Top

European Journal of Clinical Microbiology & Infectious Diseases

Published in:

01-05-2022 | Meropenem | Brief Report

Inoculum effect of Enterobacterales co-expressing OXA-48 and CTX-M on the susceptibility to ceftazidime/avibactam and meropenem

Authors: A. Mizrahi, PharmD., phD, L. Chat, M. Danjean, C. Mory, JC. Nguyen Van, G. Péan de Ponfilly, F. Caméléna, A. Le Monnier, B. Bercot, A. Birgy, H. Jacquier, B. Pilmis

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 5/2022

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.

Available only for authorised users

David S, Reuter S, Harris SR, Glasner C, Feltwell T, Argimon S, et al. (2019) Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nat. Microbiol. [Internet] [cited 2022 11];4. https://pubmed.ncbi.nlm.nih.gov/31358985/10.1038/s41564-019-0492-8

Evans BA, Amyes SGB (2014) OXA β-lactamases. Clin Microbiol Rev 27:241–263. https://doi.org/10.1128/CMR.00117-13CrossRefPubMedPubMedCentral

Poirel L, Potron A, Nordmann P (2012) OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother 67:1597–1606. https://doi.org/10.1093/jac/dks121CrossRefPubMed

Pitout JDD, Peirano G, Kock MM, Strydom K-A, Matsumura Y (2019) The global ascendency of OXA-48-type carbapenemases. Clin. Microbiol. Rev. 33. https://doi.org/10.1128/CMR.00102-19

Martin A, Fahrbach K, Zhao Q, Lodise T (2018) Association between carbapenem resistance and mortality among adult, hospitalized patients with serious infections due to Enterobacteriaceae: results of a systematic literature review and meta-analysis. Open Forum Infect. Dis.5:ofy150. https://doi.org/10.1093/ofid/ofy150

Shirley M (2018) Ceftazidime-avibactam: a review in the treatment of serious Gram-negative bacterial infections. Drugs 78:675–692. https://doi.org/10.1007/s40265-018-0902-xCrossRefPubMed

Stewart A, Harris P, Henderson A, Paterson D (2018) Treatment of infections by OXA-48-producing Enterobacteriaceae. Antimicrob. Agents Chemother. 62. https://doi.org/10.1128/AAC.01195-18

König C, Simmen HP, Blaser J (1998) Bacterial concentrations in pus and infected peritoneal fluid–implications for bactericidal activity of antibiotics. J Antimicrob Chemother 42:227–232. https://doi.org/10.1093/jac/42.2.227CrossRefPubMed

Brook I (1989) Inoculum effect. Rev Infect Dis 11:361–368. https://doi.org/10.1093/clinids/11.3.361CrossRefPubMed

10.

Meredith HR, Srimani JK, Lee AJ, Lopatkin AJ, You L (2015) Collective antibiotic tolerance: mechanisms, dynamics and intervention. Nat Chem Biol 11:182–188. https://doi.org/10.1038/nchembio.1754CrossRefPubMedPubMedCentral

11.

Davey PG, Barza M (1987) The inoculum effect with gram-negative bacteria in vitro and in vivo. J Antimicrob Chemother 20:639–644. https://doi.org/10.1093/jac/20.5.639CrossRefPubMed

12.

Wu N, Chen BY, Tian SF, Chu YZ (2014) The inoculum effect of antibiotics against CTX-M-extended-spectrum β-lactamase-producing Escherichia coli. Ann Clin Microbiol Antimicrob 12(13):45. https://doi.org/10.1186/s12941-014-0045-1CrossRef

13.

The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters, version 10.0 2020 [Internet]. [cited 2020 1];https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_10.0_Breakpoint_Tables.pdf

14.

Caméléna F, Morel F, Merimèche M, Decousser J-W, Jacquier H, Clermont O et al (2020) Genomic characterization of 16S rRNA methyltransferase-producing Escherichia coli isolates from the Parisian area. France J Antimicrob Chemother 1(75):1726–1735. https://doi.org/10.1093/jac/dkaa105CrossRef

15.

Jarlier V, Nicolas MH, Fournier G, Philippon A (1988) Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis 10:867–878CrossRef

16.

Mohanty S, Gaind R, Ranjan R, Deb M (2009) Use of the cefepime-clavulanate ESBL Etest for detection of extended-spectrum beta-lactamases in AmpC co-producing bacteria. J Infect Dev Ctries 21(4):24–29CrossRef

17.

Bogaerts P, Berger A-S, Evrard S, Huang T-D (2020) Comparison of two multiplex immunochromatographic assays for the rapid detection of major carbapenemases in Enterobacterales. J Antimicrob Chemother 1(75):1491–1494. https://doi.org/10.1093/jac/dkaa043CrossRef

18.

van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F et al (2018) Colistin versus ceftazidime-avibactam in the treatment of infections due to carbapenem-resistant Enterobacteriaceae. Clin Infect Dis Off Publ Infect Dis Soc Am 6(66):163–171. https://doi.org/10.1093/cid/cix783CrossRef

19.

Shields RK, Nguyen MH, Chen L, Press EG, Potoski BA, Marini RV et al (2017) Ceftazidime-avibactam is superior to other treatment regimens against carbapenem-resistant Klebsiella pneumoniae bacteremia. Antimicrob Agents Chemother 61:e00883-e917. https://doi.org/10.1128/AAC.00883-17CrossRefPubMedPubMedCentral

20.

Daikos GL, Markogiannakis A (2011) Carbapenemase-producing Klebsiella pneumoniae: (when) might we still consider treating with carbapenems? Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 17:1135–1141. https://doi.org/10.1111/j.1469-0691.2011.03553.xCrossRef

21.

The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters, version 11.0 2021 [Internet]. [cited 2020 1];https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_11.0_Breakpoint_Tables.pdf

22.

Tam VH, Ledesma KR, Chang K-T, Wang T-Y, Quinn JP (2009) Killing of Escherichia coli by beta-lactams at different inocula. Diagn Microbiol Infect Dis 64:166–171. https://doi.org/10.1016/j.diagmicrobio.2009.01.018CrossRefPubMed

23.

Harada Y, Morinaga Y, Kaku N, Nakamura S, Uno N, Hasegawa H et al (2014) In vitro and in vivo activities of piperacillin-tazobactam and meropenem at different inoculum sizes of ESBL-producing Klebsiella pneumoniae. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 20:O831-839. https://doi.org/10.1111/1469-0691.12677CrossRef

24.

Lahiri SD, Johnstone MR, Ross PL, McLaughlin RE, Olivier NB, Alm RA (2014) Avibactam and class C β-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance. Antimicrob Agents Chemother 58:5704–5713. https://doi.org/10.1128/AAC.03057-14CrossRefPubMedPubMedCentral

25.

Behzadi P, García-Perdomo HA, Karpiński TM, Issakhanian L (2020) Metallo-ß-lactamases: a review. Mol Biol Rep 47:6281–6294. https://doi.org/10.1007/s11033-020-05651-9CrossRefPubMed

26.

Lahiri SD, Mangani S, Durand-Reville T, Benvenuti M, De Luca F, Sanyal G et al (2013) Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC β-lactamases. Antimicrob Agents Chemother 57:2496–2505. https://doi.org/10.1128/AAC.02247-12CrossRefPubMedPubMedCentral

27.

Kuti JL, Dandekar PK, Nightingale CH, Nicolau DP (2003) Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J Clin Pharmacol 43:1116–1123. https://doi.org/10.1177/0091270003257225CrossRefPubMed

28.

Smith KP, Kirby JE (2018) The inoculum effect in the era of multidrug resistance: minor differences in inoculum have dramatic effect on MIC determination. Antimicrob. Agents Chemother. 62. https://doi.org/10.1128/AAC.00433-18

29.

Kim T, Lee SC, Bae M, Sung H, Kim M-N, Jung J et al (2020) In vitro activities and inoculum effects of ceftazidime-avibactam and aztreonam-avibactam against carbapenem-resistant Enterobacterales isolates from South Korea. Antibiot Basel Switz 15:9. https://doi.org/10.3390/antibiotics9120912CrossRef

30.

López-Cerero L, Picón E, Morillo C, Hernández JR, Docobo F, Pachón J et al (2010) Comparative assessment of inoculum effects on the antimicrobial activity of amoxycillin-clavulanate and piperacillin-tazobactam with extended-spectrum beta-lactamase-producing and extended-spectrum beta-lactamase-non-producing Escherichia coli isolates. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 16:132–136. https://doi.org/10.1111/j.1469-0691.2009.02893.xCrossRef

Title: Inoculum effect of Enterobacterales co-expressing OXA-48 and CTX-M on the susceptibility to ceftazidime/avibactam and meropenem
Authors: A. Mizrahi, PharmD., phD
L. Chat
M. Danjean
C. Mory
JC. Nguyen Van
G. Péan de Ponfilly
F. Caméléna
A. Le Monnier
B. Bercot
A. Birgy
H. Jacquier
B. Pilmis
Publication date: 01-05-2022
Publisher: Springer Berlin Heidelberg
Keywords: Meropenem
Cefepime
Carbapenem Antibiotic
Ceftazidime
Published in: European Journal of Clinical Microbiology & Infectious Diseases / Issue 5/2022
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI: https://doi.org/10.1007/s10096-022-04430-7

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Inoculum effect of Enterobacterales co-expressing OXA-48 and CTX-M on the susceptibility to ceftazidime/avibactam and meropenem

Abstract

Background

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2022

Antimicrobial activity of dalbavancin against Gram-positive bacteria isolated from patients hospitalized with bloodstream infection in United States and European medical centers (2018–2020)

Clinical and microbiological characterization of Aerococcus urinae bacteraemias at Helsinki metropolitan area, Finland

Non-structural protein 1 (NS1) variants from dengue virus clinical samples revealed mutations that influence NS1 production and secretion

Validation of Rapid Antimicrobial Susceptibility Testing directly from blood cultures using WASPLab®, including Colibrí™ and Radian® in-Line Carousel

Evaluating outcomes associated with revised fluoroquinolone breakpoints for Enterobacterales urinary tract infections: A retrospective cohort study

Gonococcal tysonitis, a rare local complication of gonorrhea: a clinical study of 15 cases

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page