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.

Evaluation of the Carba NP Test in Oregon, 2013.

Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health threat. We evaluated the capacity of the Carba NP test to detect carbapenemase production in 206 isolates: 143 Enterobacteriaceae identified by Oregon's CRE surveillance program in 2013 and 63 known carbapenemase-positive organisms. Overall, test sensitivity and specificity were 89% (59/66 isolates; 95% confidence interval [CI], 81 to 97%) and 100% (140/140 isolates; 95% CI, 98 to 100%), respectively. All KPC, NDM-1, VIM, and IMP producers but no (0/7 isolates) OXA-48-like strains were Carba NP positive prior to a post hoc protocol modification. We subsequently incorporated Carba NP into Oregon's CRE screening algorithm.

Nosocomial Outbreak of Extensively Drug-Resistant Acinetobacter baumannii Isolates Containing blaOXA-237 Carried on a Plasmid.

Carbapenem antibiotics are among the mainstays for treating infections caused by Acinetobacter baumannii, especially in the Northwest United States, where carbapenem-resistant A. baumannii remains relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant A. baumannii occurred in 16 patients from five health care facilities in the state of Oregon. All isolates were defined as extensively drug resistant. Multilocus sequence typing revealed that the isolates belonged to sequence type 2 (international clone 2 [IC2]) and were >95% similar as determined by repetitive-sequence-based PCR analysis. Multiplex PCR revealed the presence of a blaOXA carbapenemase gene, later identified as blaOXA-237 Whole-genome sequencing of all isolates revealed a well-supported separate branch within a global A. baumannii phylogeny. Pacific Biosciences (PacBio) SMRT sequencing was also performed on one isolate to gain insight into the genetic location of the carbapenem resistance gene. We discovered that blaOXA-237, flanked on either side by ISAba1 elements in opposite orientations, was carried on a 15,198-bp plasmid designated pORAB01-3 and was present in all 16 isolates. The plasmid also contained genes encoding a TonB-dependent receptor, septicolysin, a type IV secretory pathway (VirD4 component, TraG/TraD family) ATPase, an integrase, a RepB family plasmid DNA replication initiator protein, an alpha/beta hydrolase, and a BrnT/BrnA type II toxin-antitoxin system. This is the first reported outbreak in the northwestern United States associated with this carbapenemase. Particularly worrisome is that blaOXA-237 was carried on a plasmid and found in the most prominent worldwide clonal group IC2, potentially giving pORAB01-3 great capacity for future widespread dissemination.

Development and implementation of a nationwide multidrug-resistant organism tracking and alert system for Veterans Affairs medical centers.

OBJECTIVE: Develop and implement a system in the Veterans Health Administration (VA) to alert local medical center personnel in real time when an acute- or long-term care patient/resident is admitted to their facility with a history of colonization or infection with a multidrug-resistant organism (MDRO) previously identified at any VA facility across the nation. METHODS: An algorithm was developed to extract clinical microbiology and local facility census data from the VA Corporate Data Warehouse initially targeting carbapenem-resistant Enterobacterales (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). The algorithm was validated with chart review of CRE cases from 2010-2018, trialed and refined in 24 VA healthcare systems over two years, expanded to other MDROs and implemented nationwide on 4/2022 as "VA Bug Alert" (VABA). Use through 8/2023 was assessed. RESULTS: VABA performed well for CRE with recall of 96.3%, precision of 99.8%, and F1 score of 98.0%. At the 24 trial sites, feedback was recorded for 1,011 admissions with a history of CRE (130), MRSA (814), or both (67). Among Infection Preventionists and MDRO Prevention Coordinators, 338 (33%) reported being previously unaware of the information, and of these, 271 (80%) reported they would not have otherwise known this information. By fourteen months after nationwide implementation, 113/130 (87%) VA healthcare systems had at least one VABA subscriber. CONCLUSIONS: A national system for alerting facilities in real-time of patients admitted with an MDRO history was successfully developed and implemented in VA. Next steps include understanding facilitators and barriers to use and coordination with non-VA facilities nationwide.

Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations.

BACKGROUND: Fluconazole (FLC) resistance is common in C. glabrata and echinocandins are often used as first-line therapy. Resistance to echinocandin therapy has been associated with FKS1 and FKS2 gene alterations. METHODS: We reviewed records of all patients with C. glabrata bloodstream infection at Duke Hospital over the past decade (2001-2010) and correlated treatment outcome with minimum inhibitory concentration (MIC) results and the presence of FKS gene mutations. For each isolate, MICs to FLC and echinocandins (anidulafungin, caspofungin, and micafungin) and FKS1 and FKS2 gene sequences were determined. RESULTS: Two hundred ninety-three episodes (313 isolates) of C. glabrata bloodstream infection were analyzed. Resistance to echinocandins increased from 4.9% to 12.3% and to FLC from 18% to 30% between 2001 and 2010, respectively. Among the 78 FLC resistant isolates, 14.1% were resistant to 1 or more echinocandin. Twenty-five (7.9%) isolates harbored a FKS mutation. The predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, odds ratio, 19.647 [95% confidence interval, 7.19-58.1]). Eighty percent (8/10) of patients infected with FKS mutants demonstrating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially but experienced a recurrence. CONCLUSIONS: Echinocandin resistance is increasing, including among FLC-resistant isolates. The new Clinical and Laboratory Standards Institute clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.

Principles of diagnostic stewardship: A practical guide from the Society for Healthcare Epidemiology of America Diagnostic Stewardship Task Force.

We provide an overview of diagnostic stewardship with key concepts that include the diagnostic pathway and the multiple points where interventions can be implemented, strategies for interventions, the importance of multidisciplinary collaboration, and key microbiologic diagnostic tests that should be considered for diagnostic stewardship. The document focuses on microbiologic laboratory testing for adult and pediatric patients and is intended for a target audience of healthcare workers involved in diagnostic stewardship interventions and all workers affected by any step of the diagnostic pathway (ie, ordering, collecting, processing, reporting, and interpreting results of a diagnostic test). This document was developed by the Society for Healthcare Epidemiology of America Diagnostic Stewardship Taskforce.

Implementation of a Prevention Bundle to Decrease Rates of Staphylococcus aureus Surgical Site Infection at 11 Veterans Affairs Hospitals.

Importance: While current evidence has demonstrated a surgical site infection (SSI) prevention bundle consisting of preoperative Staphylococcus aureus screening, nasal and skin decolonization, and use of appropriate perioperative antibiotic based on screening results can decrease rates of SSI caused by S aureus, it is well known that interventions may need to be modified to address facility-level factors. Objective: To assess the association between implementation of an SSI prevention bundle allowing for facility discretion regarding specific component interventions and S aureus deep incisional or organ space SSI rates. Design, Setting, and Participants: This quality improvement study was conducted among all patients who underwent coronary artery bypass grafting, cardiac valve replacement, or total joint arthroplasty (TJA) at 11 Veterans Administration hospitals. Implementation of the bundle was on a rolling basis with the earliest implementation occurring in April 2012 and the latest implementation occurring in July 2017. Data were collected from January 2007 to March 2018 and analyzed from October 2020 to June 2023. Interventions: Nasal screening for S aureus; nasal decolonization of S aureus carriers; chlorhexidine bathing; and appropriate perioperative antibiotic prophylaxis according to S aureus carrier status. Facility discretion regarding how to implement the bundle components was allowed. Main Outcomes and Measures: The primary outcome was deep incisional or organ space SSI caused by S aureus. Multivariable logistic regression with generalized estimating equation (GEE) and interrupted time-series (ITS) models were used to compare SSI rates between preintervention and postintervention periods. Results: Among 6696 cardiac surgical procedures and 16 309 TJAs, 95 S aureus deep incisional or organ space SSIs were detected (25 after cardiac operations and 70 after TJAs). While the GEE model suggested a significant association between the intervention and decreased SSI rates after TJAs (adjusted odds ratio, 0.55; 95% CI, 0.31-0.98), there was not a significant association when an ITS model was used (adjusted incidence rate ratio, 0.88; 95% CI, 0.32-2.39). No significant associations after cardiac operations were found. Conclusions and Relevance: Although this quality improvement study suggests an association between implementation of an SSI prevention bundle and decreased S aureus deep incisional or organ space SSI rates after TJAs, it was underpowered to see a significant difference when accounting for changes over time.

Strategies for the implementation of a nasal decolonization intervention to prevent surgical site infections within the Veterans Health Administration.

As part of a multicenter evidence-based intervention for surgical site infection prevention, a qualitative study was conducted with infection control teams and surgical staff members at three Department of Veterans Affairs Healthcare Systems in the USA. This study aimed to identify strategies used by nurses and other facility champions for the implementation of a nasal decolonization intervention. Site visit observations and field notes provided contextual information. Interview data were analyzed with inductive and deductive content analysis. Interview data was mapped to the Expert Recommendations for Implementing Change (ERIC) compilation of implementation strategies. These strategies were then considered in the context of power and relationships as factors that influence implementation. We found that implementation of this evidence-based surgical site infection prevention intervention was successful when nurse champions drove the day-to-day implementation. Nurse champions sustained implementation strategies through all phases of implementation. Findings also suggest that nurse champions leveraged the influence of their role as champion along with their understanding of social networks and relationships to help achieve implementation success. Nurse champions consciously used multiple overlapping and iterative implementation strategies, adapting and tailoring strategies to stakeholders and settings. Commonly used implementation categories included: "train and educate stakeholders," "use evaluative and iterative strategies," "adapt and tailor to context," and "develop stakeholder interrelationships." Future research should examine the social networks for evidence-based interventions by asking specifically about relationships and power dynamics within healthcare organizations. Implementation of evidence-based interventions should consider if the tasks expected of a nurse champion fit the level of influence or power held by the champion. Trial registration: ClinicalTrials.gov, identifier: NCT02216227.

Increased carbapenemase testing following implementation of national VA guidelines for carbapenem-resistant Enterobacterales (CRE).

Objective: To describe national trends in testing and detection of carbapenemases produced by carbapenem-resistant Enterobacterales (CRE) and associate testing with culture and facility characteristics. Design: Retrospective cohort study. Setting: Department of Veterans' Affairs medical centers (VAMCs). Participants: Patients seen at VAMCs between 2013 and 2018 with cultures positive for CRE, defined by national VA guidelines. Interventions: Microbiology and clinical data were extracted from national VA data sets. Carbapenemase testing was summarized using descriptive statistics. Characteristics associated with carbapenemase testing were assessed with bivariate analyses. Results: Of 5,778 standard cultures that grew CRE, 1,905 (33.0%) had evidence of molecular or phenotypic carbapenemase testing and 1,603 (84.1%) of these had carbapenemases detected. Among these cultures confirmed as carbapenemase-producing CRE, 1,053 (65.7%) had molecular testing for ≥1 gene. Almost all testing included KPC (n = 1,047, 99.4%), with KPC detected in 914 of 1,047 (87.3%) cultures. Testing and detection of other enzymes was less frequent. Carbapenemase testing increased over the study period from 23.5% of CRE cultures in 2013 to 58.9% in 2018. The South US Census region (38.6%) and the Northeast (37.2%) region had the highest proportion of CRE cultures with carbapenemase testing. High complexity (vs low) and urban (vs rural) facilities were significantly associated with carbapenemase testing (P < .0001). Conclusions: Between 2013 and 2018, carbapenemase testing and detection increased in the VA, largely reflecting increased testing and detection of KPC. Surveillance of other carbapenemases is important due to global spread and increasing antibiotic resistance. Efforts supporting the expansion of carbapenemase testing to low-complexity, rural healthcare facilities and standardization of reporting of carbapenemase testing are needed.

A survey of infection control strategies for carbapenem-resistant Enterobacteriaceae in Department of Veterans' Affairs facilities.

A survey of Veterans' Affairs Medical Centers on control of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-producing CRE (CP-CRE) demonstrated that most facilities use VA guidelines but few screen for CRE/CP-CRE colonization regularly or regularly communicate CRE/CP-CRE status at patient transfer. Most respondents were knowledgeable about CRE guidelines but cited lack of adequate resources.

Clinician Attitudes and Beliefs Associated with More Aggressive Diagnostic Testing.

BACKGROUND: Variation in clinicians' diagnostic test utilization is incompletely explained by demographics and likely relates to cognitive characteristics. We explored clinician factors associated with diagnostic test utilization. METHODS: We used a self-administered survey of attitudes, cognitive characteristics, and reported likelihood of test ordering in common scenarios; frequency of lipid and liver testing in patients on statin therapy. Participants were 552 primary care physicians, nurse practitioners, and physician assistants from practices in 8 US states across 3 regions, from June 1, 2018 to November 26, 2019. We measured Testing Likelihood Score: the mean of 4 responses to testing frequency and self-reported testing frequency in patients on statins. RESULTS: Respondents were 52.4% residents, 36.6% attendings, and 11.0% nurse practitioners/physician assistants; most were white (53.6%) or Asian (25.5%). Median age was 32 years; 53.1% were female. Participants reported ordering tests for a median of 20% (stress tests) to 90% (mammograms) of patients; Testing Likelihood Scores varied widely (median 54%, interquartile range 43%-69%). Higher scores were associated with geography, training type, low numeracy, high malpractice fear, high medical maximizer score, high stress from uncertainty, high concern about bad outcomes, and low acknowledgment of medical uncertainty. More frequent testing of lipids and liver tests was associated with low numeracy, high medical maximizer score, high malpractice fear, and low acknowledgment of uncertainty. CONCLUSIONS: Clinician variation in testing was common, with more aggressive testing consistently associated with low numeracy, being a medical maximizer, and low acknowledgment of uncertainty. Efforts to reduce undue variations in testing should consider clinician cognitive drivers.

Coronavirus disease 2019 (COVID-19) research agenda for healthcare epidemiology.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

Quantitation of Candida CFU in initial positive blood cultures.

One potential limitation of DNA-based molecular diagnostic tests for Candida bloodstream infection (BSI) is organism burden, which is not sufficiently characterized. We hypothesized that the number of CFU per milliliter (CFU/ml) present in an episode of Candida BSI is too low for reliable DNA-based diagnostics. In this study, we determined Candida burden in the first positive blood culture and explored factors that affect organism numbers and patient outcomes. We reviewed records of consecutive patients with a positive blood culture for Candida in the lysis-centrifugation blood culture system (Isolator, Wampole Laboratories, Cranbury, NJ) from 1987 to 1991. Descriptive statistics and logistic regression analyses were performed. One hundred fifty-two episodes of Candida BSI were analyzed. Patient characteristics included adult age (72%), indwelling central venous catheters (83%), recent surgery (29%), neutropenia (24%), transplant (14%), and other immune suppression (21%). Rates of treatment success and 30-day mortality for candidemia were each 51%. The median CFU/ml was 1 (mode 0.1, range 0.1 to >1,000). In the multivariate analysis, pediatric patients were more likely than adults to have high organism burdens (odds ratio [OR], 10.7; 95% confidence interval [95% CI], 4.3 to 26.5). Initial organism density did not affect patient outcome. Candida CFU/ml in the first positive blood culture of a BSI episode varies greatly; >50% of cultures had ≤1 CFU/ml, a concentration below the experimental yeast cell threshold for reliable DNA-based diagnostics. DNA-based diagnostics for Candida BSI will be challenged by low organism density and the need for sufficient specimen volume; future research on alternate targets is warranted.

Construction and validation of an ultraviolet germicidal irradiation system using locally available components.

Coronavirus disease (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is responsible for a global pandemic characterized by high transmissibility and morbidity. Healthcare workers (HCWs) are at risk of contracting COVID-19, but this risk has been mitigated through the use of personal protective equipment such as N95 Filtering Facepiece Respirators (FFRs). At times the high demand for FFRs has exceeded supply, placing HCWs at increased exposure risk. Effective FFR decontamination of many FFR models using ultraviolet-C germicidal irradiation (UVGI) has been well-described, and could maintain respiratory protection for HCWs in the face of supply line shortages. Here, we detail the construction of an ultraviolet-C germicidal irradiation (UVGI) device using previously existing components available at our institution. We provide data on UV-C dosage delivered with our version of this device, provide information on how users can validate the UV-C dose delivered in similarly constructed systems, and describe a simple, novel methodology to test its germicidal effectiveness using in-house reagents and equipment. As similar components are readily available in many hospitals and industrial facilities, we provide recommendations on the local construction of these systems, as well as guidance and strategies towards successful institutional implementation of FFR decontamination.

Implementing daily chlorhexidine gluconate (CHG) bathing in VA settings: The human factors engineering to prevent resistant organisms (HERO) project.

BACKGROUND: Daily use of chlorhexidine gluconate (CHG) has been shown to reduce risk of healthcare-associated infections. We aimed to assess moving CHG bathing into routine practice using a human factors approach. We evaluated implementation in non-intensive care unit (ICU) settings in the Veterans Health Administration. METHODS: Our multiple case study approach included non-ICU units from 4 Veterans Health Administration settings. Guided by the Systems Engineering Initiative for Patient Safety, we conducted focus groups and interviews to capture barriers and facilitators to daily CHG bathing. We measured compliance using observations and skin CHG concentrations. RESULTS: Barriers to daily CHG include time, concern of increasing antibiotic resistance, workflow and product concerns. Facilitators include engagement of champions and unit shared responsibility. We found shortfalls in patient education, hand hygiene and CHG use on tubes and drains. CHG skin concentration levels were highest among patients from spinal cord injury units. These units applied antiseptic using 2% CHG impregnated wipes vs 4% CHG solution/soap. DISCUSSION: Non-ICUs implementing CHG bathing must consider human factors and work system barriers to ensure uptake and sustained practice change. CONCLUSIONS: Well-planned rollouts and a unit culture promoting shared responsibility are key to compliance with daily CHG bathing. Successful implementation requires attention to staff education and measurement of compliance.

Carbapenem-resistant Enterobacteriaceae epidemiology in Veterans' Affairs medical centers varies by facility characteristics.

This is an epidemiological study of carbapenem-resistant Enterobacteriaceae (CRE) in Veterans' Affairs medical centers (VAMCs). In 2017, almost 75% of VAMCs had at least 1 CRE case. We observed substantial geographic variability, with more cases in urban, complex facilities. This supports the benefit of tailoring infection control strategies to facility characteristics.

Breakthrough invasive candidiasis in patients on micafungin.

For Candida species, a bimodal wild-type MIC distribution for echinocandins exists, but resistance to echinocandins is rare. We characterized isolates from patients with invasive candidiasis (IC) breaking through >or=3 doses of micafungin therapy during the first 28 months of its use at our center: MICs were determined and hot-spot regions within FKS genes were sequenced. Eleven of 12 breakthrough IC cases identified were in transplant recipients. The median duration of micafungin exposure prior to breakthrough was 33 days (range, 5 to 165). Seventeen breakthrough isolates were recovered: FKS hot-spot mutations were found in 5 C. glabrata and 2 C. tropicalis isolates; of these, 5 (including all C. glabrata isolates) had micafungin MICs of >2 microg/ml, but all demonstrated caspofungin MICs of >2 microg/ml. Five C. parapsilosis isolates had wild-type FKS sequences and caspofungin MICs of 0.5 to 1 microg/ml, but 4/5 had micafungin MICs of >2 microg/ml. The remaining isolates retained echinocandin MICs of 2 microg/ml and clinical breakthrough or an alternative mechanism contributes to the nonsusceptible echinocandin MICs in C. parapsilosis requires further study.

Compliance with statewide regulations for communication of patients' multidrug-resistant organism and Clostridium difficile status during transitions of care.

In 2014, Oregon implemented an interfacility transfer communication law requiring notification of multidrug-resistant organism status on patient transfer. Based on 2015 and 2016 statewide facility surveys, compliance was 77% and 87% for hospitals, and 67% and 68% for skilled nursing facilities. Methods for complying with the rule were heterogeneous, and fewer than half of all facilities surveyed reported use of a standardized interfacility transfer communication form to assess a patient's multidrug-resistant organism status on transfer.

Homegrown Ultraviolet Germicidal Irradiation for Hospital-Based N95 Decontamination during the COVID-19 Pandemic.

Coronavirus disease (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is responsible for the 2020 global pandemic and characterized by high transmissibility and morbidity. Healthcare workers (HCWs) are at risk of contracting COVID-19, and this risk is mitigated through the use of personal protective equipment such as N95 Filtering Facepiece Respirators (FFRs). The high demand for FFRs is not currently met by global supply chains, potentially placing HCWs at increased exposure risk. Effective FFR decontamination modalities exist, which could maintain respiratory protection for HCWs in the midst of the current pandemic, through the decontamination and re-use of FFRs. Here, we present a locally-implemented ultraviolet-C germicidal irradiation (UVGI)-based FFR decontamination pathway, utilizing a home-built UVGI array assembled entirely with previously existing components available at our institution. We provide recommendations on the construction of similar systems, as well as guidance and strategies towards successful institutional implementation of FFR decontamination.