Department of Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado; Department of Pharmacy-Infectious Diseases, University of Colorado Hospital, Aurora, Colorado.
Department of Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.
Biol Blood Marrow Transplant. 2019 Oct;25(10):2091-2097. doi: 10.1016/j.bbmt.2019.06.021. Epub 2019 Jun 27.
Clostridioides difficile infection (CDI) is a common complication in the hematopoietic stem cell transplantation (HSCT) and hematologic malignancy (HM) population. CDI is associated with increased hospital length of stay, health care and societal costs, morbidity, and mortality. Identifying strategies for secondary prevention of CDI is of extreme importance in the HSCT/HM population. In this study, our primary objective was to evaluate the effectiveness and safety of an oral vancomycin prophylaxis (OVP) protocol for secondary prevention of CDI in a retrospective cohort of adult autologous/allogeneic HSCT recipients and patients with HM who did not undergo HSCT with a first CDI episode treated with concomitant broad-spectrum antibiotics (BSA). Patients were diagnosed and treated for CDI as inpatients and/or outpatients and were divided into 2 groups based on a preprotocol versus postprotocol analysis: the OVP group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently received OVP posttreatment and a no OVP (NOVP) group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently did not receive OVP posttreatment. OVP was defined as vancomycin 125 mg every 12 hours for up to 7 days after BSA discontinuation. The primary endpoint was recurrent CDI (rCDI), defined as symptoms of loose stools/diarrhea with high clinical suspicion for CDI prompting empiric therapy within 60 days of completion of treatment/prophylaxis for the first CDI episode. The incidence of vancomycin-resistant enterococcal (VRE) infection and 60-day mortality were also compared between the 2 groups. Multivariate logistic regression was created from associated variables to identify independent associations with rCDI. A total of 50 patients were included, 21 in the OVP group (42%) and 29 in the NOVP group (58%). The mean patient age was 58 years, and the cohort was 60% male and 86% Caucasian. HSCT was performed in 60% of the patients, and 76% of CDI cases were diagnosed during hospitalization. The rate of rCDI was significantly lower in the OVP group compared with the NOVP group (5% [1 of 21] versus 35% [10 of 29]; P= .016), with no subsequent increase in VRE infection rate (14% [3 of 21] versus 10% [3 of 29]; P = .686). By multivariable logistic regression, rCDI was inversely associated with OVP (odds ratio [OR], .14; 95% confidence interval [CI], .007 to .994; P = .049) and directly associated with outpatient CDI diagnosis (OR, 8.72; 95% CI, 1.816 to 49.158; P = .007). No between-group differences were found in 60-day mortality (10% [2 of 21] for OVP versus 7% [2 of 29] for NOVP; P > 0.999). OVP appears to be safe and effective for secondary prevention of CDI in the HSCT/HM population. Prospective trials are needed to validate the effectiveness of OVP in this vulnerable population to prevent rCDI.
艰难梭菌感染（CDI）是造血干细胞移植（HSCT）和血液恶性肿瘤（HM）人群中的常见并发症。CDI 与住院时间延长、医疗保健和社会成本增加、发病率和死亡率有关。在 HSCT/HM 人群中，确定 CDI 的二级预防策略非常重要。在这项研究中，我们的主要目的是评估口服万古霉素预防（OVP）方案在接受首次 CDI 治疗的接受过造血干细胞移植（HSCT）和未接受 HSCT 的 HM 患者的回顾性队列中的有效性和安全性，这些患者在接受伴随广谱抗生素（BSA）治疗的同时发生了首次 CDI 发作。患者在住院和/或门诊接受 CDI 的诊断和治疗，并根据预方案与后方案分析分为 2 组：OVP 组，包括接受计划单药治疗的患者，即口服万古霉素 125mg，每 6 小时一次，持续 14 天，用于治疗首次 CDI 发作，随后进行 OVP 治疗后治疗；无 OVP（NOVP）组，包括接受计划单药治疗的患者，即口服万古霉素 125mg，每 6 小时一次，持续 14 天，用于治疗首次 CDI 发作，随后未接受 OVP 治疗后治疗。OVP 定义为在停止 BSA 后最多 7 天内，每 12 小时给予万古霉素 125mg。主要终点是复发性 CDI（rCDI），定义为在首次 CDI 发作治疗/预防完成后 60 天内，出现松散粪便/腹泻症状，高度怀疑 CDI，需要经验性治疗。还比较了 2 组之间万古霉素耐药肠球菌（VRE）感染和 60 天死亡率的差异。从相关变量中创建多变量逻辑回归，以确定与 rCDI 相关的独立关联。共纳入 50 例患者，OVP 组 21 例（42%），NOVP 组 29 例（58%）。患者平均年龄为 58 岁，队列中有 60%为男性，86%为白种人。60%的患者接受了 HSCT，76%的 CDI 病例在住院期间确诊。OVP 组 rCDI 发生率明显低于 NOVP 组（5%[21 例中的 1 例]与 35%[29 例中的 10 例]；P=.016），VRE 感染率无后续增加（14%[21 例中的 3 例]与 10%[29 例中的 3 例]；P =.686）。通过多变量逻辑回归，rCDI 与 OVP 呈负相关（比值比[OR]，.14；95%置信区间[CI]，.007 至.994；P =.049），与门诊 CDI 诊断呈正相关（OR，8.72；95%CI，1.816 至 49.158；P =.007）。在 60 天死亡率方面，OVP 组和 NOVP 组之间无差异（OVP 组 10%[21 例中的 2 例]与 NOVP 组 7%[29 例中的 2 例]；P ＞ 0.999）。OVP 似乎对 HSCT/HM 人群的 CDI 二级预防安全有效。需要前瞻性试验来验证 OVP 在这一脆弱人群中的有效性，以预防 rCDI。
