Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients

Ahuja, Shama D.; Ashkin, David; Avendano, Monika; Banerjee, Rita; Bauer, Melissa; Bayona, J; Becerra, Mercedes C.; Benedetti, Andrea; Burgos, Marcos; Centis, Rosella; Chan, Eward D.; Chiang, Chifa; Cox, Helen; D’Ambrosio, Lia; DeRiemer, Kathryn; Dung, Nguyen Huy; Enarson, Donald A.; Falzon, Dennis; Flanagan, Katie L.; Flood, Jennifer; García-García, Ma. de Lourdes; Gandhi, Neel R.; Granich, Reuben; Hollm-Delgado, Maria Graciela; Holtz, Timothy H.; Iseman, Michael D.; Jarlsberg, Leah G.; Keshavjee, Salmaan; Kim, Hye‐Ryoun; Koh, Won‐Jung; Lancaster, Joey; Lange, C; Lange, Wiel C M de; Leimane, Vaira; Leung, Chi Chiu; Li, Jiehui; Menzies, Dick; Migliori, Giovanni Battista; Mishustin, Sergey P.; Mitnick, Carole D.; Narita, Michiko; O'Riordan, Philly; Pai, Madhukar; Palmero, Domingo; Park, Seung-Kyu; Pasvol, Geoffrey; Peña, José M.; Pérez-Guzmán, Carlos; Quelapio, M. I. D.; Ponce-de-León, Alfredo; Riekstiņa, Vija; Robert, Jérôme; Royce, Sarah; Schaaf, H. Simon; Seung, Kwonjune J.; Shah, Lena; Shim, Tae Sun; Shin, Sonya; Shiraishi, Yuji; Sifuentes–Osornio, José; Sotgiu, Giovanni; Strand, Matthew; Tabarsi, Payam; Tupasi, Thelma E.; Altena, R van; Walt, Martie van der; Werf, Tjip S. van der; Vargas, Mario H.; Viiklepp, Pirett; Westenhouse, Janice; Yew, Wing Wai; Yim, Jae Joon

doi:10.1371/journal.pmed.1001300

Cited by 459 publications

(429 citation statements)

References 43 publications

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“…Interestingly, prognosis was not affected by resistance to any of the group 4 drugs (ethionamide/prothionamide, cycloserine/terizidone or PAS) in the presence of resistance to all second-line drug injectables. These results are slightly in contrast to the published findings of a recent meta-analysis including the largest number of MDR-TB patients published to date, in which, in addition to FQs, the possibility of using ethionamide/prothionamide was associated with a better profognosis [18].…”

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confidence: 99%

Tuberculosis: are we making it incurable?

2013

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@ERSpublications With proper management all TB patients have a chance to be cured; it should never be thought that a TB case is incurable http://ow.ly/ksm5gTuberculosis (TB) is most probably the disease that has caused more damage to the human species throughout its history in terms of number of patients and, above all, death toll. There have been thousands of years spent fighting against Mycobacterium tuberculosis in which the human species could only rely on the efficiency of the immune system [1]. We must recall its importance as, in the pre-antibiotic era, the immune system alone could ensure important achievements such as: 1) only 50% of the people exposed to M. tuberculosis contract the infection [2]); 2) only 10% of those infected progress to active disease; and 3) up to 30% of patients with advanced TB disease heal spontaneously ( fig. 1) [3,4]. In spite of this, the fate of TB patients in the pre-chemotherapy period was very bleak, with a mortality of .50% within 5 years after the onset of disease [3,4]. For centuries, several empirical treatments were attempted to trying to change this fateful prognosis. Additionally, sanatoriums were built throughout the world for many decades ( fig. 2). However, all these interventions were not really effective, and none of them contributed significantly to improve the doom of TB patients [4]. Then, fortunately, their fate changed dramatically with the advent of the antibiotic era. The two decades from the discovery of streptomycin in 1943 to that of rifampicin in 1963 changed a devastating disease into a relatively easy to cure one. Not only were up to 11 different drugs with activity against M. tuberculosis discovered (streptomycin, p-aminosalicylate (PAS), thiacetazone, isoniazid (H), pyrazinamide, cycloserine, kanamycin, ethionamide, ethambutol, capreomycin and rifampicin (R)), but, based on multiple randomised clinical trials, the basic fundamentals of TB treatment were also established [4,5]. Probably the most essential of these was the need to combine at least two to three drugs to which the patient was sensitive, as M. tuberculosis can develop resistance to single drugs.The ability of M. tuberculosis to develop resistances to antibiotics was described in the very first randomised clinical trial conducted with streptomycin and published in 1948 [6]. The first great lesson learnt from early randomised clinical trials was that using TB drugs in monotherapy, or in poor combinations, would lead to the selection of resistance to these drugs [5]. Thus, as a result of the misuse of the available drugs, monoresistant TB started to develop, followed by poly-resistant TB (resistance to two or more drugs), multi-drug resistant (MDR)-TB (resistance to at least H+R), and extensively-drug resistant (XDR)-TB (defined as MDR-TB plus resistance to at least one fluoroquinolone (FQ) and one second-line injectable drug). The need for definitions beyond XDR-TB is a currently an issue of debate.The definitions in the field of anti-TB drug resistance should be based on two main fact...

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confidence: 99%

Tuberculosis: are we making it incurable?

2013

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“…Kanamycin was identified as the second-line injectable that had a larger effect on treatment success in the treatment of MDR-TB compared to capreomycin [17]. It is therefore surprising that only 24% of the countries reported the availability of this drug.…”

Section: Discussionmentioning

confidence: 99%

Availability, price and affordability of anti-tuberculosis drugs in Europe: a TBNET survey

et al. 2014

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Data on availability and cost of anti-tuberculosis (TB) drugs in relation to affordability at national level are scarce.We performed a cross-sectional study on availability and cost of anti-TB drugs at major TB-reference centres in 37 European countries. Costs of standardised treatment regimens used for pan-sensitive TB, multidrug-resistant (MDR) TB, pre-extensively drug-resistant (XDR) TB, and XDR-TB were compared using a purchasing power analysis. Affordability was evaluated in relation to monthly national gross domestic products per capita (GDP).At least one second-line injectable and either moxifloxacin or levofloxacin were available in all countries. Linezolid and clofazimine were available in 79% and 46% of the countries, respectively. Drug cost for XDR-TB was three-times more expensive than those for MDR-TB. The average price of treatment for pan-sensitive TB represented a maximum of 8.5% of the monthly GDP across countries, while for standard MDR-TB treatment this was <30% in only six countries and more than 100% in four countries. Treatment of XDR-TB represented more than 100% of a month's GDP in all countries where the regimen was available.High cost and limited availability of drugs for treatment of drug-resistant TB, particularly beyond resistance to first-line drugs, are a major impediment to successful TB control in Europe. @ERSpublications Limited availability and high cost of drugs hamper the treatment of drug-resistant tuberculosis in Europe

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“…These drugs are already considered cornerstone agents for the treatment of MDR tuberculosis, and the use of lategeneration drugs of this class against susceptible isolates was associated with an adjusted odds ratio of 2·5 for treatment success in an individual patient metaanalysis. 337 Fluoroquinolones form complexes with bacterial DNA and topoisomerase enzymes to inhibit bacterial replication. However, their bactericidal effect is mediated through subsequent chromosomal fragmen tation and generation of reactive oxygen species, as well as at least one other poorly characterised mechanism.…”

Section: Fluoroquinolonesmentioning

confidence: 99%

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

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Gumbo

Maartens

et al. 2017

The Lancet Respiratory Medicine

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Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients

Abstract: Dick Menzies and colleagues report findings from a collaborative, individual patient-level meta-analysis of treatment outcomes among patients with multidrug-resistant tuberculosis.

Cited by 459 publications

References 43 publications

Tuberculosis: are we making it incurable?

Tuberculosis: are we making it incurable?

Availability, price and affordability of anti-tuberculosis drugs in Europe: a TBNET survey

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

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