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Key Points: Question: Is implementation of a regional hospital and nursing home decolonization collaborative (coordinated intervention adopted by participating health care facilities) associated with a reduction in multidrug-resistant organisms (MDROs), infection-related hospitalizations, costs, and deaths? Findings: In this quality improvement study of 35 health care facilities in Orange County, California, using quasi-experimental design, chlorhexidine bathing and nasal decolonization were associated with significantly lower MDRO prevalence and incident clinical cultures. Infection-related hospitalizations, associated costs, and deaths among nursing home residents also decreased. Meaning: In this study, a regional decolonization collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in contact precautions was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths. Importance: Infections 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. Objective: To 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 Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline 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). Results: Thirty-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 Relevance: A 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. This quality improvement study evaluates whether implementation of a decolonization collaborative is associated with reduced regional multidrug-resistant organism prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Severe cases of COVID-19 pneumonia can lead to acute respiratory distress syndrome (ARDS). Release of interleukin (IL)-33, an epithelial-derived alarmin, and IL-33/ST2 pathway activation are linked with ARDS development in other viral infections. IL-22, a cytokine that modulates innate immunity through multiple regenerative and protective mechanisms in lung epithelial cells, is reduced in patients with ARDS. This study aimed to evaluate safety and efficacy of astegolimab, a human immunoglobulin G2 monoclonal antibody that selectively inhibits the IL-33 receptor, ST2, or efmarodocokin alfa, a human IL-22 fusion protein that activates IL-22 signaling, for treatment of severe COVID-19 pneumonia. DESIGN: Phase 2, double-blind, placebo-controlled study (COVID-astegolimab-IL). SETTING: Hospitals. PATIENTS: Hospitalized adults with severe COVID-19 pneumonia. INTERVENTIONS: Patients were randomized to receive IV astegolimab, efmarodocokin alfa, or placebo, plus standard of care. The primary endpoint was time to recovery, defined as time to a score of 1 or 2 on a 7-category ordinal scale by day 28. MEASUREMENTS AND MAIN RESULTS: The study randomized 396 patients. Median time to recovery was 11 days (hazard ratio [HR], 1.01 d; p = 0.93) and 10 days (HR, 1.15 d; p = 0.38) for astegolimab and efmarodocokin alfa, respectively, versus 10 days for placebo. Key secondary endpoints (improved recovery, mortality, or prevention of worsening) showed no treatment benefits. No new safety signals were observed and adverse events were similar across treatment arms. Biomarkers demonstrated that both drugs were pharmacologically active. CONCLUSIONS: Treatment with astegolimab or efmarodocokin alfa did not improve time to recovery in patients with severe COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Background Multidrug-resistant organisms (MDROs) spread between hospitals, nursing homes (NHs), and long-term acute care facilities (LTACs) via patient transfers. The Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County is a regional public health collaborative involving decolonization at 38 healthcare facilities selected based on their high degree of patient sharing. We report baseline MDRO prevalence in 21 NHs/LTACs. Methods A random sample of 50 adults for 21 NHs/LTACs (18 NHs, 3 LTACs) were screened for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum β-lactamase–producing organisms (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin (axilla/groin), and peri-rectal swabs. Facility and resident characteristics associated with MDRO carriage were assessed using multivariable models clustering by person and facility. Results Prevalence of MDROs was 65% in NHs and 80% in LTACs. The most common MDROs in NHs were MRSA (42%) and ESBL (34%); in LTACs they were VRE (55%) and ESBL (38%). CRE prevalence was higher in facilities that manage ventilated LTAC patients and NH residents (8% vs <1%, P <.001). MDRO status was known for 18% of NH residents and 49% of LTAC patients. MDRO-colonized adults commonly harbored additional MDROs (54% MDRO+ NH residents and 62% MDRO+ LTACs patients). History of MRSA (odds ratio [OR] = 1.7; confidence interval [CI]: 1.2, 2.4; P =.004), VRE (OR = 2.1; CI: 1.2, 3.8; P =.01), ESBL (OR = 1.6; CI: 1.1, 2.3; P =.03), and diabetes (OR = 1.3; CI: 1.0, 1.7; P =.03) were associated with any MDRO carriage. Conclusions The majority of NH residents and LTAC patients harbor MDROs. MDRO status is frequently unknown to the facility. The high MDRO prevalence highlights the need for prevention efforts in NHs/LTACs as part of regional efforts to control MDRO spread. [ABSTRACT FROM AUTHOR]

The article focuses on risk factors associated with bloodstream infections caused due to vancomycin resistan t enterococcal species (VRE-BSI). It discusses that the multidrug-resistant property of the enterococcal isolates, leads to unavailability of optimal treatment for VRE-BSI, and mentions that Linezolid drug has been approved the U.S. Food and Drug Administration (FDA) for the treatment of VRE-BSI. It analyses the use of daptomycin (DAP) antibiotic for treatment of VRE infections.

The longer methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) persists uncontrolled, the more pharmacotherapy is hindered. With rapid diagnostics, superior combination antimicrobial therapy, and the selective pressure consequences of prolonged in vivo persistence, MRSAB should clear within 3–4 days.Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB) is associated with poor outcomes and serious complications. The MRSA guidelines define treatment failure and persistent bacteremia as lasting ≥7 days; however, this definition requires reevaluation. Aggressively reducing the bacterial inoculum promptly is critical because factors already in place before clinical presentation are driving resistance to the few antibiotics that are available to treat MRSAB. Alternative approaches to treat MRSAB should be considered within 3–4 days of persistent MRSAB. With rapid molecular diagnostics emerging in clinical microbiology laboratories and biomarkers as a potential for early patient risk stratification, a future shorter threshold may become possible. [ABSTRACT FROM PUBLISHER]

Numerous antiretroviral therapy (ART) regimens are recommended for first-line and subsequent HIV care, but regimen selection for clinical use may not represent the full range of options. We hypothesized that despite an increase in available antiretrovirals, clinical trial data on regimen efficacy and fixed-dose combination options have lead to uniformity in initial ART. We evaluated regimen selection for ART-naïve patients at the University of Alabama at Birmingham (UAB) 1917 Clinic between January 2000 and December 2007. The annual number of unique initial regimens was quantified. Initial regimen variability was expressed as regimens per 100 patients. Subsequent ART regimens were characterized for complexity via regimen sequence trees detailing the first three generations of regimens for patients starting the two most common initial combinations. Four hundred eighty-two ART-naïve patients were treated with 39 unique initial regimens (8.0 regimens per 100 patients). Variability in initial regimen selection was highest in the first 6 years (14.9–24.4 regimens per 100 patients). A sharp decline was observed in 2006 (16.1 regimens per 100 patients) and 2007 (6.5 regimens per 100 patients). The most dramatic shift in drug selection involved an increase in emtricitabine plus tenofovir plus efavirenz, from 0% in 2003 to 85% in 2007. During the study period, 205 of 482 (43%) patients required a change in initial therapy. Of these, 156 of 205 (76%) had a unique sequence of regimens. A shift toward homogeneity of initial ART was observed (85% of patients received the same first-line regimen in 2007). In contrast, regimen sequencing beyond the first regimen remained complex. These shifts in ART prescribing patterns may have implications for collaborative HIV care. [ABSTRACT FROM AUTHOR]

An experimental technique is presented for measuring the fracture toughness of brittle thin films. In this technique, long rectangular membranes are fabricated from the film of interest using standard silicon micromachining techniques. A focused ion beam is then used to introduce pre-cracks of different lengths along the centerline of the membranes and the membranes are pressurized until rupture. The fracture stress of the membrane is measured as a function of pre-crack length and the fracture toughness of the film is determined from a simple fracture mechanics analysis. The technique is applicable to a wide range of materials and is especially suited for ultra-thin films. We have demonstrated the experimental procedure for a 150 nm AlTa intermetallic film and obtained a room-temperature fracture toughness of K 1 c = 4.44 ± 0.21 MPam1/2. [ABSTRACT FROM AUTHOR]

Background National surveillance for multidrug-resistant organisms (MDRO) are limited by narrow geographic sampling, few hospitals, and failure to account for local epidemiology. A Los Angeles County (LAC) regional antibiogram was created to inform public health interventions and provide a baseline for susceptibility patterns countywide. We present data to compare the 2015 and 2017 LAC regional antibiogram. Methods We conducted a cross-sectional survey of cumulative facility-level antibiograms from all hospitals in LAC; 83 hospitals (AH) and 9 Long-term Acute Care (LTAC). For 2015, submission was voluntary, 2017 data were collected by public health order. Non-respondents were contacted by phone and in person. Isolates from sterile sources were pooled. Countywide susceptibility was calculated by weighting each facility's isolate count by its reported susceptibility rate with minimum–maximim observed (2015) and Interquartile range (IQR) for 2017. Change from 2015 mean susceptibility is reported. Results Seventy-five (75) facilities submitted antibiograms for 2015 and 86 facilities for 2017. Among non-respondents in 2017, two facilities could not provide an adequate antibiogram and 4 were specialty hospitals with too few cultures to create an antibiogram. Regional summmary tables are presented in Tables 1–4. Klebsiella pneumoniae (n = 50 hospitals/19,382 isolates) % S to meropenem was 97% (IQR 94–100%), no change from 2015. Pseudomonas aeruginosa (PA) (n = 52 hospitals/17,770 isolates)% S to meropenem was 84% (IQR 74–93%), no change from 2015. Susceptibility to Acinetobacter baumannii (AB) was reported by 48 hospitals, including 1,4361 isolates,% S to meropenem was 39% (IQR 25–75%), 14% lower than 2015. Streptococcus agalactiae (n = 13 hospitals/647 isolates)% S to clindamycin was 43% (IQR 13–59%), a 22% increase from 2015. Conclusion LAC regional antibiograms identified stable patterns of antimicrobial resistance for most pathogens, but concerning results with AB and PA. Analysis of highly drug-resistant pathogens such as AB and PA would be improved with patient-level data to generate a combination antibiogram. We favor presenting IQR %S as done for 2017. Ongoing analysis will include multivariable analysis of observed changed S controlling for hospital characteristics. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Patient movement between hospitals, nursing homes (NH), and long-term acute care facilities (LTACs) contributes to MDRO spread. SHIELD OC is a regional decolonization collaborative among adult facilities with high patient sharing designed to reduce countywide MDRO prevalence. We report pre- and post-intervention MDRO colonization prevalence. Methods Decolonization included chlorhexidine bath (CHG) (4% liquid or 2% cloth) and twice-daily nasal swab 10% povidone–iodine (PI). LTAC and NH used CHG for all baths and PI 5 days on admission and Monday–Friday every other week. Patients in contact precautions (CP) at hospitals had daily CHG and 5-days PI on admission. Point-prevalence screening for MRSA, VRE, ESBL, and CRE using nares, axilla/groin, and peri-rectal swabs was conducted pre-intervention (September 2016–March 2017) and post-intervention (August 2018–April 2019); 50 random LTAC and 50 CP hospitalized patients were sampled; for NH up to 50 were sampled at baseline and all residents post-intervention. Raw impact of the intervention was assessed by the average change in colonization prevalence, with each facility carrying equal weight. Generalized linear mixed models (GLM) stratified by facility type were used to assess the impact on MDRO colonization when clustering by facility. Results Across 35 facilities (16 hospitals, 16 NHs, 3 LTACs), the overall MDRO prevalence was reduced 22% in NHs (OR 0.58, P < 0.001), 34% LTACs (OR = 0.27, P < 0.001), and 11% CP patients (OR = 0.67, P < 0.001, Table 1). For MRSA, raw reductions were 31% NHs (OR = 0.58, P < 0.001), 39% LTACs (OR = 0.51, P = 0.01), and 3% CP patients (OR = 0.88, P = NS). For VRE, raw reductions were 40% NHs (OR = 0.62, P = 0.001), 55% LTACs (OR = 0.26, P < 0.001), and 15% CP patients (OR = 0.67, P = 0.004). For ESBLs, raw reductions were 24% NHs (OR = 0.65, P < 0.001), 34% LTACs (OR = 0.53, P = 0.01), and 26% CP patients (OR = 0.64, P < 0.001). For CRE, raw reductions were 24% NHs (OR = 0.70, P = NS), and 23% LTACs (OR = 0.75, P = NS). CRE increased by 26% in CP averaged across hospitals, although patient -level CRE declined 2.4% to 1.8% (OR = 0.74, P = NS). Conclusion MDRO carriage was common in highly inter-connected NHs, LTACs and hospitals. A regional collaborative of universal decolonization in long-term care and targeted decolonization of CP patients in hospitals led to sizeable reductions in MDRO carriage. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

Determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBLs), and carbapenem-resistant Enterobacteriaceae (CRE) among residents and in the environment of nursing homes (NHs). Point prevalence sampling of residents and environmental sampling of high-touch objects in resident rooms and common areas. Twenty-eight NHs in Southern California from 2016 to 2017. NH participants in Project PROTECT, a cluster-randomized trial of enhanced bathing and decolonization vs routine care. Fifty residents were randomly sampled per NH. Twenty objects were sampled, including 5 common room objects plus 5 objects in each of 3 rooms (ambulatory, total care, and dementia care residents). A total of 2797 swabs were obtained from 1400 residents in 28 NHs. Median prevalence of multidrug-resistant organism (MDRO) carriage per NH was 50% (range: 24%-70%). Median prevalence of specific MDROs were as follows: MRSA, 36% (range: 20%-54%); ESBL, 16% (range: 2%-34%); VRE, 5% (range: 0%-30%); and CRE, 0% (range: 0%-8%). A median of 45% of residents (range: 24%-67%) harbored an MDRO without a known MDRO history. Environmental MDRO contamination was found in 74% of resident rooms and 93% of common areas. In more than half of the NHs, more than 50% of residents were colonized with MDROs of clinical and public health significance, most commonly MRSA and ESBL. Additionally, the vast majority of resident rooms and common areas were MDRO contaminated. The unknown submerged portion of the iceberg of MDRO carriers in NHs may warrant changes to infection prevention and control practices, particularly high-fidelity adoption of universal strategies such as hand hygiene, environmental cleaning, and decolonization. [ABSTRACT FROM AUTHOR]

Background The prevalence of MDROs in nursing homes (NH) is much higher than that of hospitals. Decolonization to reduce the reservoir of MDRO carriage in NH residents may be a strategy to address MDRO spread within and among healthcare facilities. Methods PROTECT is an 18-month cluster randomized trial of 1:1 universal decolonization vs. routine care in 28 NHs in California. Decolonization consists of chlorhexidine (CHG) bathing plus twice daily nasal iodophor on admission and Monday–Friday biweekly. We assessed pre- vs. post-intervention MDRO prevalence by sampling 50 randomly selected residents at each NH as an outcome unrelated to the trial's primary intent (infection, hospitalization reduction). NH residents had nasal swabs cultured for methicillin-resistant S. aureus (MRSA), and skin (axilla/groin) swabs taken for MRSA, vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase producers (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE). Generalized linear mixed models (GLM) assessed the difference in differences of MDRO prevalence using an arm by period interaction term, clustering by NH. Results Four NHs dropped from the trial. Among the 24 NHs that remained, MDRO colonization at baseline was 49.4% and 47.5% of residents in control (N = 650) vs. decolonization (N = 550) NHs, with no difference in MRSA, VRE, ESBL, and CRE (Table 1). Among remaining NHs, decolonization was associated with 28.8% raw decrease in MDRO prevalence in decolonization sites (GLM OR = 0.51, P < 0.001), 24.3% raw decrease in MRSA (OR = 0.66, P = 0.03), 61.0% raw decrease in VRE (OR = 0.17, P < 0.001), and 51.9% raw decrease in ESBL (OR = 0.40, P < 0.001). CRE increased, but numbers were small (Control arm: 10 in baseline, 4 in intervention; intervention arm: 1 in baseline, 2 in intervention, P = NS). Conclusion Universal NH decolonization with CHG bathing and nasal iodophor resulted in a marked decrease in Gram-positive and Gram-negative MDRO prevalence. This decrease may lower MDRO acquisition, infection, and antibiotic use within NHs, as well as regional MDRO spread to other healthcare facilities. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

Purpose Clinicians and stewardship programs are challenged with positioning of novel, higher priced antibiotic agents for the treatment of clinical infections. We developed a decision-analytic model to describe costs, including drug, total treatment costs, and health care outcomes, associated with telavancin (TLV) compared with vancomycin (VAN) for patients with Staphylococcus aureus (SA) hospital-acquired bacterial pneumonia (HABP). Methods This decision-analytic model assessed the treatment of SA-HABP with TLV versus VAN. Data were obtained from the ATTAIN (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia) clinical trials on the following: the probability of clinical cure; probability of nephrotoxicity; and prevalence of polymicrobial infection (30%), methicillin-resistant Staphylococcus aureus (MRSA) (68%), and SA with VAN MIC ≥1 µg/mL (85%). Data on length of stay for cure (10 days), failure (10 additional days), and nephrotoxicity (3.5 days) were based on literature. Cost per treated patient and incremental cost-effectiveness ratio (ICER) per additional cure were calculated for SA-HABP and for monomicrobial SA-HABP. One-way sensitivity analyses were performed. Findings Patients with SA-HABP were sub-grouped by methicillin susceptibility (n = 140, 32%) or resistance (n = 293, 68%), and occurrence of polymicrobial (n = 128, 30%) vs monomicrobial (n = 305, 70%) infections. Under the base case, hospital cost for patients with HABP treated with TLV was $42,564 and with VAN, it was $42,296. Telavancin was associated with higher drug ($2082) and nephrotoxicity ($467) costs and lower intensive care unit (−$1738) and ventilator (−$114) costs. ICER was $4156 per additional cure. ICER was sensitive to probabilities of cure, length of treatment in cures, intensive care unit cost, TLV cost, and additional length of stay due to failure. For monomicrobial SA-HABP, TLV was associated with a net cost savings of $907 per patient and yielded economic dominance. Implications Our decision-analytic model suggests that TLV for monomicrobial SA-HABP is associated with higher drug acquisition costs but a favorable ICER relative to VAN, provided that effective antimicrobial stewardship limits therapy to 7 days. Sensitivity analyses suggest a potential economic benefit of TLV treatment with appropriate patient selection. Antimicrobial stewardship programs may be able to reduce total costs through judicious use of novel antimicrobial agents. ClinicalTrials.gov identifiers: NCT00107952 and NCT00124020. [ABSTRACT FROM AUTHOR]

With the coronavirus disease 2019 (COVID-19) pandemic, one of the major concerns is the direct medical cost and resource use burden imposed on the US health care system. We developed a Monte Carlo simulation model that represented the US population and what could happen to each person who got infected. We estimated resource use and direct medical costs per symptomatic infection and at the national level, with various "attack rates" (infection rates), to understand the potential economic benefits of reducing the burden of the disease. A single symptomatic COVID-19 case could incur a median direct medical cost of $3,045 during the course of the infection alone. If 80 percent of the US population were to get infected, the result could be a median of 44.6 million hospitalizations, 10.7 million intensive care unit (ICU) admissions, 6.5 million patients requiring a ventilator, 249.5 million hospital bed days, and $654.0 billion in direct medical costs over the course of the pandemic. If 20 percent of the US population were to get infected, there could be a median of 11.2 million hospitalizations, 2.7 million ICU admissions, 1.6 million patients requiring a ventilator, 62.3 million hospital bed days, and $163.4 billion in direct medical costs over the course of the pandemic. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity and mortality. Colonization by MRSA increases the risk of infection and transmission, underscoring the importance of decolonization efforts. However, success of these decolonization protocols varies, raising the possibility that some MRSA strains may be more persistent than others. Here, we studied how the persistence of MRSA colonization correlates with genomic presence of antibiotic resistance genes. Our analysis using a Bayesian mixed effects survival model found that genetic determinants of high-level resistance to mupirocin was strongly associated with failure of the decolonization protocol. However, we did not see a similar effect with genetic resistance to chlorhexidine or other antibiotics. Including strain-specific random effects improved the predictive performance, indicating that some strain characteristics other than resistance also contributed to persistence. Study subject-specific random effects did not improve the model. Our results highlight the need to consider the properties of the colonizing MRSA strain when deciding which treatments to include in the decolonization protocol. Author summary: Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a high burden of morbidity and mortality. MRSA colonization incurs risk of MRSA infection and transmission, highlighting the need for highly effective decolonization protocols. However, decolonization protocols have had mixed success. The extent to which this mixed success is attributable to MRSA strain variations and their resistance to antibiotics, including those like mupirocin that are commonly used for decolonization, versus study subject factors, has been unclear. Here, we characterized the effect of antibiotic resistance genes on the efficiency of an MRSA decolonization protocol. We found that mupirocin resistance and strain-specific effects were associated with reduced effectiveness of an MRSA decolonization protocol, but that resistance to other antibiotics, including purported chlorhexidine resistance genes, and subject-specific effects had no discernible impact on protocol success. Our results highlight the need to consider the properties of the colonizing MRSA strain when deciding which treatments to include in the decolonization protocol. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infections: Results From a Randomized Placebo-Controlled Trial," by C. Barbosa-Cesnik, M.B. Brown, B. Foxman and colleagues that was published in the previous issue of the journal.

Background The CLEAR Trial demonstrated that a multisite body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. Here, we describe decolonization efficacy. Methods We performed a large, multicenter, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with topical chlorhexidine, oral chlorhexidine, and nasal mupirocin. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline and 1, 3, 6, and 9 months after randomization. The primary outcomes of this study are follow-up colonization differences between groups. Results Among 2121 participants, 1058 were randomized to decolonization. By 1 month, MRSA colonization was lower in the decolonization group compared with the education-only group (odds ration [OR] = 0.44; 95% confidence interval [CI],.36–.54; P ≤.001). A similar magnitude of reduction was seen in the nares (OR = 0.34; 95% CI,.27–.42; P <.001), throat (OR = 0.55; 95% CI,.42–.73; P <.001), and axilla/groin (OR = 0.57; 95% CI,.43–.75; P <.001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (P ≤.01). Conclusions In a randomized, clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventilator-associated pneumonia: a matched case-control study" by D.P. Kofteridis and colleagues in the 2010 issue.

Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicrobials in the treatment of VRE (faecium or faecalis) bacteremia from multiple centers across the United States. Methods Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant β-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive β-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs. Findings Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant β-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3-4 µg/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant β-lactam therapy (clinical success, 88% vs 79% for MIC =2 vs 3-4 µg/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced =1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients). Implications Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant β-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant β-lactams with daptomycin. [ABSTRACT FROM AUTHOR]

In our Monte Carlo model comparing management strategies for recurrent urinary tract infections in women, we found that nitrofurantoin prophylaxis was most effective, but most expensive to the payer. Other strategies resulted in payer savings but were less efficacious.Background. Recurrent urinary tract infections (UTIs) are a common problem among women. However, comparative effectiveness strategies for managing recurrent UTIs are lacking.Methods. We performed a systematic literature review of management of women experiencing ≥3 UTIs per year. We then developed a Markov chain Monte Carlo model of recurrent UTI for each management strategy with ≥2 adequate trials published. We simulated a cohort that experienced 3 UTIs/year and a secondary cohort that experienced 8 UTIs/year. Model outcomes were treatment efficacy, patient and payer cost, and health-related quality of life.Results. Five strategies had ≥2 clinical trials published: (1) daily antibiotic (nitrofurantoin) prophylaxis; (2) daily estrogen prophylaxis; (3) daily cranberry prophylaxis; (4) acupuncture prophylaxis; and (5) symptomatic self-treatment. In the 3 UTIs/year model, nitrofurantoin prophylaxis was most effective, reducing the UTI rate to 0.4 UTIs/year, and the most expensive to the payer ($821/year). All other strategies resulted in payer cost savings but were less efficacious. Symptomatic self-treatment was the only strategy that resulted in patient cost savings, and was the most favorable strategy in term of cost per quality-adjusted life-year (QALY) gained.Conclusions. Daily antibiotic use is the most effective strategy for recurrent UTI prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture. Cost savings to payers and patients were seen for most regimens, and improvement in QALYs were seen with all. Our findings provide clinically meaningful data to guide the physician–patient partnership in determining a preferred method of prevention for this common clinical problem. [ABSTRACT FROM AUTHOR]

Summary The pathogenesis of Staphylococcus aureus infective endocarditis (IE) is postulated to involve invasion and damage of endothelial cells (ECs). However, the precise relationships between S. aureus-EC interactions in vitro and IE virulence and treatment outcomes in vivo are poorly defined. Ten methicillin-resistant S. aureus (MRSA) clinical isolates previously tested for their virulence and vancomycin responsiveness in an experimental IE model were assessed in vitro for their haemolytic activity, protease production, and capacity to invade and damage ECs. There was a significant positive correlation between the in vitro EC damage caused by these MRSA strains and their virulence during experimental IE (in terms of bacterial densities in target tissues; P < 0.02). Importantly, higher EC damage was also significantly correlated with poor microbiological response to vancomycin in the IE model ( P < 0.001). Interestingly, the extent of EC damage was unrelated to a strain's ability to invade ECs, haemolytic activity and protease production, or β-toxin gene transcription. Inactivation of the agr locus in two MRSA strains caused ∼20% less damage as compared with the corresponding parental strains, indicating that a functional agr is required for maximal EC damage induction. Thus, MRSA-induced EC damage in vitro is a unique virulence phenotype that is independent of many other prototypical MRSA virulence factors, and may be a key biomarker for predicting MRSA virulence potential and antibiotic outcomes during endovascular infections. [ABSTRACT FROM AUTHOR]

Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 [treating 25% of symptomatic cases, reducing by 0.5 days, reproductive number (R0) 3.5, and starting treatment when 15% of the population has been exposed] to 44.4 million SARS-CoV-2 cases (treating 75% of all infected cases, reducing by 3.5 days, R0 2.0). With R0 2.5, reducing the average infectious period duration by 0.5 days for 25% of symptomatic cases averted 1.4 million cases and 99,398 hospitalizations; increasing to 75% of symptomatic cases averted 2.8 million cases. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R0 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study quantifies the potential effects of reducing the SARS-CoV-2 infectious period duration. Author summary: Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Our simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 to 44.4 million SARS-CoV-2 cases, varying the proportion of cases treated, average duration of the infectious period, and the reproductive rate. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective, R0 2.5). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R0 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study suggests that finding ways to reduce the infectious period of SARS-CoV-2 could help decrease its spread and impact. [ABSTRACT FROM AUTHOR]

Introduction: Given the continuing COVID-19 pandemic and much of the U.S. implementing social distancing owing to the lack of alternatives, there has been a push to develop a vaccine to eliminate the need for social distancing.Methods: In 2020, the team developed a computational model of the U.S. simulating the spread of COVID-19 coronavirus and vaccination.Results: Simulation experiments revealed that to prevent an epidemic (reduce the peak by >99%), the vaccine efficacy has to be at least 60% when vaccination coverage is 100% (reproduction number=2.5-3.5). This vaccine efficacy threshold rises to 70% when coverage drops to 75% and up to 80% when coverage drops to 60% when reproduction number is 2.5, rising to 80% when coverage drops to 75% when the reproduction number is 3.5. To extinguish an ongoing epidemic, the vaccine efficacy has to be at least 60% when coverage is 100% and at least 80% when coverage drops to 75% to reduce the peak by 85%-86%, 61%-62%, and 32% when vaccination occurs after 5%, 15%, and 30% of the population, respectively, have already been exposed to COVID-19 coronavirus. A vaccine with an efficacy between 60% and 80% could still obviate the need for other measures under certain circumstances such as much higher, and in some cases, potentially unachievable, vaccination coverages.Conclusions: This study found that the vaccine has to have an efficacy of at least 70% to prevent an epidemic and of at least 80% to largely extinguish an epidemic without any other measures (e.g., social distancing). [ABSTRACT FROM AUTHOR]

Background: Clinical testing detects a fraction of carbapenem-resistant Enterobacteriaceae (CRE) carriers. Detecting a greater proportion could lead to increased use of infection prevention and control measures but requires resources. Therefore, it is important to understand the impact of detecting increasing proportions of CRE carriers.Methods: We used our Regional Healthcare Ecosystem Analyst-generated agent-based model of adult inpatient healthcare facilities in Orange County, California, to explore the impact that detecting greater proportions of carriers has on the spread of CRE.Results: Detecting and placing 1 in 9 carriers on contact precautions increased the prevalence of CRE from 0% to 8.0% countywide over 10 years. Increasing the proportion of detected carriers from 1 in 9 up to 1 in 5 yielded linear reductions in transmission; at proportions >1 in 5, reductions were greater than linear. Transmission reductions did not occur for 1, 4, or 5 years, varying by facility type. With a contact precautions effectiveness of ≤70%, the detection level yielding nonlinear reductions remained unchanged; with an effectiveness of >80%, detecting only 1 in 5 carriers garnered large reductions in the number of new CRE carriers. Trends held when CRE was already present in the region.Conclusion: Although detection of all carriers provided the most benefits for preventing new CRE carriers, if this is not feasible, it may be worthwhile to aim for detecting >1 in 5 carriers. [ABSTRACT FROM AUTHOR]

To determine temporal associations of local measures of influenza morbidity and mortality by the Centers for Disease Control and Prevention (CDC) with influenza hospitalizations in nursing home residents. Retrospective, longitudinal panel study. Long-stay nursing home residents, aged 65 years or older in 823 nursing homes from 2011 to 2015. CDC-reported rates of influenza and pneumonia mortality and laboratory-confirmed influenza hospitalizations. We compared the CDC measures to nursing home resident hospitalizations due to (1) all-cause, (2) a primary diagnosis of respiratory or circulatory illness, and (3) a primary diagnosis of pneumonia or influenza based on Medicare Part A Claims data. Our final sample included 273,743 unique residents in 819 nursing homes in 108 cities. National laboratory-confirmed influenza-associated hospitalizations for the group aged 65 and older occurred 0 to 1 week prior to nursing home resident influenza-related hospitalizations (Spearman ρ = 0.54). CDC-reported influenza hospitalizations occurred 3 weeks prior to CDC-reported influenza deaths (ρ = 0.59). Nursing home resident influenza hospitalizations occurred 2 weeks before local CDC-reported pneumonia and influenza deaths occurred (ρ = 0.44). Publicly reported CDC measures correlate well with nursing home hospitalizations for pneumonia and influenza. Rates of laboratory-confirmed influenza hospitalizations (as reported by the CDC) may be a useful surrogate for nursing home influenza outbreaks but should be considered along with local indicators of disease outbreaks. Early community signals could be clinically leveraged as a trigger for increased infection control measures in nursing homes. [ABSTRACT FROM AUTHOR]

Ceftazidime‐avibactam (CAZ‐AVI) is a novel intravenous β‐lactam/β‐lactamase inhibitor combination used in the treatment of multidrug‐resistant (MDR) gram‐negative infections. Although renal dosing recommendations exist for the medication, limited data are available for dosing in patients receiving continuous renal replacement therapy. In this report, we describe a case in which CAZ‐AVI 2.5 g was administered as a 2‐hour infusion every 8 hours to a 50‐year‐old critically ill patient with MDR Pseudomonas aeruginosa (CAZ‐AVI minimum inhibitory concentration [MIC] 8 μg/ml) pneumonia who was also receiving continuous venovenous hemodiafiltration (CVVHDF). Total serum concentrations of both ceftazidime and avibactam were measured at ~0.5, 2, 4, and 6 hours after completion of the 2‐hour infusion of the 11th dose of CAZ‐AVI. Ceftazidime pharmacokinetic parameters were as follows: maximum serum concentration (Cmax) 152.39 μg/ml, half‐life 5.17 hours, volume of distribution at steady state (Vdss) 11.51 L, clearance 1.54 L/hour, and area under the concentration‐time curve (AUC) 1295.38 hour•μg/ml. This regimen achieved free ceftazidime serum concentrations more than 4 times the MIC for 100% of the dosing interval. Avibactam pharmacokinetic parameters were as follows: Cmax 35.83 μg/ml, half‐life 5.92 hours, Vdss 12.44 L, clearance 1.45 L/hour, and AUC 343.44 hour•μg/ml, which achieved free avibactam concentrations above 1 μg/ml for 100% of the dosing interval. Higher CAZ‐AVI dosing is critical in the treatment of pneumonia due to limited ceftazidime penetration into epithelial lining fluid; however, epithelial lining fluid drug concentrations were not collected or measured. Based on this case report and the available evidence, a dose of CAZ‐AVI 2.5 g infused over 2 hours every 8 hours appears to be appropriate for critically ill patients who are being treated for pneumonia and are receiving CVVHDF. [ABSTRACT FROM AUTHOR]

Purpose Development of scoring systems to predict the risk of aminoglycoside resistance and to guide therapy is described. Methods Infections due to aminoglycoside-resistant gram-negative rods (AR-GNRs) are increasingly common and associated with adverse outcomes; selection of effective initial antibiotic therapy is necessary to reduce adverse consequences and shorten length of stay. To determine risk factors for AR-GNR recovery from culture, cases of GNR infection among patients admitted to 2 institutions in a major academic hospital system during the period 2011–2016 were retrospectively analyzed. Gentamicin and tobramycin resistance (GTR-GNR) and amikacin resistance (AmR-GNR) patterns were analyzed separately. A total of 26,154 GNR isolates from 12,516 patients were analyzed, 6,699 of which were GTR, and 2,467 of which were AmR. Results In multivariate analysis, risk factors for GTR-GNR were presence of weight loss, admission from another medical or long-term care facility, a hemoglobin level of <11 g/dL, receipt of any carbapenem in the prior 30 days, and receipt of any fluoroquinolone in the prior 30 days (C statistic, 0.63). Risk factors for AmR-GNR were diagnosis of cystic fibrosis, male gender, admission from another medical or long-term care facility, ventilation at any point prior to culture during the index hospitalization, receipt of any carbapenem in the prior 30 days, and receipt of any anti-MRSA agent in the prior 30 days (C statistic, 0.74). Multinomial and ordinal models demonstrated that the risk factors for the 2 resistance patterns differed significantly. Conclusion A scoring system derived from the developed risk prediction models can be applied by providers to guide empirical antimicrobial therapy for treatment of GNR infections. [ABSTRACT FROM AUTHOR]

Bacterial populations that colonize a host can play important roles in host health, including serving as a reservoir that transmits to other hosts and from which invasive strains emerge, thus emphasizing the importance of understanding rates of acquisition and clearance of colonizing populations. Studies of colonization dynamics have been based on assessment of whether serial samples represent a single population or distinct colonization events. With the use of whole genome sequencing to determine genetic distance between isolates, a common solution to estimate acquisition and clearance rates has been to assume a fixed genetic distance threshold below which isolates are considered to represent the same strain. However, this approach is often inadequate to account for the diversity of the underlying within-host evolving population, the time intervals between consecutive measurements, and the uncertainty in the estimated acquisition and clearance rates. Here, we present a fully Bayesian model that provides probabilities of whether two strains should be considered the same, allowing us to determine bacterial clearance and acquisition from genomes sampled over time. Our method explicitly models the within-host variation using population genetic simulation, and the inference is done using a combination of Approximate Bayesian Computation (ABC) and Markov Chain Monte Carlo (MCMC). We validate the method with multiple carefully conducted simulations and demonstrate its use in practice by analyzing a collection of methicillin resistant Staphylococcus aureus (MRSA) isolates from a large recently completed longitudinal clinical study. An R-code implementation of the method is freely available at: . [ABSTRACT FROM AUTHOR]

Background: Rising rates of hospitalization for infective endocarditis (IE) have been increasingly tied to rising injection drug use (IDU) associated with the opioid epidemic.Objectives: This study analyzed recent trends in IDU-IE hospitalization and characterized outcomes and readmissions for IDU-IE patients.Methods: The authors evaluated the National Readmissions Database (NRD) for IE cases between January 2010 and September 2015. Patients were stratified by IDU status and surgical versus medical management. Primary outcome was 30-day readmission and cause, with secondary outcomes including mortality, length of stay (LOS), adjusted costs, and 180-day readmission. The Kruskal-Wallis and chi-square tests were used to analyze baseline differences by IDU status. Multivariable regressions were used to analyze mortality, readmissions, LOS, and adjusted costs.Results: The survey-weighted sample contained 96,344 (77.8%) non-IDU-IE and 27,432 (22.2%) IDU-IE cases. IDU-IE increased from 15.3% to 29.1% of IE cases between 2010 and 2015 (p < 0.001). At index hospitalization, IDU-IE was associated with reduced mortality (6.8% vs. 9.6%; p < 0.001) but not 30-day readmission (23.8% vs. 22.9%; p = 0.077) relative to non-IDU-IE. Medically managed IDU-IE patients had higher LOS (β = 1.36 days; 95% confidence interval [CI]: 0.71 to 2.01), reduced costs (β = -$4,427; 95% CI: -$7,093 to -$1,761), and increased readmission for endocarditis (18.1% vs. 5.6%; p < 0.001), septicemia (14.0% vs. 7.3%; p < 0.001), and drug abuse (4.3% vs. 0.7%; p < 0.001) compared with medically managed non-IDU-IE. Surgically managed IDU-IE patients had increased LOS (β = 4.26 days; 95% CI: 2.73 to 5.80) and readmission for septicemia (15.6% vs. 5.2%; p < 0.001) and drug abuse (7.3% vs. 0.9%; p < 0.001) compared with non-IDU-IE.Conclusions: The incidence of IDU-IE continues to rise nationally. Given the increased readmission for endocarditis, septicemia, and drug abuse, IDU-IE presents a serious challenge to current management of IE. [ABSTRACT FROM AUTHOR]

Background: Surgical site infections (SSIs) occur in 1% to 4% of cardiac surgery patients and are associated with significantly reduced survival. The present study evaluated trends in the incidence and bacteriology of SSIs before and after the implementation of an antimicrobial stewardship program.Methods: Starting in 2010, our institution utilized a protocol that included daily chlorhexidine baths, and strict cessation of prophylactic antibiotics after 48 hours. We used our institutional Society of Thoracic Surgery Database to identify all adult patients who underwent cardiac operations. Data from the microbiology laboratory were used to identify SSIs. Patients undergoing cardiac surgery between January 2008 and December 2010 (pre-stewardship group: PRE) and January 2011 and December 2012 (post-stewardship group: POST) were compared.Results: Of the 3233 patients who underwent cardiac surgery during the study period, 23 (0.71%) developed SSIs (PRE: 0.69%, POST: 0.75%, p = 0.843). The proportion of gram positive, gram negative, fungal, and anaerobic organisms was not significantly different between time periods. The most commonly identified organisms were Staphylococcus aureus, Enterococcus spp., and Pseudomonas aeruginosa.Conclusion: Despite changes in antibiotic prophylaxis duration and postoperative skin treatment, our data demonstrate a stable incidence and composition of surgical wound infections during the study period. doi: 10.1111/jocs.12756 (J Card Surg 2016;31:367-372). [ABSTRACT FROM AUTHOR]

A recent trial showed that universal decolonization in adult intensive care units (ICUs) resulted in greater reductions in all bloodstream infections and clinical isolates of methicillin-resistant (MRSA) than Staphylococcus aureus either targeted decolonization or screening and isolation. Since regional health-care facilities are highly interconnected through patient-sharing, focusing on individual ICUs may miss the broader impact of decolonization. Using our Regional Healthcare Ecosystem Analyst simulation model of all health-care facilities in Orange County, California, we evaluated the impact of chlorhexidine baths and mupirocin on all ICU admissions when universal decolonization was implemented for 25%, 50%, 75%, and 100% of ICU beds countywide (compared with screening and contact precautions). Direct benefits were substantial in ICUs implementing decolonization (a median 60% relative reduction in MRSA prevalence). When 100% of countywide ICU beds were decolonized, there were spillover effects in general wards, long-term acute-care facilities, and nursing homes resulting in median 8.0%, 3.0%, and 1.9% relative MRSA reductions at 1 year, respectively. MRSA prevalence decreased by a relative 3.2% countywide, with similar effects for methicillin-susceptible .We showed that a large proportion of decolonization's S. aureus benefits are missed when accounting only for ICU impact. Approximately 70% of the countywide cases of MRSA carriage averted after 1 year of universal ICU decolonization were outside the ICU. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Enterobacteriaceae (CRE), a group of pathogens resistant to most antibiotics and associated with high mortality, are a rising emerging public health threat. Current approaches to infection control and prevention have not been adequate to prevent spread. An important but unproven approach is to have hospitals in a region coordinate surveillance and infection control measures. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model and detailed Orange County, California, patient-level data on adult inpatient hospital and nursing home admissions (2011-2012), we simulated the spread of CRE throughout Orange County healthcare facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (uncoordinated control measures), and a coordinated regional effort. Aggressive uncoordinated and coordinated approaches were highly similar, averting 2,976 and 2,789 CRE transmission events, respectively (72.2% and 77.0% of transmission events), by year 5. With moderate control measures, coordinated regional control resulted in 21.3% more averted cases (n = 408) than did uncoordinated control at year 5. Our model suggests that without increased infection control approaches, CRE would become endemic in nearly all Orange County health-care facilities within 10 years. While implementing the interventions in the Centers for Disease Control and Prevention's CRE toolkit would not completely stop the spread of CRE, it would cut its spread substantially, by half. [ABSTRACT FROM AUTHOR]

Background: Treatments for health care--associated infections (HAIs) caused by antibiotic-resistant bacteria and Clostridium difficile are limited, and some patients have developed untreatable infections. Evidence-supported interventions are available, but coordinated approaches to interrupt the spread of HAIs could have a greater impact on reversing the increasing incidence of these infections than independent facility-based program efforts. Methods: Data from CDC's National Healthcare Safety Network and Emerging Infections Program were analyzed to project the number of health care--associated infections from antibiotic-resistant bacteria or C. difficile both with and without a large scale national intervention that would include interrupting transmission and improved antibiotic stewardship. As an example, the impact of reducing transmission of one antibiotic-resistant infection (carbapenem-resistant Enterobacteriaceae [CRE]) on cumulative prevalence and number of HAI transmission events within interconnected groups of health care facilities was modeled using two distinct approaches, a large scale and a smaller scale health care network. Results: Immediate nationwide infection control and antibiotic stewardship interventions, over 5 years, could avert an estimated 619,000 HAIs resulting from CRE, multidrug-resistant Pseudomonas aeruginosa, invasive methicillin-resistant Staphylococcus aureus (MRSA), or C. difficile. Compared with independent efforts, a coordinated response to prevent CRE spread across a group of inter-connected health care facilities resulted in a cumulative 74% reduction in acquisitions over 5 years in a 10-facility network model, and 55% reduction over 15 years in a 102-facility network model. Conclusions: With effective action now, more than half a million antibiotic-resistant health care-associated infections could be prevented over 5 years. Models representing both large and small groups of interconnected health care facilities illustrate that a coordinated approach to interrupting transmission is more effective than historical independent facility-based efforts. Implications for Public Health: Public health-led coordinated prevention approaches have the potential to more completely address the emergence and dissemination of these antibiotic-resistant organisms and C. difficile than independent facility-based efforts. [ABSTRACT FROM AUTHOR]

Background Antibiotic treatment failure is common among patients with community-acquired pneumonia (CAP) who are managed in the outpatient setting and is associated with higher mortality and increased health care costs. This study's objectives were to quantify the occurrence of antibiotic treatment failure (ATF) and to evaluate clinical and economic outcomes between CAP patients who experienced ATF relative to those who did not. Methods Retrospective analysis of the MarketScan Commercial & Medicare Supplemental Databases was performed, identifying patients ≥18 years old, with a pneumonia diagnosis in the outpatient setting, and who received a fluoroquinolone, macrolides, beta-lactam, or tetracycline. ATF was defined as any of the following events within 30 days of initial antibiotic: antibiotic refill, antibiotic switch, emergency room visit, or hospitalization. Outcomes included 30-day all-cause mortality and CAP-related health care costs. Results During the study period, 251 947 unique patients met inclusion criteria. The mean age was 52.2 years, and 47.7% were male. The majority of patients received a fluoroquinolone (44.4%) or macrolide (43.6%). Overall, 22.1% were classified as ATFs. Among 18–64-year-old patients, 21.2% experienced treatment failure, compared with 25.7% in those >65 years old. All-cause mortality was greater in the antibiotic failure group relative to the non–antibiotic failure group (18.1% vs 4.6%, respectively), and the differences in 30-day mortality between antibiotic failure groups increased as a function of age. Mean 30-day CAP-related health care costs were also higher in the patients who experienced treatment failure relative to those who did not ($2140 vs $54, respectively). Conclusions Treatment failure and poor outcomes from outpatient CAP are common with current guideline-concordant CAP therapies. Improvements in clinical management programs and therapeutic options are needed. [ABSTRACT FROM AUTHOR]

Background Los Angeles (LA) County is large and diverse urban southern California county with a population of over 10 million and a multitude of hospitals. The state of California required hospitals to implement ASPs in July 2015. This collaborative with the LA County Department of Public Health sought to characterize administrative structure and practices of hospital ASPs in the county. Methods A survey of LA County hospital ASPs was conducted from November 2018 to April 2019. Initial telephone and email screenings were performed to confirm individuals' involvement in hospital ASPs prior to survey participation. Results Overall, 40 of 87 (46%) hospitals responded. Of these, 90% (36/40) were private hospitals and 68% (27/40) were part of a multi-hospital network. All hospitals (40/40) reported an active ASP with 53% (21/40) established for 5 years or longer. Only 65% (26/40) reported meeting all seven CDC core elements of hospital ASPs and 85% (34/40) reported having an ASP committee. Of those with ASP committees, individuals who chaired or co-chaired the committee were predominantly ID physicians (33/34, 97%). Most held meetings quarterly (18/34, 53%). Committee member meeting attendance "all or most of the time" was highest for pharmacists (34/34, 100%) and ID physicians (33/34, 97%) and lowest for information technology (IT) personnel (9/34, 27%) and non-ID physicians (12/34, 35%). ASP committees reported to a mean of 2.4 other committees, most frequently to pharmacy and therapeutics (P&T) (32/34, 94%) and infection control (IC) (24/34, 71%). ASP committees received reports from a mean of 2.3 committees, most frequently from IC (22/34, 65%). Few ASP committees (<20%) reported to any of patient/medication safety, quality, sepsis, laboratory, risk management or nursing committees. Risk assessments and strategic planning were performed by only 35% (12/34) and 56% (19/34), respectively. Conclusion Our study demonstrates additional need in LA County hospital ASPs to meet CDC core measures as well as enhance ASP administrative structure. Notably, ASP committees appear to be siloed with P&T and IC with minimal reporting to other committees, do not frequently perform risk assessments or strategic planning, and have low meeting attendance by IT personnel and non-ID physicians. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Minimal literature exists to demonstrate the quantitative impact of bedside nurses in antimicrobial stewardship (AMS). We initiated bedside nurse-driven AMS and infection prevention (AMS/IP) rounds on three inpatient telemetry units of a community regional medical center. Rounds were nurse-driven, involved an infectious diseases (ID) pharmacist and infection preventionist, and were designed to complement traditional ID pharmacist and ID physician AMS rounds. Rounds were focused on use of antibiotics, urinary catheters (UCs), and central venous catheters (CVCs). Recommendations from rounds were communicated by the bedside nurse either directly to providers or to the ID pharmacist and ID physician for intervention. Methods This was an observational, multiple-group, quasi-experimental study conducted over 3.5 years (July 2015 to December 2018) to characterize the impact of bedside nurse-driven AMS/IP rounds on antibiotic, urinary catheter and CVC use, hospital-onset C. difficile infection (CDI), catheter-associated urinary tract infections (CAUTI), and central line-associated bloodstream infections (CLABSI). Outcomes were assessed in two cohorts based on time of AMS/IP rounds implementation (Cohort 1 implemented on one telemetry unit in July 2016, Cohort 2 implemented in two telemetry units in January 2018). Results A total of 2,273 patient therapy reviews occurred (Cohort 1: 1,736; Cohort 2: 537). Of these reviews, 1,209 (53%) were antibiotics, 879 (39%) were urinary catheters, and 185 (8%) were CVCs. Pre- vs. post-intervention, significant reductions were observed in both cohorts for mean monthly antibiotic days of therapy per 1,000 patient-days (Cohort 1: 791 vs. 688, P < 0.001; Cohort 2: 615 vs. 492, P < 0.001), UC days per patient day (Cohort 1: 0.25 vs. 0.16, P < 0.001; Cohort 2: 0.19 vs. 0.14, P < 0.001), CVC days per patient day (Cohort 1: 0.15 vs. 0.11, = 0.002; Cohort 2: 0.09 vs. 0.07, p = 0.005), and CDI per 10,000 patient-days (Cohort 1: 17.8 vs. 7.1, p = 0.035; Cohort 2: 19.1 vs. 5.4, p = 0.003). Numerical reductions were observed in CAUTI and CLABSI per 10,000 patient-days. Conclusion Bedside nurses can improve AMS and IP outcomes in a scalable fashion when supported by an interdisciplinary AMS/IP team and are complimentary to traditional AMS and IP practices. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Historically, endemic Klebsiella pneumoniae carbapenemase (KPC) has accounted for the majority of carbapenem-resistant Enterobacteriaceae (CRE) in Los Angeles County (LAC). The LAC Department of Public Health (DPH) initiated enhanced CRE surveillance in 2016 to determine CRE prevalence and track emerging non-KPC resistance mechanisms (IMP, NDM, OXA, and VIM) among CRE to describe characteristics and identify local epidemiology for novel multi-drug-resistant organism (N-MDRO) infection and colonization. Methods CRE isolates were voluntarily submitted by local clinical laboratories for mechanism detection by LAC Public Health Laboratory via MALDI-TOF and Nanosphere BC-GN. Baseline isolates were collected in 2016. Results are then presented by year through 2018. For N-MDRO cases, LACDPH interviewed healthcare facility (HCF) staff and cases to obtain case characteristics. Data were analyzed via Microsoft Access and SAS. Results CRE surveillance isolates were voluntarily submitted by 31 labs representing 34% (34/96) LAC hospitals and 1 large regional lab serving 60% of skilled nursing facilities from January 2016 to December 2018. LACDPH tested 1438 CRE isolates during the study period, 1168 (81%) were carbapenemase producing (CP). The proportion of CP CRE and KPC CRE declined over the study period (Table 1). NDM was the most common non-KPC (n = 30) followed by OXA (n = 28). The proportion of CRE with no genotypic marker increased over the course of the study. Case characteristics were obtained from 41 non-KPC CP CRE cases; median age was 66 years (range: 6–94 years); 12 (29%) expired. Among the 41 cases, 20 (49%) had a central line; 11 (27%) had surgery; 14 (34%) had antibiotics in the 6 months prior to culture date. Of the 41 cases, 11 (27%) had international healthcare exposure within 12 months with an invasive procedure and/or antibiotics. Conclusion Surveillance in a large urban setting suggests the molecular epidemiology of CRE is changing, with declining prevalence of KPC, increasing metallo-β-lactamase CP, and large proportion of isolates without resistance markers detected. Given the worrisome trends in non-KPC CRE, more systematic surveillance is warranted, potentially using more robust molecular epidemiology. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Trimethoprim inhibits sodium channels in the distal portion of the renal tubule, thereby impairing renal potassium excretion. Trimethoprim has been associated with a greater risk of hyperkalemia compared with other antibiotics (amoxicillin, nitrofurantoin, cefalexin, ciprofloxacin). An analysis of Phase 3 studies was conducted to determine whether iclaprim, under development for ABSSSI and also a selective bacterial dihydrofolate reductase inhibitor like trimethoprim, is associated with hyperkalemia, relative to vancomycin, an antibiotic not associated with hyperkalemia. Methods A post-hoc safety analysis was conducted on pooled results of two Phase 3, double-blind, randomized (1:1), active-controlled trials (REVIVE-1/-2) in patients with ABSSSI. These trials compared iclaprim 80 mg fixed doses with vancomycin 15 mg/kg; both administered intravenously every 12 hours for 5–14 days. Hyperkalemia was defined as serum potassium (K) ≥5.5 mmol/L, if normal at baseline, while on study drug. Hyperkalemia was compared between treatment groups and stratified subgroup comparisons were performed. Results Demographics and baseline disease characteristics were similar between the pooled iclaprim and vancomycin groups (table). Hyperkalemia occurred during treatment in 1.5% (9/592) and 2.5% (15/599) of patients treated with iclaprim and vancomycin, respectively. Of the patients with hyperkalemia, one patient in each treatment group had moderate to severe renal impairment (creatinine clearance [CrCl] 15–59 mL/minute). Among patients with moderate to severe renal impairment on any RAS, KSD or K supplements, hyperkalemia occurred in 1/16 and 0/16 patients in the iclaprim and vancomycin groups, respectively, and in 2/83 and 0/46 patients with mild to no renal impairment. No patients with hyperkalemia experienced adverse events of palpitations, chest pain, myalgia, muscular weakness or fatigue. Conclusion No differences in hyperkalemia were seen between the iclaprim and vancomycin groups in the Phase 3 REVIVE studies. In general, few cases of hyperkalemia occurred among patients with renal impairment treated with concomitant angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers treated with iclaprim. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Infections due to carbapenem-resistant Gram-negative rods (CR-GNR) are increasing in frequency and result in high morbidity and mortality. Appropriate initial antibiotic therapy is necessary to reduce adverse consequences and shorten length of stay. Methods To determine risk factors for recovery on culture of CR-GNR, cases were retrospectively analyzed at a major academic hospital system from 2011 to 2016. Ertapenem resistance (ER-GNR) and antipseudomonal (nonertapenem) carbapenem resistance (ACR-GNR) patterns were analyzed separately. A total of 30951 GNR isolates from 12370 patients were analyzed, 563 of which were ER and 1307 of which were ACR. Results In multivariate analysis, risk factors for ER-GNR were renal disease, admission from another health care facility, ventilation at any point before culture during the index hospitalization, receipt of any carbapenem in the prior 30 days, and receipt of any anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agent in the prior 30 days (c-statistic, 0.74). Risk factors for ACR-GNR were male sex, admission from another health care facility, ventilation at any point before culture during the index hospitalization, receipt of any carbapenem in the prior 30 days, and receipt of any anti-MRSA agent in the prior 30 days (c-statistic, 0.76). Conclusions A straightforward scoring system derived from these models can be applied by providers to guide empiric antimicrobial therapy; it outperformed use of a standard hospital antibiogram in predicting infections with ER-GNR and ACR-GNR. [ABSTRACT FROM AUTHOR]

B Learning Objectives: b Patients (pts) with carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infections (BSI) have high mortality and few treatment options. A randomized, open-label study of CRE infections (CARE; NCT01970371) demonstrated differences in mortality with a PLZ-based vs a colistin (CST)-based combination treatment. In the PLZ vs CST groups, respectively, 28-day ACM or SDRCs was observed in 0% (0/7) vs 54.5% (6/11) of pts who received prior NS-ABs to which the baseline CRE was susceptible, and 28.6% (2/7) vs 50.0% (2/4) of pts who did not receive prior NS-ABs to which the baseline CRE was susceptible. [Extracted from the article]