Patients with Clostridium difficile infection warranting admission to the ICU may benefit from a treatment regimen of combined oral vancomycin and IV metronidazole, according to recent findings.
In a retrospective, observational, comparative study, researchers evaluated 88 critically ill adult patients with C. difficile who were admitted to the ICU at Wake Forest Baptist Medical Center between June 2007 and September 2012. All patients were treated for CDI with oral vancomycin, and those in the combination therapy group received concomitant metronidazole intravenously for a minimum of 72 hours. Patients were matched and equally placed within either the combination or vancomycin-only groups using the Acute Physiology and Chronic Health Evaluation II (APACHE II) metric. The patients were clinically and demographically comparable, although the combination therapy group had a higher prevalence of moderate-to-severe renal disease.
The study’s primary outcome was in-hospital death, and secondary outcomes included clinical success at days 6, 10 and 21; hospital length of stay after diagnosis of CDI; and duration of ICU stay after diagnosis of CDI. Multivariable analysis was used to identify factors independently correlated with survival.
The researchers found the vancomycin monotherapy group had a higher rate of in-hospital mortality compared to the combination therapy group; 36.4% patients died in the monotherapy group vs. 15.9% patients in the combination therapy group (P = .03).
By day 6 of treatment, 20.5% of patients in the monotherapy group met the criteria for clinical success, as opposed to 13.6% of patients in the combination therapy group (P = .57). Also at day 6 of therapy, 47.7% of patients in the monotherapy group and 52.3% of patients in the combination group showed an improvement in diarrhea (P = .67). No differences in clinical success rates were seen between the groups at days 10 and 21.
Hospital length of stay after CDI diagnosis was a median 20.5 days in the monotherapy group vs. 18 days in the combination group (P = .99), and duration of ICU after CDI diagnosis was a median 9 days in the monotherapy group vs. 11 days in the combination group (P = .93). Recurrent CDI was seen in 4 patients (9.1%) in the monotherapy group vs. three patients (6.8%) in the combination group (P = 1.0). According to multivariable analysis, receiving concomitant IV metronidazole and increasing albumin values were two factors found to be independently associated with survival.
This treatment regimen of oral vancomycin and IV metronidazole is best reserved for patients with severe cases of CDI, according to the researchers.
“It is important to emphasize that these results are best applied in the care of the most severely ill patients with CDI,” the researchers wrote. “Prospective, randomized studies to define optimal treatment regimens in critically ill patients with CDI are warranted.” – by Jennifer Byrne
Disclosure: The researchers report no relevant disclosures.