Burden of carbapenem non-susceptible infections in high-risk patients: systematic literature review and meta-analysis

BACKGROUND: Owing to their resistance to an important class of antibiotics, the prevention and treatment of carbapenem-resistant (CR)/non-susceptible Gram-negative (GN) infections has become an important public health objective. We conducted a systematic review and meta-analysis of published literature to evaluate the burden of CR GN infections, focusing on high-risk patients such as transplant recipients, or patients with cancer, renal impairment, or sepsis. METHODS: MEDLINE®, Cochrane Central, and Embase® were searched between 2010 and March 2019. Abstracts and full-text articles were screened in duplicate. Random effects meta-analysis was conducted when reported outcomes were sufficiently similar. RESULTS: Twenty-six publications were eligible. Meta-analyses found increased mortality associated with CR infections among high-risk patients in both unadjusted analysis (8 studies; summary unadjusted odds ratio [OR]: 5.85; 95% confidence interval [CI]: 3.69, 9.26; I(2) = 19.8%) and adjusted analysis (5 studies; summary hazard ratio [HR]: 4.67; 95% CI: 2.18, 9.99; I(2) = 77.7%), compared to patients with carbapenem-susceptible (CS) infections or no infection. Increased mortality was also seen in subgroup analyses by length of follow-up (either short-term or long-term) or causative pathogen. A limited number of studies found that CR GN infections increased the risk for mechanical ventilation, adverse events such as graft failure or acute rejection in solid organ transplant recipients, increased renal failure or nephrotoxicity, and an increase in readmissions and costs, though the findings reported in the literature were not consistent. CONCLUSION: This systematic literature review and meta-analysis indicates that CR GN infections in high-risk patients are associated with increased mortality, emphasizing the need for antimicrobial stewardship and infection control in hospitals which treat high-risk patients and for the development of effective antimicrobials with favorable efficacy and safety profiles for the treatment of CR GN infections.