Variants of Concern Are Overrepresented Among Postvaccination Breakthrough Infections of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Washington State.

Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOCs) and had a median Ct of 20.2 (IQR, 17.1-23.3). When compared with 5174 contemporaneous samples sequenced in our laboratory, VOCs were significantly enriched among breakthrough infections (P < .05).

Gradually Increasing Surgical Site Infection Prevention Bundle with Monitoring of Potentially Preventable Infections Resulting in Decreasing Overall Surgical Site Infection Rate.

Objective: Reduction of surgical site infection. Methods: Retrospective evaluation of a surgical infection prevention program consisting of the gradual introduction of specific infection prevention methods and a surveillance system identifying and reporting on potentially preventable surgical site infections as defined by the omission of a preventive method. Setting: A university tertiary referral medical center. Results: The sequential introduction of infection prevention elements in the bundle resulted in a fluctuating rate of potentially preventable surgical site infections simultaneously with a slow, gradual reduction of the clean wound SSI rate. Conclusions: Change in a complex, multidisciplinary environment such as an inpatient surgical unit happens gradually and requires focused attention and input from all involved professionals.

Anti-SARS-CoV-2 Antibody Levels Measured by the AdviseDx SARS-CoV-2 Assay Are Concordant with Previously Available Serologic Assays but Are Not Fully Predictive of Sterilizing Immunity.

With the availability of widespread SARS-CoV-2 vaccination, high-throughput quantitative anti-spike protein serological testing will likely become increasingly important. Here, we investigated the performance characteristics of the recently FDA-authorized semiquantitative anti-spike protein AdviseDx SARS-CoV-2 IgG II assay compared to the FDA-authorized anti-nucleocapsid protein Abbott Architect SARS-CoV-2 IgG, Roche Elecsys anti-SARS-CoV-2-S, EuroImmun anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA), and GenScript surrogate virus neutralization assays and examined the humoral response associated with vaccination, natural protection, and vaccine breakthrough infection. The AdviseDx assay had a clinical sensitivity at 14 days after symptom onset or 10 days after PCR detection of 95.6% (65/68; 95% confidence interval [CI], 87.8 to 98.8%), with two discrepant individuals seroconverting shortly thereafter. The AdviseDx assay demonstrated 100% positive percent agreement with the four other assays examined using the same symptom onset or PCR detection cutoffs. Using a recently available WHO international standard for anti-SARS-CoV-2 antibody, we provide assay unit conversion factors to international units for each of the assays examined. We performed a longitudinal survey of healthy vaccinated individuals, finding that median AdviseDx immunoglobulin levels peaked 7 weeks after first vaccine dose at approximately 4,000 IU/ml. Intriguingly, among the five assays examined, there was no significant difference in antigen binding level or neutralizing activity between two seropositive patients protected against SARS-CoV-2 infection in a previously described fishing vessel outbreak and five health care workers who experienced vaccine breakthrough of SARS-CoV-2 infection, all with variants of concern. These findings suggest that protection against SARS-CoV-2 infection cannot currently be predicted exclusively using in vitro antibody assays against wild-type SARS-CoV-2 spike. Further work is required to establish protective correlates for SARS-CoV-2 infection.

Improving Appropriate Diagnosis of Clostridioides difficile Infection Through an Enteric Pathogen Order Set With Computerized Clinical Decision Support: An Interrupted Time Series Analysis.

BACKGROUND: Inappropriate testing for Clostridioides difficile leads to overdiagnosis of C difficile infection (CDI). We determined the effect of a computerized clinical decision support (CCDS) order set on C difficile polymerase chain reaction (PCR) test utilization and clinical outcomes. METHODS: This study is an interrupted time series analysis comparing C difficile PCR test utilization, hospital-onset CDI (HO-CDI) rates, and clinical outcomes before and after implementation of a CCDS order set at 2 academic medical centers: University of Washington Medical Center (UWMC) and Harborview Medical Center (HMC). RESULTS: Compared with the 20-month preintervention period, during the 12-month postimplementation of the CCDS order set, there was an immediate and sustained reduction in C difficile PCR test utilization rates at both hospitals (HMC, -28.2% [95% confidence interval {CI}, -43.0% to -9.4%], P = .005; UWMC, -27.4%, [95% CI, -37.5% to -15.6%], P < .001). There was a significant reduction in rates of C difficile tests ordered in the setting of laxatives (HMC, -60.8% [95% CI, -74.3% to -40.1%], P < .001; UWMC, -37.3%, [95% CI, -58.2% to -5.9%], P = .02). The intervention was associated with an increase in the C difficile test positivity rate at HMC (P = .01). There were no significant differences in HO-CDI rates or in the proportion of patients with HO-CDI who developed severe CDI or CDI-associated complications including intensive care unit transfer, extended length of stay, 30-day mortality, and toxic megacolon. CONCLUSIONS: Computerized clinical decision support tools can improve C difficile diagnostic test stewardship without causing harm. Additional studies are needed to identify key elements of CCDS tools to further optimize C difficile testing and assess their effect on adverse clinical outcomes.

How Clean Is the Linen at My Hospital? The Mucorales on Unclean Linen Discovery Study of Large United States Transplant and Cancer Centers.

Mucormycosis outbreaks have been linked to contaminated linen. We performed fungal cultures on freshly-laundered linens at 15 transplant and cancer hospitals. At 33% of hospitals, the linens were visibly unclean. At 20%, Mucorales were recovered from >10% of linens. Studies are needed to understand the clinical significance of our findings.

10-year trends in vancomycin-resistant enterococci among allogeneic hematopoietic cell transplant recipients.

OBJECTIVES: We examined VRE colonization, bacteremia (VREB) incidence and outcomes within 100 days of allogeneic hematopoietic cell transplantation (HCT). METHODS: HCT recipients screened for VRE were assessed, and colonization and VREB incidence compared over time using linear regression. Cox proportional hazards models were constructed to assess the relationship between mortality, pre-HCT colonization, and underlying disease. RESULTS: Of 1492 HCT recipients, 204 (14%) patients were colonized pre-HCT, while 90 (6%) acquired colonization post-HCT. Forty-two patients (2.8%) developed VREB within 100 days post-HCT; the majority, 32 (76%), were previously colonized. The cumulative incidence of VREB was 2.9 per 10,000 patient-days. Over the study period there were no significant changes in incidence of VRE colonization or VREB despite a number of interventions (p > 0.1). Patients with pre-HCT colonization had increased mortality compared to non-colonized patients (HR 2.1; 95% CI: 1.5, 3.3). CONCLUSIONS: We found a low burden of VRE at our center with no significant changes observed over a 10-year study period. VRE, while responsible for substantial resource consumption from routine screening and isolation, was an infrequent cause of bacteremia.

Seasonal clustering of sinopulmonary mucormycosis in patients with hematologic malignancies at a large comprehensive cancer center.

Background: Invasive Mucorales infections (IMI) lead to significant morbidity and mortality in immunocompromised hosts. The role of season and climatic conditions in case clustering of IMI remain poorly understood. Methods: Following detection of a cluster of sinopulmonary IMIs in patients with hematologic malignancies, we reviewed center-based medical records of all patients with IMIs and other invasive fungal infections (IFIs) between January of 2012 and August of 2015 to assess for case clustering in relation to seasonality. Results: A cluster of 7 patients were identified with sinopulmonary IMIs (Rhizopus microsporus/azygosporus, 6; Rhizomucor pusillus, 1) during a 3 month period between June and August of 2014. All patients died or were discharged to hospice. The cluster was managed with institution of standardized posaconazole prophylaxis to high-risk patients and patient use of N-95 masks when outside of protected areas on the inpatient service. Review of an earlier study period identified 11 patients with IMIs of varying species over the preceding 29 months without evidence of clustering. There were 9 total IMIs in the later study period (12 month post-initial cluster) with 5 additional cases in the summer months, again suggesting seasonal clustering. Extensive environmental sampling did not reveal a source of mold. Using local climatological data abstracted from National Centers for Environmental Information the clusters appeared to be associated with high temperatures and low precipitation. Conclusions: Sinopulmonary Mucorales clusters at our center had a seasonal variation which appeared to be related to temperature and precipitation. Given the significant mortality associated with IMIs, local climatic conditions may need to be considered when considering center specific fungal prevention and prophylaxis strategies for high-risk patients.

Legionnaires' disease in transplant recipients: A 15-year retrospective study in a tertiary referral center.

Legionnaires' disease (LD) can be fatal among high-risk transplant recipients. To understand the epidemiology of LD, we reviewed 15-year longitudinal data from a center in Seattle, Washington that cares for both solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients. We identified all laboratory-confirmed LD and extracted data on species, diagnostic modalities, clinical presentation, management, and outcomes from medical records. Among 32 patients with LD, transplant recipients made up the majority of diagnoses (22, 69%; SOT 10, HCT 12). Approximately 0.8% of transplant recipients who underwent Legionella-specific testing were positive. Non-pneumophila Legionella species (LNLP), which are not detected by urinary antigen test, accounted for half the cases, led by Legionella micdadei (32%). The severity and outcome between Legionella pneumophila and LNLP infections were similar (attributed mortality, 36% vs 27%); all LNLP deaths occurred in transplant recipients with L. micdadei. The clinical and radiological features mimicked other opportunistic pathogens; 32% (n=7) were not on empiric treatment at the time of diagnosis. These data add to the emerging literature describing the importance of LD and highlight the need for both routine Legionella testing on transplant recipients with pulmonary findings and empiric Legionella-active antibiotic therapy.

A collaborative, systems-level approach to eliminating healthcare-associated MRSA, central-line-associated bloodstream infections, ventilator-associated pneumonia, and respiratory virus infections.

To achieve sustainable reductions in healthcare-associated infections (HAIs), the University of Washington Medical Center (UWMC) deployed a collaborative, systems-level initiative. With the sponsorship of senior leadership, multidisciplinary teams were established to address healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA), central-line-associated bloodstream infections (CLABSI), ventilator-associated pneumonia (VAP), and respiratory virus infections. The goal of the initiative was to eliminate these four HAIs among medical center inpatients by 2012. In the first 24 months of the project, the number of healthcare-associated MRSA cases decreased 58%; CLABSI cases decreased 54%. Staff and provider compliance with infection prevention measures improved and remained strong, for example, 96% compliance with hand hygiene, 98% compliance with the recommended influenza vaccination program, and 100% compliance with the VAP bundle. Achieving these results required an array of coordinated, systems-level interventions. Critical project success factors were believed to include creating organizational alignment by declaring eliminating HAIs as an organizational breakthrough goal, having the organization's executive leadership highly engaged in the project, coordination by an experienced and effective project leader and manager, collaboration by multidisciplinary project teams, and promoting transparency of results across the organization.

The emergence of Clostridium difficile infection among peripartum women: a case-control study of a C. difficile outbreak on an obstetrical service.

OBJECTIVE: An outbreak of 20 peripartum Clostridium difficile infections (CDI) occurred on the obstetrical service at the University of Washington Medical Center (UWMC) between April 2006 and June 2007. In this report, we characterize the clinical manifestations, describe interventions that appeared to reduce CDI, and determine potential risk factors for peripartum CDI. METHODS: An investigation was initiated after the first three peripartum CDI cases. Based on the findings, enhanced infection control measures and a modified antibiotic regimen were implemented. We conducted a case-control study of peripartum cases and unmatched controls. RESULTS: During the outbreak, there was an overall incidence of 7.5 CDI cases per 1000 deliveries. Peripartum CDI infection compared to controls was significantly associated with cesarean delivery (70% versus 34%; P=0.03), antibiotic use (95% versus 56%; P=0.001), chorioamnionitis (35% versus 5%; P=0.001), and the use of the combination of ampicillin, gentamicin, and clindamycin (50% versus 3%; P<0.001). Use of combination antibiotics remained a significant independent risk factor for CDI in the multivariate analysis. CONCLUSIONS: The outbreak was reduced after the implementation of multiple infection control measures and modification of antibiotic use. However, sporadic CDI continued for 8 months after these measures slowed the outbreak. Peripartum women appear to be another population susceptible to CDI.

Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime.

BACKGROUND: The objective of the current study was to compare the efficacy and safety of imipenem and cefepime in the treatment of adult patients with cancer who had fever and neutropenia requiring hospitalization according to Infectious Disease Society of America criteria. METHODS: In the current prospective randomized clinical trial at a university-affiliated tertiary cancer center, adult patients with cancer who had fever (> or = 38.3 degrees C or > or = 38.0 degrees C for > 2 hours) and neutropenia (< or = 500/mm(3) or < 1000/mm(3) but declining) requiring hospitalization were randomized to receive either cefepime or imipenem. Vancomycin or amikacin was added on suspicion of gram-positive or gram-negative bacterial infection, respectively. RESULTS: Patients who received an imipenem regimen or a cefepime regimen were comparable in terms of age, gender, underlying malignancy, prior transplantation, degree and trend of neutropenia, and presence of central venous catheters (P > or = 0.3). An intent-to-treat analysis showed a 68% response rate to the imipenem regimen, compared with a 75% response rate to the cefepime regimen (P = 0.2). The rates of antibiotic-related adverse events and superinfections also were comparable (P = 0.6). There was no difference in response among patients who received imipenem or cefepime alone compared with patients who also received vancomycin or amikacin (P = 1.0). Leukemia was the only independent risk factor associated with a poor outcome (odds ratio, 4.6; 95% confidence interval, 1.9-10.7; P < 0.0001). CONCLUSIONS: Imipenem and cefepime had similar efficacy and safety profiles in the treatment of adult cancer patients with fever and neutropenia who required hospitalization. The addition of either vancomycin or amikacin may not be necessary.

Epidemiology, molecular mycology, and environmental sources of Fusarium infection in patients with cancer.

OBJECTIVE: To investigate the epidemiology and environmental sources of Fusarium infections in patients with cancer. DESIGN: Retrospective case-control study conducted following surveillance environmental cultures and DNA analysis of isolated organisms. SETTING: A tertiary-care, university cancer center. METHODS: In 1996 and 1997, environmental cultures were performed on air samples and water systems. A retrospective chart review was performed for 70 patients with cancer identified with fusariosis between 1987 and 1997. Patients with fusariosis were compared with 49 uninfected control patients who occupied hospital rooms with positive environmental cultures for Fusarium. With the use of random amplification of polymorphic DNA, organisms isolated from infected patients were compared with environmental organisms. RESULTS: Most of the patients with Fusarium (40, 57%) were infected on or within 3 days of admission, indicating community rather than nosocomial acquisition. Patients were comparable in terms of underlying immunocompromised status to 49 uninfected control patients. However, the duration from admission to infection in the patients with fusariosis tended to be shorter than the duration from admission to discharge in the exposed control patients (P = .06). Water cultured from the hospital tanks and from sinks and water fountains was negative for Fusarium. With the use of polymerase chain reaction, environmental isolates did not match clinical ones. Quantitative air sampling showed that the quantitative outdoor Fusarium levels were eightfold higher than the indoor levels. During the rainy summer season, outdoor air concentrations of Fusarium were at their highest, coinciding with the peak incidence of fusariosis at our center. CONCLUSION: The most likely source of fusariosis was the external environment rather than nosocomial sources, such as water.