Noncarbapenems for the Treatment of Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase-Producing Bacteria

C. Whitney White, PharmD, BCPS; Jeffrey A. Kyle, PharmD, BCPS; Crystal M. Deas, PharmD, BCPS; Jacob Campbell, PharmD


South Med J. 2019;112(8):438-443. 

In This Article


This was a retrospective cohort study approved by the St. Vincent's Birmingham institutional review board, which also waived the need for informed consent. The study took place at a single, 338-bed general medical and surgical hospital in Birmingham, Alabama. Patients with urine cultures positive for ESBL-producing organisms during hospital admissions from January 2012 to June 2016 were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes (per Health Information Management processes), and ESBL-producing isolates were confirmed by the microbiology laboratory of the health system. Antibiotic susceptibility or resistance reported were based on current Clinical & Laboratory Standards Institute breakpoints.

All patients aged 19 years or older with a urine culture with ≥104 CFU/mL ESBL-producing bacteria, diagnosis of UTI by a provider, and receipt of at least one dose of directive antibiotic therapy, as determined by culture and sensitivity report, were included in the study. Patients with both monomicrobial and polymicrobial UTIs were eligible for inclusion. Those excluded from the review included those who were pregnant, classified as having asymptomatic bacteriuria as documented by a provider, received no directive antibiotic treatment, received definitive treatment that switched from carbapenem to noncarbapenem or vice versa, and co-infection involving nonurinary systems (eg, pneumonia, intraabdominal infections, bacteremia without a urinary source). Patients with bacteremia secondary to UTI were eligible for inclusion.

Diagnosis of a UTI was based on microbiological laboratory analysis, urine bacterial colony counts of ≥104 CFU/mL (per microbiology laboratory reporting at institution), and clinical presentation, including symptoms of UTI as documented by the provider. It is important to note that for this study, all of the patients with ≥104 CFU/mL for ESBL-producing organisms were considered to have positive urine cultures, and all of the positive cultures accompanied by symptoms of UTI were considered to have infection. For patients with positive urine cultures whose symptoms were difficult to assess by chart review or which could be explained by other causes, physicians' charted diagnoses were considered adequate.

Data were obtained by performing a clinical chart review of electronic medical records. Demographic information such as age, sex, and race were recorded. Infections were classified as either community onset or hospital acquired. Hospital-acquired infections were defined by a positive culture obtained after 48 hours of admission. Community-onset infections were defined by positive cultures obtained within 48 hours of hospital admission and then further described as healthcare associated for any of the following: hospitalization within the previous 90 days, hemodialysis or outpatient intravenous antibiotics within the previous 30 days, or residence in a long-term care facility. Other variables collected included select comorbidities, history of recurrent UTIs, chronic indwelling urinary catheter, history of ESBL infection, recent antibiotic use, presence of sepsis, presence of bacteremia, and intensive care unit (ICU) stay during admission. Duration and timing of stay in the ICU (in relation to positive cultures and antibiotic therapy) were not recorded. Recent antibiotic use was defined as any antimicrobial therapy within the previous 90 days. Recurrent UTI and sepsis were identified from physician diagnoses and notes and were not further scrutinized for accuracy (ie, systemic inflammatory response syndrome criteria evaluated, scoring systems used). Of note, data reported in this study include patient admissions from periods both before and after the Society of Critical Care Medicine 2016 sepsis definitions and guidelines were published.

The following microbiology and antibiotic data were recorded: ESBL organism isolated by culture, in vitro sensitivity reports, empiric antibiotic selection, definitive antibiotic selection, and dose and duration of therapy (empiric, definitive, and combined). Antibiotic therapy was defined as empiric if given before culture and sensitivity reports were available. Definitive therapy referred to the use of an antibiotic after in vitro susceptibility was known and which demonstrated in vitro activity against the infective organism. Appropriateness of dose, route of administration, or duration of definitive regimens were not evaluated; all definitive regimens, regardless of dose, route of administration, or duration were included and analyzed.

Outcome Measures

The primary outcomes measured were infection-related mortality, length of hospital stay (LOS), and duration of definitive antibiotic therapy. LOS was calculated from the day of the first positive urine culture. Microbiological failure was assessed as a secondary measure. Failure was defined as repeated cultures that were positive for the same ESBL organism after 72 hours of definitive antibiotic therapy and within 30 days of the completion of antibiotic therapy. No differentiation was made between relapse or reinfection. Safety data were not collected. Continuous data (age, LOS, and duration of therapy) were presented as median (interquartile range [IQR]) and compared using the Student t test. Categorical variables were compared using the Fisher exact test. All P values were two-tailed; P < 0.05 was considered statistically significant.