Evaluation of Addition of Intravenous Metronidazole to Oral Vancomycin Therapy in Critically Ill Patients with Non-Fulminant Severe Clostridioides difficile Infection

Background Data on the impact of combination therapy (intravenous metronidazole [IV MTZ] plus oral vancomycin [PO VAN]) on clinical outcomes in intensive care unit (ICU) patients with severe non-fulminant Clostridioides difficile infection (CDI), including NAP1-positive samples, are lacking. Methods Retrospective observational cohort of adult patients who developed CDI in the ICU diagnosed with severe non-fulminant CDI who received PO VAN. Patients with an order for IV MTZ started within 72 hours of PO VAN and who received at least 72 hours of combined therapy composed the combination therapy group. A subset of patients had stool samples collected for NAP1 testing. An additional subset was matched by Acute Physiology and Chronic Health Evaluation (APACHE) II scores. The primary outcome was inpatient all-cause mortality within 30 days of CDI diagnosis. Results A total of 138 patients were included with 60 (43.5%) patients in the combination group. Compared with the PO VAN group, those in the combination group had higher white blood cell counts at diagnosis (15.9 [interquartile range (IQR) 10.2-21.1] vs 20.9 [IQR 16.2-29] cells/mm(3), p<0.001), respectively. Overall inpatient mortality was higher in the combination group, but 30-day mortality was not significantly different between groups (12.8% monotherapy vs 18.3% combination, p=0.371). This finding was the same for the 96 patients in the APACHE II-matched subgroup, 14.6% monotherapy versus 18.8% combination, p=0.785. NAP1 testing was completed in 42 patients; 11 were positive (26.2%). Patients who were NAP1 positive were more likely to receive IV MTZ (54.5% vs 19.4%, p=0.026). Conclusion Compared with PO VAN, combination therapy with IV MTZ was not associated with better clinical outcomes in severe non-fulminant CDI in ICU patients.