Challenging a dogma: antimicrobial susceptibility testing breakpoints for Mycobacterium tuberculosis

Ängeby, Kristian; Juréen, Pontus; Kahlmeter, Gunnar; Hoffner, Sven; Schӧn, Thomas

doi:10.2471/blt.11.096644

Cited by 94 publications

(109 citation statements)

References 10 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…One possible explanation for the observed lack of specificity for predicting phenotypic CAP resistance may lie in the WHO-recommended critical concentration for MGIT 960 DST that we used for our study. Since the current critical concentration was accepted by the WHO, it has been demonstrated that this critical concentration is substantially higher than the epidemiological cutoff (ECOFF) that separates wild-type M. tuberculosis from those with mutations conferring CAP resistance, which might result in non-wild-type isolates being classified as CAP s (38,39). Interpreted in the context of our findings, it is possible that the WHO-recommended critical concentration we used misclassified CAP-resistant organisms as susceptible, resulting in a reduced specificity of the mutation for predicting phenotypic resistance.…”

Section: Discussionmentioning

confidence: 99%

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

et al. 2014

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

et al. 2014

View full text Add to dashboard Cite

“…However, several disadvantages are associated with using CC values in DST. First, up to 5% of wild-type M. tuberculosis strains (10% for pyrazinamide) are effectively classified as drug resistant, and second, clinical outcome data for individual drugs often are not available because combination therapy is the norm for TB treatment (5). In addition, the CCs for many older anti-TB drugs, including some examined in this study, were established many years ago and have not since been revalidated; hence, any genetic variation over time, as well as the development of resistance, will not have been accounted for (3).…”

mentioning

confidence: 99%

“…For example, one analysis has reported that regional variability of M. tuberculosis susceptibility to ofloxacin would result in different CC values from isolates in different settings (6,7). As a result of these factors, together with the common occurrence that the CC is close to the MIC, there is a high probability of misclassification of M. tuberculosis strains as susceptible or resistant when using a CC-based APA method (5).…”

mentioning

confidence: 99%

A Multilaboratory, Multicountry Study To Determine MIC Quality Control Ranges for Phenotypic Drug Susceptibility Testing of Selected First-Line Antituberculosis Drugs, Second-Line Injectables, Fluoroquinolones, Clofazimine, and Linezolid

et al. 2016

Self Cite

View full text Add to dashboard Cite

jOur objective was to establish reference MIC quality control (QC) ranges for drug susceptibility testing of antimycobacterials, including first-line agents, second-line injectables, fluoroquinolones, and World Health Organization category 5 drugs for multidrug-resistant tuberculosis using a 7H9 broth microdilution MIC method. A tier-2 reproducibility study was conducted in eight participating laboratories using Clinical Laboratory and Standards Institute (CLSI) guidelines. Three lots of custom-made frozen 96-well polystyrene microtiter plates were used and prepared with 2؋ prediluted drugs in 7H9 broth-oleic acid albumin dextrose catalase. The QC reference strain was Mycobacterium tuberculosis H37Rv. MIC frequency, mode, and geometric mean were calculated for each drug. QC ranges were derived based on predefined, strict CLSI criteria. Any data lying outside CLSI criteria resulted in exclusion of the entire laboratory data set. Data from one laboratory were excluded due to higher MIC values than other laboratories. QC ranges were established for 11 drugs: isoniazid (0.03 to 0.12 g/ml), rifampin (0.03 to 0.25 g/ml), ethambutol (0.25 to 2 g/ml), levofloxacin (0.12 to 1 g/ml), moxifloxacin (0.06 to 0.5 g/ml), ofloxacin (0.25 to 2 g/ml), amikacin (0.25 to 2 g/ml), kanamycin (0.25 to 2 g/ml), capreomycin (0.5 to 4 g/ml), linezolid (0.25 to 2 g/ml), and clofazimine (0.03 to 0.25 g/ml). QC ranges could not be established for nicotinamide (pyrazinamide surrogate), prothionamide, or ethionamide, which were assay nonperformers. Using strict CLSI criteria, QC ranges against the M. tuberculosis H37Rv reference strain were established for the majority of commonly used antituberculosis drugs, with a convenient 7H9 broth microdilution MIC method suitable for use in resource-limited settings. Managing an estimated global annual incidence of 9.6 million Mycobacterium tuberculosis cases requires an arsenal of effective antituberculosis (anti-TB) drugs that are active against both susceptible and multidrug-resistant strains (1). Furthermore, maximizing the effectiveness of treatment and minimizing the risk of development of further resistance requires accurate drug susceptibility testing (DST) for M. tuberculosis clinical isolates (2, 3). To improve reliability of DST for M. tuberculosis, regulators have introduced a requirement to establish quality control (QC) ranges for new and repurposed anti-TB drugs (4).Two approaches to M. tuberculosis DST are currently employed: critical concentration (CC)-based agar proportion assay (APA) and MIC-based methodology. CC is well established and used widely for classifying the sensitivity of M. tuberculosis to anti-TB drugs. The CC, also known as the antimicrobial susceptibility testing breakpoint, is defined by international convention as the lowest concentration of a drug that inhibits growth of 95% (90% for pyrazinamide) of wild-type M. tuberculosis strains, while at the same time it does not inhibit strains that are considered to be clinically resistant (i.e., isolated from patients unres...

show abstract

“…However, as recently published by an expert group in Europe, to adjust the dose of particular drugs in treatment, especially in complicated cases involving multidrug resistance and severe side effects, there is a need to determine the true MIC. [22,55,56] This provides the possibility to increase the dose of the respective drug to overcome a reduced susceptibility. [57,58] Nowadays, MIC values of rifampicin near the breakpoint are also detected regularly.…”

Section: Drug Susceptibilitymentioning

confidence: 99%

“…Furthermore, for particular drugs, like ethambutol, the reproducibility is questionable due to the close natural distribution of the MIC and the critical concentration. [22,55,62] …”

Section: Drug Susceptibilitymentioning

confidence: 99%

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

Zuur

Bolhuis

Anthony

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment. Areas covered: Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment. Expert opinion: Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment. ARTICLE HISTORY

show abstract

Challenging a dogma: antimicrobial susceptibility testing breakpoints for Mycobacterium tuberculosis

Cited by 94 publications

References 10 publications

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

A Multilaboratory, Multicountry Study To Determine MIC Quality Control Ranges for Phenotypic Drug Susceptibility Testing of Selected First-Line Antituberculosis Drugs, Second-Line Injectables, Fluoroquinolones, Clofazimine, and Linezolid

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

Contact Info

Product

Resources

About