Critically Ill Patients With Clostridium difficile Infection: Are 2 Antibiotics Better Than One?

There is a dearth of evidence about how best to manage critically ill patients with Clostridium difficile infection (CDI) [1–3]. The study by Rao et al in this issue of Clinical Infectious Diseases provides some information that reinforces weakly graded recommendations in treatment guidelines that currently advocate combination therapy with oral vancomycin and intravenous metronidazole in preference to vancomycin monotherapy in patients with life-threatening CDI [1–4]. This is more in hope than knowledge of a possible effectiveness gain from using 2 antibiotics rather than one, noting also the general lack of evidence for superiority of combination therapy [5]. Encouragingly, Rao et al found that combination therapy was associated with a survival advantage in retrospective CDI cases that were (partly) matched according to illness severity [4]. Notably, however, CDI clinical outcomes (other than possible CDI-related mortality, which was not specifically measured) and length of stay in the intensive care unit (ICU) or hospital did not differ between the 2 treatment groups. It should be noted that the study had weak power to detect such differences. Retrospective data analyses are of course fraught with potential for confounding. In this study, for example, 4 times more patients in the combination therapy group received concurrent vancomycin per rectum, and twice as many combination therapy recipients.