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In vitro activity of ertapenem against Neisseria gonorrhoeae clinical isolates with decreased susceptibility or resistance to extended spectrum cephalosporins in Nanjing, China (2013-2019)

Xuechun Li, Wenjing Le, Xiangdi Lou, View ORCID ProfileCaroline A. Genco, Peter A. Rice, View ORCID ProfileXiaohong Su
doi: https://doi.org/10.1101/2022.01.25.477800
Xuechun Li
1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
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Wenjing Le
1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
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Xiangdi Lou
1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
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Caroline A. Genco
2Department of Immunology, School of Medicine, Tufts University, Boston, MA, USA
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Peter A. Rice
3Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, United States
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Xiaohong Su
1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
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  • For correspondence: suxh@ncstdlc.org
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ABSTRACT

Objective Neisseria gonorrhoeae isolates collected in Nanjing, China, that possessed decreased susceptibility (or resistance) to extended spectrum cephalosporins (ESCs), were examined for susceptibility to ertapenem and their sequence types determined.

Methods Ceftriaxone and cefixime minimum inhibitory concentrations (MICs) ≥ 0.125 mg/L and ≥ 0.25 mg/L, respectively, were first determined in 259 strains isolated between 2013 and 2019 and then MICs of ertapenem were measured using the antimicrobial gradient epsilometer test (Etest). Genetic determinants of ESC resistance and multi-antigen sequence typing (NG-MAST) were also determined to analyze associations with ertapenem susceptibility.

Results All isolates displayed ertapenem MICs between 0.006 mg/L-0.38 mg/L; the overall MIC50 and MIC90 were 0.032 mg/L and 0.125 mg/L. 44 (17.0%) isolates displayed ertapenem MICs of ≥ 0.125 mg/L; 10 (3.9%) had MICs ≥ 0.25 mg/L. The proportion of isolates with ertapenem MICs ≥ 0.125 mg/L increased from 4.0% in 2013, to 20.0% in 2019 (χ2= 24.144, P<0.001; Chi square test for linear trend). The penA mosaic allele was present in a significantly higher proportion of isolates with ertapenem MICs ≥ 0.125 mg/L compared to isolates with MICs ≤ 0.094 mg/L) (97.7% vs. 34.9%, respectively; χ2=58.158, P<0.001). ST5308 was the most prevalent NG-MAST type (8.5%); ST5308 was also significantly more common among isolates with ertapenem MICs ≥ 0.125 mg/L vs. isolates with MICs ≤ 0.094mg/L (22.7% and 5.6% respectively; χ2=13.815, P=0.001).

Conclusions Ertapenem may be effective therapy for gonococcal isolates with decreased susceptibility or resistance to ESCs and isolates with identifiable genetic resistance determinants.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 26, 2022.
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In vitro activity of ertapenem against Neisseria gonorrhoeae clinical isolates with decreased susceptibility or resistance to extended spectrum cephalosporins in Nanjing, China (2013-2019)
Xuechun Li, Wenjing Le, Xiangdi Lou, Caroline A. Genco, Peter A. Rice, Xiaohong Su
bioRxiv 2022.01.25.477800; doi: https://doi.org/10.1101/2022.01.25.477800
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In vitro activity of ertapenem against Neisseria gonorrhoeae clinical isolates with decreased susceptibility or resistance to extended spectrum cephalosporins in Nanjing, China (2013-2019)
Xuechun Li, Wenjing Le, Xiangdi Lou, Caroline A. Genco, Peter A. Rice, Xiaohong Su
bioRxiv 2022.01.25.477800; doi: https://doi.org/10.1101/2022.01.25.477800

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