Among skin and soft-tissue infections, necrotizing skin and soft-tissue infections (NSTIs) are by far the most frequent and the most severe cases admitted to the intensive care unit (ICU). Timely and adequate surgical and medical care are the only modifiable features in their management [1]. The heterogeneity of patients, including varying comorbidities, clinical presentations, causative microbes and treatments, requires a team approach involving multidisciplinary management [2, 3].

Early diagnosis

Typical cases are usually readily identified on clinical grounds, leading to early emergency admission and source control. In contrast, underestimation of the burden of comorbidities, slow onset or atypical symptoms without sepsis, are common risk factors for delayed diagnosis, and late adequate care. Immunocompromised patients are at particular risk and should be considered severe cases [3, 4]. NSTIs can affect any part of the body, most commonly the extremities, pelvix and cervix [4, 5]. Initial misdiagnosis, admission of these patients to a nonacute care surgery service, or interhospital transfer to tertiary centers before source control represent the most common reasons for belated surgical management.

Imaging techniques

Any imaging test should be integrated with the clinical evaluation. They may lead to delayed source control without significant benefit, except in atypical cases or to clarify underlying disease [6]. Computed tomography (CT) scans can be useful for delineating the extent of the infection process [electronic supplemental material (ESM)]. Magnetic-resonance-imaging can yield similar results, but its limited availability is a major issue. Ultrasound has been used in the emergency room, but its efficacy in the ICU setting needs additional investigation (ESM).

Early source control

Initial source control is essential in most patients and should include surgical debridement, drainage and collection of surgical samples, ideally in the first 6 h, or at least within the first 12 h after admission [1]. Surgical observations and samples can be useful for confirming the diagnosis. However, this approach might not be sufficient, because the infectious process can rapidly spread despite the reassuring aspect of an initial adequate source control. This explains the frequency of re-exploration within 12–24 h of the first debridement, usually on an individualized basis [1, 5, 7]. Worsening of local/systemic clinical signs, laboratory parameters, or persistence of necrotic lesions are additional criteria justifying a re-exploration [7]. Delayed re-exploration may impact the incidence of complications, the number of reoperations, and the mortality rate [1, 8] (ESM). Head/neck or perineal locations can be challenging infections, because mediastinal or retroperitoneal extensions are difficult to assess and to control. Optimized wound management requires additional investigations, including dressings (ESM).

Microbiological issues

NSTIs are caused by a variety of microbes and can be either monomicrobial or polymicrobial infections. A major cause of NSTIs is the beta-hemolytic Streptococcus, particularly S. pyogenes [5]. There is an association between infection of the affected body part and microbiological findings with infections of the extremities dominated by monomicrobial beta-hemolytic Streptococcus, and infections of the abdomen and ano-genital area dominated by polymicrobial infections (Fig. 1) [5]. In immunocompromised patients, significantly more nonfermenting Gram-negative bacteria and fewer streptococcal infections are reported [4].

Fig. 1
figure 1

Diagnosis and therapeutic optimization in necrotizing skin and soft-tissue infections. Microbes significantly associated with infections in the indicated body parts are shown. The frequency of affected body parts and odds ratios (ORs) for associated microbes are based on data reported in Ref. [5]. NSTI necrotizing skin and soft-tissue infection, CT computed tomography, ESBL extended-spectrum betalactamase, GNB Gram-negative bacilli, ICU intensive-care unit, MRI magnetic-resonance-imaging, MDR multi-drug resistant, MRSA methicillin-resistant Staphylococcus aureus, S. pyogenes Streptococcus pyogenes, TDM therapeutic drug monitoring

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Empirical antibiotic therapy

The quality of evidence supporting therapeutic recommendations in NSTIs is low [9]. Patients should receive empirical antimicrobial therapy, along with resuscitation measures, immediate surgical exploration, and obtention of microbiological sample collection. Antibiotics should have activity against Gram-positive, Gram-negative, and anaerobic bacteria [1]. Initial therapy should result in good tissue diffusion and pharmacokinetic/pharmacodynamic properties suitable for critically ill patients who are often in shock [10]. High loading doses, continuous infusion, and therapeutic drug monitoring are recommended.

Empirical treatment must have a broad spectrum, since many NSTIs are polymicrobial [4, 5, 7]. If no multi-drug resistance (MDR) is suspected, piperacillin–tazobactam or meropenem may be used empirically, according to the local/regional prevalence of Enterobacterales producing extended-spectrum beta-lactamases (ESBLs) [1]. In selected cases, when risk factors for MDR are present (e.g., local ecology, previous/present colonization, health care-related acquisition, or previous antimicrobial therapy) treatment should include anti methicillin-resistant Staphylococcus aureus (MRSA) coverage (vancomycin, linezolid, or daptomycin) and/or MDR Gram-negative activity (ceftazidime–avibactam, ceftolozane–tazobactam, or cefiderocol) [11, 12] (ESM).

When S. pyogenes NSTI is suspected or demonstrated (antigen detection or culture), high-dose intravenous aqueous penicillin G (3–4 million units/4 h) is the treatment of choice. The addition of clindamycin or linezolid is recommended, due to the ability of these drugs to lower mortality and to inhibit exotoxins, even in the presence of clindamycin resistance [1]. The effect of adjunctive clindamycin is negative in patients with invasive nongroup-A/B β-hemolytic streptococcal infections [13]. In Clostridium spp. myonecrosis, in addition to aggressive surgery, penicillin and clindamycin should be added. When the etiology is confirmed, de-escalation of the spectrum is recommended. Treatment is usually maintained for 48–72 h after the last surgery when the patient has improved clinically, and fever is resolved for ≥ 48 h [1].

Adjuvant therapies

Hyperbaric oxygen therapy (HBO) and polyspecific intravenous immunoglobulin (IVIG) are both options used. However, the clinical evidence is limited and their efficacy has yet to be proven in randomized clinical trials (ESM).

HBO achieves high tissue oxygen tension, resulting in antibacterial and antitoxin properties, and improved leukocyte and antibiotic activity. The key challenge is the risk of delayed standard care in cases of transfer to another facility for the procedure.

IVIGs, by virtue of their anti-inflammatory and toxin-neutralizing properties, have been frequently proposed as adjuvant therapies for NSTIs, including Group-A streptococcal gangrene. A placebo-controlled trial of IVIG in NSTI patients did not show any difference in the physical quality of life (primary endpoint) between the IVIG group and the placebo group [14]. In contrast, a prospective analysis of S. pyogenes NSTIs reported a significantly greater mortality rate in patients who did not receive IVIG [15]. Taken together, these data suggest that IVIG is beneficial for toxin-mediated S. pyogenes NSTIs, but not for NSTIs caused by other aetiologies.

Multidisciplinary management

Several groups have demonstrated the benefit of an approach combining all the medical specialities involved in NTSI care to speed up and optimize therapy [2, 3] (ESM). Gatti et al. have reported a significantly decreased ICU mortality rate, an earlier control of infection, and a faster recovery from multiple organ-dysfunction [2]. Ongoing studies in the field are likely to contribute to personalized care.