Improving Outcomes for Multidrug-Resistant Tuberculosis: Aggressive Regimens Prevent Treatment Failure and Death

Velásquez, Gustavo E.; Becerra, Mercedes C.; Gelmanova, Irina; Pasechnikov, Alexander; Yedilbayev, Askar; Shin, Sonya; Andreev, Yevgeny G.; Yanova, Galina V.; Atwood, Sidney; Mitnick, Carole D.; Franke, Molly F.; Rich, Michael; Keshavjee, Salmaan

doi:10.1093/cid/ciu209

Cited by 48 publications

(44 citation statements)

References 31 publications

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“…Study of reinforced initial regimens while awaiting the result of such a quantitative susceptibility panel appears warranted. 6,19 …”

Section: Discussionmentioning

confidence: 99%

“…5 In Tomsk, Siberia, through a recent multidisciplinary effort to individualize MDR-TB treatment, relatively high rates of favorable treatment outcomes were reported. 6 However, these patients were largely non-HIV-infected, and anti-tuberculosis treatment had been applied in an algorithmic approach based on expanded drug susceptibility testing (DST) results. The potential utility of such an approach within the HIV-infected population of Irkutsk has not been studied.…”

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confidence: 99%

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Undertreated HIV and drug-resistant tuberculosis at a referral hospital in Irkutsk, Siberia

Heysell

Огарков

Жданова

et al. 2016

int j tuberc lung dis

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SUMMARY SETTING A referral hospital for tuberculosis (TB) in Irkutsk, the Russian Federation. OBJECTIVE To describe disease characteristics, treatment and hospital outcomes of TB-HIV (human immunodeficiency virus). DESIGN Observational cohort of HIV-infected patients admitted for anti-tuberculosis treatment over 6 months. RESULTS A total of 98 patients were enrolled with a median CD4 count of 147 cells/mm3 and viral load of 205 943 copies/ml. Among patients with drug susceptibility testing (DST) results, 29 (64%) were multidrug-resistant (MDR), including 12 without previous anti-tuberculosis treatment. Nineteen patients were on antiretroviral therapy (ART) at admission, and 10 (13% ART-naïve) were started during hospitalization. Barriers to timely ART initiation included death, in-patient treatment interruption, and patient refusal. Of 96 evaluable patients, 21 (22%) died, 14 (15%) interrupted treatment, and 10 (10%) showed no microbiological or radiographic improvement. Patients with a cavitary chest X-ray (aOR 7.4, 95%CI 2.3–23.7, P = 0.001) or central nervous system disease (aOR 6.5, 95%CI 1.2–36.1, P=0.03) were more likely to have one of these poor outcomes. CONCLUSION High rates of MDR-TB, treatment interruption and death were found in an HIV-infected population hospitalized in Irkutsk. There are opportunities for integration of HIV and TB services to overcome barriers to timely ART initiation, increase the use of anti-tuberculosis regimens informed by second-line DST, and strengthen out-patient diagnosis and treatment networks.

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“…Study of reinforced initial regimens while awaiting the result of such a quantitative susceptibility panel appears warranted. 6,19 …”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Undertreated HIV and drug-resistant tuberculosis at a referral hospital in Irkutsk, Siberia

Heysell

Огарков

Жданова

et al. 2016

int j tuberc lung dis

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“…The need to provide more comprehensive molecular resistance testing information on a particular class of drug is also underlined by a recent clinical finding which shows that aggressive therapy (minimum of six drugs in the initial phase and four drugs in the continuation phase [22]) or a treatment regimen with at least five so-called efficacious drugs (27) provides a significantly better outcome for our patients. In order to adequately determine such a powerful regimen, the laboratory must rapidly guide the health care provider with a comprehensive analysis and interpretation of more-detailed molecular results.…”

Section: (Iv) Are All Mdr-tb Patients With Additional Drug Resistancementioning

confidence: 99%

Commentary: The Race Is On To Shorten the Turnaround Time for Diagnosis of Multidrug-Resistant Tuberculosis

Somoskövi

2015

J Clin Microbiol

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A ccording to the World Health Organization (WHO), there are many hot spots of multidrug-resistant tuberculosis (MDR-TB), defined as resistance to rifampin (RIF) and isoniazid (INH), in the world. In one of the hot spots, the Russian Federation, a total of 142,500 TB cases, including an estimated 41,000 MDR-TB pulmonary cases in 2013, were reported. Of all new TB cases, 19% were MDR-TB, and among retreated cases, 49% were MDR-TB cases (1). In contrast, the U.S. Centers for Disease Control and Prevention (CDC) reported 9,582 TB cases, including 96 MDR-TB cases in 2014, resulting in 1.3% of all TB cases with available antimicrobial susceptibility test (AST) results (2). The time has come to screen all TB cases in the United States for MDR-TB either at the time a sputum specimen tests positive with a nucleic acid amplification test (NAAT) or when the culture yields a positive result for Mycobacterium tuberculosis complex.The faster turnaround time for diagnosing MDR-TB, enabled by current molecular assays which yield results within hours compared to weeks and months with conventional testing, is needed in order to make up for lost time because of patient and/or health care system delays. An earlier diagnosis of MDR-TB facilitates earlier prescription of an adequate regimen benefiting patients and public health. However, in addition to screening all patients rapidly for MDR-TB, additional information is necessary from molecular assays for the successful management of MDR-TB patients.Besides the presence or absence of M. tuberculosis, the next additional answer from a routine rapid molecular test is whether the patient's specimen contains MDR-TB. In cases where MDR-TB is confirmed, the second question that such an assay will need to rapidly confirm is the presence of extensively drug-resistant tuberculosis (XDR-TB), which is defined as MDR-TB plus resistance to quinolones and second-line injectable drugs. IS RAPID CONFIRMATION OF THE FACT THAT THE PATIENT HAS MDR-OR XDR-TB ENOUGH OR DO WE NEED TO GO BEYOND WITH RAPID MOLECULAR SCREENING?In light of the accumulating evidence on the meaning of molecular mechanisms of different first-and second-line antituberculosis drugs, by appropriate characterization of known and newly identified resistance-associated mutations with quantitative phenotypic susceptibility testing, it is time to raise the question " is rapid detection of MDR and XDR-TB alone enough to successfully win the war on TB or MDR-TB?" Can we extract and utilize more meaningful diagnostic information from currently used molecular tests for our patients?In order to settle this question, we need to keep in mind that molecular markers cannot only rapidly confirm the presence of MDR-TB, they may also provide additional valuable information that can help to predict the level of phenotypic resistance or even cross-resistance to certain first-and second-line antituberculosis drugs. These molecular markers may provide such important additional information as to significantly influence the care of the patient and ultim...

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“…One third of the increase in the incidence of TB in the past five years can be linked to HIV co-infection 1 . The situation is exacerbated by occurrence of multiple drug resistant (MDR-TB) strains, extreme drug resistant (XDR-TB) strains and even total drug resistant (TDR-TB) strains that do not respond to some or most of the currently used antitubercular drugs 2 . Growing incidence of drug resistance, severe side effects of current treatment and growing number of HIV patients makes the discovery of novel more potent antitubercular compounds an important issue 3 .…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosisenoyl-acyl carrier protein reductase inhibitors as potential antituberculotics: development in the past decade

Holas¹,

Ondrejcek

Doležal³

2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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Mycobacterial enoyl-ACP-reductase, an enzyme contributing in mycolic acids biosynthesis, has been established as promising target of novel antimycobacterial drugs. The development of inhibitors active without previous activation by catalase/peroxidase system (e.g. isoniazid), seems to be rational approach. Catalase/peroxidase system is frequently responsible for resistance. We hereby present a review of direct mycobacterial enoyl-acyl carrier protein reductase inhibitors development in past decade. A special attention was paid to mechanism of inhibition, which shows relatively conserved interactions of inhibitors with Tyr 158 and cofactor. Hence, future developments of more effective antitubercular drugs should consider structural demands for potent direct mycobacterial enoyl reductase inhibitors.

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Improving Outcomes for Multidrug-Resistant Tuberculosis: Aggressive Regimens Prevent Treatment Failure and Death

Cited by 48 publications

References 31 publications

Undertreated HIV and drug-resistant tuberculosis at a referral hospital in Irkutsk, Siberia

Undertreated HIV and drug-resistant tuberculosis at a referral hospital in Irkutsk, Siberia

Commentary: The Race Is On To Shorten the Turnaround Time for Diagnosis of Multidrug-Resistant Tuberculosis

Mycobacterium tuberculosisenoyl-acyl carrier protein reductase inhibitors as potential antituberculotics: development in the past decade

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