Determining a urinary-specific antibiogram and risk factors of trimethoprim/sulfamethoxazole, ciprofloxacin and multidrug resistance among Enterobacterales in primary care.

BACKGROUND: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined. OBJECTIVES: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales. METHODS: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020. RESULTS: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with Enterobacterales (n = 199) were mostly female (93.5%) with a mean age of 48.5 years. E. coli was the predominant uropathogen isolated (n = 187/339; 55%) and had elevated trimethoprim/sulfamethoxazole (43.6%) and ciprofloxacin (29.5%) resistance, low nitrofurantoin (1.8%) resistance, and no fosfomycin resistance. Among E. coli, 10.6% were ESBL positive and 24.9% had MDR. Birth outside the U.S.A., prior (2 year) trimethoprim/sulfamethoxazole resistance, and diabetes mellitus were associated with trimethoprim/sulfamethoxazole resistance. Prior (60 day) fluoroquinolone use, prior ciprofloxacin resistance and both diabetes mellitus and hypertension were strongly associated with ciprofloxacin resistance. Prior fluoroquinolone use and a history of resistance to any studied antibiotic were associated with MDR, while pregnancy was protective. CONCLUSIONS: We found elevated resistance to UTI-relevant antimicrobials and novel factors associated with resistance; these data can be incorporated into clinical decision tools to improve organism and drug concordance.

Predicting Antibiotic Susceptibility Among Patients With Recurrent Urinary Tract Infection Using a Prior Culture.

PURPOSE: Recurrent cystitis guidelines recommend relying on a local antibiogram or prior urine culture to guide empirical prescribing, yet little data exist to quantify the predictive value of a prior culture. We constructed a urinary antibiogram and evaluated test metrics (sensitivity, specificity, and Bayes' positive and negative predictive values) of a prior gram-negative organism on predicting subsequent resistance or susceptibility among patients with uncomplicated, recurrent cystitis. MATERIALS AND METHODS: We performed a retrospective database study of adults with recurrent, uncomplicated cystitis (cystitis occurring 2 times in 6 months or 3 times in 12 months) from urology or primary care clinics between November 1, 2016, and December 31, 2018. We excluded pregnant females, patients with complicated cystitis, or pyelonephritis. Test metrics were calculated between sequential, paired cultures using standard formulas. RESULTS: We included 597 visits from 232 unique patients wherein 310 (51.2%) visits had a urine culture and 165 had gram-negative uropathogens isolated. Patients with gram-negative uropathogens were mostly females (97%), with a median age of 58.5 years. Our antibiogram found 38.0%, 27.9%, and 5.5% of Escherichia coli isolates had resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, and nitrofurantoin, respectively. Prior cultures (within 2 years) had good predictive value for detecting future susceptibility to first-line agents nitrofurantoin (0.85) and trimethoprim-sulfamethoxazole (0.78) and excellent predictive values (≥0.90) for cefepime, ceftriaxone, cefuroxime, ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin-tazobactam, and imipenem. CONCLUSIONS: Considerable antibiotic resistance was detected among E coli isolates in patients with recurrent, uncomplicated cystitis. Using a prior culture as a guide can enhance the probability of selecting an effective empirical agent.

Outpatient antibiogram and predictors of ciprofloxacin and trimethoprim-sulfamethoxazole resistant urinary tract infections.

Context: Rising antibiotic resistance has transcended hospital boundaries and impacted individuals with community acquired urinary tract infections (UTI). Scant data on antibiotic resistance in outpatient settings exists and most studies in the United States (U.S.) have identified predictors of resistance in acute-care settings. Objective: Determine the antibiogram among Escherichia coli isolates and factors associated with ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX) resistant gram-negative urinary isolates. Study Design: Retrospective cohort study. Setting: Two primary care, safety-net clinics in Houston, TX between 11/2018 and 3/2020. Population studied: Patients aged 18 and older presenting with provider suspected uncomplicated or complicated UTI. Outcome measures: Resistance and predictors of resistance to UTI-relevant antibiotics. Results: Among 1265 cultures collected, 372 (28.4%) were positive. We detected E. coli (50.3%) and Group B Streptococcus (18.6%) most frequently. Our patient population consisted mostly of Hispanic (75.7%) females (92.5%) born outside the U.S. (67.3%) with a mean age of 47. Among patients with E. coli isolated (n=189), antibiotic resistance was highest to ampicillin (63%), TMP-SMX (44%), ciprofloxacin (31%), and cefazolin (30%); no or low resistance against amikacin (0%), fosfomycin (0%), and nitrofurantoin (2.7%) was detected. Approximately 12% of E. coli isolates were extended-spectrum beta-lactamase positive. Having a prior UTI caused by a TMP-SMX resistant gram-negative organism and being born outside the U.S increased the odds of TMP-SMX resistance by 3.71 (95% confidence interval: 1.6-9.2) and 3.08 (95% CI: 1.6-6.3), respectively. Having a complicated UTI (odds ratio (OR): 3.58; 95% CI: 1.1-12.1), prior fluoroquinolone use (OR: 6.81; 95% CI: 1.7-34.1) and a prior UTI with ciprofloxacin resistance (OR: 7.84; 95% CI: 3.2-20.7) increased the odds of having a ciprofloxacin resistance. Conclusion: The Infectious Disease Society of America cautions against prescribing an antibiotic if regional resistance exceeds 20%. We constructed an antibiogram and found resistance surpassed this threshold for TMP-SMX and ciprofloxacin and identified factors associated with resistance to these agents. Assessing these characteristics during clinical decision making may improve antibiotic-organism susceptibility concordance in primary care.

Efficacy data of halogenated phenazine and quinoline agents and an NH125 analogue to veterinary mycoplasmas.

BACKGROUND: Mycoplasmas primarily cause respiratory or urogenital tract infections impacting avian, bovine, canine, caprine, murine, and reptilian hosts. In animal husbandry, mycoplasmas cause reduced feed-conversion, decreased egg production, arthritis, hypogalactia or agalactia, increased condemnations, culling, and mortality in some cases. Antibiotics reduce transmission and mitigate clinical signs; however, concerning levels of antibiotic resistance in Mycoplasma gallisepticum and M. capricolum isolates exist. To address these issues, we evaluated the minimum inhibitory concentrations (MICs) of halogenated phenazine and quinoline compounds, an N-arylated NH125 analogue, and triclosan against six representative veterinary mycoplasmas via microbroth or agar dilution methods. Thereafter, we evaluated the minimum bactericidal concentration (MBC) of efficacious drugs. RESULTS: We identified several compounds with MICs ≤25 µM against M. pulmonis (n = 5), M. capricolum (n = 4), M. gallisepticum (n = 3), M. alligatoris (n = 3), M. agassizii (n = 2), and M. canis (n = 1). An N-arylated NH125 analogue, compound 21, served as the most efficacious, having a MIC ≤25 µM against all mycoplasmas tested, followed by two quinolines, nitroxoline (compound 12) and compound 20, which were effective against four and three mycoplasma type strains, respectively. Nitroxoline exhibited bactericidal activity among all susceptible mycoplasmas, and compound 21 exhibited bactericidal activity when the MBC was able to be determined. CONCLUSIONS: These findings highlight a number of promising agents from novel drug classes with potential applications to treat veterinary mycoplasma infections and present the opportunity to evaluate preliminary pharmacokinetic indices using M. pulmonis in rodents as an animal model of human infection.

Turning the Tide against Antibiotic Resistance by Evaluating Novel, Halogenated Phenazine, Quinoline, and NH125 Compounds against Ureaplasma Species Clinical Isolates and Mycoplasma Type Strains.

Escalating levels of antibiotic resistance in mycoplasmas, particularly macrolide resistance in Mycoplasma pneumoniae and M. genitalium, have narrowed our antibiotic arsenal. Further, mycoplasmas lack a cell wall and do not synthesize folic acid, rendering common antibiotics, such as beta-lactams, vancomycin, sulfonamides, and trimethoprim, of no value. To address this shortage, we screened nitroxoline, triclosan, and a library of 20 novel, halogenated phenazine, quinoline, and NH125 analogues against Ureaplasma species and M. hominis clinical isolates from urine. We tested a subset of these compounds (n = 9) against four mycoplasma type strains (M. pneumoniae, M. genitalium, M. hominis, and Ureaplasma urealyticum) using a validated broth microdilution or agar dilution method. Among 72 Ureaplasma species clinical isolates, nitroxoline proved most effective (MIC90, 6.25 µM), followed by an N-arylated NH125 analogue (MIC90, 12.5 µM). NH125 and its analogue had significantly higher MICs against U. urealyticum isolates than against U. parvum isolates, whereas nitroxoline did not. Nitroxoline exhibited bactericidal activity against U. parvum isolates but bacteriostatic activity against the majority of U. urealyticum isolates. Among the type strains, the compounds had the greatest activity against M. pneumoniae and M. genitalium, with 8 (80%) and 5 (71.4%) isolates demonstrating MICs of ≤12.5 µM, respectively. Triclosan also exhibited lower MICs against M. pneumoniae and M. genitalium Overall, we identified a promising range of quinoline, halogenated phenazine, and NH125 compounds that showed effectiveness against M. pneumoniae and M. genitalium and found that nitroxoline, approved for use outside the United States for the treatment of urinary tract infections, and an N-arylated NH125 analogue demonstrated low MICs against Ureaplasma species isolates.

Antibacterial Resistance in Ureaplasma Species and Mycoplasma hominis Isolates from Urine Cultures in College-Aged Females.

Urinary tract infections (UTIs) affect nearly 20% of women age 15 to 29 and account for an estimated $3.5 billion in costs. Antibiotic resistance prolongs UTI treatment, and resistance profiles vary regionally. This regional variation is an important consideration in guiding empirical treatment selection. Regional studies in the United States have identified tetracycline resistance in over one-third of Ureaplasma species isolates, but no studies have evaluated antibiotic resistance levels in college-aged women with a first-time UTI. We tested a panel of antibiotics and determined the MICs of Ureaplasma species (60 U. parvum and 13 U. urealyticum) and 10 Mycoplasma hominis isolates obtained from urine from college-aged women with a first-time UTI. Low antibiotic resistance was found in this population of women with a first-time UTI. All M. hominis and U. urealyticum isolates were sensitive. However, two U. parvum isolates were resistant, with one to levofloxacin (MIC, 4 µg/ml) and one to tetracycline (MIC, 8 µg/ml). For the Ureaplasma spp., the MIC90s were highest against gentamicin (21 µg/ml) and lowest against doxycycline (0.25 µg/ml). In a comparison of MIC levels between Ureaplasma spp., U. urealyticum had significantly higher MICs against each antibiotic except doxycycline. For the resistant isolates, the genetic mechanisms of resistance were determined. PCR amplification identified tetM to be present in the tetracycline-resistant isolate and an S83W mutation within the parC gene of the quinolone-resistant isolate. To our knowledge, this study is the first to provide molecular and phenotypic evidence of the S83W parC mutation conferring levofloxacin resistance in U. parvum isolated from a patient in the United States.

Qualitative Analysis of a Twitter-Disseminated Survey Reveals New Patient Perspectives on the Impact of Urinary Tract Infection.

Few studies have harnessed social media to explore patients' experiences with urinary tract infection (UTI); therefore, we captured UTI experiences and future research suggestions through a Twitter-disseminated survey. The survey posed three qualitative questions inquiring about the impact of UTIs, greatest UTI management hurdle, and research suggestions. We also asked participants to rate how seriously others perceive UTIs and the importance of UTIs in their life (scale: 1-100 (highest)). The study period spanned from January to June 2021. Coding was performed in duplicate, followed by thematic analysis. Of 466 participants from 22 countries, 128 considered their UTIs recurrent (n = 43) or chronic (n = 85). Six major themes emerged: UTIs drastically impact (1) physical and (2) mental health and (3) cause severe limitations in life activities. Patients reported (4) negative clinician interactions and perceived inadequate care, (5) a lack of knowledge and awareness surrounding UTIs, and (6) research gaps in UTI diagnostics and treatment. The participants considered UTIs extremely important (median: 100, IQR: 90-100), but characterized others' perceptions of them as less serious (median: 20, IQR: 10-30). Our survey revealed a patient population struggling with UTIs, particularly chronic UTIs. Our findings highlight perceived shortcomings in current UTI treatment and diagnostics.

Analysis of recurrent urinary tract infection management in women seen in outpatient settings reveals opportunities for antibiotic stewardship interventions.

Objectives: We characterized antibiotic prescribing patterns and management practices among recurrent urinary tract infection (rUTI) patients, and we identified factors associated with lack of guideline adherence to antibiotic choice, duration of treatment, and urine cultures obtained. We hypothesized that prior resistance to nitrofurantoin or trimethoprim-sulfamethoxazole (TMP-SMX), shorter intervals between rUTIs, and more frequent rUTIs would be associated with fluoroquinolone or ß-lactam prescribing, or longer duration of therapy. Methods: This study was a retrospective database study of adult women with International Classification of Diseases, Tenth Revision (ICD-10) cystitis codes meeting American Urological Association rUTI criteria at outpatient clinics within our academic medical center between 2016 and 2018. We excluded patients with ICD-10 codes indicative of complicated UTI or pyelonephritis. Generalized estimating equations were used for risk-factor analysis. Results: Among 214 patients with 566 visits, 61.5% of prescriptions comprised first-line agents of nitrofurantoin (39.7%) and TMP-SMX (21.5%), followed by second-line choices of fluoroquinolones (27.2%) and ß-lactams (11%). Most fluoroquinolone prescriptions (86.7%), TMP-SMX prescriptions (72.2%), and nitrofurantoin prescriptions (60.2%) exceeded the guideline-recommended duration. Approximately half of visits lacked a urine culture. Receiving care through urology via telephone was associated with receiving a ß-lactam (adjusted odds ratio [aOR], 6.34; 95% confidence interval [CI], 2.58-15.56) or fluoroquinolone (OR, 2.28; 95% CI, 1.07-4.86). Having >2 rUTIs during the study period and seeking care from a urology practice (RR, 1.28, 95% CI, 1.15-1.44) were associated with longer antibiotic duration. Conclusions: We found low guideline concordance for antibiotic choice, duration of therapy and cultures obtained among rUTI patients. These factors represent new targets for outpatient antibiotic stewardship interventions.

Identification of novel factors associated with inappropriate treatment of asymptomatic bacteriuria in acute and long-term care.

BACKGROUND: Chart reviews often fall short of determining what drove antibiotic treatment of asymptomatic bacteriuria (ASB). To overcome this shortcoming, we searched providers' free-text for documentation of their decision-making and for misleading signs and symptoms that may trigger unnecessary treatment of ASB. METHODS: We reviewed a random sample of 10 positive urine cultures per month, per facility, from patients in acute or long-term care wards at 8 Veterans Affairs facilities. Cultures were classified as urinary tract infection (UTI) or ASB, and as treated or untreated. Charts were searched for 13 potentially misleading symptoms, and free-text documentation of providers' decision-making was classified into 5 categories. We used generalized estimating equations logistic regression to identify factors associated with ASB treatment. RESULTS: One hundred fifty-eight (27.5%) of 575 ASB cases were inappropriately treated with antibiotics. Significant factors associated with inappropriate treatment included: abdominal pain, falls, decreased urine output, urine characteristics, abnormal vital signs, laboratory values, and voiding issues. Providers prescribed an average of 1.4 antimicrobials to patients with ASB, with cephalosporins (41%) and fluoroquinolones (21%) being the most common classes prescribed. CONCLUSIONS: Chart reviews of providers' decision-making highlighted new factors associated with inappropriate ASB treatment. These findings can help design antibiotic stewardship interventions for ASB.

Prevalence and predictors of urine culture contamination in primary care: A cross-sectional study.

BACKGROUND: Antimicrobial resistance is a global health threat. To slow resistance and preserve antibiotics, stewardship interventions are increasingly promoted and mandated. Urine cultures are the most common microbiological test in the outpatient setting. Contamination most likely occurs during urine collection from surrounding vaginal, perineal, and epidermal flora. Sample contamination can lead to incorrect diagnosis, unnecessary or inappropriate treatment, poor patient outcomes, and higher costs. Therefore, ensuring proper collection of urinary samples serves as a prime diagnostic stewardship target, one that international nursing societies increasingly endorse as an opportunity for nurse involvement. OBJECTIVES: Determine the prevalence, predictors, and antibiotic prescribing associated with contaminated urine cultures in primary care clinics. DESIGN: Cross-sectional study. SETTING: Two adult safety-net clinics in Houston, Texas. PARTICIPANTS: 1265 clinical encounters among 1114 primary care patients. METHODS: We reviewed charts from office visits among patients who had a urine culture ordered between November 2018 and March 2020. Patient demographics, culture results and prescription orders were captured for each visit. Culture results were defined as no growth, contaminated (i.e., mixed flora, non-uropathogens, or ≥3 bacterial species isolated), or low-count (102-105 colony forming units (CFU)/mL) or high-count (>105 CFU/mL) uropathogen-positive. We performed multinomial logistic regression to identify predictors independently associated with contaminated cultures. RESULTS: Our study evaluated 1265 cultures from 1114 patients that were primarily female (84 %), of Hispanic/Latino (74.4 %) or Black/African American (18.9 %) race/ethnicity with a mean age of 43 years. Out of 1265 urine cultures, 264 (20.9 %) had no growth, 694 (54.9 %) were contaminated, 159 (12.6 %) were low-count positive, and 148 (11.7 %) were high-count positive. Female sex, pregnancy, and obesity were associated with contaminated cultures (multinomial adjusted odds ratios: 15.89, 14.34, 1.93, respectively; 95 % confidence intervals: 10.25-24.61, 8.03-25.61, 1.32-2.81, respectively). Antibiotic prescribing was significantly higher among symptomatic patients with contaminated cultures compared to those with no growth. CONCLUSION: Urine culture contamination occurred frequently in our clinics, and obesity, female sex and pregnancy were independent risk factors for contamination. The association of pregnancy and contamination is particularly concerning as pregnant females are routinely screened and treated for asymptomatic bacteriuria in the United States. Culture contamination may obscure underlying uropathogens, leading to pyelonephritis or potential neonatal infection if untreated. Conversely, overtreatment of false positive bacteriuria could lead to adverse effects from antibiotics and increased risk for antibiotic resistance. As nurses play a prominent role in patient education, diagnostic stewardship interventions may want to utilize nurses' educational capabilities to improve urine culture collection. TWEETABLE ABSTRACT: 55 % of urine cultures collected in primary care clinics were contaminated, revealing a major opportunity for nurse-driven diagnostic stewardship interventions.