Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing.

BACKGROUND: The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. OBJECTIVE: To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. CONCLUSIONS: The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing (December 2023).

Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19) and for identifying asymptomatic carriage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of available SARS-CoV-2 nucleic acid detection tests continues to increase as does the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) developed an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients, and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss nuances of test result interpretation in a variety of practice settings, and highlight important unmet research needs related to COVID-19 diagnostic testing. IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 12 diagnostic recommendations. Access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public health response to COVID-19 infection. Information on the clinical performance of available tests continues to grow, but the quality of evidence of the current literature to support this updated molecular diagnostic guideline remains moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is suggested for asymptomatic individuals with known or suspected contact with a COVID-19 case when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions. Evidence in support of rapid testing and testing of upper respiratory specimens other than nasopharyngeal swabs, which offer logistical advantages, is sufficient to warrant conditional recommendations in favor of these approaches.

Assessing Dose- and Sex-Dependent Antinociceptive Effects of Cannabidiol and Amitriptyline, Alone and in Combination, and Exploring Mechanism of Action Involving Serotonin 1A Receptors.

Inflammatory pain is caused by tissue hypersensitization and is a component of rheumatic diseases, frequently causing chronic pain. Current guidelines use a multimodal approach to pain and sociocultural changes have renewed interest in cannabinoid use, particularly cannabidiol (CBD), for pain. The tricyclic antidepressant amitriptyline (AT) is approved for use in pain-related syndromes, alone and within a multimodal approach. Therefore, we investigated sex- and dose-dependent effects of CBD and AT antinociception in the 2.5% formalin inflammatory pain model. Male and female C57BL/6J mice were pretreated with either vehicle, CBD (0.3-100 mg/kg), or AT (0.1-30 mg/kg) prior to formalin testing. In the acute phase, CBD induced antinociception after administration of 30-100 mg/kg in males and 100 mg/kg in females and in the inflammatory phase at doses of 2.5-100 mg/kg in males and 10-100 mg/kg in females. In the acute phase, AT induced antinociception at 10 mg/kg for all mice, and at 0.3 mg/kg in males and 3 mg/kg in female mice in the inflammatory phase. Combining the calculated median effective doses of CBD and AT produced additive effects for all mice in the acute phase and for males only in the inflammatory phase. Use of selective serotonin 1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY-100635) maleate (0.1 mg/kg) before co-administration of CBD and AT reversed antinociception in the acute and partially reversed antinociception in the inflammatory phase. Administration of AT was found to enhance cannabinoid receptor type 1mRNA expression only in female mice. These results suggest a role for serotonin and sex in mediating cannabidiol and amitriptyline-induced antinociception in inflammatory pain. SIGNIFICANCE STATEMENT: Inflammatory pain is an important component of both acute and chronic pain. We have found that cannabidiol (CBD) and amitriptyline (AT) show dose-dependent, and that AT additionally shows sex-dependent, antinociceptive effects in an inflammatory pain model. Additionally, the combination of CBD and AT was found to have enhanced antinociceptive effects that is partially reliant of serotonin 1A receptors and supports the use of CBD within a multimodal approach to pain.

Chronic administration of cannabinoid agonists ACEA (CB1), AM1241 (CB2), and CP55,940 (mixed CB1/CB2) induce sex-specific differences in tolerance and sex hormone changes in a chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy treatment, routinely manifesting as increased pain sensitivity (allodynia) in distal extremities. Despite its prevalence, effective treatment options are limited. Cannabinoids are increasingly being evaluated for their ability to treat chronic pain conditions, including CIPN. While previous studies have revealed sex differences in cannabinoid-mediated antinociception in acute and chronic pain models, there is a paucity of studies addressing potential sex differences in the response of CIPN to cannabinoid treatment. Therefore, we evaluated the long-term anti-allodynic efficacy of CB1-selective (ACEA), CB2-selective (AM1241), and CB1/CB2 mixed (CP55,940) agonists in the cisplatin CIPN model, using both male and female mice. CB1 selective agonism was observed to have sex differences in the development of tolerance to anti-allodynic effects, with females developing tolerance more rapidly than males, while the anti-allodynic effects of selective CB2 agonism lacked tolerance development. Compound-specific changes to the female estrous cycle and female plasma estradiol levels were noted, with CB1 selective agonism decreasing plasma estradiol while CB2 selective agonism increased plasma estradiol. Chronic administration of a mixed CB1/CB2 agonist resulted in increased mRNA expression of proinflammatory cytokines and endocannabinoid regulatory enzymes in female spinal cord tissue. Ovarian tissue was noted to have proinflammatory cytokine mRNA expression following administration of a CB2 acting compound while selective CB1 agonism resulted in decreased proinflammatory cytokines and endocannabinoid regulatory enzymes in testes. These results support the need for further investigation into the role of sex and sex hormones signaling in pain and cannabinoid-mediated antinociceptive effects. Significance Statement CIPN is a common side effect of chemotherapy. We have found that both CB1 and CB2 receptor agonism produce antinociceptive effects in a cisplatin CIPN model. We observed that tolerance to CB1-mediated antinociception developed faster in females and did not develop for CB¬2-mediated antinociception. Additionally, we found contrasting roles for CB1/CB¬2 receptors in the regulation of plasma estradiol in females, with CB1 agonism attenuating estradiol and CB¬2 agonism enhancing estradiol. These findings support the exploration of cannabinoid agonists for CIPN.

Are contact precautions "essential" for the prevention of healthcare-associated methicillin-resistant Staphylococcus aureus?

The recently updated SHEA/IDSA/APIC practice recommendations for MRSA prevention in acute care facilities list contact precautions (CP) for patients known to be infected or colonized with MRSA as an "essential practice", meaning that it should be adopted in all acute care facilities. We argue that existing evidence on benefits and harms associated with CP do not justify this recommendation. There are no controlled trials that support broad use of CP for MRSA prevention. Data from hospitals that have discontinued CP for MRSA have found no impact on MRSA acquisition or infection. The burden and harms of CP remain concerning, including the environmental impact of increased gown and glove use. We suggest that CP be included among other "additional approaches" to MRSA prevention that can be implemented under specific circumstances (e.g. outbreaks, evidence of ongoing transmission despite application of essential practices).

The Impact of Universal Glove and Gown Use on Clostridioides Difficile Acquisition: A Cluster-Randomized Trial.

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infections in the United States. It is unknown whether universal gown and glove use in intensive care units (ICUs) decreases acquisition of C. difficile. METHODS: This was a secondary analysis of a cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from 4 January 2012 to 4 October 2012. After a baseline period, ICUs were randomized to standard practice for glove and gown use versus the intervention of all healthcare workers being required to wear gloves and gowns for all patient contact and when entering any patient room (contact precautions). The primary outcome was acquisition of toxigenic C. difficile determined by surveillance cultures collected on admission and discharge from the ICU. RESULTS: A total of 21 845 patients had both admission and discharge perianal swabs cultured for toxigenic C. difficile. On admission, 9.43% (2060/21 845) of patients were colonized with toxigenic C. difficile. No significant difference was observed in the rate of toxigenic C. difficile acquisition with universal gown and glove use. Differences in acquisition rates in the study period compared with the baseline period in control ICUs were 1.49 per 100 patient-days versus 1.68 per 100 patient-days in universal gown and glove ICUs (rate difference, -0.28; generalized linear mixed model, P = .091). CONCLUSIONS: Glove and gown use for all patient contact in medical and surgical ICUs did not result in a reduction in the acquisition of C. difficile compared with usual care. CLINICAL TRIALS REGISTRATION: NCT01318213.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing.

BACKGROUND: Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. OBJECTIVE: The IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and non-medical settings. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through April 1, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel made ten diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. CONCLUSIONS: U.S. Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared to nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms, and in symptomatic patients, on timing of testing after symptom onset. In contrast, Ag tests have high specificity, and, in most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared to testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remains the testing method of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Role of Cannabinoid Signaling in Cardiovascular Function and Ischemic Injury.

Cardiovascular disease represents a leading cause of death, morbidity, and societal economic burden. The prevalence of cannabis use has significantly increased due to legalization and an increased societal acceptance of cannabis. Therefore, it is critically important that we gain a greater understanding of the effects and risks of cannabinoid use on cardiovascular diseases as well as the potential for cannabinoid-directed drugs to be used as therapeutics for the treatment of cardiovascular disease. This review summarizes our current understanding of the role of cannabinoid receptors in the pathophysiology of atherosclerosis and myocardial ischemia and explores their use as therapeutic targets in the treatment of ischemic heart disease. Endocannabinoids are elevated in patients with atherosclerosis, and activation of cannabinoid type 1 receptors (CB1Rs) generally leads to an enhancement of plaque formation and atherosclerosis. In contrast, selective activation of cannabinoid type 2 receptors (CB2Rs) appears to exert protective effects against atherosclerosis. Endocannabinoid signaling is also activated by myocardial ischemia. CB2R signaling appears to protect the heart from ischemic injury, whereas the role of CB1R in ischemic injury is less clear. This narrative review serves to summarize current research on the role of cannabinoid signaling in cardiovascular function with the goal of identifying critical knowledge gaps and future studies to address those gaps in a way that facilitates the development of new treatments and better cardiovascular health. SIGNIFICANCE STATEMENT: Cardiovascular diseases, including atherosclerosis and myocardial infarction, are a leading cause of death. Cannabinoid drugs have well known acute effects on cardiovascular function, including tachycardia and orthostatic hypotension. The recent legalization of marijuana and cannabinoids for both medical and recreational use has dramatically increased their prevalence of use. This narrative review on the role of cannabinoid signaling in cardiovascular disease contributes to a better understanding of this topic by integrating current knowledge and identifying critical gaps.

Cannabinoid Tolerance in S426A/S430A x ß-Arrestin 2 Knockout Double-Mutant Mice.

Tolerance to compounds that target G protein-coupled receptors (GPCRs), such as the cannabinoid type-1 receptor (CB1R), is in part facilitated by receptor desensitization. Processes that mediate CB1R desensitization include phosphorylation of CB1R residues S426 and S430 by a GPCR kinase and subsequent recruitment of the ß-arrestin2 scaffolding protein. Tolerance to cannabinoid drugs is reduced in S426A/S430A mutant mice and ß-arrestin2 knockout (KO) mice according to previous work in vivo. However, the presence of additional phosphorylatable residues on the CB1R C-terminus made it unclear as to whether recruitment to S426 and S430 accounted for all desensitization and tolerance by ß-arrestin2. Therefore, we assessed acute response and tolerance to the cannabinoids delta-9-tetrahydrocannabinol (Δ9-THC) and CP55,940 in S426A/S430A x ß-arrestin2 KO double-mutant mice. We observed both delayed tolerance and increased sensitivity to the antinociceptive and hypothermic effects of CP55,940 in male S426A/S430A single- and double-mutant mice compared with wild-type littermates, but not with Δ9-THC. Female S426A/S430A single- and double-mutant mice were more sensitive to acute antinociception (CP55,940 and Δ9-THC) and hypothermia (CP55,940 only) exclusively after chronic dosing and did not differ in the development of tolerance. These results indicate that phosphorylation of S426 and S430 are likely responsible for ß-arrestin2-mediated desensitization as double-mutant mice did not differ from the S426A/S430A single-mutant model in respect to cannabinoid tolerance and sensitivity. We also found antinociceptive and hypothermic effects from cannabinoid treatment demonstrated by sex-, agonist-, and duration-dependent features. SIGNIFICANCE STATEMENT: A better understanding of the molecular mechanisms involved in tolerance will improve the therapeutic potential of cannabinoid drugs. This study determined that further deletion of ß-arrestin2 does not enhance the delay in cannabinoid tolerance observed in CB1R S426A/S430A mutant mice.

Diagnostic stewardship: what impacts antibiotics use?

PURPOSE OF REVIEW: The aim of this study was to review recently published diagnostic stewardship studies of common clinical infectious syndromes and the impact on antibiotic prescribing. RECENT FINDINGS: Diagnostic stewardship can be implemented within healthcare systems and tailored to infectious syndromes, including urinary tract, gastrointestinal, respiratory and bloodstream infections. In urinary syndromes, diagnostic stewardship can decrease unnecessary urine culturing and associated antibiotic prescribing. Diagnostic stewardship of Clostridium difficile testing can decrease antibiotics and test ordering with a reduction in healthcare-associated C. difficile infections. Respiratory syndrome multiplex arrays can decrease time to results and increase detection of clinically relevant pathogens but may not decrease antibiotics use, or worse, could increase over-prescribing if diagnostic stewardship of ordering practices is not exercised. Lastly, blood culturing practices can be improved by clinical decision support to safely decrease collection and broad-spectrum antibiotic use. SUMMARY: Diagnostic stewardship decreases unnecessary antibiotic use in a way that is different from and complementary to antibiotic stewardship. Further studies are needed to quantify the full impact on antibiotic use and resistance. Future considerations should be to institutionalize diagnostic stewardship in patient care activities to leverage integration into systems-based interventions.

Advancing Diagnostic Stewardship for Healthcare-Associated Infections, Antibiotic Resistance, and Sepsis.

Diagnostic stewardship means ordering the right tests for the right patient at the right time to inform optimal clinical care. Diagnostic stewardship is an integral part of antibiotic stewardship efforts to optimize antibiotic use and improve patient outcomes, including reductions in antibiotic resistance and treatment of sepsis. The Centers for Disease Control and Prevention's Division of Healthcare Quality Promotion hosted a meeting on improving patient safety through diagnostic stewardship with a focus on use of the laboratory. At the meeting, emerging issues in the field of diagnostic stewardship were identified, awareness of these issues among stakeholders was raised, and strategies and interventions to address the issues were discussed-all with an emphasis on improved outcomes and patient safety. Here, we summarize the key takeaways of the meeting including needs for diagnostic stewardship implementation, promising future avenues for diagnostic stewardship implementation, and areas of needed research.

Clinical Decision Support Systems to Reduce Unnecessary Clostridioides difficile Testing Across Multiple Hospitals.

BACKGROUND: Inappropriate Clostridioides difficile testing has adverse consequences for patients, hospitals, and public health. Computerized clinical decision support (CCDS) systems in the electronic health record (EHR) may reduce C. difficile test ordering; however, effectiveness of different approaches, ease of use, and best fit into healthcare providers' (HCP) workflow are not well understood. METHODS: Nine academic and 6 community hospitals in the United States participated in this 2-year cohort study. CCDS (hard stop or soft stop) triggered when a duplicate C. difficile test order was attempted or if laxatives were recently received. The primary outcome was the difference in testing rates pre- and post-CCDS interventions, using incidence rate ratios (IRRs) and mixed-effect Poisson regression models. We performed qualitative evaluation (contextual inquiry, interviews, focus groups) based on a human factors model. We identified themes using a codebook with primary nodes and subnodes. RESULTS: In 9 hospitals implementing hard-stop CCDS and 4 hospitals implementing soft-stop CCDS, C. difficile testing incidence rate (IR) reduction was 33% (95% confidence interval [CI]: 30%-36%) and 23% (95% CI: 21%-25%), respectively. Two hospitals implemented a non-EHR-based human intervention with IR reduction of 21% (95% CI: 15%-28%). HCPs reported generally favorable experiences and highlighted time efficiencies such as inclusion of the patient's most recent laxative administration on the CCDS. Organizational factors, including hierarchical cultures and communication between HCPs caring for the same patient, impact CCDS acceptance and integration. CONCLUSIONS: CCDS systems reduced unnecessary C. difficile testing and were perceived positively by HCPs when integrated into their workflow and when displaying relevant patient-specific information needed for decision making.

Optimal Urine Culture Diagnostic Stewardship Practice-Results from an Expert Modified-Delphi Procedure.

BACKGROUND: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship. METHODS: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed. RESULTS: One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions. CONCLUSIONS: These 18 guidance statements can optimize use of urine cultures for better patient outcomes.

Acquisition of Antibiotic-Resistant Gram-negative Bacteria in the Benefits of Universal Glove and Gown (BUGG) Cluster Randomized Trial.

BACKGROUND: The Benefits of Universal Glove and Gown (BUGG) cluster randomized trial found varying effects on methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus and no increase in adverse events. The aim of this study was to assess whether the intervention decreases the acquisition of antibiotic-resistant gram-negative bacteria. METHODS: This was a secondary analysis of a randomized trial in 20 hospital intensive care units. The intervention consisted of healthcare workers wearing gloves and gowns when entering any patient room compared to standard care. The primary composite outcome was acquisition of any antibiotic-resistant gram-negative bacteria based on surveillance cultures. RESULTS: A total of 40 492 admission and discharge perianal swabs from 20 246 individual patient admissions were included in the primary outcome. For the primary outcome of acquisition of any antibiotic-resistant gram-negative bacteria, the intervention had a rate ratio (RR) of 0.90 (95% confidence interval [CI], .71-1.12; P = .34). Effects on the secondary outcomes of individual bacteria acquisition were as follows: carbapenem-resistant Enterobacteriaceae (RR, 0.86 [95% CI, .60-1.24; P = .43), carbapenem-resistant Acinetobacter (RR, 0.81 [95% CI, .52-1.27; P = .36), carbapenem-resistant Pseudomonas (RR, 0.88 [95% CI, .55-1.42]; P = .62), and extended-spectrum ß-lactamase-producing bacteria (RR, 0.94 [95% CI, .71-1.24]; P = .67). CONCLUSIONS: Universal glove and gown use in the intensive care unit was associated with a non-statistically significant decrease in acquisition of antibiotic-resistant gram-negative bacteria. Individual hospitals should consider the intervention based on the importance of these organisms at their hospital, effect sizes, CIs, and cost of instituting the intervention. CLINICAL TRIALS REGISTRATION: NCT01318213.

Impact of the Centers for Medicare and Medicaid Services Sepsis Core Measure on Antibiotic Use.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) implemented a core measure sepsis (SEP-1) bundle in 2015. One element was initiation of broad-spectrum antibiotics within 3 hours of diagnosis. The policy has the potential to increase antibiotic use and Clostridioides difficile infection (CDI). We evaluated the impact of SEP-1 implementation on broad-spectrum antibiotic use and CDI occurrence rates. METHODS: Monthly adult antibiotic data for 4 antibiotic categories (surgical prophylaxis, broad-spectrum for community-acquired infections, broad-spectrum for hospital-onset/multidrug-resistant [MDR] organisms, and anti-methicillin-resistant Staphylococcus aureus [MRSA]) from 111 hospitals participating in the Clinical Data Base Resource Manager were evaluated in periods before (October 2014-September 2015) and after (October 2015-June 2017) policy implementation. Interrupted time series analyses, using negative binomial regression, evaluated changes in antibiotic category use and CDI rates. RESULTS: At the hospital level, there was an immediate increase in the level of broad-spectrum agents for hospital-onset/MDR organisms (+2.3%, P = .0375) as well as a long-term increase in trend (+0.4% per month, P = .0273). There was also an immediate increase in level of overall antibiotic use (+1.4%, P = .0293). CDI rates unexpectedly decreased at the time of SEP-1 implementation. When analyses were limited to patients with sepsis, there was a significant level increase in use of all antibiotic categories at the time of SEP-1 implementation. CONCLUSIONS: SEP-1 implementation was associated with immediate and long-term increases in broad-spectrum hospital-onset/MDR organism antibiotics. Antimicrobial stewardship programs should evaluate sepsis treatment for opportunities to de-escalate broad therapy as indicated.

Antibiotic Use and Bacterial Infection among Inpatients in the First Wave of COVID-19: a Retrospective Cohort Study of 64,691 Patients.

Hospitalized patients with SARS-CoV-2 infection (COVID-19) often receive antibiotics for suspected bacterial coinfection. We estimated the incidence of bacterial coinfection and secondary infection in COVID-19 using clinical diagnoses to determine how frequently antibiotics are administered when bacterial infection is absent. We performed a retrospective cohort study of inpatients with COVID-19 present on admission to hospitals in the Premier Healthcare Database between April and June 2020. Bacterial infections were defined using ICD-10-CM diagnosis codes and associated "present on admission" coding. Coinfections were defined by bacterial infection present on admission, while secondary infections were defined by bacterial infection that developed after admission. Coinfection and secondary infection were not mutually exclusive. A total of 18.5% of 64,961 COVID-19 patients (n = 12,040) presented with bacterial infection at admission, 3.8% (n = 2,506) developed secondary infection after admission, and 0.9% (n = 574) had both; 76.3% (n = 49,551) received an antibiotic while hospitalized, including 71% of patients who had no diagnosis of bacterial infection. Secondary bacterial infection occurred in 5.7% of patients receiving steroids in the first 2 days of hospitalization, 9.9% receiving tocilizumab in the first 2 days of hospitalization, and 10.3% of patients receiving both. After adjusting for patient and hospital characteristics, bacterial coinfection (adjusted relative risk [aRR], 1.15; 95% confidence interval [CI], 1.11 to 1.20) and secondary infection (aRR 1.93; 95% CI, 1.82 to 2.04) were both independently associated with increased mortality. Although 1 in 5 inpatients with COVID-19 presents with bacterial infection, secondary infections in the hospital are uncommon. Most inpatients with COVID-19 receive antibiotic therapy, including 71% of those not diagnosed with bacterial infection.

To Expand the Evidence Base About Harms from Tests and Treatments.

Rigorous evidence about the broad range of harms that might be experienced by a patient in the course of testing and treatment is sparse. We aimed to generate recommendations for how researchers might more comprehensively evaluate potential harms of healthcare interventions, to allow clinicians and patients to better include this evidence in clinical decision-making. We propose seven domains of harms of tests and treatments that are relevant to patients: (1) physical impairment, (2) psychological distress, (3) social disruption, (4) disruption in connection to healthcare, (5) labeling, (6) financial impact, and (7) treatment burden. These domains will include a range of severity of harms and variation in timing after testing or treatment, attributable to the service itself or a resulting care cascade. Although some new measures may be needed, diverse data and tools are available to allow the assessment of harms comprehensively across these domains. We encourage researchers to evaluate harms in sub-populations, since the harms experienced may differ importantly by demographics, social determinants, presence of comorbid illness, psychological state, and other characteristics. Regulators, funders, and editors might require either assessment or reporting of harms in each domain or require justification for inclusion and exclusion of different domains.

The Overton Window and a Less Dogmatic Approach to Antibiotics.

This analysis summarizes a set of recent, innovative trials in infectious diseases that redefine previous, non-evidence based "rules" for antibiotics. Recent trials in infectious diseases have led to reconsidering the traditional treatment of infectious diseases by changing the duration or type of traditional antibiotics or evaluating new antibiotics for approval. These trials have used the noninferiority trial approach. The noninferiority trial design and recent infectious disease trials of relevance are discussed in this viewpoint. My objective was to analyze recent trials in infectious disease and consider needs for future trials.

Imprecision Medicine: Challenges in Diagnosis, Treatment, and Measuring Quality for Catheter-Associated Urinary Tract Infection.

We question the reliability of the vague symptoms that most commonly define catheter-associated urinary tract infection (CAUTI) and encourage further examination of whether the current CAUTI definition reflects a true infection. While diagnosing CAUTI using the current surveillance definition, physicians may be missing a number of nonurinary etiologies for fever, prematurely diagnosing urinary tract infection, and prescribing unnecessary antibiotics. We believe it is time to reconsider the quality metric of CAUTI. By doing so, we can improve antibiotic use and quality of patient care.