Successful bedaquiline-containing antimycobacterial treatment in post-traumatic skin and soft-tissue infection by Mycobacterium fortuitum complex: a case report

Abstract

Background: Mycobacterium fortuitum complex is a group of rapidly growing nontuberculous mycobacteria (NTM) associated with skin and soft-tissue infections after surgery or trauma. Treatment of NTM is challenging, due to resistance to multiple antimycobacterial agents. Bedaquiline is a diarylquinoline that inhibits mycobacterial ATP-synthase. The drug has recently been approved for the treatment of multidrug-resistant tuberculosis and evidence of its in vitro efficacy against NTM, including Mycobacterium fortuitum complex, has been published.

Case presentation: A 20-year-old Caucasian woman with chronic skin and soft tissue infection in the lower leg following a traffic accident in Vietnam underwent a tedious journey of healthcare visits, hospital admissions, empiric antimicrobial treatments, surgical debridement and plastic reconstruction before definite diagnosis of Mycobacterium fortuitum complex-infection was established by culture from a tissue biopsy and targeted antimycobacterial therapy was administered. Histopathological examination revealed granulomatous purulent inflammation, which strongly supported the diagnosis. Genotypic identification was performed and broth microdilution for susceptibility testing showed macrolide resistance. Five weeks of induction treatment with intravenous amikacin, imipenem / cilastin, and oral levofloxacin was administered, followed by all-oral treatment with bedaquiline combined with levofloxacin for four months, which was well-tolerated and led to persistent healing with scars but without signs of residual infection.

Conclusions: Bedaquiline is a promising novel agent for NTM treatment, although clinical data are limited and trials evaluating efficacy, safety, and resistance of bedaquiline are required. To our knowledge, this is the first reported case of successful in vivo use of bedaquiline for a skin and soft tissue infection caused by Mycobacterium fortuitum complex.

Keywords: Bedaquiline; Case report; Chronic wound infection; Mycobacterium fortuitum complex; Nontuberculous mycobacteria; Rapidly growing mycobacteria.

Fig. 1

Timecourse of the antimicrobial treatments, surgical procedures, diagnostics and hospital admissions. Links to the respective photos depicted in Fig. 2 have been included. CT, computer tomography; d, day; GER, Germany; LH, local hospital; metron., metronidazole; MRI, magnet resonance imaging; UH, university hospital; US, ultrasound; Nov., November; w, weeks; XR, Xray

Fig. 2

Serial images of the patient’s right foreleg. (a) Photograph taken four days after the traffic accident at a hospital in Hanoi following surgical debridement and suture of the wound. (b, c) Six weeks after the accident a firm subcutaneous nodule was noted (b), which drained spontaneously the next day (c). The soft tissue infection persisted despite four weeks of empiric antimicrobial treatment (sixth to tenth week after the accident) (d) leading to the decision to perform surgical debridement and subsequent skin grafting as well as local flap surgery 11 weeks after the trauma (e). (f) A tissue biopsy was obtained 19 weeks after the accident when abscesses and nodules reappeared within a few weeks upon surgical debridement and intravenous empiric antibiotic therapy. (g-i) After 20 weeks, antimycobacterial treatment was initiated following susceptibility testing of the identified Mycobacterium fortuitum: Photographs show the status before (g), eight weeks after antimycobacterial therapy (h) and upon completion of the four-month therapy regimen (i). The patient was followed-up, continuous improvement was noticed nine months (j), 12 months (k) and 14 months after the initial accident (l)