Prediction of Aztreonam Effectiveness Against Klebsiella pneumoniae Based on the Results of Antimicrobial Susceptibility Testing with Increased Inoculum

Background. The minimum inhibitory concentration (MIC) does not predict the risk of antibacterial resistance development due to a small sample of tested bacteria. Minimum inhibitory concentration at an increased inoculum (MIC_HI) may become a suitable parameter for this purpose as a sample of tested bacteria is larger while the method of determination remains easy.

The aim of the study was to evaluate the potential of using MIC_HI as a parameter for predicting the resistance development in Klebsiella pneumoniae to aztreonam.

Methods. Aztreonam MIC and MIC_HI values were assessed against two strains of K. pneumoniae using the microdilution method (0.2 ml volume; inoculum of 5×10⁵ and 5×10⁷ CFU/ml, respectively) and compared the results with the effect of aztreonam in a dynamic in vitro model, in which  aztreonam regimen of 2 grams every 8 hours as a 2-hour infusion for 5 days was simulated.

Results. The efficacy of aztreonam against K. pneumoniae observed in the dynamic model was consistent with the MIC_HIs values assessed based on bacterial viability. During the visual assessment, the MIC_HIs values were greatly overestimated due to excessive turbidity caused by the formation of filamentous forms of bacteria exposed to aztreonam.

Conclusions. The MIC_HI parameter can be used to predict the development of resistance in K. pneumoniae to aztreonam when assessing the values of this parameter by the number of viable cells, but not by the visual boundary of bacterial growth.

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