Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT).

BACKGROUND: Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics. METHODS: In DISRUPT, a superiority-design phase 3 study, patients with S. aureus bacteremia/endocarditis were randomly assigned to receive a single dose of IV exebacase or placebo in addition to standard-of-care antibiotics. The primary efficacy outcome was clinical response at Day 14 in the MRSA population. RESULTS: A total of 259 patients were randomized before the study was stopped for futility based on the recommendation of the unblinded Data Safety Monitoring Board. Clinical response rates at Day 14 in the MRSA population (n = 97) were 50.0% (exebacase + antibiotics; 32/64) vs. 60.6% (antibiotics alone; 20/33) (P = 0.392). Overall, rates of adverse events were similar across groups. No adverse events of hypersensitivity related to exebacase were reported. CONCLUSIONS: Exebacase + antibiotics failed to improve clinical response at Day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of Day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis.

Disinfection of vascular catheter connectors that are protected by antiseptic caps is unnecessary.

OBJECTIVE: Determination of whether vascular catheter disinfecting antiseptic-containing caps alone are effective at decreasing microbial colonization of connectors compared to antiseptic-containing caps plus a 5-second alcohol manual disinfection. SETTING: The study was conducted in a 718-bed, tertiary-care, academic hospital. PATIENTS: A convenience sample of adult patients across intensive care units and acute care wards with peripheral and central venous catheters covered with antiseptic-containing caps. METHODS: Quality improvement study completed over 5 days. The standard-of-care group consisted of catheter connectors with antiseptic-containing caps cleaned with a 5-second alcohol wipe scrub prior to culture. The comparison group consisted of catheter connectors with antiseptic-containing caps without a 5-second alcohol wipe scrub prior to culture. The connectors were pressed directly onto blood agar plates and incubated. Plates were assessed for growth after 48-72 hours. RESULTS: In total, 356 catheter connectors were cultured: 165 in the standard-of-care group, 165 in the comparison group, and 26 catheters connectors without an antiseptic-containing cap, which were designated as controls. Overall, 18 catheter connectors (5.06%) yielded microbial growth. Of the 18 connectors with microbial growth, 2 (1.21%) were from the comparison group, 1 (0.61%) was from the standard-of-care group, and 15 were controls without an antiseptic-containing cap. CONCLUSIONS: Bacterial colonization rates were similar between the catheter connectors cultured with antiseptic-containing caps alone and catheter connectors with antiseptic-containing caps cultured after a 5-second scrub with alcohol. This finding suggests that the use of antiseptic-containing caps precludes the need for additional disinfection.

Hospital return-to-work practices for healthcare providers infected with severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

A survey of academic medical-center hospital epidemiologists indicated substantial deviation from Centers for Disease Control and Prevention guidance regarding healthcare providers (HCPs) recovering from coronavirus disease 2019 (COVID-19) returning to work. Many hospitals continue to operate under contingency status and have HCPs return to work earlier than recommended.

Clinical outcomes associated with blood-culture contamination are not affected by utilization of a rapid blood-culture identification system.

OBJECTIVE: Contaminated blood cultures result in extended hospital stays and extended durations of antibiotic therapy. Rapid molecular-based blood culture testing can speed positive culture detection and improve clinical outcomes, particularly when combined with an antimicrobial stewardship program. We investigated the impact of a multiplex polymerase chain reaction (PCR) FilmArray Blood Culture Identification (BCID) system on clinical outcomes associated with contaminated blood cultures. METHODS: We conducted a retrospective cohort study involving secondary data analysis at a single institution. In this before-and-after study, patients with contaminated blood cultures in the period before PCR BCID was implemented (ie, the pre-PCR period; n = 305) were compared to patients with contaminated blood cultures during the period after PCR BCID was implemented (ie, the post-PCR implementation period; n = 464). The primary exposure was PCR status and the main outcomes of the study were length of hospital stay and days of antibiotic therapy. RESULTS: We did not detect a significant difference in adjusted mean length of hospital stay before (10.8 days; 95% confidence interval [CI], 9.8-11.9) and after (11.2 days; 95% CI, 10.2-12.3) the implementation of the rapid BCID panel in patients with contaminated blood cultures (P = .413). Likewise, adjusted mean days of antibiotic therapy between patients in pre-PCR group (5.1 days; 95% CI, 4.5-5.7) did not significantly differ from patients in post-PCR group (5.3 days; 95% CI, 4.8-5.9; P = .543). CONCLUSION: The introduction of a rapid PCR-based blood culture identification system did not improve clinical outcomes, such as length of hospital stay and duration of antibiotic therapy, in patients with contaminated blood cultures.

Nosocomial outbreak of SARS-CoV-2 delta variant among vaccinated healthcare workers and immunocompromised patients on a solid-organ transplant unit: Complexities of an epidemiologic and genomic investigation.

In September 2021, a cluster of 6 patients with nosocomial coronavirus disease 2019 (COVID-19) were identified in a transplant unit. A visitor and 11 healthcare workers also tested positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). Genomic sequencing identified 3 separate introductions of SARS-CoV-2 with related transmission among the identified patients and healthcare workers.

Patient-specific risk factors contributing to blood culture contamination.

Objective: Contaminated blood cultures result in extended hospital stays and unnecessary antibiotic therapy. Patient-specific factors associated with blood culture contamination remain largely unexplored. Identifying patients at higher risk of blood culture contamination could alert healthcare providers to take extra precautionary measures to limit contamination in these patients, and thereby prevent associated adverse outcomes. We sought to identify patient-related factors that contribute to blood culture contamination in hospitalized patients. Design and setting: We conducted a secondary data analysis of a retrospective cohort study at an academic medical center. Patients: Study participants included 19,255 adult patients who had blood culture(s) performed during a hospital admission between June 2014 and December 2016. Methods: Data were analyzed to evaluate risk factors for blood culture contamination using logistic regression. Results: Among adult patients, we identified 464 contaminated episodes and 11,010 negative blood-culture episodes. Chronic obstructive pulmonary disease (adjusted odds ratio [AOR], 1.67; 95% confidence interval [CI], 1.20-2.34) and stay in an intensive care unit (ICU) during an admission (AOR, 1.41; 95% CI, 1.14-1.74) were associated with blood culture contamination. Other risk factors included race, body mass index, and admission from the emergency department. Subgroup analyses of patients admitted from the emergency department showed similar results. Conclusions: We identified patient-specific factors that increase the odds of false-positive blood cultures. By introducing mitigation strategies to limit contamination in patients with these risk factors, it may be possible to reduce the adverse clinical impact of blood culture contamination.

Evaluation of cycle threshold values at deisolation.

The decision to discontinue isolation in hospitalized patients with persistently positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) molecular testing is nuanced. Improvement in clinical status should be evaluated with expert consultation when considering whether discontinuation of isolation is appropriate. The cycle threshold value may serve as a useful adjunct to this decision-making process.

Improving antibiotic prescribing for acute bronchitis in the ambulatory setting using a multifaceted approach.

Antibiotics are frequently prescribed inappropriately for acute respiratory infections in the outpatient setting. We report the implementation of a multifaceted outpatient antimicrobial stewardship initiative resulting in a 12.3% absolute reduction of antibiotic prescribing for acute bronchitis in primary care clinics receiving active interventions.

Prevention of Central-Line Associated Bloodstream Infections: 2021 Update.

Despite a large volume of research in prevention, central line-associated bloodstream infections and catheter-related bloodstream infections continue to cause significant morbidity, mortality, and increased health care costs. Strategies in prevention, including decision about catheter placement, insertion bundles, adherence to standard of care guidelines, and technologic innovations, shown to decrease rates of catheter-related bloodstream infections and central line-associated bloodstream infections are described in this update. The coronavirus disease 2019 pandemic has resulted in increased health care-acquired infections, including central line-associated bloodstream infections.

Improving hospital-based point-of-care ultrasound cleaning practices using targeted interventions: a pre-post study.

BACKGROUND: Point-of-care ultrasound (POCUS) devices are becoming more widely used in healthcare and have the potential to act as fomites. The objective of this project was to study the thoroughness of cleaning of POCUS machines before and after a quality improvement initiative. We designed a mixed-methods, pre/post study which took place over the course of one year at a university-affiliated health center. Cleaning rates of four ultrasound machines used by hospital medicine and critical care medicine services were evaluated using fluorescent marking. Interventions targeted physicians' knowledge of best practices and improved access to cleaning supplies. Pre- and post-intervention cleaning rates were compared using a generalized linear model. The impact of the corona virus disease of 2019 (COVID-19) pandemic on baseline cleaning rates was also evaluated. Physicians' attitudes and knowledge of cleaning practices were evaluated via unpaired pre/post surveys. RESULTS: There was significant improvement in thoroughness of cleaning following intervention (pre 0.62, SE 0.05; post 0.89, SE 0.07), p < 0.0001). There was no difference in baseline cleaning rates before (0.63, SE 0.09) and after (0.61, SE 0.1) the onset of the COVID-19 pandemic (p = 0.78). Post-intervention surveying found improved understanding of guideline-based cleaning practice, better performance on knowledge-based questions, and fewer reported barriers to machine cleaning. CONCLUSION: Thoroughness of cleaning of POCUS machines can be improved with practical interventions that target knowledge and access to cleaning supplies.

Antibacterial use in the age of SARS-CoV-2.

BACKGROUND: Balancing the use of antibacterial therapy against selection for resistance in this pandemic era has introduced both questions and guidelines. In this project, we explored how prescription of empirical antibacterial therapy differs between those with and without SARS-CoV-2 infection. METHODS: Multivariable logistic regression was used to determine whether COVID-19 status and other factors play a role in the prescription of antibacterial therapy in an inpatient setting at a large referral academic medical centre. Further analysis was conducted to determine whether these factors differ between those testing positive and negative for SARS-CoV-2. RESULTS: Of 405 patients in the cohort, 175 received antibacterial therapy and 296 tested positive for SARS-CoV-2. A positive SARS-CoV-2 test carried an OR of 0.3 (95% CI: 0.19, 0.49) for receiving antibacterial treatment in the first 48 h after admission (P < 0.0001) adjusting for age and procalcitonin results. Patients were 1% and 3% less likely to receive antibacterials for every year increase in age in the overall group and among those testing negative for SARS-CoV-2, respectively. Younger age was found to impact use of antibacterial therapy in both the overall analysis as well as the SARS-CoV-2 negative subgroup (P = 0.03 and P = 0.01). High procalcitonin values were found to be associated with increased antibacterial therapy use in both the overall and stratified analyses. CONCLUSIONS: Antibacterial therapy prescription differs by COVID-19 disease status, and procalcitonin results are most highly associated with antibacterial use across strata.

A Practical Approach to Filtering Facepiece Respirator Decontamination and Reuse: Ultraviolet Germicidal Irradiation.

Purpose of review: Prior outbreaks of respiratory viruses have demonstrated the need for adequate personal protective equipment (PPE) for healthcare workers, particularly filtering facepiece respirators (FFR). Due to shortfalls of PPE during the SARS CoV-2 pandemic, the need for FFR decontamination and reuse (FFR-DR) strategies is paramount. This paper aims to discuss primary decontamination strategies, with an in-depth analysis of ultraviolet germicidal irradiation (UVGI), arriving at the decontamination strategy utilized at the Nebraska Medical Center (NMC). Methods: Review of the primary literature in regard to FFR-DR as well as a synopsis of the current protocol for FFR-DR at NMC. Recent findings: UVGI demonstrates effective decontamination of multiple pathogens-including several human respiratory viruses-while maintaining mask integrity and filtering capacity. UVGI was associated with degradation of strap integrity at higher doses than that utilized for decontamination or with reuse beyond 20 times. Summary: UVGI effectively decontaminates N95 FFRs without significant reduction to fit or strap integrity and can be employed as a strategy for FFR-DR in times of emergency.

The Effect of Insurance on Appropriate Hospital Discharge Antibiotics for Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: Inappropriate antimicrobial therapy of Staphylococcus aureus bacteremia (SAB) is associated with worsened outcomes. The impact of insurance coverage on appropriate selection of antibiotics at discharge is poorly understood. METHODS: We used a retrospective cohort design to evaluate whether patients with SAB at a large academic medical center over 2 years were more likely to receive inappropriate discharge antibiotics, depending on their category of insurance. Insurance was classified as Medicare, Medicaid, commercial, and none. Logistic regression was used to determine the odds of being prescribed inappropriate discharge therapy. RESULTS: A total of 273 SAB patients met inclusion criteria, with 14.3% receiving inappropriate discharge therapy. In the unadjusted model, there was 2-fold increased odds of being prescribed inappropriate therapy for Medicare, Medicaid, and no insurance, compared with commercial insurance, respectively (odds ratio [OR], 2.08; 95% CI, 1.39-3.13). After controlling for discharge with nursing assistance and infectious diseases (ID) consult, there were 1.6-fold increased odds (OR, 1.57; 95% CI, 0.998-2.53; P = .064) of being prescribed inappropriate therapy for Medicare, Medicaid, and no insurance, compared with commercial insurance, respectively. We found that being discharged home without nursing assistance resulted in 4-fold increased odds of being prescribed inappropriate therapy (OR, 4.16; 95% CI, 1.77-9.77; P < .01), and failing to consult an ID team resulted in 59-fold increased odds of being prescribed inappropriate therapy (OR, 59.2; 95% CI, 11.4-306.9; P < .001). CONCLUSIONS: We found strong evidence that noncommercial insurance, discharging without nursing assistance, and failure to consult ID are risk factors for being prescribed inappropriate antimicrobial therapy for SAB upon hospital discharge.

Utility of repeat testing for COVID-19: Laboratory stewardship when the stakes are high.

As the coronavirus disease 2019 (COVID-19) continues to circulate, testing strategies are of the utmost importance. Given national shortages of testing supplies, personal protective equipment, and other hospital resources, diagnostic stewardship is necessary to aid in resource management. We report the low utility of serial testing in a low-prevalence setting.

Clinical consequences of contaminated blood cultures in adult hospitalized patients at an institution utilizing a rapid blood-culture identification system.

OBJECTIVE: To assess the clinical impact of contaminated blood cultures in hospitalized patients during a period when rapid diagnostic testing using a FilmArray Blood Culture Identification (BCID) panel was in use. DESIGN: Retrospective cohort study. SETTING: Single academic medical center. PARTICIPANTS: Patients who had blood culture(s) performed during an admission between June 2014 and December 2016. METHODS: Length of hospital stay and days of antibiotic therapy were assessed in relation to blood-culture contamination using generalized linear models with univariable and multivariable analyses. RESULTS: Among 11,474 patients who had blood cultures performed, the adjusted mean length of hospital stay for patients with contaminated blood-culture episodes (N = 464) was 12.3 days (95% confidence interval [CI], 11.4-13.2) compared to 11.5 days (95% CI, 11.0-11.9) for patients (N = 11,010) with negative blood-culture episodes (P = .032). The adjusted mean durations of antibiotic therapy for patients with contaminated and negative blood-culture episodes were 6.0 days (95% CI, 5.3-6.7) and 5.2 days (95% CI, 4.9-5.4), respectively (P = .011). CONCLUSIONS: Despite the use of molecular-based, rapid blood-culture identification, contamination of blood cultures continues to result in prolonged hospital stay and unnecessary antibiotic therapy in hospitalized patients.

Effect of an external urinary collection device for women on institutional catheter utilization and catheter-associated urinary tract infections.

External urinary collection devices (EUCDs) may reduce indwelling catheter usage and catheter-associated urinary tract infections (CAUTIs). In this retrospective quasi-experimental study, we demonstrated that EUCD implementation in women was associated with significantly decreased indwelling catheter usage and a trend (P = .10) toward decreased CAUTI per 1,000 patient days.