Modeling relaxed policies for discontinuation of methicillin-resistant Staphylococcus aureus contact precautions.

OBJECTIVE: To evaluate the economic costs of reducing the University of Virginia Hospital's present "3-negative" policy, which continues methicillin-resistant Staphylococcus aureus (MRSA) contact precautions until patients receive 3 consecutive negative test results, to either 2 or 1 negative. DESIGN: Cost-effective analysis. SETTINGS: The University of Virginia Hospital. PATIENTS: The study included data from 41,216 patients from 2015 to 2019. METHODS: We developed a model for MRSA transmission in the University of Virginia Hospital, accounting for both environmental contamination and interactions between patients and providers, which were derived from electronic health record (EHR) data. The model was fit to MRSA incidence over the study period under the current 3-negative clearance policy. A counterfactual simulation was used to estimate outcomes and costs for 2- and 1-negative policies compared with the current 3-negative policy. RESULTS: Our findings suggest that 2-negative and 1-negative policies would have led to 6 (95% CI, -30 to 44; P < .001) and 17 (95% CI, -23 to 59; -10.1% to 25.8%; P < .001) more MRSA cases, respectively, at the hospital over the study period. Overall, the 1-negative policy has statistically significantly lower costs ($628,452; 95% CI, $513,592-$752,148) annually (P < .001) in US dollars, inflation-adjusted for 2023) than the 2-negative policy ($687,946; 95% CI, $562,522-$812,662) and 3-negative ($702,823; 95% CI, $577,277-$846,605). CONCLUSIONS: A single negative MRSA nares PCR test may provide sufficient evidence to discontinue MRSA contact precautions, and it may be the most cost-effective option.

Improving antimicrobial use through better diagnosis: The relationship between diagnostic stewardship and antimicrobial stewardship.

Antimicrobial stewardship programs (ASPs) exist to optimize antibiotic use, reduce selection for antimicrobial-resistant microorganisms, and improve patient outcomes. Rapid and accurate diagnosis is essential to optimal antibiotic use. Because diagnostic testing plays a significant role in diagnosing patients, it has one of the strongest influences on clinician antibiotic prescribing behaviors. Diagnostic stewardship, consequently, has emerged to improve clinician diagnostic testing and test result interpretation. Antimicrobial stewardship and diagnostic stewardship share common goals and are synergistic when used together. Although ASP requires a relationship with clinicians and focuses on person-to-person communication, diagnostic stewardship centers on a relationship with the laboratory and hardwiring testing changes into laboratory processes and the electronic health record. Here, we discuss how diagnostic stewardship can optimize the "Four Moments of Antibiotic Decision Making" created by the Agency for Healthcare Research and Quality and work synergistically with ASPs.

Donor-derived Transmission of Hepatitis A Virus Following Kidney Transplantation: Clinical Course of Two Cases From One Donor.

Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood. Methods: In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. Results: The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. Conclusions: Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548.

Good Long-Term Outcome Following Liver Transplant in a Patient With Common Variable Immunodeficiency Syndrome Despite Multiple Infections and Recurrent Nodular Regenerative Hyperplasia.

Common variable immunodeficiency can be associated with various hepatic conditions, the most common being nodular regenerative hyperplasia. Multiple cases of liver transplant in adults with common variable immunodeficiency have been reported. Here, we report a 51-year-old man with common variable immunodeficiency and noncirrhotic portal hypertension due to nodular regenerative hyperplasia who underwent liver transplant. The patient received tacrolimus/steroid immunosuppression and remained rejection free; however, he developed cytomegalovirus infection, disseminated nocardiosis, Pseudomonas pneumonia, and Clostridioides difficile- associated colitis. All infections were successfully managed. The graft was well functioning after 18 months; however, alkaline phosphatase remained elevated and a liver biopsy showed evidence of recurrent nodular regenerative hyperplasia. The patient was started on a steroid taper, which led to normalization of the alkaline phosphatase. Two years later, a repeat biopsy confirmed recurrent nodular regenerative hyperplasia. Immunosuppression was kept low, and intravenous immunoglobulin infusions were continued. More than 10 years later, the patient is alive with a functioning graft. This case emphasizes that intensified prophylaxis for infections and less intense immunosuppression may be strategies to enable long-term survival in liver transplant recipients with common variable immunodeficiency and nodular regenerative hyperplasia relapse despite recently reported poor outcomes in this patient population.

Eliminated routine postorthotopic liver transplant antibiotics in uncomplicated patients leads to equivalent safety outcomes.

Objective: The purpose of this retrospective study was to evaluate safety and efficacy end points of a postoperative antibiotic prophylaxis protocol in liver transplant (LT) patients, which was revised to limit antibiotic use. Methods: In the routine antibiotics group (RA), patients routinely received prophylactic antibiotics for around 3 days postoperatively for a variety of rationales, versus the limited antibiotics group (LA), in which patients received antibiotics for the treatment of secondary peritonitis. Patients were included if they were 18 or older and underwent liver transplant between January 2016 and September 2019. In total, 216 patients remained after exclusion: 118 patients in the RA group and 98 patients in the LA group. Results: We detected a significant difference in the primary end point of postoperative antibiotic days of therapy. The median days of therapy was 2 for the RA group and 0 for the LA group (P < 0.005). Significantly fewer patients received only intraoperative antibiotics in the RA group versus the LA group: 42 (35.6%) versus 76 (73.5%) respectively (P < .005). There was no significant difference in secondary or safety outcomes, including surgical site infections. Conclusions: This study provides evidence that limiting the duration of prophylactic antibiotics postoperatively and treating most patients with only intraoperative antibiotics is safe.

Validation of Clinical Risk Models for Clostridioides difficile-Attributable Outcomes.

Clostridioides difficile is the leading health care-associated pathogen, leading to substantial morbidity and mortality; however, there is no widely accepted model to predict C. difficile infection severity. Most currently available models perform poorly or were calibrated to predict outcomes that are not clinically relevant. We sought to validate six of the leading risk models (Age Treatment Leukocyte Albumin Serum Creatinine (ATLAS), C. difficile Disease (CDD), Zar, Hensgens, Shivashankar, and C. difficile Severity Score (CDSS)), guideline severity criteria, and PCR cycle threshold for predicting C. difficile-attributable severe outcomes (inpatient mortality, colectomy/ileostomy, or intensive care due to sepsis). Models were calculated using electronic data available within ±48 h of diagnosis (unavailable laboratory measurements assigned zero points), calibrated using a large retrospective cohort of 3,327 inpatient infections spanning 10 years, and compared using receiver operating characteristic (ROC) and precision-recall curves. ATLAS achieved the highest area under the ROC curve (AuROC) of 0.781, significantly better than the next best performing model (Zar 0.745; 95% confidence interval of AuROC difference 0.0094-0.6222; P = 0.008), and highest area under the precision-recall curve of 0.232. Current IDSA/SHEA severity criteria demonstrated moderate performance (AuROC 0.738) and PCR cycle threshold performed the worst (0.531). The overall predictive value for all models was low, with a maximum positive predictive value of 37.9% (ATLAS cutoff ≥9). No clinical model performed well on external validation, but ATLAS did outperform other models for predicting clinically relevant C. difficile-attributable outcomes at diagnosis. Novel markers should be pursued to augment or replace underperforming clinical-only models.

Influence of critically appraising exemption requests from healthcare personnel along a spectrum of influenza vaccine hesitancy.

OBJECTIVES: This study was performed to assess whether an intervention for critically appraising influenza vaccine exemption requests from healthcare personnel (HCP) affected (1) the overall rate of influenza vaccine exemption within a healthcare institution and/or (2) the rates of postintervention vaccine acceptance among those who inconsistently request exemption from annual vaccination and those who consistently request exemption from vaccination. DESIGN: Retrospective, before-and-after intervention study. SETTING: We conducted the study at a single academic medical center. PARTICIPANTS: This study included 29,663 HCP. METHODS: Between 2010 and 2019, HCP were permitted to request an exemption from influenza vaccination without critical appraisal of exemption requests. After January 2019, medical center policy required critical appraisal of exemption requests. Of those employed 3 or more years who requested an exemption at least once during the preintervention period (n = 1,177), those with unchanging exemption reasons annually were termed "consistent exempters." Those who changed reasons or accepted vaccination n ≥ 1 times were termed "inconsistent exempters." RESULTS: The overall exemption rate from influenza vaccine decreased from 3.8% to 1.2% (P < .001; N = 29,663) after the intervention. Of those requesting exemption at least once before the intervention, 329 (28.0%) of 1,177 were consistent exempters and 878 (72.0%) were inconsistent exempters. Of inconsistent exempters employed after the intervention, 442 (88.9%) of 497 accepted vaccine postintervention compared with 118 (59.6%) of 198 consistent exempters (P < .001). Of all exempters who changed from exemption to acceptance after the intervention, 442 (78.9%) of 560 were inconsistent exempters. CONCLUSIONS: Critical appraisal of HCP exemption requests promotes influenza vaccine acceptance, and acceptance by inconsistent exempters drives the effect of the intervention. Analysis of changes in annual exemption requests represents a novel objective method for describing those on the spectrum of vaccine hesitancy.

Propensity-Matched Cost of Clostridioides difficile Infection Overdiagnosis.

BACKGROUND: Clostridioides difficile is the leading health care-associated pathogen, but clinicians lack a test that can reliably differentiate colonization from infection. Health care costs attributed to C. difficile are substantial, but the economic burden associated with C. difficile false positives is poorly understood. METHODS: A propensity score matching model for cost per hospitalization was developed to estimate the costs of both true infection and false positives. Predictors of C. difficile positivity used to estimate the propensity score were age, Charlson comorbidity index, white cell count, and creatinine. We used polymerase chain reaction (PCR) cycle threshold to identify and compare 3 groups: (1) true infection, (2) C. difficile colonization, and (3) C. difficile negative. RESULTS: A positive test was associated with $3018 higher unadjusted hospital cost. Among the 3 comparisons made with propensity-matched negative controls (all positives [+$179; P = .934], true positives [-$1892; P = .100], and colonized positives), only colonization was associated with significantly increased (+$3418; P = .012) cost. Differences in lengths of stay (all positives 0 days, P = .126; true 0 days, P = .919; colonized 1 day, P = .019) appeared to underly cost differences. CONCLUSIONS: In the first C. difficile cost analysis to utilize PCR cycle threshold to differentiate colonization, we found high propensity-matched hospital costs associated with colonized but not true positives. This unexpected finding may be due to misdiagnosis of non-C. difficile diarrhea or unadjusted factors associated with colonization.

Clinical Ordering Practices of the SARS-CoV-2 Antibody Test at a Large Academic Medical Center.

BACKGROUND: The novel severe acute respiratory coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) originated in December 2019 and has now infected almost 5 million people in the United States. In the spring of 2020, private laboratories and some hospitals began antibody testing despite limited evidence-based guidance. METHODS: We conducted a retrospective chart review of patients who received SARS-CoV-2 antibody testing from May 14, 2020, to June 15, 2020, at a large academic medical center, 1 of the first in the United States to provide antibody testing capability to individual clinicians in order to identify clinician-described indications for antibody testing compared with current expert-based guidance from the Infectious Diseases Society of America (IDSA) and the Centers for Disease Control and Prevention (CDC). RESULTS: Of 444 individual antibody test results, the 2 most commonly described testing indications, apart from public health epidemiology studies (n = 223), were for patients with a now resolved COVID-19-compatible illness (n = 105) with no previous molecular testing and for asymptomatic patients believed to have had a past exposure to a person with COVID-19-compatible illness (n = 60). The rate of positive SARS-CoV-2 antibody testing among those indications consistent with current IDSA and CDC guidance was 17% compared with 5% (P < .0001) among those indications inconsistent with such guidance. Testing inconsistent with current expert-based guidance accounted for almost half of testing costs. CONCLUSIONS: Our findings demonstrate a dissociation between clinician-described indications for testing and expert-based guidance and a significantly different rate of positive testing between these 2 groups. Clinical curiosity and patient preference appear to have played a significant role in testing decisions and substantially contributed to testing costs.

Patient Outcomes With Prevented vs Negative Clostridioides difficile Tests Using a Computerized Clinical Decision Support Tool.

BACKGROUND: Overtesting and overdiagnosis of Clostridioides difficile infection are suspected to be common. Reducing inappropriate testing through interventions designed to promote evidence-based diagnostic testing (ie, diagnostic stewardship) may improve C. difficile test utilization. However, the safety of these interventions is not well understood despite the potential risk for missed or delayed diagnoses. METHODS: This retrospective case-control study examined the outcomes of patients admitted to the University of Virginia Medical Center following introduction of a computerized clinical decision support tool without hard-stops designed to reduce inappropriate tests. Outcomes were compared between patients with a prevented C. difficile nucleic acid amplification test and those with a negative result. Chart reviews were performed for patients with a subsequent positive within 7 days, as well as those patients who received C. difficile-active antibiotics after implementation of the computerized clinical decision support tool. RESULTS: Multivariate analysis of 637 cases (490 negative, 147 prevented) showed that a prevented test was not significantly associated with the primary composite outcome (inpatient mortality or intensive care unit transfer) compared with a negative test (adjusted odds ratio, 0.912; P = .747). Fifty-four of 147 (37%) prevented tests were followed by a completed test within 7 days; 11 of these results were positive, resulting in a potential delay in diagnosis. Individual case reviews found that either clinical changes warranted the delay in testing or no adverse events occurred attributable to C. difficile infection. C. difficile treatment without a positive test was not identified. CONCLUSIONS: Diagnostic stewardship of C. difficile testing using computerized clinical decision support may be both safe and effective for reducing inappropriate inpatient testing.

Reduced Clostridioides difficile Tests Among Solid Organ Transplant Recipients Through a Diagnostic Stewardship Bundled Intervention.

BACKGROUND Clostridioides difficile infection (CDI) is a frequent complication of solid organ transplantation, especially in the early post-transplantation period. Overdiagnosis of CDI is likely common in hospitals using nucleic acid amplification testing (NAAT), potentially leading to unnecessary iatrogenesis and cost. Recently, multiple studies have shown that computerized clinical decision support (CCDS)-based interventions can significantly reduce inappropriate C. difficile testing and healthcare facility-onset CDI events across hospitals and health systems. We aimed to determine if a CCDS-based intervention could reduce C. difficile testing and surveillance infection events among recent solid organ transplant recipients, a population at high risk for CDI. We also sought to determine the safety of the CCDS intervention. MATERIAL AND METHODS Quasi-experimental census-adjusted interrupted time-series analyses were performed retrospectively to examine testing and CDI events pre- and post-intervention. Mortality and readmissions rates were also examined. RESULTS A significant 33% relative reduction in tests and a nonsignificant trend towards fewer CDI events were observed following the intervention, without significant differences in mortality or 30-day readmission. A review of patients with positive C. difficile NAATs after prevented tests revealed no specific adverse events attributable to a possible delay in CDI diagnosis. CONCLUSIONS CCDS may be a helpful and safe adjunctive strategy to reduce unnecessary testing in accordance with guideline recommendations among solid organ transplant recipients.

Human Rabies - Virginia, 2017.

On May 9, 2017, the Virginia Department of Health was notified regarding a patient with suspected rabies. The patient had sustained a dog bite 6 weeks before symptom onset while traveling in India. On May 11, CDC confirmed that the patient was infected with a rabies virus that circulates in dogs in India. Despite aggressive treatment, the patient died, becoming the ninth person exposed to rabies abroad who has died from rabies in the United States since 2008. A total of 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis (PEP). The total pharmaceutical cost for PEP (rabies immunoglobulin and rabies vaccine) was approximately $235,000. International travelers should consider a pretravel consultation with travel health specialists; rabies preexposure prophylaxis is warranted for travelers who will be in rabies endemic countries for long durations, in remote areas, or who plan activities that might put them at risk for a rabies exposures.

The Caenorhabditis elegans Model of Legionella Infection.

Caenorhabditis elegans can serve as a simple genetic host to study interactions between Legionellaceae and their hosts and to examine the contribution of specific gene products to virulence and immunity. C. elegans nematodes have several appealing attributes as a host organism; they are inexpensive, have robust genetic analysis tools, have a simple anatomy yet display a wide range of complex behaviors, and, as invertebrates, do not require animal ethics protocols. Use of C. elegans as a host model complements cell-based models, providing additional support and consistency of the experimental data obtained from multiple models. The C. elegans innate immune system functions similarly to that of the alveolar macrophage including the apoptosis [a.k.a. programmed cell death (PCD)] pathway located within the germline. The digestive tract of C. elegans is a primary interface between the innate immune system and bacterial pathogens. Thus, the C. elegans host model provides an alternative approach to investigate L. pneumophila immunopathogenesis, particularly in the view of the recent discovery of Legionella-containing vacuoles within the gonadal tissues of Legionella-colonized nematodes supporting the plausible evolutionary origin of the strategies employed by L. pneumophila to counteract macrophage cellular responses.