Impact of an Antimicrobial Stewardship Initiative on Ertapenem Use and Carbapenem Susceptibilities at Four Community Hospitals

Delgado, Andrew; Lee, Grace C.; Gawrys, Gerard; Duhon, Bryson M.; Koeller, Jim M.

doi:10.1093/ofid/ofv133.1004

Cited by 4 publications

(3 citation statements)

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“…Within this CRE collection, E. coli was NCPE and/or had an ErMs phenotype more frequently than K. pneumoniae (Table 2). The fact that 72% (21/29) of the collected E. coli displayed an ErMs phenotype has important implications for current practice, as ertapenem susceptibility is selectively "suppressed" or not reported on microbiological reports coinciding with antimicrobial stewardship efforts to reduce ertapenem use in some hospitals [17]. Not reporting the ertapenem phenotype may lead to mistreatment of patients infected with this CRE subtype.…”

Section: Discussionmentioning

confidence: 99%

Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales

Black,

Benavides,

Bandy

et al. 2024

Antibiotics

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Among carbapenem-resistant Enterobacterales (CRE) are diverse mechanisms, including those that are resistant to meropenem but susceptible to ertapenem, adding further complexity to the clinical landscape. This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 to 2018. The majority of the CRE isolates were non-carbapenemase producers (NCP; 54%; 41/76); 56% of all NCP isolates had an ErMs phenotype. Among ErMs strains, E. coli comprised the majority (72%). ErMs strains carrying blaCTX-M had, on average, 9-fold higher copies of blaCTX-M than CP-ErMs strains as well as approximately 4-fold more copies than blaCTX-M-positive but ertapenem- and meropenem-susceptible (EsMs) strains (3.7 vs. 0.9, p < 0.001). Notably, carbapenem hydrolysis was observed to be mediated by strains harboring blaCTX-M with and without a carbapenemase(s). ErMs also carried more mobile genetic elements, particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p < 0.0001). MGE- ISVsa5 was uniquely more abundant in ErMs than either EsMs or ErMr strains, with over 30 more average ISVsa5 counts than both phenotype groups (p < 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, our findings characterize both collaborative and independent efforts between blaCTX-M and OmpC in ErMs strains, indicating the need to reappraise the term “non-carbapenemase (NCP)”, particularly for strains highly expressing blaCTX-M. To improve outcomes for CRE-infected patients, future efforts should focus on mechanisms underlying the emerging ErMs subphenotype of CRE strains to develop technologies for its rapid detection and provide targeted therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales

Black,

Benavides,

Bandy

et al. 2024

Antibiotics

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“…Furthermore, aminoglycoside therapy does not mediate resistance to other antimicrobial classes and is effective in single dose therapy and feasible as monotherapy for non-bacteremic ESBL-EB UTIs [ 10 – 12 ]. While limiting the use of an antimicrobial class through substitution has been a mainstay of antimicrobial stewardship efforts, national surveillance programs have identified that reduction in selective pressure is the key component of an effective strategy e.g., Delgado and colleagues’ retrospective study reported substantial reduction of ertapenem utilization while maintaining susceptibilities of Pseudomonas aeruginosa and Enterobacteriaceae [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Retrospective assessment of antimicrobial stewardship initiative in outpatient use of ertapenem for uncomplicated extended spectrum beta lactamase Enterobacteriaceae urinary tract infections

et al. 2021

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Background Urinary tract infections (UTI) are often over-diagnosed and over-treated, which can induce and select for resistant pathogens. After observing wide-spread outpatient use of ertapenem, a broad-spectrum antibiotic, a structured antimicrobial stewardship initiative (ASI) to improve appropriate antimicrobial prescribing was undertaken. ASI objectives were to achieve a goal of reducing ertapenem utilization for extended spectrum beta lactamase Enterobacteriaceae (ESBL-EB) UTI by 10% and evaluate the clinical outcomes associated with the ASI. Methods A pre-to-post cohort study was conducted at a single-center integrated healthcare system between November 1, 2014 and February 26, 2017. An intensive, 90-day, pharmacist-driven, structured ASI was implemented between November 1, 2015 and January 29, 2016. Female patients aged ≥18 years who were treated for an uncomplicated, ESBL-EB urinary tract infection (UTI) were included. Primary outcome was clinical resolution defined as cure, persistence, relapse and recurrence. Secondary outcome measured was monthly ertapenem use expressed as number of days of therapy (DOT)/1000 adjusted patient days (APD). Segmented regression analysis for interrupted time series was performed to estimate ASI intervention effect. Results A total of 184 patients were included in the study. Ertapenem utilization decreased from 0.0145 DOT/1000 APD in Nov. 2014 to 0.0078 DOT/1000 APD Feb. 2017(p < 0.01). The mean ertapenem DOT declined 19% overall from the pre vs. post intervention periods (32 vs 26, p < 0.01). Frequency of recurrent UTIs between treatments did not significantly differ and no adverse effects were reported in patients treated with aminoglycosides. Conclusions A structured ASI for uncomplicated ESBL-EB UTI was associated with a clinically meaningful decrease in ertapenem utilization and once-daily, 5-day aminoglycoside treatment was well-tolerated.

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“…8,9 While limiting the use of an antimicrobial class through substitution has been a mainstay of antimicrobial stewardship efforts, national surveillance programs have identi ed that reduction in selective pressure is the key component of an effective strategy (e.g., Delgado and colleagues' retrospective study reported substantial reduction of ertapenem utilization while maintaining susceptibilities of Pseudomonas aeruginosa and Enterobacteriaceae. 10 Accelerating trends in overall ertapenem use and initial cases of carbapenem-resistant Enterobacteriaceae (CRE) were observed in a community medical center. A collaborative antimicrobial stewardship initiative (ASI), thus, was launched to improve antimicrobial utilization in the outpatient antibiotic parenteral therapy (OPAT) setting.…”

Section: Introductionmentioning

confidence: 99%

Retrospective Assessment of Antimicrobial Stewardship Initiative in Outpatient Use of Ertapenem for Uncomplicated Extended Spectrum Beta Lactamase Enterobacteriaceae Urinary Tract Infections

Wong

Delate

Hudson

et al. 2021

Preprint

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Background: Urinary tract infections (UTI) are often over-diagnosed and over-treated, which can induce and select for resistant pathogens. After observing wide-spread outpatient use of ertapenem, a broad-spectrum antibiotic, a structured antimicrobial stewardship initiative (ASI) to improve appropriate antimicrobial prescribing was undertaken. ASI objectives were to achieve a goal of reducing ertapenem utilization for extended spectrum beta lactamase Enterobacteriaceae (ESBL-EB) UTI by 10% and evaluate the clinical outcomes associated with the ASI.Methods: A pre-to-post cohort study was conducted at a single-center integrated healthcare system between November 1, 2014 and February 26, 2017. An intensive, 90-day, pharmacist-driven, structured ASI was implemented between November 1, 2015 and January 29, 2016. Female patients aged ≥18 years who were treated for an uncomplicated, ESBL-EB urinary tract infection (UTI) were included. Primary outcome was monthly ertapenem use expressed as number of days of therapy (DOT)/1,000 adjusted patient days (APD). Segmented regression analysis for interrupted time series was performed to estimate ASI intervention effect. Results: A total of 184 patients were included in the study. Ertapenem utilization decreased from 0.0145 DOT/1,000 APD in Nov. 2014 to 0.0078 Dot/1,000 APD Feb. 2017(p<0.01). The mean ertapenem DOT declined 19% overall from the pre vs. post intervention periods (32 vs 26, p<0.01). Frequency of recurrent UTIs was reduced and no adverse effects were reported in patients treated with aminoglycosides.Conclusions: A structured ASI for uncomplicated ESBL-EB UTI was associated with a clinically meaningful decrease in ertapenem utilization and once-daily, 5-day aminoglycoside treatment was well-tolerated.

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Impact of an Antimicrobial Stewardship Initiative on Ertapenem Use and Carbapenem Susceptibilities at Four Community Hospitals

Cited by 4 publications

References 0 publications

Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales

Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales

Retrospective assessment of antimicrobial stewardship initiative in outpatient use of ertapenem for uncomplicated extended spectrum beta lactamase Enterobacteriaceae urinary tract infections

Retrospective Assessment of Antimicrobial Stewardship Initiative in Outpatient Use of Ertapenem for Uncomplicated Extended Spectrum Beta Lactamase Enterobacteriaceae Urinary Tract Infections

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