1457 - Serial Passage of Enterobacteriaceae to Explore Development of Carbapenem Resistance

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Presenting Author(s)

Yosef Nissim

Infectious Diseases Pharmacy Specialist
Hackensack Meridian Health Ocean Medical Center
Lakewood, New Jersey
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

Douglas Slain

Professor and Chair, Department of Clinical Pharmacy
West Virginia University
Morgantown, West Virginia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
RL

Rocco LaSala

Medical Director of Clinical Laboratories
West Virginia University
Morgantown, West Virginia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Background: Carbapenems are broad-spectrum antibacterials that have seen increased usage for the Enterobacteriales family in recent years. While carbapenem usage has been associated with increased antibacterial resistance, there is currently a lack of data comparing the risk of reduced susceptibility selection by the two most commonly used carbapenems in the US, ertapenem (ERT) and meropenem (MER). We conducted a novel serial passage experiment with clinical isolates of Enterobacteriales to assess the impact of repeated exposure to ERT or MER on phenotypic susceptibility patterns.

Methods: Non-duplicate clinical Enterobacteriales isolates were selected randomly for inclusion. Antimicrobial susceptibility testing was performed by CLSI disc diffusion methods. Standardized suspensions of isolates were plated on Mueller-Hinton agar, and ERT (10mcg) and MER (10mcg) discs applied. Zones of inhibition were measured and recorded after 16-18 hours incubation. Growth from the innermost zone of inhibition around each disc was used to prepare subsequent suspensions for serial susceptibility testing. This process would be repeated daily for 10 days. Each subsequent serially-passaged isolated was tested against both ERT and MER. Daily zones of inhibition were measured and interpreted. Baseline & final susceptibilities were determined by automated methods (Vitek 2).

Results: Seventeen Enterobacteriaceae isolates were selected, including: Klebsiella pneumoniae (n=11), Klebsiella oxytoca (n=2), Escherichia coli (n=1), Morganella morganii (n=1), and Enterobacter cloacae (n=2). Despite a greater degree of reductions in zones of inhibition with repeated ERT exposure (vs MER), the overall 10 day trends were not found to be significant different (P=0.529). Resistance developed to ERT in six isolates compared to one MER-resistant isolate (P = 0.053). E. cloacae was the only species to show a significant change between drugs (P=0.010). Two of three isolates that developed reduced zone changes > 10mm to MER were initially exposed to ERT on an earlier plate.

Conclusion: This novel experiment identified the development of some nonsignificant reductions in susceptibility with ERT after serial exposure. Results from this pilot study should encourage larger well-designed studies in this area.