Multidrug resistant organisms can be difficult to treat due to limited options and are a public health threat. Increasing rates of antimicrobial resistance have led to high rates of mortality and greater costs for the healthcare system. Isolates are labeled as carbapenem-resistant Enterobacteriaceae (CRE) if noted to have resistance to at least one carbapenem agent or produce a carbapenemase. There are multiple mechanisms of carbapenem resistance including carbapenemase production, porin channel mutations, and overexpression of efflux pumps. The literature suggests that the risk of carbapenemase production is less than 3% in isolates that are resistant to ertapenem but susceptible to meropenem and imipenem-cilastatin. A study by Wang et al showed that ertapenem-mono-resistant isolates were more likely to be susceptible or intermediate to beta-lactams and beta-lactam/beta-lactamase inhibitor combination agents when compared to meropenem and imipenem-cilastatin resistant isolates. However, current Infectious Diseases Society of America (IDSA) guidelines recommend that they be treated with extended infusion of meropenem or imipenem-cilastatin. The Clinical and Laboratory Standards Institute (CLSI) recently lowered the susceptibility breakpoint of ertapenem from a mean inhibitory concentration (MIC) of <2 to <0.5 µg/mL, increasing the number of isolates that would be labeled as CRE. The purpose of this study was to describe the outcomes in patients with ertapenem mono-resistant Enterobacteriaceae infections, and to compare the use of carbapenem and non-carbapenem antibiotics in ertapenem mono-resistant isolates. This study was a single-center, retrospective chart review of mono-resistant Enterobacterales isolates from January 1st, 2023 to December 31st, 2024. Mono-resistance is defined as having an ertapenem MIC of > 1 mg/L and meropenem MIC of < 1 mg/L. Patients were included if they were > 18 years old at time of culture collection, were inpatient, and completed an antibiotic course for an infection with a positive culture. At our institution, genotyping data was only available for some blood cultures. Patients were excluded from analysis if cultures were collected at an outside facility, belonged to protected population, and did not receive antibiotic treatment. The comparative groups were patients treated with carbapenems, non-carbapenem beta-lactams, and non-beta-lactam antibiotics. The primary outcome was clinical cure of infection. To strengthen our analysis of the primary outcome, an infectious diseases physician validated the primary outcome. Secondary outcomes included microbiological cure, in-house mortality, and inpatient length of stay. For statistical analysis, chi-square tests and student t-tests were conducted when appropriate. Ninety-eight isolates were reviewed: 25 (26%) were treated with a carbapenem, 51 (52%) were treated with a non-carbapenem beta-lactam, and 22 (22%) were treated with a non-beta-lactam. Most isolates came from a respiratory (34%) or urinary (20%) sample. Clinical cure rates were similar across three groups, 76% vs 80% vs 77%, respectively (p=0.8955). A multivariable regression analysis adjusted for sex, age, bed-type, polymicrobial culture status, and specimen type revealed no difference in clinical cure between antibiotic groups. When comparing carbapenem and non-carbapenem treated patients, the portion of patients who died was significantly smaller in the non-carbapenem group, (7 patients [28%] vs 4 patients [6%], p=0.006). Length of stay was longer in the carbapenem group when compared to the non-carbapenem group, but this difference was not statistically significant (76 days vs 32 days, p=0.184). Similar rates of clinical cure were observed in the three different groups (carbapenem, non-carbapenem beta-lactam, and non-beta lactam antibiotics), despite the current IDSA recommendation to use extended-infusion carbapenems for these mono-resistant isolates. Longer rates of length of stay in the carbapenem-treated group may cause a significant burden on our healthcare system. This suggests that most mono-resistant isolates are not carbapenemase producing and could be treated with beta-lactam therapy, if reported as susceptible.
