title: Second line drug susceptibility testing to inform the treatment of rifampin-resistant tuberculosis: a quantitative perspective.
abstract: Treatment failure and resistance amplification are common among patients with rifampin-resistant tuberculosis (TB). Drug susceptibility testing (DST) for second-line drugs is recommended for these patients, but logistical difficulties have impeded widespread implementation of second-line DST in many settings. To provide a quantitative perspective on the decision to scale up second-line DST, we synthesize literature on the prevalence of second-line drug resistance, the expected clinical and epidemiologic benefits of using second-line DST to ensure that patients with rifampin-resistant TB receive effective regimens, and the costs of implementing (or not implementing) second-line DST for all individuals diagnosed with rifampin-resistant TB. We conclude that, in most settings, second-line DST could substantially improve treatment outcomes for patients with rifampin-resistant TB, reduce transmission of drug-resistant TB, prevent amplification of drug resistance, and be affordable or even cost-saving. Given the large investment made in each patient treated for rifampin-resistant TB, these payoffs would come at relatively small incremental cost. These anticipated benefits likely justify addressing the real challenges faced in implementing second-line DST in most high-burden settings.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, PCTB Suite 211, 725 N. Wolfe St, Baltimore, MD 21205, USA. Electronic address: ekendal2@jhmi.edu.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Kendall
authors.affiliation: Department of Epidemiology, Yale School of Public Health, 60 College Street, New Haven, CT 06510, USA. Electronic address: theodore.cohen@yale.edu.
authors.forename: Ted
authors.initials: T
authors.lastname: Cohen
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, 641 Huntin, gton Ave., Boston, MA, USA. Electronic address: carole_mitnick@hms.harvard.edu.
authors.forename: Carole D
authors.initials: CD
authors.lastname: Mitnick
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615N. Wolfe St., Baltimore, MD 21205, USA. Electronic address: ddowdy1@jhmi.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: Dowdy
mesh_terms: D000995:Antitubercular Agents / Q000191:economics / Q000627:therapeutic use*; D023801:Directly Observed Therapy / Q000191:economics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D015995:Prevalence; D012293:Rifampin / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000191:economics / Q000276:immunology
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin
keywords: Cost effectiveness; Diagnostics; Drug resistance; Regimen selection; Treatment outcomes