Purulent Right Ankle Wound in a 3-Year-Old Boy

A 3-year-old, fully immunized, nonverbal boy with autism spectrum disorder presented to the emergency department in March with a 2-day history of a right ankle pustule and pain. The pustule had worsened despite daily washing with soap and water and topical neomycin/polymyxin B/bacitracin ointment. He remained afebrile but developed an antalgic gait and refused to bear full weight; he was still able to toe walk. Examination revealed a right lateral ankle pustule with a central punctum and surrounding 1-cm area of erythema, swelling, and tenderness. No tests or imaging were performed. Oral cephalexin and topical mupirocin were prescribed for suspected cellulitis, and he was discharged home.Despite medication adherence, the boy’s right ankle swelling, erythema, and pain worsened. He developed spontaneous drainage of purulent fluid from the wound, fever of 102 °F (38.9 °C), and refusal to bear weight, prompting a return to the emergency department 3 days later.The boy’s parents denied recent travel, preceding injury, history of skin disorders, boils or staphylococcal infection, or exposure to animals or bodies of water. He lives in Cincinnati. He had been closely observed when playing outside at parks. He had not been camping nor playing in the woods. His parents did not recall any insect bites or exposure to ticks, fleas, or arachnids.Physical examination revealed a well-appearing boy in pain with vital signs as follows: temperature 100.0 °F (37.8 °C), heart rate 152 beats/min, respiratory rate 28 breaths/min, blood pressure 97/61 mm Hg. There was a 3 × 1 cm area of erythema and induration with central skin breakdown and scant purulent drainage on the right lateral ankle just superior to the lateral malleolus (Figure 1). He refused to bear weight and resisted dorsiflexion of the right foot. He grimaced with palpation of the right gastrocnemius muscle. Movement of the right knee, right hip, and left leg was normal, and there was no inguinal lymphadenopathy. Bilateral dorsalis pedis and posterior tibial pulses were 2+, and capillary refill was 2 seconds.Laboratory studies were significant for a white blood cell (WBC) count of 17 300/μL (17.3 × 109/L) (reference range 6000–17 000/μL [6.0–17.0 × 109/L]) with an absolute neutrophil count of 12 060/ μL (12.06 × 109/L) (reference range 1500–8500/μL [1.5–8.5 × 109/L]). C-reactive protein (CRP) was 5.31 mg/dL (53.1 mg/L) (reference range ≤0.3 mg/dL [≤3 mg/L]), and erythrocyte sedimentation rate was 12 mm/h (reference range 0–10 mm/h). Gram stain of the purulent drainage demonstrated many WBCs but no organisms. Aerobic wound and blood cultures were sent. Right ankle radiograph showed soft-tissue swelling without fracture or osseous erosion. Due to treatment failure on cephalexin and inability to walk, the boy was admitted to the hospital.Initial differential diagnosis focused on cellulitis, osteomyelitis, septic arthritis, and/or necrotizing fasciitis. Upon admission, intravenous (IV) clindamycin (40 mg/kg/d) was initiated to cover for methicillin-resistant Staphylococcusaureus and anaerobes. His pain was controlled with scheduled acetaminophen and ibuprofen. With the unremarkable exposure history, nontuberculous mycobacterial and fungal infections seemed less likely. His medical history was not suggestive of immunodeficiency. Given his inability to bear weight, there was concern for progression to osteomyelitis or septic arthritis. Necrotizing fasciitis was considered; however, the lack of rapidly progressing erythema and absence of soft-tissue crepitus and vesicular or bullous lesions reassured against this diagnosis.On hospital day (HD) 1, a sedated magnetic resonance imaging was ordered to better characterize the lesion and help determine an adequate empirical treatment. It revealed extensive soft-tissue cellulitis with myofasciitis (Figures 2 and 3) extending from the distal right thigh to the ankle joint and significant right inguinal and popliteal lymphadenopathy with necrotic components (Figures 4 and 5). There was no evidence of osteomyelitis or septic arthritis. Given the degree of involvement and concern for progression to necrotizing soft-tissue infection, plastic surgery was consulted, which recommended chlorhexidine gluconate soaks and warm compresses to the right ankle, as tolerated, with close monitoring.On HD 2, the blood and wound cultures remained negative. Repeat CRP was 5.6 mg/dL (56 mg/L). The child remained afebrile and hemodynamically stable on IV clindamycin; however, his right ankle wound had minimal improvement. Gram stain of the purulent drainage again demonstrated WBCs but no organisms. A repeat aerobic wound culture was sent. The infectious disease service was consulted and recommended adding rifampin (20 mg/kg/d) for improved tissue penetration.By HD 3, the erythema and drainage had decreased. Repeat CRP was 3.6 mg/dL (36 mg/L). Aerobic wound cultures on blood and chocolate agar plates grew dry, cream-colored, pitted colonies, and Gram stain revealed beaded Gram-positive branching rods. The organism was acid fast on modified Ziehl-Neelsen stain, suggesting Nocardia. The boy was diagnosed with primary lymphocutaneous nocardiosis, likely acquired through an unrecognized penetrating injury with environmental contamination given the presence of a central punctum on first presentation.Nocardia are Gram-stain–positive, aerobic, filamentous bacilli that are ubiquitous saprophytes found in water, soil, and decaying organic matter.1 Immunocompetent individuals typically acquire Nocardia through traumatic inoculation of the skin and soft tissues, which results in cutaneous or ascending lymphocutaneous disease. Nocardia often acts as an opportunistic pathogen in immunocompromised hosts. It is often acquired through inhalation of dust particles resulting in pulmonary nocardiosis and can have hematogenous dissemination to the bone, brain, or skin.2–4 Those with T-cell–mediated immune dysfunction (eg, transplant patients receiving immunosuppressive medications, patients with HIV infection, patients on chronic high-dose corticosteroid therapy or calcineurin inhibitors) and neutrophil defects (eg, chronic granulomatous disease [CGD]) are at greatest risk of pulmonary or disseminated disease.1–3,5 Skin and soft-tissue infections can also be seen in immunocompromised individuals.2Isolation of Nocardia species from appropriate clinical specimens (eg, wound drainage with cutaneous disease or respiratory specimens with pulmonary disease) confirms the diagnosis.1Nocardia stains Gram-stain positive and weakly or partially “acid fast” by modified Kinyoun or Ziehl-Neelsen staining with light microscopy.6 Species identification and susceptibility reports usually require testing in a reference laboratory.7Trimethoprim/sulfamethoxazole (TMP/SMX) is the antibiotic of choice for empirical treatment of localized or mild Nocardia infections.1 However, certain Nocardia species, including Nocardia farcinica and Nocardia nova, may have intrinsic resistance to TMP/SMX.8,9 Therefore, combination antibiotic therapy is recommended for empirical treatment of immunocompromised patients and those with serious disease (eg, pulmonary, central nervous system, or disseminated disease) until identification and susceptibilities return.1 Identification of the specific Nocardia species can aid in choosing the second antibiotic to overcome resistance.Primary cutaneous and lymphocutaneous infections are most often associated with Nocardia brasiliensis.4 Immunocompetent individuals usually improve after 6 to 12 weeks of TMP/SMX monotherapy.1Immunocompromised patients with pulmonary disease should have cerebrospinal fluid and/or neuroimaging studies because Nocardia has a propensity for hematogenous spread to the brain.1 If brain abscesses are present, antibiotics that cross the blood–brain barrier (eg, TMP/SMX, carbapenems) are recommended.2 Immunocompromised patients and those with serious infections are treated for at least 6 to 12 months and for at least 3 months after apparent cure due to the propensity for relapse.1The second wound culture also grew Nocardia after approximately 72 hours of incubation. The blood culture remained sterile. Clindamycin and rifampin were stopped on HD 3. The severity of infection, association of Nocardia infections with CGD, and the boy’s young age raised concern for possible immunodeficiency. As such, the infectious disease team recommended initiation of dual therapy with oral TMP/SMX (15 mg/kg/d) and IV ceftriaxone (50 mg/kg/d) until further identification and susceptibilities returned. On HD 5, the wound culture identified N brasiliensis, which was unexpected given that this species is most often associated with tropical and subtropical environments,10 and he had not traveled to these areas. Given most strains of N brasiliensis are susceptible to amoxicillin/clavulanate,4,8,9 coupled with its excellent bioavailability, the infectious disease team recommended transitioning from IV ceftriaxone to oral amoxicillin (90 mg/kg/d)/clavulanate to continue dual therapy with TMP/SMX until immunologic testing (flow cytometric neutrophil oxidative burst and pneumococcal titers) and susceptibilities returned. He was discharged home on HD 6 to continue dual therapy.Flow cytometric neutrophil oxidative burst was normal, and he had appropriate pneumococcal antibody titers in response to his prior pneumococcal conjugate (13-valent) vaccine series. Based on these results, the boy was deemed immunocompetent. Susceptibility testing at the University of Texas Health Center at Tyler, Department of Microbiology Research, Mycobacteria/Nocardia Laboratory confirmed the isolate as N brasiliensis susceptible to TMP/SMX, amoxicillin/clavulanate, linezolid, tobramycin, and moxifloxacin 8 days after discharge.11 Amoxicillin/clavulanate was stopped. CRP level after 18 days of appropriate antibiotics was normal. The boy completed 3 months of TMP/SMX, and the wound healed without complication.Consider Nocardia infection in patients with persistent symptoms of pneumonia, cavitary lung lesions on imaging, and/or skin findings that may be associated with soil-contaminated trauma, such as pustules, penetrating injury, abscesses, cellulitis, and lymphangitis.Individuals with T-cell impairments (eg, bone marrow and solid organ transplant recipients on immunosuppressive medications, patients with HIV, those with history of cytomegalovirus, those on high-dose corticosteroid therapy or calcineurin inhibitors) or CGD are at highest risk of infection and disseminated disease.Due to the neurotropic nature of Nocardia and propensity for hematogenous spread, patients with suspected or confirmed Nocardia infection require thorough evaluation for disseminated disease and consideration of immunodeficiency.TMP/SMX is the antibiotic of choice for empirical treatment of localized or mild Nocardia infections. In the case of immunocompromised individuals or serious disease, combination antibiotic therapy is recommended until susceptibilities result.