Global epidemiology and mortality trends of necrotizing fasciitis: a systematic review and meta-analysis with a focus on monomicrobial Gram-negative infections

BACKGROUND: Necrotizing fasciitis (NF) is a fulminant soft-tissue infection with high in-hospital mortality. Although NF is traditionally classified into types I-IV by microbiology, emerging data - particularly from East Asia - suggest that monomicrobial Gram-negative (mono-GNB) NF is epidemiologically and prognostically distinct. This systematic review and meta-analysis aimed to quantify global subtype distributions and in-hospital mortality, with a focus on mono-GNB NF. METHODS: We searched PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library from inception to 1 September 2023, for eligible studies reporting NF microbiology. Included cases were classified as polymicrobial, monomicrobial Gram-positive, mono-GNB, culture-negative, or other pathogen-related. The primary outcomes were the pooled proportion of mono-GNB NF cases and the associated in-hospital mortality. We used random-effects models to estimate pooled proportions and mortality rates, and we conducted subgroup analyses by time period (before 2000 vs. from 2000 onward) and the six World Health Organization (WHO) regions. RESULTS: A total of 142 studies encompassing 6740 patients were included. Globally, the pooled proportion of mono-GNB NF increased from 12% before 2000 to 18% from 2000 onward (P = 0.03). Between-study heterogeneity was substantial (I2 > 95%). The proportion of mono-GNB cases was highest in the WHO regions of the Western Pacific, South-East Asia, and Africa. Among NF subtypes, mono-GNB NF exhibited the highest in-hospital mortality (28% before 2000 vs. 22% from 2000 onward; P = 0.70). Between-study heterogeneity was moderate (I2 = 41%). CONCLUSION: The rising proportion and persistently high in-hospital mortality of mono-GNB NF support its recognition as a distinct NF subtype and warrant reconsideration of the conventional NF classifications. In high-prevalence regions, empiric antimicrobial regimens should include prompt Gram-negative coverage to complement surgical debridement, while sustained epidemiological surveillance remains essential.