Necrotizing soft-tissue infections in pediatric intensive care: a prospective multicenter case-series study

To the Editor,

Necrotizing soft-tissue infections (NSTIs) are severe diseases with documented high morbidity and mortality rates in adults [1]. In pediatric patients, data are scant and prospective studies extremely scarce [2]. Eneli et al. [3] reported 36 cases collected prospectively in Ontario from 2001 to 2003. The largest studies used North-American databases and exhibited the biases inherent in this methodology [4, 5]. We designed a prospective international observational study of all severe NSTI cases seen in pediatric intensive care units (PICUs), to evaluate the outcomes and treatments.

From February 2011 to July 2016, we included consecutive patients with NSTI aged 1 month to 18 years and admitted to 33 PICUs located in high-resource countries (continental France and French overseas territories, Switzerland, Canada, and The Netherlands). Institutional review board approval (IRB-0006477) and parental consent to data recording were obtained. NSTIs are infections of any of the soft tissue layers during which tissue necrosis occurs. For this study, we defined NSTI as painful, rapidly progressive, superficial, spreading erythema or skin necrosis, with laboratory evidence of inflammation and a fever (> 38.5 °C) or hypothermia (< 36 °C). We collected demographics; clinical, laboratory, and bacteriological data; radiological findings; and medical and surgical treatments. Descriptive data, collected without a statistical analysis plan, are reported as median [25th; 75th centiles], mean ± SD, or n (%).

In the 50 patients included during the 4.5-year period (Table 1), time from symptom onset to PICU admission was 2 [1; 2] days. Triggers were postoperative care (n = 12; 24%) and trauma or animal bite (n = 11; 22%). Severe comorbidities included cancer (n = 10; 20%), varicella (n = 9; 18%), and preexisting chronic skin disease (n = 3; 6%). No predisposing factors were identified in 8 (16%) patients. At diagnosis, 10 (20%) patients had received non-steroidal antiinflammatory drugs, 5 (10%) immunosuppressive agents, and 3 (6%) glucocorticoids. Most patients had severe critical illness at admission, often with respiratory and circulatory failure, translating into high mortality prediction scores. Bacteria were recovered from 43 (86%) patients in blood cultures (n = 16; 32%), skin swabs (n = 16; 32%), and skin biopsies (n = 4; 8%) (Table 2). Treatment combined respiratory support (58%), hemodynamic support (70%), antitoxin antibiotic (84%), and surgery (68%) (Table 2). Three (6%) patients died; all had severe comorbidities (mitochondrial cytopathy, solid tumor, and leukemia). Most patients had long hospital stays. Our sample was too small to identify factors associated with surgery or mortality.

Table 1 Characteristics of the study patients during the first 24 h after admission

Table 2 Assessments, treatments, and course of the disease during the PICU stay

The results of this largest prospective study of pediatric NSTIs to date confirm that this disease is rare in PICUs [2,3,4,5,6]. Predisposing conditions have shifted from varicella to healthcare and trauma [2, 3]. The percentage of body surface area involved on PICU admission was consistent with studies in adults [1], whereas a major difference in absolute value was noted (about 5 cm² in children vs. 12 cm² in adults), which may contribute to diagnostic delays in children. MRI was rarely used to assess lesion depth. As reported by others [2, 6], surgery was performed in two-thirds of patients, usually within 24 h, and aggressive medical treatments were used. This may explain the low mortality rate, in agreement with recent data [6], despite the high predicted mortality on admission. Most NSTIs were monobacterial and many were due to Gram-positive organisms, including methicillin-resistant S. aureus in a few patients, as previously reported [3]. Polyvalent immunoglobulin therapy was often used, perhaps due to frequent circulatory failure suggesting toxic shock, and might also have influenced mortality rates, as suggested in a recent adult study [1]. Strong collaboration between surgeons, anesthesiologists, and pediatric intensivists should be the cornerstone of NSTI management.