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PubMed2005

Influence of 1-week Helicobacter pylori eradication therapy with rabeprazole, clarithromycin, and metronidazole on 13C-aminopyrine breath test.

Helicobacter pylori eradication therapy is commonly prescribed in the general population. Treatment consists of drugs that are mainly metabolized by the liver cytochrome P-450 (CYP) enzymatic pool. Most H. pylori-infected patients often take drugs for comorbid illnesses, therefore increasing the potential for drug-drug interactions. We aimed to evaluate the interactions of rabeprazole, clarithromycin, and metronidazole 1-week H. pylori eradication therapy with CYP-dependent liver metabolic function in clinical practice. Ten patients referred to our unit for H. pylori infection underwent 1-week eradication therapy with rabeprazole (20 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and metronidazole (500 mg, b.i.d.). We chose the 13C-aminopyrine breath test (13C-ABT) to evaluate CYP-dependent liver function since it is noninvasive and nonharmful. All patients underwent 13C-ABT at three time points: before therapy (to), at the end of therapy (t8), and after 1 month of follow-up (t38). Mean 13C-ABT dose/hr (t0 = 14.0 +/- 5.4, t8 = 13.5 +/- 4.0, t38 = 16.1 +/- 5.6) as well as 13C-ABT cumulative dose (t0 = 2.4 +/- 1.1, t8 = 2.4 +/- 0.8, t38 = 2.6 +/- 1.0) were not statistically different at the three time points of the study. These results did not seem to be influenced by drugs being administered concomitantly. In everyday clinical practice rabeprazole-based H. pylori eradication therapy does not seem to display any significant interactions with CYP-dependent liver function, even in patients on multiple drugs.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Efficacy of clarithromycin in preventing viridans streptococcal bacteremia following autologous stem cell transplantation.

BACKGROUND: In a study involving 200 patients, we previously found that 17.5% of patients developed viridans streptococcal (VS) bacteremia following autologous peripheral blood stem cell transplantation (aPBSCT) when ciprofloxacin or ciprofloxacin plus ampicillin was used for prophylaxis. PATIENTS AND METHODS: A retrospective evaluation of 100 consecutive recipients of aPBSCT was conducted to ascertain the incidence and outcome of VS bacteremia when a combination of ciprofLoxacin and clarithromycin was utilized for antimicrobiaL prophylaxis following transplantation. The 200 patients from our previous study, in which ciprofloxacin alone or ciprofloxacin with ampicillin was used for prophylaxis, were combined with the current group for the purpose of statistical analysis. RESULTS: Streptococcus mitis was isolated from the blood of five individuals at a median of 5 days following stem cell infusion. Each of these patients was neutropenic and presented with fever. Three isolates demonstrated intermediate resistance to macrolides in vitro. However, all episodes of bacteremia were treated successfully with systemic antibiotic therapy. CONCLUSION: Age, duration of neutropenia, type of underlying malignancy and type of conditioning chemotherapy regimen failed to have a significant impact on subsequent VS bacteremia. Only female sex and use of ciprofloxacin without clarithromycin as antimicrobiaL prophyLaxis predicted a significantly increased risk of VS bacteremia in both univariate and Logistic regression analyses.

Adolescent↗
PubMed1995

Liquid chromatographic determination of the macrolide antibiotics roxithromycin and clarithromycin in plasma by automated solid-phase extraction and electrochemical detection.

A liquid chromatographic method for the determination of the macrolide antibiotics, roxithromycin and clarithromycin, in plasma is described. The method is fully automated, employing on-line solid-phase extraction for sample clean-up, using the Prospekt unit. Plasma samples, mixed with internal standard, were injected onto exchangeable CN cartridges. After washing, the compounds were eluted and transferred to a C18 analytical column for separation and electrochemical detection. Clarithromycin was used as internal standard when assaying roxithromycin and vice versa. The recovery of the solid-phase extraction method was 90% and higher, and the relative standard deviation was about 3%. The limit of quantitation was 0.5 mumol/l when 25 microliters of plasma was injected. Comparison with a liquid-liquid extraction method for sample clean-up showed good agreement.

Chromatography, High Pressure Liquid↗
PubMed1991

A comparison of the in-vitro activity of clarithromycin, a new macrolide antibiotic, with erythromycin and other oral agents.

On the basis of minimum inhibitory concentrations clarithromycin (6-O-methylerythromycin), a new macrolide, was found to be slightly more active than erythromycin against Staphylococcus aureus, enterococci. Moraxella catarrhalis, Gardnerella vaginalis, Bacteroides fragilis (sensu stricto) and B. ureolyticus and slightly less active against coagulase-negative staphylococci, alpha- and beta-haemolytic streptococci, Haemophilus influenzae, Campylobacter coli/jejuni and the B. melaninogenicus/oralis groups. There was complete cross-resistance between the two agents. Reports of potentiation of the activity against Haemophilus influenzae of clarithromycin by its own metabolite and by human serum appear to operate in vivo, and therefore the new agent shows great promise, especially for the treatment of respiratory tract infections.

Administration, Oral↗
PubMed1996

Uveitis during treatment of disseminated Mycobacterium avium-intracellulare complex infection with the combination of rifabutin, clarithromycin and ethambutol.

Three patients with a cellular immunodeficiency were treated with rifabutin, clarithromycin and ethambutol for a disseminated infection with Mycobacterium avium-intracellulare complex (MAC). The patients developed uveitis, sometimes in combination with a transient rash, arthralgia, arthritis, jaundice and pseudojaundice. It seems likely that these reactions were caused by rifabutin, alone or together with other drugs such as clarithromycin. These adverse reactions probably depend on the dose, metabolism and excretion of the drug. Inhibition of cytochrome P450 seems to be an important mechanism.

AIDS-Related Opportunistic Infections↗
PubMed1996

Ion-pair high-performance liquid chromatographic assay method for the assessment of clarithromycin stability in aqueous solution and in gastric juice.

A simple and selective ion-pair HPLC method has been developed for the analysis of clarithromycin in aqueous solutions and in gastric juice. A Hypersil ODS 5-microns (150 x 4.6 mm I.D.) column was used with a mobile phase consisting of acetonitrile-aqueous 0.05 M phosphate buffer (pH 4.6) containing 5 mM l-octanesulphonic acid (50:50, v/v). The column temperature was 50 degrees C and detection was by UV absorption (210 nm). The limits of detection of 50-microliters samples were 0.4 microgram/ml (aqueous) and 0.78 microgram/ml (0.5 ml gastric juice) or better. The assay was linear in the range of 1.56 to 100 micrograms/ml with r2 values greater than 0.99. The recovery from the gastric juice samples was 98.5 +/- 2.9%. The method was applied successfully to determine the stability of clarithromycin in 0.01 M HCl and gastric juice.

Anti-Bacterial Agents↗
PubMed2004

Application of 3'-mismatched reverse primer PCR compared with real-time PCR and PCR-RFLP for the rapid detection of 23S rDNA mutations associated with clarithromycin resistance in Helicobacter pylori.

Helicobacter pylori clarithromycin (Cla) resistance dramatically reduces efficacy of eradication therapy. In this study, 3'-mismatched reverse primer PCR (3M-PCR), real-time PCR (LightCycler), and PCR-RFLP assays were investigated to determine their sensitivity for detecting clarithromycin resistance associated with 23S rDNA mutations (A2142G, A2142C, and A2143G). For 84.8% (123/145) of isolates, the same allelic type was detected by each method although methods differed in efficiency of detecting mutations in cultures either containing mixtures of two alleles (24 isolates), or that were dual allelic variants (two isolates). The novel 3M-PCR assay format was the most sensitive, detecting all alleles at > or =0.02 ng/microl in DNA mixtures, and thus provides more precise information to guide clinical management of patients at risk of treatment failure.

Anti-Bacterial Agents↗
PubMed2004

Comparison of E-test and disk diffusion assay to evaluate resistance of Helicobacter pylori isolates to amoxicillin, clarithromycin, metronidazole and tetracycline in Costa Rica.

MIC distribution and susceptibility to four antimicrobial agents were determined by E-test for 94 Helicobacter pylori isolates from Costa Rica. Disk diffusion was evaluated as an alternative method to determine susceptibility and compared with the E-test results by linear regression analysis and an error-rate bounded method. Thirty-eight (40.4%) of the isolates were resistant to metronidazole, 5.3% to clarithromycin and 5.3% to amoxicillin. No isolate was resistant to tetracycline. Multiple resistance was found in 4.3% of the isolates. H. pylori isolates were categorised as resistant to amoxicillin, clarithromycin and tetracycline when inhibition diameters were less than 25, 21 and 25 mm, respectively, in the disk diffusion assay. A breakpoint diameter for metronidazole with disk diffusion could not be firmly established.

Amoxicillin↗
PubMed2004

Silica coatings on clarithromycin.

Pre-crystallized clarithromycin (6-O-methylerythromycin A) particles were coated with silica from the tetraethyl orthosilicate (TEOS)-ethanol-aqueous ammonia system. The coatings had a typical thickness of 100-150 nm and presented about 15 wt.% of the silica-drug composite material. The properties of the coatings depended on reactant concentration, temperature and mixing rate and, in particular, on the presence of a cationic surfactant (cetylpyridinium chloride). In the presence of cetylpyridinium chloride the silica coatings slightly decreased the rate of pure clarithromycin dissolution.

Anti-Bacterial Agents↗
PubMed2000

Clarithromycin targeting to lung: characterization, size distribution and in vivo evaluation of the human serum albumin microspheres.

Microspheres of clarithromycin have been prepared from human serum albumin using the emulsion polymerization technique. Albumin microspheres containing the active substance were injected into the tail vein of mice. Mice were sacrificed at intervals and microspheres collected from lungs and livers. The clarithromycin amount in microspheres was determined by reversed phase high performance liquid chromatographic (HPLC) method from the mice organs. Morphological and histopathological observations were also reported. The microsphere accumulation began at 10 min, and increased gradually until 6 h, then a decrease was observed. The microspheres were still present after 24 h. In the liver sample, no microsphere accumulation was observed at any time.

Albumins↗
PubMed1995

Azithromycin and clarithromycin.

Azithromycin and clarithromycin are alternatives to conventional macrolides in the routine treatment of many dermatologic, upper respiratory, and lower respiratory tract infections. In this role as alternative therapy, they are better tolerated, less toxic, and more convenient to take, although at a greater cost to the patient. This dosing convenience is an important consideration for the clinician; as shown by Nelson, patient compliance ranges from 95% with once-daily dosing to 58% with four-times-a-day dosing. Thus, less frequent dosing with both drugs as well as the shorter course of therapy possible with azithromycin may be therapeutically advantageous. In addition to their role as alternatives to conventional macrolide therapy, azithromycin and clarithromycin extend the spectrum of macrolides and offer new therapeutic options for H. influenzae, MAC in AIDS, MOTT, and leprosy. Finally, experimental therapy may extend their use for additional opportunistic infections, such as toxoplasmosis and cryptosporidiosis.

Azithromycin↗
PubMed2000

Clarithromycin in the management of community-acquired pneumonia.

OBJECTIVE: To review the epidemiology and diagnosis of community-acquired pneumonia (CAP) and examine factors that influence the choice of empiric antimicrobial therapy. BACKGROUND: CAP remains a common disease with substantial associated morbidity and mortality. Outpatient management of patients with CAP has become increasingly complex because of the availability of newer antimicrobial agents, evolving patterns of resistance, and the increasing recognition of atypical pathogens. Although Streptococcus pneumoniae remains a commonly encountered pathogen, the development and increasing prevalence of antibiotic resistance has become an area of concern, especially in outpatients. The newer macrolide antimicrobial drugs-clarithromycin and azithromycin-are effective against commonly encountered pathogens, are well tolerated, and have an established tolerability profile, although the low serum levels achieved by azithromycin hinder its use in patients with suspected bacteremia. METHODS: A MEDLINE search was performed of English-language articles published from 1990 to 2000 on the treatment of CAP. This article reviews the treatment of CAP, with emphasis on the use of clarithromycin. CONCLUSION: Although laboratory surveillance studies have reported macrolide-resistant S. pneumoniae, recent evidence defining the mechanism of this resistance, coupled with the pharmacokinetic properties of the macrolide agents, suggests that the actual rate of clinical macrolide resistance is low.

Anti-Bacterial Agents↗
PubMedDate not supplied

Efficacy of ciprofloxacin and clarithromycin in acute bacterial exacerbations of complicated chronic bronchitis: interim analysis. Bronchitis Study Group.

In a multicenter, community-based study involving more than 300 primary care physicians in the United States, the efficacy and safety of ciprofloxacin and clarithromycin were compared in the treatment of patients with complicated or severe acute bacterial exacerbations of chronic bronchitis (i.e., those who had failed previous antibiotic treatment within the prior 2 to 4 weeks; those with susceptibility data suggestive of a resistant pathogen; those having three or more acute exacerbations of chronic bronchitis [AECB] within the past year; and those having three or more comorbid conditions). Patients were randomized to either ciprofloxacin (CIP) 750 mg BID or clarithromycin (CLR) 500 mg BID, both administered for 10 days; all patients were treated on an outpatient basis. Clinical response at the end of therapy was the primary efficacy variable. An interim analysis was performed on the results from 743 patients (369 CIP, 374 CLR) with clinical and bacteriologic evidence of a bronchopulmonary infection who had completed an ongoing study as of the end of May 1997. Three hundred nine pathogens were isolated before therapy, including Haemophilus spp (75 isolates), Moraxella catarrhalis (67 isolates), Staphylococcus aureus (55 isolates), and Streptococcus pneumoniae (23 isolates). Seven hundred eighteen patients (97%) were included in the efficacy-valid population. Clinical success at the end of therapy was observed in 90% (272 of 302) and 88% (274 of 313) of efficacy-valid patients treated with CIP and CLR, respectively (95% confidence interval [CI] = -2.4 to 7.6). Corresponding rates for the intent-to-treat population were also 90% (283 of 314) and 88% (281 of 321), respectively (95% CI = -2.3 to 7.5). The bacteriologic response for efficacy-valid patients at the end of therapy was 98% (119 of 122) for CIP-treated and 93% (103 of 111) for CLR-treated patients (95% CI = -0.8 to 10.2). The eradication rates for the three most commonly isolated gram-negative pathogens were 100% for CIP-treated and 95% for CLR-treated patients and 96% each for the two most commonly isolated gram-positive organisms. Superinfections due to respiratory tract pathogens were more common in the CLR group (10 organisms) than in the CIP group (4 organisms). Seventy-four (20%) CIP-treated and 62 (17%) CLR-treated patients reported 118 and 103 respective study-emergent adverse events. Headache, abdominal pain, diarrhea, nausea, and vomiting in CIP-treated patients and diarrhea, nausea, vomiting, and taste perversion in CLR-treated patients were the most commonly reported adverse events. Treatment of patients with complicated or severe AECB with CIP 750 mg BID was associated with rates of clinical success and bacteriologic eradication similar to those with CLR.

Anti-Bacterial Agents↗
PubMed1997

Clarithromycin-induced ventricular tachycardia.

Clarithromycin is a relatively new macrolide antibiotic that offers twice-daily dosing. It differs from erythromycin only in the methylation of the hydroxyl group at position 6. Although the side-effect profile of erythromycin is established, including gastroenteritis and interactions with other drugs subject to hepatic mixed-function oxidase metabolism, experience with the newer macrolides is still being recorded. Cardiotoxicity has been demonstrated after both intravenous and oral administration of erythromycin but has never been reported with the newer macrolides. We report a case of ventricular dysrhythmias that occurred after six therapeutic doses of clarithromycin. The dysrhythmias resolved after discontinuation of the drug.

Adult↗
PubMed1996

Clarithromycin-associated visual hallucinations in a patient with chronic renal failure on continuous ambulatory peritoneal dialysis.

Visual hallucinations are a rare event in chronic renal failure and not related to uremia per se. Unreported in the literature is visual hallucinations occurring in association with the new macrolide antibiotic, clarithromycin. We describe such a case in a patient with end-stage renal disease (ESRD) maintained on continuous ambulatory peritoneal dialysis (CAPD). The combination of a relatively high dose of clarithromycin in face of chronic renal failure in a functionally anephric patient, with underlying aluminum intoxication, may have facilitated the appearance of this neurotoxic side effect. It is important to understand the pharmacokinetics of medications in face of chronic renal failure, the possibility of drug interactions, and how these factors should help guide medication therapy in the ESRD patient.

Anti-Bacterial Agents↗
PubMed2001

Study on the electrochemical detection of the macrolide antibiotics clarithromycin and roxithromycin in reversed-phase high-performance liquid chromatography.

The optimal conditions of the amperometric detection of the macrolide antibiotics clarithromycin and roxithromycin were found by cyclic voltammetric studies and HPLC-electrochemical detection responses obtained in different temperatures (25.5-60 degrees C) and different but almost isoelutropic binary, ternary and quaternary mixtures of aqueous buffer (pH 7), methanol, acetonitrile and isopropanol. These conditions were also proved to be applicable for the quantitative detection of clarithromycin in human plasma using roxithromycin as an internal standard and vice versa. It was demonstrated that increased attention has to be paid to eluent composition and column temperature to ensure sensitive and reproducible electrochemical responses as well as regularly shaped peaks for both macrolides tested.

Anti-Bacterial Agents↗
PubMed1999

In vitro activity of gatifloxacin, compared with ciprofloxacin, clarithromycin, erythromycin, and rifampin, against Legionella species.

Gatifloxacin, a new advanced-generation, 8-methoxy fluoroquinolone, has shown efficacy against a broad spectrum of microorganisms. In this study, the in vitro activity of gatifloxacin was compared with that of ciprofloxacin, clarithromycin, erythromycin, and rifampin against 214 Legionella spp. Species tested in order of frequency were: L. pneumophila serogroups 1 to 9 (181 strains); L. dumoffii (10 strains); L. micdadei (9 strains); L. longbeachae (7 strains); and other Legionella spp. (7 strains). MICs were determined by a standard dilution procedure using buffered yeast extract agar. Gatifloxacin and rifampin were the most active agents against all strains of Legionella tested. Moreover, against L. pneumophila strains tested, gatifloxacin was found to be more active (highest MIC90 = 0.03 mg/L) than ciprofloxacin (highest MIC90 = 0.06 mg/L) and clarithromycin (highest MIC90 = 0.12 mg/L). L. pneumophila serogroups 1 to 4 and 6 to 9 (MIC90 = 0.016 mg/L) were more susceptible to gatifloxacinthan L. pneumophila serogroup 5 (MIC90 = 0.03 mg/L). The activity of gatifloxacin against L. micdadei was equal to that of ciprofloxacin (MIC90 = 0.016 mg/L) and greater than that of erythromycin (MIC90 = 1.0 mg/L). The activity of gatifloxacin against L. dumoffii and L. longbeachae was equal to that of ciprofloxacin (MIC90 = 0.03 mg/L). The activity of gatifloxacin was similar against isolates obtained from both patients and environmental sources.

Anti-Bacterial Agents↗
PubMed2001

An unusual case of clarithromycin associated ergotism.

A 41-year-old woman presented to the Emergency Department complaining of a 4-day history of worsening lower leg pain, pallor, and a sensation of coolness aggravated by exertion. Evaluation revealed severe lower extremity vasospasm. She recently had been prescribed clarithromycin for "flu-like" symptoms, and for many years had been taking a caffeine-ergotamine preparation for migraine headaches. Clarithromycin is known to interfere with ergotamine metabolism. This drug interaction is often not recognized. Ergot alkaloids are commonly used for migraine headaches and have vasoconstrictive properties. In a patient with ergotamine toxicity, these vasoconstrictive properties can lead to frank ischemia. We reviewed the literature for reports of ergotamine-associated ischemia and for reports of ergotamine toxicity caused by drug-drug interaction.

Adult↗