Emergence of rifampin-resistant staphylococci after rifaximin administration in cirrhotic patients

Objectives
Rifaximin, a poorly absorbed antibiotics, has gut-specific therapeutic effects. Although frequently prescribed to manipulate intestinal luminal bacterial population in various diseases, the possible induction of antibacterial cross-resistance to a target pathogen is a major concern in long-term rifaximin administration. We aimed to evaluate whether rifampin-resistant staphylococci could evolve after rifaximin treatment in cirrhotic patients.
Method
A total of 25 cirrhotic patients who were administered rifaximin for the prevention of hepatic encephalopathy were enrolled. Swabs from both hands and the perianal skin were acquired on day 0 (before rifaximin treatment), period 1 (1–7 weeks after treatment), and period 2 (8–16 weeks after treatment) the staphylococcal strain identification and rifampin-resistance testing.
Results
A total of 198 staphylococcal isolates from 15 species were identified. Staphylococcus epidermidis was isolated most frequently, and Staphylococcus haemolyticus was the most common resistant species both from hands and perianal skin. Eleven patients (44.0%) developed rifampin-resistant staphylococcal isolates in period 1. Among these patients, only six (54.5%) were found to have rifampin-resistant isolates in period 2, with no significant infectious events. Rifampin-resistant staphylococcal isolates were more frequently found in perianal skin than from the hands. No patients acquired a newly resistant strain in period 2.
Conclusions
About one-half of cirrhotic patients in this study developed rifampin-resistant staphylococcal isolates after rifaximin treatment. Although the resistant strains were no longer detected in about half of the patients in the short-term, the long-term influence of this drug treatment should be determined.

研究目的
利福昔明（rifaximin）是一种肠道吸收极差的抗生素，具有肠道特异性治疗作用。尽管其常被用于调控多种疾病状态下的肠道腔内细菌群落，但长期使用利福昔明时，其可能诱导靶标病原菌产生抗菌交叉耐药性，是临床长期应用该药物的主要安全隐患。本研究旨在探讨肝硬化患者接受利福昔明治疗后，是否会出现耐利福平（rifampin）葡萄球菌。

研究方法
本研究共纳入25例因预防肝性脑病而接受利福昔明治疗的肝硬化患者。分别于给药前第0天、治疗后第1阶段（1~7周）及第2阶段（8~16周）采集双手及肛周皮肤拭子，开展葡萄球菌菌株鉴定及利福平耐药性检测。

研究结果
本研究共分离鉴定出15个菌种共计198株葡萄球菌分离株。其中表皮葡萄球菌（Staphylococcus epidermidis）的分离率最高，而溶血葡萄球菌（Staphylococcus haemolyticus）是双手及肛周皮肤标本中最常见的耐药菌种。第1阶段共有11例患者（占比44.0%）检出耐利福平葡萄球菌分离株。在上述11例患者中，仅6例（54.5%）在第2阶段仍可检出耐利福平葡萄球菌分离株，且期间未发生显著感染事件。耐利福平葡萄球菌分离株在肛周皮肤标本中的检出率显著高于手部标本。第2阶段未发现患者出现新的耐药菌株。

研究结论
本研究中约半数肝硬化患者接受利福昔明治疗后，出现了耐利福平葡萄球菌分离株。尽管短期随访中约半数患者不再检出耐药菌株，但仍需明确该药物治疗的长期临床影响。