AACC Guidance Document on the Clinical Use of Procalcitonin.

BACKGROUND: Procalcitonin (PCT), a peptide precursor of the hormone calcitonin, is a biomarker whose serum concentrations are elevated in response to systemic inflammation caused by bacterial infection and sepsis. Clinical adoption of PCT in the United States has only recently gained traction with an increasing number of Food and Drug Administration-approved assays and expanded indications for use. There is interest in the use of PCT as an outcomes predictor as well as an antibiotic stewardship tool. However, PCT has limitations in specificity, and conclusions surrounding its utility have been mixed. Further, there is a lack of consensus regarding appropriate timing of measurements and interpretation of results. There is also a lack of method harmonization for PCT assays, and questions remain regarding whether the same clinical decision points may be used across different methods. CONTENT: This guidance document aims to address key questions related to the use of PCT to manage adult, pediatric, and neonatal patients with suspected sepsis and/or bacterial infections, particularly respiratory infections. The document explores the evidence for PCT utility for antimicrobial therapy decisions and outcomes prediction. Additionally, the document discusses analytical and preanalytical considerations for PCT analysis and confounding factors that may affect the interpretation of PCT results. SUMMARY: While PCT has been studied widely in various clinical settings, there is considerable variability in study designs and study populations. Evidence to support the use of PCT to guide antibiotic cessation is compelling in the critically ill and in some lower respiratory tract infections but is lacking in other clinical scenarios, and evidence is also limited in the pediatric and neonatal populations. Interpretation of PCT results requires guidance from multidisciplinary care teams of clinicians, pharmacists, and clinical laboratorians.

Real-World Application of Oral Therapy for Infective Endocarditis: A Multicenter, Retrospective, Cohort Study.

BACKGROUND: We sought to compare the outcomes of patients treated with intravenous (IV)-only vs oral transitional antimicrobial therapy for infective endocarditis (IE) after implementing a new expected practice within the Los Angeles County Department of Health Services (LAC DHS). METHODS: We conducted a multicentered, retrospective cohort study of adults with definite or possible IE treated with IV-only vs oral therapy at the 3 acute care public hospitals in the LAC DHS system between December 2018 and June 2022. The primary outcome was clinical success at 90 days, defined as being alive and without recurrence of bacteremia or treatment-emergent infectious complications. RESULTS: We identified 257 patients with IE treated with IV-only (n = 211) or oral transitional (n = 46) therapy who met study inclusion criteria. Study arms were similar for many demographics; however, the IV cohort was older, had more aortic valve involvement, were hemodialysis patients, and had central venous catheters present. In contrast, the oral cohort had a higher percentage of IE caused by methicillin-resistant Staphylococcus aureus. There was no significant difference between the groups in clinical success at 90 days or last follow-up. There was no difference in recurrence of bacteremia or readmission rates. However, patients treated with oral therapy had significantly fewer adverse events. Multivariable regression adjustments did not find significant associations between any selected variables and clinical success across treatment groups. CONCLUSIONS: These results demonstrate similar outcomes of real-world use of oral vs IV-only therapy for IE, in accord with prior randomized, controlled trials and meta-analyses.

Prognostic significance of early platelet dynamics in Staphylococcus aureus bacteremia.

BACKGROUND: Platelets are recognized as key immune effectors, but they are targets of bacterial virulence factors. In the present study, we aimed to examine the relationship between early platelet dynamics and the outcome of Staphylococcus aureus bacteremia (SAB). METHOD: Electronic medical records of adult patients hospitalized for SAB between July 2012 and November 2020 were retrospectively reviewed for relevant demographic, laboratory, and clinical data. The outcome endpoints were mortality and microbial persistence. RESULTS: Among the 811 patients evaluated, 29% experienced thrombocytopenia on Day 1. Platelet count nadir occurred on Days 2-3 following SAB onset, and Day 4 was a determining point of platelet count trajectory and mortality. Mortality risk was 6% or less for those with normal platelet count by Day 4 regardless of whether they experienced thrombocytopenia on Day 1, but the risk increased to 16-21% for those who experienced thrombocytopenia on Day 4 regardless of whether they had normal platelet count on Day 1 or sustained thrombocytopenia. The duration of bacteremia was prolonged by one day (median 3 d vs. 2 d) for those with sustained thrombocytopenia compared to those without. CONCLUSION: Early platelet dynamics during SAB have prognostic significance and represent an early window for potential platelet-directed therapeutic interventions to improve outcome.

Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection.

Background: Among patients with nosocomial bacterial pneumonia, those who decompensated to requiring mechanical ventilation (vHABP) faced the highest mortality followed by ventilator-associated pneumonia (VABP) and non-ventilated hospital-acquired pneumonia (nvHABP). The objectives of this study were to identify risk factors associated with the development and mortality of vHABP and to evaluate antibiotic management. Methods: A multicenter retrospective cohort study of adult inpatients with nosocomial pneumonia during 2014-2019 was performed. Groups were stratified by vHABP, nvHABP, and VABP and compared on demographics, clinical characteristics, treatment, and outcomes. Multivariable models were generated via machine learning to identify risk factors for progression to vHABP as well as pneumonia-associated mortality for each cohort. Results: 457 patients (32% nvHABP, 37% vHABP, and 31% VABP) were evaluated. The vHABP and nvHABP groups were similar in age (median age 66.4 years) with 77% having multiple comorbidities but more vHABP patients had liver disease (18.2% vs. 7.7% p = 0.005), alcohol use disorder (27% vs. 7.1%, p < 0.0001), and were hospitalized within the past 30 days (30.4% vs. 19.5%, p = 0.02). An immediate need for ventilatory support occurred in 70% of vHABP patients on the day of diagnosis. Mortality was the highest in vHABP followed by VABP and nvHABP groups (44.6% vs. 36% vs. 14.3%, p < 0.0001). Nearly all (96%) vHABP patients had positive cultures, with Gram-negative pathogens accounting for 58.8% whereby 33.0% were resistant to extended-spectrum ß-lactams (ESBLs), ceftriaxone (17.5%), fluoroquinolones (20.6%), and carbapenems (12.4%). Up to half of the vHABP patients with ESBL-Enterobacterales or P. aeruginosa did not receive an effective empiric regimen; over 50% increase in mortality rate was observed among patients whom effective therapy was initiated past the day of pneumonia diagnosis. Risk factors associated with vHABP development were alcohol use disorder, APACHE II score, vasopressor therapy prior to infection, and culture positive for ESBL-Enterobacterales whereas history of hospitalization in the past 30 days, active malignancy, isolation of ceftriaxone-resistant pathogens or Pseudomonas aeruginosa, and vasopressor therapy were risk factors for vHABP-associated mortality. Conclusion: Patients with vHABP experienced an acute and severe decompensation upon diagnosis. The risk factors identified in this study could provide actionable data for clinicians to identify those at risk for vHABP at the onset of pneumonia and to target antimicrobial stewardship efforts to improve treatment success.

How to change the course: practical aspects of implementing shorter is better.

BACKGROUND: Based on multiple randomized-controlled clinical trials, shorter antibiotic courses are equally effective as traditional longer courses for many types of infections. However, longer courses are still being used widely in the clinical practice. OBJECTIVES: To describe four components involved in the successful implementation of shorter antibiotic courses in our health care institutions, including an academic, public hospital and a community hospital staffed primarily by private practitioners. SOURCES: Clinical trials and peer-reviewed publications. CONTENT: We provide practical advice on how to support the change in clinical practice to shorten antibiotic duration. Specifically, we list the steps that we have successfully used to develop and implement an institutional practice change regarding the duration of antibiotic therapy: (a) establishing consensus documents outlining a data-driven expected practice for using antibiotics, (b) antibiotic stewardship programme support, (c) provider education, and (d) reinforcing behaviour through psychological and other tools. The implementation of these processes has successfully led to shorter antibiotic courses and decreased antibiotic use in our diverse practice settings. IMPLICATIONS: Intentional improvement in decreasing the duration of antibiotic therapy can be achieved by a specific antibiotic stewardship programme strategy and tactics. The implementation of shorter antibiotic courses has effects at individual and societal levels in an era of increasing antibacterial resistance and health care costs.

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Acute Bacterial Infections and Longitudinal Risk of Readmissions and Mortality in Patients Hospitalized with Heart Failure.

AIMS: Infections are associated with worse short-term outcomes in patients with heart failure (HF). However, acute infections may have lasting pathophysiologic effects that adversely influence HF outcomes after discharge. Our objective was to describe the impact of acute bacterial infections on longitudinal outcomes of patients hospitalized with a primary diagnosis of HF. METHODS AND RESULTS: This paper is based on a retrospective cohort study of patients hospitalized with a primary diagnosis of HF with or without a secondary diagnosis of acute bacterial infection in Optum Clinformatics DataMart from 2010-2015. Primary outcomes were 30 and 180-day hospital readmissions and mortality, intensive care unit admission, length of hospital stay, and total hospital charge, compared between those with or without an acute infection. Cohorts were compared after inverse probability of treatment weighting. Multivariable logistic regression was used to examine relationship to outcomes. Of 121,783 patients hospitalized with a primary diagnosis of HF, 27,947 (23%) had a diagnosis of acute infection. After weighting, 30-day hospital readmissions [17.1% vs. 15.7%, OR 1.11 (1.07-1.15), p < 0.001] and 180-day hospital readmissions [39.6% vs. 38.7%, OR 1.04 (1.01-1.07), p = 0.006] were modestly greater in those with an acute infection versus those without. Thirty-day [5.5% vs. 4.3%, OR 1.29 (1.21-1.38), p < 0.001] and 180-day mortality [10.7% vs. 9.4%, OR 1.16 (1.11-1.22), p < 0.001], length of stay (7.1 ± 7.0 days vs. 5.7 ± 5.8 days, p < 0.001), and total hospital charges (USD 62,200 ± 770 vs. USD 51,100 ± 436, p < 0.001) were higher in patients with an infection. CONCLUSIONS: The development of an acute bacterial infection in patients hospitalized for HF was associated with an increase in morbidity and mortality after discharge.

Evaluation of step-down oral antibiotic therapy for uncomplicated streptococcal bloodstream infections on clinical outcomes.

BACKGROUND: Despite the severity and frequency of streptococcal bloodstream infections (BSIs), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the clinical outcomes of step-down oral antibiotics for the treatment of uncomplicated streptococcal BSIs. METHODS: In this retrospective cohort study, adult patients admitted with uncomplicated streptococcal BSI between June 2015 and June 2017 were included. Patients were excluded if they received <48 h of antibiotic therapy; therapy was started >48 h after first positive culture; had complicated infections of endocarditis, bone and joint infections, or central nervous system infections; Pitt bacteremia score (PBS) ⩾ 4; or failed to respond to effective therapy necessitating continued intravenous (IV) therapy. Patients were grouped by receipt of step-down oral antibiotic therapy (PO group) versus continued IV therapy (IV group). Outcomes included hospital length of stay (LOS), 30-day recurrence of BSI, 30-day readmission, 30-day all-cause mortality, and catheter-related or drug-related adverse events (AEs). RESULTS: Of 244 patients included, 40% received step-down oral therapy (n = 98). Overall, the most common source of BSI was pneumonia (22%), followed by skin and soft tissue infections (SSTI) (18%). Severity of illness measured by intensive care unit (ICU) admission and PBS was similar. The IV group had significantly longer LOS [median 10 (interquartile range [IQR] = 5-21) versus 5 (4-6) days, p < 0.01] compared with the PO group. BSI recurrence, readmission, all-cause mortality within 30 days, and AEs were similar between the groups (p = ns). CONCLUSION: In uncomplicated streptococcal BSI, patients treated with step-down oral antibiotic therapy had significantly shorter LOS compared with continued IV therapy without compromise of clinical outcomes.

Distance Between Home and the Admitting Hospital and Its Effect on Survival of Low Socioeconomic Status Population With Staphylococcus aureus Bacteremia.

OBJECTIVE: Bacteremia is the presence of bacteria in the bloodstream. The objective of this study was to determine the relationship between low socioeconomic status (SES) and the epidemiology, process of care, and outcomes of patients with Staphylococcus aureus bacteremia (SAB). METHODS: We conducted a multicenter, retrospective, cohort study that evaluated adult patients with SAB in 3 Los Angeles County hospitals from July 15, 2012, through May 31, 2018. We determined SES (low SES, intermediate SES, and high SES) for each patient and compared sociodemographic and epidemiologic characteristics, management of care received by patients with SAB (ie, process of care), and outcomes. We used a Cox proportional hazards model to determine predictors of 30-day mortality for each SES group. RESULTS: Of 915 patients included in the sample, 369 (40%) were in the low-SES group, 294 (32%) in the intermediate-SES group, and 252 (28%) in the high-SES group. Most significant predictors of 30-day mortality in the Cox proportional hazards model were admission to an intensive care unit (hazard ratio [HR] = 9.04; 95% CI, 4.26-19.14), Pitt bacteremia score ≥4 indicating critical illness (HR = 4.30; 95% CI, 2.49-7.44), having ≥3 comorbidities (HR = 2.05; 95% CI, 1.09-3.85), and advanced age (HR = 1.03; 95% CI, 1.01-1.05). Distance between home and admitting hospital affected mortality only in the low-SES group (HR = 1.02; 95% CI, 1.00-1.02). CONCLUSIONS: SES did not independently affect the outcome of SAB; however, the farther the patient's residence from the hospital, the greater the negative effect on survival in a low-SES population. Our findings underscore the need to develop multipronged, targeted public health efforts for populations that have transportation barriers to health care.

Temporal Dynamics of Host Immune Response Associated With Disease Severity and Time to Recovery in Patients Hospitalized for COVID-19.

OBJECTIVES: The objective of this study was to compare the temporal dynamics of two viral-induced inflammatory proteins interferon gamma inducible protein-10 (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as C-reactive protein (CRP) among patients hospitalized for COVID-19 and examine their prognostic significance. DESIGN: Prospective observational cohort study. SETTING: Multicenter, inpatient. PATIENTS: Adult patients infected with severe acute respiratory syndrome coronavirus 2 between March 2021 and October 2021. INTERVENTIONS: Patient sera were collected on days 1, 3, 5, and 7 of hospitalization. Levels of IP-10, TRAIL, and CRP were measured using a point-of-need diagnostic immunoassay platform (MeMed BV, MeMed, Haifa, Israel) and compared between patients grouped by disease severity (severe vs nonsevere). MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar regardless of severity except for a higher prevalence of diabetes and heart failure among severe patients. The immune profile at admission was similar between groups; IP-10 and CRP levels generally decreased while TRAIL levels increased over time in all patients. However, the severe group had higher IP-10 (median 713 vs 328 pg/mL; p = 0.045) and lower TRAIL levels (median 21 vs 30 pg/mL; p = 0.003) on day 3 compared with nonsevere patients. A breakpoint IP-10 level of greater than or equal to 570 pg/mL and TRAIL level of less than 25 pg/mL on day 3 were associated with COVID-19 severity. Patients with elevated day 3 IP-10 levels (≥ 570 pg/mL) were more likely to experience prolonged recovery time (median 12 vs 3 d; p < 0.001). The severe group had prolonged use of corticosteroids (12 vs 5 d; p < 0.001) and had a higher rate of secondary infections (20% vs 6%; p = 0.04) and in-hospital mortality (20% vs 0%; p < 0.001) as compared with nonsevere patients. CONCLUSIONS: The observed patterns in host immune response revealed a turning point in COVID-19 disease on hospital day 3 and the potential utility of IP-10 and TRAIL as sensitive markers associated with disease severity and time to recovery.

Increased Risk of Thrombocytopenia and Death in Patients with Bacteremia Caused by High Alpha Toxin-Producing Methicillin-Resistant Staphylococcus aureus.

Alpha toxin (Hla) is a major virulence factor of Staphylococcus aureus that targets platelets but clinical data on Hla pathogenesis in bacteremia (SAB) is limited. We examined the link between in vitro Hla activity and outcome. Study isolates obtained from 100 patients with SAB (50 survivors; 50 non-survivors) were assessed for in vitro Hla production by Western immunoblotting in a subset of isolates and Hla activity by hemolysis assay in all isolates. Relevant demographics, laboratory and clinical data were extracted from patients' medical records to correlate Hla activity of the infecting isolates with outcome. Hla production strongly correlated with hemolytic activity (rs = 0.93) in vitro. A trend towards higher hemolytic activity was observed for MRSA compared to MSSA and with high-risk source infection. Significantly higher hemolytic activity was noted for MRSA strains isolated from patients who developed thrombocytopenia (median 52.48 vs. 16.55 HU/mL in normal platelet count, p = 0.012) and from non survivors (median 30.96 vs. 14.87 HU/mL in survivors, p = 0.014) but hemolytic activity of MSSA strains did not differ between patient groups. In vitro Hla activity of MRSA strains obtained from patients with bacteremia is significantly associated with increased risk for thrombocytopenia and death which supports future studies to evaluate feasibility of bedside phenotyping and therapeutic targeting.

Cytokine measurements add value to clinical variables in predicting outcomes for Staphylococcus aureus bacteremia.

BACKGROUND: We demonstrated that an early dysregulated cytokine response [high interleukin-10 to tissue necrosis factor (IL-10/TNF) ratio] predicted poor outcomes in patients with Staphylococcus aureus bacteremia (SAB). However, high interpatient variability in cytokine levels were observed. We grouped cytokine measurements in quartiles and assessed their additive value to clinical variables for predicting bacterial persistence and 30-day mortality in patients with SAB. METHODS: A multicenter observational study was conducted in hospitalized patients with SAB. Medical charts were reviewed for relevant information. Blood samples were obtained for cytokine measurements by ELISA: interferon-gamma (IFNγ), interleukin (IL-1ß, IL-6, IL-8, IL-10, IL-17) and tissue necrosis factor (TNF). Cytokine measurements were grouped into quartiles. Significant predictors for bacterial persistence and 30-day mortality were determined by multivariable logistic regression analysis. Area under the ROC curve (AUC) analysis was performed and predictive performance was compared between models with and without cytokine quartiles. RESULTS: Among 606 patients with SAB, a subset of patients (n = 239) had Day 1 cytokine measurements and clinical data collected; of those, 53 (22%) had persistent bacteremia. Accounting for septic shock, the addition of either IL-10 (AUC 0.708) or TNF (AUC 0.714) quartiles measured on Day 1 improved model performance for predicting bacterial persistence. All patients had Day 4 cytokine measurements; 52 patients (8.5%) died within 30-days of SAB onset. Inclusion of either IL-10 (AUC 0.873) or TNF (AUC 0.879) quartiles, but not both, measured on Day 4 to the significant clinical predictors (coronary artery disease, Pitt bacteremia score ≥ 4, and septic shock) improved model performance for mortality. CONCLUSIONS: IL-10 or TNF levels falling within the range in the upper quartiles, when combined with clinical variables, improved model performance for predicting outcomes, and may potentially be used to support aggressive management and biomarker-guided studies to evaluate the benefit of adjunctive immunotherapy for SAB in the future.

Impact of Socioeconomic Status and Race on Sepsis Epidemiology and Outcomes.

BACKGROUND: Socioeconomic status (SES) is a complex variable that is derived primarily from an individual's education, income, and occupation and has been found to be inversely related to outcomes of health conditions. Sepsis is the sixth most common admitting diagnosis and one of the most costly conditions for in-hospital spending in the United States. The objective of this review is to report on the relationship between SES and sepsis incidence and associated outcomes. CONTENT: Sepsis epidemiology varies when explored by race, education, geographic location, income, and insurance status. Sepsis incidence was significantly increased in individuals of Black race compared with non-Hispanic white race; in persons who have less formal education, who lack insurance, and who have low income; and in certain US regions. People with low SES are likely to have onset of sepsis significantly earlier in life and to have poorly controlled comorbidities compared with those with higher SES. Sepsis mortality and hospital readmission is increased in individuals who lack insurance, who reside in low-income or medically underserved areas, who live far from healthcare, and who lack higher level education; however, a person's race was not consistently found to increase mortality. SUMMARY: Interventions to minimize healthcare disparity for individuals with low SES should target sepsis prevention with increasing measures for preventive care for chronic conditions. Significant barriers described for access to care by people with low SES include cost, transportation, poor health literacy, and lack of a social network. Future studies should include polysocial risk scores that are consistently defined to allow for meaningful comparison across studies.

Cost-benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycin.

OBJECTIVES: Area under the time-concentration curve (AUC) -guided dosing provides better estimates of exposure than vancomycin trough concentrations. Though clinical benefits have been reported, the costs of AUC-guided dosing are uncertain. The objective of this study was to quantify the costs of single-sample Bayesian or two-sample AUC strategies versus trough-guided dosing. METHODS: A cost-benefit analysis from the institutional perspective was conducted using a decision tree to model the probabilities and costs of acute kidney injury (AKI) associated with vancomycin administered over 48 hours up to 21+ days. Costs included vancomycin concentrations, Bayesian software and AKI hospitalization costs, and probabilities were obtained from primary literature. Robustness was assessed via both one-way and probabilistic sensitivity analyses. RESULTS: In the base-case model, two-sample AUC versus trough dosing saved an average of US$ 846 per patient encounter, and single-sample Bayesian AUC versus trough dosing saved an average of US$ 2065 per patient encounter. This translates into annual cost-savings of US$ 846 810 and US$ 2 065 720 for two-sample and single-sample Bayesian methods versus trough dosing, respectively, assuming 1000 vancomycin-treated patients per year. Assuming a budget of US$ 100 000 per year for Bayesian software, an institution would need to treat ≥41 patients with vancomycin for at least 48 hours to break even. CONCLUSIONS: There are significant institutional cost benefits using two-sample AUC or single-sample Bayesian methods over trough dosing, even after accounting for the annual costs of Bayesian programs. The potential to decrease rates of AKI, improve clinical outcomes and reduce costs to the institution strongly warrants consideration of improved dosing methods for vancomycin.

Defining the Breakpoint Duration of Staphylococcus aureus Bacteremia Predictive of Poor Outcomes.

BACKGROUND: Persistent Staphylococcus aureus bacteremia (SAB) is defined based on varying duration in literature. The primary objective was to determine the risk of poor outcomes in relation to bacteremia duration. METHODS: Multicenter, prospective, observational study of adult hospitalized patients with SAB. Medical records were reviewed for pertinent data. Patients were grouped by bacteremia duration: short (1-2 days), intermediate (3-6 days), and prolonged (≥7 days) and compared for risk factors and outcomes. RESULTS: Of 884 patients, 63% had short, 28% intermediate, and 9% prolonged bacteremia. Overall mean age was 57 years, and 70% were male. The prolonged group had the highest proportion of methicillin-resistant SAB (P < .0001). Choice of antibiotic therapy did not significantly affect bacteremia duration; however, time to source-control procedure was delayed in the prolonged and intermediate groups compared with the short group (3.5 vs 3 vs 1 day, P < .0001). Metastatic complications, length of stay, and 30-day mortality were progressively worse as bacteremia duration increased (P < .0001). Every continued day of bacteremia was associated with a relative risk of death of 1.16 (95% confidence interval, 1.10-1.22; P < .0001), with a significant increase in risk starting at 3 days as determined by receiver operating characteristic analysis. CONCLUSIONS: Optimal management of SAB should target bacterial clearance as soon as possible to minimize incremental risk of mortality with each day of positive blood culture. Delay in source control but not type of antistaphylococcal therapy was significantly associated with prolonged bacteremia and worse outcomes.

Don't Get Wound Up: Revised Fluoroquinolone Breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa.

Fluoroquinolones remain some of the more commonly prescribed antimicrobial agents in the United States, despite the wide array of reported side effects that are associated with their use. In 2019, the Clinical and Laboratory Standards Institute revised the fluoroquinolone antimicrobial susceptibility testing breakpoints for both Enterobacteriaceae and Pseudomonas aeruginosa This breakpoint revision was deemed necessary on the basis of pharmacokinetic and pharmacodynamic analyses suggesting that the previous breakpoints were too high, in addition to the inability of the previous breakpoints to detect low-level resistance to this antibiotic class. In this minireview, we review the published data in support of this revision, as well as the potential challenges that these breakpoint revisions are likely to pose for clinical laboratories.

Utility of qSOFA score in identifying patients at risk for poor outcome in Staphylococcus aureus bacteremia.

BACKGROUND: The prognostic capability of the quick Sequential Organ Failure Assessment (qSOFA) bedside scoring tool is uncertain in non-ICU patients with sepsis due to bacteremia given the low number of patients previously evaluated. METHODS: We performed a retrospective cohort study of adult hospitalized patients with Staphylococcus aureus bacteremia (SAB). Medical charts were reviewed to determine qSOFA score, systemic inflammatory response syndrome (SIRS) criteria, and Pitt bacteremia score (PBS) at initial presentation; their predictive values were compared for ICU admission within 48 h, ICU stay duration > 72 h, and 30-day mortality. RESULTS: Four hundred twenty-two patients were included; 22% had qSOFA score ≥2. Overall, mean age was 56y and 75% were male. More patients with qSOFA ≥2 had altered mentation (23% vs 5%, p < 0.0001), were infected with MRSA (42% vs 30%, p = 0.03), had endocarditis or pneumonia (29% vs 15%, p = 0.0028), and bacterial persistence ≥4d (34% vs 20%, p = 0.0039) compared to qSOFA <2 patients. Predictive performance based on AUROC was better (p < 0.0001) with qSOFA than SIRS criteria for all three outcomes, but similar to PBS ≥2. qSOFA≥2 was the strongest predictor for poor outcome by multivariable analysis and showed improved specificity but lower sensitivity than SIRS ≥2. CONCLUSIONS: qSOFA is a simple 3-variable bedside tool for use at the time of sepsis presentation that is more specific than SIRS and simpler to calculate than PBS in identifying septic patients at high risk for poor outcomes later confirmed to have S. aureus bacteremia.

Expected Practice as a Novel Antibiotic Stewardship Intervention.

"Expected practice" is a recently described method to alter clinical behavior. We implemented an expected practice around short-course antibiotic therapy, which was associated with decreased antibiotic utilization for multiple bacterial infections. Thus, we describe this expected practice as a novel, simple, and inexpensive tool to enhance antibiotic stewardship.