Abstract Background Urinary Tract Infections (UTIs) are commonly overdiagnosed. Some labs conduct urinalysis (UA) as a preliminary screening before proceeding to urine culture to reduce processing unnecessary samples. However, the optimal UA cutoffs for this diagnostic stewardship intervention are not well defined. UA squamous epithelial cells were not graphed b/c the value crossed the diagonal at multiple points. Methods We performed a retrospective, cross-sectional analysis of urine studies performed from 2/1/21-1/31/23 at the Los Angeles County Department of Health Services (4 medical centers & 20 clinics). We examined patient encounters in which a UA was ordered synchronously with a urine culture. We excluded patients who were pregnant, undergoing a urologic procedure, < 3 months of age, or neutropenic. We examined the diagnostic accuracy, receiver operating characteristic (ROC) curves, and area under the curve (AUC) for pre-screening urinalysis parameters prior to urine culture performance. From the macroscopic test, we examined leukocytes and nitrite. From the microscopic exam, we examined bacteria, white blood cells (WBC), and squamous epithelial cells. We investigated each test’s correlation with a uropathogen isolated from culture. Sensitivity and specificity of urinalysis WBC cutpoints for identifying uropathogens Results We examined 81,907 paired urinalysis and urine cultures (17,842 inpatient and 64,065 outpatient). Among the urine cultures, organisms isolated included 24,683 (30%) uropathogens, 4,373 (5%) organisms sometimes considered uropathogens, 3,000 (4%) organisms rarely considered a uropathogen, 30,511 (37%) multiple organisms, and 293 (0.7%) a non-uropathogen of clinical significance; 19,047 (23%) cultures were negative. When predicting a urine culture positive for a uropathogen, the UA parameter with the best diagnostic accuracy was WBCs (AUC: 0.758), followed by leukocytes, bacteria, nitrite, and squamous epithelial cells. (AUC: 0.723, 0.707, 0.652, and < 0.500, respectively) (Figure). The sensitivity and specificity of WBC cutoffs are outlined in the Table. Conclusion In a large dataset of paired urinalysis and urine cultures, WBC on microscopic urinalysis showed highest diagnostic accuracy at predicting isolation of a uropathogen on urine culture. Stewardship programs should consider this parameter as the screening test for urine culture performance. Disclosures Amy Y. Kang, Pharm.D., BCIDP, Paratek Pharmaceutical: Grant/Research Support Loren G. Miller, MD MPH, Armata: Grant/Research Support|Contrafect: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support

Abstract Background United States hospitals produce over 5.9 million tons of waste yearly. Disposable personal protective equipment (PPE) causes up to 70% of hospital municipal plastic waste. Contact precautions, often requiring disposable gowns and gloves, are frequently used to prevent MRSA/VRE transmission. We determined the scope and environmental impact of contact precaution use for MRSA and VRE in LA County. Methods We observed patient care at LA acute care hospitals to quantify PPE used for patients in MRSA/VRE contact precautions, as well as for patients with methicillin-susceptible Staphylococcus aureus (MSSA) and vancomycin-susceptible Enterococcus (VSE). We matched observations by hospital type (community, academic safety-net) and care location (intensive care, telemetry, ward). We conducted 24 observations for each organism. To determine the extent of PPE used for MRSA/VRE, the LA County Department of Public Health surveyed acute care hospitals for the average daily number of hospitalized patients in 2023 in MRSA/VRE contact precautions. We modeled the county-wide solid waste and carbon dioxide (CO2) emissions from MRSA/VRE contact precautions. Results Mean gown use was higher for MRSA vs. MSSA (2.33 vs. 0.17 gowns/hour, p< 0.01) and VRE vs. VSE (2.50 vs. 0.59 gowns/hour, p< 0.01). Glove use did not vary between MRSA vs. MSSA (5.08 vs. 4.33 gloves/hour, p = 0.45) or VRE vs. VSE (5.88 vs. 5.46 gloves/hour, p = 0.50). In total, ∼3% of LA County hospitals’ licensed beds are occupied by patients in contact precautions for MRSA and VRE. In our model this level of occupancy equaled 7.3 million gowns per year for MRSA and VRE contact precautions, which generate 461,400 kilograms (kg) of plastic waste and 2.27 million kg of CO2 emissions annually. Conclusion We found that care for patients in MRSA/VRE contact precautions requires significantly more gown use than for patients with MSSA/VSE. Glove use did not differ between patients with antibiotic-resistant infections vs. their antibiotic-sensitive counterparts. LA County’s MRSA/VRE PPE causes abundant plastic waste and greenhouse gas emissions equal to 5.8 million miles driven in an average car. Routine MRSA/VRE contact precautions need to be reconsidered given the paucity of supporting evidence as well as their potential harm to the environment. Disclosures Loren G. Miller, MD MPH, Armata: Grant/Research Support|Contrafect: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support

Importance:Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access. Objective:To evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteremia. Design, Setting, and Participants:Open-label, assessor-masked, randomized clinical trial conducted from April 2021 to December 2023 at 23 medical centers in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus bacteremia who achieved blood culture clearance following at least 72 hours but no more than 10 days of initial antibacterial therapy were included. Participants were excluded if they had central nervous system infection, retained infected prosthetic material, left-sided endocarditis, or severe immune compromise. Interventions:Participants were randomly assigned to receive either 2 doses of intravenous dalbavancin (n = 100; 1500 mg on days 1 and 8) or 4 to 8 total weeks of standard intravenous therapy (n = 100; cefazolin or antistaphylococcal penicillin if methicillin susceptible; vancomycin or daptomycin if methicillin resistant). Main Outcomes and Measures:The primary outcome was the desirability of outcome ranking (DOOR) at day 70, which involved 5 components (clinical success, infectious complications, safety complications, mortality, and health-related quality of life) and was assessed for superiority (achieved if the 95% CI for the probability of dalbavancin having a superior DOOR was >50%). Secondary outcomes included clinical efficacy at day 70 (prespecified noninferiority margin of 20%) and safety. Results:Of 200 participants randomized (mean [SD] age, 56 [16.2] years; 62 females [31%]), 167 (84%) survived to day 70 and had an efficacy assessment. Participants without a day 70 efficacy assessment were treated as clinical failures in the analyses. The probability of a more desirable day 70 outcome with dalbavancin vs standard therapy was 47.7% (95% CI, 39.8% to 55.7%). Regarding secondary outcomes, clinical efficacy was documented in 73 of 100 for dalbavancin and 72 of 100 for standard therapy (difference, 1.0% [95% CI, -11.5% to 13.5%]), meeting the noninferiority criterion. Serious adverse events were reported in 40 of 100 participants who received dalbavancin and 34 of 100 participants who received standard therapy; treatment-related adverse events were uncommon in both groups. Conclusions and Relevance:Among adult participants with complicated S aureus bacteremia who achieved blood culture clearance, dalbavancin was not superior to standard therapy by desirability of outcome ranking. When considered with other efficacy and safety outcomes these findings may help inform use of dalbavancin in clinical practice. Trial Registration:ClinicalTrials.gov Identifier: NCT04775953.

Abstract Background Contact precautions are frequently used to prevent in-facility transmission of MRSA, but their efficacy has been questioned. We hypothesized that contact precautions use would not correlate with MRSA bloodstream infection (BSI) rates in LA County hospitals. Methods The LA County Department of Public Health conducted a survey of LA County acute care hospitals’ use of contact precautions for MRSA colonization, history of MRSA infection/colonization, and active MRSA infection with or without uncontained purulence. We modeled National Healthcare Safety Network (NHSN) reported healthcare-associated MRSA BSI rates from 2022-23 via a negative binomial multivariable regression model. We controlled for hospital type (general acute care hospitals vs. long-term acute care hospitals (LTACHs)), number of intensive care unit (ICU) beds, and MRSA BSI admission prevalence rates. Results Of the 82 acute care hospitals in LA County, 69 completed the survey (84% response rate). MRSA contact precaution use was stratified into three groups: Least strict (no contact precautions or contact precautions only for active infection with uncontained purulence, 24% of hospitals), intermediate (contact precautions for any active infection, 32% of hospitals), and most strict (contact precautions for >2 reasons, 44% of hospitals). We found higher MRSA BSI in LTACHs vs. hospitals (Incidence rate ratio [IRR] 3.50, 95% CL 1.80-6.80, p = 0.0002), but no relationship with ICU beds (IRR 1.00, 95% CL 0.99-1.01, p = 0.15), MRSA BSI admission prevalence rates (IRR = 4.40, 95% CL 0.30-63.10, p = 0.27), or contact precaution use (IRR 0.80, 95% CL 0.50-1.30, p = 0.29 for the least strict group; IRR 1.40, 95% CL 0.89-2.20, p = 0.14 for the intermediate group, both in comparison to the most strict group). Conclusion Our survey of hospitals across LA County, which has a population of ∼10 million, found no significant association between stringency of MRSA contact precaution use and healthcare-associated MRSA BSI rate. Our findings support other data that fail to find clinical benefit to contact precautions for MRSA colonization/infection. Considering potential downsides of contact precautions for MRSA, the assumption that MRSA requires contact precautions may need to be reconsidered. Disclosures Loren G. Miller, MD MPH, Armata: Grant/Research Support|Contrafect: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support

Abstract Background Drug-resistant E. coli is a leading cause of antimicrobial resistance-associated deaths globally. Specifically, resistance to ceftriaxone (CRO-R) is increasing in E. coli. High-risk clonal group ST131 and its pandemic H30 subclone are of high concern yet studies characterizing these infections are limited. We evaluated baseline characteristics and clinical outcomes associated with H30 ST131, non-H30 ST131 and non-ST131 E. coli bloodstream infections (BSI). Methods Patients with monomicrobial carbapenem-susceptible E. coli BSI that were matched 1:1 by study site (CRO-R and CRO-susceptible community-acquired and hospital onset cases) were prospectively enrolled from 14 United States hospitals between November 12, 2020 to April 28, 2021 in the multicenter Study of Highly Resistant E. coli (SHREC). Isolates underwent whole genome sequencing. The primary outcome was a 30-day Desirability of Outcome Ranking (DOOR) after index culture including clinical response to treatment and all-cause mortality. Results There were 92 (33%) H30 ST131, 29 (10%) non-H30 ST131, and 161 (57%) non-ST131 isolates in 282 E. coli BSI (Table 1). Most ceftriaxone resistance was conferred by CTX-M-15 produced by H30 ST131 isolates (Figure 1, Table 1). H30 ST131 BSI patients were older (median age [IQR] 70.5 [63,76] vs. 67 [56,77] vs 65 [51,74] years, p = 0.017), had higher Charlson comorbidity indices (3 [2,5] vs. 2 [1,4] vs. 2 [1,4], p=0.009), and were more often admitted from long-term care facilities (18/92 [20%] vs. 3/29 [10%] vs. 7/161 [4%], p = 0.003) compared to non-H30 ST131 and non-ST131 BSI patients. Among H30 ST131 isolates, high rates of antibiotic resistance were observed to cephalosporins and fluoroquinolones, resulting in significantly more carbapenem use compared with non-H30 ST131 and non-ST131 isolates (75/92 [82%] vs. 14/29 [48%] vs. 50/161 [31%], p < 0.001) (Figure 2). 30-day DOOR and hospital length of stay did not differ between groups (Table 2). Conclusion Compared with non-H30 ST131 and non-ST131 E. coli BSI, H30 ST131 E. coli BSI have a unique epidemiology with more healthcare exposures, comorbidities and antibiotic resistance and are more likely to be treated with carbapenems, though no significant difference in clinical outcomes was observed. Disclosures Yohei Doi, MD, PHD, AbbVie: Honoraria|Entasis: Grant/Research Support|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Meiji Seika: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria Elie Saade, MD, MPH, FIDSA, Janssen Global Services: Advisor/Consultant|Janssen Global Services: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant Loren G. Miller, MD MPH, Armata: Grant/Research Support|Contrafect: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support Michael J. Satlin, MD, AbbVie: DSMB participant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Selux Diagnostics: Grant/Research Support|SNIPRBiome: Grant/Research Support W. Charles Huskins, MD, MSc, ADMA Biologics: Advisor/Consultant|Bristol Myers Squibb: Stocks/Bonds (Public Company)|Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds (Public Company)|Zimmer Biomet: Stocks/Bonds (Public Company) Carol Hill, PhD, Glaxo SmithKline: Retirement Health, Cash Balance Plan|Glaxo SmithKline: Stocks/Bonds (Public Company) Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support

BACKGROUND:Urinary tract infections are commonly overdiagnosed. To minimize overdiagnosis, some laboratories utilize reflex algorithms that use urinalyses as preliminary screening before potentially proceeding to urine culture. However, the optimal urinalysis cutoffs for this diagnostic stewardship intervention remain poorly defined. METHODS:We performed a retrospective, cross-sectional analysis from 2/1/21-1/31/23 in the Los Angeles County Department of Health Services healthcare system. We examined patient encounters in which urinalysis was ordered synchronously with urine culture. We categorized urine culture isolates as uropathogens or non-uropathogens. We calculated receiver operating characteristic curves of urinalysis parameters' ability, singularly or in combination, to identify uropathogens. RESULTS:Among 80,949 paired urinalysis and urine cultures (17,488 inpatient, 20,716 emergency department, 42,745 outpatient), cultures yielded 35% (n = 28,993) uropathogens, 4% (n = 2960) non-uropathogens, 37% (n = 29,951) contaminants, and 24% (n = 19,045) no growth. Among urinalysis parameters, white blood cells (WBCs) had the highest diagnostic accuracy (area under the curve (AUC)=0.722, [95% CI 0.718-0.725]), followed by leukocyte esterase (AUC = 0.700, [95% CI 0.690-0.701]), bacteria (AUC = 0.673, [95% CI 0.670-0.677]), nitrite (AUC = 0.627, [95% CI 0.625-0.630]), and squamous epithelial cells (AUC = 0.530, [95% CI 0.526-0.534]). WBC AUC values were consistent across healthcare settings (outpatient, emergency department, and inpatient). The urinalysis parameter combination with the highest AUC, WBC plus bacteria, performed worse than WBCs alone (AUC = 0.711 vs. AUC = 0.722, p = 0.001). CONCLUSION:WBC on microscopic urinalysis demonstrated the highest diagnostic accuracy for predicting uropathogens in urine cultures. Stewardship programs should consider prioritizing urinalysis WBC count as the screening tool to optimize urine culture utilization.

Background: The pharmaceutical industry is estimated to have a larger environmental footprint than the automotive industry. Discarded and unused doses of pharmaceuticals generate financial waste and pollution, and exacerbate antibiotic shortages. The antibiotic daptomycin is dispensed in standard-sized single-use vials and dosed based on patient weight. Residual daptomycin in the vial after dose preparation must be disposed of and cannot be used for another patient. We hypothesized that daptomycin dosing nomogram use would reduce daptomycin waste, environmental impact, and financial costs. Methods: We performed a retrospective chart review quantifying daptomycin waste, defined as disposed of unused daptomycin, at Harbor-UCLA Medical Center, a 400-bed Level 1 Trauma Center, from 1/1/2023 to 12/31/2023. We then adjusted dosing using a daptomycin dosing nomogram. We modeled the difference in daptomycin waste (mg of daptomycin disposed of unused), pharmaceutical waste (weight of excess daptomycin vials required due to wasted antibiotic), and cost between the two dosing strategies. Our model assumed a daptomycin vial weight of 16.8g and cost of $30 per 500mg daptomycin vial. We conservatively estimated pharmaceutical waste as waste only from daptomycin vials, ignoring all other supplies and materials necessary to prepare daptomycin. Results: During the 1 year time period at our Medical Center, 138,882mg daptomycin was wasted. This level of daptomycin waste equates 4671g excess pharmaceutical waste and $8332 spent on unused, discarded daptomycin. In our model, we found that nomogram implementation would have reduced mean monthly daptomycin waste from 11,002mg to 1387mg (p<0.001). This reduction would have decreased the proportion of daptomycin wasted from a mean of 19% to 3% of all consumed daptomycin (Figure 1). Nomogram use would also have saved $7333 and averted 4111g of pharmaceutical waste in 2023. Conclusion: A daptomycin dosing nomogram would have prevented 122,322mg of daptomycin from being wasted and saved over $7000 at a 400 bed Medical Center over one year. Given the 4111 g of pharmaceutical waste is a conservative estimate, and ignores waste from other supplies/materials as well as upstream waste and emissions from daptomycin manufacturing, the overall generated environmental impact prevented by nomogram use is likely significantly higher. Our findings demonstrate that intentionally designed dosing strategies aimed at reducing drug waste can save hospital costs and reduce the environmental footprint of clinical care. When implemented at large health systems these strategies are likely to result in substantial cost savings and reduction in the negative environmental impact associated with pharmaceuticals.

Abstract Background The incidence of bone and joint infections (BJIs) continues to increase, and existing oral BJI antibiotics have limitations. Omadacycline may be a potential treatment option for BJI treatment due to activity against doxycycline-resistant S. aureus and ESBL-producing Enterobacterales for which there are often no viable oral options. However, the safety of omadacycline in this setting is poorly defined. Methods We performed an open label, randomized, controlled clinical trial of adults with BJIs in the outpatient setting. Participants were randomized to omadacycline-containing regimen (omadacycline 300mg po daily) or Standard-of-Care (SOC) antibiotics. Adjunctive antibiotics were permitted in addition to omadacycline. Safety labs were performed at regular intervals. Herein, we report an interim, descriptive analysis of safety data. Results Among the 59 participants enrolled to date, 31 (53%) were randomized to the omadacycline-containing regimen and 28 (47%) to SOC. Median age was 58 years old, 52 (88%) were male, 44 (75%) identified as Hispanic, 8 (14%) as African-American, and 4 (6%) as white. The most common BJIs were diabetic foot infections (52, 88%) and device infections (5, 8%). (Table) Combination therapy was used in 16 (52%) vs. 12 (43%) in the omadacycline-containing vs. SOC arms, and IV only therapy was used in 0 (%) vs. 5 (18%) in the two arms, respectively. Most commonly used SOC regimens included ciprofloxacin (8, 29%), doxycycline (7, 25%), amoxicillin/clavulanate (6, 21%), and levofloxacin (3, 11%). Commonly associated laboratory abnormalities included new or worsening renal insufficiency (2 (6%) in the omadacycline-containing arm vs. 5 (18%) in SOC) and transaminitis (2 (6%) vs. 4 (14%)). Adverse events were similar in the omadacycline-containing vs. SOC arms including nausea (6 (19%) vs. 4 (14%)), vomiting (0 (0%) vs. 4 (14%)), and diarrhea (5 (16%) vs. 2 (7%)). (Table) There was 1 drug-related serious adverse event in the omadacycline-containing arm due to likely hypersensitivity to omadacycline; the event resolved after drug discontinuation. Conclusion In this interim analysis of our ongoing trial, the safety of omadacycline for BJI appears to be similar to the SOC. More robust data on long-term safety is warranted. Disclosures Amy Y. Kang, Pharm.D., BCIDP, Paratek Pharmaceutical: Grant/Research Support Loren G. Miller, MD MPH, Armata: Grant/Research Support|Contrafect: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support

BACKGROUND:Nursing homes residents have a high prevalence of multidrug-resistant organism (MDRO) colonization. Recent trials demonstrated that decolonizing residents reduces infection. However, decolonization's impact on environmental MDRO contamination is not well understood. METHODS:We performed a 9-month pilot (3-month baseline, 3-month phase-in and 3-month intervention) in 3 nursing homes implementing routine chlorhexidine bathing/showering and nasal iodophor. We repeatedly tested for colonization via skin and nasal swabs for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum beta-lactamase producers (ESBLs), and carbapenem-resistant Enterobacterales (CRE). We also swabbed high-touch surfaces in rooms of MDRO carriers for MDRO fomite contamination. RESULTS:Decolonization decreased the odds of MDRO colonization in nursing home residents by 55% (OR 0.45, P < 0.001, raw reduction from 46% (411/900) to intervention: 29% (262/900); colonization with MRSA, VRE, and ESBL all significantly decreased (P < 0.001). Among residents who remained colonized with any MDRO, 288/330 (87%) of high-touch bedroom objects were colonized with ≥1 MDRO. In a multivariable analysis, MDRO fomite contamination in rooms of MDRO carriers was associated with antibiotic use (OR = 1.54 [95% CI: 1.19-1.98], wound presence (OR = 1.34 (95% CI: 1.02-1.77), and specific fomites such as bedside table/bedrails (OR = 12.7 (95% CI: 9.37-17.25), but not the intervention period (OR = 1.02 [0.81-1.27]). CONCLUSION:Routine chlorhexidine bathing and nasal iodophor significantly reduced MDRO body colonization among nursing home residents. However, in rooms of residents who remained MDRO carriers, environmental contamination was unchanged during the decolonization intervention. Efforts to ensure fomite surface clearance in rooms of MDRO carriers may be key to reducing environmental MDRO spread.

Background: Correctional populations have been disproportionately affected by COVID-19, and many large outbreaks have occurred in jails and prisons. Vaccination is a key strategy to reduce the SARS-CoV-2 transmission in carceral settings. Although implementation can be challenging due to vaccine hesitancy and medical mistrust, correctional settings provide largely equitable healthcare access and present a unique opportunity to identify potential predictors of vaccine hesitancy independent of access issues. Methods: We retrospectively analyzed electronic health record data for individuals offered COVID-19 vaccination at the Los Angeles County Jail between January 19, 2021, and January 31, 2023, and used multivariable logistic regression to determine predictors of COVID-19 vaccine refusal. Results: Of the 21,424 individuals offered COVID-19 vaccination, 2,060 (9.6 %) refused. Refusal was associated with male sex ([aOR] = 2.3, 95 % CI (1.9, 2.8)), age 18-34 ([aOR] = 1.2, 95 % CI (1.1, 1.4), referent group: age 45-54), Black race ([aOR] = 1.2, 95 % CI (1.1, 1.4)), reporting ever being houseless ([aOR] = 1.2, 95 % CI (1.1, 1.3)), and having a history of not receiving influenza vaccination while incarcerated ([aOR] = 2.4, 95 % CI (2.0, 2.8)). When analyzing male and female populations separately, male-specific trends reflected those seen in the overall population, whereas the only significant predictor of vaccine refusal in the female population was not receiving influenza vaccination while in custody ([aOR] = 6.5, 95 % CI (2.4, 17.6)). Conclusion: Identifying predictors of vaccine refusal in correctional populations is an essential first step in the development and implementation of targeted interventions to mitigate vaccine hesitancy.

BACKGROUND:Chlamydia and gonorrhea are 2 of the most common sexually transmitted infections (STIs) worldwide, presenting major public health challenges and resulting in billions of dollars in direct medical costs in the United States. Incarcerated women have a particularly elevated risk of these infections, which can result in serious sequelae if left untreated. On December 13, 2021, the Los Angeles County Jail system began offering opt-out urogenital chlamydia and gonorrhea screening to all newly incarcerated women. METHODS:We retrospectively analyzed electronic health record data for completed urogenital chlamydia/gonorrhea screening among newly incarcerated women between December 13, 2021, and May 31, 2023. We used multivariable logistic regression to examine the association of STIs and treatment non-initiation outcomes with various demographic and self-reported variables. RESULTS:Of the 13,739 female entrants offered STI testing, 10,717 (78%) completed screening, with 1151 (11%) having a chlamydial infection, 788 (7%) having a gonococcal infection, and 1626 (15%) having ≥1 infection. Sexually transmitted infection positivity was associated with age 18 to 34 years, reported houselessness, amphetamine use, and history of a positive prior treponemal antibody test result. Sexually transmitted infection treatment non-initiation was associated with shorter jail stay for both chlamydial (adjusted odds ratio, 87.4; 95% confidence interval, 34.2-223.2) and gonococcal (adjusted odds ratio, 9.0; 95% confidence interval, 5.2-15.7) infections. CONCLUSION:The STI prevalence among female detainees tested was many-fold higher than that of the general population. The implementation of routine opt-out STI screening in carceral settings provides a unique opportunity to benefit the health of both the correctional population and potentially that of the surrounding community.

Artificial propagation and wild release may influence the genetic integrity of wild populations. This practice has been prevalent in fisheries for centuries and is often termed 'stocking'. In the Laurentian Great Lakes (Great Lakes here-on), walleye populations faced declines from the 1950s to the 1970s, prompting extensive stocking efforts for restoration. By the mid-2010s, walleye populations showed signs of recovery, but the genetic legacy of stocking on population structure at the genomic level remains unclear. Using a dataset of 45,600 genome-aligned SNP loci genotyped in 1075 walleye individuals, we investigated the genetic impacts of over 50 years of stocking across the Great Lakes. Population structure was associated with both natural geographic barriers and stocking from non-native sources. Admixture between Lake Erie walleye and walleye from the re-populated Tittabawassee River indicate that stocking may have re-distributed putatively adaptive alleles around the Great Lakes. Genome scans identified FST outliers and evidence of selective sweeps, indicating local adaptation of spawning populations is likely. Notably, one genomic region showed strong differentiation between Muskegon River and walleye from the Tittabawassee River, which was re-populated by Muskegon strain walleye, suggesting admixture and selection both impact the observed genetic diversity. Overall, our study underscores how artificial propagation and translocations can significantly alter the evolutionary trajectory of populations. The findings highlight the complex interplay between stocking practices and population genetic diversity, emphasising the need for careful management strategies to preserve the genetic integrity of wild populations amidst conservation efforts.

ObjectiveA genetically distinct strain of Walleye Sander vitreus (southern Minnesota strain [SMS]) persists in southern Minnesota lakes despite decades of stocking more easily obtained strains from outside of the region. Because of the regional performance advantage inferred by this persistence, we conducted in situ experiments to compare survival and stocking cost of SMS Walleye fry against those of a frequently stocked northern Minnesota strain (Mississippi headwaters strain [MIS]) to determine whether it is beneficial to expand SMS fry stocking in lieu of historic practices.MethodsWe conducted four paired stockings of oxytetracycline-marked SMS fry and MIS fry into six southern Minnesota lakes and then sampled the fish as fall fingerlings during 2018, 2019, 2021, and 2022. We then used fluorescent microscopy and parentage-based tagging techniques to discern the stocked strains for comparison of growth and survival. We also obtained production and stocking cost data from agency records to calculate relative stocking costs.ResultBy the end of their first summer, SMS Walleye from all but two stockings exhibited higher survival than MIS Walleye. Despite higher initial costs to produce SMS fry, their higher survival to fall fingerlings made the stocking of SMS fry more cost effective than MIS fry stocking. Natural reproduction was also identified in several stocked lakes, most of which consisted of either high or increasing levels of SMS ancestry.ConclusionA local strain can outperform nonlocal strains at a level that can overcome additional costs of developing a new egg source. In addition, natural reproduction of local-strain Walleye may reduce or eliminate the need for future stocking. Impact statement We show that a local Walleye strain can outperform nonlocal strains at a level that can overcome additional costs of developing a new egg source. In addition, higher natural reproduction of the local strain may reduce or eliminate the need for future stocking.

ABSTRACT Objective: To investigate whether empiric carbapenem therapy, compared to empiric non-carbapenem therapy, was associated with improved clinical outcomes among hospitalized, non-intensive care unit (ICU) patients with extended-spectrum β-lactamase (ESBL)-producing Enterobacterales infections. Methods: We performed a retrospective cohort study of adult, non-ICU patients admitted with ESBL-producing Enterobacterales infections. Primary outcome was time to clinical stability from the first empiric antibiotic dose. Secondary outcomes were early clinical response and 30-day all-cause hospital readmission. We used multivariate regression methods to examine time to clinical stability. Results: Of the 142 patients, 59 (42%) received empiric carbapenems and 83 (58%) received empiric non-carbapenems, most commonly ceftriaxone (49/83, 59%). Median age was 59 years. The most common infection source was urinary (71%). The carbapenem group had a higher proportion of patients who received antibiotics within 6 months of admission (55% vs 28%, P < .01) and history of ESBL (57% vs 17%, P < .01). There were no significant differences in hours until clinical stability between the carbapenem and non-carbapenem groups (22 (IQR: 0, 85) vs 19 (IQR: 0, 69), P = .54). Early clinical response (88% vs 90%, P = .79) and 30-day all-cause hospital readmission (17% vs 8%, P = .13) were similar between groups. Conclusion: Among hospitalized non-ICU patients with ESBL-producing Enterobacterales infection, we found no difference in time to clinical stability after the first empiric antibiotic dose between those receiving carbapenems and those who did not. Our data suggest that empiric carbapenem use may not be an important driver of clinical response in patients with less severe ESBL-producing Enterobacterales infection.

Little Shoepack and Shoepack lakes in Voyageurs National Park, Minnesota, are home to native populations of Muskellunge (Esox masquinongy). Due to the small size of these lakes, 20.8 ha and 123 ha, respectively, and the associated, predicted small size of these Muskellunge populations, resource managers are concerned about their persistence. A recent population assessment completed for Shoepack Lake Muskellunge indicated that the population may be below a threshold at which a genetic bottleneck could threaten its persistence. Since Little Shoepack Lake is approximately 20% of the size of Shoepack Lake, resource managers were concerned that its Muskellunge population is likely smaller and at even greater risk of extirpation due to lack of genetic variability. To assess whether additional protections were warranted and whether increasing genetic diversity through stocking might allow for genetic rescue, a population estimate was completed for the Muskellunge in Little Shoepack Lake, and a genetic assessment of Muskellunge from Little Shoepack and Shoepack lakes was completed. The estimated abundance of Muskellunge ? 420 mm in Little Shoepack Lake in 2021 was 137 with a 95% confidence interval of 87 to 277. The density of this population, 6.6 per ha, is the highest of any Muskellunge population assessed in Minnesota. The Muskellunge from Little Shoepack and Shoepack lakes had substantially lower genetic diversity than other regional populations. The two populations were genetically similar, yet distinct, from one another and were far more distinct from other Muskellunge populations in the region. As anticipated, the population estimate for Muskellunge in Little Shoepack Lake indicates that the population is near or below a threshold at which the risk of low genetic diversity may impact population persistence. The genetic analysis showed that cross stocking native Muskellunge between Shoepack and Little Shoepack lakes would not likely provide enough genetic diversity to greatly increase the chances of the two populations persisting. Considering the long duration that this population has persisted (up to 8,900 years in Little Shoepack Lake) and the importance of maintaining these unique strains of Muskellunge to protect regional biodiversity, cross stocking of Muskellunge between Little Shoepack and Shoepack lakes or stocking Muskellunge from other lakes is not recommended at this time. We recommend that resource managers continue to use fishing regulations, controls on angling pressure, and prevention of introductions of both fish species and aquatic invasive species as tools to help sustain these populations. Considering the fishery is effectively catch-and-release due to minimum length harvest regulations in Minnesota and that difficulty of access limits fishing pressure and catch-and-release mortality, we recommend that Little Shoepack Lake remains open for a Muskellunge angling opportunity.

OBJECTIVES:The objective of this study is to assess the frequency of the novel sodium bicarbonate (NaHCO3)-responsive phenotype, wherein clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates are rendered susceptible to standard-of-care β-lactams in the presence of NaHCO3, in a collection of 103 clinical U.S. MRSA skin and soft-tissue infection (SSTI) isolates and 22 clinical European SSTI isolates. This study determined the correlation between specific phenotypic and genotypic metrics and the NaHCO3-responsive phenotype among U.S. SSTI isolates. METHODS:Antimicrobial susceptibility testing was performed to determine susceptibility phenotypes. Targeted and whole-genome sequencing with a genome-wide sequence analysis were conducted to identify specific and novel genotypes of interest that may be associated with the NaHCO3-responsive phenotype. Gene expression analysis and targeted gene deletion were performed to assess the role of a specific novel genetic locus in the NaHCO3-responsive phenotype. RESULTS:The NaHCO3-responsive phenotype was identified in 78/103 U.S. isolates and 4/22 UK isolates to cefazolin (CFZ), and in 17/103 U.S. isolates and 1/22 UK isolates to oxacillin. In U.S. isolates, a significant association was identified between NaHCO3-responsiveness to CFZ and: (a) susceptibility to amoxicillin-clavulanate; (b) a specific mecA genotype; (c) clonal complex type 8; and (d) spa type t008. Genome-wide sequence analysis identified single nucleotide polymorphisms (SNPs) in an AraC family regulator (SAUSA300_RS00540) to be exclusively found in NaHCO3-non-responsive SSTI strains. In vitro HCO3 exposures of NaHCO3-responsive strains, but not -non-responsive strains, caused >2-fold upregulated expression of this gene. Deletion of this gene rendered NaHCO3-responsive strain MRSA 11/11 no longer NaHCO3-responsive to CFZ; we have termed this gene the staphylococcal AraC bicarbonate-response regulator. DISCUSSION:NaHCO3-responsiveness is highly associated with clonal complex type 8/spa type t008, a commonly circulating genetic background in North America. The AraC bicarbonate-response regulator, staphylococcal AraC bicarbonate-response regulator, appears to be associated with the mechanism of NaHCO3-responsiveness, but more work is needed to verify.

ImportanceInfections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections.ObjectiveTo evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths.Design, Setting, and ParticipantsThis quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California.ExposuresChlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP).Main Outcomes and MeasuresBaseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs).ResultsThirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%).Conclusions and RelevanceA regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.

Abstract Background Skin and Soft Tissue Infections (SSTIs) are one of the most common bacterial infections that drive persons to seek medical care. We hypothesized that during the COVID-19 pandemic, SSTI rates would significantly decrease due to Public Health directives to avoid unneeded care and due to attenuated risk behaviors, such as skin injury and person to person contact, that drive SSTIs. Methods We performed a health system wide retrospective study using databases from the Los Angeles Department of Health Services, the second largest U.S. safety net healthcare system which is composed of 4 major medical centers and 20 clinics and ambulatory care centers. We examined all patients who had ≥1 medical encounter (inpatient, Emergency Department [ED], outpatient, or observation) for an SSTI. SSTIs were identified using ICD-10 diagnosis code between March 16, 2017 and March 15, 2022. Pre-pandemic and intra-pandemic SSTI rates were compared using a student’s t-test. Results During the study period there was a mean of 426,995 empaneled of patients per month. In total there were 72,218 SSTIs, 36,167 in the outpatient setting, 21,035 in the ED, 1143 in the observation unit, and 13,433 in the inpatient setting. Intra-pandemic SSTI rate was significantly lower than pre-pandemic (2.3 cases/1000 empaneled patient-months versus 3.3 cases/1000 empaneled patient-months, p< 0.0001). SSTI subgroups stratified by site of care all had significant SSTI decreases between the intra-pandemic and pre-pandemic time periods (inpatient (0.5 vs 0.6 empaneled patient-months), observation unit (0.05 vs 0.07), ED (0.6 vs 1.0), and outpatient clinics (1.2 vs 1.6), p< 0.0001 for all comparisons, see Figure). Skin and Soft Tissue Infection Rates Pre- and Intra- COVID-19 Pandemic Conclusion Compared to the pre-COVID-19 pandemic period, SSTI rates in our large U.S. safety net healthcare system significantly decreased by over 30% during the COVID-19 pandemic. Decreases occurred at all levels of care delivery. Whether the results of this study reflect a true reduction in SSTI incidence rates or a reduction in health system utilization for SSTIs requires further examination. Our data provide some insights as to expected changes in common bacterial infections during subsequent pandemics. Disclosures Loren G. Miller, MD MPH, ContraFect: Grant/Research Support|GSK: Grant/Research Support|Medline: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support