Isoniazid resistance did not impact time to sputum culture conversion (tSCC) or initial outcomes in patients treated for pulmonary tuberculosis (TB), according to results from a retrospective cohort study published in Clinical Infectious Diseases. The study is the first to compare tSCC — defined as the number of days from initiation of treatment for TB to the first of 2 negative sputum cultures — in patients with isoniazid-resistant and isoniazid-susceptible TB.
The research team, led by Marcos Coutinho Schechter, MD, of Emory University School of Medicine, assessed inpatient, local health department, and Georgia State Electronic Notifiable Surveillance System (SEDNSS) records for patients treated for culture-confirmed pulmonary TB at a safety-net hospital in Atlanta between January 2008 and October 2015. That period was characterized by an outbreak of isoniazid-resistant TB in the local homeless population.
Patients with known rifampin-resistant TB and those with incomplete records on treatment course or sputum culture results were excluded from the study. The study population ultimately consisted of 236 patients, 59 (25%) of whom had isoniazid-resistant TB. Almost half (46%) of the cohort was formerly or presently homeless. “This rate of isoniazid-resistance is much higher than published worldwide and US rates and is a stark reminder of how a drug-resistant M tuberculosis strain can take hold and rapidly spread among high-risk populations,” wrote the investigators.
Results showed a median tSCC of 35 days for patients with isoniazid-resistant TB and 29 days for patients with isoniazid-susceptible TBs, a difference that did not reach statistical significance (P =.39). The cases of acquired drug resistance (n=1, P =.25) and TB recurrence (n=3, P =.01) involved patients who were isoniazid resistant. Cure rates and mortality did not differ between groups.
In an email interview with Infectious Disease Advisor, Dr Schechter noted that isoniazid has the highest early bactericidal activity of the 4 first-line TB drugs (rifampin, isoniazid, pyrazinamide, and ethambutol). “Since tSCC was similar between patients with isoniazid-resistant and susceptible TB and most patients achieved culture conversion while on first-line drugs, the data suggest that isoniazid has some activity against isoniazid-resistant strains or that the other 3 first-line drugs can make up for the loss of isoniazid activity.”
Dr Schechter advised that in settings with high rates of low-level isoniazid resistance where rapid susceptibility testing for isoniazid is not available, isoniazid should be continued until conventional susceptibility test results are available. “In practical terms, this means patients will receive approximately 30 days of isoniazid given the long turnaround time for conventional susceptibility tests.”
Dr Schechter further advised that the study findings should be interpreted with caution. “While tSCC is a marker frequently used in the TB literature, it offers limited predictive value for long-term outcomes such as relapse,” he noted. “Unfortunately, the TB world is in great need of better biomarkers.”
Schechter MC, Bizune D, Kagei M, et al. Time to sputum culture conversion and treatment outcomes among patients with isoniazid-resistant tuberculosis in Atlanta, Georgia [published online August 3, 2017]. Clin Infect Dis. doi:10.1093/cid/cix686