1. ORIGINAL STUDIES
Characteristics, Therapies, and Outcome of Children With
Necrotizing Soft Tissue Infections
Frederick W. Endorf, MD,* Michelle M. Garrison, PhD,† Matthew B. Klein, MD,‡§
Andrea Richardson, MS,¶ and Frederick P. Rivara, MD, MPH‡§ʈ
Accordingly, little is known about the risk factors, treatment
Objectives: Necrotizing soft tissue infections (NSTIs) are uncommon but
patterns, and outcomes of these infections in children. We sought
potentially lethal infections that are well described in adults. Little is
to use a large multihospital pediatric database to examine charac-
known about pediatric patients with NSTI. We sought to examine patients’
teristics of pediatric NSTI patients, as well as treatment patterns
characteristics, infection characteristics, treatment patterns, and outcomes
and outcomes of these patients at children’s hospitals.
of children with NSTIs using a large multicenter pediatric database.
Study Design: The Pediatric Health Information System database was
used to examine demographics, diagnoses, procedures, medications, hos- METHODS
pital charges, and outcomes of pediatric patients with NSTI during a 5-year This retrospective cohort study was approved by the Insti-
period. tutional Review Board of Children’s Hospital and Regional Med-
Results: A total of 334 patients with NSTI were identified. Times from ical Center. The Pediatric Health Information System database was
admission to initial amputations and reconstructive surgeries were similar developed by the Child Health Corporation of America. This
between the 2 groups, but nonsurvivors had a longer time from admission database is drawn from 41 freestanding pediatric hospitals, and
to their first debridement (median, 2 vs. 1 day, P ϭ 0.03). On multivariate provides detailed data, including demographic characteristics, di-
analysis, no other significant risk factors for increased mortality were agnoses, procedures, medications, diagnostic testing, hospital
identified, although increased age (P ϭ 0.10), noncommercial insurance charges, and other services. Previous work using this database has
(P ϭ 0.12), and use of corticosteroid therapy (P ϭ 0.06) showed trends examined such topics as inpatient resource utilization4 and varia-
toward increased mortality. Diagnoses of streptococcal (P ϭ 0.03) or tions in antibiotic therapies after surgery.5 Inclusion criteria in-
staphylococcal infection (P ϭ 0.03) were associated with a lower mortality cluded patients with age ranging from 1 month to 18 years, with
on multivariate analysis. NSTIs identified by ICD-9 codes for necrotizing fasciitis (728.86),
Conclusions: NSTIs are a rare but significant diseases in children. It seems gas gangrene (040.0), and Fournier gangrene (608.83). Demo-
that, as in the adult population, prompt surgical debridement is the most graphic variables included age, sex, gender, race, and use of
important intervention. Corticosteroid therapy may be associated with a noncommercial insurance (Medicaid, Medicare, or other govern-
worse prognosis. ment program as primary payer). We identified medications used
in therapy, with particular attention to antibiotic agents, cortico-
Key Words: necrotizing soft tissue infection, therapy, outcome
steroids, and vasopressors. We also noted administration of non-
(Pediatr Infect Dis J 2012;31: 221–223) drug therapies such as parenteral nutrition and blood products.
Procedural ICD-9 codes were used to identify the type and
number of surgical and other clinical interventions, including
debridements, reconstructions, and amputations. Time from admis-
N ecrotizing soft tissue infections (NSTIs) are uncommon but
potentially lethal infections of the superficial fascia, subcu-
taneous tissues, and skin. Historically, a large number of terms
sion to each surgical procedure was noted. ICD-9 codes for various
organ failures were used as markers for complications during
hospital stay. Outcome measures examined were ICU days, dura-
have been used, including necrotizing fasciitis, necrotizing cellu- tion of mechanical ventilation (greater than or less than 96 hours),
litis, necrotizing erysipelas, synergistic necrotizing cellulitis, he- total hospital length of stay, hospital charges, and in-hospital
molytic streptococcal gangrene, bacterial synergistic gangrene, mortality.
and gangrenous erysipelas.1 The most common clinical entities are
necrotizing fasciitis and Fournier gangrene, the latter involves the Statistical Analyses
perineum or genitalia. Although well described in adults, studies of Descriptive statistics were calculated, examining the char-
pediatric patients with NSTI are rare and involve fewer patients.2,3 acteristics of the overall population, and separately for survivors
versus nonsurvivors. Differences between survivors and nonsurvi-
vors were assessed using ␹2 tests for categorical variables and
Accepted for publication October 16, 2011. Wilcoxon rank sum tests for continuous variables. We then per-
From the *Department of Surgery, Regions Hospital, St. Paul, MN; †Center for formed a multivariate regression analysis examining risk factors
Child Health, Behavior, and Development, Seattle Children’s Research for mortality from NSTI, with demographic factors and treatment
Institute, Seattle, WA; ‡Department of Nutrition, University of North
Carolina at Chapel Hill, Chapel Hill, NC; §Carolina Population Center, as potential covariates. The regression analysis was explored as a
Chapel Hill, NC; ¶Harborview Medical Center, Seattle, WA; and ࿣Harbor- fixed-effects logistic model to control for unmeasured hospital-
view Injury Prevention Research Center, Seattle, WA. level confounders; this means that patients were only compared
F.W.E. wrote the first draft of the manuscript, and received no payment for with other patients within the same hospital.
writing the manuscript.
The authors have no funding or conflicts of interest to disclose.
Address for correspondence: Frederick W. Endorf, MD, The Burn Center, RESULTS
Regions Hospital, 640 Jackson St, St. Paul, MN 55101. E-mail:
endorf01@yahoo.com. Demographics
Copyright © 2012 by Lippincott Williams & Wilkins
ISSN: 0891-3668/12/3103-0221 A total of 334 patients with NSTI were identified. The mean
DOI: 10.1097/INF.0b013e3182456f02 age was 7.9 years. In all, 68% of the patients were male, and 47%
The Pediatric Infectious Disease Journal • Volume 31, Number 3, March 2012 www.pidj.com | 221

2. Endorf et al The Pediatric Infectious Disease Journal • Volume 31, Number 3, March 2012
TABLE 1. Treatments and Outcomes
All N ϭ 334 Survivors N ϭ 312 Nonsurvivors N ϭ 22 P
Median length of stay, d (IQR) 13.5 (5–26) 12.5 (4.5–25) 26.0 (8 –35) 0.09
ICU days (%) 0.001
0–4 65.9 67.3 45.5
5–14 17.1 17.6 9.1
15ϩ 17.1 15.1 45.5
Vent Ͻ96 h (%) 7.5 6.4 22.7 0.005
Vent Ͼ96 h (%) 17.1 15.1 45.5 Ͻ0.001
Transfusions (%) 23.1 21.2 50.0 0.002
Parenteral nutrition (%) 12.6 11.5 27.3 0.03
Median hospital charges (IQR) $76, 513 (24, 876 –169, 195) $69, 789 (19, 856.50 –153, 210) $319, 502 (123, 957– 450, 329) Ͻ0.0001
Mortality (%) 6.6 0 100 NA
Values shown in bold are P Ͻ 0.05.
Vent indicates ventilator; NA, not applicable.
TABLE 2. Surgical Procedures TABLE 3. Risk Factors for Mortality—Multivariate
Analysis
All Survivors Nonsurvivors
P
N ϭ 334 N ϭ 312 N ϭ 22 Odds Ratio Confidence Interval P
Any surgical procedures (%) 80.2 81.1 68.2 0.14 Age 1.09 0.98 –1.21 0.10
Any amputations (%) 4.2 3.9 9.1 0.24 Gender (male) 1.24 0.33– 4.64 0.75
Any reconstructions (%) 29.3 30.5 13.6 0.09 Race (Non-white) 1.98 0.46 – 8.57 0.36
Any debridement (%) 78.4 79.2 68.2 0.23 Payer status 3.78 0.71–20.04 0.12
Time to surgery (d) (Noncommercial)
Amputation 4 4 6 0.85 Immunosuppression 1.94 0.40 –9.48 0.41
Reconstruction 8 7 13 0.16 Streptococcus infection 0.05 0.00 – 0.76 0.03
Debridement 1 1 2 0.03 Staphylococcus infection 0.10 0.01– 0.82 0.03
Value shown in bold are P Ͻ 0.05. Penicillins 0.88 0.16 – 4.70 0.88
Clindamycin 1.11 0.19 – 6.55 0.91
Cephalosporins 1.79 0.45–7.05 0.41
Aminoglycosides 1.91 0.38 –9.67 0.43
Vancomycin 3.10 0.33–29.40 0.32
were white. Overall, the proportion of patients with private insur- Corticosteroids 4.16 0.93–18.55 0.06
ance/HMO and noncommercial payer status was similar (49.7% Values shown in bold are P Ͻ 0.05.
vs. 50.3%). Although not statistically significant, a lower percent-
age (36.4%) of nonsurvivors had private insurance or an HMO
(P ϭ 0.20). There were no major differences in baseline patient
characteristics between survivors and nonsurvivors. Medications
Nearly all classes of antibiotics were used in this patient
population. The use of most antibiotic classes was significantly
Patient Outcomes higher in the nonsurvivors, with the exceptions being penicillin
Patient outcomes are shown in Table 1. Median length of (54.6% vs. 45.8%, P ϭ 0.43) and clindamycin (54.6% vs. 56.4%,
stay, though not statistically significant, was more than twice as P ϭ 0.87). Other commonly used drugs in critical illness were also
long for nonsurvivors (26 vs. 12.5 days, P ϭ 0.09). Nonsurvivors used at higher rates in the nonsurvivors, including antiarrhythmic
had significantly longer ICU stays (median, 11.5 vs. 1 day; P ϭ and adrenergic agents, antidiabetic medications, and corticoste-
0.002) and were more likely to have prolonged (Ͼ96 hours) roids.
mechanical ventilation (45.5% vs. 15.1%, P Ͻ 0.001). Nonsurvi-
vors were significantly more likely to have received blood trans-
Multivariate Analysis
fusions (50% vs. 21.2%, P ϭ 0.002) and parenteral nutrition A multivariate analysis was undertaken to determine inde-
(27.3% vs. 11.5%, P ϭ 0.03) during their hospital course. Hospital pendent risk factors for mortality (Table 3). On multivariate
charges were much higher for the nonsurvivors, in accordance with analysis, no significant risk factors for increased mortality were
their prolonged length of stay (median, $319,502 vs. $69,789; P Ͻ identified, although increased age (P ϭ 0.10), noncommercial
0.0001). Overall, 22 of 334 patients with NSTI died in the hospital insurance (P ϭ 0.12), and use of corticosteroids (P ϭ 0.06)
(6.6%). showed trends toward increased mortality. Diagnoses of strepto-
coccal (P ϭ 0.03) or staphylococcal infection (P ϭ 0.03) were
actually associated with a lower mortality on multivariate analysis.
Surgical Procedures
Surgical procedures were divided into amputations, recon- DISCUSSION
structive procedures, and debridements. Similar percentages of NSTIs are severe and often life threatening in the adult
patients from each group underwent surgical procedures (81.1% of population. Descriptions of this disease process in the pediatric
survivors vs. 68.2% of nonsurvivors, P ϭ 0.14). Table 2 illustrates population have been limited to case reports and smaller case
that the times from admission to initial amputations and recon- series. Mortality has been reported to be as low as 9.4% in the
structive surgeries were similar between the 2 groups, but nonsur- pediatric population,3 although in neonates mortality may be as
vivors had a longer time from admission to their first debridement high as 59%.6 Reports are predominately in children that are
(median, 2 vs. 1 day; P ϭ 0.03). immunosuppressed2 from causes such as chemotherapy.7,8 Suc-
222 | www.pidj.com © 2012 Lippincott Williams & Wilkins

3. The Pediatric Infectious Disease Journal • Volume 31, Number 3, March 2012 Soft Tissue Infection
cessful treatment has been reported with aggressive surgical man- coccal or staphylococcal infections, and thus appropriate empiric
agement in concert with broad-spectrum antibiotics.9 We used a antibiotics were given at the onset of their NSTI.
large multihospital pediatric database to examine characteristics of Limitations of this study are in large part inherent to the use
pediatric patients with NSTI and to investigate treatment patterns of large administrative databases. There may be differences in
and outcomes of this patient population at children’s hospitals. coding between institutions leading to heterogeneity of the dis-
Patients in this database were dispersed among all pediatric eases coded as NSTIs. Markers of disease severity such as specific
age groups, and no particular age group seemed to be at greater laboratory values were not available. Therefore, it is difficult to
risk. Patients were predominately male, but there were no major stratify these patients by severity of illness at presentation. Also,
demographic differences between survivors and nonsurvivors the types of surgical procedures were recorded, but not their
among our patient population. A larger percentage of the nonsur- extent, so that there may be wide variations in the body surface
vivors did have noncommercial insurance, which has been shown area that required debridement but that may not be reflected in the
to be a marker for poorer baseline health.10 Overall mortality was coding for this database. The low overall mortality also makes it
low (6.6%). This is lower than reported in other adult series1 and difficult to demonstrate any independent risk factors for mortality.
may represent “overcoding” of non-NSTI disease processes that
carry a better prognosis. In fact, only 80.2% of these patients
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