Xpert(®) MTB/RIF detection of rifampin resistance and time to treatment initiation in Harare, Zimbabwe.
Patients at elevated risk of drug-resistant tuberculosis (TB) are prioritized for Xpert(®) MTB/RIF testing; however, the clinical usefulness of the test in this population is understudied.



From November 2011 to June 2014, consecutive out-patients with a history of previous TB in high-density suburbs of Harare, Zimbabwe, were tested using Xpert, solid and liquid culture, and the microscopic observation drug susceptibility assay. Diagnostic accuracy for rifampin (RMP) resistance and time to initiation of second-line regimens were ascertained. The rpoB gene was sequenced in cases with culture-confirmed RMP resistance and genotypic susceptibility.



Among 352 retreatment patients, 71 (20%) were RMP-resistant, 98 (28%) RMP-susceptible, 64 (18%) culture-negative/Xpert-positive, and 119 (34%) culture-negative/Xpert-negative. Xpert had a sensitivity of 86% (95%CI 75-93) and a specificity of 98% (95%CI 92-100) for RMP-resistant TB. The positive predictive value of Xpert-determined RMP resistance for multidrug-resistant TB (MDR-TB) was 82% (95%CI 70-91). Of 71 (83%) participants, 59 initiated treatment with second-line drugs, with a median time to treatment initiation of 18 days (IQR 10-44).



The diagnostic accuracy of Xpert for RMP resistance is high, although the predictive value for MDR-TB was lower than anticipated. Xpert allows for faster initiation of second-line treatment than culture-based drug susceptibility testing under programmatic conditions.
Curry International Tuberculosis Center, Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA.
J Z
JZ
Metcalfe
Biomedical Research & Training Institute, Harare, Zimbabwe.
S
S
Makumbirofa
Biomedical Research & Training Institute, Harare, Zimbabwe.
B
B
Makamure
National Tuberculosis Control Program, Harare, Zimbabwe.
C
C
Sandy
Harare City Health Department, Harare, Zimbabwe.
W
W
Bara
Biomedical Research & Training Institute, Harare, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
P
P
Mason
Curry International Tuberculosis Center, Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA.
P C
PC
Hopewell
D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D019233:Retreatment; D012293:Rifampin / Q000627:therapeutic use*; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology; D015030:Zimbabwe
D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin