Etest to detect drug-resistant Neisseria gonorrhoeae to contemporary treatment; methodological issues concerning accuracy and reproducibility

Abstract

I was interested to read the paper by Papp and colleagues published in the Journal of Medical Microbiology 2018. Neisseria gonorrhoeae is a sexually transmitted bacterial pathogen that continues to evolve to become resistant to known antibiotics. The authors aimed to examine the intra-laboratory variability of using the Etest method to provide consistent MIC values for N. gonorrhoeae and also compared the results of the Etest to known agar dilution MIC values [1]. Clinical N. gonorrhoeae isolates, 100 paired duplicates, were tested by 8 laboratories for antibiotic susceptibility to ceftriaxone, cefixime and azithromycin using Etest strips. The authors reported that, overall, >80 % of the paired Etest MIC values were within one log 2 dilution of the replicate. When compared to the agar dilution reference method, the cefixime Etest MIC values were consistently underreported by one dilution (seven laboratories) or two dilutions (one laboratory). The azithromycin Etest MIC values agreed 90.7 % with the agar dilution MIC values, while the agreement with ceftriaxone was 90.9 %.However, these results are not the most appropriate estimates to assess accuracy (validity) and reproducibility (precision). First, reproducibility (precision, repeatability and reliability) is a completely different methodological issue compared to accuracy (validity). Reproducibility is the degree to which measures are free from error and therefore yield consistent results (i.e. the consistency of a measurement procedure). If a measurement device or procedure consistently assigns the same score to individuals or objects with equal values, the instrument is considered reliable. Validity (accuracy) has been defined by 'the extent to which [a test] measures what it claims to measure'. A measure is valid if it measures what it is supposed to measure, and does so cleanly -without accidentally including other factors. It is crucial to know that, in reproducibility analysis, our approach should be individual-based; however, to assess accuracy, a global average approach is usually applied [2]. It is good to know that to assess reproducibility for quantitative variables, the intra-class correlation coefficient (ICCC) single measure or Bland-Altman plot can be applied. Regarding accuracy, depending on the type of the variable (qualitative or quantitative), well-known statistical tests can be considered. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), positive likelihood ratio, negative likelihood ratio and the diagnostic odds ratio (the ratio of true to false results) are the most appropriate estimates to evaluate the validity of a test compared to a gold standard. In the case of quantitative variables, depending on the distribution of the variable, the Pearson r or Spearman rho can be applied. Therefore, to assess reproducibility and accuracy, appropriate tests as well as correct interpretations should be considered [2][3][4][5].In this letter, I emphasized methodological and statistical issues in reproduc...

Detection and Drug Susceptibility Testing of Neisseria gonorrhoeae Using Isothermal Microcalorimetry

“…With respect to antimicrobial susceptibility testing, our results show that with rather low concentration susceptibility could be determined within 12 h. At this point isolation would be needed before running a calorimetry measurement. As isolation takes 24 h and testing takes another 12 h, results can be expected within 36 h. Overall this is still 12 h faster than conventional methods [49,50]. Use of a higher initial inoculum is expected to speed up the detection, and we estimate that with an inoculum of 10 6 CFU•mL −1 the time to results could be lowered to 28 h. This would be similar to drug susceptibility testing using direct qPCR [51].…”