Antimicrobial Activity of Tebipenem and Comparators against Enterobacterales from diverse Outpatient Centers and Nursing Homes in the United States

Tomefa E Asempa; April M Bobenchik; Lori Bourassa; Andrew E Clark; Morgan T Hatch; Holly K Huse; Isabella W Martin; A Brian Mochon; Erik Munson; Maroun M Sfeir; Monica Srodon; Yungchou Wang; David P Nicolau

doi:10.1016/j.ijantimicag.2023.106733

Antimicrobial Activity of Tebipenem and Comparators against Enterobacterales from diverse Outpatient Centers and Nursing Homes in the United States

Int J Antimicrob Agents. 2023 Mar;61(3):106733. doi: 10.1016/j.ijantimicag.2023.106733. Epub 2023 Jan 20.

Authors

Affiliations

¹ Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT. Electronic address: Tomefa.asempa@hhchealth.org.
² Department of Pathology, Division of Clinical Pathology, Penn State Milton S. Hershey Medical Center, Hershey, PA.
³ Division of Microbiology, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA.
⁴ Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
⁵ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.
⁶ Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA.
⁷ Department of Pathology and Laboratory Medicine, Dartmouth Health, Lebanon, NH.
⁸ Banner Health, Phoenix, AZ; Sonora Quest Laboratories, Phoenix, AZ; Department of Pathology, University of Arizona College of Medicine, Phoenix, AZ.
⁹ Department of Medical Laboratory Science, Marquette University, Milwaukee, WI.
¹⁰ Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, CT.
¹¹ Department of Pathology, Eastern Connecticut Health Network, Manchester, CT.
¹² Cape Regional Health System, Cape May Court House, NJ.
¹³ Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT; Division of Infectious Diseases, Hartford Hospital, Hartford, CT.

PMID: 36690122
DOI: 10.1016/j.ijantimicag.2023.106733

Abstract

Introduction: Tebipenem is a potential option for the treatment of a range of infections because of its oral dosing coupled with the safety profile of the β-lactam antimicrobial class.

Objectives: To evaluate tebipenem in vitro activity against a challenge set of clinical Enterobacterales collected from outpatient and community settings.

Methods: 618 Enterobacterales isolates were submitted by 11 geographically dispersed U.S medical centers that processed cultures from affiliated outpatient centers in 2022. Susceptibility tests for tebipenem and comparator agents were performed by broth microdilution. Extended-spectrum-β-lactamase (ESBL)-like isolates were identified phenotypically. Multidrug-resistant isolates were non-susceptible to ≥1 agent in ≥3 antimicrobial classes. Genotypic testing (CarbaR) was conducted on select isolates.

Results: Isolates (59% Escherichia coli) were recovered from patients seen predominantly in urology/nephrology (24%), nursing home/long-term care (21%), and ambulatory/primary care (21%) clinics. Comparator agent susceptibility rates against all isolates were as follows: levofloxacin (67.5%), amoxicillin/clavulanate (73.6%), cefixime (70.4%), cefpodoxime (70%), cephalexin (61.7%), ceftriaxone (74.4%), cefazolin (63.8%), ertapenem (97.6%), meropenem (99.7%), nitrofurantoin (64.9%), and sulfamethoxazole/trimethoprim (70.9%). Overall, 90.3% (558/619) of isolates were inhibited at a tebipenem MIC of ≤0.125 mg/L (MIC_50/90, 0.016/0.125 mg/L), including 85.7% inhibition of ESBL-phenotype isolates (n=161; MIC_50/90, 0.03/0.25 mg/L), 86.3% of levofloxacin and sulfamethoxazole/trimethoprim co-resistant isolates (n=95; MIC_50/90, 0.016/0.25 mg/L) and 84.3% of multidrug-resistant isolates (n = 172; MIC_50/90, 0.03/0.25 mg/L). Carbapenemase genes were observed in 2 ESBL-phenotype isolates with a tebipenem MIC of ≥0.5 mg/L.

Conclusion: Relative to common oral comparators, these data demonstrate excellent tebipenem in vitro activity against Enterobacterales isolated from patients receiving care in outpatient settings, including urology clinics and nursing homes.

Keywords: Outpatient; Surveillance; Susceptibility testing; carbapenems, ESBL.

MeSH terms

Anti-Bacterial Agents* / pharmacology
Escherichia coli
Humans
Levofloxacin*
Microbial Sensitivity Tests
Nursing Homes
Outpatients
Sulfamethoxazole
Trimethoprim
United States
beta-Lactamases / genetics

Substances

Anti-Bacterial Agents
tebipenem
Levofloxacin
beta-Lactamases
Sulfamethoxazole
Trimethoprim