Sensititre MycoTB Plate Compared to Bactec MGIT 960 for First- and Second-Line Antituberculosis Drug Susceptibility Testing in Tanzania: a Call To Operationalize MICs

Abstract

c MIC testing for Mycobacterium tuberculosis is now commercially available. Drug susceptibility testing by the MycoTB MIC plate has not been directly compared to that by the Bactec MGIT 960. We describe a case of extensively drug-resistant tuberculosis (XDR-TB) in Tanzania where initial MIC testing may have prevented acquired resistance. From testing on archived isolates, the accuracy with the MycoTB plate was >90% for important first-and second-line drugs compared to that with the MGIT 960, and clinically useful quantitative interpretation was also provided.A mong other factors, the total numbers of drugs and drug class to which a Mycobacterium tuberculosis isolate is resistant predict the treatment outcomes (1, 2). Despite the advantage of rapid susceptibility testing results, the molecular mechanisms of drug resistance remain incomplete for many drugs used in the treatment of multidrug-resistant tuberculosis (MDR-TB) (3). Phenotypic methods rely on mycobacterial cultures, but the testing is ultimately qualitative, reporting a threshold of growth in the presence of a single "critical" drug concentration. In contrast to the quantitative results used in the testing of other rapidly growing pathogens, the critical concentrations for M. tuberculosis are based in part on the epidemiological breakpoints, which for some drugs are very near the MIC (4). The World Health Organization (WHO) endorsed phenotypic methods for drug susceptibility testing (DST), including the agar proportion method (APM) on solid medium and an automated system in liquid medium, the Bactec MGIT 960 (BD, Franklin Lakes, NJ, USA).To overcome the prior limitations with MIC testing, a commercially available microtiter plate of lyophilized antituberculosis drugs (Sensititre MycoTB; Trek Diagnostics, Cleveland, OH, USA) was introduced (5). Prior comparisons of the MycoTB plate with the APM on Middlebrook agar found excellent agreement for most drugs (Ͼ94%) (5-7). To our knowledge, the MycoTB plate has not been compared to the Bactec MGIT 960.The Kilimanjaro Clinical Research Institute in Moshi, Tanzania, supports a biosafety level 3 facility for M. tuberculosis research and receives study specimens from the national MDR-TB hospital, the Kibong'oto Infectious Diseases Hospital (KIDH). We hence compared DST results from the MycoTB plate and the Bactec MGIT 960 using archived specimens and now describe an illustrative clinical case from the KIDH.Isolates were originally obtained from patients with known or suspected MDR-TB who had provided written informed consent for a protocol approved by the institutional review boards of the Tanzania National Institute for Medical Research and the University of Virginia. The M. tuberculosis complex was identified by Gen-Probe (San Diego, CA). Molecular testing results for rpoB or inhA and katG mutations by the Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) and the GenoType MTBDRplus (Hain Lifescience, Nehren, Germany), respectively, were recorded if the tests were performed for clinical purposes. In previous studies, ...

Reduced Chance of Hearing Loss Associated with Therapeutic Drug Monitoring of Aminoglycosides in the Treatment of Multidrug-Resistant Tuberculosis

“…This means that analytical techniques in order to analyze amikacin or kanamycin in serum with high-throughput rates should be made available in all TB programs to deliver fast and accurate results. In addition, simple drug susceptibility testing in order to establish a precise MIC value should also be available (35). Both PK and PD analysis requires trained and experienced personnel with equipment.…”

Individualizing management of extensively drug-resistant tuberculosis: diagnostics, treatment, and biomarkers

“…However, individualized treatment is based on true minimum inhibitory concentration (MIC) of drugs when testing the MTB isolate [17,51,52]. In addition to easy-to-implement MIC testing [109], a central reference laboratory is crucial for optimal treatment outcome in XDR-TB.…”

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

“…The MIC of a drug was considered the lowest concentration able to inhibit the visible growth of a microorganism in a well. The resistance breakpoints were based on previously established concentrations [STR– 2.0, RMP– 1.0, rifabutin (RFB)– 0.5, INH– 0.2, EMB– 5.0, OFX– 2.0, MFX– 0.5, KAN–>5.0, AMK–>4.0, PAS– 2, ETH– 5, and D-cycloserine– 30 μg/ml] [17]. A correlation analysis of the MICs for pairs of drugs was performed using the Statistica software version 10 (Dell Software, Tulsa, OK, USA).…”

“…MycoTB is an inexpensive method to simultaneously identify the minimal inhibitory concentrations (MICs) of twelve first- and second-line drugs. Previous studies have demonstrated the method’s good reliability and reproducibility for most drugs compared with the agar proportion method [8, 11, 16] and the MGIT method [8, 17]. In this study, we compared these two phenotypic methods using clinical strains isolated in the Moscow region of Russia.…”