Past Rifampicin Dosing Determines Rifabutin Resistance of Helicobacter pylori

Abstract

Background: Recently, the number of Helicobacter pylori isolates showing antibiotic resistance has been increasing. Rifabutin (RFB) is one of the possible candidates for H. pylori eradication. In the present study, the RFB minimum inhibitory concentrations (MICs) and the resistance-determining genes to RFB (rpoB) were examined to clarify the relationship between drug MICs, rpoB mutations, and past history of rifampicin (RFP) treatment. Methods: The MICs of RFB and rpoB mutations were examined for 48 strains with failure of H. pylori eradication in the University Hospital and 46 isolated from patients at a specialized hospital for chronic respiratory diseases without past H. pylori eradication. Past RFP treatment was also examined. Results: Eight of 94 strains showed high RFB MICs and 6 of the 8 strains showed rpoB point mutations. Although no strains showed high RFB MICs among 48 strains from the patients in the University Hospital, all 7 strains isolated from patients with past RFP treatment showed high RFB MICs (≥0.12 mg/l). Conclusion: Although RFB might be a potential candidate component of a new H. pylori eradication regimen following the first- or second-line failure, it should be used after examining a past history of RFP treatment.

Helicobacter pylori Resistance to Rifabutin in the Last 7 Years

“…We previously investigated the MICs of rifabutin and also the point mutations of the rpoB gene in 48 strains of H. pylori isolated from patients of a general hospital (Keio University Hospital) and 46 strains isolated from patients at a specialized hospital for chronic respiratory diseases (Minami-Yokohama Hospital) (14). Although all the strains isolated from the patients at the general hospital were susceptible to rifabutin, 8 of the 46 strains (17.4%) isolated from the patients at the specialized hospital for chronic respiratory diseases showed resistance to rifabutin; 6 of these 8 strains also showed point mutations of the rpoB gene.…”

“…Of the total, 19 patients had no history of H. pylori eradication therapy, 263 patients had had one treatment failure, 116 patients had had two treatment failures, and 16 patients had had three treatment failures (first-line treatment was triple therapy with 800 mg/day clarithromycin, 1,500 mg/day amoxicillin, and a proton pump inhibitor [PPI] for 7 days; second-line treatment was triple therapy with 500 mg/day metronidazole, 1,500 mg/day amoxicillin, and a PPI for 7 days; and third-line treatment was triple therapy with a fluoroquinolone [400 mg/day levofloxacin, gatifloxacin, or sitafloxacin], 2,000 mg/day amoxicillin, and a PPI for 7 days) (3, 9, 11). Among the 386 patients, the 48 strains isolated between September 2004 and June 2005 that were used in the present study had been previously examined, and a comparison of the rifabutin resistance rates between isolates from the general hospital patients and patients at the specialized hospital for chronic respiratory diseases was reported (14).…”

“…Isolates were considered resistant to rifabutin if the MIC of the drug was Ն0.25 g/ml (14). The MIC of rifabutin for one of the 414 (0.24%) strains was high (MIC ϭ 2 g/ml), whereas the MIC values for the other strains were low (MIC Ͻ 0.015 l/ml).…”

Current recommendations forHelicobacter pyloritherapies in a world of evolving resistance

“…Resistance to rifampins (point mutations on the rpoB gene) 22 may be found in patients previously treated with rifampicin especially for tuberculosis. 23 Resistance to tetracycline requires the change in a nucleotidic triplet occurring on the 16S rRNA gene which inhibits tetracycline binding to the h1 loop, 24 a very rare event indeed, seldomly reported except in Korea and which concentrates the most in gastric juice. It has been explained by the pH partition hypothesis, i.e., weak bases are trapped in the acidic compartment of the stomach.…”

Up-to-date standarts of eradication therapy. аre all the qUestions answered? R.A. AbdoulkhAkov, S.R. AbdoulkhAkov

“…Сложным и до настояще-го времени не решенным остается вопрос о тактике веде-ния пациентов, у которых неэффективными оказываются оба курса терапии -первой и второй линии. В этой ситуации предлагается эмпирическое (без определения чувствительности) использование одного из следующих препаратов: рифабутина [19] или фуразолидона [10]. При применении рифабутина рекомендуется следующая схема: ИПП, рифабутин (150 мг), амоксициллин (1000 мг) 2 раза в день в течение 14 дней.…”