Challenging the management of drug-resistant tuberculosis

Abstract

The management of multidrug-resistant tuberculosis is notoriously difficult. Christoph Lange and colleagues1Lange C Dheda K Chesov D Mandalakas AM Udwadia Z Horsburgh Jr, CR Management of drug-resistant tuberculosis.Lancet. 2019; 394: 953-966Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar rightly mention that therapeutic drug monitoring can guide optimal personalised care. However, since the first recommendation for therapeutic drug monitoring in multidrug-resistant tuberculosis two decades ago,2Peloquin CA Therapeutic drug monitoring of the antimycobacterial drugs.Clin Lab Med. 1996; 16: 717-729Summary Full Text PDF PubMed Google Scholar and despite strong evidence that suboptimal drug exposure is a key contributor to drug resistance amplification, little has changed. Therapeutic drug monitoring is an important tool to help clinicians make informed decisions about optimal dosing. This approach is particularly beneficial during altered drug exposure due to malabsorption (eg, HIV), diabetes, or renal dialysis, in patients with drug–drug interactions or an unexplained, poor treatment response,3Nahid P Dorman SE Alipanah N et al.Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis.Clin Infect Dis. 2016; 63: e147-e195Crossref PubMed Scopus (401) Google Scholar or for drugs with considerable pharmacokinetic variability or narrow toxicity profiles, or both, such as fluoroquinolones, linezolid, and aminoglycosides.4WHOWHO consolidated guidelines on drug-resistant tuberculosis treatment. World Health Organization, Geneva2019Google Scholar The authors foresee that personalised treatment of multidrug-resistant tuberculosis, guided by therapeutic drug monitoring, host-directed therapies, and biomarker-informed therapy duration might become available for patients treated at adequately resourced centres.1Lange C Dheda K Chesov D Mandalakas AM Udwadia Z Horsburgh Jr, CR Management of drug-resistant tuberculosis.Lancet. 2019; 394: 953-966Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar However, the number of patients in these centres is low, and although individuals will benefit, the contribution to global multidrug-resistant tuberculosis control would be minimal. To provide access to therapeutic drug monitoring for most patients, we need to change its practice dramatically.5Alffenaar J-WC Tawanda Gumbo KD Peloquin C et al.Integrating pharmacokinetics and pharmacodynamics in operational research to end TB.Clin Infect Dis. 2019; (published online Sept 27.)DOI:10.1093/cid/ciz942Crossref Scopus (25) Google Scholar Clinically actionable pharmacokinetic thresholds that are associated with outcomes in diverse tuberculosis disease states are being investigated (clinicaltrials.gov NCT03559582), but further randomised controlled trials would better inform the incremental gain for programmatic planning. Furthermore, less invasive assays using urine, saliva, or dried blood spots are undergoing development or implementation to deliver semi-quantitative and inexpensive point-of-care tests, to distinguish between low, acceptable, and high drug concentrations, which would allow for more widespread scale-up. We declare no competing interests. Management of drug-resistant tuberculosisDrug-resistant tuberculosis is a major public health concern in many countries. Over the past decade, the number of patients infected with Mycobacterium tuberculosis resistant to the most effective drugs against tuberculosis (ie, rifampicin and isoniazid), which is called multidrug-resistant tuberculosis, has continued to increase. Globally, 4·6% of patients with tuberculosis have multidrug-resistant tuberculosis, but in some areas, like Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, this proportion exceeds 25%. Full-Text PDF Challenging the management of drug-resistant tuberculosis – Authors' replyIt is obvious that more efforts are needed, both in research and development and in implementation, to reduce the drug-resistant tuberculosis epidemic.1 Our concerns are supported by projections suggesting that the number of patients with drug-resistant tuberculosis in high-burden countries will increase in coming decades.2 Without an effective vaccine, identifying individuals with latent Mycobacterium tuberculosis infection and administration of preventive chemotherapy are highly effective interventions for preventing active tuberculosis when M tuberculosis is susceptible to isoniazid or rifamycin. Full-Text PDF Challenging the management of drug-resistant tuberculosisAlthough we were pleased to read the Series paper by Christoph Lange and colleagues1 on the management of drug-resistant tuberculosis, we were disappointed by the section on management of multidrug-resistant tuberculosis contacts, which we found to perpetuate unsubstantiated platitudes, confusing clinicians and misrepresenting guidance. Full-Text PDF