Research Service, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA.
Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S121-6. doi: 10.1093/cid/cis440.
Fidaxomicin causes less disruption of anaerobic microbiota during treatment of Clostridium difficile infection (CDI) than vancomycin and has activity against many vancomycin-resistant enterococci (VRE). In conjunction with a multicenter randomized trial of fidaxomicin versus vancomycin for CDI treatment, we tested the hypothesis that fidaxomicin promotes VRE and Candida species colonization less than vancomycin. Stool was cultured for VRE and Candida species before and after therapy. For patients with negative pretreatment cultures, the incidence of VRE and Candida species acquisition was compared. For those with preexisting VRE, the change in concentration during treatment was compared. The susceptibility of VRE isolates to fidaxomicin was assessed. Of 301 patients, 247 (82%) had negative VRE cultures and 252 (84%) had negative Candida species cultures before treatment. In comparison with vancomycin-treated patients, fidaxomicin-treated patients had reduced acquisition of VRE (7% vs 31%, respectively; P < .001) and Candida species (19% vs 29%, respectively; P = .03). For patients with preexisting VRE, the mean concentration decreased significantly in the fidaxomicin group (5.9 vs 3.8 log(10) VRE/g stool; P = .01) but not the vancomycin group (5.3 vs 4.2 log(10) VRE/g stool; P = .20). Most VRE isolates recovered after fidaxomicin treatment had elevated fidaxomicin minimum inhibitory concentrations (MICs; MIC(90), 256 µg/mL), and subpopulations of VRE with elevated fidaxomicin MICs were common before therapy. Fidaxomicin was less likely than vancomycin to promote acquisition of VRE and Candida species during CDI treatment. However, selection of preexisting subpopulations of VRE with elevated fidaxomicin MICs was common during fidaxomicin therapy.
非达霉素在治疗艰难梭菌感染（CDI）时引起的厌氧微生物群紊乱比万古霉素少，并且对许多万古霉素耐药肠球菌（VRE）具有活性。在一项非达霉素与万古霉素治疗 CDI 的多中心随机试验中，我们检验了这样一个假设，即非达霉素促进 VRE 和念珠菌定植的可能性小于万古霉素。在治疗前后对粪便进行 VRE 和念珠菌种培养。对于预处理培养物为阴性的患者，比较 VRE 和念珠菌种获得的发生率。对于那些预先存在 VRE 的患者，比较治疗期间浓度的变化。评估 VRE 分离株对非达霉素的敏感性。在 301 名患者中，247 名（82%）VRE 培养物阴性，252 名（84%）念珠菌种培养物阴性。与万古霉素治疗的患者相比，非达霉素治疗的患者 VRE 的获得率降低（分别为 7%和 31%，P <.001）和念珠菌种（分别为 19%和 29%，P =.03）。对于预先存在 VRE 的患者，非达霉素组的平均浓度显著下降（5.9 对 3.8 log(10) VRE/g 粪便；P =.01），而万古霉素组没有（5.3 对 4.2 log(10) VRE/g 粪便；P =.20）。在非达霉素治疗后恢复的大多数 VRE 分离株具有升高的非达霉素最小抑菌浓度（MIC；MIC(90)，256 µg/mL），并且治疗前就存在具有升高的非达霉素 MIC 的 VRE 亚群。非达霉素比万古霉素更不可能在 CDI 治疗期间促进 VRE 和念珠菌种的获得。然而，在非达霉素治疗期间，常见的是预先存在的 VRE 亚群具有升高的非达霉素 MIC。
