Necrotizing fasciitis following rapidly deteriorating neonatal omphalitis with good initial presentation

Abstract

Neonatal omphalitis is a postpartum infection of periumbilical superficial soft tissues that usually has a good prognosis in developed countries. In rare cases, it could progress to periumbilical necrotizing fasciitis (NF), which is an infection of the deep soft tissues, including muscle fascia, and has a high mortality rate. However, the signs and timing of developing NF secondary to omphalitis are unclear. We encountered a neonatal case of NF following omphalitis. In the initial days of the clinical course, general symptoms and condition of the patient were good, and abdominal physical findings were mild; however, the patient rapidly developed NF. The patient was successfully treated by emergent surgical debridement, broad-spectrum antibiotics, and intensive care. To determine the area of blood perfusion, we intravenously injected indocyanine green by intraoperative angiography, and then extensively removed necrotic and hypoperfused tissues. In neonatal omphalitis, the deterioration can suddenly occur despite good initial conditions; intensive monitoring should be required during the first few days of the clinical course.

Introduction

Neonatal omphalitis is a postpartum infection of the umbilicus and/or periumbilical superficial soft tissues. Neonatal omphalitis is a relatively common disease, particularly in developing countries, where it is reported to occur in 0.2–5.4% [1], but is also seen in developed countries, where it occurs in 0.7–2%, according to previous reports [2], [3]. In developed countries, the prognosis is generally good [4]; however, it could progress to necrotizing fasciitis (NF) and cause death [2], [5]. NF is a bacterial infection of the deep soft tissues, including muscle fascia, and is clinically characterized by rapid deterioration of the general condition. Its mortality rate is very high, estimated to be more than 40% [2], [6], [7], [8]. NF is such a rare complication of omphalitis that it is not widely known to clinicians. The typical clinical course is not sufficiently clarified, including the signs and symptoms that progress to NF [2] and the timing of the deteriorating clinical condition. Furthermore, the information regarding skin appearance over time is also limited. Here we report a neonatal case of NF secondary to omphalitis, deteriorating early and rapidly despite good initial presentation, together with clear skin pictures.

Case report

A 6-day-old female neonate presented with erythema and swelling around the umbilicus within 24 h of the initial symptoms (Fig. 1A). She was born to a healthy mother with a birth weight of 3726 g. A sibling of her grandfather died in early life for unknown reasons but there was no apparent family history of primary immunodeficiencies. She was afebrile, her vital signs were stable, and her milk intake was fair. Redness and swelling around the umbilicus were localized, and no purulent discharge was noted. The umbilical cord, which was black and dry, had not yet fallen off. Laboratory tests showed elevated white blood cell count (20,080/µL with 58.5% neutrophils) and mildly elevated CRP (0.66 mg/dL). Cerebrospinal fluid (CSF) examination was not performed because of the absence of fever and good general condition. Neonatal omphalitis was diagnosed and treatment with intravenous cefotaxime (100 mg/kg/day) and vancomycin (30 mg/kg/day) was initiated after peri-umbilical swab and blood samples were sent for cultures. The antibiotic regimen was designed to cover Staphylococcus aureus (including methicillin-resistant S. aureus), Streptococcus pyogenes, Streptococcus agalactiae, and Enterobacteriaceae.

Fig. 1.

Skin appearance. (A, B, C) Abdominal findings on the first (A), second (B), and third (C) day from onset. Redness and swelling were progressing and expanding slightly but were obscured and mild. The black points were marked as the edge of swelling on the second day. (D) On the third day, the redness rapidly turned purple with the general condition deteriorating, which implied the progression of inflammation and necrosis. (E) Surgical debridement. (F) Three months after skin grafting.

For two days after the initiation of antibiotic therapy, the erythematous swelling in the abdomen became slightly expanded, poorly marginated, and indurated (Fig. 1B, C). Her general condition was still good; vital signs showed intermittent fever of less than 38.0 °C and mild tachycardia. At Day 3 of hospitalization, we changed cefotaxime to meropenem (120 mg/kg/day), due to a lack of cutaneous improvement and increased leukocytes (42,830/µL) and CRP level (6.99 mg/dL).

On the same day, the erythema became dark purple (Fig. 1D) and her general condition rapidly deteriorated with hypothermia and hypotensive shock. Contrast-enhanced computed tomography (CT) showed effusion and abscess formation between muscle layers that constituted the chest and abdominal walls (Fig. 2). NF that developed from omphalitis was clinically suspected, emergent surgical debridement was performed, and catecholamine was administered (Fig. 1E). Intraoperative findings were consistent with NF. To determine the area of blood perfusion, we intravenously injected 0.5 mg/kg of indocyanine green (ICG) immediately before incision for an intraoperative angiography. We extensively removed necrotic skin, subcutaneous fat, fascia, and a part of the left external oblique muscle that were confirmed by the absence of ICG fluorescence. Exudate from the chest and abdominal walls, and necrotized or inflamed periumbilical soft tissues, were sent for culture during the operation.

Fig. 2.

Contrast-enhanced computed tomogram shows inflammatory effusion and abscess formation between muscle layers that constitute the chest (A) and abdominal (B) walls.

After surgery, the wound remained open for infection source control, and she received intensive treatment, including intravenous clindamycin (30 mg/kg/day) (for expected anti-toxin activity) and intravenous immunoglobulins. Culture of the umbilical swab at admission detected polymicrobials (Staphylococcus epidermidis, Staphylococcus haemolyticus, Enterococcus faecalis, and Citrobacter freundii). The soft tissue cultures obtained from the surgical operation showed Escherichia coli, Staphylococcus epidermidis, and Pseudofalvonifacter capillosus. These organisms were susceptible to either cefotaxime or vancomycin, which were both used as empirical therapy. Blood and exudate cultures were negative. No anaerobes were found in any of the cultures. As a result, the causative organism(s) could not be determined definitively. Her immunological condition was investigated (Table 1) A blood sample collected before administering immunoglobulins did not reveal neutropenia, abnormal differential leukocyte count, or apparent reduction of antibody level. C3, C4 levels, and CH50 transiently decreased because of inflammation, which were all confirmed as normal at the outpatient visit 3 months after discharge. No abnormal findings were obtained in the flowcytometric analysis, either for lymphocyte subpopulations or for neutrophil oxidative respiratory burst response with dihydroergotamine. The thymus was detected by CT. Although she had a cerebral infarction probably due to infectious disseminated intravascular coagulation, resulting in hemiplegia, her general condition became improved after both the antibiotic therapy and the surgical procedure. After the second additional debridement at Day 13, negative pressure wound therapy was applied to the open wound, followed by skin grafting after the complete removal of the necrotic tissue on Day 42 (Fig. 1F). The patient was discharged on Day 67 of hospitalization. Follow-up at the outpatient clinic showed only hemiplegia as a sequela at the age of 2 years.

Table 1.

Immunological profile.

Variables		Unit
Leukocyte count	42,830	/µL
Neutrophils	76.5	%
Lymphocytes	8.9	%
Complement 3	37	mg/dL
Complement 4	6	mg/dL
CH50	< 12	U/mL
IgM	20	mg/dL
IgG	1058	mg/dL
IgA	< 23	mg/dL
IgE	9.5	U/mL
Lymphocyte subset
CD3+ T cell	77.1	%
CD4+ T cell	71.6	%
CD8+ T cell	24.7	%
CD20+ B cell	12.3	%
CD3–/CD56+ NK cell	6.5	%

Abbreviation: CH50, complement hemolytic activity (50%).

Discussion

We encountered a case of neonatal omphalitis that was exacerbated by very rapidly progressing NF despite good initial presentation, but survived after intensive and aggressive medical treatment. Although NF has a very high mortality rate [2], [6], [7], [8], this case was rescued possibly owing to early intervention, i.e., administering broad-spectrum antibiotics, surgical debridement, and intensive care [2], [7], [9], [10], [11], [12], [13], [14].

Previous reports of most NF cases secondary to omphalitis had at least one of the following symptoms before developing NF: apparent fever, irritability, or poor feeding [7], [9], [10]. In our case, however, the patient did not clearly show these symptoms during the first few days of the hospitalization. In addition, the general condition (including vital signs and abdominal skin findings) was also relatively stable until just before developing NF. In neonatal omphalitis cases, given these facts, clinicians should be aware that the possibility of developing NF cannot be denied based on good clinical conditions and mild skin findings.

The typical timing of deterioration or development of NF in neonatal omphalitis has not been sufficiently clarified. Weber, et al. reported that the timing of progression to NF was 1.9 (1−4) days on average (range) in 18 neonatal omphalitis cases [11]. In our case, the patient rapidly developed hypovolemic septic shock 3 days after the onset. Therefore, neonatal patients with omphalitis should be carefully monitored particularly for the first few days in the clinical course. As NF patients require intensive treatment including aggressive surgical intervention [2], [7], [9], [10], [11], [12], [13], [14], it would be better to consider transfer to a tertiary center if the clinical response to antibiotic treatment for omphalitis is insufficient during the first few days of therapy.

The known risk factors for progression to NF from neonatal omphalitis are extremely limited [2]. Lin, et al. reported a 25-day-old female baby with lymphopenia who developed NF on her back, but correlation between the type of immunodeficiency and risk of NF is still unknown [15]. In our case, there were no findings of apparent immunodeficiency, and it was difficult to presume the reason why this patient developed NF in this regard. In other words, an infant with omphalitis without any medical history including immunodeficiency may nevertheless progress to NF, therefore necessitating watchful waiting in all neonatal omphalitis cases.

In conclusion, we encountered a neonatal NF case rapidly deteriorating secondary to omphalitis despite a good general condition. In neonatal omphalitis, intensive monitoring should be required for the first few days during the clinical course because sudden deterioration could occur even under good initial conditions. Further investigations are required to determine the risk factors for developing NF secondary to omphalitis.

Funding

Funding was provided by grants from the National Center for Child Health and Development (2020E-1 and 2020E-2).

Ethical approval

Ethics approval was waived for this study in accordance with international as well as institutional guidelines.

Consent

Written informed consent was obtained from the patient’s guardian for the publication of this case report and any accompanying images.

CRediT authorship contribution statement

Jin Sato: Conceptualization, Data curation, Writing – original draft. Nobuyuki Yotani: Conceptualization, Writing – review & editing. Kensuke Shoji: Conceptualization, Writing – review & editing. Teizaburo Mori: Writing – review & editing, Supervision. Akihiro Fujino: Writing – review & editing, Supervision. Makoto Hikosaka: Writing – review & editing, Supervision. Mitsuru Kubota: Writing – review & editing, Supervision. Akira Ishiguro: Writing – review & editing, Supervision.

Author contributions

JS wrote the first draft of the manuscript. NY and KS reviewed and modified the manuscript. TM, AF, MH, MK, and AI supervised and revised the manuscript. All authors approved the final manuscript.

Declaration of Competing Interest

All authors do not have any potential, perceived, or real conflicts of interest.