Impact of a Multifaceted Intervention on Antibiotic Prescribing for Cystitis and Asymptomatic Bacteriuria in 23 Community Hospital Emergency Departments.

Background: Urinary tract infections (UTIs) are over-diagnosed and over-treated in the emergency department (ED) leading to unnecessary antibiotic exposure and avoidable side effects. However, data describing effective large-scale antimicrobial stewardship program (ASP) interventions to improve UTI and asymptomatic bacteriuria (ASB) management in the ED are lacking. Methods: We implemented a multifaceted intervention across 23 community hospital EDs in Utah and Idaho consisting of in-person education for ED prescribers, updated electronic order sets, and implementation/dissemination of UTI guidelines for our healthcare system. We compared ED UTI antibiotic prescribing in 2021 (post-intervention) to baseline data from 2017 (pre-intervention). The primary outcomes were the percent of cystitis patients prescribed fluoroquinolones or prolonged antibiotic durations (>7 days). Secondary outcomes included the percent of patients treated for UTI who met ASB criteria, and 14-day UTI-related readmissions. Results: There was a significant decrease in prolonged treatment duration for cystitis (29% vs 12%, P < .01) and treatment of cystitis with a fluoroquinolone (32% vs 7%, P < .01). The percent of patients treated for UTI who met ASB criteria did not change following the intervention (28% pre-intervention versus 29% post-intervention, P = .97). A subgroup analysis indicated that ASB prescriptions were highly variable by facility (range 11%-53%) and provider (range 0%-71%) and were driven by a few high prescribers. Conclusions: The intervention was associated with improved antibiotic selection and duration for cystitis, but future interventions to improve urine testing and provide individualized prescriber feedback are likely needed to improve ASB prescribing practice.

Real-World Effectiveness of Intravenous and Oral Antibiotic Stepdown Strategies for Gram-Negative Complicated Urinary Tract Infection With Bacteremia.

Background: Robust data are lacking regarding the optimal route, duration, and antibiotic choice for gram-negative bloodstream infection from a complicated urinary tract infection source (GN-BSI/cUTI). Methods: In this multicenter observational cohort study, we simulated a 4-arm registry trial using a causal inference method to compare effectiveness of the following regimens for GN-BSI/cUTI: complete course of an intravenous ß-lactam (IVBL) or oral stepdown therapy within 7 days using fluoroquinolones (FQs), trimethoprim-sulfamethoxazole (TMP-SMX), or high-bioavailability ß-lactams (HBBLs). Adults treated between January 2016 and December 2022 for Escherichia coli or Klebsiella species GN-BSI/cUTI were included. Propensity weighting was used to balance characteristics between groups. The 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results: Of 2571 patients screened, 759 (30%) were included. Characteristics were similar between groups. Compared with IVBLs, we did not observe a difference in effectiveness for FQs (adjusted hazard ratio, 1.09 [95% confidence interval, .49-2.43]) or TMP-SMX (1.44 [.54-3.87]), and the effectiveness of TMP-SMX/FQ appeared to be optimal at durations of >10 days. HBBLs were associated with nearly 4-fold higher risk of recurrence (adjusted hazard ratio, 3.83 [95% confidence interval, 1.76-8.33]), which was not mitigated by longer treatment durations. Most HBBLs (67%) were not optimally dosed for bacteremia. Results were robust to multiple sensitivity analyses. Conclusions: These real-world data suggest that oral stepdown therapy with FQs or TMP-SMX have similar effectiveness as IVBLs. HBBLs were associated with higher recurrence rates, but dosing was suboptimal. Further data are needed to define optimal dosing and duration to mitigate treatment failures.

Oral ß-Lactams, Fluoroquinolones, or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Uncomplicated Escherichia coli or Klebsiella Species Bacteremia From a Urinary Tract Source.

Background: Fluoroquinolones (FQs) are effective for oral step-down therapy for gram-negative bloodstream infections but are associated with unfavorable toxic effects. Robust data are lacking for trimethoprim-sulfamethoxazole (TMP-SMX) and high-bioavailability ß-lactams (HBBLs). Methods: In this multicenter observational cohort study, we simulated a 3-arm registry trial using causal inference methods to compare the effectiveness of FQs, TMP-SMX, or HBBLs for gram-negative bloodstream infections oral step-down therapy. The study included adults treated between January 2016 and December 2022 for uncomplicated Escherichia coli or Klebsiella species bacteremia of urinary tract origin who were who were transitioned to an oral regimen after ≤4 days of effective intravenous antibiotics. Propensity weighting was used to balance characteristics between groups. 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results: Of 2571 patients screened, 648 (25%) were included. Their median age (interquartile range) was 67 (45-78) years, and only 103 (16%) were male. Characteristics were well balanced between groups. Compared with FQs, TMP-SMX had similar effectiveness (adjusted hazard ratio, 0.91 [95% confidence interval, .30-2.78]), and HBBLs had a higher risk of recurrence (2.19 [.95-5.01]), although this difference was not statistically significant. Most HBBLs (70%) were not optimally dosed for bacteremia. A total antibiotic duration ≤8 days was associated with a higher recurrence rate in select patients with risk factors for failure. Conclusions: FQs and TMP-SMX had similar effectiveness in this real-world data set. HBBLs were associated with higher recurrence rates but suboptimal dosing may have contributed. Further studies are needed to define optimal BL dosing and duration to mitigate treatment failures.

Antibiotic prescribing for adults with group A streptococcal bacteremia in a large healthcare system.

Purpose: Limited data exist regarding treatment of invasive group A streptococcal (GAS) infections, including safety and efficacy of oral (PO) step-down therapy. We sought to describe current prescribing practices and clinical outcomes for patients with GAS bacteremia across a large health system, including a prespecified subset of patients who stepped down to PO antibiotics. Methods: This retrospective cohort study included adult patients with a positive blood culture for GAS between July 2018 and July 2021. Primary outcomes included frequency of PO step-down, total duration of therapy, duration of intravenous (IV) therapy prior to PO switch, and antimicrobial selection. Secondary outcomes included length of stay (LOS), mortality, adverse events, and clinical failure leading to readmission within 90 days. Results: In total, 280 patients met inclusion criteria. Of these, 46.7% were stepped down to PO antibiotics. Median total duration of therapy was 15 days. Median duration of IV therapy prior to PO switch was 5 days. The predominant definitive antibiotic choice was a beta-lactam. Median LOS was 5 days. Ninety-day mortality was 16.7%. One patient developed an occluded line and one developed Clostridioides difficile-associated diarrhea within 90 days. Ninety-day readmission due to clinical failure was 12.5%. Among cases of uncomplicated skin and soft tissue source, mortality (6.1% vs 2.4%) and readmission (15.2% vs 16.9%) were similar between definitive IV and PO groups. Conclusions: Group A streptococcal bacteremia is a severe infection with a high readmission and mortality rate. Use of PO step-down therapy was common with similar readmission and mortality rates compared with definitive IV therapy.

Outcomes of patients with bacteriuria/pyuria of clinically undetermined significance (BPCUS) treated with antibiotics in 23 community hospital emergency departments.

The optimal management of bacteriuria/pyuria of clinically undetermined significance (BPCUS) is unknown. Among 220 emergency department patients prescribed antibiotics for BPCUS, we found frequent readmissions, which were mitigated by outpatient follow-up visits. Observation and follow-up for an unknown diagnosis should be emphasized over antibiotics due to high likelihood of readmissions.

Influence of Body Weight Category on Outcomes in Candidemia Patients Treated With Anidulafungin.

BACKGROUND: Case reports and pharmacokinetic data suggest off-label echinocandin dosing may be needed to reach adequate serum concentrations in obese patients. Few outcome studies exist evaluating this population. OBJECTIVES: Of this study were to (1) determine the association of body mass index (BMI) with clinical outcomes of candidemia patients on standard doses of anidulafungin and (2) characterize fungal infections by body weight. METHODS: A retrospective cohort was conducted to evaluate hospitalized patients treated for candidemia with anidulafungin at Food and Drug Administration-labeled dosing for at least 72 hours from January 1, 2014, through January 31, 2018. Candidemia was diagnosed by blood culture or T2 magnetic resonance (T2MR). Patients were compared according to BMI category. RESULTS: One hundred seventy-three patients were included. Candida albicans and Candida glabrata were identified in 58 (33%) and 57 (33%) patients, respectively. Mortality was comparable according to BMI category: 4 (36.4%) underweight, 8 (25.8%) normal weight, 16 (32.0%) overweight, 20 (33.9%) obese, and 7 (31.8%) morbidly obese, P = .976. Variables associated with mortality included: severe sepsis (adjusted odds ratio [OR] = 5.1, 95% CI: 1.7-14.8) and liver disease (adjusted OR = 3.2, 95% CI: 1.1-9.4). Variables that were protective of mortality included: line removal (adjusted OR = 0.05, 95% CI: 0.02-0.2) and receipt of anidulafungin for at least 5 days (adjusted OR = 0.35, 95% CI: 0.15-0.8). CONCLUSION: There was no difference detected in mortality among patients with candidemia across BMI category. Larger studies are needed to confirm whether standard doses of anidulafungin are sufficient for candidemia in obese patients.

The long-term sustainability of a respiratory culture nudge.

Resource-intensive interventions and education are susceptible to a lack of long-term sustainability and regression to the mean. The respiratory culture nudge changed reporting to "Commensal Respiratory Flora only: No S. aureus/MRSA or P. aeruginosa." This study demonstrated sustained reduction in broad-spectrum antibiotic duration and long-term sustainability 3 years after implementation.

Assessment of invitrosynergy of daptomycin or vancomycin plus ceftaroline for daptomycin non-susceptible Staphylococcus aureus.

The combination of vancomycin or daptomycin plus ceftaroline has showed synergistic results in vitro. This study aimed to investigate in vitro synergy of vancomycin or daptomycin plus ceftaroline for seven patients with daptomycin non-susceptible Staphylococcus aureus (SA) bacteremia Thirteen isolates from seven patients were evaluated: two methicillin-susceptible and five methicillin-resistant SA infections. All patients were treated with daptomycin and became non-susceptible (minimum inhibitory concentration (MIC) >1 µg/mL) with therapy or had resistant strains initially. Time kill experiments were completed with 0.25 × MIC, 0.5 × MIC, and 0.75 × MIC concentrations. No synergy was seen at 0.25 × MIC. Synergy was observed for 4 isolates with vancomycin plus ceftaroline and with daptomycin plus ceftaroline for 2 isolates at 0.5 × MIC. These results are in accordance with literature that supports synergistic combinations of daptomycin or vancomycin with ceftaroline for SA bacteremia. Daptomycin non-susceptible SA bacteremia presents a treatment challenge.

Building the infrastructure for nationwide cancer surveillance and control--a comparison between the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology, and End Results (SEER) Program (United States).

OBJECTIVE: In preparation for jointly publishing official government cancer statistics, the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) compared incidence rates from NCI's Surveillance Epidemiology and End Results (SEER) Program and CDC's National Program of Cancer Registries (NPCR). METHODS: Data for 1999 covering 78% of the US population were obtained from SEER and selected NPCR registries that met high quality data criteria. Incidence rates (per 100,000 population) were age-adjusted to the 2000 US standard population, and 95% gamma confidence intervals were estimated. RESULTS: NPCR rates for all sites combined were higher than SEER rates (males: NPCR 553.6, SEER 538.7; females: NPCR 420.8, SEER 412.5), but rates for specific cancer sites varied by registry program. Rates for colon cancer (males: NPCR 47.0, SEER 42.7; females: NPCR 36.5, SEER 33.8) and tobacco-related cancers were higher in NPCR than SEER. In contrast, NPCR rates were lower than SEER rates for cancers of the female breast (NPCR 134.0, SEER 135.9), prostate (NPCR 162.0, SEER 170.2), and melanoma as well as for cancers more common among Asians and Pacific Islanders (e.g., stomach cancer). CONCLUSIONS: Rate differences may arise from population differences in socio-demographic characteristics, screening use, health behaviors, exposure to cancer causing agents or registry operations factors.

A vision for cancer incidence surveillance in the United States.

A comprehensive framework for cancer surveillance should span the entire lifespan and be capable of providing information on risk, burden, disparity, cost, cancer care, survival, and death. Cancer incidence, the point in the continuum when an individual is diagnosed with cancer, has a strong, well-developed system to produce information about newly diagnosed cancer cases. However, in the future, this system must be enhanced and integrated with other cancer surveillance networks and other systems to provide timely information on the burden of newly diagnosed patients with respect to various cross-cutting population characteristics (e.g., social, economic, race/ethnic, urbanicity, or access to care) to define, monitor, and reduce incidence and various disparities noted among population groups. Collaboration in data collection, standard setting, surveillance activities, research, education and training, data use, and advocacy among all registries and national programs will be important to the continued success of the cancer incidence surveillance system. The cancer registry is an integral part of the infrastructure to reduce the burden of cancer, including the numbers of newly diagnosed cases.