Abstract We describe a case of progressive cutaneous mucormycosis, which caused gangrenous necrotizing fasciitis, in an immunocompetent neonate from Oman. Extensive wound contamination and a favorable environment for the growth of Mucorales were the predisposing factors. Early aggressive management including frequent wound debridement, targeted pharmacotherapy with liposomal amphotericin B and supportive care is pivotal for improved outcomes. mucormycosis, cutaneous mucormycosis, gangrenous necrotizing fascitis, immunocompetent neonate, neonate, Oman INTRODUCTION Mucormycosis is the third most common invasive fungal infection after candidiasis and aspergillosis in all age groups . Gastrointestinal and cutaneous mucormycosis are the most common forms of mucormycosis in neonates . Cutaneous mucormycosis can be life threatening if not diagnosed early, and aggressive treatment not initiated promptly . We describe the first reported case of cutaneous mucormycosis in Oman. CASE REPORT A female neonate, 5–7 days of age, was found abandoned in a remote area in the midst of grass and stones covered by insects and ants. She was rushed to a nearby hospital by the emergency medical services. On arrival, she exuded an offensive body odor, with injuries on the scalp, abdomen and back and was lethargic, severely dehydrated, with hypothermia, bradycardia and bradypnea. After resuscitation and correction of hypoglycemia, she was transferred to the neonatal intensive care unit of Nizwa Hospital, Oman. At admission, she was a term, small for gestational age, critically ill neonate weighing 1950 g. She had 10% dehydration with a doughy feel to the skin, umbilical discharge, a right parieto-occipital hematoma, measuring 5 cm × 6 cm in size and ill-defined abrasions and wounds in the right iliac fossa and the lumbar paraspinal region. The skin over the back was parched with excoriated areas. Her body temperature was 36.5 °C, respiratory rate 36 breaths per minute, heart rate 115 per minute, blood pressure 54/39 mm Hg and oxygen saturation of 92% in room air. Respiratory, cardiovascular, abdominal and neurological examinations were unremarkable. Baseline investigations revealed neutrophilic leukocytosis, hypernatremic dehydration, deranged renal function and thrombocytopenia. Radiological investigations revealed a normal skeletal survey and an unremarkable abdominal ultrasound. Blood gas showed mixed respiratory and metabolic acidosis. Lumbar puncture was not contemplated owing to local infection. A heavy growth of Streptococcus agalactiae was recovered from the scalp abscess, umbilical swab and wound swabs from the loin. Results of serological tests for syphilis, gonorrhea and human immunodeficiency virus and ‘TORCH’ screen were negative. Her initial treatment included gradual correction of hypernatremic dehydration, broad spectrum antibiotics, local care of wounds, drainage of scalp abscess, need-based analgesia and incremental feeds. After 48 h of admission, she developed a brief tonic-clonic seizure, which was attributed to the rapid decrease in serum sodium levels during correction of hypernatremic dehydration. Blood culture revealed no bacterial or fungal growth. After initial improvement, on the fifth day of admission, a blackish discoloration (2 cm × 2 cm) was noted in the left paraspinal area in relation to thoraco-lumbar spine, which was tender without crepitus or discharge. She also developed intermittent fever (up to 39 °C). Neither did ultrasound examination show subcutaneous collection nor did KOH smear reveal fungal elements. She was started on piperacillin-tazobactam, and clindamycin was continued. However, the blackish area continued to enlarge and by seventh day of admission was 4 cm × 5 cm (Fig. 1). The neonate underwent debridement of necrotic skin and subcutaneous tissues. Tissue samples were sent for bacterial and fungal cultures. A whitish cotton like growth was seen on the surface of the debrided area with a black necrotic eschar. Although the initial KOH smear was negative for fungal elements, there was a strong suspicion of mucormycosis. Liposomal amphotericin B (5 mg.kg/day) was added to the ongoing antibiotic regimen. She underwent debridement of the wound thrice with extensive excision of necrotic areas. During the subsequent 3 days, despite aforementioned treatment, there was a relentless worsening of the wound with marked blackening and active erythematous edges (Fig. 2). She developed refractory hypotension and multi-organ failure and died on the 12th day of admission despite intensive care support. A markedly elevated C-reactive protein, progressive hypoalbuminemia and thrombocytopenia were the key laboratory markers of her deterioration. Tissue biopsy revealed typical hyphae of Mucorales with angioinvasion and tissue necrosis suggestive of invasive cutaneous mucormycosis. Fungal cultures revealed growth of Mucorales but no subtyping was possible. Biopsy and culture confirmation reports were available only postmortem. Autopsy could not be conducted owing to local customs and absence of valid consent. Fig. 1. View largeDownload slide Cutaneous mucormycosis with blackened area and pinkish red margins. Fig. 1. View largeDownload slide Cutaneous mucormycosis with blackened area and pinkish red margins. Fig. 2. View largeDownload slide ‘Hairy Pus’ with black necrotic eschar. Fig. 2. View largeDownload slide ‘Hairy Pus’ with black necrotic eschar. DISCUSSION Mucormycosis is an emerging, aggressive, rapidly progressive opportunistic infection caused by environmental fungi of the order Mucorales, family Mucoraceae, and class Zygomycetes . Cutaneous mucormycosis is the third most common form of mucormycosis after rhino-orbito-cerebral and pulmonary forms in all age groups although it is the most common form seen in children . In a review of 78 cases of cutaneous mucormycosis in all age groups, Skiada and Petrikoss (2009) reported that 28% were children and 10% were infants . Prematurity, low birth weight, corticosteroid therapy, broad spectrum antibiotic usage and local trauma to the skin are the most common predisposing factors . There are few published reports in the English literature on cutaneous mucormycosis in neonates [2, 6–9]. Clinical manifestations of cutaneous mucormycosis are variable, often resembling ecthyma gangrenosum or superficial granulomatous pyoderma . The diagnosis may be confused to be polymicrobial infections, especially because gram negative bacteria may co-exist. In most cases of cutaneous mucormycosis, there is a central blackened necrotic eschar, surrounded by pinkish purple soft tissue induration. In open wounds, mucormycosis has a cottony bread mold appearance, a clinical sign known as ‘hairy pus’ . On failure of early recognition, the lesion can progress to invade subcutaneous tissues, fasciae, muscles, tendons or bones leading to mucormycotic gangrenous cellulitis or aggressive necrotizing fasciitis, with a high mortality, as in our case . Depending on the severity, cutaneous mucormycosis is classified as localized, deep or disseminated . Two salient features of cutaneous mucormycosis are that it often occurs in immunocompetent hosts as in our case; and the fungi Apophysomyces and Saskenea are the most common species involved [1, 11, 12]. Trauma is a major trigger of cutaneous mucormycosis (posttraumatic cutaneous mucormycosis [PTM]) . Trauma could be trivial such as insect or spider bites, scorpion stings, pecking by birds, animal bites or scratches, or major such as road traffic accidents, burns, crush injuries and injuries during natural disasters [13, 14]. During trauma, implantation of fungal spores from contaminated soil occurs into damaged skin or open wound. Extensive tissue damage and poor tissue viability of soil-contaminated wounds promote acidosis and local immunosuppression, which enhance the pathogenicity of Mucorales. Bacterial co-infections should make clinicians suspect mucormycosis because it generally indicates a massive soiled contamination. Lelievre et al.  studied 122 cases of PTM. They reported that symptoms occurred at a mean age of 9.5 days after trauma, with necrosis and bacterial co-infection found in 76.2% and 41% of the cases, respectively; most patients did not present any underlying condition. Interestingly, they found that 19% of the cases occurred in the Middle East or in India. Absidia corymbifera and Apophysomyces elegans were the leading pathogens (21.1% and 31.7%, respectively) in their series . Nosocomial cutaneous mucormycosis occurs as a sequelae of iatrogenic trauma owing to intravenous (IV) access sites or long lines, adhesive tapes, Elastoplast bandages, occlusive dressings, burns, postoperative wounds and environmental contamination at construction sites of hospital expansion projects . An outbreak of cutaneous infection with Rhizopus microsporus in a nursery was reported in preterm infants in association with the use of wooden tongue depressors as splints for IV and arterial cannulation sites . Recently, an outbreak of cutaneous mucormycosis in a pediatric hospital was attributed to contaminated hospital linens . The gold standard for confirmation of diagnosis of mucormycosis is histopathological examination of the tissues, which typically shows broad, hyaline, ribbon like, pauciseptate, irregular fungal hyphae with right angle branching, accompanied by tissue necrosis and angioinvasion, which is mandatory to establish the diagnosis. Detection of typical hyphae on KOH-smeared scrapings on direct microscopy helps in preliminary diagnosis. All Mucorales grow rapidly on Sabouraud dextrose agar . However, cultures may be negative or, when positive, could represent wound contamination and not true infection. Fungal elements can be stained with Gomori methenamine-silver, Periodic acid-Schiff or calcofluor-white stains. Management of cutaneous mucormycosis includes surgical debridement, prompt antifungal therapy and supportive therapy, including control of any underlying illness. At the first suspicion of cutaneous mucormycosis, broad-spectrum antifungal therapy with liposomal amphotericin should be initiated without waiting for tissue culture/biopsy results . Debridement should be performed early, and repeated if progression continues unabated till all necrotic tissue is removed. Amputation may be required in cases of extensive cutaneous infection over extremities . Split skin grafting is required once the lesion is fully healed, usually by the tumescent technique in neonates . Posaconazole and caspofungin are suitable antifungal alternatives in selected cases [21, 22]. Negative pressure wound therapy is helpful . The newer add-on therapies such as hyperbaric oxygen, granulocyte macrophage colony stimulating factor and oral iron chelating agents hold promise for management of refractory mucormycosis . The mortality of cutaneous mucormycosis varies and is 4–10% in localized infection, 26–29% in deep extension and 83–94% in disseminated disease [5, 12]. This case underscores the need for increased awareness of cutaneous mucormycosis among pediatric health-care professionals and early, aggressive intervention to achieve better outcomes. ACKNOWLEDGMENT I thank the staff of the NICU, Department of Pediatrics and Pediatric Surgery, Nizwa Hospital who were involved in the clinical management of the neonate. REFERENCES 1 Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect 2004; 10(Suppl. 1): 31– 47. Google Scholar CrossRef Search ADS PubMed 2 Roilides E, Zaoutis TE, Walsh TJ. Invasive zygomycosis in neonates and children. Clin Microbiol Infect 2009; 15(Suppl. 5): 50– 4. 10.1111/j.1469-0691.2009.02981.x. Google Scholar CrossRef Search ADS PubMed 3 Chakrabarti A. Cutaneous zygomycosis: major concerns. Indian J Med Res 2010; 131: 739– 41. Google Scholar PubMed 4 Linder N, Keller N, Huri C, et al. 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Journal of Tropical Pediatrics – Oxford University Press
Published: Dec 15, 2017
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