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.

A survey of patient practices regarding leftover antibiotics reveals a potential source of antibiotic overuse.

Taking leftover prescribed antibiotics without consulting a healthcare professional is problematic for the efficacy, safety, and antibiotic stewardship. We conducted a cross-sectional survey of adult patients in English and Spanish between January 2020 and June 2021 in six safety-net primary care clinics and two private emergency departments. We assessed the reasons for stopping prescribed antibiotics early and what was done with the leftover antibiotics. Additionally, we determined 1) prior leftover antibiotic use, 2) intention for future use of leftover antibiotics, and 3) sociodemographic factors. Of 564 survey respondents (median age of 51), 45% (251/564) reported a history of stopping antibiotics early, with 171/409 (42%) from safety net and 80/155 (52%) from the private clinics. The most common reason for stopping prescribed antibiotics early was "because you felt better" (194/251, 77%). Among survey participants, prior use of leftover antibiotics was reported by 149/564 (26%) and intention for future use of leftover antibiotics was reported by 284/564 (51%). In addition, higher education was associated with a higher likelihood of prior leftover use. Intention for future use of leftover antibiotics was more likely for those with transportation or language barriers to medical care and less likely for respondents with private insurance. Stopping prescribed antibiotics early was mostly ascribed to feeling better, and saving remaining antibiotics for future use was commonly reported. To curb nonprescription antibiotic use, all facets of the leftover antibiotic use continuum, from overprescribing to hoarding, need to be addressed.

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.

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.

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.

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.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

The Five Ds of Outpatient Antibiotic Stewardship for Urinary Tract Infections.

Urinary tract infections (UTI) are one of the most common indications for antibiotic prescriptions in the outpatient setting. Given rising rates of antibiotic resistance among uropathogens, antibiotic stewardship is critically needed to improve outpatient antibiotic use, including in outpatient clinics (primary care and specialty clinics) and emergency departments. Outpatient clinics are in general a neglected practice area in antibiotic stewardship programs, yet most antibiotic use in the United States is in the outpatient setting. This article provides a comprehensive review of antibiotic stewardship strategies for outpatient UTI in the adult population, with a focus on the "five Ds" of stewardship for UTI, including right diagnosis, right drug, right dose, right duration, and de-escalation. Stewardship interventions that have shown success for improving prescribing for outpatient UTI are discussed, including diagnostic stewardship strategies, such as reflex urine cultures, computerized decision support systems, and modified reporting of urine culture results. Among the many challenges to achieving stewardship for UTI in the outpatient setting, some of the most important are diagnostic uncertainty, increasing antibiotic resistance, limitations of guidelines, and time constraints of stewardship personnel and front-line providers. This article presents a stewardship framework, built on current evidence and expert opinion, that clinicians can use to guide their own outpatient management of UTI.

Envisioning Future Urinary Tract Infection Diagnostics.

Urinary tract infections (UTIs) are among the most common bacterial infections in the United States and are a major driver of antibiotic use, both appropriate and inappropriate, across healthcare settings. Novel UTI diagnostics are a strategy that might enable better UTI treatment. Members of the Antibacterial Resistance Leadership Group Laboratory Center and the Infectious Diseases Society of America Diagnostics Committee convened to envision ideal future UTI diagnostics, with a view towards improving delivery of healthcare, patient outcomes and experiences, and antibiotic use, addressing which types of UTI diagnostics are needed and how companies might approach development of novel UTI diagnostics.

Optimal Urine Culture Diagnostic Stewardship Practice-Results from an Expert Modified-Delphi Procedure.

BACKGROUND: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship. METHODS: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed. RESULTS: One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions. CONCLUSIONS: These 18 guidance statements can optimize use of urine cultures for better patient outcomes.

Identifying Causative Microorganisms in Left Ventricular Assist Device Infections as a Guide for Developing Bacteriophage Therapy.

BACKGROUND: As more left ventricular-assist devices (LVADs) are implanted, multidrug-resistant LVAD infections are becoming increasingly common, partly due to bacterial biofilm production. To aid in developing bacteriophage therapy for LVAD infections, we have identified the most common bacterial pathogens that cause LVAD driveline infections (DLIs) in our heart transplant referral center. MATERIALS AND METHODS: We studied a retrospective cohort of patients who received LVADs from November 2003 to August 2017 to identify the common causative organisms of LVAD infection. We also studied a prospective cohort of patients diagnosed with DLIs from October 2018 to May 2019 to collect bacterial strains from DLIs for developing bacteriophages to lyse causative pathogens. LVAD infections were classified as DLI, bacteremia, and pump/device infections in the retrospective cohort. RESULTS: In the retrospective cohort of 582 patients, 186 (32.0%) developed an LVAD infection, with 372 microbial isolates identified. In the prospective cohort, 96 bacterial strains were isolated from 54 DLIs. The microorganisms causing DLIs were similar in the two cohorts; the most common isolate was Staphylococcus aureus. We identified 6 prospective S. aureus strains capable of biofilm formation. We developed 3 bacteriophages that were able to lyse 5 of 6 of the biofilm-forming S. aureus strains. CONCLUSIONS: Similar pathogens caused LVAD DLIs in our retrospective and prospective cohorts, indicating our bacterial strain bank will be representative of future DLIs. Our banked bacterial strains will be useful in developing phage cocktails that can lyse ≥80% of the bacteria causing LVAD infections at our institution.

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.

Postoperative Work and Activity Restrictions After Abdominal Surgery: A Systematic Review.

OBJECTIVE: This systematic review aims to assess what is known about convalescence following abdominal surgery. Through a review of the basic science and clinical literature, we explored the effect of physical activity on the healing fascia and the optimal timing for postoperative activity. BACKGROUND: Abdominal surgery confers a 30% risk of incisional hernia development. To mitigate this, surgeons often impose postoperative activity restrictions. However, it is unclear whether this is effective or potentially harmful in preventing hernias. METHODS: We conducted 2 separate systematic reviews using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The first assessed available basic science literature on fascial healing. The second assessed available clinical literature on activity after abdominal surgery. RESULTS: Seven articles met inclusion criteria for the basic science review and 22 for the clinical studies review. The basic science data demonstrated variability in maximal tensile strength and time for fascial healing, in part due to differences in layer of abdominal wall measured. Some animal studies indicated a positive effect of physical activity on the healing wound. Most clinical studies were qualitative, with only 3 randomized controlled trials on this topic. Variability was reported on clinician recommendations, time to return to activity, and factors that influence return to activity. Interventions designed to shorten convalescence demonstrated improvements only in patient-reported symptoms. None reported an association between activity and complications, such as incisional hernia. CONCLUSIONS: This systematic review identified gaps in our understanding of what is best for patients recovering from abdominal surgery. Randomized controlled trials are crucial in safely optimizing the recovery period.

Engaging patients and caregivers to establish priorities for the management of diabetic foot ulcers.

OBJECTIVE: Effective diabetic foot ulcer (DFU) care has been stymied by a lack of input from patients and caregivers, reducing treatment adherence and overall quality of care. Our objectives were to capture the patient and caregiver perspectives on experiencing a DFU and to improve prioritization of patient-centered outcomes. METHODS: A DFU-related stakeholder group was formed at an urban tertiary care center. Seven group meetings were held across 4 months, each lasting ∼1 hour. The meeting facilitator used semistructured questions to guide each discussion. The topics assessed the challenges of the current DFU care system and identified the outcomes most important to stakeholders. The meetings were audio recorded and transcribed. Directed and conventional content analyses were used to identify key themes. RESULTS: Six patients with diabetes (five with an active DFU), 3 family caregivers, and 1 Wound Clinic staff member participated in the stakeholder group meetings. The mean patient age was 61 years, four (67%) were women, five (83%) were either African American or Hispanic, and the mean hemoglobin A1c was 8.3%. Of the five patients with a DFU, three had previously required lower extremity endovascular treatment and four had undergone at least one minor foot amputation. Overall, stakeholders described how poor communication between medical personnel and patients made the DFU experience difficult. They felt overwhelmed by the complexity of DFU care and were persistently frustrated by inconsistent medical recommendations. Limited resources further exacerbated their frustrations and barriers to care. To improve DFU management, the stakeholders suggested a centralized healthcare delivery pathway with timely access to a coordinated, multidisciplinary DFU team. The clinical outcomes most valued by stakeholders were (1) avoiding amputation and (2) maintaining or improving health-related quality of life, which included independent mobility, pain control, and mental health. From these themes, we developed a conceptual model to inform DFU care pathways. CONCLUSIONS: Current DFU management lacks adequate care coordination. Multidisciplinary approaches tailored to the self-identified needs of patients and caregivers could improve adherence. Future DFU-related comparative effectiveness studies will benefit from direct stakeholder engagement and are required to evaluate the efficacy of incorporating patient-centered goals into the design of a multidisciplinary DFU care delivery system.

Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial.

Importance: Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness. Objective: To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized. Interventions: Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment. Main Outcomes and Measures: The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication. Results: Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group. Conclusions and Relevance: Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI. Trial Registration: ClinicalTrials.gov identifier: NCT01994538.

Imprecision Medicine: Challenges in Diagnosis, Treatment, and Measuring Quality for Catheter-Associated Urinary Tract Infection.

We question the reliability of the vague symptoms that most commonly define catheter-associated urinary tract infection (CAUTI) and encourage further examination of whether the current CAUTI definition reflects a true infection. While diagnosing CAUTI using the current surveillance definition, physicians may be missing a number of nonurinary etiologies for fever, prematurely diagnosing urinary tract infection, and prescribing unnecessary antibiotics. We believe it is time to reconsider the quality metric of CAUTI. By doing so, we can improve antibiotic use and quality of patient care.

Use of Antibiotics Without a Prescription in the U.S. Population: A Scoping Review.

Background: Use of antibiotics without a prescription may increase unnecessary and inappropriate drug use or doses as well as global risk for antimicrobial resistance. Purpose: To perform a scoping review of research on the prevalence of nonprescription antibiotic use in the United States and to examine the factors that influence it. Data Sources: Searches of PubMed, EMBASE, CINAHL, Scopus, and relevant Web sites without language restrictions from January 2000 to March 2019. Study Selection: Studies reporting nonprescription use of antibiotics, storage of antibiotics, intention to use antibiotics without a prescription, and factors influencing nonprescription use. Data Extraction: Two reviewers independently screened citations and full texts and performed data abstraction. Data Synthesis: Of 17 422 screened articles, 31 met inclusion criteria. Depending on population characteristics, prevalence of nonprescription antibiotic use varied from 1% to 66%, storage of antibiotics for future use varied from 14% to 48%, and prevalence of intention to use antibiotics without a prescription was 25%. Antibiotics were obtained without a prescription from various sources, including previously prescribed courses, local markets or stores, and family or friends. Reported factors contributing to nonprescription use included easy access through markets or stores that obtain antibiotics internationally for under-the-counter sales, difficulty accessing the health care system, costs of physician visits, long waiting periods in clinics, and transportation problems. Limitation: Scarce evidence and heterogeneous methods and outcomes. Conclusion: Nonprescription antibiotic use is a seemingly prevalent and understudied public health problem in the United States. An increased understanding of risk factors and pathways that are amenable to intervention is essential to decrease this unsafe practice. Primary Funding Source: None.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.