In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial
ABSTRACT Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales continue to pose a major threat to human health worldwide. Given the limited therapeutic options available to treat infections caused by these pathogens, identifying additional effective antimicrobials or revisiting existing...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2021-09-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/Spectrum.00226-21 |
| _version_ | 1818755152302047232 |
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| author | Adam G. Stewart Kyra Cottrell Andrew Henderson Kanthi Vemuri Michelle J. Bauer David L. Paterson Patrick N. A. Harris |
| author_facet | Adam G. Stewart Kyra Cottrell Andrew Henderson Kanthi Vemuri Michelle J. Bauer David L. Paterson Patrick N. A. Harris |
| author_sort | Adam G. Stewart |
| collection | DOAJ |
| description | ABSTRACT Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales continue to pose a major threat to human health worldwide. Given the limited therapeutic options available to treat infections caused by these pathogens, identifying additional effective antimicrobials or revisiting existing drugs is important. Ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae containing CTX-M-type ESBLs or AmpC, in addition to narrow-spectrum OXA and SHV enzymes, were selected from blood culture isolates obtained from the MERINO trial. Isolates had previously undergone whole-genome sequencing (WGS) to identify antimicrobial resistance genes. Cefotetan MICs were determined by broth microdilution (BMD) testing with a concentration range of 0.125 to 64 mg/liter; CLSI breakpoints were used for susceptibility interpretation. BMD was performed using an automated digital antibiotic dispensing platform (Tecan D300e). One hundred ten E. coli and 40 K. pneumoniae isolates were used. CTX-M-15 and CTX-M-27 were the most common beta-lactamases present; only 7 isolates had coexistent ampC genes. Overall, 98.7% of isolates were susceptible, with MIC50s and MIC90s of 0.25 mg/liter and 2 mg/liter (range, ≤0.125 to 64 mg/liter), respectively. MICs appeared higher among isolates with ampC genes present, with an MIC50 of 16 mg/liter, than among those containing CTX-M-15, which had an MIC50 of only 0.5 mg/liter. Isolates with an ampC gene exhibited an overall susceptibility of 85%. Presence of a narrow-spectrum OXA beta-lactamase did not appear to alter the cefotetan MIC distribution. Cefotetan demonstrated favorable in vitro efficacy against ESBL-producing E. coli and K. pneumoniae bloodstream isolates. IMPORTANCE Carbapenem antibiotics remain the treatment of choice for severe infection due to ESBL- and AmpC-producing Enterobacterales. The use of carbapenems is a major driver of the emergence of carbapenem-resistant Gram-negative bacilli, which are often resistant to most available antimicrobials. Cefotetan is a cephamycin antibiotic developed in the 1980s that demonstrates enhanced resistance to beta-lactamases and has a broad spectrum of activity against Gram-negative bacteria. Cefotetan holds potential to be a carbapenem-sparing treatment option. Data on the in vitro activity of cefotetan against ESBL-producing Enterobacterales remain scarce. Our study assessed the in vitro activity of cefotetan against ceftriaxone-nonsusceptible blood culture isolates obtained from patients enrolled in the MERINO trial. |
| first_indexed | 2024-12-18T05:34:36Z |
| format | Article |
| id | doaj.art-a3ca144c99e44fc3a7a2468ada11acab |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-18T05:34:36Z |
| publishDate | 2021-09-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-a3ca144c99e44fc3a7a2468ada11acab2022-12-21T21:19:21ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972021-09-019110.1128/Spectrum.00226-21In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO TrialAdam G. Stewart0Kyra Cottrell1Andrew Henderson2Kanthi Vemuri3Michelle J. Bauer4David L. Paterson5Patrick N. A. Harris6Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, AustraliaCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women’s Hospital Campus, Brisbane, AustraliaCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women’s Hospital Campus, Brisbane, AustraliaDepartment of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, AustraliaCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women’s Hospital Campus, Brisbane, AustraliaDepartment of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, AustraliaCentre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women’s Hospital Campus, Brisbane, AustraliaABSTRACT Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales continue to pose a major threat to human health worldwide. Given the limited therapeutic options available to treat infections caused by these pathogens, identifying additional effective antimicrobials or revisiting existing drugs is important. Ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae containing CTX-M-type ESBLs or AmpC, in addition to narrow-spectrum OXA and SHV enzymes, were selected from blood culture isolates obtained from the MERINO trial. Isolates had previously undergone whole-genome sequencing (WGS) to identify antimicrobial resistance genes. Cefotetan MICs were determined by broth microdilution (BMD) testing with a concentration range of 0.125 to 64 mg/liter; CLSI breakpoints were used for susceptibility interpretation. BMD was performed using an automated digital antibiotic dispensing platform (Tecan D300e). One hundred ten E. coli and 40 K. pneumoniae isolates were used. CTX-M-15 and CTX-M-27 were the most common beta-lactamases present; only 7 isolates had coexistent ampC genes. Overall, 98.7% of isolates were susceptible, with MIC50s and MIC90s of 0.25 mg/liter and 2 mg/liter (range, ≤0.125 to 64 mg/liter), respectively. MICs appeared higher among isolates with ampC genes present, with an MIC50 of 16 mg/liter, than among those containing CTX-M-15, which had an MIC50 of only 0.5 mg/liter. Isolates with an ampC gene exhibited an overall susceptibility of 85%. Presence of a narrow-spectrum OXA beta-lactamase did not appear to alter the cefotetan MIC distribution. Cefotetan demonstrated favorable in vitro efficacy against ESBL-producing E. coli and K. pneumoniae bloodstream isolates. IMPORTANCE Carbapenem antibiotics remain the treatment of choice for severe infection due to ESBL- and AmpC-producing Enterobacterales. The use of carbapenems is a major driver of the emergence of carbapenem-resistant Gram-negative bacilli, which are often resistant to most available antimicrobials. Cefotetan is a cephamycin antibiotic developed in the 1980s that demonstrates enhanced resistance to beta-lactamases and has a broad spectrum of activity against Gram-negative bacteria. Cefotetan holds potential to be a carbapenem-sparing treatment option. Data on the in vitro activity of cefotetan against ESBL-producing Enterobacterales remain scarce. Our study assessed the in vitro activity of cefotetan against ceftriaxone-nonsusceptible blood culture isolates obtained from patients enrolled in the MERINO trial.https://journals.asm.org/doi/10.1128/Spectrum.00226-21extended-spectrum beta-lactamaseampC beta-lactamaseantimicrobial susceptibility testingAmpCcefotetanEnterobacterales |
| spellingShingle | Adam G. Stewart Kyra Cottrell Andrew Henderson Kanthi Vemuri Michelle J. Bauer David L. Paterson Patrick N. A. Harris In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial Microbiology Spectrum extended-spectrum beta-lactamase ampC beta-lactamase antimicrobial susceptibility testing AmpC cefotetan Enterobacterales |
| title | In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial |
| title_full | In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial |
| title_fullStr | In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial |
| title_full_unstemmed | In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial |
| title_short | In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial |
| title_sort | in vitro activity of cefotetan against esbl producing escherichia coli and klebsiella pneumoniae bloodstream isolates from the merino trial |
| topic | extended-spectrum beta-lactamase ampC beta-lactamase antimicrobial susceptibility testing AmpC cefotetan Enterobacterales |
| url | https://journals.asm.org/doi/10.1128/Spectrum.00226-21 |
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