Publications by authors named "Nicole Aalders"

2 Publications

  • Page 1 of 1

Implementation of Semiautomated Antimicrobial Susceptibility Interpretation Hardware for Nontuberculous Mycobacteria May Overestimate Susceptibility.

J Clin Microbiol 2019 04 28;57(4). Epub 2019 Mar 28.

Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands

Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) guideline-approved manual readout of microtiter plates for antimicrobial susceptibility testing (AST) to determine antibiotic minimum inhibitory concentrations (MICs). Interpretation of these plates leads to different outcomes between laboratories. The SensiTitre Vizion digital MIC viewing system (Vizion) offers a more streamlined approach using semiautomated reading. Here, we conducted a blinded trial comparing the outcome of AST between manual readout and Vizion readout for 132 NTM isolates, amounting to 727 individual tests for antibiotic susceptibility ranging across 13 individual antibiotics with established CLSI breakpoints. From this, we calculated specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and the F1 value, as well as assessing major error (ME) and very major error (VME) rates. We find that Vizion-assisted AST produces significantly lower MICs (paired Wilcox signed rank test; < 0.0001). The Vizion had an accuracy of 89,40%, producing 61 MEs (8.39%) and 16 VMEs (2.20%). The calculated specificity was 0.8370, the sensitivity was 0.9550, the PPV was 0.8460, the NPV was 0.9520, and the F1 score was 0.8970. We show that discrepant readings mostly stem from CLSI guideline breakpoints being close to, or overlapping, the MIC values, leading to small discrepancies crossing the breakpoint, contributing to VMEs and MEs. Using the Vizion in standard clinical diagnostics for NTM might lead to an overestimation of antibiotic susceptibility.
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April 2019

Linking minimum inhibitory concentrations to whole genome sequence-predicted drug resistance in Mycobacterium tuberculosis strains from Romania.

Sci Rep 2018 06 26;8(1):9676. Epub 2018 Jun 26.

Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.

Mycobacterium tuberculosis drug resistance poses a major threat to tuberculosis control. Current phenotypic tests for drug susceptibility are time-consuming, technically complex, and expensive. Whole genome sequencing is a promising alternative, though the impact of different drug resistance mutations on the minimum inhibitory concentration (MIC) remains to be investigated. We examined the genomes of 72 phenotypically drug-resistant Mycobacterium tuberculosis isolates from 72 Romanian patients for drug resistance mutations. MICs for first- and second-line drugs were determined using the MycoTB microdilution method. These MICs were compared to macrodilution critical concentration testing by the Mycobacterium Growth Indicator Tube (MGIT) platform and correlated to drug resistance mutations. Sixty-three (87.5%) isolates harboured drug resistance mutations; 48 (66.7%) were genotypically multidrug-resistant. Different drug resistance mutations were associated with different MIC ranges; katG S315T for isoniazid, and rpoB S450L for rifampicin were associated with high MICs. However, several mutations such as in rpoB, rrs and rpsL, or embB were associated with MIC ranges including the critical concentration for rifampicin, aminoglycosides or ethambutol, respectively. Different resistance mutations lead to distinct MICs, some of which may still be overcome by increased dosing. Whole genome sequencing can aid in the timely diagnosis of Mycobacterium tuberculosis drug resistance and guide clinical decision-making.
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June 2018