Hematogenous Osteoarticular Infection Due to Clostridium innocuum in an Adolescent With Sickle Cell Disease

To the Editors: Pediatric osteoarticular infections typically result from hematogenous spread due to gram-positive aerobes like Staphylococcus aureus or Streptococcus pyogenes. Infections due to anaerobic gram positives are less commonly reported and, when reported, are typically associated with polymicrobial infection in the setting of trauma, hardware placement or contiguous spread.1 We describe an adolescent with sickle cell disease (hemoglobin SS) who developed acute hematogenous osteomyelitis (AHO) due to Clostridium innocuum without preceding gastrointestinal illness or trauma. A 17-year-old male with hemoglobin SS disease presented with a 1-week history of bilateral hip and thigh pain and a 1-day history of fever to 103°F. Laboratory studies revealed an elevated white blood cell count (12.4 × 109/L, 80% neutrophils) and C-reactive protein (19 mg/dL). Contrasted magnetic resonance imaging demonstrated multifocal and bone marrow signal abnormalities within bilateral femurs and left iliac bone, including a right femoral subperiosteal abscess on post-contrast T1-weighted imaging, a mild left hip and mild bilateral knee joint effusions with enhancement of the synovium (Fig. 1). Ultrasound-guided aspiration and biopsy of the right femur demonstrated acute inflammatory changes consistent with osteomyelitis. Both culture and 16S rRNA gene polymerase chain reaction (PCR) of the femur biopsy specimen identified C. innocuum. The left hip and bilateral knee effusions were also drained, and cultures were negative, but PCR testing from the left hip also revealed C. innocuum. Two peripheral blood cultures obtained 12 hours apart were also positive for C. innocuum within 24 hours of collection. He was started on metronidazole therapy with subsequent negative peripheral blood cultures. A transthoracic echocardiogram showed no evidence of endocarditis, and due to rapid clearance of bacteremia and good cardiac windows, a transesophageal echocardiogram was not pursued. He denied gastrointestinal or dental complaints, and an abdominal ultrasound was unrevealing. The patient underwent incision and drainage of the subperiosteal abscess and drainage of bilateral knee and left hip effusions. He received treatment for sickle cell pain crisis and was subsequently treated with intravenous and then oral metronidazole. C-reactive protein remained elevated at 3.8 mg/dL at 4 weeks of therapy, and given the multifocal nature of the infection, treatment was extended to a total of 6 weeks with resolution of symptoms and normalization of inflammatory markers at that time.FIGURE 1.: T1-weighted magnetic resonance imaging with contrast media gadolinium of the right femur demonstrated a 1.1 × 1.6 cm subperiosteal abscess on coronal post-contrast series.Clostridium innocuum is an intrinsically vancomycin-resistant gram-positive anaerobe that infrequently causes infection in humans.2,3 Most reported infections occur in immunocompromised patients.2–4 In 1 report, C. innocuum osteomyelitis was the cause of sepsis and pelvic osteomyelitis in an adult receiving induction chemotherapy for acute lymphoblastic leukemia, requiring more than 12 weeks of antibiotics.4 Similar to our case, the presumed mechanism of infection was hematogenous spread from the intestinal tract to the bone rather than contiguous spread. Notably, neither our patient nor the literature report had clear preceding gastrointestinal symptoms. Other cases of clostridial osteomyelitis have been reported in the literature among children with sickle cell disease, most typically Clostridioides difficile.5–8 An 11-year-old child with sickle cell disease was hospitalized with fever and right shoulder pain. Joint aspiration revealed C. difficile.8 This patient completed 5 weeks of metronidazole therapy and had no preceding diarrheal illness or positive blood cultures.8 Another adolescent with hemoglobin SS disease presented with a 6-month history of multifocal bone pain; imaging was concerning for multifocal chronic osteomyelitis, and bone biopsy revealed C. difficile despite negative stool testing and blood cultures.6 Bowel ischemia leading to hematogenous spread was suspected. Finally, in 1 report, a 15-year-old female with hemoglobin SS disease and chronic osteomyelitis was found to have C. difficile on bone biopsy for osteomyelitis. Although stool studies were negative and intra-abdominal imaging showed no source of infection, she did have chronic abdominal pain and known inflammation of the colon, and was suspected to have translocation due to ischemic bowel mucosa.7 She received 8 weeks of therapy followed by prolonged suppressive therapy given the chronic nature of the infection. Anaerobic organisms, particularly Clostridial species, should be considered in children with hemoglobin SS disease who have AHO, even in the absence of gastrointestinal symptoms. Ischemic injury of bones and intestines, combined with underlying immunodeficiency, may predispose them to anaerobic infections from the intestinal tract. Anaerobic cultures should be obtained from bone or joint fluid biopsies of children with hemoglobin SS disease to identify pathogens like C. innocuum, as most routine empiric AHO treatment would not cover this intrinsically vancomycin-resistant organism. Bacterial PCR testing from the bone biopsy also supported the diagnosis in this case and should be considered in children without bacteremia or with bacteremia with an unusual pathogen to confirm the diagnosis, particularly in children who receive antibiotics before biopsy (pretreated) or who are immunocompromised.