Contemporary Evaluation of Tebipenem In Vitro Activity against Enterobacterales Clinical Isolates Causing Urinary Tract Infections in US Medical Centers (2019-2020)

The occurrence of urinary-tract Enterobacterales pathogens producing ESBL enzymes in community and nosocomial settings continues to increase, as does the coresistance to fluoroquinolones, trimethoprim-sulfamethoxazole and nitrofurantoin often exhibited by these pathogens. This scenario complicates the clinical empirical and guided management of UTI by precluding the use of oral and many intravenous options. Tebipenem pivoxil is an oral broad-spectrum carbapenem. This study evaluated the activity of tebipenem and comparators against UTI Enterobacterales from US hospitals (2019-2020). 3,576 Enterobacterales causing UTI in 52 centers in 9 US Census Divisions were included. Susceptibility testing followed the CLSI broth microdilution method. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis with an MIC of >= 2 mu g/mL for ceftazidime, ceftriaxone, and/or aztreonam were designated ESBL. Isolates were also grouped based on MDR phenotype. Tebipenem, meropenem, and ertapenem had MIC90 against Enterobacterales of 0.06 mu g/mL, 0.06 mu g/mL and 0.03 mu g/mL, respectively. Low susceptibility results for aztreonam (87.1% susceptible), cefazidime (88.1%), ceftriaxone (84.8%), and other agents were observed. Tebipenem and ertapenem were equally potent (MIC90, 0.015 to 0.03 mu g/mL) against E. coli and K. pneumoniae, whereas ertapenem showed an MIC 8-fold lower than tebipenem against P. mirabilis. Oral agents, such as amoxicillin-clavulanate, levofloxacin, and trimethoprim-sulfamethoxazole, showed elevated nonsusceptibility rates in the Middle Atlantic region (26, 45, 47, and 41%, respectively). ESBL prevalence varied from 7% to 16%, except in the Middle Atlantic region (42%). The carbapenems were active against ESBL and MDR isolates (93.7 to 96.8% susceptible). Elevated rates of ESBL in UTI pathogens in US hospitals were noted as well as a uniform in vitro potency (MIC90) of tebipenem and the intravenous carbapenems, regardless of phenotype.IMPORTANCE The occurrence of urinary-tract Enterobacterales pathogens producing ESBL enzymes in community and nosocomial settings continues to increase, as does the coresistance to fluoroquinolones, trimethoprim-sulfamethoxazole and nitrofurantoin often exhibited by these pathogens. This scenario complicates the clinical empirical and guided management of UTI by precluding the use of oral and many intravenous options. Oral options appear compromised even among some ESBL-negative isolates, against which the use of parenteral agents may be required. In addition, the interregional variability of susceptibility results of US UTI pathogens provides a less predictable susceptibility pattern to inform empirical treatment decisions. This study evaluated the in vitro activity of tebipenem against contemporary uropathogens, including those resistant to currently available oral options.

Automated summary

The occurrence of urinary-tract Enterobacterales pathogens producing ESBL enzymes in community and nosocomial settings continues to increase, posing challenges to the management of UTI. Tebipenem, a broad-spectrum carbapenem, showed promising activity against UTI pathogens. However, there was variability in susceptibility patterns and resistance rates among different regions and isolates.