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Background: Community-acquired UTI is the most common bacterial infection managed in general medical practice that can lead to life-threatening outcomes. While UTIs are primarily caused by Escherichia coli colonizing the patient's gut, it is unclear whether the gut resident E. coli profiles can predict the person's risks for UTI and optimal antimicrobial treatments. Thus, we conducted an eighteen-month long community-based observational study of fecal E. coli colonization and UTI in women aged 50 years and above. Methods and Findings: We enrolled a total of 1,804 women distributed among age groups 50-59 yo (437 participants), 60-69 yo (632), 70-79 yo (532), and above 80 yo (203), lacking antibiotic prescriptions for at least one year. The provided fecal samples were plated for the presence of E. coli and other enterobacteria resistant to trimethoprim/sulfamethoxazole (TMP/STX), ciprofloxacin (CIP) and 3rd generation cephalosporins (3GC). E. coli was also characterized as belonging to the pandemic multi-drug resistant clonal groups ST131 (subclone H30) and ST1193. Following sample collection, the women were monitored for 18 months for occurrence of UTI.E. coli was cultured from 90.8% fecal samples, with 24.1% containing bacteria resistant to TMP/STX, 19.4% to CIP, and 7.9% to 3GC. In 62.5% samples, only all-susceptible E. coli were present. Overall, there were no age-related differences in resistance prevalence. However, while the total E. coli H30 and ST1193 carriage rates were similar (4.3% and 4.2%, respectively), there was a notable increase of H30 carriage with age (P = .001), while carriage decreased with age for ST1193 (P = .057).Within 18 months, 184 women (10.2%) experienced at least one episode of UTI - 10.9% among the gut E. coli carriers and 3.0% among the non-carriers (P=.0013). The UTI risk among carriers of E. coli H30 but not ST1193 was significantly above average (24.3%, P = .0004). The UTI probability increased with age, occurring in 6.4% of 50-59 yo and 19.7% of 80+ yo (P<.001), with the latter group being especially at high risk for UTI, if they were colonized by E. coli H30 (40.0%, P<.001).E. coli was identified in 88.1% of urine samples, with 16.1% resistant to TMP/STX, 16.1% to CIP, 4.2% to 3GC and 73.1% to none of the antibiotics. Among tested urinary E. coli resistant to antibiotics, 86.1% matched the resistance profile of E. coli in the fecal samples, with the clonotyping and whole genome sequencing confirming the matching strains' identity. Positive predictive value (PPV) of using gut resistance profiles to predict UTI pathogens' susceptibility to TMP/STX, CIP, 3GC and all three antibiotics were 98.4%, 98.3%, 96.6% and 95.3%, respectively. Corresponding negative predictive values (NPV) were 63.0%, 54.8%, 44.4% and 75.8%, respectively. The AUC ROC curve values for the accuracy of fecal diagnostic testing for the prediction of UTI resistance ranged .86-.89. The fecal test-guided drug-bug mismatch rate for empirical (pre-culture) prescription of TMP-SXT or CIP is reduced to ≤2% in 89.6% of patients and 94.8% of patients with an optional 3GC prescription. Conclusion: The resistance profile and clonal identity of gut colonizing E. coli, along with the carrier's age, can inform personalized prediction of a patients' UTI risk and the UTI pathogen's antibiotic susceptibility within an 18-month period.
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BACKGROUND: Community circulating gut microbiota is the main reservoir for uropathogenic Escherichia coli, including those resistant to antibiotics. Ciprofloxacin had been the primary antibiotic prescribed for urinary tract infections, but its broad use has been discouraged and steadily declined since 2015. How this change in prescriptions affected the community circulation of ciprofloxacin-resistant E. coli is unknown. METHODS: We determined the frequency of isolation and other characteristics of E. coli resistant to ciprofloxacin in 515 and 1604 E. coli-positive fecal samples collected in 2015 and 2021, respectively. The samples were obtained from non-antibiotic-taking women of age 50+ receiving care in the Kaiser Permanente Washington healthcare system. RESULTS: Here we show that despite a nearly three-fold drop in the prescription of ciprofloxacin between 2015 and 2021, the rates of gut carriage of ciprofloxacin-resistant E. coli increased from 14.2 % to 19.8% (P = .004). This is driven by a significant increase of isolates from the pandemic multi-drug resistant clonal group ST1193 (1.7% to 4.2%; P = .009) and isolates with relatively few ciprofloxacin-resistance determining chromosomal mutations (2.3% to 7.4%; P = .00003). Though prevalence of isolates with the plasmid-associated ciprofloxacin resistance dropped (59.0% to 30.9%; P = 2.7E-06), the isolates co-resistance to third generation cephalosporins has increased from 14.1% to 31.5% (P = .002). CONCLUSIONS: Despite reduction in ciprofloxacin prescriptions, community circulation of the resistant uropathogenic E. coli increased with a rise of co-resistance to third generation cephalosporins. Thus, to reduce the rates of urinary tract infections refractory to antibiotic treatment, greater focus should be on controlling the resistant bacteria in gut microbiota.
The alarming rise of bacteria causing infections that are difficult to treat with antibiotics, known as multidrug-resistant bacteria, is a major problem in medicine. The reduction in the use of antibiotics has been encouraged to control the spread of antibiotic-resistant bacteria. Some multidrug-resistant bacteria reside in the gut of healthy individuals and can cause various forms of urinary tract infections (UTIs). Ciprofloxacin is an antibiotic that was widely used to treat UTIs, but strong recommendations to reduce its prescription have been recently introduced. We compared the presence of bacteria in the gut that could not be killed by ciprofloxacin in women aged 50 and above who do not use antibiotics and reside in the Seattle area. Despite a nearly three-fold drop in the prescription of ciprofloxacin between 2015 and 2021, antibiotic-resistant bacteria in the gut were found more frequently, affecting one in five women. Our study demonstrates that antibiotic-resistant bacteria continue to be present even when antibiotic prescriptions are reduced, demonstrating the need to undertake further similar studies.
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OBJECTIVE: The authors sought to characterize the 3-year prevalence of mental disorders and nonnicotine substance use disorders among male and female primary care patients with documented opioid use disorder across large U.S. health systems. METHODS: This retrospective study used 2014-2016 data from patients ages ≥16 years in six health systems. Diagnoses were obtained from electronic health records or claims data; opioid use disorder treatment with buprenorphine or injectable extended-release naltrexone was determined through prescription and procedure data. Adjusted prevalence of comorbid conditions among patients with opioid use disorder (with or without treatment), stratified by sex, was estimated by fitting logistic regression models for each condition and applying marginal standardization. RESULTS: Females (53.2%, N=7,431) and males (46.8%, N=6,548) had a similar prevalence of opioid use disorder. Comorbid mental disorders among those with opioid use disorder were more prevalent among females (86.4% vs. 74.3%, respectively), whereas comorbid other substance use disorders (excluding nicotine) were more common among males (51.9% vs. 60.9%, respectively). These differences held for those receiving medication treatment for opioid use disorder, with mental disorders being more common among treated females (83% vs. 71%) and other substance use disorders more common among treated males (68% vs. 63%). Among patients with a single mental health condition comorbid with opioid use disorder, females were less likely than males to receive medication treatment for opioid use disorder (15% vs. 20%, respectively). CONCLUSIONS: The high rate of comorbid conditions among patients with opioid use disorder indicates a strong need to supply primary care providers with adequate resources for integrated opioid use disorder treatment.
