A 56-year-old non-smoking male, retired army personnel, presented to the pulmonary outpatient clinic with symptoms of fever, productive cough and weight loss in March 2015 at AIIMS, New Delhi. He had initially presented with symptoms of fever, expectoration, weight loss and loss of appetite in 2012. He was given empirical anti-tubercular treatment for a clinical diagnosis of tuberculosis for 13 consecutive months with no improvement in 2013. The patient had been treated for pleural effusion in 1997, and declared cured. In March 2015 the patient reported to our institute. Examination revealed bilateral bronchial breath sounds in the upper and lower chest regions. His sputum samples were acid-fast bacilli (AFB)-positive and indicated suspected relapse of tuberculosis (TB); treatment was initiated with six drugs, including rifampicin, isoniazid, ethambutol, clarithromycin, levofloxacin and linezolid with a supplement of vitamin B6. However, his symptoms worsened (Fig. 1).
A complete blood count showed elevated lymphocyte and monocyte counts of 14.9 * 103 microl-1 and 8.9 * 103 microl-1, respectively, as well as an elevated erythrocyte sedimentation rate (ESR) of 40 mm after 1 h. Blood chemistry findings were normal. The patient was non-reactive for HIV 1 and 2 as well as hepatitis B and C. The workup for other bacteria and fungi was negative. A chest X-ray showed pleural thickening with hydropneumothorax and bilateral fibrous parenchymal lesions (Fig. 2). Sputum microscopy was positive with a Revised National Tuberculosis Control Program grading of (1+). A Gene Xpert assay was performed on the sample and was found to be negative. Culture on Lowenstein-Jensen (LJ) medium and Mycobacteria Growth Indicator Tube (MGIT 960) grew short, slender and curved AFB within 5 and 3 days, respectively, indicating a rapidly growing organism. An MGIT TBc identification test (Becton Dickinson) was negative and other bacteria were ruled out by culture. Subculture on LJ medium showed buff and pasty colonies within 5 days, indicating a rapid grower. The isolate was negative for a niacin accumulation test, a heat-stable catalase test and a nitrate reductase test, while it was NaCl-tolerant and grew on MacConkey's medium. Hence, it was identified as  Mycobacterium abscessus . A second sputum sample was also identified as  M. abscessus . Hence,  M. abscessus  was clearly the pathogen in this case scenario (ATS, American Thoracic Society guidelines). The isolate was subsequently sequenced for the 16S ribosomal gene and confirmed as  M. abscessus , and the sequence was submitted to GenBank and assigned accession no. MF287216.
  M. abscessus  is intrinsically resistant to many antibiotics and in vitro susceptibility correlates poorly with clinical response, especially in pulmonary disease. Drug susceptibility testing on the isolate demonstrated resistance to amikacin, imipenem, moxifloxacin and linezolid based on established minimum inhibitory concentration (MIC) breakpoints. Of note, the isolate was susceptible to clarithromycin. Several studies have demonstrated synergy between antibiotics against  M. abscessus  in vitro, which has the potential to decrease the MIC of both drugs and overcome antibiotic resistance. Synergy between linezolid and clarithromycin and linezolid and amikacin, as well as several carbapenems and rifampicin, have been described. Additionally, although the MIC of ethambutol was not specifically tested and many  M. abscessus  isolates tend to harbour inherent resistance to ethambutol, cases of ethambutol inclusion in treatment regimens against  M. abscessus  have been documented. Given the extensive resistance profile of this isolate, the potential for synergy of the above-listed drugs in combination with faropenem was tested (Table 1). The MIC results from these tests, in addition to the synergy studies cited above, were used to develop an antibacterial treatment regimen for the patient. Adjunctive surgical resection unfortunately could not be considered in this case due to the involvement of more than half of the right lung.
Given the reported disconnect between the in vitro susceptibility of  M. abscessus  and clinical response, the decision was made to treat the patient with linezolid (300 mg daily), clarithromycin (500 mg twice daily), ethambutol (1 g daily) and faropenem (200 mg three times daily) for 1 year, with the addition of intravenous amikacin for the initial 2-month induction phase. After 3 weeks of treatment, the patient reported improvement of symptoms, including weight gain and decreased cough. Follow-up sputum cultures converted to negative within 1 month of treatment and the patient continued on this regimen as an outpatient without any adverse effects. His condition continued to improve gradually and he became persistently culture-negative for 12 months after starting treatment, at which time antibiotics were stopped as per American Thoracic Society (ATS) recommendations. The patient remained asymptomatic for the next 9 months, but subsequently developed recurrence of respiratory symptoms. He unfortunately succumbed to an acute exacerbation of fever and respiratory failure before he could report to our institute.