CHAPTER 10 Case Series and Review of the Literature of Mycobacterium chelonae Infections of the Lower Extremities Edmund Yu, DPM Patricia Forg, DPM Nancy F. Crum-Cianflone, MD, MPH INTRODUCTION outbreaks of rapid growing NTM infections (M chelonae, M abscessus) linked to water exposure in the context of pedicures Mycobacterial infections include Mycobacterium tuberculosis or recent surgery/trauma (10-13). complex (e.g., M tuberculosis, Mycobacterium bovis, Mycobacterium The clinical manifestations of M chelonae infections include leprae), Mycobacterium avium complex (MAC), and other skin/soft tissue or skeletal (tendon, joint, bone) infections non-tuberculosis mycobacteria (NTM), the latter of which after local inoculation of the organism. Examination findings includes over 150 diverse species. NTM are differentiated can resemble cellulitis, subcutaneous abscesses, or multiple from mycobacteria that cause tuberculosis because they are vesicular lesions (1), however there are no pathognomonic not spread by human-to-human transmission, rather are signs to differentiate it from other microbiologic causes ubiquitous in the environment including water, soil, and (6,14). Their proliferation can be masked within a chronic plant material, with tap water being considered the major non-healing wound or a prior non-healing surgical site. The reservoir for human infections (1). Routes of infection include non-pathognomonic and often indolent findings associated cutaneous inoculation including in the setting of open wounds. with M chelonae infections signify the need for a thorough Organisms are identified as acid-fast bacilli (AFB) positive on clinical and diagnostic work-up for their identification. This staining and subsequent growth on specialized mycobacterium includes early clinical suspicion and collection of mycobacterial culture media (2,3). NTM were classically categorized by cultures and acid fast stains to achieve early diagnosis and to growth rate (rapid, immediate, or slow-growing species) help prevent progressive disease including bone and joint and colony characteristics including pigmentation (e.g., involvement (8). Runyon System); however, today isolates are increasingly This article consists of a case series illustrating the identified using molecular systems (3-5). Rapidly growing importance of considering M chelonae infections in the mycobacteria (defined as mature growth on plates by <7 days) diagnosis of non-healing infections of the feet that develop include 6 specific complexes and include pigmented and non- in the setting of prior trauma/surgery and environmental pigmented pathogenic species. Mycobacterium chelonae is a non- exposures. Multiple AFB tissue cultures and antimicrobial pigmented, rapid-grower closely related to the Mycobacterium susceptibility testing should be obtained for making the abscessus group (6). diagnosis and directing optimal antimicrobial therapy. We The incidence of NTM infections, including rapid also conducted a comprehensive review of the literature of growers, have significantly increased since they were M chelonae infections occurring in the feet/lower extremities identified as human pathogens in 1950 (3). For example, published since 1946 to summarize the predisposing since 1981, the rates of NTM infections have risen to an conditions, clinical manifestations, treatment approaches, estimated 1.8 cases/100,000 person-years, however, the and outcomes of this rare but emerging clinical entity. exact number of annual cases in the US is unknown since While the number of atypical mycobacterium infections are NTM infections are not reportable conditions (7). The increasing, there is a paucity of detailed and systemically rising incidence may be related to an increasing number summarized data on M chelonae infections in the current of immunosuppressed persons as well as environmental published literature. exposures (3,8). NTM produce a protective biofilm in aquatic environments that allows them to withstand harsh CASE 1 conditions and persist in water collection and piping systems. Additionally, their resistance to sterilizing agents An 86-year-old man with a medical history of hypothyroidism such as formaldehyde and household disinfectants makes and dementia presented with pain and erythema of his left them formidable pathogens (9). Studies have shown foot. He had received 2 courses of oral cephalexin (14 increasing incidences of NTM released from piped water days) with no notable improvement in May 2017. Four systems in both public and household water supplies leading weeks after the initial development of his foot pain and to an increased risk of exposure (1,9). This is exemplified by erythema, he presented to the emergency department and 44 CHAPTER 10 was admitted in June 2017. Examination revealed normal aspiration of a lesion on the left foot and blood cultures vital signs with a temperature of 36.5C. An examination of were both negative. A magnetic resonance image (MRI) of the left foot revealed pain on range of motion of the second the left foot demonstrated mild tenosynovitis of the anterior digit and multiple vesicular lesions and erythema localized tibialis tendon near the navicular bone. He was empirically to the midfoot (Figure 1). Standard left foot radiographs treated with intravenous cefazolin and vancomycin for 5 showed no evidence of soft tissue or osseous abnormalities days, followed by 14 days of intravenous vancomycin and (Figure 2). Initial white blood cell (WBC) count was 11.4 ciprofloxacin with only mild improvement. x 103/μl (93% neutrophils), the C-reactive protein (CRP) The patient returned to the emergency department 4 level was 11.9 mg/liter, and the erythrocyte sedimentation times after the initial hospitalization for similar symptoms. rate (ESR) was 42 mm/hour. Bacterial wound cultures from He was again prescribed a variety of antibiotics including amoxicillin/clavulanic acid and doxycycline, which provided Figure 2A. Nonweightbearing lateral radiograph of left foot, and B, Non- weightbearing medial oblique radiograph of left foot demonstrating no soft tissue gas or osseous abnormality. Figure 1A. View of patient’s left foot demonstrating multiple vesicular lesions; B, Extent of erythema marked with a pen up to level of the distal leg. Figure 3A. Coronal T2-weighted view of the left foot demonstrating a Figure 4A. Multiple firm vesicular lesions on dorsal left foot 8.1 mm-sized fluid collection bewteen the first and second metatarsals. refractory to prior multiple courses of standard antibiotic therapies. B, Saggital T2-weighted view of the left foot demonstrating trace B, 2ml sanguineous bedside aspiration from the lesion at base of peripheral enhancement and edema of the extensor hallucis longus second digit. tendon. CHAPTER 10 45 only minimal improvement. Ultimately, numerous vesicular after 8 weeks of therapy due to thrombocytopenia, a known lesions with increased erythematous changes to the left side effect associated with its prolonged use. The patient lower extremity warranted a second hospital admission 6 responded well to the treatment plan with near resolution of months later. All laboratory markers including WBC, CRP, the wounds at 12 weeks postoperatively without evidence of ESR, and uric acid were within normal limits. A repeat MRI recurrence (Figure 7). He has finished his course of antibiotics of the left lower extremity was obtained revealing additional (imipenem and azithromycin) in June of 2018 and continues findings including tenosynovitis of the extensor hallucis to have monthly follow-up visits with no new symptoms. longus tendon and trace fluid collection between bases of the first and second metatarsals (Figure 3). A bedside aspiration of the largest vesicular lesion at the base of the second digit (Figure 4) was negative for bacterial organisms and crystals. Upon further history, the patient recalled that his foot condition began as a small pruritic lesion that started in between his hallux and second digit of the left foot with subsequent water exposure of this area. The patient consented to surgical debridement with cultures for bacterial, fungal, Nocardia, and AFB, as well as pathology. Intraoperative findings included a small pocket of necrotic tissue in the first interspace. The postoperative appearance is shown in Figure 5. The histological findings from the samples showed neutrophil aggregation and poorly formed granulomas with central microabscesses (Figure 6). AFB cultures grew M chelonae with susceptibilities to tobramycin, imipenem, clarithromycin, and linezolid. The patient was started on intravenous imipenem 500 mg every 6 hours, azithromycin 250 mg oral daily, and linezolid 600 mg oral daily due to the extent of infection and the fact that complete resection was not possible. Linezolid was stopped Figure 5. Postoperative day 1 following surgical debridement of left foot for obtaining intra-operative soft tissue cultures. Figure 6. Hematoxylin and eosin stain. A, High resolution, 10x magnification of a soft tissue pathology sample from the left foot first interspace> Arrow indicates a poorly formed granuloma and Figure 7. Left foot 3 months after surrounding neutrophils. B, Low resolution, 4x surgical debridement while receiving magnification of the above same finding. anti-mycobacterial therapy. 46 CHAPTER 10 CASE 2 be nearly or fully resected and he had no other cutaneous findings, therapy with azithromycin 500 mg oral daily alone A 72-year-old man with a medical history of well-controlled was commenced with a planned