Rifampin-Resistant TB Infection Linked to HIV Infection, Increased Mortality

All forms of rifampin-resistant tuberculosis (TB) may be positively associated with HIV and increased mortality, according to a study published in Clinical Infectious Diseases.

Although the percentage of drug-resistant cases of TB has remained stable in the United States over the last 2 decades, drug resistance still poses barriers to identification of appropriate treatment, treatment completion, and achievement of TB elimination. Among the rifamycin family of antibiotics, which is the first-line medication for treatment of TB, rifampin is the principal antibiotic used worldwide. This likely the result of rifampin’s effectiveness against Mycobacterium tuberculosis and its bactericidal activity in both the log growth and stationary phases of bacterial replication

Combining rifampin with pyrazinamide has reduced the duration of drug-susceptible TB treatment from 18 to 6 months. The United States National TB Surveillance System captures demographic, clinical, and laboratory information for each reported TB case in the 50 states and District of Columbia, including initial drug susceptibility testing results, which is usually performed within 30 days of TB diagnosis. Investigating factors associated with rifampin resistance further using national surveillance data may help better characterize rifampin-monoresistant and acquired rifampin-resistant TB. Therefore, this study examined characteristics and mortality associated with rifampin monoresistant TB found on initial drug-susceptibility testing and possible acquired, rifampin-resistant TB in the United States.

Using data from the National TB Surveillance System, M tuberculosis culture-positive cases were analyzed. Of note, data from California were excluded since HIV infection was not reported to the US Centers for Disease Control and Prevention during 2005 to 2010. In total, 126,431 cases were eligible for analysis with 359 (0.28%) of these cases reported as rifampin monoresistant. Initial drug susceptibility testing reports were used to categorize cases as rifampin-monoresistant TB. Possible acquired rifampin-resistant TB was defined as rifampin susceptibility on the initial drug susceptibility testing and resistance on the final testing. Temporal trends in rifampin-monoresistant TB were assessed. For both classifications of rifampin resistance, adjusted risk ratios (adjRRs) for social and clinical characteristics associated with mortality were calculated and compared with those of drug-susceptible TB in multivariable models. The outcome of mortality was compared to a combined outcome of treatment completion or stopping therapy because of an adverse treatment event, and other outcomes (ie, lost, refused treatment, other, unknown) were excluded.

Results suggested that all forms of rifampin resistance were positively associated with HIV infection and increased mortality. From 1998 to 2014, the percentage of rifampin-monoresistant TB cases with HIV declined 4% annually. People with either prior TB or current HIV and people with HIV with no prior TB were more likely to have rifampin-monoresistant TB (adjRR=25.9 and 3.1, respectively) when compared with those without either characteristic. Cases of rifampin-monoresistant TB also had greater mortality (adjRR=1.4), even when controlling for HIV and other variables. Similarly, those with HIV had a greater risk for acquired rifampin-resistant TB than those without HIV (adjRR=9.6). Acquired rifampin-resistant TB was also associated with increased mortality even when controlling for HIV and other variables.

Overall, the study authors concluded that, “Persons with HIV were found to be at greatest risk of [rifampin-monoresistant TB] and [acquired rifampin-resistant TB]. All forms of rifampin resistance were positively associated with HIV infection, delayed culture conversion, and increased mortality.”

Reference

Sharling L, Marks SM, Goodman M, Chorba T, Mase S. Rifampin-resistant tuberculosis in the United States, 1998-2014 [published online June 22, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz491