Prevention of healthcare-associated Clostridium difficile infection: What works?

Prevention of Clostridium difficile infection (CDI) has become extremely important because of increases in CDI incidence and severity. Unfortunately CDI prevention efforts are hampered by lack of data to support optimal prevention methods, especially for endemic CDI. Studies are needed to define optimal prevention practices and to investigate novel prevention methods

A randomized, placebo-controlled trial of fidaxomicin for prophylaxis of Clostridium difficile-associated diarrhea in adults undergoing hematopoietic stem cell transplantation

Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients. Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. The primary endpoint analysis counted confirmed CDAD, receipt of CDAD-effective medications (for any indication), and missing CDAD assessment (for any reason, including death) as failures; this composite analysis is referred to as prophylaxis failure to distinguish from the pre-specified sensitivity analysis, which counted only confirmed CDAD (by toxin immunoassay or nucleic acid amplification test) as failure. Results: Of 611 subjects enrolled, 600 were treated and analyzed. Prophylaxis failure was similar in fidaxomicin and placebo recipients (28.6% vs 30.8%; difference 2.2% [-5.1, 9.5], P = .278). However, most failures were due to non-CDAD events. Confirmed CDAD was lower in fidaxomicin vs placebo recipients (4.3% vs 10.7%; difference 6.4% [2.2, 10.6], P = .0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients. Conclusions: While no difference was demonstrated between arms in the primary analysis, results of the sensitivity analysis demonstrated that fidaxomicin significantly reduced the incidence of CDAD in HSCT recipients. Clinical Trials Registration: NCT01691248

Frequent hospital readmissions for Clostridium difficile infection and the impact on estimates of hospital-associated C. difficile burden

ObjectiveClostridium difficile infection (CDI) is associated with hospitalization and may cause readmission following admission for any reason. We aimed to measure the incidence of readmissions due to CDI.DesignRetrospective cohort study.PatientsAdult inpatients in Orange County, California, who presented with new-onset CDI within 12 weeks of discharge.MethodsWe assessed mandatory 2000-2007 hospital discharge data for trends in hospital-associated CDI (HA-CDI) incidence, with and without inclusion of postdischarge CDI (PD-CDI) events resulting in rehospitalization within 12 weeks of discharge. We measured the effect of including PD-CDI events on hospital-specific CDI incidence, a mandatory reporting measure in California, and on relative hospital ranks by CDI incidence.ResultsFrom 2000 to 2007, countywide hospital-onset CDI (HO-CDI) incidence increased from 15 per 10,000 to 22 per 10,000 admissions. When including PD-CDI events, HA-CDI incidence doubled (29 per 10,000 in 2000 and 52 per 10,000 in 2007). Overall, including PD-CDI events resulted in significantly higher hospital-specific CDI incidence, although hospitals had disproportionate amounts of HA-CDI occurring postdischarge. This resulted in substantial shifts in some hospitals' rankings by CDI incidence. In multivariate models, both HO and PD-CDI were associated with increasing age, higher length of stay, and select comorbidities. Race and Hispanic ethnicity were predictive of PD-CDI but not HO-CDI.ConclusionsPD-CDI events associated with rehospitalization are increasingly common. The majority of HA-CDI cases may be occurring postdischarge, raising important questions about both accurate reporting and effective prevention strategies. Some risk factors for PD-CDI may be different than those for HO-CDI, allowing additional identification of high-risk groups before discharge

Risk factors for recurrent Clostridium difficile infection (CDI) hospitalization among hospitalized patients with an initial CDI episode: A retrospective cohort study

BACKGROUND: Recurrent Clostridium difficile infection (rCDI) is observed in up to 25% of patients with an initial CDI episode (iCDI). We assessed risk factors for rCDI among patients hospitalized with iCDI. METHODS: We performed a retrospective cohort study at Barnes-Jewish Hospital from 1/1/03 to 12/31/09. iCDI was defined as a positive toxin assay for C. difficile with no CDI in previous 60 days, and rCDI as a repeat positive toxin ≤42 days of stopping iCDI treatment. Three demographic, 13 chronic and 12 acute disease characteristics, and 21 processes of care were assessed for association with rCDI. Cox modeling identified independent risk factors for rCDI. RESULTS: 425 (10.1%) of 4,200 patients enrolled developed rCDI. Of the eight risk factors for rCDI on multivariate analyses, the strongest three were 1) high-risk antimicrobials following completion of iCDI treatment (HR 2.95, 95% CI 2.25-3.86), 2) community-onset healthcare-associated iCDI (HR 1.80, 95% CI 1.41-2.29) and 3) fluoroquinolones after completion of iCDI treatment (HR 1.56, 95% CI 1.63-2.08). Other risk factors included gastric acid suppression, ≥2 hospitalizations within prior 60 days, age, and IV vancomycin after iCDI treatment ended. CONCLUSIONS: The rCDI rate was 10.1%. Recognizing such modifiable risk factors as certain antimicrobial treatments and gastric acid suppression may help optimize prevention efforts