抗生素和PPI或可引发社区相关性艰难梭菌感染

有调查结果显示，在社区相关性艰难梭菌感染(CDI)患者中，1/3以上在诊断前12周内未使用过抗生素，半数以上报告在同一时期内无或仅有有限的卫生保健接触史(JAMA Intern. Med. 2013;173:1359-67)。

为了评估社区相关性CDI的潜在传染源，美国疾病预防控制中心(CDC)的Amit S. Chitnis博士及其同事对美国8个州的984例新发社区相关性CDI患者的病历进行了复查并对患者进行了访谈。这些患者的中位年龄为51岁，中位Charlson并发症指数为0，近90%为白人，2/3为女性；41%曾接受过高水平的门诊治疗，比如手术或透析。

研究者们在评估CDI危险因素时发现，400例(41%)患者报告了低水平的卫生保健暴露，比如到内科或牙科就诊，而177例(18%)报告无暴露。在用药方面，64%(631例)的患者报告在诊断的12周内使用过抗生素，而28%(273例)报告使用了1种质子泵抑制剂(PPI)，9%(90例)报告使用过1种H2受体拮抗剂。无抗生素用药史的患者31%在前12周内曾使用1种PPI。

研究者表示，基于现有的数据判定，如果减少PPI不必要使用对社区相关性CDI的影响仅限于那些近期未使用过抗生素的患者，那这种干预可能仅会预防11.2%的社区相关性CDI。

在177例无卫生保健接触史的患者中，44%使用过抗生素，24%使用过一种PPI，12%使用过H2受体拮抗剂。无卫生保健接触史或这类接触史有限的患者与活动期CDI病例居住在一起或接触1岁以下婴儿(往往是无症状的难辨梭状芽孢杆菌携带者)的几率较大。CDI与食品或动物暴露之间无相关性。在64%的有抗生素用药史的患者中，可能有很大比例的患者接受了不当的抗生素治疗，耳、鼻窦及上呼吸道感染是最常见的用药指征。

社区相关性CDI的预防应该主要侧重于减少门诊抗生素不合理使用和优化感染控制实践。本研究的数据支持对其他策略进行评价，其中包括对门诊和居家环境中难辨梭状芽孢杆菌的传播做进一步的检查及减少PPI的使用。

本研究由CDC资助。作者们报告称无相关利益冲突。

随刊述评：控制PPI使用以控制艰难梭菌感染

Kent Sepkowitz医生表示，本研究为“使用质子泵抑制剂与艰难梭菌感染有关”的观点提供了大量证据。在本研究中，无抗生素用药史的患者1/3在之前12周内一直在服药，这个比例很高；在同一时期无卫生保健接触史的患者中，超过1/3在服用抑酸剂。现已证实，使用PPI与发生艰难梭菌性腹泻之间有明确的相关性，PPI使用越少，发病就应该越少。但限制PPI过度使用很难，几乎每例患者在服用这种药后都会感觉更舒适，至少在短期如此，而停药时又会引起胃酸分泌反弹，继而导致症状复发，为了缓解不适，就要服用更多的PPI。但最令人感到不安的是，PPI无需处方就能买到，还有大量的直销广告撑腰(JAMA Intern. Med. 2013;173:1367-8)。

Sepkowitz医生与纪念斯隆-凯特琳癌症中心传染病服务部合作，是威尔-康奈尔医学院的医学教授，他本人报告称无相关利益冲突。

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By: M. ALEXANDER OTTO, Internal Medicine News Digital Network

Among patients with community-associated Clostridium difficile infection, more than a third had not used antibiotics in the 12 weeks prior to diagnosis and more than half reported limited or no health care contact over the same period.

To assess possible sources of infection, Dr. Amit S. Chitnis and his colleagues at the Centers for Disease Control and Prevention reviewed the medical records of, and interviewed, 984 patients with new-onset community-associated Clostridium difficile infection (CDI) in eight states as identified through CDC surveillance efforts.

The patients’ median age was 51 years and median Charlson comorbidity index 0. Almost 90% of were white and two-thirds were women; 41% had preceding high-level outpatient care, such as surgery or dialysis.

In assessing risk factors for CDI, investigators found that 400 patients (41%) reported low-level health care exposure, such as a visit to a physician or dentist, while 177 (18%) reported no exposure (JAMA Intern. Med. 2013;173:1359-67).

Regarding medication use, 64% (631) reported antibiotic use within 12 weeks of diagnosis, while 28% (273) reported using a PPI, and 9% (90) reported using an H2-reception antagonist.

Just under a third (31%) of patients with no antibiotic history had used a PPI in the previous 12 weeks. "Based on our data, if the effect of reducing unnecessary PPI use on community-associated CDI is limited to those patients who have not received recent antibiotics, such an intervention would prevent only 11.2% of community-associated CDI," the investigators noted.

Among 177 patients with no health care contact, 44% had used antibiotics, 24% used a PPI, and 12% had used H2-receptor antagonists.

Patients with no – or limited – health care contact were significantly more likely to live with an active CDI case, or have contact with infants under a year old, who are often asymptomatic carriers of C. difficile. There were no associations between CDI and food or animal exposure.

Among the 64% of patients who had received antibiotics, "it is likely that a substantial proportion ... received antibiotics inappropriately," the investigators said. Ear, sinus, and upper respiratory tract infections were the most common indications.

"Prevention of community-associated CDI should primarily focus on reducing inappropriate antibiotic use and better infection control practices in outpatient settings. Our data support evaluation of additional strategies, including further examination of C. difficile transmission in outpatient and household settings and reduction of PPI use," the investigators concluded.

The CDC funded the work. The authors reported no conflicts of interest.

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Curb PPI use to curb C. diff.

The study adds "substantially more evidence" to the link between proton pump inhibitor use and C. difficile infection, Dr. Kent Sepkowitz wrote in an accompanying editorial.

A third of cases with no antibiotic use had been on the drugs in the preceding 12 weeks, "a disturbingly high proportion," and among patients with no health care contact during that time, "more than one-third were taking acid-reducing medications," he noted (JAMA Intern. Med. 2013;173:1367-8).

By now, it’s clear that "PPI use is surely associated with the development of C. difficile–associated diarrhea, and less PPI use should lead to less disease," he said.

But curbing overuse will be difficult. "PPIs make just about everyone feel better, at least in the short term. In addition, PPIs cause a stomach acid rebound when stopped "that can provoke a symptom flare that begs for more PPIs to relieve the discomfort. But most disturbingly, the medication is available over the counter, propped up by substantial direct-to-consumer advertising muscle," he said.

Dr. Sepkowitz is with the infectious disease service at Memorial Sloan-Kettering Cancer Center and is professor of medicine at Weill Cornell Medical College, in New York. He reported no relevant disclosures.