A 72-year-old healthy man with chronic cough and CXR abnormalities was referred to our clinic. He was a current smoker and his smoking index was 92 pack-years. His CXR (Fig. 1A) and computed tomography (CT) (Fig. 1B) revealed infiltrations of cavity lesions at the right upper lobe. Direct sputum smears were positive for acid-fast bacilli (AFB), although the DNAs of Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC) were not detected by polymerase chain reaction (PCR) techniques (SRL co., Tokyo, Japan). AFB cultures in 2% Ogawa egg slant medium (Kyokuto, Tokyo, Japan) under standard conditions showed no growth. His CXR abnormalities were diagnosed as non-tuberculosis mycobacteria infection with unknown causes. His home doctor followed up the patient, as the chronic cough was relieved with temporary cough medicines or spontaneously.
Four years later, he revisited our clinic with cough recurrence and a weight loss of 5 kg/year with 16.4 kg/m2 of body mass index. His vital signs were almost normal and his body temperature was 36.7  C. His white blood cells count was 5000 cells/muL and serum C-reactive protein level was 2.26 mg/L. His chest CT revealed worsened cavity lesions with surrounding infiltrative shadows at the right upper lobe (Fig. 1C).
Direct sputum smears were positive for AFB, although MTB and MAC-DNA could not be detected by PCR techniques and standard AFB cultures; AFB was ultimately successfully cultured in the mycobacterium growth indicator tubes (MGIT) system (BD Biosciences, Sparks, MD, USA). A specie of M. heckeshornense was finally identified with the MALDI-TOF MS techniques, although no match of 18 mycobacterial species (not involving M. heckeshornense) were identified among the cultured AFB strains by the commercial kits of the DNA-DNA hybridization techniques (DDH Mycobacteria, Kyokuto, Japan). The progressive pulmonary M. heckeshornense infections were defined in the patient, because the species was isolated repeatedly from sputum samples on different days after fiberoptic bronchoscopy.
We summarized the characteristics of 11 patients (number of male, 6; median age at diagnosis, 52.6 years [range: 30-72 years]) with pulmonary M. heckeshornense infections based on our case and previous case reports (Table 1, Table 2). Five patients were in the immunocompetent state, and the remaining 6 patients had some underlying diseases. Only two patients had no symptoms, although most patients had similar respiratory and general symptoms with other NTM infections. The number of patients diagnosed with lung M. heckeshornense infections were 7, by the 16S rRNA sequence analysis, 2 by the DNA strip assay and 2 by the MALDI-TOF MS techniques, respectively. The CXR and CT abnormalities of lung fields were limited to the right upper lobe in six patients and 6 had cavity lesions. The regimens for M. heckeshornense infections varied, although multidrug therapy was selected for all the patients including anti-tuberculous drugs, CAM, aminoglycosides, and some new quinolones. The limited lung lesions were successfully resected in 2 patients after anti-mycobacterial chemotherapies. Except for two patients, the number (population) of patients who had improved, not changed and worsened were 7 (64%), 2 (18%) and 1 (9%), respectively, after the treatments.
The indirect drug susceptibility of M. heckeshornense strain was tested according to the absolute concentration method using a microtiter technique developed by a commercial laboratory (BML. Tokyo, Japan). The minimum inhibitory concentrations (MIC) of isoniazid, RFP, EB, and streptomycin used were 0.2 g/mL, 40 g/mL, 2.5 g/ml, and 10 g/ml, respectively. According to the previous reports, M. heckeshornense was resistant to INH, but susceptible to RFP, EB, amikacin, CAM, and ciprofloxacin (1). Our case showed similar susceptibility to previous reports. Triple anti-mycobacterial therapy with RFP, EB and CAM at 450, 750, and 600 mg/day, respectively (his body weight was under 50 kg) was started against the progressive pulmonary M. heckeshornense infections based on the results of MIC and the regimens in the previous reports. His symptoms and abnormal shadows on chest CT improved 6 months after the treatments without adverse events (Fig. 1D). Mycobacterial cultures remained negative.