利福平联合治疗或可预防艰难梭菌相关性结肠炎

旧金山——瑞士日内瓦大学的Caroline Landelle博士在抗微生物制剂与化疗跨学科会议(ICAAC)上报告称，正在长期接受抗生素治疗的骨关节感染患者加用利福平可显著降低艰难梭菌相关性结肠炎风险。

在这项回顾性队列研究中，研究者对一家瑞士矫形外科医院1996~2012年收治的393例患者进行了分析，其中55%为关节成形术后感染患者。艰难梭菌核糖体027型未在该地区流行。受试者中位年龄69岁，女性占41%，31%为免疫抑制患者。

研究结果显示，在接受利福平(口服，600 mg/d)联合治疗的患者(占42%)中，发生艰难梭菌相关性结肠炎的几率显著降低，尽管他们接受抗生素治疗中位时间长达63天(范围为20~294天)。使用利福平与艰难梭菌相关性结肠炎呈负相关，校正后危险比(HR)为0.18。据Landelle博士介绍，通常长期接受抗生素治疗与艰难梭菌相关性结肠炎相关，校正后HR为1.01。

研究还表明，使用抗厌氧菌抗生素 (占患者的38%)、静注万古霉素(占患者的45%，中位治疗时间13天)、年龄或性别均与结肠炎风险(无论增加还是降低)无关。

14例患者(4%)在接受中位时间14天(范围为8~193天)的抗生素治疗后发生症状性艰难梭菌结肠炎。其中6例(43%)使用万古霉素，2例(14%)使用利福平。研究者指出，虽然骨关节感染患者长期应用抗生素，但艰难梭菌结肠炎仍然罕见。与静注万古霉素治疗相比，添加口服利福平的联合用药可预防艰难梭菌相关性结肠炎的发生。

在骨关节感染部位分离的401株微生物中，32%为甲氧西林敏感金葡菌，16%为耐甲氧西林金葡菌，凝固酶阴性葡萄球菌和革兰阴性杆菌各占17%，其他微生物占18%。

研究者推测，利福平或其衍生物联合治疗之所以能够预防艰难梭菌结肠炎，是因为罕见利福平相关性假膜性结肠炎病例报告，并且长期接受抗生素联合治疗的骨关节感染患者很少发生症状性艰难梭菌相关性疾病。目前正在进行有关利福平及其他大环内酯类抗生素作为艰难梭菌相关性疾病替代治疗的研究。已有研究显示，欧洲耐利福平艰难梭菌比例较高，但研究者所在单位艰难梭菌耐受率较低。在瑞士，利福霉素类抗生素应用已有数十年，但利福平没有被批准用于肝性脑病、腹泻和旅行者腹泻的治疗以及胃肠道手术患者的预防，这也许是耐受率较低的原因。

该研究排除了有艰难梭菌相关病史患者、正在接受甲硝唑治疗患者以及脓毒性关节炎患者。

研究者无利益冲突披露。

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By: SHERRY BOSCHERT, Internal Medicine News Digital Network

SAN FRANCISCO – The addition of rifampin to long-term antibiotic regimens significantly lowers the risk for Clostridium difficile–associated colitis in patients being treated for osteoarticular infections.

The retrospective cohort study comprised 393 treatment episodes – 55% of them for infections subsequent to arthroplasty – among patients admitted to a Swiss orthopedic surgery unit from 1996 to 2012. The ribotype 027 was not endemic in the region.

The 42% of patients who were treated with combination therapy that included oral rifampin (600 mg/day) were significantly less like to develop C. difficile colitis despite being on the antibiotics for a median of 63 days (ranging from 20-294 days), Caroline Landelle, Pharm.D., Ph.D. and her associates reported at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Rifampin use was inversely associated with C. difficile colitis, with an adjusted hazard ratio of 0.18, Dr. Landelle reported in a poster presentation.

In general, longer duration of antibiotics treatment was associated with C. difficile colitis, with an adjusted hazard ratio of 1.01, said Dr. Landelle of the University of Geneva.

Factors not associated with colitis risk (either positively or negatively) included the use of antianaerobic antibiotics (in 38% of patients), treatment with intravenous vancomycin (in 45%, for a median of 13 days), age, or sex.

Fourteen patients (4%) developed symptomatic C. difficile colitis after a median of 14 days of antibiotic treatment (ranging from 8-193 days). Of these, six patients were on vancomycin (43%) and two patients were receiving rifampin (14%) prior to development of the colitis, Dr. Landelle reported at the meeting, sponsored by the American Society for Microbiology.

"C. difficile colitis was rare despite long-term antibiotic use among patients with osteoarticular infection. In contrast to intravenous vancomycin, combination antibiotic therapy with oral rifampin might protect against C. difficile–associated colitis," the investigators suggested.

The cohort had a median age of 69 years; 41% was female, and 31% of patients were immunosuppressed.

Of the 401 microorganisms isolated from the osteoarticular infections, 32% were methicillin-sensitive Staphylococcus aureus, 16% were methicillin-resistant S. aureus, 17% each were coagulase-negative Staphylococcus or gram-negative bacilli, and 18% were other organisms.

The investigators hypothesized that combination therapy with rifampin or derivative medications might protect against C. difficile colitis because very few cases have been reported of rifampin-associated pseudomembranous colitis, and patients undergoing treatment with long-term antibiotic combination therapy for osteoarticular infections rarely develop symptomatic C. difficile–associated disease.

Rifaximin and other antibiotics belonging to the macrocyclic family are being investigated as alternative therapies for C. difficile–associated disease, Dr. Landelle said. Some studies have shown high rates of C. difficile resistance to rifampin in Europe, but the rate of resistance at her institution was low. In Switzerland, rifamycin antibiotics have been used for decades, but rifaximin is not licensed for the treatment of hepatic encephalopathy, diarrhea, and traveler’s diarrhea or for prophylaxis in patients undergoing GI surgery, which may explain the low rate of resistance there.

The study excluded patients with prior episodes of C. difficile–associated disease, patients being treated with metronidazole, and patients with septic arthritis.

Dr. Landelle did not provide her financial disclosures.