergic alpha-Antagonists↗
PubMed1990

Uptake of clarithromycin by rat lung cells.

To evaluate the affinity of clarithromycin (6-O-methylerythromycin A) for lung tissue, the in-vivo and in-vitro uptake of [14C]clarithromycin and [14C]erythromycin by rat lung cells was compared, and the characteristics of the uptake mechanism were investigated. After the administration into the external jugular vein of rats, clarithromycin was found in much higher concentrations in the lung tissue than erythromycin. In isolated lung cells, clarithromycin was also found in greater concentrations than erythromycin. The amount of clarithromycin was ten times that of erythromycin after 5 min incubation. This uptake profile was quite different from that observed in isolated liver cells. Uptake by lung cells for both antibiotics was shown to be an active process, as revealed by the need for cell viability, a suitable environmental temperature and ATP. Clarithromycin uptake proved to be dependent in part upon mitochondrial oxidative respiration. Kinetic analysis indicated that clarithromycin transport was saturable, with a relatively high binding affinity and velocity of uptake. Clarithromycin transport was significantly inhibited by 6-O-methylerythromycin analogues, but was not influenced by other analogues, including erythromycin. Competitive inhibition of clarithromycin uptake was demonstrated by 6,11,12.4"-tetra-O-methylerythromycin, one of the mutual inhibitors. These findings may suggest that clarithromycin utilizes a carrier-mediated transport system in the lung cells, which is common to 6-O-methylerythromycins. This difference of uptake mechanism between both antibiotics may account in part for the greater clarithromycin uptake by the lung cells.

Animals↗
PubMed1991

Individual and combined activities of clarithromycin and its 14-hydroxy metabolite in a murine model of Haemophilus influenzae infection.

Clarithromycin is metabolised in man mainly to the 14-hydroxy derivative, which is also biologically active. As this metabolite is not produced in rodents, we used a murine model of Haemophilus influenzae pulmonary infection to compare the in-vivo activity of clarithromycin and 14-hydroxy clarithromycin, alone and in combination, and erythromycin. In terms of bacterial killing, clarithromycin's 14-hydroxy metabolite was much more active than clarithromycin and erythromycin at doses of 100 mg/kg. For the combination tests, low doses of 14-hydroxy clarithromycin (12, 16 and 24 mg/kg) were ineffective alone but potentiated the bactericidal activity of clarithromycin (100 mg/kg) (P less than 0.01-0.001). The in-vivo results can be explained by in-vitro and pharmacokinetic data: the MIC and MBC of 14-hydroxy clarithromycin are half those of clarithromycin and erythromycin, while the combination of clarithromycin and its metabolite was synergistic in terms of bacteriostatic and bactericidal activities. Potentially useful levels of 14-hydroxy clarithromycin were found after oral administration of low doses, with a prolonged half-life compared with that of the parent compound. On the basis of these results it appears that the 14-hydroxy metabolite may have an important role to play in the treatment of bronchopulmonary infections in man due to H. influenzae.

Administration, Cutaneous↗
PubMed1997

Clarithromycin. A review of its efficacy in the treatment of respiratory tract infections in immunocompetent patients.

Clarithromycin is a broad spectrum macrolide antibacterial agent active in vitro and effective in vivo against the major pathogens responsible for respiratory tract infections in immunocompetent patients. It is highly active in vitro against pathogens causing atypical pneumonia (Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp.) and has similar activity to other macrolides against Staphylococcus aureus. Streptococcus pyogenes, Moraxella catarrhalis and Streptococcus pneumoniae. Haemophilus influenzae is susceptible or intermediately susceptible to clarithromycin alone, but activity is enhanced when the parent drug and metabolite are combined in vitro. Absorption of clarithromycin is unaffected by food. More than half of an oral dose is systemically available as the parent drug and the active 14-hydroxy metabolite. Pharmacokinetics are nonlinear, with plasma concentrations increasing in more than proportion to the dosage. First-pass metabolism results in the rapid appearance of the active metabolite 14-hydroxy-clarithromycin in plasma. Clarithromycin and its active metabolite are found in greater concentrations in the tissues and fluids of the respiratory tract than in plasma. Dosage adjustments are required for patients with severe renal failure, but not for elderly patients or those with hepatic impairment. Drug interactions related to the cytochrome P450 system may occur with clarithromycin use. In addition to the standard immediate-release formulation for administration twice daily, a modified-release formulation of clarithromycin is now available for use once daily. In dosages of 500 to 1000 mg/day for 5 to 14 days, clarithromycin was as effective in the treatment of community-acquired upper and lower respiratory tract infections in hospital and community settings as beta-lactam agents (with or without a beta-lactamase inhibitor), cephalosporins and most other macrolides. Clarithromycin was similar in efficacy to azithromycin in comparative studies and is as effective as and better tolerated than erythromycin. Adverse events are primarily gastrointestinal in nature, but result in fewer withdrawals from therapy than are seen with erythromycin. Clarithromycin provides similar clinical and bacteriological efficacy to that seen with beta-lactam agents, cephalosporins and other macrolides. It offers a cost-saving alternative to intravenous erythromycin use in US hospitals and is available in both once-daily and twice-daily formulations. The spectrum of activity of clarithromycin against common and emerging respiratory tract pathogens may make it suitable for use in the community as empirical therapy of respiratory tract infections in both children and adults.

Adult↗
PubMed2004

The effect of oral clarithromycin on bronchial airway inflammation in moderate-to-severe stable COPD: a randomized controlled trial.

INTRODUCTION: COPD is characterized by bronchial neutrophilic inflammation. Clarithromycin is a macrolide antibiotic that has antibacterial and anti-inflammatory properties. Macrolide antibiotics have been shown to improve airway inflammation in diffuse pan-bronchiolitis but their role in COPD is undetermined. The aim of the study was to determine if 3 months of therapy with modified-release oral clarithromycin (Klaricid XL) 500 mg/day reduced bronchial airway inflammation in patients with moderate-to-severe stable COPD compared with placebo. METHODS: A prospective, double-blind controlled trial randomized patients with moderate-to-severe stable COPD to 3 months' therapy with oral modified-release clarithromycin 500 mg/day or placebo. Patients underwent saline sputum induction before and after treatment with clarithromycin. The effects of clarithromycin on sputum total cell and neutrophil counts, supernatant interleukin-8 (IL-8), leukotriene B(4) (LTB(4)), tumor necrosis factor (TNF)-alpha, neutrophil elastase (NE), and neutrophil chemotaxis were assessed in comparison with placebo. RESULTS: Of a total of 67 patients included in the trial, 31 were treated with clarithromycin and 36 with placebo. The groups were similar in age, body mass index, history of smoking, and spirometry. Of 60 evaluable patients, 26 and 34 completed 3 months' therapy with clarithromycin and placebo, respectively. Clarithromycin had no significant effect on sputum total cell count, neutrophil count, IL-8, LTB(4), TNFalpha levels or neutrophil elastase. However, clarithromycin did cause a small reduction in the neutrophil differential (p = 0.04 relative to placebo) and neutrophil chemotaxis (p = 0.058 relative to placebo). CONCLUSIONS: Oral clarithromycin 500 mg/day administered for 3 months had no significant effect on sputum neutrophil numbers or cytokine levels in patients with moderate-to-severe stable COPD. However, clarithromycin did cause a small reduction in the neutrophil differential and neutrophil chemotaxis. Further studies may be warranted to determine the clinical significance of these findings.

Administration, Oral↗
PubMed2006

[Preparation and evaluation of clarithromycin emulsion for injection].

AIM: To prepare clarithromycin emulsion and investigate its pharmacokinetics in rats. And to do irritation test of the emulsion. METHODS: High pressure homogenization method was used to prepare clarithromycin emulsion, and the Nicomp380 machine was used to test the mean particle size and zeta-potential of clarithromycin emulsion. Irritation of emulsion was also evaluated compared with the positive control of clarithromycin solution using rat paw lick test and rabbit ear vein irritation test. Microbiological assay method was used for determining the drug concentration in plasma. Pharmacokinetics of two dosage forms in rats was also studied. RESULTS: The mean particle size and zeta potential of clarithromycin emulsion were 156 nm and -31.8 mV, respectively. The emulsion was stable during the storage time at 4 degrees C for 6 month. The pain caused by emulsion reduced significantly compared with that of clarithromycin solution based on the results of rat paw lick test and rabbit ear vein test. The drug concentration-time curves of clarithromycin emulsion and clarithromycin solution were similar and could be described by two compartment model. AUC(0-1) of clarithromycin emulsion and clarithromycin solution were (66.76 +/- 16.34) and (59.00 +/- 11.20) microg x h x mL(-1), respectively. CONCLUSION: Stable emulsion could be prepared using high pressure homogenization method, and irritation caused by i.v. injection could be reduced significantly by using clarithromycin emulsion.

Animals↗
PubMed2001

Comparison of the efficacy of extended-release clarithromycin tablets and amoxicillin/clavulanate tablets in the treatment of acute exacerbation of chronic bronchitis.

BACKGROUND: Clarithromycin has established efficacy and safety in the treatment of respiratory infections. OBJECTIVE: This study examined the efficacy and safety of a new extended-release formulation of clarithromycin compared with amoxicillin/clavulanate in the treatment of acute exacerbation of chronic bronchitis (AECB). METHODS: This phase IIIB, multicenter, randomized, parallel-group, investigator-blinded study in patients with AECB and productive cough with purulent sputum compared treatment with extended-release clarithromycin (two 500-mg tablets once daily for 7 days) and amoxicillin/clavulanate (one 875-mg tablet twice daily for 10 days). Assessments were performed before treatment, between study days 10 and 12 (or within 48 hours after premature discontinuation), and between study days 17 and 21 (test of cure). RESULTS: Of 287 patients randomized and treated, 270 were clinically evaluable (137 clarithromycin, 133 amoxicillin/clavulanate). Treatment groups were well matched in terms of demographic characteristics, medical condition, and history. Among clinically evaluable patients at test of cure, 85% and 87% of clarithromycin- and amoxicillin/clavulanate-treated patients, respectively, demonstrated clinical cure (as defined in 1998 draft US Food and Drug Administration guidelines); among clinically and bacteriologically evaluable patients, 92% versus 89%, respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were similar in the 2 groups (88% clarithromycin, 89% amoxicillin/clavulanate). Rates of premature discontinuation of study drug for any reason differed between treatments: 3% (4/142) of clarithromycin-treated patients versus 12% (17/145) of amoxicillin/clavulanate-treated patients (P = 0.005). One percent (2/142) and 6% (8/145) of the respective treatment groups discontinued study drug because of adverse events. Adverse events generally occurred with a similar frequency in the 2 groups; however, taste alteration was more common with clarithromycin (9/142 [6%]) than with amoxicillin/clavulanate (1/145 [1%]; P = 0.01). Mean severity scores for gastrointestinal adverse events showed a significant difference between groups (1.16 for clarithromycin-treated patients and 1.58 for amoxicillin/clavulanate-treated patients: P = 0.016). CONCLUSIONS: The results of this study demonstrate the clinical and bacteriologic equivalence and improved gastrointestinal tolerability of a 7-day course of once-daily extended-release clarithromycin relative to a 10-day course of twice-daily amoxicillin/clavulanate in the treatment of AECB.

Acute Disease↗
PubMed2001

In vitro activity and pharmacodynamics of azithromycin and clarithromycin against Streptococcus pneumoniae based on serum and intrapulmonary pharmacokinetics.

BACKGROUND: Multidrug-resistant strains of Streptococcus pneumoniae are increasingly common worldwide, but the clinical significance of their resistance to the macrolide antibiotics is controversial. Applying pharmacokinetic and pharmacodynamic principles can assist in the selection of appropriate antimicrobial therapy. OBJECTIVES: The purpose of this study was to determine the in vitro activity of penicillin, azithromycin, clarithromycin, and clindamycin against clinical isolates of S. pneumoniae and to evaluate the pharmacodynamics of azithromycin and clarithromycin based on serum and epithelial lining fluid (ELF) concentrations. METHODS: The minimum inhibitory concentrations (MICs) of penicillin, azithromycin, clarithromycin, and clindamycin were determined for 307 isolates of S. pneumoniae using broth microdilution. Using serum and ELF concentrations after standard dosing, we calculated the proportion of isolates against which it would be possible to obtain a ratio of azithromycin area under the curve to MIC > or =25 and clarithromycin concentrations that exceeded the MIC for > or =40% of the dosing interval. RESULTS: Overall, 19.5%, 25.4%, 25.1%, and 7.2% of the 307 pneumococcal isolates were resistant to penicillin, azithromycin, clarithromycin, and clindamycin, respectively. However, 71.7% of penicillin-resistant strains were also resistant to azithromycin and clarithromycin. Based on serum concentrations, clarithromycin achieved its pharmacodynamic target in 76.9% of isolates, compared with 59.9% for azithromycin. Based on ELF concentrations, clarithromycin achieved its pharmacodynamic target in 93.5% of isolates, compared with 74.6% for azithromycin. Based on ELF concentrations, clarithromycin achieved its pharmacodynamic target in 86.7% of penicillin-resistant isolates, compared with 28.3% for azithromycin. CONCLUSIONS: On the basis of serum and ELF concentrations, clarithromycin achieved pharmacodynamic targets against a greater proportion of S. pneumoniae isolates than did azithromycin. Clinical studies are needed to determine the efficacy of these agents against pneumococci that demonstrate in vitro resistance using current susceptibility breakpoints.

Anti-Bacterial Agents↗
PubMed2001

Comparison of once- and twice-daily clarithromycin in the treatment of adults with severe acute lower respiratory tract infections.

BACKGROUND: Although the modified-release (MR) formulation of clarithromycin has demonstrated bioequivalence to the immediate-release (IR) formulation and thus can be prescribed for lower respiratory tract infections (LRTIs), a MEDLINE search from 1995 through 1998 and information on file with the manufacturer indicate that no data are available on the effectiveness of this new formulation in the treatment of severe LRTIs such as community-acquired pneumonia. OBJECTIVE: This study was designed to compare clinical success rates (percentage of patients with clinical cure or improvement) with once- and twice-daily regimens of clarithromycin in the treatment of patients with severe, acute LRTIs requiring oral antibiotic therapy. METHODS: In this multicenter, investigator-blinded, randomized, parallel-group study, adult patients with clinical evidence suggesting severe, acute LRTI were recruited from 22 general practices in the United Kingdom. Patients were randomly allocated to receive either clarithromycin 500 mg BID (IR tablets) or clarithromycin 1 g OD (two 500-mg MR tablets) for 7 to 14 days. The outcome measures were resolution of or improvement in clinical signs and symptoms (including resolution of cough), unscheduled visits for the same symptom, days to resumption of normal activities, and improvements in quality of life (assessed using the EQ-5D version of the EuroQoL questionnaire). Clinical, microbiologic, and serologic assessments were performed before, during, and after treatment. Efficacy and safety data were analyzed on an intent-to-treat basis. RESULTS: One hundred sixty men (n = 83) and women (n = 77) between the ages of 19 and 88 years took part in the study, 78 receiving clarithromycin 500 mg BID and 82 receiving clarithromycin 1 g OD. At 4 weeks after the start of treatment, the high clinical success rates were comparable between groups: 84.6% with clarithromycin 500 mg BID and 90.2% with clarithromycin 1 g OD. No significant differences in outcome measures were noted between the 2 regimens. Both treatments were well tolerated, with taste disturbance being the most commonly reported adverse event (10.6% vs 6.1% with clarithromycin 500 mg BID and 1 g OD, respectively). CONCLUSIONS: The 2 clarithromycin regimens were equally efficacious and well tolerated in the treatment of severe, acute LRTIs. However, caution should be exercised in applying these results to the general population, because the study excluded certain categories of patients who would normally be treated. In addition, the small sample size may have obscured clinically significant differences between the 2 regimens.

Administration, Oral↗
PubMed2002

Drug combinations with amoxycillin reduce selection of clarithromycin resistance during Helicobacter pylori eradication therapy.

This study investigated the relationship between the drug combinations of the eradication regimens and the prevalence of acquired resistance to clarithromycin. Of 540 patients treated with anti-Helicobacter pylori regimens containing clarithromycin, 55 patients (31 males, mean age, 45.6 years) with failed eradication of H. pylori that was susceptible to clarithromycin before treatment were included. The E test was used to test for susceptibility to clarithromycin (minimum inhibitory concentration (MIC) <1 mg/l). Of the 55 patients, 33 (60.0%) developed clarithromycin resistance after failed eradication. Of the dual therapies, the combination of a proton pump inhibitor (PPI) and clarithromycin resulted in 88.9% (8/9) of the patients acquiring clarithromycic-resistance. With the triple therapies, the percentages of patients acquiring clarithromycin resistant strains after using a PPI+clarithromycin+amoxycillin or a PPI+clarithromycin+metronidazole were 38.7% (12/31) and 90.0% (9/10), respectively (P<0.01). These data suggest that regimens containing amoxycillin may prevent the selection of secondary clarithromycin resistance.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Low rate of emergence of clarithromycin-resistant Helicobacter pylori with amoxycillin co-therapy.

BACKGROUND: Patients with persistent Helicobacter pylori infection following treatment with clarithromycin or omeprazole plus clarithromycin often develop clarithromycin resistance. AIM: To assess pre- and post-treatment antibiotic resistance in three double-blind trials of triple therapy with omeprazole, amoxycillin and clarithromycin. METHODS: Patients with H. pylori and duodenal ulcer (studies 1 and 2) or history of duodenal ulcer (study 3) were randomly assigned to 10 day courses of omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) or placebo, amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (AC). Endoscopy was performed at baseline and 4 weeks after completion of therapy in studies 1 and 2, and at 4-6 weeks after therapy in study 3. At baseline, H. pylori was diagnosed by CLO test with confirmation by histology, or by culture. Eradication was defined as no positive biopsy test and > or = 2 negative tests. Susceptibility testing was performed using the Etest. RESULTS: In the 91 patients with pre-treatment susceptible isolates who had persistent infection after AC, 10 developed resistance, eight had intermediate susceptibility and 73 continued to have clarithromycin-susceptible H. pylori isolates. In the 10 patients with pre-treatment susceptible isolates who had persistent infection after OAC, three developed clarithromycin resistance and seven still had susceptible isolates. CONCLUSIONS: Use of amoxycillin co-therapy results in a low rate of clarithromycin resistance developing in patients with persistent H. pylori infection following therapy with a clarithromycin-containing regimen.

Amoxicillin↗