Generic and additional names: Clarithromycin CAS name: 6-O-Methylerythromycin CAS registry #: 81103-11-9 Molecular formula: C38 H69 NO13 Molecular weight: 747.95 Intellectual property rights: Generic Brand names: Biaxin (Abbott); Clathromycin (Taisho); Cyllind (Abbott); Klacid (Abbott); Klaricid (Abbott); Macladin (Guidotti); Naxy (Sanofi Winthrop); Veclam (Zambon); Zeclar (Abbott) Solubility: Clarithromycin is soluble in acetone, slightly soluble in methanol, ethanol, and acetonitrile, and practically insoluble in water [FDA label]. Water solubility 0.33 mg/l [DrugBank]. Polarity: Log P 2.69 [DrugBank]. Other authors have obtained values of Log P = 1.7 at pH 7.4.1 Acidity/basicity: pKa 8.99 [DrugBank] Melting point: 217–220ºC [DrugBank] Formulation and optimal human dosage: Biaxin is available as immediate-release tablets, extended-release tablets, and granules for oral suspension. Each Biaxin tablet contains 250 mg or 500 mg of clarithromycin. After constitution, each 5 ml of Biaxin suspension contains 125 mg or 250 mg of clarithromycin. Dose 250–1000 mg daily, higher amounts given in multiple doses [FDA label].
Objective Some central hypersomnolence syndromes are associated with a positive allosteric modulator of γ‐aminobutyric acid (GABA)‐A receptors in cerebrospinal fluid. Negative allosteric modulators of GABA‐A receptors, including clarithromycin, have been reported to reduce sleepiness in these patients. We sought to systematically assess the effects of clarithromycin on objective vigilance and subjective sleepiness. Methods This was a 5‐week, randomized, placebo‐controlled, double‐blind, crossover trial of clarithromycin 500mg with breakfast and lunch, in patients with hypersomnolence syndromes (excluding narcolepsy with cataplexy) and evidence for abnormal cerebrospinal fluid potentiation of GABA‐A receptors. The study occurred at a university‐affiliated medical center. The primary outcome measure was median reaction time on the psychomotor vigilance task (PVT) at week 2 in each condition. Secondary outcomes included the Epworth Sleepiness Scale, Stanford Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Pittsburgh Sleep Quality Index, SF‐36, and additional PVT measures. Results Twenty‐three patients began treatment. Three patients dropped out, and final analyses were performed on 20 complete cases. Median reaction time was not significantly different between clarithromycin and placebo. Subjective measures of sleepiness were significantly improved on clarithromycin versus placebo. Altered taste perception occurred, but was the only side effect more common on clarithromycin than placebo. No serious adverse events occurred. Interpretation Subjective sleepiness, but not psychomotor vigilance, improved during a 2‐week course of clarithromycin. Although additional studies are needed, this suggests that clarithromycin may be a reasonable treatment option in patients with treatment‐refractory hypersomnolence. This trial was registered at ClinicalTrials.gov (NCT01146600) and supported by the American Sleep Medicine Foundation. Ann Neurol 2015 Ann Neurol 2015;78:454–465
Background and Aim: Clarithromycin‐based triple therapy has been commonly applied as the first‐line therapy for Helicobacter pylori eradication. Levofloxacin could serve as an alternative in either first‐line or second‐line regimens. This study surveyed the prevalence of levofloxacin resistance of H. pylori isolates in naive patients and in patients with a failed clarithromycin‐based triple therapy. Methods: The study collected the H. pylori isolates from 180 naive patients and 47 patients with a failed clarithromycin‐based triple therapy. Their in vitro antimicrobial resistance was determined by E‐test. Results: The naive H. pylori isolates had resistance rates for amoxicillin, levofloxacin, clarithromycin and metronidazole of 0%, 9.4%, 10.6% and 26.7%, respectively. An evolutional increase of the primary levofloxacin resistance was observed in isolates collected after 2004, as compared to isolates collected before 2004 (16.3% vs 3.2%, P = 0.003). There was no evolutional increment of the primary clarithromycin resistance. The clarithromycin resistance elevated significantly after a failed clarithromycin‐based triple therapy (78.7% vs 10.6%, P < 0.001). The post‐treatment isolates remained to have a levofloxacin resistance rate of near 17%, but the levofloxacin‐resistant isolates were correlated with a higher incidence of metronidazole resistance (P = 0.023). No strain was found to be resistant to amoxicillin even after eradication failure. Conclusion: The levofloxacin resistance of naive H. pylori remains less than 10% in Taiwan. With relatively lower resistance to levofloxacin than to metronidazole of the H. pylori isolates collected after a failed clarithromycin‐based therapy, proton pump inhibitor–levofloxacin–amoxicillin may be an alternative choice to serve as the second‐line therapy.
Background Increasing clarithromycin resistance reduces Helicobacter pylori eradication rates with conventional triple regimens. We evaluated effectiveness and safety of a 10‐day‐quadruple nonbismuth containing regimen, as first‐line treatment or second‐line treatment (after conventional triple) for H. pylori, and assessed impact of antibiotic resistance on treatment success. Materials and methods Eligible patients had upper GI endoscopy and positive CLO‐test, also confirmed by histology and/or culture. The eradication scheme comprised: Esomeprazole 40 mg, Metronidazole 500 mg, Amoxicillin 1000 mg, and Clarithromycin 500 mg, twice daily, for 10 days. Treatment adherence and adverse effects were recorded. Eradication was tested by 13C‐urea breath test or histology. Results One hundred and ninety out of 198 patients (115M/83F, aged 18–81, mean 52 years, 37% smokers, 27% ulcer disease) who completed the study protocol were evaluated for eradication. Adherence to treatment was 97.7% (95% CI 95.9–99.6). Six (3.2%) patients experienced severe side effects and discontinued treatment. Intention to treat and per protocol analysis in first line was 91.5% (95% CI 86.2–94.8) and 95% (95% CI 90.4–97.4) and in second line was 60.6% (95% CI 43.6–75.3) and 64.5% (95% CI 46.9–78.8), respectively. Antibiotic susceptibility tests were performed in 106 of 124 (85%) patients who gave consent. Among them 42 (40%) harbored clarithromycin resistant strains. Eradication rates were significantly higher in sensitive and single clarithromycin or metronidazole resistant (37/37, 100% and 43/47, 91%) than in dual resistant strains (12/22, 55%) (p < .0001). Specifically, concomitant regimen eradicated 7/10, 70% of dual resistant strains as first‐line treatment and 5/12, 42% as second‐line treatment. Multivariate analysis showed that dual resistance was the only independent significant predictor of treatment failure. Conclusions The 10‐days “concomitant” regimen is effective and safe first‐line H. pylori treatment, in a high clarithromycin resistance area, although dual antibiotic resistance may compromise its effectiveness.
Background: Using quadruple clarithromycin‐containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance. Aim: To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple (concomitant) therapy in a setting with cure rates <80% for triple and sequential therapies. Methods: 209 consecutive naive H. pylori‐positive patients without susceptibility testing were empirically treated with 10‐day concomitant therapy (proton pump inhibitors (PPI), amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg; all drugs b.i.d.). Simultaneously, 89 patients with positive H. pylori culture were randomized to receive triple versus concomitant therapy for clarithromycin‐susceptible H. pylori, and sequential versus concomitant therapy for clarithromycin‐resistant strains. Eradication was confirmed with 13C‐urea breath test or histology 8 weeks after completion of treatment. Results: Per‐protocol (PP) and intention‐to‐treat eradication rates after empirical concomitant therapy without susceptibility testing were 89% (95%CI:84–93%) and 87% (83–92%). Antibiotic resistance rates were: clarithromycin, 20%; metronidazole, 34%; and both clarithromycin and metronidazole, 10%. Regarding clarithromycin‐susceptible H. pylori, concomitant therapy was significantly better than triple therapy by per protocol [92% (82–100%) vs 74% (58–91%), p = 0.05] and by intention to treat [92% (82–100%) vs 70% (57–90%), p = 0.02]. As for antibiotic‐resistant strains, eradication rates for concomitant and sequential therapies were 100% (5/5) vs 75% (3/4), for clarithromycin‐resistant/metronidazole‐susceptible strains and 75% (3/4) vs 60% (3/5) for dual‐resistant strains. Conclusions: Empirical 10‐day concomitant therapy achieves good eradication rates, close to 90%, in settings with multiresistant H. pylori strains. Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin‐susceptible H. pylori and at least as effective as sequential therapy for resistant strains.
Background The eradication rate of vonoprazan‐based first‐line triple therapy (combined with clarithromycin and amoxicillin) (V‐AC) was reported to be 97.6% in patients with clarithromycin (CAM)‐susceptible Helicobacter pylori in a phase III study, whereas our real‐world, prospective, multicenter cohort study yielded an eradication rate <90%. Objective To validate the eradication rate of V‐AC using CAM‐susceptible testing in a multicenter, prospective, randomized trial. Methods We included 147 treatment‐naïve H. pylori‐positive patients [41 with CAM‐resistant infections and 106 with CAM‐susceptible infections]. The CAM‐susceptible group patients were randomized to either the V‐AC group (vonoprazan 20 mg bid, amoxicillin 750 mg bid, and clarithromycin 200 or 400 mg bid) or PPI‐AC group (lansoprazole 30 mg, rabeprazole 10 mg, or esomeprazole 20 mg bid; amoxicillin 750 mg bid; and clarithromycin 200 or 400 mg bid). All CAM‐resistant H. pylori were eradicated by V‐AC, as measured by the urea breath test around 8 weeks after eradication. Safety was evaluated by patient questionnaires. Results The intention‐to‐treat and per‐protocol eradication rates of V‐AC in the CAM‐susceptible H. pylori‐infected patients were 87.3% (95% confidence interval 75.5%‐94.7%) and 88.9% (77.4%‐95.8%). The respective eradication rates of PPI‐AC were 76.5% (62.5%‐87.2%) and 86.7% (73.2%‐94.9%). No significant difference was observed between the V‐AC and PPI‐AC regimes in terms of the intention‐to‐treat (P = .21) or per‐protocol (P = .77) analyses. The questionnaire scores did not differ significantly between the groups. Both the intention‐to‐treat and per‐protocol eradication rates of V‐AC in the CAM‐resistant patients were 82.9% (67.9%‐92.8%). Conclusion The eradication rate of V‐AC treatment in the CAM‐susceptible H. pylori‐infected patients was <90%, as was that by PPI‐AC, thus V‐AC is not ideal regimen in CAM‐susceptible H. pylori. However, the 82.9% eradication rate of V‐AC in the CAM‐resistant infections may indicate the potential of V‐AC with modified dose, dosing interval, and treatment duration. (UMIN000016337).
Background Influenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir combination for treatment of serious influenza. Methods From February to April 2015, we conducted a prospective open-label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30-day mortality. The secondary end points were 90-day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor-resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay. Results Among the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P =.01), less frequent high dependency unit admission (P =.009), and shorter hospital stay (P <.0001). The virus titer and PSI (days 1-3; P <.01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1-2; P <.01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04). Conclusions Combination treatment reduced both 30- and 90-day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted. Trial Registry BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879
Display omitted] •Novel 3-substituted derivatives of clarithromycin were synthesized and evaluated.•Some of them showed potent activity against both susceptible and resistant strains.•Compound 7z exhibited potent and balanced antibacterial activity. A novel series of 3-O-arylalkylcarbamoyl-3-O-descladinosyl-9-O-(2-chlorobenzyl)oxime clarithromycin derivatives, were designed, synthesized and evaluated for their in vitro antibacterial activity. These derivatives were found to have strong activity against susceptible and resistant bacteria strains. Among them, compounds 7a and 7q showed the most potent activity (0.125 µg/mL) against erythromycin-resistant S. pneumoniae expressing the mefA gene. Moreover, compounds 7f, 7i, 7p and 7z displayed remarkably improved activity (4 µg/mL) against penicillin-resistant S. aureus ATCC31007, and compounds 7a, 7b, 7f, 7p and 7z showed improved activity (8 µg/mL) against erythromycin-resistant S. pyogenes. In particular, compound 7z exhibited potent and balanced activity against the tested drug-susceptible and -resistant bacterial strains.
Background Cryptogenic organizing pneumonia (COP) is a clinicopathological syndrome of unknown origin. Corticosteroids are the standard treatment, but clarithromycin (CAM) is also effective. The aim of this observational retrospective study was to compare the results of CAM versus prednisone (PRE) treatment in patients with biopsy-proven OP without respiratory insufficiency. Material and methods In a 15-year period, 40 patients were treated with CAM (500 mg twice daily orally for 3 months) and 22 with PRE (mean initial dose of 0.67 +/- 0.24 mg/kg/d for a mean of 8.59 +/- 3.05 months). Results The clinical presentation, laboratory, and radiological findings did not differ markedly between patients treated with CAM and PRE, with the exception of a higher frequency of sweats (55% vs. 23%; p 80% identified patients who might be successfully treated with CAM with a sensitivity of 60% and a specificity of 88.57% (AUC 0.869; 95% CI 0.684-1; p = 0.008); the figures for the FEV1 were > 70%, a sensitivity of 60%, and a specificity of 91.43% (AUC 0.809; 95% CI 0.609-1; p = 0.027). Conclusions CAM can be used to treat COP patients in whom the pulmonary function parameters are within normal limits. Such therapy is shorter, better tolerated, and associated with fewer adverse events and relapses than is PRE. However, the therapy is ineffective in some patients.
Summary Background Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication. Methods We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative13 C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov , number NCT00669955. Findings 12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of −10% (95% CI 15·1–32·3; p<0·0001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0·0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders. Interpretation Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori , especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy. Funding Axcan Pharma Inc.