Insights into Treatment Alternatives for Neurosyphilis: Systematic Literature Review and Meta-Analysis.

ABSTRACT: We conducted a systematic literature review and meta-analysis to assess the efficacy of alternative treatments for neurosyphilis. We searched MEDLINE, CINAHL, Embase, Cochrane, Scopus, and Web of Science from database inception to September, 2023, for studies in neurosyphilis that compared penicillin monotherapy to other treatments. We focused on the impact of these therapies on treatment response, but also assessed data regarding reinfection and adverse drug events. Random-effect models were used to obtain pooled mean differences. Of 3,415 screened studies, six met the inclusion criteria for the systematic literature review. Three studies provided quantitative data that allowed for inclusion in the meta-analysis. Our analysis revealed that the efficacy of intravenous ceftriaxone 2 g daily for 10 days (51 patients) did not appear statistically different compared to intravenous penicillin G 18-24 million units daily for 10 days (185 patients) for neurosyphilis (pooled OR, 2.85; 95% CI, 0.41-19.56; I2 = 49%). No statistical difference between ceftriaxone and penicillin was identified in people living with HIV (pooled OR, 4.51; 95% CI, 0.50-40.49; I2 = 34%). We concluded that alternative therapy with IV ceftriaxone appears similar to penicillin, potentially expanding treatment options for neurosyphilis. Other treatment options including doxycycline warrant further study.

Understanding and Improving Vaccine Effectiveness Estimates in the Age of Widespread Background Immunity: A Step Toward Improved Science Communication.

Medical decision making and scientific communication around coronavirus disease 2019 (COVID-19) vaccines and booster doses requires proper understanding of how vaccine effectiveness estimates are determined and the potential biases inherent in current estimates. The importance of background immunity from prior infection is reviewed along with ideas for improving the vaccine effectiveness estimates.

Diagnostic Accuracy of Hospital Antibiograms in Predicting the Risk of Antimicrobial Resistance in Enterobacteriaceae Isolates: A Nationwide Multicenter Evaluation at the Veterans Health Administration.

BACKGROUND: Many clinical guidelines recommend that clinicians use antibiograms to inform empiric antimicrobial therapy. However, hospital antibiograms are typically generated by crude aggregation of microbiologic data, and little is known about an antibiogram's reliability in predicting antimicrobial resistance (AMR) risk at the patient-level. We aimed to assess the diagnostic accuracy of antibiograms as a tool for selecting empiric therapy for Escherichia coli and Klebsiella spp. for individual patients. METHODS: We retrospectively generated hospital antibiograms for the nationwide Veterans Health Administration (VHA) facilities from 2000 to 2019 using all clinical culture specimens positive for E. coli and Klebsiella spp., then assessed the diagnostic accuracy of an antibiogram to predict resistance for isolates in the following calendar year using logistic regression models and predefined 5-step interpretation thresholds. RESULTS: Among 127 VHA facilities, 1 484 038 isolates from 704 779 patients for E. coli and 671 035 isolates from 340 504 patients for Klebsiella spp. were available for analysis. For E. coli and Klebsiella spp., the discrimination abilities of hospital-level antibiograms in predicting individual patient AMR were mostly poor, with the areas under the receiver operating curve at 0.686 and 0.715 for ceftriaxone, 0.637 and 0.675 for fluoroquinolones, and 0.576 and 0.624 for trimethoprim-sulfamethoxazole, respectively. The sensitivity and specificity of the antibiogram varied widely by antimicrobial groups and interpretation thresholds with substantial trade-offs. CONCLUSIONS: Conventional hospital antibiograms for E. coli and Klebsiella spp. have limited performance in predicting AMR for individual patients, and their utility in guiding empiric therapy may be low.

Effectiveness of Ultraviolet-C Disinfection on Hospital-Onset Gram-Negative Rod Bloodstream Infection: A Nationwide Stepped-Wedge Time-Series Analysis.

BACKGROUND: The effectiveness of enhanced terminal room cleaning with ultraviolet C (UV-C) disinfection in reducing gram-negative rod (GNR) infections has not been well evaluated. We assessed the association of implementation of UV-C disinfection systems with incidence rates of hospital-onset (HO) GNR bloodstream infection (BSI). METHODS: We obtained information regarding UV-C use and the timing of implementation through a survey of all Veterans Health Administration (VHA) hospitals providing inpatient acute care. Episodes of HO-GNR BSI were identified between January 2010 and December 2018. Bed days of care (BDOC) was used as the denominator. Over-dispersed Poisson regression models were fitted with hospital-specific random intercept, UV-C disinfection use for each month, baseline trend, and seasonality as explanatory variables. Hospitals without UV-C use were also included to the analysis as a nonequivalent concurrent control group. RESULTS: Among 128 VHA hospitals, 120 provided complete survey responses with 40 reporting implementations of UV-C systems. We identified 13 383 episodes of HO-GNR BSI and 24 141 378 BDOC. UV-C use was associated with a lower incidence rate of HO-GNR BSI (incidence rate ratio: 0.813; 95% confidence interval: .656-.969; P = .009). There was wide variability in the effect size of UV-C disinfection use among hospitals. CONCLUSIONS: In this large quasi-experimental analysis within the VHA System, enhanced terminal room cleaning with UV-C disinfection was associated with an approximately 19% lower incidence of HO-GNR BSI, with wide variability in effectiveness among hospitals. Further studies are needed to identify the optimal implementation strategy to maximize the effectiveness of UV-C disinfection technology.

Active Surveillance and Contact Precautions for Preventing Methicillin-Resistant Staphylococcus aureus Healthcare-Associated Infections During the COVID-19 Pandemic.

BACKGROUND: Statistically significant decreases in methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) occurred in Veterans Affairs (VA) hospitals from 2007 to 2019 using a national policy of active surveillance (AS) for facility admissions and contact precautions for MRSA colonized (CPC) or infected (CPI) patients, but the impact of suspending these measures to free up laboratory resources for testing and conserve personal protective equipment for coronavirus disease 2019 (COVID-19) on MRSA HAI rates is not known. METHODS: From July 2020 to June 2022 all 123 acute care VA hospitals nationwide were given the rolling option to suspend (or re-initiate) any combination of AS, CPC, or CPI each month, and MRSA HAIs in intensive care units (ICUs) and non-ICUs were tracked. RESULTS: There were 917 591 admissions, 5 225 174 patient-days, and 568 MRSA HAIs. The MRSA HAI rate/1000 patient-days in ICUs was 0.20 (95% confidence interval [CI], .15-.26) for facilities practicing "AS + CPC + CPI" compared to 0.65 (95% CI, .41-.98; P < .001) for those not practicing any of these strategies, and in non-ICUs was 0.07 (95% CI, .05-.08) and 0.12 (95% CI, .08-.19; P = .01) for the respective policies. Accounting for monthly COVID-19 facility admissions using a negative binomial regression model did not change the relationships between facility policy and MRSA HAI rates. There was no significant difference in monthly facility urinary catheter-associated infection rates, a non-equivalent dependent variable, in the policy categories in either ICUs or non-ICUs. CONCLUSIONS: Facility removal of MRSA prevention practices was associated with higher rates of MRSA HAIs in ICUs and non-ICUs.

Days of Antibiotic Spectrum Coverage: A Novel Metric for Inpatient Antibiotic Consumption.

BACKGROUND: Days of therapy (DOT), the most widely used benchmarking metric for antibiotic consumption, may not fully measure stewardship efforts to promote use of narrow-spectrum agents and may inadvertently discourage the use of combination regimens when single-agent alternatives have greater adverse effects. To overcome the limitations of DOT, we developed a novel metric, days of antibiotic spectrum coverage (DASC), and compared hospital performances using this novel metric with DOT. METHODS: We evaluated 77 antibiotics in 16 categories of antibacterial activity to develop our spectrum scoring system. DASC was then calculated as cumulative daily antibiotic spectrum coverage (ASC) scores. To compare hospital benchmarking using DOT and DASC, we conducted a retrospective cohort study of adult patients admitted to acute care units within the Veterans Health Administration system in 2018. Antibiotic administration data were aggregated to calculate each hospital's DOT and DASC per 1000 days present (DP) for ranking. RESULTS: The ASC score for each antibiotic ranged from 2 to 15. There was little correlation between DOT per 1000 DP and DASC per DOT, indicating that lower antibiotic consumption at a hospital does not necessarily mean more frequent use of narrow-spectrum antibiotics. The differences in each hospital's ranking between DOT and DASC per 1000 DP ranged from -29.0% to 25.0%, respectively, with 27 hospitals (21.8%) having differences >10%. CONCLUSIONS: We propose a novel composite metric for antibiotic stewardship, DASC, that combines consumption and spectrum as a potential replacement for DOT. Further studies are needed to evaluate whether benchmarking using the DASC will improve evaluations of stewardship.

Epidemiology and outcomes associated with carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa: a retrospective cohort study.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to describe CRAB and CRPA epidemiology and identify factors associated with mortality and length of stay (LOS) post-culture. METHODS: This was a national retrospective cohort study of Veterans with CRAB or CRPA positive cultures from 2013 to 2018, conducted at Hines Veterans Affairs Hospital. Carbapenem resistance was defined as non-susceptibility to imipenem, meropenem and/or doripenem. Multivariable cluster adjusted regression models were fit to assess the association of post-culture LOS among inpatient and long-term care (LTC) and to identify factors associated with 90-day and 365-day mortality after positive CRAB and CRPA cultures. RESULTS: CRAB and CRPA were identified in 1,048 and 8,204 unique patients respectively, with 90-day mortality rates of 30.3% and 24.5% and inpatient post-LOS of 26 and 27 days. Positive blood cultures were associated with an increased odds of 90-day mortality compared to urine cultures in patients with CRAB (OR 6.98, 95% CI 3.55-13.73) and CRPA (OR 2.82, 95% CI 2.04-3.90). In patients with CRAB and CRPA blood cultures, higher Charlson score was associated with increased odds of 90-day mortality. In CRAB and CRPA, among patients from inpatient care settings, blood cultures were associated with a decreased LOS compared to urine cultures. CONCLUSIONS: Positive blood cultures and more comorbidities were associated with higher odds for mortality in patients with CRAB and CRPA. Recognizing these factors would encourage clinicians to treat these patients in a timely manner to improve outcomes of patients infected with these organisms.

Temporal Trends of Candidemia Incidence Rates and Potential Contributions of Infection Control Initiatives Over 18 Years Within the United States Veterans Health Administration System: A Joinpoint Time-Series Analysis.

BACKGROUND: Candidemia is one of the most common causes of nosocomial bloodstream infections, but the impacts of factors affecting its incidence have not been evaluated. METHODS: We analyzed a retrospective cohort of all candidemia patients at 130 acute care hospitals in the Veterans Health Administration (VHA) system from January 2000 through December 2017. Cases were classified as hospital-onset (HO) and non-hospital-onset (NHO). We used Joinpoint regression analysis to assess temporal associations between significant changes in candidemia incidence rates and guidelines or horizontal infection control (IC) interventions. RESULTS: Over 18 years, 17 661 candidemia episodes were identified. Incidence rates of HO cases were increasing until the mid-2000s, followed by a sustained decline, while NHO cases showed a steady decline. The first change in HO candidemia incidence rates (August 2004 [95% confidence interval {CI}, February 2003-April 2005]) was preceded by the publication of catheter-related bloodstream infection (CRBSI) prevention guidelines and the CRBSI surveillance initiation. The second (September 2007 [95% CI, September 2006-June 2009]) had close temporal proximity to the expansion of IC resources within the VHA system. Collectively, these trend changes resulted in a 77.1% reduction in HO candidemia incidence rates since its peak in 2004. CONCLUSIONS: A substantial and sustained systemwide reduction in candidemia incidence rates was observed after the publication of guidelines, VHA initiatives about CRBSI reporting and education on CRBSI prevention, and the systemwide expansion of IC resources.

Impact of Sex and Metabolic Comorbidities on Coronavirus Disease 2019 (COVID-19) Mortality Risk Across Age Groups: 66 646 Inpatients Across 613 U.S. Hospitals.

BACKGROUND: The relationship between common patient characteristics, such as sex and metabolic comorbidities, and mortality from coronavirus disease 2019 (COVID-19) remains incompletely understood. Emerging evidence suggests that metabolic risk factors may also vary by age. This study aimed to determine the association between common patient characteristics and mortality across age-groups among COVID-19 inpatients. METHODS: We performed a retrospective cohort study of patients discharged from hospitals in the Premier Healthcare Database between April-June 2020. Inpatients were identified using COVID-19 ICD-10-CM diagnosis codes. A priori-defined exposures were sex and present-on-admission hypertension, diabetes, obesity, and interactions between age and these comorbidities. Controlling for additional confounders, we evaluated relationships between these variables and in-hospital mortality in a log-binomial model. RESULTS: Among 66 646 (6.5%) admissions with a COVID-19 diagnosis, across 613 U.S. hospitals, 12 388 (18.6%) died in-hospital. In multivariable analysis, male sex was independently associated with 30% higher mortality risk (aRR, 1.30, 95% CI: 1.26-1.34). Diabetes without chronic complications was not a risk factor at any age (aRR 1.01, 95% CI: 0.96-1.06), and hypertension without chronic complications was a risk factor only in 20-39 year-olds (aRR, 1.68, 95% CI: 1.17-2.40). Diabetes with chronic complications, hypertension with chronic complications, and obesity were risk factors in most age-groups, with highest relative risks among 20-39 year-olds (respective aRRs 1.79, 2.33, 1.92; P-values ≤ .002). CONCLUSIONS: Hospitalized men with COVID-19 are at increased risk of death across all ages. Hypertension, diabetes with chronic complications, and obesity demonstrated age-dependent effects, with the highest relative risks among adults aged 20-39.

Risk Factors Associated With Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Positive Cultures in a Cohort of US Veterans.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) cause approximately 13 100 infections, with an 8% mortality rate in the United States annually. Carbapenemase-producing CRE (CP-CRE) a subset of CRE infections infections have much higher mortality rates (40%-50%). There has been little research on characteristics unique to CP-CRE. The goal of the current study was to assess differences between US veterans with non-CP-CRE and those with CP-CRE cultures. METHODS: A retrospective cohort of veterans with CRE cultures from 2013-2018 and their demographic, medical, and facility level covariates were collected. Clustered multiple logistic regression models were used to assess independent factors associated with CP-CRE. RESULTS: The study included 3096 unique patients with cultures positive for either non-CP-CRE or CP-CRE. Being African American (odds ratio, 1.44 [95% confidence interval, 1.15-1.80]), diagnosis in 2017 (3.11 [2.13-4.54]) or 2018 (3.93 [2.64-5.84]), congestive heart failure (1.35 [1.11-1.64]), and gastroesophageal reflux disease (1.39 [1.03-1.87]) were associated with CP-CRE cultures. There was no known antibiotic exposure in the previous year for 752 patients (24.3% of the included patients). Those with no known antibiotic exposure had increased frequency of prolonged proton pump inhibitor use (17.3%) compared to those with known antibiotic exposure (5.6%). DISCUSSION: Among a cohort of patients with CRE, African Americans, patients with congestive heart failure, and those with gastroesophageal reflux disease had greater odds of having a CP-CRE culture. Roughly 1 in 4 patients with CP-CRE had no known antibiotic exposure in the year before their positive culture.

Antibiotic Stewardship Implementation and Antibiotic Use at Hospitals With and Without On-site Infectious Disease Specialists.

BACKGROUND: Many US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist. METHODS: This retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions. RESULTS: Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85-.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54-.70) and higher narrow-spectrum ß-lactam use (1.43; 1.22-1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86-.99). CONCLUSIONS: Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship.

Expanding an Economic Evaluation of the Veterans Affairs (VA) Methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative to Include Prevention of Infections From Other Pathogens.

BACKGROUND: In October 2007, Veterans Affairs (VA) launched a nationwide effort to reduce methicillin-resistant Staphylococcus aureus (MRSA) transmission called the National MRSA Prevention Initiative. Although the initiative focused on MRSA, recent evidence suggests that it also led to a significant decrease in hospital-onset (HO) gram-negative rod (GNR) bacteremia, vancomycin-resistant Enterococci (VRE), and Clostridioides difficile infections. The objective of this analysis was to evaluate the cost-effectiveness and the budget impact of the initiative taking into account MRSA, GNR, VRE, and C. difficile infections. METHODS: We developed an economic model using published data on the rate of MRSA hospital-acquired infections (HAIs) and HO-GNR bacteremia in the VA from October 2007 to September 2015, estimates of the attributable cost and mortality of these infections, and the costs associated with the intervention obtained through a microcosting approach. We explored several different assumptions for the rate of infections that would have occurred if the initiative had not been implemented. Effectiveness was measured in life-years (LYs) gained. RESULTS: We found that during fiscal years 2008-2015, the initiative resulted in an estimated 4761-9236 fewer MRSA HAIs, 1447-2159 fewer HO-GNR bacteremia, 3083-3602 fewer C. difficile infections, and 2075-5393 fewer VRE infections. The initiative itself was estimated to cost $561 million over this 8-year period, whereas the cost savings from prevented MRSA HAIs ranged from $165 to $315 million and from prevented HO-GNR bacteremia, CRE and C. difficile infections ranged from $174 to $200 million. The incremental cost-effectiveness of the initiative ranged from $12 146 to $38 673/LY when just including MRSA HAIs and from $1354 to $4369/LY when including the additional pathogens. The overall impact on the VA's budget ranged from $67 to$195 million. CONCLUSIONS: An MRSA surveillance and prevention strategy in VA may have prevented a substantial number of infections from MRSA and other organisms. The net increase in cost from implementing this strategy was quite small when considering infections from all types of organisms. Including spillover effects of organism-specific prevention efforts onto other organisms can provide a more comprehensive evaluation of the costs and benefits of these interventions.

Comparative Effectiveness of Switching to Daptomycin Versus Remaining on Vancomycin Among Patients With Methicillin-resistant Staphylococcus aureus (MRSA) Bloodstream Infections.

BACKGROUND: Patients with methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA BSI) usually receive initial treatment with vancomycin but may be switched to daptomycin for definitive therapy, especially if treatment failure is suspected. Our objective was to evaluate the effectiveness of switching from vancomycin to daptomycin compared with remaining on vancomycin among patients with MRSA BSI. METHODS: Patients admitted to 124 Veterans Affairs Hospitals who experienced MRSA BSI and were treated with vancomycin during 2007-2014 were included. The association between switching to daptomycin and 30-day mortality was assessed using Cox regression models. Separate models were created for switching to daptomycin any time during the first hospitalization and for switching within 3 days of receiving vancomycin. RESULTS: In total, 7411 patients received vancomycin for MRSA BSI. Also, 606 (8.2%) patients switched from vancomycin to daptomycin during the first hospitalization, and 108 (1.5%) switched from vancomycin to daptomycin within 3 days of starting vancomycin. In the multivariable analysis, switching to daptomycin within 3 days was significantly associated with lower 30-day mortality (hazards ratio [HR] = 0.48; 95% confidence interval [CI]: .25, .92). However, switching to daptomycin at any time during the first hospitalization was not significantly associated with 30-day mortality (HR: 0.87; 95% CI: .69, 1.09). CONCLUSIONS: Switching to daptomycin within 3 days of initial receipt of vancomycin is associated with lower 30-day mortality among patients with MRSA BSI. This benefit was not seen when the switch occurred later. Future studies should prospectively assess the benefit of early switching from vancomycin to other anti-MRSA antibiotics.

A comprehensive assessment of carbapenem use across 90 Veterans Health Administration hospitals with defined stewardship strategies for carbapenems.

OBJECTIVES: Carbapenems are an important target for antimicrobial stewardship (AS) efforts. In this study, we sought to compare different hospital-based strategies for improving carbapenem use. METHODS: We analysed a cohort of all patients hospitalized at Veterans Health Administration (VHA) acute care hospitals during 2016 and a mandatory survey that characterized each hospital's carbapenem-specific AS strategy into one of three types: no strategy (NS), prospective audit and feedback (PAF) or restrictive policies (RP). Carbapenem use was compared using risk-adjusted generalized estimating equations that accounted for clustering within hospitals. Two infectious disease (ID) physicians independently performed manual chart reviews in 425 randomly selected cases. Auditors assessed carbapenem appropriateness with an assessment score on Day 4 of therapy. RESULTS: There were 429 062 admissions in 90 sites (24 NS, 8 PAF, 58 RP). Carbapenem use was lower at PAF than NS sites [rate ratio (RR) 0.6 (95% CI 0.4-0.9); P = 0.01] but similar between RP and NS sites. Carbapenem prescribing was considered appropriate/acceptable in 215 (50.6%) of the reviewed cases. Assessment scores were lower (i.e. better) at RP than NS sites (mean 2.3 versus 2.7; P < 0.01) but did not differ significantly between NS and PAF sites. ID consultations were more common at PAF/RP than NS sites (51% versus 29%; P < 0.01). ID consultations were associated with lower (i.e. better) assessment scores (mean 2.3 versus 2.6; P < 0.01). CONCLUSIONS: In this VHA cohort, PAF strategies were associated with lower carbapenem use and ID consultation and RP strategies were associated with more appropriate carbapenem prescribing. AS and ID consultations may work complementarily and hospitals could leverage both to optimize carbapenem use.

The feasibility of implementing antibiotic restrictions for fluoroquinolones and cephalosporins: a mixed-methods study across 15 Veterans Health Administration hospitals.

INTRODUCTION: The optimal method for implementing hospital-level restrictions for antibiotics that carry a high risk of Clostridioides difficile infection has not been identified. We aimed to explore barriers and facilitators to implementing restrictions for fluoroquinolones and third/fourth-generation cephalosporins. METHODS: This mixed-methods study across a purposeful sample of 15 acute-care, geographically dispersed Veterans Health Administration hospitals included electronic surveys and semi-structured interviews (September 2018 to May 2019). Surveys on stewardship strategies were administered at each hospital and summarized with descriptive statistics. Interviews were performed with 30 antibiotic stewardship programme (ASP) champions across all 15 sites and 19 additional stakeholders at a subset of 5 sites; transcripts were analysed using thematic content analysis. RESULTS: The most restricted agent was moxifloxacin, which was restricted at 12 (80%) sites. None of the 15 hospitals restricted ceftriaxone. Interviews identified differing opinions on the feasibility of restricting third/fourth-generation cephalosporins and fluoroquinolones. Some participants felt that restrictions could be implemented in a way that was not burdensome to clinicians and did not interfere with timely antibiotic administration. Others expressed concerns about restricting these agents, particularly through prior approval, given their frequent use, the difficulty of enforcing restrictions and potential unintended consequences of steering clinicians towards non-restricted antibiotics. A variety of stewardship strategies were perceived to be effective at reducing the use of these agents. CONCLUSIONS: Across 15 hospitals, there were differing opinions on the feasibility of implementing antibiotic restrictions for third/fourth-generation cephalosporins and fluoroquinolones. While the perceived barrier to implementing restrictions was frequently high, many hospitals were effectively using restrictions and reported few barriers to their use.

Household transmission of carbapenemase-producing Enterobacteriaceae: a prospective cohort study.

OBJECTIVES: To estimate the transmission rate of carbapenemase-producing Enterobacteriaceae (CPE) in households with recently hospitalized CPE carriers. METHODS: We conducted a prospective case-ascertained cohort study. We identified the presence of CPE in stool samples from index subjects, household contacts and companion animals and environmental samples at regular intervals. Linked transmissions were identified by WGS. A Markov model was constructed to estimate the household transmission potential of CPE. RESULTS: Ten recently hospitalized index patients and 14 household contacts were included. There were seven households with one contact, two households with two contacts, and one household with three contacts. Index patients were colonized with blaOXA-48-like (n = 4), blaKPC-2 (n = 3), blaIMP (n = 2), and blaNDM-1 (n = 1), distributed among divergent species of Enterobacteriaceae. After a cumulative follow-up time of 9.0 years, three family members (21.4%, 3/14) acquired four different types of CPE in the community (hazard rate of 0.22/year). The probability of CPE transmission from an index patient to a household contact was 10% (95% CI 4%-26%). CONCLUSIONS: We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.

Risk-Standardized Home Time as a Novel Hospital Performance Metric for Pneumonia Hospitalization Among Medicare Beneficiaries: a Retrospective Cohort Study.

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) use hospital readmissions as a performance metric to incentivize hospital care for acute conditions including pneumonia. However, there are limitations to using readmission alone as a hospital performance metric. OBJECTIVE: To characterize 30-day risk-standardized home time (RSHT), a novel patient-centered post-discharge performance metric for acute pneumonia hospitalizations in Medicare patients, and compare hospital rankings based on this metric with mortality and readmissions. STUDY DESIGN: Retrospective, cohort study. PARTICIPANTS: A cohort of Medicare fee-for-service beneficiaries admitted between January 01, 2015 and November 30, 2017. INTERVENTIONS: None. MAIN MEASURES: Risk-standardized hospital-level home time within 30 days of discharge was evaluated as a novel performance metric. Multilevel regression models were used to calculate hospital-level estimates and rank hospitals based on RSHT, readmission rate (RSRR), and mortality rate (RSMR). KEY RESULTS: A total of 1.7 million pneumonia admissions admitted to one of the 3116 hospitals were eligible for inclusion. The median 30-day RSHT was 20.5 days (interquartile range: 18.9-21.9 days; range: 5-29 days). Hospital-level characteristics such as case volume, bed size, for-profit ownership, rural location of the hospital, teaching status, and participation in the bundled payment program were significantly associated with home time. We found a modest, inverse correlation of RSHT with RSRR (rho: -0.233, p< 0.0001) and RSMR (rho: -0.223, p< 0.0001) for pneumonia. About 1/3rd of hospitals were reclassified as high performers based on their RSHT metric compared with the rank on their RSRR and RSMR metrics. CONCLUSION: Home time is a novel, patient-centered, hospital-level metric that can be easily calculated using claims data and accounts for mortality, readmission to an acute care facility, and admission to a skilled nursing facility or long-term care facility after discharge. Utilization of this patient-centered metric could have policy implications in assessing hospital performance on delivery of healthcare to pneumonia patients.

Inpatient Fluoroquinolone Stewardship Improves the Quantity and Quality of Fluoroquinolone Prescribing at Hospital Discharge: A Retrospective Analysis Among 122 Veterans Health Administration Hospitals.

BACKGROUND: Despite increasing awareness of harms, fluoroquinolones are still frequently prescribed to inpatients and at hospital discharge. Our goal was to describe fluoroquinolone prescribing at hospital discharge across the Veterans Health Administration (VHA) and to contrast the volume and appropriateness of fluoroquinolone prescribing across 3 antimicrobial stewardship strategy types. METHODS: We analyzed a retrospective cohort of patients hospitalized at 122 VHA acute-care hospitals during 2014-2016. Data from a mandatory VHA survey were used to identify 9 hospitals that self-reported 1 of 3 strategies for optimizing fluoroquinolone prescribing: prospective audit and feedback (PAF), restrictive policies (RP), and no strategy. Manual chart reviews to assess fluoroquinolone appropriateness at hospital discharge (ie, postdischarge) were performed across the 9 hospitals (3 hospitals and 125 cases per strategy type). RESULTS: There were 1.7 million patient admissions. Overall, there were 1 727 478 fluoroquinolone days of therapy (DOTs), with 674 918 (39.1%) DOTs prescribed for inpatients and 1 052 560 (60.9%) DOTs prescribed postdischarge. Among the 9 reviewed hospitals, postdischarge fluoroquinolone exposure was lower at hospitals using RP, compared to no strategy (3.8% vs 9.3%, respectively; P = .012). Postdischarge fluoroquinolones were deemed inappropriate in 154 of 375 (41.1%) patients. Fluoroquinolones were more likely to be inappropriate at hospitals without a strategy (52.8%) versus those using either RP or PAF (35.2%; P = .001). CONCLUSIONS: In this retrospective cohort, the majority of fluoroquinolone DOTs occurred after hospital discharge. A large proportion of postdischarge fluoroquinolone prescriptions were inappropriate, especially in hospitals without a strategy to manage fluoroquinolone prescribing. Our findings suggest that stewardship efforts to minimize and improve fluoroquinolone prescribing should also focus on antimicrobial prescribing at hospital discharge.

Perceived Benefits and Challenges of Ebola Preparation Among Hospitals in Developed Countries: A Systematic Literature Review.

The 2014-2016 Ebola epidemic in West Africa provided an opportunity to improve our response to highly infectious diseases. We performed a systematic literature review in PubMed, Cochrane Library, CINAHL, EMBASE, and Web of Science of research articles that evaluated benefits and challenges of hospital Ebola preparation in developed countries. We excluded studies performed in non-developed countries, and those limited to primary care settings, the public health sector, and pediatric populations. Thirty-five articles were included. Preparedness activities were beneficial for identifying gaps in hospital readiness. Training improved health-care workers' (HCW) infection control practices and personal protective equipment (PPE) use. The biggest challenge was related to PPE, followed by problems with hospital infrastructure and resources. HCWs feared managing Ebola patients, affecting their willingness to care for them. Standardizing protocols, PPE types, and frequency of training and providing financial support will improve future preparedness. It is unclear whether preparations resulted in sustained improvements. Prospero Registration. CRD42018090988.

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.