Cellulitis and Abscess in a 2-Year-Old’s Cheek: Cutaneous Nocardia Infection

Two days before presenting to his primary care pediatrician, a previously well, 27-month-old boy had developed a solitary papule below his left eye, which soon became pustular with surrounding cellulitis. At no time during his illness had the boy been febrile. His mother initially did not recall any insect bite or facial trauma in the recent past, and he had never been ill with a deep tissue infection.

A culture of the serous drainage was obtained, but no organisms were seen on the 5% sheep blood agar plate after 48 hours of incubation. Cephalexin suspension was prescribed at 40 mg/kg/day in 3 divided doses. However, during the following 2 days, the area of cellulitis advanced, and the lower eyelid became very swollen. The child was taken to a pediatric emergency department and was admitted to the hospital.

At admission, his vital signs included the following: temporal artery temperature, 38°C; heart rate, 153 beats/min; respiratory rate, 28 breaths/min; and blood pressure, 116/73 mm Hg. A 1 × 3-cm area of erythema was present below the boy’s left eye, with swelling and warmth over a draining abscess (Photo). There was no proptosis and no loss of extraocular muscle mobility. The rest of the physical examination findings were unremarkable.

Results of a complete blood count at admission showed elevations of total leukocytes (white blood cell count, 18,270/µL) and absolute neutrophils (13,000/µL). Monocytes (18%), hemoglobin level, and platelet count were normal. A sonographic image of the left cheek revealed a small abscess cavity measuring 4 × 2 × 5 mm. The following morning, the abscess was incised, drained, and debrided. Purulent material obtained from the cavity was processed in the hospital microbiology laboratory.

Hospital Course

Ten days after admission, the inoculated area of a Sabouraud agar plate grew an organism that initially was believed to be fungal but soon was correctly identified as Nocardia bacteria, later speciated as Nocardia brasiliensis.

On further questioning, the boy’s mother recalled that several weeks ago, he had been quarreling with another child at day care over who should play with a toy truck. The boy had sustained an abrasion injury to his left fourth metacarpophalangeal joint. He had been observed several times to be sucking the injured area. The abraded skin soon formed a papulopustular lesion, which had healed spontaneously.

After surgical drainage, the appearance of the left cheek and lower eyelid markedly improved. There was no palpable regional lymphadenopathy, and the child was in no pain. The rest of the physical examination findings were normal. Orally administered trimethoprim-sulfamethoxazole (TMP-SMX), 20 mg/kg/day in 2 divided doses for a 3-month duration, was prescribed by his primary care physician after consultation with a pediatric infectious disease specialist.

The results of imaging studies, including chest radiographs and contrast-enhanced magnetic resonance imaging (MRI), to look for silent brain abscess were normal. Because N brasiliensis is a unique pathogen in our hospital and is strongly associated with chronic granulomatous disease (CGD) in children, a pediatric immunologist was consulted. Whole blood was obtained and sent for neutrophil oxidative burst testing, the results of which were negative for CGD.

Discussion

Long considered of fungal origin, Nocardia, a large group of several hundred ubiquitous obligate aerobic organisms in the Actinomycetales order, are long, delicate, rod-shaped, weakly gram-positive, moderately acid-fast rod-shaped bacteria (confirmed by gene sequence molecular analysis) that in vitro have the gross appearance of yeast colonies with delicate pseudohyphae.¹

Unusual skin pathogens such as N brasiliensis should be suspected when a traumatic, draining abscess does not respond to the recommended therapeutic measures. Nocardia are rather slow-growing on synthetic media, taking at least 3 days to become visible on the agar surface. After 48 hours of incubation, no growth will have occurred on a blood agar culture plate. A Gram-stained preparation of purulent material often will contain gram-positive, delicate, branching pseudohyphae. A modified acid-fast stain with 1% sulfuric acid and no alcohol is recommended to complement the Gram stain and to identify acid-fastness of the organism, an important identifying feature of nocardiosis. Because a single Gram-stained smear and simultaneous culture are both positive only a third of the time, multiple culture specimens should be taken, including purulent material and also a scraping from the base of the infection.²

The Gram-stained surface pseudohyphae display a characteristic branching, beaded appearance (we call it a positive “buckyball sign”). Some of the older pseudohyphae will have fragmented into small bacillary (rod) or coccoid forms. Pseudohyphae can be seen growing on the agar surface, into the substrate, or both. Should pathogenic Nocardia species be strongly suspected, a positive modified acid-fast (modified by 1% sulfuric acid instead of acid/alcohol stain) or Gomori methenamine-silver stain of a clinical specimen can be ordered. Sabouraud agar or improved specific Nocardia agar plates containing buffered charcoal-yeast extract (similar to Pneumocystis agar) will enhance optimal growth compared with 5% sheep blood agar.

Nocardia are saprophytes living in soil, dust (including household dust), decaying vegetable matter, or freshwater lakes and rivers that are rich in organic matter.² Pathogenic Nocardia comprise at least 30 of the several hundred distinct species. Approximately 60% of human nocardiosis cases occur in immunocompromised individuals.¹ The clinical, microbiologic, and antibiotic resistance patterns of Nocardia species vary. The most common pathogenic species previously had been grouped in the Nocardia asteroides complex; current correct terminology now comprises approximately 6 specific species, including N asteroides sensu strico, Nocardia abscessus, Nocardia nova, Nocardia farcinica, and others.

Deep systemic nocardiosis originates with inhalation into the bronchial tree of spores from N abscessus, N nova, or N farcinica.² Approximately 30% of cases of pulmonary nocardiosis spread to the brain.³ Therefore, several investigators have recommended that all children with pulmonary nocardiosis should have MRI of the brain to detect indolent silent brain abscesses.⁴ Deep intracellular Nocardia infections occur primarily in persons who are immunodeficient or immunosuppressed during corticosteroid therapy or chemotherapy, after solid organ transplantation, and in those with diabetes mellitus, autoimmune disease, T-cell deficiency, HIV infection, and lymphoreticular neoplasia, as well as in children with neutrophil dysfunction, notably CGD. Antibiotic susceptibility results differ among the 30 or so pathogenic Nocardia species, especially with deep tissue infections. Deep Nocardia infections have a strong tendency to relapse or metastasize; as such, 6- to 12-month or longer courses of effective antibiotic combinations should be prescribed for nocardiosis of the lung or brain.

Infections caused by N brasiliensis in a normal host usually are uncomplicated, localized, suppurative, cutaneous infections. N brasiliensis almost always is susceptible to TMP-SMX.^5-8

Nocardia Cutaneous Infections

Smego and Gallis reviewed the medical literature in 1984 and identified 46 cases of N brasiliensis infection in children and adults.⁷ Prerequisites include a Nocardia-contaminated break in the epidermal-dermal barrier from an abrasion, a thorn puncture, wood splinters, a laceration, or a contaminated scratched insect bite.^7,9,10 Fergie and Purcell described 31 children with cutaneous infection caused by N brasiliensis.⁵

The 3 types of N brasiliensis cutaneous infections are superficial, lymphocutaneous, and mycetoma. Superficial cellulitis, pustular lesions, or abscesses are the most frequent cutaneous clinical presentation of N brasiliensis infection. An uncommon, atypical cervicofacial variant of cutaneous nocardiosis also has been described.

The second most common clinical presentation of skin infection is lymphocutaneous linear lesions resembling sporotrichosis (Sporothrix schenckii) or swimming pool granuloma (Mycobacterium marinum). Other organisms that can produce similar skin lesions include Bacillus anthracis, cutaneous Corynebacterium diphtheriae, Francisella tularensis, and Leishmania donovani. Lymphocutaneous nocardiosis comprises papules and pustules, plus nodules, lymphangitis streaking, and palpable, painful, regional lymphadenitis. The nodules are granulomatous abscesses that originate in the wall of delicate cutaneous lymphatic vessels.

The third presentation is mycetoma, a chronic, progressive, slowly growing destructive infection that spreads along fascial planes. It presents as an indurated, tumor-like granulomatous lesion, usually on a foot. Nocardia mycetomas contain tiny, yellow or white, granular, gritty masses of dense, branching pseudomycelia radiating from a central core. Sulfur granules, as these are called, are prone to form draining sinus or fistulous tracts in the upper or lower extremity.⁷ Careful surgical debridement is necessary, because aspiration will not provide adequate drainage of mycetomas. To prevent local recurrence of mycetoma, TMP-SMX therapy is extended to 1 year or more.¹¹

Cutaneous N brasiliensis infections are not contagious to an immunocompetent caretaker or to young children.¹

Antibiotic Treatment for Cutaneous Infection

Localized cutaneous abscesses or granulomatous lymphocutaneous infections usually respond to a 6- to 12-week course of TMP-SMX monotherapy (50 mg/kg/day in 2 divided doses of the SMX component). It is the drug of choice for cutaneous nocardiosis. Cure rates with TMP-SMX for localized cutaneous disease approach 100%.² After initiation of targeted antibiotic therapy, clinical improvement can be expected within 10 days. Minocycline (100-200 mg/day in 2 divided doses) is an alternative oral antibiotic choice for N brasiliensis infection. Linezolid, a costly oral antibiotic that is uniformly effective against all Nocardia strains in vitro, may cause serious hematologic adverse events or neurotoxicity with a duration of treatment greater than a few weeks.

Salma Haneef, MD, is a pediatric resident at Inova Children’s Hospital in Fairfax, Virginia.

Richard H. Schwartz, MD, is a pediatrician at Inova Children’s Hospital in Fairfax, Virginia.

Rebecca Levorson, MD, is a pediatric infectious disease specialist at Inova Children’s Hospital in Fairfax, Virginia.

References

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