Management of TB/HIV Coinfection - Drug-Resistant TB

Authors: Francesca Conradie, MBBCh; Richard E. Chaisson, MD
Editor In Chief: Ian M. Sanne, MBBCH, FCP(SA) (More Info)

Last Reviewed: July 8, 2016 (What's New)

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inPractice® Africa’s Continuing Education Unit (CEU) provider, the South African Medical Association, offers physicians 3 CPD points on a 70% pass rate for completing this individual module. Nonphysicians who successfully complete the module will receive a participation certificate. To learn more on CPD credits and participation certificates, click here.

Introduction to Drug-Resistant Tuberculosis

According to the South Africa National Department of Health guidelines for the management of drug-resistant tuberculosis (DR-TB) (Management Guidelines)[ZA NDOH MDR TB 2013]: “Despite highly effective drugs, disease and deaths due to Mycobacterium tuberculosis are increasing in South Africa, fuelled by the HIV epidemic. The most serious aspect of the TB epidemic has been the emergence of DR-TB in the country. DR-TB is a man-made problem largely due to human error in any or all of the following:

  • Management of drug supply
  • Patient management
  • Prescription of chemotherapy
  • Patient adherence

Anti-TB drugs constitute a 2-edged sword—they kill the mycobacteria; they also select for naturally resistant mycobacteria. In this way, strains can become sequentially resistant to several agents. Patients can also acquire these drug-resistant strains through reinfection or superinfection.”

In the 1990s, the World Health Organisation (WHO) recommended a new approach to global TB control using standardised short-course (SCC) anti-TB treatment given under direct and supportive observation, coupled with governmental commitment to TB control, use of sputum microscopy for diagnosis, a reliable drug supply system, and effective monitoring and evaluation of outcomes—a policy known as directly observed therapy, short course, or DOTS.[Mitchison 2012] Isoniazid and rifampicin formed the backbone of the regimen and were administered for the full 6 months of the SCC, along with ethambutol and pyrazinamide during the first 2 months, which is termed the intensive phase. When DOTS was first promulgated, the incidence of DR-TB was low or unknown in most settings, and diagnosing it was time-consuming and expensive, so this strategy was appropriate. Smear microscopy, which was the primary method of diagnosing TB, cannot distinguish live organisms from dead ones, does not differentiate M tuberculosis from other mycobacterial species, and cannot measure drug sensitivity. In most settings, appropriate culture testing was performed only in patients who were at increased risk of having drug resistance, such as patients with recurrent TB and patients who did not achieve negative smear microscopy results (“smear-convert”) after 2 months of SCC therapy.

M tuberculosis has the ability to undergo spontaneous mutation that may be selected for by drug pressure, resulting in the emergence of drug-resistant organisms, similar to selection of drug-resistant HIV. This natural phenomenon is genetically determined and varies depending on the drugs that a particular patient is receiving. The chromosomal locations of resistance to different drugs are usually not linked. Therefore, spontaneously occurring multidrug resistance is extremely rare, and the development of multidrug-resistant (MDR)-TB is almost always the result of mismanagement or patient nonadherence.

As the prevalence of DR-TB increases, the likelihood of its transmission also increases. This likelihood has been compounded by the time involved in making the diagnosis. However, with the recent commercial availability of molecular diagnostics, the delay before appropriate therapy can be initiated will decrease.

In the absence of evidence from controlled clinical trials on the management of MDR-TB (ie, resistant to isoniazid and rifampicin), the current global guidelines for management of MDR-TB are based on expert opinion and retrospective clinical cohorts, which recommend lengthy, poorly tolerated, and expensive treatment options.[WHO Guidelines] As a result, implementation has been difficult, and results have remained modest.