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An unreported side effect of topical clarithromycin when used successfully to treat Mycobacterium avium-intracellulare keratitis.

PURPOSE: To report a case of Mycobacterium avium-intracellulare (MAI) keratitis successfully treated with topical clarithromycin. An unreported side effect of the topical medication is described. METHODS: A regular follow-up in the corneal clinic was arranged, and a pertinent literature search performed. RESULTS: The use of topical clarithromycin was successful in treating the keratitis. The patient did not complain of any ocular discomfort. Corneal subepithelial deposits that appeared during treatment with clarithromycin resolved shortly after the therapy was discontinued. CONCLUSION: This case report demonstrates that a rare infection like MAI keratitis can be successfully treated with topical clarithromycin. It also highlights the possible corneal deposition of this drug, which resolved after cessation of therapy.

Administration, Topical↗

Comparison of spiramycin and clarithromycin for community-acquired lower respiratory tract infections.

This open multicentre study compared the efficacy and tolerability of clarithromycin and spiramycin in the treatment of lower respiratory tract infections in Brazil and Colombia. A total of 125 patients with a clinical and radiological diagnosis of pneumonia, acute bronchitis or exacerbation of chronic bronchitis were randomised to receive oral doses of either clarithromycin (500 mg) or spiramycin (3 MIU) every 12 hours for courses of 5-10 days. Patients were assessed before the start of treatment, and at days 3-4 and days 9-17. Twenty-six (26) patients (16 in the spiramycin group and 10 in the clarithromycin group) reported adverse events, seven of whom withdrew from the trial. Statistical analysis detected no significant differences between efficacy (p = 0.768) or tolerability (p = 0.236) for the two treatment groups. Spiramycin therefore has similar efficacy to clarithromycin in the treatment of community-acquired lower respiratory tract infections.

Adolescent↗

Clarithromycin for safe and cost-effective reduction of cyclosporine doses in lung allograft recipients.

BACKGROUND: This study was done to analyze the economic effect of clarithromycin on the daily dosing of cyclosporine in lung transplantation. METHODS: Nine consecutive patients (mean age +/- SEM, 34.6 +/- 5.2 years) had transplantation from June 1995 to June 1996. Median follow-up time was 649 days (range, 431 to 799 days). Preoperative diagnoses were cystic fibrosis (n = 4), idiopathic pulmonary fibrosis (n = 2), emphysema, bronchiectasis, and obliterative bronchiolitis. Median time from transplantation to addition of clarithromycin to a standard immunosuppressive regimen was 86 days (range, 14 to 181 days). RESULTS: Baseline cyclosporine dose (9.9 +/- 2.2 mg/kg/day) was reduced to 5.8 +/- 1.0 mg/kg/day and 4.1 +/- 0.8 mg/kg/day at 1 month and 1 year, respectively, after initiation of clarithromycin therapy. Estimated annual savings were $3,400 per patient. There was no increase in infection or rejection episodes. CONCLUSIONS: Clarithromycin safely reduced the dose and cost of cyclosporine in this series.

Adult↗

Are twelve days of omeprazole, amoxicillin and clarithromycin better than six days for treating H. pylori infection in peptic ulcer and in non-ulcer dyspepsia?

BACKGROUND/AIMS: To evaluate whether omeprazole, amoxicillin and clarithromycin for 12 days is more effective for Helicobacter pylori eradication than the same regimen for only 6 days; and to verify whether these eradication regimens are more effective in peptic ulcer disease than in non-ulcer dyspepsia. METHODOLOGY: We studied 411 patients in whom a gastroscopy was carried out due to symptoms related to the upper gastrointestinal tract and who were diagnosed with duodenal ulcer (175 patients, 43%), gastric ulcer (42 patients, 10%), or non-ulcer dyspepsia (194 patients, 47%), and concomitant infection by H. pylori. At endoscopy, biopsies were obtained for rapid urease test, and a 13C-urea breath test was carried out. Urea breath test was repeated four weeks after completing eradication treatment with 1) omeprazole (20 mg b.i.d.), amoxicillin (1 g b.i.d.) and clarithromycin (500 mg b.i.d.) for six days (239 patients), or 2) the same regimen for 12 days (172 patients). RESULTS: H. pylori eradication was achieved in 73.6% (95% CI, 68-79%) of the patients treated during 6 days, and in 84.3% (79-90%) of those receiving 12 days of therapy (P < 0.01). The overall eradication rate with both regimens (6 plus 12 days), respectively in patients with duodenal ulcer, gastric ulcer and non-ulcer dyspepsia, was 84.6% (79-90%), 75.6% (61-86%), and 72.8% (67-79%) (P < 0.01 when comparing duodenal ulcer vs. non-ulcer dyspepsia). Twelve-day regimen was more effective than 6-day regimen only in non-ulcer dyspepsia (62% vs. 83%, P < 0.01), but not in duodenal or gastric ulcer. In the multivariate analysis the duration (6 vs. 12 days) of eradication therapy (odds ratio: 2.2; 1.3-3.7) and the type of disease (duodenal ulcer vs. non-ulcer dyspepsia; odds ratio: 2.3; 1.3-3.8) were the only variables which influenced on H. pylori eradication efficacy (chi 2 model, 17; P < 0.001). CONCLUSIONS: Efficacy with omeprazole-amoxicillin-clarithromycin regimen in patients with duodenal ulcer is higher than in those patients with non-ulcer dyspepsia. The increase of H. pylori eradication rate by 21% in our non-ulcer dyspepsia patients justifies the prolongation from 6 to 12 days of omeprazole-amoxicillin-clarithromycin therapy, whilst the increase of cure rates in duodenal or gastric ulcer patients with a 12-day therapy would not be cost-effective.

Adult↗

Clarithromycin-induced digoxin toxicity: a case report and a review of the literature.

A 70-year-old woman with a history of atrial fibrillation, on digoxin, presented with nausea, vomiting, and dizziness two days after initiation of clarithromycin therapy. Laboratory results revealed a serum digoxin level of 3.9 ng/ml (normal range 0.5-2.0) and creatinine of 1.1 mg/dl. The patient was admitted to the hospital and digoxin and clarithromycin were discontinued. The patient's symptoms were resolved within 24 hours and her serum digoxin level was 1.9 on the second hospital day. A review of recent literature suggests that clarithromycin may induce digoxin toxicity by three different mechanisms, including reduction of renal excretion of digoxin, alteration of intestinal flora, and inhibition of cytochrome P-450 in the liver. Digoxin toxicity was reported three to 17 days after the initiation of clarithromycin (8.1 +/- 4.8 days, n = 9). The wide variation in the time required for the appearance of toxicity may imply the different mechanisms involved in each case.

Aged↗

A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers.

Atorvastatin is a common option among the HMG-CoA reductase inhibitors for the treatment of lipid disorders because of its excellent lipid-lowering efficacy and overall safety profile. Although these agents can rarely cause rhabdomyolysis by themselves, macrolides, among other agents, have been demonstrated to increase the likelihood of this via inhibition of CYP metabolism of the lipid agent. This study investigated the potential for azithromycin and clarithromycin to inhibit the metabolism of atorvastatin. Although there was no interaction between azithromycin and atorvastatin, clarithromycin did have a significant effect on atorvastatin pharmacokinetic parameters. When coadministered, clarithromycin raised subject exposure (AUC24) by 82% and peak plasma concentrations by 56%. These data suggest that while azithromycin appears to be safe to coadminister with atorvastatin, clarithromycin should be avoided in patients taking this and similarly metabolized HMG-CoA inhibitors.

Adolescent↗

Genotypic characterization of clarithromycin-resistant Helicobacter pylori strains.

UNLABELLED: Helicobacterpylori (Hp) resistance to clarithromycin, one of the antibiotics most used to eradicate infection, is connected with the presence of a point mutation on the level of adenine at position 2143 or 2144 of 23S rRNA. AIM: The aim of the study is to evaluate of the presence of these mutation vs control clarithromycin resistant Hp strains present in North Sardinia; to verify the real association between the type of mutation and the resistance-level; to use easier molecular biology methods to quickly locate the resistance-associated mutations beginning with the bioptic material. The clarithromycin susceptibility of Hp isolates was tested by the E-test method (antibiotic assay). Genomic DNA of Hp strains was amplified using specific primers for the domain V. of ribosomic 23S rRNA and sequenced after the reaction with a primer within the fragment 23S. At the same time PCR-RFLP reliability was examined underlining the presence of these mutations with BsaI, BbsI, MboII restriction enzymes. Two mutations in 2143 (A- - G) and 2144 (A- - G) were found by domain V sequencing. The strains with mutation 2143 are characterized by a greater resistance level (MIC>64 g/ml) than those with mutation 2144 (MIC <64 g/ml). Restriction endonucleases BbsI and MboII recognise the site containing the mutation 2143 (A- - G), while BsaI recognise the mutation 2144 (A- - G). These methods might enable us to identify the presence of Hp directly from bioptic material and possible clarithromycin resistance and plan a suitable therapeutic strategy and consequently a better control of the infection.

Anti-Bacterial Agents↗

[Ototoxicity induced by clarithromycin].

A 76-year-old man developed a progressive bilateral hearing loss 4 days after starting a high dose of clarithromycin for atypical pulmonary tuberculosis. When the clarithromycin was discontinued the hearing improved subjectively but it worsened again upon reexposure. Halving the dose resulted in both an objective and subjective improvement in hearing, yet the original level of hearing was only obtained once clarithromycin had been permanently withdrawn. It would seem that this adverse effect is dose dependent. This seems to be the first published case study that demonstrates ototoxicity as a result of clarithromycin use.

Aged↗

[In vitro activity of clarithromycin and metronidazole against Helicobacter pylori in different incubation atmospheres].

The aim of this study was to determine the in vitro activity of clarithromycin and metronidazole using an agar dilution method to compare two different incubation atmospheres: a CO2 incubator and a jar with a microaerobic gas-generating system. Antibiotics were placed on plates in twofold dilutions ranging from 128 to 0.064 mg/l in Mueller-Hinton agar supplemented with 7% horse blood. The inoculum was prepared from 31 Helicobacter pylori isolates and was inoculated using a Steers replicator. Plates were incubated for 3 to 5 days and MICs were recorded as the lowest concentration of antibiotic inhibiting visible growth. Two different incubation atmospheres were used: a CO2 incubator set at 95% humidity and 10% CO2, and a jar with a gas-generating envelope that produces 7-10% O2 and 14% CO2 (BioMerieux). Clarithromycin resistance was found in 19% of strains both in the gas-generating system and the CO2 incubator. Metronidazole resistance was 23% in both atmospheres. MICs for clarithromycin in both atmospheres showed two dilutions of difference for 100% of the strains, and were slightly higher in the jar with a gas-generating envelope. However, MICs for metronidazole were higher when it was incubated in the CO2 incubator, and in 86.7% of strains the MICs showed < or = 2 dilutions of difference. No great discrepancies were found for either metronidazole or clarithromycin using the two methods.

Anti-Bacterial Agents↗

[Detection of resistance to clarithromycin in clinical isolates of Helicobacter pylori from children and adults].

Several methods have been used to detect clarithromycin resistance. Agar dilution is now recommended by the NCCLS (susceptible to clarithromycin: MIC<=0.25 mg/l; intermediate resistance: MIC=0.5 mg/l; resistant: MIC>=1 mg/l), and the detection of mutations involved in resistance is used in many laboratories. We analyzed 36 clarithromycin-resistant strains isolated from children and 30 from adults. In vitro susceptibility to clarithromycin was determined by an agar dilution method. DNA from the isolates was extracted using the method published by Ge and Taylor. A2142G and A2143G mutations were identified by PCR-RFLP. A 1.4 Kpb of the 23S rRNA gene was amplified and digested using MboII or BsaI restriction enzymes to detect mutations. The prevalence of the A-G transition mutation at position 2143 was higher in the children (80.55%) than in the adult patients (46.66%) (p<0.05); however, the prevalence of the mutation at position 2142 was higher in adults than in children (36.66% vs. 5.55%; p<0.05). In children, a higher MIC (2-64 mg/l) was observed when the A-G mutation was detected at position 2143. However, in adult patients higher MICs were observed when the A-G mutation was detected at position 2142.

Adult↗

High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin.

BACKGROUND/AIMS: Some patients are refractory to the usual triple therapy for eradication of Helicobacter pylori, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, so there needs to be an alternative strategy for retreatment after failure to eradicate the infection. METHODOLOGY: The study group comprised 17 H. pylori-positive patients who had failed to clear H. pylori infection after 1 week of treatment with usual doses of proton pump inhibitor, amoxicillin and clarithromycin. The sensitivity of H. pylori to clarithromycin and amoxicillin, and the CYP2C19 genotype status of each patient were determined and treatment with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2 weeks was started. RESULTS: Eleven patients were infected with a clarithromycin-resistant strain of H. pylori. Twelve patients had the homozygous extensive metabolizer genotype, 5 had the heterozygous extensive metabolizer genotype and there were none with the poor metabolizer genotype of CYP2C19. All patients were successfully cleared of their H. pylori infection without any adverse effects, irrespective of CYP2C19 genotype status (100%, 95% confidence interval: 76-100%). CONCLUSIONS: High-dose dual therapy with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2 weeks appears useful treatment strategy after failure of eradication of H. pylori by the usual triple proton pump inhibitor/amoxicillin/clarithromycin therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Pharmacoeconomic analysis of community-acquired pneumonia treatment with telithromycin or clarithromycin].

A pharmacoeconomic analysis was carried out comparing the efficacy of two treatment options for community-acquired pneumonia (CAP): telithromycin and clarithromycin. It was a retrospective analysis using a decision tree model. The efficacy of the two treatment options was estimated from a randomized, double-blind clinical trial, in which 800 mg/day oral telithromycin for 10 days was compared to 1000 mg/day oral clarithromycin for 10 days in patients with CAP (162 and 156 respectively). The use of resources was estimated based on the clinical trial and Spanish sources, and the unit costs from a Spanish health costs database. Costs were evaluated for the acquisition of antibiotic treatments, change of antibiotic due to therapeutic failure, hospital admissions, adverse reactions to treatment, primary care visits, tests and indirect costs (working days lost). The model was validated by a panel of Spanish clinical experts. As the clinical trial was designed to show equivalence, there were no significant differences in efficacy between the treatment options (clinical cure rate 88.3% and 88.5%, respectively), and a cost minimization analysis was performed. In the base case, the average cost of the disease per patient was 308.29 euros with telithromycin and 331.5 euros with clarithromycin (a difference of 23.21 euros). The results were stable in the susceptibility analysis, with differences favorable to telithromycin ranging between 5.50 and 45.45 euros. Telithromycin results in a cost savings of up to 45.45 euros per CAP patient compared to clarithromycin.

Anti-Bacterial Agents↗

Can lansoprazole, amoxicillin, and clarithromycin combination still be used as a first-line therapy for eradication of helicobacter pylori?

BACKGROUND/AIMS: To determine H. pylori eradication rate with lansoprazole-amoxicillin-clarithromycin treatment regimen, which is the most frequently used as first-line therapy, in the Kirikkale region. METHODS: One hundred and five patients (44 male, 61 female) with H. pylori infection were included in the study. Patients were divided into two groups based on the endoscopic findings: non-ulcer dyspepsia (n=84, 31 male, 53 female) and acute gastric or duodenal ulcer (n=21, 13 male, 8 female) groups. The diagnosis of H. pylori infection was confirmed if both the urease test and histological examination, which were performed on endoscopic biopsies, were positive. Lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg were given twice daily for 14 days to all patients. Endoscopic biopsies were repeated for the evaluation of eradication three months after the treatment. RESULTS: Ninety-six patients completed the study. Eradication rates were found to be 45.8% (44 of 96) in all patients, 42.1% (32 of 76 patients) in the non-ulcer dyspepsia group and 60% (12 of 20 patients) in the gastric or duodenal ulcer group for per protocol analysis, and the difference between non-ulcer dyspepsia and gastric or duodenal ulcer groups was not statistically significant (p=0.208). CONCLUSIONS: Lansoprazole-amoxicillin-clarithromycin treatment regimen, the most frequently preferred regimen in H. pylori eradication, is ineffective in our region. The low eradication rates observed with lansoprazole-amoxicillin-clarithromycin, at least in our region, bring into question its use as a first-line therapy. The use of alternative treatment protocols or antibiotic susceptibility test before the treatment may be helpful in achieving successful eradication with first-line therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Combination therapy with clarithromycin and sofalcone for eradication of Helicobacter pylori.

OBJECTIVE: To clarify the efficacy of combination therapy with clarithromycin and sofalcone for eradication of Helicobacter pylori. DESIGNS: We studied 42 patients with H. pylori-positive gastroduodenal diseases, who were divided into two groups according to treatment period. Group 1 comprised 27 patients (seven with gastric ulcers, 14 with duodenal ulcers and six with gastritis) treated with a combination of clarithromycin (200 mg, three times a day) + sofalcone (100 mg, three times a day) for 3 weeks. Group 2 comprised 15 patients with chronic active gastritis treated with the same doses of clarithromycin + sofalcone but for only 2 weeks (group 2). The H. pylori status of all patients was assessed by culture, rapid urease test and histological examination at the end of treatment and 4 weeks after the end of treatment. The gastritis score, the index of intracellular periodic acid-Schiff-positive substance in the antral mucosa and the ammonia concentration in gastric secretions were also estimated before and after treatment. RESULTS: In group 1, with over half the patients excluded from the follow-up, H. pylori was eradicated in nine out of 13 patients (69.2%) compared with six out of the complete group of 15 (40.0%) patients in group 2, without serious side effects. In these patients, significant improvements were seen in the gastritis score (P < 0.025), the index of periodic acid-Schiff-positive substances in the antral mucosa (P < 0.025) and the ammonia concentration in gastric secretions (P < 0.02) after treatment. CONCLUSION: These results suggest that modification of the treatment regimen is needed, with higher doses of clarithromycin and combination therapy with proton-pump inhibition.

Ammonia↗

[Helicobacter pylori therapy with omeprazole and clarithromycin: current status].

Clarithromycin and its 14-OH-metabolite are highly effective against Helicobacter pylori in vitro. This drug is acid stable and soluble and reaches considerable concentrations in the gastric mucosa and the mucus layer after oral administration. Several studies have meanwhile demonstrated that combined treatment with omeprazole and clarithromycin may eradicate. H. pylori infection in a remarkable proportion of treated patients. On the basis of the results of a recently published randomized doubleblind multicenter trial, at two-week therapy course comprising omeprazole 40 mg once in the morning and clarithromycin 500 mg thrice daily can be recommended for routine practice. One-week low dose triple therapy regimens combining omeprazole, clarithromycin and tinidazole or metronidazole might be a valuable alternative to omeprazole enhanced antibiotic monotherapy in the future, but the encouraging results of three pilot studies (H. pylori cure rates: 90%-100%) have to be confirmed in randomized and controlled trials.

Clarithromycin↗

Clarithromycin, tetracycline, and bismuth: a new non-metronidazole therapy for Helicobacter pylori infection.

OBJECTIVE: Metronidazole resistance has become an increasing problem that has limited the usefulness of the original triple therapy. Our objective was to evaluate clarithromycin, a new macrolide compound active against Helicobacter pylori. METHODS: We evaluated a new clarithromycin triple therapy for H. pylori infection consisting of the combination of clarithromycin (500 mg t.i.d.), tetracycline (500 mg q.i.d.), and bismuth subsalicylate tablets (2 q.i.d.) for 14 days. Patients with ulcer also received concomitant ranitidine, 300 mg after the evening meal, for 6 wk. RESULTS: Thirty men with documented H. pylori infection were studied; 29 had peptic ulcer disease. Seven had previously failed antimicrobial therapy, including three with metronidazole-based triple therapy. H. pylori status was determined by histology. H. pylori status and ulcer status were evaluated 4 wk after the end of antimicrobial therapy. The ulcer was healed in 90%. The H. pylori infection was cured in 93%, including all three patients who previously failed metronidazole-based triple therapy. CONCLUSION: We conclude that the combination of clarithromycin, tetracycline, and bismuth is an effective new therapy for treatment of H. pylori infection.

Adult↗

In vitro evaluation of activities of azithromycin, clarithromycin and sparfloxacin against Chlamydia trachomatis.

The in vitro activities of azithromycin, clarithromycin and sparfloxacin were evaluated by studying inhibition of in vitro Chlamydia trachomatis propagation in McCoy cells, comparatively with erythromycin, ofloxacin and tetracycline. Fifteen clinical isolates of C. trachomatis were tested with an inoculum of 5.10(3) inclusion--forming units in a 96--well microtiter plate. Minimal inhibitory concentration (MIC) ranges were as follows: azithromycin, 0.06 to 0.125 microgram/ml; clarithromycin, 0.008 microgram/ml; erythromycin, 0.06 to 0.125 microgram/ml; ofloxacin 0.5 to 1 microgram/mg; sparfloxacin, 0.03 to 0.06 microgram/ml; and tetracycline 0.125 to 0.25 microgram/ml. Minimal bactericidal concentration (MBC) ranges, calculated from passage into antibiotic--free medium, were as follows: azithromycin 0.25 to 0.5 microgram/ml; clarithromycin, 0.03 to 0.125 microgram/ml; erythromycin, 0.25 to 2 micrograms/ml; ofloxacin, 0.5 to 1 microgram ml; sparfloxacin, 0.03-0.06 microgram/ml; and tetracycline, 1 to 4 micrograms/ml. Clarithromycin and sparfloxacin showed the greatest activity and clinical studies of these agents in C. trachomatis infections are therefore indicated.

Anti-Bacterial Agents↗

Efficacy of clarithromycin vs. amoxicillin/clavulanate in the treatment of acute maxillary sinusitis.

A new macrolide drug, clarithromycin (Biaxin) was compared with amoxicillin/clavulanate (Augmentin) in a single-blind (investigator-blind), randomized, multicenter study of 497 outpatients with acute maxillary sinusitis; treatment was 500 mg clarithromycin bid (n = 246) or 500 mg amoxicillin/clavulanate tid (n = 251). Pathogens included Streptococcus pneumoniae in 22% of patients, Staphylococcus aureus in 16%, Haemophilus influenzae in 10%, and Moraxella catarrhalis in 7%. For evaluable patients, clinical success (cure or improvement) was noted for 97% (128/132) of clarithromycin recipients and 93% (119/128) amoxicillin/clavulanate recipients. Clinically significant improvement in signs and symptoms was comparable between groups. Bacteriologic cure rates were 87% (115/132) and 90% (115/128), respectively. Respective pathogen eradication rates were 87% (125/143) and 90% (125/139). Adverse events not due to concurrent conditions occurred in 41% of the former and 46% of the latter group; most were mild to moderate gastrointestinal upsets (21% and 38%, respectively; P < 0.001). We conclude that clarithromycin appears to be as effective as amoxicillin/clavulanate in acute maxillary sinusitis and may cause fewer gastrointestinal upsets.

Acute Disease↗