A Mizrahi1,2, L Chat3, M Danjean4, C Mory5, J C Nguyen Van3, G Péan de Ponfilly3,6, F Caméléna7,8, A Le Monnier3,6, B Bercot7,8, A Birgy4,8, H Jacquier7,8, B Pilmis8,9. 1. Service de Microbiologie Clinique, Groupe Hospitalier Paris Saint-Joseph, 185 rue Raymond Losserand, 75014, Paris, France. amizrahi@ghpsj.fr. 2. UMR 1319, Institut Micalis, Université Paris-Saclay, INRAeChâtenay Malabry, AgroParisTech, France. amizrahi@ghpsj.fr. 3. Service de Microbiologie Clinique, Groupe Hospitalier Paris Saint-Joseph, 185 rue Raymond Losserand, 75014, Paris, France. 4. Service de Microbiologie Clinique, Hôpital Universitaire Robert Debré, Paris, France. 5. Plateforme de Dosages Des Anti-Infectieux, Groupe Hospitalier Paris Saint-Joseph, Paris, France. 6. UMR 1319, Institut Micalis, Université Paris-Saclay, INRAeChâtenay Malabry, AgroParisTech, France. 7. Service de Bactériologie, AP-HP Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal Site Saint Louis, Paris, France. 8. UMR1137, IAME, Université de Paris, INSERM, Paris, France. 9. Équipe Mobile de Microbiologie Clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
Abstract
BACKGROUND: The treatment of infections caused by OXA-48/CTX-M-coproducing Enterobacterales may be based on new beta-lactam/beta-lactamase inhibitors, such as ceftazidime/avibactam (CZA), or on high dose of meropenem (MER). However, bacterial density at the infection site may vary widely, and the inoculum effect of such antimicrobial strategies has never been specifically investigated. To determine if CZA or MER susceptibilities are impacted by high inocula of Enterobacterales co-expressing both enzymes: OXA-48 like and CTX-M. METHODS: Determination of an inoculum effect was performed with a standard inoculum of 108 CFU/mL (0.5 McFarland) as recommended by EUCAST guidelines and compared to a twofold increase as well as a tenfold increase (1 McFarland and 5 McFarland respectively). RESULTS: Thirty-nine isolates of ceftazidime-resistant Enterobacterales were included of which 27 (70%) co-expressed OXA-48 + CTX-M-15, 6 (15%) OXA-48 + CTX-M-14, and 6 (15%) OXA-181 + CTX-M-15. The susceptibility to the CZA combination was preserved whatever the inoculum used. Regarding MER, 24 (61.5%) of the isolates were susceptible to MER with the standard inoculum, 19 (48.7%) with a twofold increase, and only 15 (38.5%) with a tenfold increase. CONCLUSION: We showed that in vitro inoculum effect was observed with meropenem but not with CZA for OXA-48- combined with CTX-M-producing Enterobacterales.
BACKGROUND: The treatment of infections caused by OXA-48/CTX-M-coproducing Enterobacterales may be based on new beta-lactam/beta-lactamase inhibitors, such as ceftazidime/avibactam (CZA), or on high dose of meropenem (MER). However, bacterial density at the infection site may vary widely, and the inoculum effect of such antimicrobial strategies has never been specifically investigated. To determine if CZA or MER susceptibilities are impacted by high inocula of Enterobacterales co-expressing both enzymes: OXA-48 like and CTX-M. METHODS: Determination of an inoculum effect was performed with a standard inoculum of 108 CFU/mL (0.5 McFarland) as recommended by EUCAST guidelines and compared to a twofold increase as well as a tenfold increase (1 McFarland and 5 McFarland respectively). RESULTS: Thirty-nine isolates of ceftazidime-resistant Enterobacterales were included of which 27 (70%) co-expressed OXA-48 + CTX-M-15, 6 (15%) OXA-48 + CTX-M-14, and 6 (15%) OXA-181 + CTX-M-15. The susceptibility to the CZA combination was preserved whatever the inoculum used. Regarding MER, 24 (61.5%) of the isolates were susceptible to MER with the standard inoculum, 19 (48.7%) with a twofold increase, and only 15 (38.5%) with a tenfold increase. CONCLUSION: We showed that in vitro inoculum effect was observed with meropenem but not with CZA for OXA-48- combined with CTX-M-producing Enterobacterales.
Authors: S D Lahiri; M R Johnstone; P L Ross; R E McLaughlin; N B Olivier; R A Alm Journal: Antimicrob Agents Chemother Date: 2014-07-14 Impact factor: 5.191
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