Surgical site infection due to <i>Mycobacterium fortuitum</i> in a lung transplant recipient

Dear Editor, Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and lung infections are the most common manifestation in the general population.1 In contrast, surgical site infections (SSIs) are uncommon manifestations among NTM infections.2 Solid organ transplant (SOT) recipients are at higher risk of SSIs due to the surgical complexity of transplant procedures, intense immunosuppression especially early after transplant surgeries, and comorbidities.3 Nonetheless, NTM are rare causes of SSIs after SOT.3 Here, we report a case of SSI involving rib osteomyelitis due to Mycobacterium fortuitum after lung transplant with a literature review. A 54-year-old Japanese man with a history of bilateral lung transplant presented to the transplant surgery clinic with a persistent discharge from small nonhealing surgical wounds at the right chest wall. Six months earlier, he had undergone a bilateral lung transplant from a cadaveric donor for chronic respiratory failure secondary to idiopathic pulmonary fibrosis. The post-transplant course was uneventful except that his surgical wound on the right chest wall was slow to heal and eventually developed pain and discharge from the wound. He was discharged home on post-transplant day 38 in a stable condition. After discharge, he continued to have pain and discharge from the wound but no swelling, or redness over the months. The discharge fluid obtained on post-transplant day 249 was sent for culture and grew acid-fast bacilli after 5 days. It was later identified as M. fortuitum using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Biotyper (Library version 6.0, Bruker Daltonics); therefore, he was called in for antimycobacterial treatment on post-transplant day 256. His past medical history included pneumothorax and herpes zoster. His immunosuppressive regimen consisting of methylprednisolone 250 mg daily, mycophenolate mofetil 1000 mg daily, and tacrolimus 0.7 mg daily was started at the time of transplantation. Their doses were slowly reduced to prednisolone 5 mg daily, mycophenolate mofetil 500 mg daily, and tacrolimus 0.4 mg daily upon this presentation. He had no allergy and did not consume alcohol, cigarettes, or recreational drugs. On admission, he was afebrile, and other vital signs were normal. Physical examination was remarkable for small nonhealing surgical wounds on the suture line at the right chest wall with a small amount of purulent discharge noted on the dressing. There was no swelling or erythema but tenderness to the right 5th rib. Laboratory examination revealed white blood cell counts of 4900/mL and a C-reactive protein level of 0.15 mg/dL (reference, 0−0.3 mg/dL). Renal and liver functions were within normal limits. An X-ray of the chest was unrevealing. A magnetic resonance imaging with intravenous contrast showed a decreased signal on T1 images and an increased signal on T2 images at the right 5th rib beneath the surgical wound compatible with rib osteomyelitis (Figure 1). A diagnosis of SSI involving right rib osteomyelitis caused by M. fortuitum was made. The susceptibility test of M. fortuitum was performed using a microdilution method, BrothMIC RGM (Kyokuto Pharmaceutical Industrial Co.). The isolate was susceptible to imipenem, meropenem, amikacin, moxifloxacin, and linezolid based on the Clinical & Laboratory Standards Institute M62 Ed1.4 Minimum inhibitory concentrations of levofloxacin and clofazimine were less than 1 and 0.25 µg/mL, respectively. A combination of intravenous imipenem-cilastatin 2 g daily and intravenous levofloxacin 500 mg daily was initiated on post-transplant day 258. Intravenous levofloxacin was switched to oral levofloxacin due to phlebitis on treatment post-transplant day 260. On post-transplant day 262, oral linezolid 600 mg daily and oral clofazimine 100 mg daily were added. On post-transplant day 278, linezolid was discontinued due to thrombocytopenia with platelet counts of 41000/µL. On post-transplant day 288, imipenem-cilastatin was discontinued because of intractable nausea. After recovery of platelet counts, oral linezolid 300 mg daily was reinstituted on post-transplant day 293. However, he developed intractable abdominal pain and nausea; therefore, linezolid was discontinued on post-transplant day 317. We switched levofloxacin to moxifloxacin on post-transplant day 343 without improvement of symptoms. The decision was made to discontinue oral moxifloxacin and clofazimine on post-transplant day 349 after 91 days of antimycobacterial treatment. The investigation including colonoscopy was unremarkable. He was discharged home on post-transplant day 407. The surgical wound slowly healed over the course of treatment and completely resolved without discharge or tenderness at the completion of the antimycobacterial treatment. Abdominal pain and nausea slowly improved after discharge. He had no recurrence of rib osteomyelitis at the 1-year follow-up. NTM are uncommon but important pathogen for SOT recipients, especially for lung transplant recipients given NTM's predisposition to the airway. NTM can remain colonized but can also result in clinical disease. While gram-positive bacteria accounted for the majority, followed by gram-negative bacteria, and yeast,3 NTM are uncommon pathogens for SSI. Our literature review on SSIs due to NTM after SOT found five studies and three case reports (Table 1).3, 5-11 Overall, NTM accounted for 1.5−3.2% of causative pathogens. This could be an underestimate as the proportion of culture-negative SSIs was variable and testing with mycobacterial culture might not have been systematically performed. Mycobacterium abscessus was the most common species and lung transplant recipients were the most common host reported.12 It is perceivable because lung transplant recipients are more often colonized with NTM before transplantation due to structural problem from underlying pulmonary disease and, therefore, at a higher risk for progression to clinical disease after transplantation.12 Of note, our patient did not have colonization before transplantation. Lung 553 Heart 282 Lung 1 Heart 1 Treatment for SSI due to NTM is challenging for several reasons: (i) the species are often susceptible to the limited number of agents; (ii) the treatment constitutes at least two active agents with in vitro activity; and (iii) the treatment has to be continued for months.12 It is more problematic in SOT recipients given their immunosuppressive status, interaction between macrolides and calcineurin inhibitors or and mammalian target of rapamycin, and increased chance of adverse events such as nephrotoxicity and gastrointestinal symptoms13 as illustrated in our case. Because we anticipated the prolonged course of oral treatment in the setting of limited number of agents susceptible and acknowledged the time to achieve its effective concentration,14 we elected to use clofazimine upfront in our patient. While its use has been increasingly used for multi-drug-resistant tuberculosis and pulmonary NTM infections, mainly with Mycobacterium avium complex and M. abscessus,13, 15 data on its use for extrapulmonary disease or infections with other NTMs is scarce. Although it was discontinued together with other medication after 3 months in our patient, clofazimine may be an option for long-term oral treatment for extrapulmonary NTM infections, with limited treatment options. In conclusion, we report a case of SSI concomitant with rib osteomyelitis caused by M. fortuitum after lung transplant which was successfully treated with clofazimine-containing regimen for 3 months. Transplant physicians should be vigilant of SSI due to NTM, uncommon but important causative agents. In addition, considering the drug−drug interactions and adverse drug events, clofazimine may be an option for extrapulmonary NTM infections in this challenging population. MA-K and KO conceived the study. MA-K, KO, and CK were responsible for the clinical management of the patient. All authors revised the drafts and approved the final manuscript. We thank Yoshimi Higurashi and Yusuke Nomura for performing the microbiological analysis. Data sharing is not applicable to this article as no new data were created or analyzed in this study.