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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/mm3 , p

Imipenem-cilastatin-relebactam (IMI-REL) is a novel β-lactam-β-lactamase inhibitor combination recently approved for the treatment of complicated urinary tract infections (cUTIs) and complicated intraabdominal infections (cIAIs). Relebactam is a β-lactamase inhibitor with the ability to inhibit a broad spectrum of β-lactamases such as class A and class C β-lactamases, including carbapenemases. The addition of relebactam to imipenem restores imipenem activity against several imipenem-resistant bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa. Clinical data demonstrate that IMI-REL is well tolerated and effective in the treatment of cUTIs and cIAIs due to imipenem-resistant bacteria. In a phase III trial comparing IMI-REL with imipenem plus colistin, favorable clinical response was achieved in 71% and 70% of patients, respectively. Available clinical and pharmacokinetic data support the approved dosage of a 30-minute infusion of imipenem 500 mg-cilastatin 500 mg-relebactam 250 mg every 6 hours, along with dosage adjustments based on renal function. In this review, we describe the chemistry, mechanism of action, spectrum of activity, pharmacokinetics and pharmacodynamics, and clinical efficacy, and safety and tolerability of this new agent. The approval of IMI-REL represents another important step in the ongoing fight against multidrug-resistant gram-negative pathogens.