In this retrospective multicenter study, using a large data warehouse, we focused on adult patients hospitalized in intensive care units for surgically confirmed NSTIs. Our study aimed to evaluate the care trajectory of critically ill NSTI patients and identify the factors associated with a complicated hospital course. We report key figures depicting the hospital care trajectory of patients managed in the ICU for skin and soft tissue infections: (1) An inter-hospital transfer was necessary for 52.4% of patients; (2) The median time from admission to first surgical debridement was 1 day; (3) The median duration of ICU and total hospital stay were 8 and 37 days, respectively; (4) 69.9% of the patients were re-operated with a median number of 1 additional debridement performed; (5) 32.3% of the patients required a remote skin graft, performed after a median time lag of 28 days after the first surgical debridement; (6) The mortality rates in the ICU and in the hospital were 21.8% and 28.8%, respectively; and (7) 62.3% of the patients were re-hospitalized within 6 months, including 10.1% in the ICU.
Our study confirms the heterogeneity found in previous studies regarding the comorbidities, and the clinical and microbiological features of patients with NSTIs. Our patients, consistent with previous studies [15, 16], carried numerous comorbidities, in particular diabetes (55.3%) and peripheral vascular disease (15.3%). 25.3% of the patients in our population were also immunosuppressed. This is higher than reported in previous studies, which reported a frequency of immunosuppression of 13%  or 16% , but closer to more recent studies (22.9%) . In the latter study, a significantly higher mortality was found in immunocompromised patients than in others (39.1% versus 19.4%). Such findings are consistent with ours, as immunocompromised patients showed significantly higher ICU and in-hospital mortality rates than non-immunocompromised patients (37.2% vs. 16.5%, p = 0.009, and 53.5% vs. 20.5%, p < 0.001). Immunocompromised patients had significantly more infection with non-fermenting Gram-negative bacteria, but less frequent Streptococcus species and Enterococcus faecalis and may have an atypical clinical and biological presentation, often without fever or hyperleukocytosis .
Before and after hospital discharge, NSTI patients are important consumers of hospital care. Indeed, 52.4% of our patients required hospital transfers before surgery, with a median time from admission to the first surgical debridement of 1 day. It was unfortunately not possible to calculate this time period in hours, which is a limitation of our study. It is controversial whether inter-hospital transfer, which may be associated with a prolonged delay before the first surgical debridement, is a risk factor for mortality or, in the contrary, may be beneficial to patients. In previous studies inter-hospital transfers were not harmful, providing the volume of patients managed per center was sufficiently high. In such cases, in contrast, referring patients to these high-volume centers was associated with a benefit on mortality [13, 19]. In the current study, patients managed in high volume centers (i.e., caring for ≥ 3 NSTI patients/year) were less likely to have a complicated hospital course in univariable analysis, but there was no more significant relationship after multivariable adjustment. A previous retrospective study underlined the interest of a multidisciplinary management in a center having an expertise in this rare, severe, and complex diagnostic condition . Grouping patients in reference centers that manage a high volume of NSTI cases per year, with specialized and experienced personnel, could optimize management, essentially the time to diagnosis and surgery [8, 13]. However, the optimal annual procedural case volume remains to be defined and a recent study suggested a threshold of ≥ 8 patients/year/center, which was higher than the one we considered in the current study possibly explaining the discrepant results .
The importance of time to surgery has been demonstrated in numerous retrospective studies  and is one of the most important modifiable risk factor. More recently, Kobayasshi et al. showed an increase in morbidity and number of surgical debridements associated with delayed management . A meta-analysis of more than 1000 patients found a significant decrease in mortality for delays of less than 6 h and 12 h before surgery .
NSTI patients frequently require repeated surgeries. In our selected population, all patients had surgical debridement, per inclusion criteria. Interestingly, about 70% of the patients were returned to the operating room for additional surgery with a median number of additional debridement performed of 1 for the whole cohort, increasing to 3 in the subgroup of patients with abdomino-perineal NSTIs. Indeed, it has already been reported that Fournier’s gangrene requires more surgeries, as reported by Chawla et al.  with 3.5 debridement, and confirmed by Czymek et al. , with up to 4 debridements required. These large and disfiguring wounds form mutilating scars, and sometimes require amputations (15.7% of our population, consistent to previous literature 13.7%  and 18.4% , in two recent studies). About a third (32.3%) of the patients required a remote skin graft, within an average of 28 days after the first surgical debridement. At ICU discharge, 43.4% of survivors were transferred to surgical wards, and 50.6% to medical wards. Surprisingly, although NSTIs have been shown to lead to functional deficits and to greatly affect the quality of life of survivors, only 6% of patients were transferred to rehabilitation centers .
The median duration of stay in hospital and in the ICU were 37 and 8 days, respectively, consistent with previous literature , 24. Importantly, these durations of hospital stay are longer than those reported for patients with non-NSTI-related septic shock, having a median stay ranging from 9 to 18 days in the hospital, and 7 to 9 days in the ICU [25,26,27], pointing out the heavy burdens of NSTIs in terms of hospitalization. Moreover, 62.3% of patients were re-hospitalized within 6 months, including 10.1% in intensive care. The re-hospitalizations are higher than the data in the literature for non-NSTI-related septic shock .
In our study, the mortality rates in the intensive care unit and in the hospital were, respectively, 21.8% and 28.8%, consistent with previous literature [9, 29]. We wished to define a patient-centered and clinically meaningful endpoint in the context of NSTI management. We therefore used a composite criterion grouping an in-hospital death or a total length of stay > 6 weeks or a number of re-interventions > 3. Although we acknowledge that these thresholds may be debatable, these were chosen because they were considered clinically relevant to select a subgroup of patients with a particularly severe hospital course. We identified several risk factors for such a complicated course, including a polybacterial infection, a bacteremia with positive blood cultures, and a high SAPS 2 severity score on ICU admission.
This work has several limitations, the first of which being its retrospective design, limiting the access to available data and the generalization of its results, making our results exploratory. The selection of patients based on International Classification of Diseases 10 codes, which is sometimes very specific, may also be at the origin of a selection bias. The composite primary endpoint combines the occurrence of several developments and thus may constitute an interpretation bias, as these developments do not have the same incidence or severity.
The strengths of our work are as follows. We were able, with the support of the AP-HP data warehouse, to establish a large multicenter cohort of patients hospitalized for NSTIs in the ICU. The number of patients included, the multicentric design of the cohort, and the relatively short inclusion period (5 years) during which medical practices have changed little, have made it possible to obtain original epidemiological data enriching our knowledge of the care trajectory of these patients. The determinants of a complicated course have been identified. This study has good internal validity, as all patients had a definite and definitive diagnosis of NSTI, confirmed by surgical exploration and intraoperative findings; thus, at low risk of selection bias.
In conclusion, patients with NSTI required complex management and are major consumers of care. Two-thirds of them will undergo a complicated hospital course, associated with a higher SAPS II score, a polymicrobial NSTI and a bacteremia.