Antibiotic Stewardship Interventions for Urinary Tract Infections in Outpatient Settings: A Narrative Review.

Inappropriate antibiotic choice or duration of therapy for urinary tract infections (UTIs) in outpatients is common and is a major contributor to antibiotic overuse. Most studies on outpatient antibiotic stewardship for UTIs follow a pre-design or post-design with a multifaceted intervention; these trials generally have found improvement in appropriateness of antibiotic use for UTI. Audit and feedback was one of the most commonly employed strategies across these trials but may not be sustainable. Future research on antibiotic stewardship for UTIs in outpatients should measure both effectiveness and implementation success.

Managing External Urinary Catheters.

This narrative review explores the use of external urinary catheters. These devices are available in various types and materials for male and female patients. The indications for the use of external urinary catheters include managing incontinence linked to overactive bladder and neurogenic lower urinary tract dysfunction. Contraindications to the use of external urinary catheters include urinary obstruction. Proper skin care and proactive infection control measures are necessary to prevent complications. The collection of a urine specimen for culture requires a standardized technique to prevent contamination. Clinician-led patient education on catheter management plays a important role in ensuring patient comfort and safety.

Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. RESULTS: Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. CONCLUSIONS: Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

Assessing clinicians' and trainees' knowledge and practice of the IDSA guidelines for asymptomatic bacteriuria in older adults.

A survey of advanced practice clinicians (APCs), physicians, residents, and medical students at an academic medical center and community practices in southeastern Texas revealed a gap in knowledge and practice related to testing and treatment for asymptomatic bacteriuria (ASB) in older adults.

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.

Impact of routine urine cultures on antibiotic usage in those undergoing a routine annual spinal cord injury evaluation.

OBJECTIVE: The Veterans Health Administration (VHA), the largest single provider of spinal cord injury and disorder (SCI/D) care in the United States, currently mandates that every patient receives a screening urine culture during the annual evaluation, a yearly comprehensive history and physical examination. This testing has shown in a small subset of patients to overidentify asymptomatic bacteriuria that is then inappropriately treated with antibiotics. The objective of the current analysis was to assess the association of the annual evaluation on urine testing and antibiotic treatment in a national sample of Veterans with SCI/D. DESIGN/METHOD: A retrospective cohort study using national VHA electronic health record data of Veterans with SCI/D seen between October 1, 2017-September 30, 2019 for their annual evaluation. RESULTS: There were 9447 Veterans with SCI/D who received an annual evaluation; 5088 (54%) had a urine culture obtained. 2910 cultures (57%) were positive; E. coli was the most common organism obtained (12.9% of total urine cultures). Of the patients with positive urine cultures, 386 were prescribed antibiotics within the 7 days after that encounter (13%); of the patients with negative cultures (n = 2178), 121 (6%) were prescribed antibiotics; thus, a positive urine culture was a significant driver of antibiotic use (p < 0.001). CONCLUSION: The urine cultures ordered at the annual exam are often followed by antibiotics; this practice may be an important target for antibiotic stewardship programs in SCI.

Acculturation and Subjective Norms Impact Non-Prescription Antibiotic Use among Hispanic Patients in the United States.

Using antibiotics without medical guidance (non-prescription antibiotic use) may contribute to antimicrobial resistance. Hispanic individuals are a growing demographic group in the United States (US) with a high prevalence of non-prescription antibiotic use. We investigated the effects of acculturation and subjective norms on Hispanic individuals' intentions to use antibiotics without a prescription from the following sources: (1) markets in the United States (not legal), (2) other countries (abroad), (3) leftovers from previous prescriptions, and (4) friends/relatives. We surveyed self-identified Hispanic outpatients in eight clinics from January 2020 to June 2021 using the previously validated Short Acculturation Scale for Hispanics (SASH). Of the 263 patients surveyed, 47% reported previous non-prescription use, and 54% expressed intention to use non-prescription antibiotics if feeling sick. Individuals with lower acculturation (Spanish-speaking preferences) expressed greater intentions to use antibiotics from abroad and from any source. Individuals with more friends/relatives who obtain antibiotics abroad were over 2.5 times more likely to intend to use non-prescription antibiotics from friends/relatives (p = 0.034). Other predictors of intention to use non-prescription antibiotics included high costs of doctor visits and perceived language barriers in the clinic. Antibiotic stewardship interventions in Hispanic communities in the United States should consider the sociocultural and healthcare barriers influencing non-prescription use and promote language-concordant healthcare.

Strategies to prevent catheter-associated urinary tract infections in acute-care hospitals: 2022 Update.

The intent of this document is to highlight practical recommendations in a concise format designed to assist physicians, nurses, and infection preventionists at acute-care hospitals in implementing and prioritizing their catheter-associated urinary tract infection (CAUTI) prevention efforts. This document updates the Strategies to Prevent Catheter-Associated Urinary Tract Infections in Acute-Care Hospitals published in 2014. It is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission.

Quantifying the Implementation and Cost of a Multisite Antibiotic Stewardship Intervention for Asymptomatic Bacteriuria.

Objective: The intensity of an antibiotic stewardship intervention to achieve clinical impact is not known. We conducted a multisite dissemination project of an intervention to reduce treatment of asymptomatic bacteriuria (ASB) and studied: (1) the association between implementation metrics and clinical outcomes and (2) the cost of implementation. Design/Setting/Participants: A central site facilitated a multimodality intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB at 4 Veterans Affairs medical centers. Methods: The intervention consisted of a decision support aid algorithm and interactive teaching cases that provided in the moment audit and feedback on how to manage ASB. Implementation outcomes included minutes spent in intervention delivery, number of healthcare professionals reached, and number of sessions delivered. Clinical outcomes included days of antibiotic therapy (DOT), length of antibiotic therapy (LOT), and number of urine cultures ordered per 1000 bed days. Personnel reported weekly time logs. Results: Minutes spent in intervention delivery were inversely correlated with two clinical outcomes, DOT (R -0.3, P = .04) and LOT (R -0.3, P = .02). Number of healthcare professionals reached and number of sessions delivered were not correlated with clinical outcomes of DOT (R -0.003, P = .98, R = -0.059, P = .69) or LOT (R +0.073, P = .62, R -0.102, P = .49). Physician champions spent an average of 3.8% of effort on the intervention. The implementation cost was USD 22,299/year per site on average. Conclusions: The amount of time local teams spent in delivery of an antibiotic stewardship intervention was correlated with the desired decrease in antibiotic use. Implementing this successful antibiotic stewardship intervention required minimal time.

A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes.

BACKGROUND: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections. METHODS: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded. RESULTS: Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported. CONCLUSIONS: Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.

Older patient age and prior antimicrobial use strongly predict antimicrobial resistance in Escherichia coli isolates recovered from urinary tract infections among female outpatients.

BACKGROUND: Increasing prevalence of antimicrobial resistance (AMR), including multidrug resistance (MDR), among Escherichia coli (E. coli) makes treatment of uncomplicated urinary tract infection (uUTI) difficult. We assessed risk factors for fluoroquinolone (FQ)-not-susceptible (NS) and MDR E. coli among US female outpatients. METHODS: This retrospective cohort study utilized data from female outpatients aged ≥ 12 years with E. coli positive urine culture and oral antimicrobial prescription ± 1 day from index. We assessed patient-level factors within 90 and 91-360 days prior to index as predictors of FQ NS (intermediate/resistant) and MDR (NS to ≥ 1 drug across ≥ 3 classes) E. coli: age, prior oral antimicrobial dispensing, prior AMR phenotypes, prior urine culture, and prior hospitalization. RESULTS: Among 1,858 outpatients with urine-isolated E. coli, 369 (19.9%) had FQ NS and 59 (3.2%) had MDR isolates. After multivariable adjustment, independent risk factors (p < 0.03) for FQ NS E. coli were older age, prior FQ NS isolates, prior dispensing of FQ, and dispensing of any oral antibiotic. Independent risk factors (p < 0.02) for MDR were prior extended-spectrum ß-lactamase-producing isolates (ESBL+), prior FQ dispensing, and prior oral antibiotic dispensing. CONCLUSIONS: In women with uUTI due to E. coli, prior dispensing of FQ or any oral antibiotic within 90 days predicted FQ NS and MDR urine E. coli. Prior urine culture with FQ NS isolates and older age were predictive of FQ NS E. coli. Prior ESBL+ was predictive of MDR E. coli. These data could help identify patients at risk for AMR E. coli and inform empiric prescribing.

Perspectives on Non-Prescription Antibiotic Use among Hispanic Patients in the Houston Metroplex.

BACKGROUND: Non-prescription antibiotic use includes taking an antibiotic without medical guidance (e.g., leftovers, from friends/relatives, or purchased without a prescription). Non-prescription use contributes to antimicrobial resistance, adverse drug reactions, interactions, superinfection, and microbiome imbalance. Qualitative studies exploring perspectives regarding non-prescription use among Hispanic patients are lacking. We used the Kilbourne Framework for Advancing Health Disparities Research to identify factors influencing patients' non-prescription use and organize our findings. METHODS: Our study includes Hispanic primary care clinic patients with different types of health insurance coverage in the Houston metroplex who endorsed non-prescription use in a previous survey. Semistructured interviews explored the factors promoting non-prescription use in Hispanic adults. Interviews were conducted remotely, in English or Spanish, between May 2020 and October 2021. Inductive coding and thematic analysis identified motives for non-prescription use. RESULTS: Participants (n = 35) were primarily female (68.6%) and aged 27 to 66. Participants reported obtaining antibiotics through trusted persons, sold under-the-counter in US markets, and purchased without a prescription abroad. Factors contributing to non-prescription use included beliefs that the doctor visit was unnecessary, limited access to healthcare (due to insurance constraints, costs, and clinic wait times), and communication difficulties (e.g., language barriers with clinicians and perceived staff rudeness). Participants expressed confidence in medical recommendations from pharmacists and trusted community members. CONCLUSIONS: Patient, healthcare system, and clinical encounter factors contribute to non-prescription use in Hispanic communities. Antibiotic stewardship interventions that involve pharmacists and trusted persons, improve access to care, and address communication barriers and cultural competency in the clinic may help reduce non-prescription use in these communities.

Real-world experience with cefiderocol therapy for Pseudomonas aeruginosa and other multidrug resistant gram-negative infections within the Veterans Health Administration, 2019-2022.

Objective: Single-center and regional studies have reported outcomes after treatment with cefiderocol, a novel siderophore cephalosporin. We report on real-world use, clinical outcomes, and microbiological outcomes with cefiderocol therapy within the Veterans' Health Administration (VHA). Design: Prospective, observational descriptive study. Setting: Veterans' Health Administration, 132 sites across the United States, during 2019-2022. Patients: This study included patients admitted to any VHA medical center who received cefiderocol for ≥2 days. Methods: Data were obtained from the VHA Corporate Data Warehouse and through manual chart review. We extracted clinical and microbiologic characteristics and outcomes. Results: In total, 8,763,652 patients received 1,142,940,842 prescriptions during the study period. Of these, 48 unique individuals received cefiderocol. The median age of this cohort was 70.5 years (IQR, 60.5-74), and the median Charlson comorbidity score was 6 (IQR, 3-9). The most common infectious syndromes were lower respiratory tract infection in 23 patients (47.9%) and urinary tract infection in 14 patients (29.2%). The most common pathogen cultured was P. aeruginosa in 30 patients (62.5%). The clinical failure rate was 35.4% (17 of 48), and 15 (88.2%) of these 17 patients died within 3 days of clinical failure. The 30-day and 90-day all-cause mortality rates were 27.1% (13 of 48) and 45.8% (22 of 48), respectively. The 30-day and 90-day microbiologic failure rates were 29.2% (14 of 48) and 41.7% (20 of 48), respectively. Conclusions: In this nationwide VHA cohort clinical and microbiologic failure occurred in >30% of patients treated with cefiderocol, and >40% of these died within 90 days. Cefiderocol is not widely used, and many of the patients who received it had substantial comorbidities.

Antibiotic Use Without a Prescription: A Multisite Survey of Patient, Health System, and Encounter Characteristics.

BACKGROUND: Using antibiotics without a prescription is potentially unsafe and may increase the risk of antimicrobial resistance. We evaluated the effect of patient, health system, and clinical encounter factors on intention to use antibiotics without a prescription that were (1) purchased in the United States, (2) obtained from friends or relatives, (3) purchased abroad, or (4) from any of these sources. METHODS: The survey was performed January 2020-June 2021 in 6 publicly funded primary care clinics and 2 private emergency departments in Texas, United States. Participants included adult patients visiting 1 of the clinical settings. Nonprescription use was defined as use of antibiotics without a prescription; intended use was professed intention for future nonprescription antibiotic use. RESULTS: Of 564 survey respondents (33% Black and 47% Hispanic or Latino), 246 (43.6%) reported prior use of antibiotics without a prescription, and 177 (31.4%) reported intent to use antibiotics without a prescription. If feeling sick, respondents endorsed that they would take antibiotics obtained from friends/relatives (22.3% of 564), purchased in the United States without a prescription (19.1%), or purchased abroad without a prescription (17.9%). Younger age, lack of health insurance, and a perceived high cost of doctor visits were predictors of intended use of nonprescription antibiotics from any of the sources. Other predictors of intended use were lack of transportation for medical appointments, language barrier to medical care, Hispanic or Latino ethnicity, and being interviewed in Spanish. CONCLUSIONS: Patients without health insurance who report a financial barrier to care are likely to pursue more dangerous nonprescription antimicrobials. This is a harm of the US fragmented, expensive healthcare system that may drive increasing antimicrobial resistance and patient harm.

Prevalence and Predictors of Using Antibiotics without a Prescription in a Pediatric Population in the United States.

Non-prescription antibiotic use (using antibiotics without clinical guidance) increases the risk of the development of antibiotic resistance, adverse drug reactions, and other potential patient harm. Few studies have explored non-prescription use in children in the U.S. From January 2021 to April 2022, a diverse sample of caregivers of children under 18 years were surveyed in English and Spanish at two safety net clinics in Texas. We assessed the prevalence of antibiotic use in children in the previous 12 months, storage of antimicrobials, and intended use of non-prescription antibiotics (professed intention for future non-prescription antibiotic use). We also measured sociodemographic factors, types of antibiotics used, and symptoms that trigger non-prescription use. The response rate was 82%, and 17% were surveyed in Spanish. Of 322 participants surveyed, three Spanish-speaking caregivers reported giving non-prescription antibiotics to their child in the previous 12 months. Approximately 21% (n = 69) reported storing antimicrobials at home, specifically amoxicillin (n = 52), clindamycin (n = 10), cephalexin (n = 5), penicillin (n = 3), and trimethoprim/sulfamethoxazole (n = 3). Nearly 15% (n = 46) reported intention to give non-prescription antibiotics to their children. Younger caregiver age was associated with storage and intended use of non-prescription antibiotics. Our findings will guide the development of an educational intervention to decrease non-prescription antibiotic use.

Mortality difference from Klebsiella aerogenes vs Enterobacter cloacae bloodstream infections.

Members of the order Enterobacterales, including Escherichia coli , Klebsiella species and Enterobacter species, are important pathogens in healthcare-associated infections. Higher mortality has been reported from infections due to Klebsiella pneumoniae than from E. coli , but prior studies comparing Enterobacter aerogenes (recently renamed Klebsiella aerogenes ) bacteraemia and Enterobacter cloacae complex bacteraemia have yielded conflicting results regarding whether clinical outcomes differ. We found bacteraemia with K. aerogenes was independently associated with greater risk of 30-day mortality than bacteraemia with Enterobacter cloacae complex.

Acute and Chronic Infectious Prostatitis in Older Adults.

Acute and chronic bacterial prostatitis are clinically significant entities that can be difficult to diagnose and appropriately treat. Herein, we review when to suspect these clinical conditions, how to diagnose them, and how to effectively treat them based on the extant literature. Our aim was to equip the practicing clinician with the ability to proficiently diagnose and manage acute and chronic bacterial prostatitis, particularly in older patients.

Bacteriuria in older adults triggers confusion in healthcare providers: A mindful pause to treat the worry.

The evidence base for refraining from screening for or treating asymptomatic bacteriuria (ASB) in older adults is strong, but both practices remain prevalent. Clinical confusion over how to respond to a change from baseline, when to order a urinalysis and urine culture, and what to do with a positive urine culture fuels unnecessary antibiotic use for ASB. If the provider can take a mindful pause to apply evidenced-based assessment tools, the resulting increased clarity in how to manage the situation can reduce overtreatment of ASB.