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.

Keywords: Cost effectiveness; Diagnostics; Drug resistance; Regimen selection; Treatment outcomes.

Figure 1. Rifampin-resistant tuberculosis (RR TB) patients and spending in context

By applying estimated outcomes and costs for a high-burden, low-income setting, we compare expenditures on overall and drug-resistant TB diagnostics and treatment in a hypothetical cohort of 10,000 individuals evaluated for TB, using sputum smear or Xpert MTB/RIF as the initial diagnostic test. Assumptions about procedures and outcomes include: initial TB diagnosis by sputum smear, 2 smears (or one Xpert) collected per suspect, 10 suspects per TB case,^, 3% prevalence of rifampin-resistant TB among TB cases (near the global average), 6% failure or relapse after first-line treatment,^, rifampin susceptibility testing (e.g. by Xpert) after unsuccessful first-line therapy (if initial diagnosis is by smear), and 15% failure or relapse after treatment for rifampin-resistant TB. Cost estimates are in US dollars and include $2 per smear, $500 per first-line treatment, $25 per Xpert, $4000 per initial MDR TB treatment, $8,000 per salvage regimen, and $100 per rifampin-resistant case for second-line DST (second-line line probe assay plus culture and phenotypic second-line DST, including fixed costs, in a low-income, high-burden setting). The yellow oval shows the relatively small cost of performing second-line DST for all individuals diagnosed with rifampin resistance, relative to total TB and rifampin-resistant TB spending. Note that secondary drug-resistant cases – an added potential cost of ineffective treatment for rifampin-resistant TB – are not included in this figure.