Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance

Cegielski, J. Peter; Kurbatova, Ekaterina V.; Walt, Martie van der; Brand, Jeannette; Ershova, Julia; Tupasi, Thelma E.; Caoili, Janice Campos; Dalton, Tracy; Contreras, Carmen; Yagui, Martín; Bayona, Jaime; Kvasnovsky, Charlotte; Leimane, Vaira; Kukša, Līga; Chen, Michael P.; Via, Laura E.; Hwang, Sung-Kyun; Wolfgang, Melanie; Volchenkov, Grigory; Somova, Tatiana R.; Smith, Sarah E.; Akksilp, Somsak; Wattanaamornkiet, Wanpen; Kim, Hee Jin; Kim, Changki; Kazennyy, Boris Y.; Khorosheva, Tatiana; Kliiman, Kai; Viiklepp, Piret; Jou, Ruwen; Huang, Angela; Vasilyeva, Irina; Demikhova, Olga V.; Investigators, Global Petts; Lancaster, Joey; Odendaal, Ronel; Diem, Lois; Perez, Therese C; Gler, Tarcela; Tan, K K; Bonilla, César; Jave, Oswaldo; Asencios, Luis; Yale, Gloria; Suarez, Carmen; Walker, Allison Taylor; Norvaisha, Inga; Šķenders, Ģirts; Sture, Ingrida; Riekstiņa, Vija; Cīrule, Andra; Sigman, Erika; Cho, Sung Rae; Cai, Ying; Eum, Seok-Yong; Lee, Jong-Seok; Park, Seung-Kyu; Jeon, Doosoo; Shamputa, Isdore Chola; Metchock, Beverly; Кузнецова, Т. А.; Akksilp, Rattanawadee; Sitti, Wanlaya; Inyapong, Jirapan; Kir'yanova, E. V.; Degtyareva, I. I.; Nemtsova, E.; Levina, Klavdia; Danilovitš, Manfred; Kummik, Tiina; Lei, Yung-Chao; Huang, Wei‐Lun; Erokhin, V V; Черноусова, Л. Н.; Andreevskaya, Sofya; Ларионова, Е. Е.; Смирнова, Т. Г.

doi:10.1093/cid/civ910

Cited by 73 publications

(69 citation statements)

References 19 publications

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“…In the case of rifampin, a prior study found that phenotypic DST does not capture some clinically relevant resistance conferred by disputed rpoB mutations that had previously been considered of indeterminate significance; these were associated with a rate of failure or relapse of first-line retreatment of 63% (6). For pyrazinamide, only a few studies have directly evaluated the correlation between in vitro resistance with clinical outcomes (12,(29)(30)(31)(32). One of these reported that patients whose isolates had an MIC breakpoint of over 50 mg/liter had poor sputum conversion rates (12).…”

Section: Discussionmentioning

confidence: 99%

Pyrazinamide Resistance Assays and Two-Month Sputum Culture Status in Patients with Multidrug-Resistant Tuberculosis

Velásquez

Calderón

Mitnick

et al. 2016

Antimicrob Agents Chemother

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h Phenotypic drug susceptibility testing is the current "gold standard" for detecting Mycobacterium tuberculosis susceptibility to antituberculous drugs. Pyrazinamide is one antituberculous drug for which the correlation between in vitro resistance and clinical outcomes remains unclear. Here we performed latent class analysis (LCA) to develop a consensus gold standard definition of pyrazinamide resistance using three paired standard pyrazinamide resistance assays. We then compared this consensus measure to the 2-month culture results for patients with multidrug-resistant tuberculosis (MDR-TB) who were treated for 2 months with first-line antituberculous drugs before their resistance results were known. Among 121 patients with MDR-TB, 60 (49.6%) were resistant to pyrazinamide by the Wayne method (L. G. Wayne, Am Rev Respir Dis 109:147-151, 1974), 71 (58.7%) were resistant by the Bactec MGIT 960 method, and 68 (56.2%) were resistant by pncA sequencing. LCA grouped isolates with positive results by at least two assays into a category which we considered the "consensus gold standard" for pyrazinamide resistance. The sensitivity and specificity for this consensus gold standard were 82.4% and 92.5%, respectively, for the Wayne method; 95.6% and 88.7%, respectively, for the Bactec MGIT 960 method; and 92.6% and 90.6%, respectively, for pncA sequencing. After we adjusted for other factors associated with poor outcomes, including age, sex, alcohol use, and baseline ethambutol resistance, patients whose isolates were resistant by the LCA-derived consensus gold standard were more likely to be culture positive at 2 months with an odds ratio of 1.95 (95% confidence interval, 0.74 to 5.11), but this result was not statistically significant. These findings underscore the need for improved diagnostics for routine use in programmatic settings.

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Section: Discussionmentioning

confidence: 99%

Pyrazinamide Resistance Assays and Two-Month Sputum Culture Status in Patients with Multidrug-Resistant Tuberculosis

Velásquez

Calderón

Mitnick

et al. 2016

Antimicrob Agents Chemother

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“…The use of aminoglycosides is essential in MDR-TB treatment (20). However, pharmacokinetic monitoring is essential in selecting the optimal dose.…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations up to 10 mg/liter (0.3, 0.5, 1.5, 3.0, 5.0, 7.0, and 10.0 mg/liter) were analyzed without a dilution step. Concentrations between 10 and 40 mg/liter were diluted 1:6 with deionized water (20,30, and 40 mg/liter). High concentrations (60 to 80 mg/liter) were diluted 1:12 before analysis.…”

Section: Methodsmentioning

confidence: 99%

Immunoassay Analysis of Kanamycin in Serum Using the Tobramycin Kit

Dijkstra

Voerman

Greijdanus

et al. 2016

Antimicrob Agents Chemother

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bKanamycin is one of the aminoglycosides used in the treatment of multidrug-resistant tuberculosis. Blood concentrations of kanamycin are predictive for the treatment efficacy and the occurrence of side effects, and dose adjustments can be needed to optimize therapy. However, an immunoassay method for the quantification of kanamycin is not commercially available. We modified the existing tobramycin immunoassay to analyze kanamycin. This modified method was tested in a concentration range of 0.3 to 80.0 mg/liter for inaccuracy and imprecision. In addition, the analytical results of the immunoassay method were compared to those obtained by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method using Passing and Bablok regression. Within-day imprecision varied from 2.3 to 13.3%, and between-day imprecision ranged from 0.0 to 11.3%. The inaccuracy ranged from ؊5.2 to 7.6%. No significant cross-reactivity with other antimicrobials and antiviral agents was observed. The results of the modified immunoassay method were comparable with the LC-MS/MS analytical outcome. This new immunoassay method enables laboratories to perform therapeutic drug monitoring of kanamycin without the need for complex and expensive LC-MS/MS equipment.T uberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Unfortunately, resistance to the two firstline drugs in TB treatment, isoniazid and rifampin, is emerging (1). Treatment regimens for multidrug-resistant TB (MDR-TB) include a quinolone and an injectable: amikacin, kanamycin, or capreomycin (2). Unfortunately, the use of aminoglycosides comes with toxic effects, such as renal failure and irreversible hearing loss (3).Recently, a study with MDR-TB patients showed that the toxicity of aminoglycosides was correlated with the cumulative area under the curve (4). For efficacy, it is well recognized that the top serum concentration (C max ) is related to the efficacy of aminoglycosides (5). In addition, pharmacokinetic (PK) guided dosing reduced the daily dose of aminoglycosides, with excellent treatment outcome (6). This indicates that serum concentration monitoring may be of added value in the treatment of tuberculosis. The targeted peak concentration for kanamycin in MDR-TB is 20 to 30 mg/liter (7), while the trough concentration should be as low as reasonably achievable in order to prevent toxicity.Although analytical methods to quantify the serum or plasma concentrations of amikacin and kanamycin using liquid chromatography-tandem mass spectrometry (LC-MS/MS) (8-11) have been described, this technique is commonly not available in most developing countries (12). However, in contrast to the case for amikacin, no analytical immunoassay kit to analyze kanamycin is commercially available.Kanamycin is more structurally related to tobramycin than to amikacin (Fig. 1). The product insert of the tobramycin immunoassay kit, based on the enzyme multiplied immunoassay technique (EMIT), indicates cross-reactivity for kanamycin (13). We therefore explored the...

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“…Data from research design to evaluate the mechanism and its guiding principles demonstrate the impact and effectiveness of the initiative since its launch. In one large multinational prospective cohort study evaluating treatment approaches and comparing outcomes for MDR-TB patients in countries using the GLC mechanism versus those that did not showed that treatment success among patients in countries using the mechanism was substantially greater [83% versus 60%, respectively; (p < 0.001)] and by extension the initiative was shown to have reduced further emergence of anti-TB drug resistance [52]. The GLC mechanism may be useful in the development of other partnerships needed in the rational allocation of resources and tools for combating AMR more broadly.…”

Section: Examples Of Stewardshipmentioning

confidence: 99%

The global response to the threat of antimicrobial resistance and the important role of vaccines

Utt

Wells

2016

PPL

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Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance

Cited by 73 publications

References 19 publications

Pyrazinamide Resistance Assays and Two-Month Sputum Culture Status in Patients with Multidrug-Resistant Tuberculosis

Pyrazinamide Resistance Assays and Two-Month Sputum Culture Status in Patients with Multidrug-Resistant Tuberculosis

Immunoassay Analysis of Kanamycin in Serum Using the Tobramycin Kit

The global response to the threat of antimicrobial resistance and the important role of vaccines

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