Meropenem MICs at Standard and High Inocula and Mutant Prevention Concentration Inter-Relations: Comparative Study with Non-Carbapenemase-Producing and OXA-48-, KPC- and NDM-Producing Klebsiella pneumoniae

Maria V Golikova; Elena N Strukova; Kamilla N Alieva; Vladimir A Ageevets; Alisa A Avdeeva; Ofeliia S Sulian; Stephen H Zinner

doi:10.3390/antibiotics12050872

Meropenem MICs at Standard and High Inocula and Mutant Prevention Concentration Inter-Relations: Comparative Study with Non-Carbapenemase-Producing and OXA-48-, KPC- and NDM-Producing Klebsiella pneumoniae

Antibiotics (Basel). 2023 May 8;12(5):872. doi: 10.3390/antibiotics12050872.

Authors

Maria V Golikova¹, Elena N Strukova¹, Kamilla N Alieva¹, Vladimir A Ageevets², Alisa A Avdeeva², Ofeliia S Sulian², Stephen H Zinner³

Affiliations

¹ Department of Pharmacokinetics & Pharmacodynamics, Gause Institute of New Antibiotics, 11 Bolshaya Pirogovskaya Street, 119021 Moscow, Russia.
² Pediatric Research and Clinical Center for Infectious Diseases, 9 Prof. Popov Street, 197022 St. Petersburg, Russia.
³ Department of Medicine, Harvard Medical School, Mount Auburn Hospital, 330 Mount Auburn St., Cambridge, MA 02138, USA.

Abstract

The minimal inhibitory concentration (MIC) is conventionally used to define in vitro levels of susceptibility or resistance of a specific bacterial strain to an antibiotic and to predict its clinical efficacy. Along with MIC, other measures of bacteria resistance exist: the MIC determined at high bacterial inocula (MIC_HI) that allow the estimation of the occurrence of inoculum effect (IE) and the mutant prevention concentration, MPC. Together, MIC, MIC_HI and MPC represent the bacterial "resistance profile". In this paper, we provide a comprehensive analysis of such profiles of K. pneumoniae strains that differ by meropenem susceptibility, ability to produce carbapenemases and specific carbapenemase types. In addition, we have analyzed inter-relations between the MIC, MIC_HI and MPC for each tested K. pneumoniae strain. Low IE probability was detected with carbapenemase-non-producing K. pneumoniae, and high IE probability was detected with those that were carbapenemase-producing. MICs did not correlate with the MPCs; significant correlation was observed between the MIC_HIs and the MPCs, indicating that these bacteria/antibiotic characteristics display similar resistance properties of a given bacterial strain. To determine the possible resistance-related risk due to a given K. pneumoniae strain, we propose determining the MIC_HI. This can more or less predict the MPC value of the particular strain.

Keywords: KPC carbapenemase; Klebsiella pneumoniae; NDM carbapenemase; OXA-48 carbapenemase; antibiotic resistance; carbapenems; inoculum effect; meropenem; mutant prevention concentration.

Grants and funding

21-74-10090/Russian Science Foundation