Drug Utilization and Evaluation for C. Difficile Associated Disease (CDAD) at Two NYC Hospitals

Background: CDAD has increased in both frequency and severity over the last 10 years. Treatment decisions are hampered by a toxin assay with limited sensitivity and specificity. Consensus is also lacking on the appropriate use of metronidazole vs oral vancomycin. The 1995 IDSA guidelines recommend metronidazole for mild to moderate CDAD and oral vancomycin for severe CDAD, which has been variously defined as >10 episodes of diarrhea/day, wbc>20, or a weighted combination of age>60, temp >38.3, wbc>15, albumin <2.5, Cr 1.5 times baseline, ICU admission, or colonoscopy showing pseudomembranes, as suggested by Zar et al in CID, 2007. Combination therapy is also used in severe disease, though evidence is limited.
Objective: 1. Describe the prescribing practices of physicians treating CDAD including choice of drug and duration of therapy 2. Investigate the clinical and laboratory criteria that influence these practices
Methods: This is a retrospective cohort study of adult patients who received metronidazole and/or oral vancomycin at NYU Medical Center and Bellevue Hospital Center in Aug 2009. Patients who received metronidazole for another clearly defined infection were excluded. Medical records of the remaining 100 cases were reviewed for age, gender, history of antibiotic use, diarrhea, fever, leukocytosis, creatinine, albumin, imaging, hemodynamics and toxin assays.
Results: Of the 100 included cases, 57 were women and the mean age was 62 years (22-96). 57 received metronidazole alone, 14 received oral vancomycin alone, 20 received combination therapy, and 9 were escalated from metronidazole to vancomycin or combination therapy. Zar’s criteria for severe CDAD was met by 35 (61%) of those who received metronidazole, 12 (86%) of those given oral vancomycin, 16 (80%) of those given combination therapy, and 9 (100%) of those escalated. Positive toxin assays were present in only 7 (12%) of the metronidazole group, 3 (21%) of the oral vancomycin group, 8 (40%) of the combination group, and 9 (100%) of the escalation group.

	Metronidazole  n =  57 (57%)	Oral vancomycin  n = 14 (14%)	Combination  n = 20 (20%)	Escalation n = 9 (9%)
Mean duration of therapy (days):
-          Assay not sent	11 (5-21)		13
-          Assay negative	7 (2-20)	13 (2-10)	11 (2-36)
-          Assay positive	15 (13-20)	16 (6-36)	20 (1-3)	26 (5-48)

Conclusions: This data suggests that Zar’s criteria for severe CDAD is met by >60% of all cases and has limited effect on antibiotic choice. Similarly, positive toxin assays were present in <40% of cases, except for the group with escalated therapy. Mean metronidazole duration of therapy was significantly longer in assay-positive vs negative cases (p=0.002). However no significant difference in duration was noted in all other drug classes, suggesting that testing has little impact on clinical decision-making or drug utilization. This has implications for surveillance, antimicrobial utilization, and cost of care.