Resilience and extensively drug-resistant tuberculosis: the unlikely ally.

Despite recent advances and well-known treatment options, cure rates for resistant tuberculosis (TB) cases remain extraordinarily low. We present in first person the case of a patient who suffered from TB for over 7 years, and travelled to four countries in search of a cure. This experience shows how resistance patterns worsen under poor programme conditions and illustrates many of the obstacles faced by patients to obtain appropriate care: late diagnosis, lack of experienced care capacity and drug availability, and absence of psychosocial support during toxic and lengthy regimens. In addition to new tools, patient-centred systems are needed to tackle the drug-resistant TB epidemic.

Successful management of multidrug-resistant tuberculosis under programme conditions in the Dominican Republic.

SETTING: The Dominican Republic is a high-incidence area for multidrug-resistant tuberculosis (MDR-TB; 6.6% of initial cases). Standardised treatment regimens for MDR-TB may be a potential solution. OBJECTIVE: To present the effectiveness of standard regimens under routine national conditions. DESIGN: We reviewed all MDR-TB patients treated under routine conditions from 29 August 2006 to 30 June 2010, showing interim and final outcomes. Patients were treated with regimens that were standardised or individualised based on previously received second-line anti-tuberculosis drugs. RESULTS: Population description and culture conversion data are reported for the 289 MDR-TB patients. The median patient age was 31 years. Most had failed first-line treatment (72.6%). Culture negativity was obtained within 4 months (median 2 months) in 78.6%. Among the 150 patients treated between 2006 and 2008, 74% had favourable results on standardised and 66% on individualised regimens (P = 0.211). The efficacy of the standardised and individualised regimens was respectively 92.8% and 81% (P = 0.056). The relapse rate was approximately 1%. A median of five drug side effects occurred per patient. More than 2 months to culture conversion and bilateral cavitation on chest X-ray were found to be unfavourable outcome risk factors. CONCLUSIONS: Standardised MDR-TB regimens may be effective at the national level, even in resource-poor settings.

Xpert® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how?

Xpert ® MTB/RIF offers new and important possibilities for the diagnosis of sputum smear-negative tuberculosis (TB) and/or rifampicin (RMP) resistance, and many are encouraging rapid and widespread implementation. This simple test can be implemented almost everywhere, and it provides results within a few hours. In low-income countries (LICs), however, its cost, environmental limitations (stable and regular electricity, adequate room temperature) and difficulties involved in supply and maintenance are major obstacles. While it may be suitable for major reference hospitals, operational research is needed to evaluate the test and its additional yield above high-quality smear microscopy and clinical algorithms before its use at the peripheral level. In the meantime, direct microscopy should remain the initial diagnostic test for TB suspects. In most LICs, the prevalence of RMP resistance among new TB patients is very low; an Xpert MTB/RIF result indicating RMP resistance will thus always need confirmation by another test. In a population at high risk of RMP resistance (> 15%), however, the positive predictive value for RMP resistance by Xpert MTB/RIF is high, and identification of RMP resistance is an excellent proxy for multidrug-resistant TB (MDR-TB). The assay should be widely used for this purpose if, and only if, excellent MDR-TB management is available, both for ethical reasons and to reduce the risk of extensively drug-resistant TB.

Evidence for promoting fixed-dose combination drugs in tuberculosis treatment and control: a review.

Uptake of fixed-dosed combinations (FDCs) of anti-tuberculosis drugs remains low worldwide, despite decades of recommendations. FDCs are thought to be important tools for tuberculosis (TB) control and drug resistance (DR) prevention. However, evidence relating to this is limited. This article provides a critical review of the most relevant studies on anti-tuberculosis FDCs. The majority of published studies have sought to demonstrate that FDCs and single drugs have similar efficacy. This hypothesis has been proved with relation to similar sputum conversion, cure and relapse rates in a range of studies over the last 20 years using FDCs of two, three and four anti-tuberculosis drugs. However, one of the most relevant features of FDCs, the prevention of DR, has been addressed in only one study. Nevertheless, based on their similar efficacy, user-friendliness, lower costs, and operational and logistical advantages, generalised use of FDCs should continue to be recommended.

A basis for the clinical management of complicated MDR-TB cases

Successful multidrug-resistant tuberculosis (MDR-TB) treatment and programme performance is possible even in complex circumstances. Governments are subject to strong pressure from donors concerning both DOTS (directly observed treatment; short course) expansion initiatives and especially MDR management.1Nevertheless; anyone assuming an MDR programme can be launched just with money and drugs is probably labouring under a grave misapprehension. A sound understanding of the clinical management of both susceptible and resistant TB is one of the basic fundamentals. The substandard use of second-line drugs is not only measured in low cure rates but in drug resistance mplification in the community; and hence potentially circulating extensively drug-resistant (XDR) TB strains. From a clinical point of view; MDR management is lengthy and complicated; involving the entire range of problems attendant upon chronic disease plus the high toxicity profile of second-line drugs. In addition; in developing countries with high HIV/TB co-infection levels; the complexity in terms of clinical and drug management issues increases. Poverty and lack of access to care and treatment can reduce adherence and further complicate the recovery process. This paper provides a brief summary of the best practice in MDR-TB patients including the most frequent side-effects and practical advice on managing TB/HIV co-infection based upon the most recent evidence

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