Monotherapy versus Combination Therapy against Nonbacteremic Carbapenem-resistant Gram-negative Infections: A Retrospective Observational Study

BACKGROUND: Superiority of colistin–carbapenem combination therapy (CCCT) over colistin monotherapy (CMT) against carbapenem-resistant Gram-negative bacterial (CRGNB) infections is not conclusively proven. AIM: The aim of the current study was to analyze the effectiveness of both strategies against CRGNB nonbacteremic infections. DESIGN: This was a retrospective observational cohort study. SUBJECTS AND METHODS: Case record analysis of patients who had CRGNB nonbacteremic infections identified over a period of 4 years (January 2012–December 2015) was done by medical record review at a tertiary care center in India. STATISTICAL ANALYSIS: P < 0.05 was considered as significant. Multivariate analysis was performed using Cox regression. RESULTS: Out of 153 patients (pneumonia 115, urinary tract infection 17, complicated skin and soft-tissue infection 18, intra-abdominal infection 1, and meningitis 2), 92 patients received CCCT and 61 received CMT. Univariate analysis revealed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, pneumonia as the diagnosis, and Klebsiella as the causative organism to be the risk factors for higher 28-day mortality (P = 0.036, 0.006, 0.016, respectively). Combination therapy had no significant impact on mortality (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.327–2.535, P = 0.857). Multivariate analysis revealed that higher APACHE II score and infection due to Klebsiella were found to be independent risk factors for higher mortality (OR = 3.16 and 4.9, 95% CI = 1.34–7.4 and 2.19–11.2, P = 0.008 and 0.0001, respectively). CONCLUSIONS: In our retrospective single-center series of CRGNB nonbacteremic infections, CCCT was not superior to CMT. Multicenter large observational studies or prospective randomized clinical trials are the need of the hour.