Xpert MTB/RIF false detection of rifampin-resistant tuberculosis from prior infection.

A 71-year-old man with two prior episodes of pulmonary tuberculosis (TB) in China (2008–2009) and San Francisco, California (2009–2010) presented in July 2013 with progressive shortness of breath. The patient immigrated to San Francisco in November 2008, at which time he was noted to have right upper lobe scarring with cavity formation (Figures 1A and 1B); three sputa were smear-negative and culture-negative for acid-fast bacilli (AFB). In July 2009, the man developed right upper lobe (RUL) consolidation in the area of the previously noted cavitary lesion, as well as pleural effusion (Figure 1C). Pan-susceptible Mycobacterium tuberculosis complex (MTBC) was isolated from both sputum and pleural biopsy. The patient completed standard short-course TB treatment in March 2010, when follow-up chest radiograph demonstrated interval decrease of the 3 3 2 cm RUL opacity; three sputa were again smear-negative and culturenegative. Persistent RUL opacity was noted at 12-month posttreatment follow-up in 2011, although sputum cultures remained negative. The patient returned intermittently to China and declined 18-month follow-up. In July 2013, the patient presented to our emergency department with 2 days of progressive shortness of breath without fevers, night sweats, cough, or weight loss. Computed tomography showed bilateral pleural effusions and persistent RUL opacification (Figures 1D and 1E). On hospital day 2, a sputum specimen sent for concentrated smear demonstrated few AFB. Xpert MTB/RIF (Cepheid, Sunnyvale, CA) testing of this specimen showed MTBC at very low quantity (mean cycle threshold, 30.6), with rifampin resistance detected within the region of probe A (see Figure E1 in the online supplement). On hospital day 3, rifampin, isoniazid, pyrazinamide, ethambutol, moxifloxacin, capreomycin, and linezolid were initiated pending confirmatory testing. Complete blood count was within normal limits, hemoglobin A1c level (15.7 mg/dL) indicated poorly controlled diabetes mellitus, HIV testing was negative, and blood cultures demonstrated no growth. The concentrated sputum specimen tested by Xpert was sent to the Microbial Diseases Laboratory of the California Department of Public Health for pyrosequencing (1). The molecular target of IS6110 for MTBC identification and six loci, including rpoB for drug resistance detection, yielded no sequences, implying insufficient DNA or no MTBC present. Repeat sputum smears were AFB-negative. Diagnostic thoracentesis demonstrated transudative pleural fluid and no AFB on smear examination. On hospital day 8, the specimen tested by Xpert became culture-positive, with morphology consistent with non-TB mycobacteria (NTM). Repeat pyrosequencing and Xpert testing from the broth culture (BacT/ALERT 3D system; bioMerieux Inc., Durham, NC) were negative. The culture tested negative for MTBC twice, using AccuProbe (Hologic, Inc., San Diego, CA); was plated to Remel Middlebrook 7H11 Agar, where it demonstrated growth after 3 days; and was identified as a member of the Mycobacterium fortuitum-chelonae group. Three additional sputum cultures showed no growth of any organism. These data, along with low clinical suspicion for TB, prompted discontinuation of all anti-TB therapy on hospital day 14, and the patient was discharged. At 12-month follow-up, the patient remained asymptomatic without radiographic progression or clinical evidence of active TB, and three additional sputum specimens were smear-negative and culture-negative. Our patient’s short interval of symptoms and evidence of volume overload strongly suggested a non-TB etiology of respiratory distress. In addition, reinfection with multidrugresistant TB (MDR-TB) or acquisition of MDR-TB during treatment of pan-susceptible disease in California is rare (z0.05%) Figure 1. Computed tomography of the lungs. Computed tomographic scans of the lungs without administration of contrast at time of immigration to the United States (A and B), second diagnosis of pulmonary tuberculosis in 2011 (C), and re-presentation in 2013 (current case report; D and E).