BACKGROUND: Necrotizing skin and soft tissue infections (NSTIs) are rare but serious and rapidly progressive infections characterized by necrosis of subcutaneous tissue, fascia and even muscle. The care pathway of patients with NSTIs is poorly understood. A better characterization of the care trajectory of these patients and a better identification of patients at risk of a complicated evolution, requiring prolonged hospitalization, multiple surgical re-interventions, or readmission to the intensive care unit (ICU), is an essential prerequisite to improve their care. The main objective of this study is to obtain large-scale data on the care pathway of these patients. We performed a retrospective multicenter observational cohort study in 13 Great Paris area hospitals, including patients hospitalized between January 1, 2015 and December 31, 2019 in the ICU for surgically confirmed NSTIs.
RESULTS: 170 patients were included. The median duration of stay in ICU and hospital was 8 (3-17) and 37 (14-71) days, respectively. The median time from admission to first surgical debridement was 1 (0-2) day but 69.9% of patients were re-operated with a median of 1 (0-3) additional debridement. Inter-hospital transfer was necessary in 52.4% of patients. 80.2% of patients developed organ failures during the course of ICU stay with 51.8% of patients requiring invasive mechanical ventilation, 77.2% needing vasopressor support and 27.7% renal replacement therapy. In-ICU and in-hospital mortality rates were 21.8% and 28.8%, respectively. There was no significant difference between patients with abdomino-perineal NSTIs (n = 33) and others (n = 137) in terms of in-hospital or ICU mortality. Yet, immunocompromised patients (n = 43) showed significantly higher ICU and in-hospital mortality rates than non-immunocompromised patients (n = 127) (37.2% vs. 16.5%, p = 0.009, and 53.5% vs. 20.5%, p < 0.001). Factors associated with a complicated course were the presence of a polymicrobial infection (adjusted odds ratio [aOR = 3.18 (1.37-7.35); p = 0.007], of a bacteremia [aOR = 3.29 (1.14-9.52); p = 0.028] and a higher SAPS II score [aOR = 1.05 (1.02-1.07); p < 0.0001]. 62.3% of patients were re-hospitalized within 6 months.
CONCLUSIONS: In this retrospective multicenter study, we showed that patients with NSTI required complex management and are major consumers of care. Two-thirds of them underwent a complicated hospital course, associated with a higher SAPS II score, a polymicrobial NSTI and a bacteremia.

BACKGROUND: Necrotizing skin and soft tissue infections (NSTIs) require both prompt medical and surgical treatment. The coordination of multiple urgent interventions by care bundles has improved outcome in other settings. This study aimed to assess the impact of a multidisciplinary care bundle on management and outcome of patients with NSTIs.
METHODS: Patients with NSTIs admitted between 2006 and 2017 were compared according to admission before or after bundle implementation (2012-2013). This bundle consisted mainly in (1) the creation of a multidisciplinary task force; (2) management guidelines on empirical antibiotics, intensive care unit admission criteria, a triage algorithm to accelerate operating room access; and (3) an active communication policy. Patient recruitment and management were compared between pre- and post-implementation periods. Main outcome was day 60-censored hospital survival.
RESULTS: Overall, 224 patients were admitted: 60 before, 35 during, and 129 after bundle implementation. Admission after implementation was associated with increased yearly admissions (10 [8-13] vs 30 [24-43] patients/year, p = 0.014) and decreased mortality (30 vs 15%, HR = 0.49 [0.26-0.92]; p = 0.026) but was no longer a protective factor for mortality after adjustment on confounding factors (adjusted HR = 0.90 [0.43-1.88], p = 0.780). There was no significant difference regarding time to surgery (0 [0-1] vs 0 [0-1] days, p = 0.192) or rate of antibiotic treatment within 24 h (98% vs 99%, p > 0.99).
CONCLUSIONS: Implementation of a multidisciplinary care bundle for NSTIs was feasible, but in a retrospective study from an already experienced center was not associated with significantly increased survival after adjustment.

Necrotizing soft tissue infections (NSTIs) are the most severe and rapidly progressing class of skin and soft tissue infections (SSTIs). They are a surgical emergency and are associated with high mortality and morbidity. While NSTIs remain relatively rare, their incidence is steadily rising. Earlier diagnosis and more focused antibiotic treatments can potentially improve patient outcome, but both of these solutions require a more accurate understanding of the microbial component of these infections. While molecular detection methods, namely 16S sequencing, have not been traditionally used to identify the causative microorganisms in NSTIs, they are becoming more commonplace for other types of SSTIs, especially for chronic wound infections. In chronic wound infections, 16S sequencing has revealed a higher than previously detected prevalence of obligate anaerobes. Therefore, it is possible that 16S sequencing may also detect a higher than expected proportion of obligate anaerobes in NSTIs. In this review, we discuss the current state of knowledge concerning the diagnosis and treatment of NSTIs and present reasons why the role of anaerobes may be significantly underestimated.

Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to sequence the whole genome of isolates 5448 and AP1 for comparative analysis. Strain 5448 is known to acquire inactivating mutations in the CovRS two-component system during mouse infection, producing hypervirulent progeny such as 5448AP. Isolates AP1 and 5448AP, more than 5448, caused disseminating infections that became systemic and lethal. SF370 was not pathogenic. Phages caused gross genetic differences and increased the gene content of AP1 by 8% as compared to 5448 and SF370. Each of six examined M1 genomes contained two CRISPR-Cas systems. Phage insertion destroyed a type II CRISPR-Cas system in AP1 and other strains of serotypes M1, M3, M6 and M24, but not in M1 strains 5448, SF370, MGAS5005, A20 or M1 476. A resulting impaired defence against invading genetic elements could have led to the wealth of phages in AP1. AP1 lacks genetic features of the MGAS5005-like clonal complex including the streptodornase that drives selection for hypervirulent clones with inactivated CovRS system. Still, inactivating mutations in covS were a common genetic feature of AP1 and the MGAS5005-like isolate 5448AP. Abolished expression of the cysteine proteinase SpeB, due to CovRS inactivation could be a common cause for hypervirulence of the two isolates. Moreover, an additional protein H-coding gene and a mutation in the regulator gene rofA distinguished AP1 form other M1 isolates. In conclusion, hypervirulence of S. pyogenes M1 in mice is not limited to the MGAS5005-like genotype.