The index case (Case 1) was an aboriginal man who was a tunnel worker. He lived in the village of Wan-Rong, Taiwan which had a TB incidence of 512.5 cases per population of 100,000 in 2006. He was first diagnosed with pulmonary TB in November 2000, when he was 43 years old. Sputum smears were positive for acid-fast bacilli, and sputum cultures grew Mycobacterium tuberculosis. This isolate was sensitive to all first-line drugs. The patient was cured after 8 months of standardized treatment, but due to a relapse in February 2002, antituberculosis treatment was restarted.
During the second treatment course, the patient showed poor compliance with the treatment regimen. Sputum cultures were again positive in April 2004, and chest radiography revealed worsening of left lung infiltrations and cavitations (Fig. 1A). The results of a drug-susceptibility test (DST) of the sputum culture 2 months later revealed resistance to isoniazid (H) and rifampicin (R), so the patient's regimen was changed to ethambutol (E), pyrazinamide (Z), streptomycin (S), prothionamide (Pto), and moxifloxacin (Mfx). In September 2005, sputum cultures still grew M. tuberculosis, and repeated DST showed resistance to HERS.
The patient was enrolled in a directly observed therapy program (DOT-plus) in 2007, and continued treatment with E, Z, Pto, Mfx, para-aminosalicylic acid, and rifabutin (Rfb). However, this sputum cultures remained positive. Despite the use of Group I:V antitu- berculosis drugs, the patient's sputum cultures remained positive at the time of this report. He was diagnosed to have chronic MDR- TB in 2009 and was placed in long-term isolation in a negative- pressure room.
Case 2 is the third daughter of the index case. In 2002, she was diagnosed with pulmonary TB at the age of 19 years. At that time, the isolated strain was sensitive to HERS. She completed 8 months of treatment with HERZ and was cured in June 2003. However, in November 2006, a follow-up chest radiograph (Fig. 1B) and sputum cultures confirmed recurrent disease. DST showed resistance to HR, so she was treated with E, Z, S, Pto, and Mfx. Streptomycin was used for 6 months, and she completed an 18-month treatment course and was cured in September 2008.
Case 3 is the index patient's older son. He was diagnosed with pulmonary TB in May 2005, at the age of 14 years, during a regular health checkup. A chest radiograph revealed infiltrations in the left upper lobe (Fig. 1C). He was treated with HERZS, but 2 months later DST showed HER resistance. The regimen was switched to Z, S, Pto, Rfb, and Mfx. Streptomycin was used for 7 months. He completed 18 months of treatment and was cured in January 2007.
Case 4 is the index patient's younger son. He was first diagnosed in November 2006, at the age of 13 years. A chest radiograph revealed infiltrations and cavitations over the left upper lobe (Fig. 1D). The first M. tuberculosis isolate was fully drug susceptible, and he was treated with HERZ. However, due to persistent positive sputum cultures 3 months after starting treatment, DST was repeated and revealed resistance to HERS. The regimen was switched to Z, kanamycin, para-aminosalicylic acid, Pto, Rfb, and Mfx. He was cured in March 2009 after sputum conversion for 18 months. All four patients were tested for antibodies to HIV by enzyme immunoassay, and all were found to be negative (Fig. 2).
Drug susceptibility testing was performed by the indirect proportion method. M. tuberculosis isolated from all four patients revealed similar multiple drug resistance to first-line HER and second-line ofloxacin. Fortunately, the strains were sensitive to kanamycin (Table 1). Isolates of MDR-TB stains from the four patients showed identical genotypes indistinguishable from each other by spoligotyping and Mycobacterium interspersed repetitive units:variable-number tandem-repeat (MIRU-VNTR) typing (Table 2).