Study Design and Patients

This investigation was a retrospective, nationwide, propensity score-matched analysis study of patients ≥18 years of age treated for recurrent CDI from any Veterans Affairs Medical Center (VAMC) between June 1, 2011 and October 31, 2016. Approval for the conduct of the study was obtained from the University of Oklahoma Institutional Review Board, Oklahoma City VA Health Care System Research and Development Committee, and the Veterans Health Administration (VHA) Corporate Data Warehouse (CDW). Patients were included in this study if the patient had the following: (1) a positive result from the facility’s pertinent VAMC test for presence of C difficile toxin (positive enzyme immunoassay [EIA] or positive polymerase chain reaction [PCR] for toxigenic C difficile); (2) a documented first or second recurrence of CDI; and (3) begun treatment within 72 hours of positive toxin result with a 7- to 21-day course of vancomycin OR a more prolonged course known as a “vancomycin taper.” A vancomycin taper was defined as a course of therapy that continues for at least 21 days and involves a declining vancomycin dose. Documentation of the first or second recurrent CDI case was defined as follows: (1) a positive test outcome (positive EIA or positive PCR for toxigenic C difficile) with the pertinent VAMC test for presence of C difficile toxin, preceded within the previous 90 days by (2) a positive test outcome with the pertinent VAMC test for presence of C difficile toxin. Concomitant intravenous or oral metronidazole beginning within 72 hours of the oral vancomycin initiation was allowed for inclusion. Exclusion criteria consisted of cases with the following: evident intent to prescribe less than 7 days of therapy, fecal transplant treatment, or discharge diagnosis, surgical report, or radiologic report consistent with toxic megacolon. Patients with conversion to alternative therapy before 72 hours of therapy initiation were also excluded from analysis. De-escalation was only allowed in the vancomycin 7- to 21-day course group, defined as initiation of oral vancomycin for ≥72 hours with conversion to intravenous or oral metronidazole monotherapy for the remainder of CDI treatment. A severe episode was defined as a baseline leukocytosis with a white blood cell count ≥15000 cells/mL and/or a serum creatinine level ≥1.5 times the premorbid level consistent with current guidelines [5]. Clinical failure of CDI therapy was defined as any switch ≥72 hours after initiation of therapy through 14 days, except for cases of de-escalation.

The outcome of recurrence of CDI was defined as follows: (1) a positive test outcome with the pertinent VAMC test for presence of C difficile toxin (positive EIA or positive PCR for toxigenic C difficile) and (2) treatment with any antimicrobial directed at CDI within 180 days of the index case. Given the comparison of vancomycin regimens differing only by the continuation or lack of a tapered regimen, only cases that successfully completed therapy without clinical failure within the first 14 days were included.

Data were collected through the Veterans Affairs Informatics and Computing Infrastructure (VINCI) database across the VHA. The VHA consists of 132 acute care VAMCs, each with active ambulatory care services and over 800 community-based outpatient clinics [14]. The VHA maintains the CDW, a central clinical and administrative relational database containing comprehensive electronic medical record information from each VAMC. Researchers, upon obtaining approval through a rigorous information security process, can access the VINCI workspace on the VHA intranet servers through a secure gateway. Patients are automatically assigned a de-identified patient identification number (“PatientSID”) within VINCI, making them unidentifiable to the investigators. Baseline demographic data, current and past diagnosis codes, admission and discharge data, laboratory values, vital signs, date of birth, date of death, administration data for each inpatient unit dose antibiotic given, and prescription data for each outpatient antibiotic given were collected (refer to Table 1 for detailed listing).

Comparative Baseline Demographic Characteristics of the All Episodes and Propensity Score-Matched Episodes by Treatment Regimen Group

Abbreviations: CDI, Clostridium difficile infection; SD, standard deviation.

^aMetronidazole or fidaxomicin.