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J Ped Surg Case Reports 10 (2016) 35e38

Journal of Pediatric Surgery CASE REPORTS

journal homepage: www.jpscasereports .com

Clostridium sordellii necrotizing omphalitis: A case report andliterature review

Eric J. Rellinger a, Brian T. Craig a, Laura D. Craig-Owens b, M. Cristina Pacheco b,Dai H. Chung a, Melissa E. Danko a,*

aDepartment of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, USAbDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA

a r t i c l e i n f o

Article history:Received 17 March 2016Received in revised form30 March 2016Accepted 9 April 2016

Key words:OmphalitisClostridium sordelliiNecrotizing infection

* Corresponding author. Department of Pediatric SuHospital, 2200 Children’s Way, DOT 7100 Nashville, TN1050; fax: þ1 615 936 1046.

E-mail address: melissa.danko@vanderbilt.edu (M.

2213-5766/� 2016 The Authors. Published by Elsevierhttp://dx.doi.org/10.1016/j.epsc.2016.04.008

a b s t r a c t

Omphalitis is an infrequent neonatal infection of the umbilicus. Necrotizing infections are a rarecomplication of omphalitis that requires prompt antibiotic therapy, surgical debridement, and supportivecare. Here, we present a rare case of Clostridium sordellii necrotizing omphalitis that progressed to severetoxemia characterized by refractory hypotension, massive capillary leak, leukemoid reaction, andabsence of fever. These clinical features are common in C. sordellii infections and harbor a poor prognosiswith only one reported survivor (out of 12) of C. sordellii omphalitis reported in the literature. Earlyantibiotic and surgical intervention remain the mainstay of care as no early detection assays or antitoxinsare commercially available.� 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND

license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Omphalitis is an infection of the umbilicus and its surroundingtissues that occurs in approximately 0.7% of all hospital-born chil-dren in developed countries [1]. The incidence of omphalitis isgreater in developing countries where rates are reported to be ashigh as 6% [2]. Identified risk factors for neonatal omphalitisinclude: low birth weight, prolonged delivery and rupture ofmembranes, nonsterile delivery, and delivery at home [2,3].Omphalitis most commonly presents with signs of umbilicalinflammation (erythema, induration, and swelling) with or withoutdrainage from the umbilical stalk. Potential sequelae of omphalitisinclude necrotizing fasciitis, sepsis, portal vein thrombosis, andhepatic abscesses [4]. Omphalitis is typically treated with topicalantiseptics and systemic antibiotics targeting the most commoncausative agents, including Staphylococcus aureus, Group A Strep-tococcus, Escherichia coli, and Klebsiella pneumonia [4]. Closeobservation and a high degree of clinical suspicion for the devel-opment of localized fluid collections or necrotizing infection arecritical given the potential need for surgical intervention in cases ofneonatal omphalitis [5].

rgery, Vanderbilt Children’s37232, USA. Tel.: þ1 615 936

E. Danko).

Inc. This is an open access article u

1. Case report

An 8-day old male born at 39 weeks gestational age to a GroupB Streptococcus-negative mother (G3P3) by uncomplicated cesar-ean section presented to our emergency department with a oneday history of increasing abdominal redness and indurationlocalized around the umbilicus. On the day prior to presentation,he was noted to have small volume bleeding from the umbilicusfollowing recommended cleaning that self-resolved. The childwas acting well and without fevers. At initial evaluation, he wasnoted to have a desiccated umbilical stalk with faint surroundingerythema and induration of approximately 3 cm diameter sur-rounding the umbilicus. No evidence of crepitus, fluctuance ordrainage was appreciable. He had focal umbilical tenderness thatwould awaken him from sleep with examination. An ultrasoundstudy demonstrated increased periumbilical echogenicity withouta drainable fluid collection. Initial laboratory data demonstrated amoderate leukocytosis (22.5 � 103 cells/mm3), normal hematocrit(43.0%), and normal electrolytes. Cerebrospinal fluid (CSF)analysis was normal and blood, urine, and CSF cultures werenegative.

The neonate was admitted to the general pediatrics service (day1), started on vancomycin and cefotaxime for empiric treatment ofomphalitis, and a surgical consultationwas obtained due to concernfor necrotizing omphalitis. Infectious disease was consulted and

nder the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

E.J. Rellinger et al. / J Ped Surg Case Reports 10 (2016) 35e3836

metronidazole was initiated. Overnight, his umbilicus developed apurplish hue and his periumbilical induration progressed laterallyto the bilateral flanks and inferiorly towards the inguinal regionwithout erythema progression. A CT scan obtained on day 2demonstrated marked subcutaneous edema of the chest, abdomen,and pelvis with mild hyperenhancement, greatest at the umbilicusand no evidence of subcutaneous air or fluid collection (Fig. 1). Theantibiotic regimen was switched to vancomycin, cefepime, andclindamycin for Pseudomonas coverage and to potentially blockexotoxin production.

On the evening of day 2, the infant remained afebrile and wasnoted to have increased anasarca, decreased urine output, andincreased periumbilical discoloration. Leukocytosis rose to53.6 � 103 cells/mm3 with 51% neutrophils and evidence ofhemoconcentration (Hct at 51%), but persistently low C-reactiveprotein (5.7 mg/L). He developed progressive hyponatremia(121 mEq/L), hypoalbulminenia (1.0 g/dL) with a marked metabolicacidosis (pH-7.13, HCO3-11 mEq/L) requiring aggressive fluidresuscitation and was transferred to the intensive care unit (eve-ning of day 2). On day 3, he developed increasing respiratorydistress requiring endotracheal intubation. The infant was taken tothe operating room for exploration of his umbilicus. Infraumbilicalbiopsy demonstrated diffuse bleeding from the wound bed withserous exudate and no foul odor. No purulence or separation of thesubcutaneous tissues and fascia was noted. A full-thicknessabdominal wall skin biopsy was submitted for frozen sectionevaluationwhich demonstrated inflamed dermis and subcutaneousnecrosis without evidence of fascial or muscular involvement.Acute inflammation was sparse when compared to the degree ofnecrosis (Fig. 2a and b). Further debridement was foregone, hiswound was packed, and the patient was transferred back to theintensive care unit.

In the early post-operative period, the infant developed pro-gressive shock with refractory hypotension, metabolic acidosis, andmultisystem organ failure. He was emergently placed on venoar-terial (VA) ECMO support. His overall condition continued toworsen with poor ECMO flows, refractory hypotension, and pro-gressive abdominal distension. Concern for abdominal compart-ment syndrome prompted an emergent decompressive laparotomyat bedside with minimal improvement in ECMO flows. Futility ofongoing care was discussed with the family, care was withdrawn,and the child died early on the first post-operative day (day 4 ofhospitalization).

Fig. 1. Representative image of an IV contrasted CT scan obtained on hospitalizationday 2 demonstrating diffuse subcutaneous edema with inflammatory changes mostpronounced at the umbilicus. No subcutaneous air was appreciable.

Final operative pathology of the anterior abdominal wall and aseparately submitted piece of abdominal wall muscle demonstratednecrotizing omphalitis with evidence of necrotizing panniculitis,fasciitis, and myocyte necrosis. Special stains for bacteria and fun-gus were negative (Fig. 2c and d). An autopsy was completed. At thetime of dissection, no evidence of abscess formation was seen andthere was no separation of the fascial planes. Histology sectionsfrom the umbilicus and surrounding skin showed findings similarto those taken at surgery. Inflammation was increased over theprior biopsies but areas with minimal neutrophilic infiltrateremained (Fig. 2e and f). Additional findings at autopsy includeddiffuse anasarca with bilateral serous effusions secondary toresuscitative efforts and hemorrhagic cystitis, subcapsular liverhematoma, blood within the gastrointestinal tract, and brain andcerebellar hemorrhages consistent with disseminated intravascularcoagulopathy.

Intraoperative tissue cultures yielded light growth of Entero-coccus faecium and Staphylococcus epidermidis and heavy growth ofClostridium sordellii. Both Enterococcus and Staphylococcal isolateswere susceptible to administered antibiotics. Anaerobic suscepti-bility panel demonstrated susceptibility of the C. sordellii isolate toall tested antimicrobials (meropenem, ampicillin/sulbactam,pipericillin/tazobactam, penicillin, metronidazole).

2. Discussion

Necrotizing omphalitis is a rare disease of the newborn withonly 120 cases reported in the literature [5e8]. It is a rapidly pro-gressive soft tissue infection that arises from the umbilicus andclassically spreads along low resistance fascial planes, resulting intissue necrosis and overwhelming sepsis. S. aureus, Pseudomonasaeruginosa, E. coli and anaerobes are the most common pathogensimplicated in necrotizing omphalitis. Reported survival rates forneonatal necrotizing omphalitis range anywhere from 19 to 40%,reflecting an aggressive disease with significant morbidity andmortality [9,10]. Immunodeficiency and prior skin breaches arecommon inciting factors. The infant in our case developed severeleukocytosis (peaking at 79.8 � 103 cells/mm3 in the early post-operative period) and overwhelming septic shock, but remainedafebrile with a normal C-reactive protein (5.7 mg/L; normal range0.3e6.1). These findings prompted concern for a potential under-lying immunodeficiency. Leukocyte adhesion deficiency type I(LADI) has a known association with delayed umbilical corddetachment. The disease characteristically presents early in lifewith severe bacterial infection and in one study greater than halfthe patients initially presented with omphalitis [11]. Patients withLADI have decreased leukocyte adhesion markers (CD11b andCD18) [12]. Leukocyte adhesion testing sent prior to death wasnormal. Additionally, flow cytometry was performed on autopsybone marrow aspirates and did not reveal any abnormalities sug-gestive of an immune deficiency.

The mainstays of treatment for necrotizing omphalitis are earlyinitiation of broad-spectrum antibiotics, surgical debridement, andsupportive measures in the intensive care unit [4,5,10]. For ourpatient, operative exploration was delayed for 48 h followingadmission. Lack of erythema progression, absence of fever, initialhemodynamic stability and normal activity were falsely reassuringfeatures that delayed operative intervention. Intriguingly, ourtiming of operative exploration was delayed until clinical deterio-ration with hemodynamic instability became obvious, but no evi-dence of necrotizing fasciitis was grossly appreciable at surgicalexploration or on frozen pathology. Specifically, brisk bleeding wasobserved from the wound bed, the subcutaneous tissues failed toseparate from the underlying fascia, and exudate was serous innature without odor. It is unlikely that further debridement at the

Fig. 2. Anterior abdominal wall biopsy: (A) Permanent section of intraoperative frozen section with paucicellular necrotizing panniculitis. H&E 2�. (B) Higher power demonstratingthe interface of acute inflammation and necrosis. H&E 20�. (C and D) Biopsy with no evidence of organisms, gram stain, (C) and Grocott’s methenamine silver stain, (D) 40�.Autopsy findings: (E) Abdominal skin, full thickness with necrosis, myocyte injury, and acute inflammation H&E 20�, (F) Myocyte injury and necrosis, H&E 40�.

E.J. Rellinger et al. / J Ped Surg Case Reports 10 (2016) 35e38 37

time of operative exploration would have altered the course of caregiven the absence of grossly apparent fasciitis and his rapid dete-rioration in the first several hours following his operation.

Our intraoperative cultures demonstrated mixed aerobic andanaerobic growth with C. sordellii as the predominant organism.C. sordellii is an anaerobic spore-forming bacillus that is found in thesoil and less frequently in the intestines of animals and humans(0.5%) [13]. Infections with C. sordellii are rare, but frequentlyassociated with a fatal, toxic shock-like syndrome. Recent trauma,childbirth, and gynecologic procedures are the most commonroutes of exposure, but clinical outbreaks associated with subcu-taneous and intravenous drug use have also been reported [13].Vaginal colonization rates following childbirth have been reportedto be as high as 29%, but a recent multi-center cohort study esti-mated that only 3.4% of women of reproductive age are colonizedwith C. sordellii [13,14]. Recent gynecologic procedure (within 3months) was the only identifiable risk factor for C. sordellii vaginalor rectal colonization [14]. C. sordellii infections are associated witha high rate of mortality with an all-cause mortality of 69% with 85%of all fatal cases occurring within a 2e6 day period [13]. The

antibiotic resistance profile of C. sordellii has been previously re-ported with sensitivity to b-lactams, clindamycin, metronidazole,and chloramphenicol, but resistance to aminoglycosides and sul-fonamides [13]. Given the early age of onset of omphalitis in ourpatient and prior reports of high rates of C. sordellii colonization inpregnant mothers, perinatal transmission may explain acquisitionof this pathogen through umbilical stalk colonization. However, it isimportant to note that our patient was delivered via cesarean sec-tionwithout transit through the birth canal. Gormley et al. [15] havepreviously reported isolation of C. sordellii from maternal vaginalcultures obtained from the mother of a child that succumbed toC. sordellii omphalitis, providing the strongest correlative evidenceof this association available in the literature.

We identified eleven prior cases of C. sordellii omphalitis re-ported in the literature [5,13,16,17]. Of these twelve total cases, in-clusive of the present case, only one survivor has been reported.Survival in this case followed early, aggressive surgical debridementwith resection of the umbilical vessels and urachal remnant [18]. Inour literature review, we were able to directly link C. sordelliiomphalitis with mortality in 10 of the 12 cases, suggesting an

E.J. Rellinger et al. / J Ped Surg Case Reports 10 (2016) 35e3838

attributable mortality of 90% in neonates with C. sordellii necro-tizing omphalitis [5,16,17]. Common clinical features of necrotizingC. sordellii infections include 1) refractory hypotension with severetachycardia, 2) massive capillary leak with anasarca and hemo-concentration, 3) marked leukocytosis (>50 � 103 cell/mm3)commonly referred to as a leukemoid reaction, and 4) absence offever [13]. All four of these clinical features were observed in ourpatient, highlighting the unique presentation and severe progres-sion of C. sordellii necrotizing infections.

The virulence of C. sordellii infections is closely tied to toxinproduction. A total of seven toxins have been identified forC. sordellii [13]. The two major virulence factors of C. sordellii arelethal and hemorrhagic toxins, which function as glycosyl-transferases and are closely related to toxins A and B produced byClostridium difficile. Lethal toxin production has been linked to theintense capillary link in animalmodels of C. sordellii.Antitoxins haveeffectively blocked the cytotoxicity of lethal toxin in cell culture andprevented death in animal models of C. sordellii toxemia, but noantitoxins are commercially available at this time [19]. In addition,no rapid or routine detection tests are available to facilitate earlydiagnosis. Given the rarity of C. sordellii fasciitis, we do not believethe development and implementation of an early detection assay forC. sordellii would be a cost-effective addition to the management ofneonatal omphalitis. Rather, the authors recommend close obser-vation and a low threshold for aggressive surgical debridement ininfants who develop clinical features of C. sordellii infection.

3. Conclusion

Necrotizing infections are rare sequelae of omphalitis with highmorbidity andmortality. We present a case of C. sordellii necrotizingomphalitis, highlighting its unique clinical features, includingmassive capillary leak, hemoconcentration, and marked leukocy-tosis in the absence of fevers. C. sordellii infections are associatedwith significant mortality in the reported literature with featuresarising from overwhelming toxin production. Clinicians shouldhave a high degree of clinical suspicion for C. sordellii in the settingof these clinical features. Broad-spectrum antibiotics, early surgicaldebridement, and supportive care are the mainstays of currenttherapeutics. Commercially available antitoxins are currently

lacking but represent an opportunity to improve outcomes of thisrare infection.

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