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PubMed1995

Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin.

The intrapulmonary pharmacokinetics of orally administered clarithromycin (500 mg every 12 h for five doses) or erythromycin (250 mg every 6 h for nine doses) were studied in 32 healthy adult volunteers. Four of the subjects, two in the clarithromycin group and two in the erythromycin group, were smokers. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed at 4, 8, 12, 24, and 48 h after administration of the last dose of clarithromycin and at 4, 8, and 12 h after administration of the last dose of erythromycin. Clarithromycin was measured by high-performance liquid chromatography, and erythromycin was measured by a microbiological assay. No systemic sedation was used. There were no major adverse events. The concentrations of antibiotics in epithelial lining fluid (ELF) were calculated by the urea dilution method. The volumes (mean +/- standard deviation) of ELF were 1.9 +/- 2.0 ml and 1.5 +/- 0.7 ml in the clarithromycin and erythromycin groups, respectively (P > 0.05). There was no effect of smoking on the amount of bronchoalveolar lavage fluid recovered, the volume of ELF, or the number of erythrocytes present in the lavage fluid (P > 0.05 for all comparisons). The total number of alveolar cells, however, was almost threefold greater in the smokers versus that in the nonsmokers (P < 0.05). Clarithromycin was concentrated in ELF (range, 72.1 +/- 73.0 micrograms/ml at 8 h to 11.9 +/- 3.6 micrograms/ml at 24 h) and alveolar cells (range, 505.8 +/- 293.1 micrograms/ml at 4 h to 17.0 +/- 34.0 micrograms/ml at 48 h). 14-(R)-Hydroxyclarithromycin was also present in these compartments, but at lower concentrations than the parent compound. The concentrations of erythromycin in ELF and alveolar cells were low at 4, 8, and 12 h following the last dose of drug (range, 0 to 0.8 +/- microgram/ml in ELF and 0 to 0.8 +/- 1.3 microgram/ml in alveolar cells). The clinical significance of any antibiotic concentrations in these compartments in unclear. The data suggest, and we conclude, that clarithromycin may be a useful drug in the treatment of pulmonary infections, particularly those caused by intracellular organisms.

Adult↗

PubMed1996

Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects.

The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bronchoscopy and bronchoalveolar lavage at timed intervals following drug administration. Drug concentrations, including those of 14-hydroxyclarithromycin (14H), were determined in serum, bronchoalveolar lavage fluid, and alveolar cells (ACs) by high-pressure liquid chromatography. Concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The maximum observed concentrations (mean +/- standard deviation) of azithromycin, clarithromycin, 14H, ciprofloxacin, and cefuroxime in serum were 0.13 +/- 0.07, 1.0 +/- 0.6, 0.60 +/- 0.41, 0.95 +/- 0.32, and 1.1 +/- 0.3 microgram/ml, respectively (all at 6 h). None of the antibiotics except clarithromycin (39.6 +/- 41.1 micrograms/ml) was detectable in ELF at the 6-h bronchoscopy. The movement into and persistence in cells was different for azithromycin and clarithromycin. In ACs azithromycin was not detectable at 6 h, reached its highest concentration at 120 h, and exhibited the greatest area under the curve (7,403 micrograms.hr ml-1). The peak concentration of clarithromycin (181 +/- 94.1 micrograms/ml) was greater and occurred earlier (6 h), but the area under the curve (2,006 micrograms.hr ml-1) was less than that observed for azithromycin. 14H was detectable in ACs at 6 h (40.3 +/- 5.2 micrograms/ml) and 12 h (32.8 +/- 57.2 micrograms/ml). The peak concentration of ciprofloxacin occurred at 6 h (4.3 +/- 5.2 micrograms/ml), and the area under the curve was 35.0 micrograms.hr ml-1. The data indicate that after the administration of a single dose, azithromycin, clarithromycin, and ciprofloxacin penetrated into ACs in therapeutic concentrations and that only clarithromycin was present in ELF. The correlation of these kinetic observations with clinical efficacy or toxicity was not investigated and is unclear, but the data provide a basis for further kinetic and clinical studies.

Administration, Oral↗

PubMed1997

Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection.

The use of antiretroviral agents and drugs for the treatment and prophylaxis of opportunistic infections has lengthened the survival of persons with AIDS. In the era of multidrug therapy, drug interactions are important considerations in designing effective and tolerable regimens. Clarithromycin has had a significant impact on the treatment of disseminated Mycobacterium avium complex infection, and zidovudine is the best-studied and one of the most widely used antiretroviral agents in this population. We conducted a study to determine the maximally tolerated dose of clarithromycin and the pharmacokinetics of clarithromycin and zidovudine individually and in combination. Mixing studies were conducted to simulate potential interaction in the gastric environment. The simultaneous administration of zidovudine and clarithromycin had little impact on the pharmacokinetics of clarithromycin or of its major metabolite. However, coadministration of zidovudine and clarithromycin at three doses (500 mg orally [p.o.] twice daily [b.i.d.], 1,000 mg p.o. b.i.d., and 2,000 mg p.o. b.i.d.) reduced the maximum concentration of zidovudine by 41% (P < 0.005) and the area under the concentration-time curve from 0 to 4 h for zidovudine by 25% (P < 0.05) and increased the time to maximum concentration of zidovudine by 84% (P < 0.05), compared with zidovudine administered alone. Mixing studies did not detect the formation of insoluble complexes due to chelation, suggesting that the decrease in zidovudine concentrations results from some other mechanism. Simultaneous administration of zidovudine and clarithromycin appears to decrease the levels of zidovudine in serum, and it may be advisable that these drugs not be given at the same time. Drug interactions should be carefully evaluated in persons with advanced human immunodeficiency virus infection who are receiving multiple pharmacologic agents.

Adult↗

PubMed2003

Influence of macrolide susceptibility on efficacies of clarithromycin and azithromycin against Streptococcus pneumoniae in a murine lung infection model.

We evaluated the activities of clarithromycin and azithromycin against 19 isolates of Streptococcus pneumoniae using a neutropenic lung infection model. The isolates included five susceptible isolates (clarithromycin and azithromycin MICs, </=0.12 micro g/ml), nine isolates exhibiting low-level, mefA-mediated resistance (clarithromycin and azithromycin MICs, 0.5 to 32 micro g/ml), and five isolates expressing high-level, ermB-mediated macrolide resistance (clarithromycin and azithromycin MICs, >/=64 micro g/ml). Infected mice were administered either saline (control), clarithromycin (4, 40, or 200 mg/kg of body weight twice daily or 200 mg/kg once daily), or azithromycin (4, 40, or 200 mg/kg once daily or 40 mg/kg twice daily) by oral gavage for 72 h. Mortality was assessed at regular intervals for 10 days, and survival in each group was compared to that of untreated controls. Animals infected with susceptible isolates demonstrated significant improvement in survival compared to the controls following treatment with either agent at doses of >/=40 mg/kg. In contrast, none of the regimens improved the survival of animals infected with isolates exhibiting high-level macrolide resistance. Among mice infected with strains expressing low-level resistance, significant improvement in survival compared to the controls was noted among isolates treated with clarithromycin at 40 (seven of nine isolates) and 200 (nine of nine isolates) mg/kg twice a day and with azithromycin at 40 (one of nine isolates) and 200 (three of nine isolates) mg/kg once a day. Animals infected with isolates of S. pneumoniae exhibiting low-level, mefA-mediated macrolide resistance responded to treatment with clarithromycin at rates similar to those observed among mice infected with fully susceptible isolates.

Animals↗

PubMed2004

Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa.

Clarithromycin was administered intravenously to 55 rabbits to evaluate its effect on experimental sepsis caused by multidrug-resistant Pseudomonas aeruginosa. Acute pyelonephritis was induced after ligation of the right ureter and injection of 10(8) CFU of the test isolate per kg of body weight into the renal pelvis. The animals were divided into six groups: group A, controls; group B, rabbits that received one intravenous dose of 80 mg of clarithromycin per kg concomitantly with bacterial challenge; group C, rabbits that received two doses of clarithromycin, the second one of which was given 2 h after the first one; group D, rabbits that received 15 mg of amikacin per kg; group E, rabbits that received one dose of clarithromycin and amikacin; and group F, rabbits that received two doses of clarithromycin and amikacin. Serum endotoxin levels were estimated by the QCL-1000 Limulus amoebocyte lysate assay, tumor necrosis factor alpha (TNF-alpha) levels were measured by a bioassay, and malondialdehyde (MDA) levels were measured by the thiobarbiturate assay. Viable bacterial counts in various tissue samples were also assessed. The mean survival times of the animals in groups A, B, C, D, E, and F were 4.50, 7.69, 4.07, 4.55, 11.55, and 11.60 days, respectively (P = 0.033 for group D versus group F, P = 0.006 for group D versus group E, P = not significant for group B versus group E, P = 0.042 for group C versus group F). Serum endotoxin levels were similar between groups at all sampling times; TNF-alpha and MDA levels in groups B, C, E, and F decreased significantly over follow-up. The numbers of viable bacterial cells in the infected kidney were similar among the groups; those in the liver, spleen, lungs, and mesenteral lymph nodes were significantly decreased in groups B, E, and F compared to those in groups A and D. It is concluded that a prolongation of survival in animals with experimental sepsis caused by multidrug-resistant P. aeruginosa was achieved after coadministration of clarithromycin and amikacin and that the increased survival was probably attributable to the immunomodulatory properties of clarithromycin.

Acute Disease↗

PubMed2000

Clarithromycin attenuates mastectomy-induced acute inflammatory response.

Based on the observation that administration of clarithromycin led to an attenuation of the inflammatory response induced by surgical trauma in a guinea pig model, we investigated the potential beneficial effects of clarithromycin on the local and systemic inflammatory response in patients undergoing mastectomy in an open-label prospective study. During a 16-month period, 54 patients who underwent mastectomy were randomly divided into two groups. In one group, the patients received oral clarithromycin at a dose of 500 mg twice a day, from the day before to 3 days after mastectomy. There was no significant difference in the incidence of antibiotic prophylaxis-related toxicities or postoperative infections between the patients who received clarithromycin and those who did not. Clarithromycin treatment was significantly associated with an attenuation of febrile response, tachycardia, tachypnea, and an increase in monocyte counts (P, <0.0001, <0.01, <0.05, and <0.01, respectively). Clarithromycin also reduced the intensity and duration of postoperative pain (P, <0.05 and <0.005, respectively) and increased the range of motion of the involved shoulder (P < 0.05 for abduction and flexion). We conclude that clarithromycin effectively modulates the acute inflammatory response associated with mastectomy and produces a better clinical outcome.

Acute-Phase Reaction↗

PubMed1998

Antipneumococcal activities of levofloxacin and clarithromycin as determined by agar dilution, microdilution, E-test, and disk diffusion methodologies.

The activities of levofloxacin and clarithromycin against 199 penicillin- and macrolide-susceptible and -resistant pneumococci were tested by agar and microdilution methods in air and by disk diffusion and E-test methods in air and CO2. For levofloxacin, >/=99. 0% of strains were susceptible at </=2.0 microgram/ml with zone diameters of >/=17 mm, regardless of incubation in air or CO2. Although zone sizes were smaller and E-test MICs were higher for clarithromycin in CO2 than those in air, category differences were minor, and susceptibility rates for clarithromycin were similar to those obtained by agar and microdilution in air (range, 76.9 to 80.9% by all methods). For clarithromycin, adjustment of breakpoints based upon distribution of results resulted in susceptibility rates which were similar by all methods (75.8 to 76.9% susceptible, 0 to 1.5% intermediate, 22.6 to 23.1% resistant). Minor discrepancies were obtained with levofloxacin for one strain (0.5%) by microdilution and two strains (1.0%) by disk diffusion in CO2. For clarithromycin, minor discrepancies were found in three strains (1.5%) by microdilution, seven strains (3.5%) by agar dilution, four strains (2.0%) by E-test in air, six strains (3.0%) by disk diffusion in air, and five strains (2.5%) by disk diffusion in CO2. Major discrepancies occurred with levofloxacin in one strain (0.5%) by microdilution but were not found with clarithromycin. Very major discrepancies were not seen with levofloxacin, but occurred with clarithromycin in five strains (2.5%) by microdilution, three strains (1.5%) by agar dilution, two strains (1.0%) by E-test in air, eight strains (4.0%) by disk diffusion in air, and one strain (0.5%) by disk diffusion in CO2.

Anti-Bacterial Agents↗

PubMed2003

Fast and accurate quantitative detection of Helicobacter pylori and identification of clarithromycin resistance mutations in H. pylori isolates from gastric biopsy specimens by real-time PCR.

Rapid identification of patients infected with clarithromycin-resistant Helicobacter pylori without the need for culture can help to avoid useless prescriptions of clarithromycin. We developed and tested a routine real-time quantitative PCR assay dedicated to that purpose. One hundred ninety-six consecutive gastric biopsy specimens were examined by culture, histology performed by a trained physician, and rapid PCR with the LightCycler apparatus. Infection was defined as (i) positivity of culture, (ii) positivity of histology, or (iii) positivity of PCR if confirmed by positivity of a concomitant indirect test (serology or urea breath test). Susceptibility to clarithromycin was tested by E-test and PCR. The prevalence of infection was 33.7% (66 of 196 samples). The sensitivities of culture, histology, and PCR were 90.9% (60 of 66 samples), 87.9% (58 of 66 samples), and 97.0% (64 of 66 samples), respectively. The specificity of PCR was 94.6% (123 of 130 samples). The linearity of the PCR results was achieved over a 6-log range of input DNA, and we were able to accurately quantify as few as 300 bacteria and to qualitatively detect as few as 30 bacteria per DNA sample. For clarithromycin susceptibility testing, there was 98.2% (55 of 56 samples) concordance between E-test and PCR. Forty-eight strains were clarithromycin susceptible, and 9 strains were clarithromycin resistant. The single discrepancy concerned a culture which was a mixture of mutant and wild type, with a susceptible-to-resistant ratio of 11.5: the resistant population was detected by E-test but not by PCR. Our PCR assay is accurate for fast detection of H. pylori as well as of clarithromycin resistance and is also able to objectively determine bacterial density.

Anti-Bacterial Agents↗

PubMed2005

Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial.

OBJECTIVE: To determine if the macrolide clarithromycin affects mortality and cardiovascular morbidity in patients with stable coronary heart disease. DESIGN: Centrally randomised multicentre trial. All parties at all stages were blinded. Analyses were by intention to treat. SETTING: Five Copenhagen University cardiology departments and a coordinating centre. PARTICIPANTS: 13,702 patients aged 18 to 85 years who had a discharge diagnosis of myocardial infarction or angina pectoris in 1993-9 and alive in August 1999 were invited by letter; 4373 were randomised. INTERVENTIONS: Two weeks' treatment with clarithromycin 500 mg/day or matching placebo. MAIN OUTCOME MEASURES PRIMARY OUTCOME: composite of all cause mortality, myocardial infarction, or unstable angina pectoris during three years' follow-up. Secondary outcome: composite of cardiovascular mortality, myocardial infarction, or unstable angina pectoris. The outcomes were obtained from Danish registers and were blindly assessed by the event committee. RESULTS: 2172 participants were randomised to clarithromycin and 2201 to placebo. We found no significant effects of clarithromycin on the primary outcome (hazard ratio 1.15, 95% confidence interval 0.99 to 1.34) or secondary outcome (1.17, 0.98 to 1.40). Mortality was significantly higher in the clarithromycin arm (1.27, 1.03 to 1.54; P = 0.03) as a result of significantly higher cardiovascular mortality (1.45, 1.09 to 1.92; P = 0.01). CONCLUSIONS: Short term clarithromycin in patients with stable coronary heart disease may cause significantly higher cardiovascular mortality. The long term safety of clarithromycin in patients with stable ischaemic heart disease should be examined. Trial registration ClinicalTrials.gov NCT00121550.

Adolescent↗

PubMed2005

Effects of clarithromycin on inflammatory cell mediator release and survival.

BACKGROUND: Clarithromycin exhibits anti-inflammatory as well as antimicrobial activity, leading to decreased symptoms of asthma and chronic sinusitis. The mode of anti-inflammatory effects of clarithromycin on inflammatory cells is not well understood. We hypothesized that clarithromycin inhibits inflammatory cell mediator release and survival. METHODS: We investigated the effects of this drug on survival and mediator release from mast cells, eosinophils and neutrophils. RESULTS: Human eosinophil and neutrophil respiratory burst was inhibited by up to 54% after 1-2 h pretreatment with 100 microg/ml clarithromycin. Similar doses of erythromycin did not affect respiratory burst responses in these cells. Clarithromycin at doses of up to 100 microg/ml had no effect on granule-derived mediators released from mast cells and neutrophils. However, we found that clarithromycin (100 microg/ml) induced cell death in mast cells and eosinophils after 16-48 h incubation. CONCLUSION: Clarithromycin inhibited inflammatory cell mediator release and survival, which may enhance its ability to reduce the symptoms of chronic sinusitis and asthma.

Anti-Bacterial Agents↗

PubMed1991

Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. A controlled clinical trial.

Disseminated Mycobacterium avium infection is common in patients with acquired immune deficiency syndrome (AIDS), but no drug studies have been reported establishing antimicrobial activity against this organism in a controlled, randomized trial. Clarithromycin, a new macrolide, has activity against M. avium in vitro and in animals, but it has not been studied in humans. In this randomized, double-blind, placebo-controlled trial, we measured the ability of clarithromycin to reduce M. avium bacteremia in patients with AIDS and disseminated infection. Of 23 patients initially enrolled, 15 men with late-stage AIDS qualified for the study. One group received clarithromycin alone for 6 wk, then placebo plus rifampin, isoniazid, ethambutol, and clofazimine for 6 wk. The other group received placebo alone, then clarithromycin plus the other four drugs. Colony-forming units (CFU) of M. avium per milliliter of blood were determined by quantitative cultures taken at baseline and every 2 wk thereafter. Minimum inhibitory concentration of clarithromycin for 90% of the strains isolated from patients at baseline, as measured on 7H11 agar at pH 6.6, was 8 micrograms/ml. Eight eligible patients with initial positive cultures who were initially receiving clarithromycin alone had marked declines in blood M. avium CFU; in six cases, CFU decreased to zero. When seven patients were switched to placebo plus the other four drugs, CFU rose in four patients and remained undetectable in three. The five eligible patients initially treated with placebo had progressive CFU increases; when three were switched to clarithromycin plus the four drugs, their CFU declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1992

Clarithromycin: review of a new macrolide antibiotic with improved microbiologic spectrum and favorable pharmacokinetic and adverse effect profiles.

OBJECTIVE: To compare the new macrolide antibiotic clarithromycin with erythromycin in terms of in vitro activity, pharmacokinetics, pharmacodynamics, clinical efficacy, and toxicity. DATA IDENTIFICATION: An English-language literature search employing MEDLINE (1987-91), Index Medicus (1987-91), Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy (1990), Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (1991), and bibliographic reviews of related textbooks and review articles. STUDY SELECTION: Eighty-five articles were selected. Clinical trials with clarithromycin have been limited, and emphasis was placed on trials reported in the Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy and Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. DATA EXTRACTION: Articles were assessed for study quality and specific information addressing the stated purpose. In articles reporting the results of clinical trials, emphasis was placed on comparative efficacy and toxicity. RESULTS OF DATA ANALYSIS: A review of 24 human trials suggests that clarithromycin is equally effective as erythromycin, penicillin VK, ampicillin, or amoxicillin for treatment of a variety of upper and lower respiratory tract or skin infections. Clarithromycin also appears to be better tolerated than these agents, with a lower incidence of gastrointestinal adverse effects. Limited clinical studies in patients with Mycobacterium leprae or Mycobacterium avium-intracellulare complex (MAI) suggest that clarithromycin may prove to be efficacious and well tolerated in the treatment of these infections. CONCLUSIONS: Clarithromycin is as effective in vivo as erythromycin, with less gastrointestinal irritation. Additionally, clarithromycin appears to expand the traditional spectrum of macrolide antibiotics, with promising activity against M. leprae and MAI.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Digoxin toxicity secondary to clarithromycin therapy.

OBJECTIVE: To report a case of digoxin toxicity thought to be secondary to clarithromycin therapy. CASE SUMMARY: A 78-year-old white woman with congestive heart failure taking digoxin 0.25 mg po qd presented to our hospital with nausea, vomiting, and diarrhea. She had taken clarithromycin 500 mg po bid for 3 days, and a serum digoxin concentration obtained the day of admission was 4.4 mug/L. An electrocardiogram (ECG) done on admission revealed ST segment changes consistent with digoxin effect and later asymptomatic, nonsustained ventricular tachycardia (NSVT). Clarithromycin was discontinued and digoxin was withheld at admission, resulting in the resolution of symptoms, ECG abnormalities, and NSVT on day 3 of hospitalization. On day 5 her serum digoxin concentration was 1.5 micrograms/L and digoxin therapy was reinstituted at a dose of 0.125 mg/d po. DISCUSSION: This is the fourth published case implicating clarithromycin as the cause of digoxin toxicity. This interaction is most likely due to clarithromycin eradication of digoxin-metabolizing gut flora, thereby increasing digoxin bioavailability. CONCLUSIONS: Approximately 10% of patients are thought to be extensive presystemic metabolizers of digoxin and may therefore be most susceptible to a drug interaction with clarithromycin. Serum digoxin concentrations in such patients should be monitored closely during clarithromycin therapy.

Aged↗

PubMed1997

Potential interaction between clarithromycin and warfarin.

OBJECTIVE: To report a possible drug interaction between clarithromycin and warfarin in a patient with chronic atrial fibrillation. CASE SUMMARY: A patient with chronic atrial fibrillation was placed on warfarin therapy. International normalized ratios (INRs) ranged from 1.61 to 3.99 while the dosage was being adjusted during the first 5 months of warfarin therapy. The dosage was titrated to 20 mg/wk; laboratory tests obtained 2 weeks after this dosage was started indicated an INR of 2.1. The same dosage was continued. Clarithromycin 500 mg bid was started for an acute exacerbation of bronchitis 10 days after the last INR was obtained and was continued for 14 days of therapy. An INR obtained 3 days after completion of the clarithromycin therapy was 16.8. The warfarin was withheld and vitamin K 20 mg im was administered. The INR obtained the next day was 1.52. The warfarin was restarted and the dosage was titrated to between 22.5 and 25 mg/wk, with INRs ranging from 0.85 to 3.14. DISCUSSION: Many factors influence the metabolism of warfarin, including disease states, medications, age, and diet. Data collected in this case suggested clarithromycin may have contributed to the increase in the effect of warfarin. Inhibition of the cytochrome P450 oxidizing system appears to be the reason for the increase. Numerous drugs and disease states affect the rate at which this system metabolizes drugs. CONCLUSIONS: The potential interaction between clarithromycin and warfarin warrants prudent monitoring of the INR during concurrent administration of these drugs. Warfarin dosages may need to be reduced during concurrent clarithromycin therapy to prevent bleeding complications. Further controlled clinical trials are needed to substantiate the interaction between clarithromycin and warfarin.

Aged↗

PubMed1997

Clarithromycin-induced digoxin intoxication.

OBJECTIVE: To report a case of clarithromycin-induced digoxin intoxication. CASE SUMMARY: A 78-year-old white man with ischemic cardiomyopathy and chronic renal insufficiency was admitted 4 days after being prescribed clarithromycin for a suspected episode of bronchitis. He reported weakness, asthenia, and gastrointestinal symptoms; the digoxin serum concentration was measured at 3.89 ng/mL. The patient recovered uneventfully after digoxin and clarithromycin were discontinued. DISCUSSION: Erythromycin frequently interacts with other drugs that are also metabolized by the CYP3A4 isoenzyme. However, erythromycin is hypothesized to interact with digoxin by inhibiting Eubacterium lentum, which is a normal inhabitant of the human gut and is responsible for intestinal metabolism of digoxin in 10% of patients. Since clarithromycin shares a comparable antibacterial spectrum with erythromycin, the possibility of a drug interaction with digoxin remains. Only four cases of clarithromycin interacting with digoxin have been reported to date. Clinically, this interaction may have been more obvious because of our patient's moderate renal dysfunction and serum digoxin concentrations in the upper therapeutic range prior to clarithromycin initiation. Other causes for digoxin intoxication could not be identified. CONCLUSIONS: Clarithromycin may inhibit the growth of E. lentum, which can lead to an increase in digoxin bioavailability and blood concentrations in patients in whom this intestinal metabolic pathway is present. Patients at risk include those with renal dysfunction, with serum concentrations in the upper therapeutic range, or with measured digoxin concentrations that are much lower than predicted by pharmacokinetic calculations. For these patients, appropriate therapy includes the selection of an alternative, noninteracting antibiotic or, if this is not possible, a temporary reduction of digoxin dosage.

Aged↗

PubMed2004

Comparison of hospitalization rates in patients with community-acquired pneumonia treated with 10 days of telithromycin or clarithromycin.

AIMS: To compare the impact on hospitalization rates and the clinical efficacy of oral telithromycin and clarithromycin treatment in patients with community-acquired pneumonia (CAP). PATIENTS AND METHODS: Outpatients aged >or= 18 years (n = 448) with CAP were enrolled in a randomized, double-blind, multinational study and received telithromycin 800 mg once daily (n = 224) or clarithromycin 500 mg twice daily (n = 224) for 10 days. The primary outcome measure was clinical efficacy at post-therapy/test of cure (Days 17-24) in the per-protocol population. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use were compared by treatment group (intent to treat population) up to the late post-therapy visit (Days 31-36). Study investigators who were blinded to the treatment arm assessed whether hospital admissions were CAP related or not. Hospitalization costs (USdollars) associated with telithromycin and clarithromycin treatment were compared. RESULTS: Per-protocol clinical cure rates for telithromycin and clarithromycin were statistically reduced number of hospitalizations/days required equivalent (88.3% [143/162] vs 88.5% [138/156] - difference: -0.2%; 95% CI: -7.8, 7.5). There were four CAP-related hospitalizations (1.8 events/100 patients) among patients treated with telithromycin vs eight (3.6 events/100 patients) among clarithromycin patients (p = 0.281). Total CAP-related hospitalization costs for telithromycin and clarithromycin patients were $25 360 vs $70 567, respectively (difference: -20 182 per 100 patients; 95% CI: -49 531; 9168) [corrected]. CONCLUSIONS: This study demonstrates that telithromycin is an effective therapy for outpatients with CAP. There were no significant differences in hospitalization rates between treatments; however, a tendency towards a numerically in hospital among telithromycin patients was observed. This could potentially translate into reduced hospitalization costs for telithromycin vs clarithromycin in the treatment of CAP.

Administration, Oral↗

PubMed1990

Comparative efficacy and tolerability of clarithromycin and amoxycillin in the treatment of out-patients with acute maxillary sinusitis.

The efficacy and tolerability of clarithromycin and amoxycillin in the treatment of acute maxillary sinusitis were compared in an open, Phase III multi-centre study. Sixty-one out-patients (40 males, 21 females) received clarithromycin (two 250 mg tablets twice daily) and 59 (34 males, 25 females) out-patients received amoxycillin (two 500 mg capsules twice daily). Fifty-seven and 47 patients in the clarithromycin group were evaluable for clinical efficacy and bacteriological effectiveness, respectively. In the amoxycillin group, 57 and 40 patients were evaluated for clinical efficacy and bacteriological effectiveness, respectively. Body temperature, bacteriological culture results, blood and urine chemistries, and clinical signs and symptoms were evaluated prior to drug administration, between Days 4 to 6 and between Days 9 to 11 of treatment, and within 48 hours and, if required, 6 weeks after the end of treatment. Clinical signs and symptoms improved significantly (p less than 0.001) in both treatment groups. When evaluated within 48 hours after the end of treatment, there was no significant difference between the clinical success rate for clarithromycin (91%) and amoxycillin (84%) nor in the number of patients whose original pathogen was eradicated (89% clarithromycin, 93% amoxycillin). Six patients reported adverse events, 2 with clarithromycin (urticaria, gastro-intestinal) and 4 with amoxycillin (2 urticaria, 2 gastro-intestinal). Clarithromycin was comparable to amoxycillin with respect to clinical efficacy and tolerability and offers a useful addition to the available therapies for the treatment of acute maxillary sinusitis.

Administration, Oral↗

PubMed1996

Clarithromycin and omeprazole as helicobacter pylori eradication therapy in patients with H. pylori-associated gastric disorders.

Helicobacter pylori is susceptible to many antibacterial drugs in vitro but has proved difficult to eradicate in vivo. The macrolide clarithromycin has good activity against H. pylori in vitro and has demonstrated the highest eradication rate for any antibacterial monotherapy in vivo. However, it is clear that antibacterial monotherapy is not a sufficiently effective treatment for patients with H. pylori infection. The suggestion that high intragastric acidity impairs the action of antibacterial drugs led to the evaluation of combination H. pylori eradication regimens including H+,K+-ATPase inhibitors and antibacterial drug(s) with or without bismuth compounds. Noncomparative studies evaluating the efficacy of dual therapy with clarithromycin plus omeprazole in patients with H. pylori infection have reported eradication rates of between 58 and 83% > or = 4-weeks after therapy. In comparative studies, clarithromycin plus omeprazole was at least as effective as amoxicillin plus omeprazole. However, direct comparisons have shown that eradication rates achieved by dual therapy are not as high as those achieved by triple therapy. Indeed, triple therapy with clarithromycin plus omeprazole in combination with amoxicillin or a nitroimidazole has achieved eradication rates of up to 100%. Although 14-day triple drug regimes were initially considered necessary for effective eradication, it now seems clear that 7-day regimes are equally effective. Factors known to influence response to H. pylori eradication therapy include bacterial resistance and patient compliance. A review of 4 studies evaluating the efficacy of dual eradication therapy with clarithromycin plus omeprazole reported an overall incidence of adverse events (patient or investigator reported, whether related to treatment or not) of 45%. The most common adverse event was taste disturbance (an adverse event commonly reported during the development of clarithromycin); nausea, headache, diarrhoea, vomiting and abdominal pain occurred less frequently. Although dual therapy might be expected to cause fewer adverse events than triple therapy this has not been the case in direct comparisons conducted to date. Thus, although clarithromycin plus omeprazole is associated with an H. pylori eradication rate of approximately 70%, 1 week of triple therapy with these 2 drugs together with amoxicillin or a nitroimidazole, which eradicates the organism in approximately 90% of cases, may represent optimal H. pylori eradication therapy.

Anti-Bacterial Agents↗