Use Of Clarithromycin Research Articles

S27 Cardiovascular events following Clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies

BackgroundPrevious studies have suggested that use of macrolide antibiotics may increase cardiovascular risk.ObjectiveTo study the effects of clarithromycin on cardiovascular events in the setting of acute exacerbations of chronic obstructive...

Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study

Although fluoroquinolones are sometimes associated with mild, transient elevations in aminotransferase levels, serious acute liver injury is uncommon. Regulatory warnings have identified moxifloxacin as presenting a particular risk of hepatotoxicity. Thus, we examined the risk of idiosyncratic acute liver injury associated with the use of moxifloxacin relative to other selected antibiotic agents. We conducted a population-based, nested, case-control study using health care data from Ontario for the period April 2002 to March 2011. We identified cases as outpatients aged 66 years or older with no history of liver disease, and who were admitted to hospital for acute liver injury within 30 days of receiving a prescription for 1 of 5 broad-spectrum antibiotic agents: moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil or clarithromycin. For each case, we selected up to 10 age- and sex-matched controls from among patients who had received a study antibiotic, but who were not admitted to hospital for acute liver injury. We calculated odds ratios (ORs) to determine the association between admission to hospital and previous exposure to an antibiotic agent, using clarithromycin as the reference. A total of 144 patients were admitted to hospital for acute liver injury within 30 days of receiving a prescription for one of the identified drugs. Of these patients, 88 (61.1%) died while in hospital. After multivariable adjustment, use of either moxifloxacin (adjusted OR 2.20, 95% confidence interval [CI] 1.21-3.98) or levofloxacin (adjusted OR 1.85, 95% CI 1.01-3.39) was associated with an increase in risk of acute liver injury relative to the use of clarithromycin. We saw no such risk associated with the use of either ciprofloxacin or cefuroxime axetil. Among older outpatients with no evidence of liver disease, moxifloxacin and levofloxacin were associated with an increased risk of acute liver injury relative to clarithromycin.

Use of Clarithromycin and Adverse Cardiovascular Events among Older Patients Receiving Donepezil

Donepezil is a commonly used drug in older people that due to its procholinergic effects can provoke bradycardia and neurocardiogenic syncope. Donepezil is metabolized by the cytochrome P450 isozyme 3A4 (CYP3A4). Clarithromycin is a potent inhibitor of CYP3A4, and patients taking both of these drugs may be at increased risk of cardiac adverse events. The aim of this study was to evaluate the association between recent use of clarithromycin and adverse cardiovascular events in elderly patients receiving donepezil. A population-based, nested case-control study using provincial healthcare databases was conducted. The base cohort was made up of persons 66 years of age or older who were prescribed donepezil and also were prescribed clarithromycin, erythromycin, azithromycin, cefuroxime, moxifloxacin or levofloxacin. Cases were those members of the base cohort hospitalized for bradycardia, syncope or complete atrioventricular block. For each case patient, five controls were matched according to age, sex and residence (community or long-term care). Between July 2002 and March 2010, 17,712 patients continuously receiving donepezil were prescribed one of the antibacterials. In 1400 person-years of follow-up, 59 cases were identified. As compared with azithromycin, there was no statistically significant association between use of clarithromycin in donepezil users and subsequent adverse cardiovascular events (odds ratio 0.67; 95% CI 0.28, 1.63). There was no significant risk associated with exposure to either cefuroxime or respiratory quinolones. The use of clarithromycin in elderly donepezil users did not significantly increase the risk of adverse cardiovascular outcomes. However, our study cannot rule out a possible small increase in risk. Although antibacterials can be beneficial, care should be taken in selecting antibacterials for use in older people receiving donepezil.

Clarithromycin use in community-acquired pneumonia

Clarithromycin use in community-acquired pneumonia

Digoxin Toxicity Precipitated by Clarithromycin Use: Case Presentation and Concise Review of the Literature

We present a case of digoxin toxicity in the context of dehydration, renal dysfunction and concomitant use of the macrolide antibiotic, clarithromycin, which is known to inhibit P-glycoprotein–mediated efflux mechanisms of digoxin. A focused review of the literature is presented. Health care providers need to be vigilant of this mechanism of drug–drug interaction, which is also relevant to other commonly used cardiovascular drugs.

A case of Mycobacterium intracellulare infection with chronic empyema

A 83-year-old man had been treated for pulmonary infiltration was referred to a nearby hospital because of slight fever and cough. His chest radiograph and CT showed right chronic empyema, and in which pleural aspirate was smear positive for acid-fast bacilli and positive for PCR-Mycobacterium intracellulare. He was diagnosed as chronic empyema caused by M. intracellulare. A month later exacerbation of bronchopleural fistula was observed and M. intracellulare infection expanded into the lung. He was treated with combined use of ethambutol, rifampicin, clarithromycin, and streptomycin for six months, and his chest radiograph showed improvement, however, finally he died as he was in advanced age and emaciation due to chronic lung infection.

Serum sickness‐like reaction with clarithromycin

Serum sickness-like reaction is a rare immunological condition which may develop following exposure to certain drugs such as penicillins, cephalosporins, and trimethoprim-sulfamethoxazole, among many others. It is described classically as a type III hypersensitivity response to heterologous proteins. Its true mechanism is still unclear. We present a case of serum sickness-like reaction to clarithromycin, a commonly prescribed drug for the treatment of respiratory tract infections. The patient had been taking this drug for 3 days when she experienced generalized body aches, rash, arthralgia, and shortness of breath, prompting presentation to the emergency department. Laboratory studies showed decreased C4 and total complement with a slightly elevated sedimentation rate. After exclusion of other possible causes, the diagnosis of serum sickness-like reaction was made. The patient responded well to nonsteroidal antiinflammatory medication, antihistamines, and a short, tapering dose of steroids. To our knowledge, serum sickness-like reaction to clarithromycin has never been reported previously. This case emphasizes the need for increased clinical awareness of such an adverse outcome to clarithromycin use.

Clarithromycin for prevention of bronchiolitis obliterans syndrome in lung allograft recipients

Bronchiolitis obliterans syndrome (BOS) is the major limitation to long-term survival following lung transplantation and strategies to reduce its incidence have remained elusive. Macrolides may stabilize lung function in patients with established BOS. Their role, however, in prevention of BOS remains unexamined. Survival and BOS-free survival of 102 lung allograft recipients (LARs), transplanted at a single center between July 1995 and December 2001 who routinely received clarithromycin, were compared with two different control groups. The first control group consisted of 44 LARs from the same center who were transplanted from January 2002 onwards and did not receive clarithromycin. The second control group consisted of a contemporaneous cohort of 5089 recipients, transplanted between 1995 and 2001, reported to the United Network for Organ Sharing database. When compared with the first control group, BOS-free survival was reduced in LARs receiving clarithromycin. Univariate (hazard ratio [HR] 3.13, p-value = 0.004) and multivariate (HR 3.49, p-value = 0.04) analyses showed that routine use of clarithromycin was associated with an increased risk of developing BOS. When compared with the second control group, the five-yr survival of clarithromycin group was similar (p-value = 0.24). Routine use of clarithromycin does not delay development of BOS or improve survival.

The risk of hypotension following co-prescription of macrolide antibiotics and calcium-channel blockers

The macrolide antibiotics clarithromycin and erythromycin may potentiate calcium-channel blockers by inhibiting cytochrome P450 isoenzyme 3A4. However, this potential drug interaction is widely underappreciated and its clinical consequences have not been well characterized. We explored the risk of hypotension or shock requiring hospital admission following the simultaneous use of calcium-channel blockers and macrolide antibiotics. We conducted a population-based, nested, case-crossover study involving people aged 66 years and older who had been prescribed a calcium-channel blocker between Apr. 1, 1994, and Mar. 31, 2009. Of these patients, we included those who had been admitted to hospital for the treatment of hypotension or shock. For each antibiotic, we estimated the risk of hypotension or shock associated with the use of a calcium blocker using a pair-matched analytic approach to contrast each patient's exposure to each macrolide antibiotic (erythromycin, clarithromycin or azithromycin) in a seven-day risk interval immediately before admission to hospital and in a seven-day control interval one month earlier. Of the 7100 patients admitted to hospital because of hypotension while receiving a calcium-channel blocker, 176 had been prescribed a macrolide antibiotic during either the risk or control intervals. Erythromycin (the strongest inhibitor of cytochrome P450 3A4) was most strongly associated with hypotension (odds ratio [OR] 5.8, 95% confidence interval [CI] 2.3-15.0), followed by clarithromycin (OR 3.7, 95% CI 2.3-6.1). Azithromycin, which does not inhibit cytochrome P450 3A4, was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8). We found similar results in a stratified analysis of patients who received only dihydropyridine calcium-channel blockers. In older patients receiving a calcium-channel blocker, use of erythromycin or clarithromycin was associated with an increased risk of hypotension or shock requiring admission to hospital. Preferential use of azithromycin should be considered when a macrolide antibiotic is required for patients already receiving a calcium-channel blocker.

Clarithromycin Use and Risk of Death in Patients with Ischemic Heart Disease

Objectives: To examine whether treatment with clarithromycin was associated with an increased risk of death in patients with preexisting ischemic heart disease (IHD). Methods: Employing nationwide registers, all patients with IHD events from 1997 to 2007 who subsequently claimed prescriptions for dual antibiotic treatment for eradication treatment were identified. The primary endpoint was all-cause mortality. Results: The study included 214,330 individuals with IHD; 5,265 (2.5 %) of these claimed prescriptions for dual antibiotics. Compared with IHD patients not undergoing eradication therapy, no increase in the risk of all-cause mortality was demonstrated (HR 1.02; 95% CI 0.84–1.23, p = 0.87) after 5 years. Conclusions: The use of clarithromycin in the setting of eradication treatment for Helicobacter pylori in patients with IHD was not associated with an increased risk of death.

Concomitant use of clarithromycin, cotrimoxazole, fluconazole or levofloxacin appears to increase the risk of severe hypoglycaemia

Concomitant use of clarithromycin, cotrimoxazole, fluconazole or levofloxacin appears to increase the risk of severe hypoglycaemia

Review Article: Mycobacterium Marinum Infection of the Hand and Wrist

Misdiagnosis and delayed treatment of Mycobacterium marinum infection is common because of its diverse manifestations. This leads to inappropriate use of antimicrobials, extension of the infection from the skin to the tenosynovium, and a poor prognosis (loss of tendons and prolonged immobilisation, secondary to multiple debridements and joint contractures). Clinicians should be aware of this type of infection, especially in subjects at risk (fishermen and aquarium enthusiasts), and those with a history of trauma coupled with exposure to water or marine life. A proactive approach to obtain a biopsy for histopathological and microbiological diagnosis is advised. Anti-mycobacterial treatment should be started promptly. The combined use of rifampicin, ethambutol, and clarithromycin appears to be effective, and debridement is indicated in patients with deep-seated infections.

Clarithromycin resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Malaysia

To determine the prevalence of primary clarithromycin resistance amongst Helicobacter pylori (H. pylori) strains in Malaysian patients with gastroduodenal diseases, by using restriction fragment length polymorphism (RFLP) in domain V of 23S rRNA. Gastric biopsies were obtained from H. pylori positive patients undergoing gastroscopy. DNA extraction was followed by PCR amplification using the primers Hp23-1 and Hp23-2 flanking a region of 425bp within the bacterial 23S rRNA peptidyltranferase (Hp23S fragment). Analysis of the 23S rRNA gene mutations is based on the generation of restriction sites for two restriction enzymes: BbsI and BsaI, which correspond to the base substitutions characteristic of clarithromycin resistance from A to G at positions 2142 and 2143, respectively. Gastric biopsy samples were obtained from 107 patients. A fragment of size 425bp corresponding to that expected from amplification of domain V of 23S rRNA was PCR-amplified from only 105 samples. The amplicon was subsequently subjected to restriction by BbsI and BsaI. Only 1 sample (0.95%) had the BbsI mutation (base substitution at A2142G) and 2 samples (1.90%) the BsaI mutation (base substitution at A2143G). Thus 3 of 105 (2.9%) samples harbored clarithromycin resistant strains. In our experience, PCR-RFLP is a rapid and precise method to detect the resistance of H. pylori to clarithromycin. Using this method, a low prevalence of clarithromycin resistance was detected in our local Malaysian strains. This augurs well for the continued use of clarithromycin as a first line drug in the treatment and eradication of H. pylori infection.

Эффективность раннего назначения кЛаритромицина и азитромицина у боЛьных внебоЛьничной пневмонией на амбуЛаторном Этапе

Эффективность раннего назначения кЛаритромицина и азитромицина у боЛьных внебоЛьничной пневмонией на амбуЛаторном Этапе

Current treatment of atypical mycobacteriosis

Background: Atypical mycobacteria are a heterogeneous group of organisms that are of increasing importance because of the growing number of infections they cause. This rising rate of infection is due mainly to the increase in the number of susceptible (and especially immunosuppressed) patients. Objective: To revise the currently used treatment schemes of the most commonly isolated atypical mycobacteria. Methods: Literature review using reference books and PubMed with specific keywords for each mycobacteria. Results/conclusion: The first important step in the management of atypical mycobacteria is to recognize the true infections caused by these organisms. The treatment required varies according to species. Well-characterized combinations exist for most common isolates, with the use of first-line antituberculous drugs (isoniazid, rifampin, ethambutol), clarithromycin, aminoglycosides and/or quinolones for slowly growing species (Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium ulcerans, Mycobacterium marinum, Mycobacterium lentiflavum, Mycobacterium malmoense) and macrolides, quinolones, amikacin and other antibiotics for rapidly growing mycobacteria (Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum). Surgical therapy is also important for some species (Mycobacterium ulcerans, Mycobacterium scrofulaceum) and for localized infections. The treatment of uncommon species is not well defined and is determined by the results of in vitro tests of individual strains. Because of the increasing number of resistant strains, new antibiotics need to be used for the treatment of these strains.

The role of efflux pumps in macrolide resistance in Mycobacterium avium complex

Mycobacterium avium complex (MAC) is clinically important since it can cause severe infections in acquired immune deficiency syndrome (AIDS) patients and other immunocompromised individuals. Use of the macrolides clarithromycin and azithromycin has improved the outcome of MAC infections, but therapeutic failure is still a major problem. In this work, we studied efflux pump activity in MAC clinical strains and evaluated the contribution of active efflux to macrolide resistance. Eighteen clinical strains isolated from AIDS patients were evaluated for macrolide resistance in the presence and absence of the efflux pump inhibitors (EPIs) thioridazine, chlorpromazine and verapamil. The efflux activity of these strains was then assessed by a semi-automated fluorometric method that detects extrusion of ethidium bromide (EtBr), a known efflux pump substrate. Resistance to clarithromycin was significantly reduced in the presence of thioridazine, chlorpromazine and verapamil. The same EPIs were effective in decreasing the efflux of EtBr from MAC cells. Moreover, increased retention of [ 14C]-erythromycin in the presence of these EPIs further demonstrated that active efflux contributes to MAC resistance to macrolides. This study demonstrates that efflux pumps play an important role in MAC resistance to antibiotics.

Torsade de pointes in a patient with bronchopenumonia and atrial fibrillation treated with clarithromycin

Clarithromycin is a macrolide antibiotic widely used in pulmonary infection and Helicobacter pylori eradication. QT prolongation on an electrocardiogram with torsade de pointes is an uncommon fatal side effect. We report a patient with atrial fibrillation and congestive heart failure who develops torsade de pointes after clarithromycin, tamoxifen, amoxillin/clavulanate, digoxin and verapamil use, and discuss the pharmacological mechanism and prevention. Key words: Torsade de pointes, clarithromycin, atrial fibrillation, QT interval.

Rhabdomyolysis caused by co-medication with simvastatin and clarithromycin

Rhabdomyolysis is a rare side-effect of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase-inhibitors. Co-medication with inhibitors of the cytochrome P450 3A4 (CYP34A) pathway may increase this risk. We describe the case of a female patient who developed severe rhabdomyolysis due to concomitant use of simvastatin (20 mg) and clarithromycin. Previous reports on this interaction involved patients on high doses of statins. This case demonstrates that even low-dose therapy of CYP3A4metabolized statins is associated with an increased risk of rhabdomyolysis when combined with CYP3A4 inhibitors. Due to the wide use of statins in stroke medicine, a knowledge of this interaction has significant clinical

Prevalence of A2143G mutation of H. pylori-23S rRNA in Chinese subjects with and without clarithromycin use history

BackgroundA2143G mutation of 23S rRNA gene of H. pylori results in clarithromycin (CLR) resistance. To investigate the prevalence of the CLR resistance-related A2143G mutation of the H. pylori-specific 23S rRNA gene in Chinese subjects with and without CLR use history, 307 subjects received the treatment with amoxicillin and omeprazole (OA) and 310 subjects received a placebo in 1995, and 153 subjects received a triple therapy with OA and CLR (OAC) in 2000. DNA was extracted from fasting gastric juice at the end of the intervention trial in 2003. H. pylori infection was determined by H. pylori-specific 23S rRNA PCR, ELISA, and13C-urea breath test assays. Mutations of the 23S rRNA gene were detected by RFLP assays.ResultsThe presence of 23S rRNA due to H. pylori infection in the OA group remained lower than that in the placebo group 7.3 yrs after OA-therapy [51.1% (157/307) vs. 83.9% (260/310), p = 0.0000]. In the OAC group, the 23S rRNA detection rate was 26.8% (41/153) three yrs after OAC-treatment. The A2143G mutation rate among the 23S rRNA-positive subjects in the OAC group [31.7% (13/41)] was significantly higher than that in the OA group [10.2% (16/157)] and the placebo group [13.8% (36/260)]. The frequency of the AAGGG → CTTCA (2222–2226) and AACC → GAAG (2081–2084) sequence alterations in the OAC group was also significantly higher than those in the OA group and the placebo group.ConclusionPrimary prevalence of the A2143G mutation was 10~14% among Chinese population without history of CLR therapy. Administration of CLR to eliminate H. pylori infection increased the prevalence of the A2143G mutation in Chinese subjects (32%) significantly.

Medications for Extensively Drug-Resistant Tuberculosis: Back to the Future?

Objective: To reexamine the existing medications for the potential treatment of extensively drug-resistant tuberculosis (XDR-TB), based on susceptibility data, and to identify potential future medications from the literature. Data Sources: Relevant information was identified through a search of MEDLINE (1966–November 2007), PubMed (1955–November 2007), American Search Premier (1975–November 2007), International Pharmaceutical Abstracts (1960–November 2007), Science Citation Index Expanded (1996–November 2007), Cochrane Databases (publications archived until November 2007), and various tertiary sources as listed in the references, using the terms extensively drug-resistant tuberculosis (XDR-TB), ethambutol, pyrazinamide, para-aminosalicylic acid, cycloserine, linezolid, diarylquinoline, nitroimidazopyran, fluoroquinolones, β-lactams, new treatments, and ethionamide alone or in combination regimens. Study Selection and Data Extraction: After identification of the relevant information, the data presented in this article were selected based on clinical relevance and value of information. Data Synthesis: Based on susceptibility data, pyrazinamide, ethambutol, para-aminosalicylic acid, cycloserine, and ethionamide may be used for the treatment of tuberculosis. However, due to the emergence of XDR-TB, many of these agents are no longer successful treatment regimens. We have found limited data supporting potential future use of β-lactams, clarithromycin, and linezolid in resistant TB infections. TMC207, nitroimidazopyran, and SQ109 compounds may also prove to be viable options in the near future for treatment of tuberculosis, especially in cases with resistance to mainstay medications. Conclusions: Extensively resistant tuberculosis appears to be a potentially catastrophic disease if allowed to spread. Due to its resistance profile, very few potentially effective agents are available, calling attention to this growing problem.