The Inappropriateness of Using Rifampicin E-Test to Predict Rifabutin Resistance in Helicobacter pylori

Abstract

Background The aim of this study was to evaluate the rifamycin cross-resistance in Helicobacter pylori, and whether the use of rifampicin E-test strips to screen H. pylori rifabutin resistance is appropriate. Methods A total of 89 H. pylori isolates were included. Rifampicin minimum inhibitory concentrations (MICs) were obtained by E-test, while the MICs for rifapentine, rifaximin, and rifabutin were determined by agar dilution method. The rifamycin resistance rates based on different breakpoints were compared. Isolates with high-level rifampicin resistance were subjected to whole-genome sequencing. Results A wide distribution of MICs (mostly in the range 0.125–8 mg/L) was observed for rifampicin, rifapentine, and rifaximin. Using MIC >1, ≥ 4, and > 4 mg/L as the breakpoints, resistance rates to rifampicin/rifapentine/rifaximin were 60.4%/48.3%/38.2%, 28.1%/25.8%/23.6%, and 15.7%/16.9%/7.9%, respectively. However, the rifabutin MICs of all the tested H. pylori isolates were extremely low (≤0.016 mg/L). Applying MIC ≥ 0.125 mg/L as the breakpoint, rifabutin resistance was nil. No mutation was found in the rpoB gene sequences of the 2 isolates with high-level rifampicin resistance. Conclusions There is a lack of cross-resistance between rifabutin and other rifamycins in H. pylori. The use of rifampicin E-test to predict H. pylori rifabutin resistance is inappropriate.

Refractory Helicobacter pylori infection in Australia: updated multicentre antimicrobial resistance

“…20 Nevertheless, recent studies have demonstrated that even a breakpoint concentration of 4 mg/L may be a poor marker of rifabutin resistance, so the generalisability of rifampicin resistance to rifabutin may be questionable. 21 The high rate of multidrug resistance seen in the current study (63%) is comparable to what has been reported in various regions of South East Asia. 17 Of these multiresistant strains, 90% had resistance to both clarithromycin and metronidazole, whereas 30% were resistant to levofloxacin.…”

“…However, whereas EUCAST recommends using rifampicin MIC >1.0 mg/L as the rifabutin breakpoint, studies have shown that H. pylori isolates with moderate rifampicin resistance were susceptible to rifabutin, so it has been suggested that rifampicin resistance can be used to screen for rifabutin resistance using a breakpoint of 4 mg/L 20 . Nevertheless, recent studies have demonstrated that even a breakpoint concentration of 4 mg/L may be a poor marker of rifabutin resistance, so the generalisability of rifampicin resistance to rifabutin may be questionable 21 …”