Mycobacterium mantenii (M. mantenii) is a slow-growing non-tuberculous mycobacterial (NTM) species first described as a human pathogen in 2009.[[1]] Information regarding the spectrum of clinical presentation, pathogenicity and geographic distribution of this rare mycobacterial species is scarce. M. mantenii has not previously been reported to be a cause of human disease in the southern hemisphere. We therefore report the case of a woman with a chronic non-healing ulcer due to M. mantenii infection.

Case report

A 43-year-old, immunocompetent woman presented with an eight-month history of a non-healing ulcer on her right and dominant hand. Twelve months earlier she sustained a flap-laceration to the dorsal surface of the hand while drying a glass tumbler. The wound was sutured in the emergency department on the day of the injury. No radio-opaque foreign body or bony injury was evident on plain X-ray. The wound repair failed within a week. The patient left the wound open but dressed until she was seen by her general practitioner, who re-sutured the wound one month later. Once again the sutures broke down. Multiple courses of beta-lactam antibiotics were prescribed, which all failed to result in healing. Four months later she underwent excision of the ulcer and transposition flap repair. Despite initial complete healing of the surgical wound, a new ulcer appeared at the wound edge several weeks after the surgery.

Twelve months after the initial injury, assessment in a dermatology clinic revealed a deep inflammatory ulcer characterised by exquisite tenderness and significant limitation of movement of the hand (Figure 1). The clinical impression was of an atypical mycobacterial or deep fungal infection. Foreign body retention was excluded by repeat plain X-ray of the hand, ultrasound and cone beam CT. Skin biopsy revealed ulceration with a chronic mixed inflammatory cell infiltrate. There were no granulomata. No organisms were identified on Ziehl–Nielsen, Wade–Fite or periodic acid–Schiff staining.

Figure 1: Ulcerated lesion with significant inflammatory response at presentation.

Biopsy tissue was concurrently sent for mycobacterial PCR (Anyplex plus MTB/NTM, Seegene Incorporated, Korea). This detected non-tuberculous mycobacterial DNA. After five weeks, culture (MGIT 960 system, Becton-Dickinson and Company, Sparks, USA) growth of a yellow pigmented organism was observed. The isolate was identified by sequencing of the 16S ribosomal RNA gene, which revealed a 488/489 (99%) base pair match to Mycobacterium mantenii strain NLA000401474 (NR_116538.1) in GenBank (accessed 22.09.2020).

Based on previously reported antimicrobial susceptibility testing,[[1]] oral therapy with clarithromycin 500mg BD and rifampicin 450mg BD was commenced. This resulted in dramatic improvement and complete healing of the ulceration at three months (Figure 2).

Figure 2: Significant healing of ulcerated lesion following three months of treatment with oral clarithromycin and rifampicin.

Discussion

Non-tuberculous mycobacterial species occur ubiquitously in the environment. Brackish water and soil are frequent reservoirs. Mycobacterial species causing skin infections include both rapidly growing mycobacteria (RGM), such as M. abscessus, and slow-growing mycobacteria (SGM), such as M. avium complex (MAC) and M. marinum. In contrast to RGM, the slower growing mycobacteria take longer than seven days to form colonies visible to the naked eye on subculture media. Approximately 50 mycobacterial species are now recognised as opportunistic human pathogens. Many species have a geographical predilection. Mycobacterium ulcerans, for example, is endemic to regions of Africa and Australia.

M. mantenii belongs to the scotochromogenic (producers of pigment in the absence of light) SGM group and matures beyond 28 days of incubation.[[1]] It was first identified in 2009 by van Ingen et al, who described five isolates: four in patients residing in the Netherlands and one environmental isolate. The clinical isolates were identified from two cases of cervical lymphadenitis (both immunocompetent children) and from respiratory secretions in two adults (considered clinically insignificant). M. mantenii was also cultured by the authors from a water sample taken from the Zambezi River.[[1]]

Since then, a handful of reports of M. mantenii environmental isolates and cases of human infection occurring in the northern hemisphere have been published (Table 1). This organism has not, as far as the authors are aware, been identified as a pathogen in humans in the southern hemisphere. Cases of cutaneous infection have been reported in only two further patients since 2009. In the first case, extensive M. mantenii skin infection was reported in 2015 by Honda et al[[5]] in an immunosuppressed Japanese patient with a history of Castleman’s disease and previous pulmonary multi-species NTM. The second case occurred in a 65-year-old Japanese patient and involved disseminated systemic infection (bone, bronchus, lymph nodes) with chronic skin ulceration. The patient was subsequently discovered to have anti-interferon gamma neutralising auto-antibodies and was therefore immunocompromised.[[4]]

Table 1: Reportedoccurrences of Mycobacterium mantenii (environment andclinical isolates).

The diagnosis of NTM skin infection can be very difficult given the wide variation in morphologic skin findings (pustules, deep abscesses, ulcerations, nodules) as well as often non-specific histopathologic findings.[[7]] Our case highlights this clinical challenge. Tissue culture eventually led to the correct diagnosis following initial detection of mycobacterial DNA on PCR testing.

Treatment of SGM can be particularly challenging, requiring antibiotic regimens that are long and often arduous.[[8]] No single susceptibility method is recommended for all species[[9]] and treatment recommendations are often made on the basis of only a few reported cases. Indeed, for M. mantenii, comprehensive drug susceptibility testing using the agar dilution method has been conducted on only four clinical isolates.[[1]] Those four isolates were only susceptible in vitro to rifampicin, rifabutin, clarithromycin, cycloserine, clofazimine and prothionamide. The drug susceptibility pattern is similar to that of M. scrofulaceum and members of the MAC, except for the remarkable in vitro susceptibility to rifamycins (ie, rifampicin and rifabutin).[[1]] In contrast, Nebreda Mayoral et al undertook drug susceptibility testing on the MGIT 960 (Becton-Dickinson and Company, Sparks, USA) following the manufacturer’s recommendations. The strain from their first patient was sensitive to cycloserine and clarithromycin, and the strain from the second patient was sensitive only to clarithromycin.[[6]] As outlined in Table 1, only a partial clinical response was noted despite at least three months of macrolide monotherapy. It seems probable then that successful treatment of M. mantenii-associated infection requires a combination antibiotic approach, ideally with the inclusion of a rifamycin. At a more general level, atypical mycobacterial skin and soft tissue infections in immunocompetent patients are usually treated for many months and outcomes are mostly favourable, as in this case.

Conclusion

We have described a patient with a chronic ulcer due to M. mantenii occurring in the southern hemisphere. This novel case demonstrates the pathogenicity of this species and its ability to cause serious chronic skin infection in an immunocompetent patient. The successful clinical outcome supports the use of empiric treatment of Mycobacterium mantenii with the combination of clarithromycin and rifampicin.

Ethical statement

Consent was obtained from the patient described in this case report.