Risk Factors for Recurrence of Community-Onset Urinary Tract Infections Caused by Extended-Spectrum Cephalosporin-Resistant Enterobacterales

Abstract

Background Extended spectrum cephalosporin-resistant Enterobacterales (ESCrE) are an increasingly important cause of community-onset urinary tract infections (UTIs), including recurrent infections. We evaluated risk factors for recurrence among patients with community-onset ESCrE UTI. Methods This retrospective cohort study included adults with community-onset ESCrE UTI in Duke University Health System from April 2018 through December 2021. ESCrE UTI recurrence by the same species was assessed 14 to 180 days (i.e. 6 months) after completion of antibiotic treatment. We evaluated the relationships between candidate risk factors and time to recurrence using Cox proportional hazards regression models. Results Among 1,347 patients with community-onset ESCrE UTI, 202 (15.0%) experienced recurrent infection during the 6-month follow-up period. Independent risk factors for recurrence included neurogenic bladder (adjusted HR [aHR] = 1.8, 95% CI = 1.2 to 2.6, p = 0.005), prior history of UTI (aHR = 2.4, 95% CI = 1.7 to 3.3, p < 0.001), and fluoroquinolone non-susceptibility of the index UTI (aHR = 1.5, 95% CI = 1.1 to 2.1, p = 0.02). Klebsiella pneumoniae infection was associated with recurrence in univariate analysis (HR = 1.6, 95% CI = 1.1 to 2.1, p = 0.007) but not multivariate analysis (aHR = 1.4, 95% CI = 1.0 to 1.9, p = 0.06). Inappropriate initial or definitive antibiotic therapy were not predictive of ESCrE UTI recurrence. Conclusions Recurrence of community-onset ESCrE UTI was common and associated with several patient and pathogen-level risk factors. Future studies should evaluate microbial risk factors for recurrence and improve the management of ESCrE UTI.

SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

“…A larger sample size from the 2016 national Healthcare-Associated Infections prevalence survey in the UK found that the percentage of OAT overuse was 62.5% [50]. Therefore, it appears that non-compliance with professional society guidelines and AMS for cystitis are the likely major contributors to AMR [15,40,41], but other factors may also be involved, so further investigation is warranted.…”

“…A history of two or more episodes of bacterial cystitis is an independent risk factor [15,79] for recurrent cystitis, defined as ≥2 episodes in 6 months or ≥3 in a year. Compared to men, the higher incidence of cystitis in women is generally linked to their shorter urethra and infrequent voiding [69] that thins the urothelial barrier [12,62,80] for the proximal seeding of uropathogens from the adjacent cavities of the vagina and anus [81].…”

“…Uropathogens can adapt to OAT through a panoply of pathways [15], including negative tropism, the acceleration of mutations [121], sheltering under biofilm [91], and expulsion of the drug by membrane pumps [111]. Biodiversity suggests that there may be other mechanisms as well [121].…”

“…The infection of the urothelium can only occur after uropathogens successfully compete for available nutrients with the commensal microbiome [13] by employing mechanisms of commensalism [14], mutualism, and parasitism [15,16]. Many groups have suggested that the biochemical mechanisms driving the adaptability of uropathogens in the variable pH and osmolality of urine [17,18] are as dogged as the signaling pathways driving the gain of virulence [19][20][21] and antimicrobial resistance (AMR) [22].…”

“…While there has been a lot of discussion on the role of the genetic [21,22] and phenotypic attributes of adaptable uropathogens [31] in AMR development, this review is focused on oral antimicrobial treatments (OATs), specifically their interaction with the human body (pharmacokinetics), delaying the achievement of MIC in urine [32,33], and the potential consequences. Uropathogens exposed to below-MIC levels in urine bestow The infection of the urothelium can only occur after uropathogens successfully compete for available nutrients with the commensal microbiome [13] by employing mechanisms of commensalism [14], mutualism, and parasitism [15,16]. Many groups have suggested that the biochemical mechanisms driving the adaptability of uropathogens in the variable pH and osmolality of urine [17,18] are as dogged as the signaling pathways driving the gain of virulence [19][20][21] and antimicrobial resistance (AMR) [22].…”