To describe the real-world clinical impact of a commercially available plasma cell-free DNA metagenomic next-generation sequencing assay, the Karius test (KT).

We retrospectively evaluated the clinical impact of KT by clinical panel adjudication. Descriptive statistics were used to study associations of diagnostic indications, host characteristics, and KT-generated microbiologic patterns with the clinical impact of KT. Multivariable logistic regression modeling was used to further characterize predictors of higher positive clinical impact.

We evaluated 1000 unique clinical cases of KT from 941 patients between January 1, 2017–August 31, 2023. The cohort included adult (70%) and pediatric (30%) patients. The overall clinical impact of KT was positive in 16%, negative in 2%, and no clinical impact in 82% of the cases. Among adult patients, multivariable logistic regression modeling showed that culture-negative endocarditis (OR 2.3; 95% CI, 1.11–4.53; P .022) and concern for fastidious/zoonotic/vector-borne pathogens (OR 2.1; 95% CI, 1.11–3.76; P .019) were associated with positive clinical impact of KT. Host immunocompromised status was not reliably associated with a positive clinical impact of KT (OR 1.03; 95% CI, 0.83–1.29; P .7806). No significant predictors of KT clinical impact were found in pediatric patients. Microbiologic result pattern was also a significant predictor of impact.

Our study highlights that despite the positive clinical impact of KT in select situations, most testing results had no clinical impact. We also confirm diagnostic indications where KT may have the highest yield, thereby generating tools for diagnostic stewardship.

To understand how healthcare facilities employ contact precautions for patients with multidrug-resistant organisms (MDROs) in the post–coronavirus disease 2019 (COVID-19) era and explore changes since 2014.

Cross-sectional survey.

Emerging Infections Network (EIN) physicians involved in infection prevention or hospital epidemiology.

In September 2022, we sent via email an 8-question survey on contact precautions and adjunctive measures to reduce MDRO transmission in inpatient facilities. We also asked about changes since the COVID-19 pandemic. We used descriptive statistics to summarize data and compared results to a similar survey administered in 2014.

Of 708 EIN members, 283 (40%) responded to the survey and 201 reported working in infection prevention. A majority of facilities (66% and 69%) routinely use contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) respectively, compared to 93% and 92% in 2014. Nearly all (>90%) use contact precautions for Candida auris, carbapenem-resistant Enterobacterales (CRE), and carbapenem-resistant Acinetobacter baumannii. More variability was reported for carbapenem-resistant Pseudomonas aeruginosa and extended-spectrum β-lactamase–producing gram-negative organisms. Compared to 2014, fewer hospitals perform active surveillance for MRSA and VRE. Overall, 90% of facilities used chlorhexidine gluconate bathing in all or select inpatients, and 53% used ultraviolet light or hydrogen peroxide vapor disinfection at discharge. Many respondents (44%) reported changes to contact precautions since COVID-19 that remain in place.

Heterogeneity exists in the use of transmission-based precautions and adjunctive infection prevention measures aimed at reducing MDRO transmission. This variation reflects a need for updated and specific guidance, as well as further research on the use of contact precautions in healthcare facilities.

To determine the frequency and predictors of antibiotic escalation in response to the inpatient sepsis screen at our institution.

Retrospective cohort study.

Two affiliated academic medical centers in Los Angeles, California.

Hospitalized patients aged 18 years and older who had their first positive sepsis screen between January 1, 2019, and December 31, 2019, on acute-care wards.

We described the rate and etiology of antibiotic escalation, and we conducted multivariable regression analyses of predictors of antibiotic escalation.

Of the 576 cases with a positive sepsis screen, antibiotic escalation occurred in 131 cases (22.7%). New infection was the most documented etiology of escalation, with 76 cases (13.2%), followed by known pre-existing infection, with 26 cases (4.5%). Antibiotics were continued past 3 days in 17 cases (3.0%) in which new or existing infection was not apparent. Abnormal temperature (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.91–4.70) and abnormal lactate (aOR, 2.04; 95% CI, 1.28–3.27) were significant predictors of antibiotic escalation. The patient already being on antibiotics (aOR, 0.54; 95% CI, 0.34–0.89) and the positive screen occurred during a nursing shift change (aOR, 0.36; 95% CI, 0.22–0.57) were negative predictors. Pneumonia was the most documented new infection, but only 19 (50%) of 38 pneumonia cases met full clinical diagnostic criteria.

Inpatient sepsis screening led to a new infectious diagnosis in 13.2% of all positive sepsis screens, and the risk of prolonged antibiotic exposure without a clear infectious source was low. Pneumonia diagnostics and lactate testing are potential targets for future stewardship efforts.

To evaluate the impact of discontinuing routine contact precautions (CP) for endemic methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) on hospital adverse events.

Retrospective, nonrandomized, observational, quasi-experimental study.

Academic medical center with single-occupancy rooms.

Inpatients.

We compared hospital reportable adverse events 1 year before and 1 year after discontinuation of routine CP for endemic MRSA and VRE (preintervention and postintervention periods, respectively). Throughout the preintervention period, daily chlorhexidine gluconate bathing was expanded to nearly all inpatients. Chart reviews were performed to identify which patients and events were associated with CP for MRSA/VRE in the preintervention period as well as the patients that would have met prior criteria for MRSA/VRE CP but were not isolated in the postintervention period. Adverse events during the 2 periods were compared using segmented and mixed-effects Poisson regression models.

There were 24,732 admissions in the preintervention period and 25,536 in the postintervention period. Noninfectious adverse events (ie, postoperative respiratory failure, hemorrhage/hematoma, thrombosis, wound dehiscence, pressure ulcers, and falls or trauma) decreased by 19% (12.3 to 10.0 per 1,000 admissions, P=.022) from the preintervention to the postintervention period. There was no significant difference in the rate of infectious adverse events after CP discontinuation (20.7 to 19.4 per 1,000 admissions, P=.33). Patients with MRSA/VRE showed the largest reduction in noninfectious adverse events after CP discontinuation, with a 72% reduction (21.4 to 6.08 per 1,000 MRSA/VRE admissions; P<.001).

After discontinuing routine CP for endemic MRSA/VRE, the rate of noninfectious adverse events declined, especially in patients who no longer required isolation. This suggests that elimination of CP may substantially reduce noninfectious adverse events.

Infect Control Hosp Epidemiol 2018;788–796

To evaluate the impact of discontinuation of contact precautions (CP) for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) and expansion of chlorhexidine gluconate (CHG) use on the health system.

Retrospective, nonrandomized, observational, quasi-experimental study.

Two California hospitals.

Inpatients.

We compared hospital-wide laboratory-identified clinical culture rates (as a marker of healthcare-associated infections) 1 year before and after routine CP for endemic MRSA and VRE were discontinued and CHG bathing was expanded to all units. Culture data from patients and cost data on material utilization were collected. Nursing time spent donning personal protective equipment was assessed and quantified using time-driven activity-based costing.

Average positive culture rates before and after discontinuing CP were 0.40 and 0.32 cultures/100 admissions for MRSA (P=.09), and 0.48 and 0.40 cultures/100 admissions for VRE (P=.14). When combining isolation gown and CHG costs, the health system saved $643,776 in 1 year. Before the change, 28.5% intensive care unit and 19% medicine/surgery beds were on CP for MRSA/VRE. On the basis of average room entries and donning time, estimated nursing time spent donning personal protective equipment for MRSA/VRE before the change was 45,277 hours/year (estimated cost, $4.6 million).

Discontinuing routine CP for endemic MRSA and VRE did not result in increased rates of MRSA or VRE after 1 year. With cost savings on materials, decreased healthcare worker time, and no concomitant increase in possible infections, elimination of routine CP may add substantial value to inpatient care delivery.

Infect Control Hosp Epidemiol 2016;1–8

Studies have suggested that contact precautions (CP) for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus may have risks that outweigh the benefits. These risks, coupled with more widespread use of horizontal interventions such as daily bathing with chlorhexidine gluconate, have brought into question the value of routine CP for these organisms.

To assess the state of utilization of CP as well as adjunctive measures to reduce the risk of transmission in US hospitals.

Cross-sectional survey.

Total of 751 physician members of the Emerging Infections Network.

An 8-question electronic survey distributed by email.

A total of 426/751 (57%) responded to the survey; 337/364 (93%) of respondents use routine CP for methicillin-resistant S. aureus and 335/364 (92%) use routine CP for vancomycin-resistant enterococcus. The most widely used trigger for initiation of CP for both pathogens was positive clinical culture. Practices for discontinuation of isolation varied widely. We found that 325/354 (92%) perform routine chlorhexidine gluconate bathing and 236/353 (67%) perform S. aureus decolonization with mupirocin for 1 or more subsets of inpatients, and 82/356 (23%) reported using either hydrogen peroxide vapor or ultraviolet-C room disinfection at discharge. Free text responses noted frustration and variation in the application, practice, and process for initiation and discontinuation of CP.

Use of CP for methicillin-resistant S. aureus and vancomycin-resistant enterococcus remains commonplace, although horizontal interventions such as chlorhexidine gluconate bathing are increasingly used. The heterogeneity of practices and policies was striking. Evidence-based guidelines regarding CP and horizontal interventions are needed.

Infect. Control Hosp. Epidemiol. 2015;37(1):36–40

To design better antimicrobial stewardship programs, detailed data on the primary drivers and patterns of antibiotic use are needed.

To characterize the indications for antibiotic therapy, agents used, duration, combinations, and microbiological justification in 6 acute-care US facilities with varied location, size, and type of antimicrobial stewardship programs.

Retrospective medical chart review was performed on a random cross-sectional sample of 1,200 adult inpatients, hospitalized (>24 hrs) in 6 hospitals, and receiving at least 1 antibiotic dose on 4 index dates chosen at equal intervals through a 1-year study period (October 1, 2009–September 30, 2010).

Infectious disease specialists recorded patient demographic characteristics, comorbidities, microbiological and radiological testing, and agents used, dose, duration, and indication for antibiotic prescriptions.

On the index dates 4,119 (60.5%) of 6,812 inpatients were receiving antibiotics. The random sample of 1,200 case patients was receiving 2,527 antibiotics (average: 2.1 per patient); 540 (21.4%) were prophylactic and 1,987 (78.6%) were therapeutic, of which 372 (18.7%) were pathogen-directed at start. Of the 1,615 empirical starts, 382 (23.7%) were subsequently pathogen-directed and 1,231 (76.2%) remained empirical. Use was primarily for respiratory (27.6% of prescriptions) followed by gastrointestinal (13.1%) infections. Fluoroquinolones, vancomycin, and antipseudomonal penicillins together accounted for 47.1% of therapy-days.

Use of broad-spectrum empirical therapy was prevalent in 6 US acute care facilities and in most instances was not subsequently pathogen directed. Fluoroquinolones, vancomycin, and antipseudomonal penicillins were the most frequently used antibiotics, particularly for respiratory indications.

Infect. Control Hosp. Epidemiol. 2015;37(1):70–79