Mycobacterium ulcerans lung infection in an immunocompetent patient

Abstract

Mycobacterium ulcerans has been implicated in cutaneous manifestations in humans, causing persistent wounds called Buruli ulcer. However, it has not been associated with pulmonary infections in humans to date. Herein, we report a case of an immunocompetent adult man with no underlying medical problems presenting with dyspnoea and generalised malaise and diagnosed with M. ulcerans lung infection. The patient was prescribed clarithromycin 500 mg two times per day, rifampin 300 mg two tablets daily and moxifloxacin 400 mg daily for 6 months, with complete resolution of his symptoms.

Background

Mycobacterium ulcerans is a non-motile, non-spore-forming, slow-growing, Gram-positive acid-fast bacillus found in various aquatic environments causing a devastating, necrotising tropical skin disease called Buruli ulcer.¹ Pulmonary infections caused by M. ulcerans have not been reported in the literature to date. Herein, we report the first case of an immunocompetent adult man with no underlying medical problems presenting with M. ulcerans lung infection.

Case presentation

A previously healthy man in his late 20s with a body mass index of around 19 kg/m² presented to the clinician in the outpatient setting for dyspnoea on minimal exertion and generalised weakness of 6 months’ duration. He reported a 5 kg unintentional weight loss over the same period; however, he did not have fever, cough or sputum production. On physical examination, the patient appeared cachectic, with notable left basal crackles on lung examination and normal heart sounds. Laboratory tests revealed a normal white cell count (10.3×10⁹/L), with neutrophilia (73%). The patient also had an elevated erythrocyte sedimentation rate of 56 mm/hour and a C reactive protein of 14 mg/dL. The patient had no history of diabetes and had normal fasting blood sugar, taken at an outside hospital prior to his initial presentation to our clinic. He denied smoking and use of steroids or immunosuppressive agents. He also denied travel history, contacts with pets or swimming in lakes or oceans, as well as any family history of Buruli ulcer.

Investigations

A CT scan of the chest showed left lower lobe consolidation with air bronchograms and a cavitating lesion suggestive of an infectious process or abscess formation (figure 1). Tuberculin skin test was positive at 20 mm after 72 hours of reading. HIV antibodies were negative. A bronchoscopy revealed mucopurulent secretions in the left bronchus. Bronchoalveolar lavage (BAL) taken from the left lower lobe yielded positive acid-fast bacillus smear. PCR for M. tuberculosis was negative. However, PCR using the Bio-Rad PCR kit was positive for non-tuberculous mycobacteria.

Figure 1.

Chest CT showing left lower consolidation with air bronchograms and a cavitating lesion.

Differential diagnosis

The clinical picture was suggestive of Mycobacterium other than tuberculosis (MOTT). Samples from the patient’s BAL were sent to SYNLAB Laboratory for MOTT speciation and susceptibility. The report indicated the possibility of either M. ulcerans or M. marinum. A further work-up to assess his CD4 and CD8 counts as well as his immunoglobulin levels was requested but not performed due to financial reasons. However, the patient denied any history of recurrent bacterial or fungal infections and had never been hospitalised.

Treatment

The patient was advised to start clarithromycin 500 mg two times per day, with one of the following: rifampin 300 mg two tablets daily or ethambutol 1200 mg daily.

Ten days later, the patient returned reporting new-onset cough and low-grade fever. He had not started treatment yet. The mycobacterial isolate from the BAL was referred to bioMérieux laboratory foundation for sequencing, which confirmed the identification of M. ulcerans. Accordingly, the patient was advised to take clarithromycin 500 mg two times per day, rifampin 300 mg two tablets daily and moxifloxacin 400 mg daily for 6 months, with a close follow-up of his symptoms. On follow-up after 4 months of therapy, he reported marked improvement in his dyspnoea and a gradual recovery of his weight.

Outcome and follow-up

The patient received a combination of clarithromycin 500 mg two times per day and rifampin 300 mg two tablets daily for 11 months and moxifloxacin 400 mg once daily for 10 months. He was followed up in the clinic after finishing his treatment and reported no residual symptoms as well as full recovery of his weight. The patient was also following up with a pulmonologist at another hospital, with a new CT scan of the chest showing improvement. The patient was advised to follow up in another 6 months.

Discussion

M. ulcerans is closely related to M. marinum, from which it evolved nearly one million years ago.¹ While there are no other reported cases of M. ulcerans pulmonary infections in humans to date, several cases of M. marinum in the lungs are described in the literature.^2–5 One of the cases of isolated pulmonary lesion due to M. marinum was reported in an immunocompetent patient who was started on a combination therapy with isoniazid 300 mg daily, rifampin 450 mg daily and ethambutol 800 mg daily for a total of 6 months.² Some of the other case reports were associated with exposure to marine environments, while the majority occurred in patients with certain immunosuppressive conditions, including diabetes mellitus, anorexia nervosa, AIDS and sarcoidosis.^3–6

On the other hand, systemic infections associated with M. ulcerans have been reported in the literature. In one case report, a 4-year-old boy with sickle cell trait presented with two cutaneous ulcerations and osteomyelitis of the left knee and right ankle. The case documented the ability of M. ulcerans to spread haematogenously, although in an immunosuppressed child. However, there was no documentation of pulmonary infection.⁷

It is unclear where our patient acquired M. ulcerans as he has no known exposures to near-stagnant, slow-moving waters, nor has he been exposed to agriculture or hydraulic installations or muddy farming fields previously linked to M. ulcerans.⁸ The diagnosis was confirmed by internationally acknowledged kits and laboratory. There are currently no standardised treatment regimens for M. ulcerans infection of the lungs. According to case reports, as well as the guidelines by the WHO, the antibiotics tetracyclines, clarithromycin and rifampin are usually used as monotherapy in case of superficial infection limited to the skin and soft tissues, or as combination therapy in case of more severe and deeper infections.⁹ It is not required to do susceptibility testing on M. ulcerans isolates except in the context of no response to therapy after several months. In that case, the isolates should be tested for susceptibility to doxycycline, ethambutol, sulfonamides and rifampin.¹⁰

This case is the first of its kind and reveals an important clinical presentation of M. ulcerans causing pulmonary infection in an immunocompetent patient. Our patient presented with systemic findings of unintentional weight loss, dyspnoea and weakness, which add to the clinical spectrum of M. ulcerans infections. The patient responded very well to a combination of three drugs, with marked improvement of his symptoms at 4-month follow-up.

Patient’s perspective.

The treatment was well-tolerated with improvement of my symptoms such as cough and weight loss. The toughest part was the duration of the treatment. I benefited from the close follow-up provided by my physician, which made me trust the treatment plan despite the rarity of this condition. The physician took my approval to submit this case for publication. I gave consent for publication to increase awareness of this rare condition among clinicians. (Authors’ translation of the patient’s words).

Learning points.

• An immunocompetent patient who initially presented with weight loss and subsequently developed a low-grade fever with dry cough was diagnosed with pneumonia caused by Mycobacterium ulcerans.

• Our investigation highlighted the possibility of M. ulcerans causing pulmonary infections, even without a history of cutaneous ulcers in the patient.

• Despite the rarity of M. ulcerans lung infections, adhering to the guidelines suggested by the WHO as well as case reports on cutaneous M. ulcerans infections led to the proper treatment with correct choice of antibiotics.

Ethics statements

Patient consent for publication

Obtained.