Cefoxitin for Intra-amniotic Infections and Endometritis: A Retrospective Comparison to Traditional Antimicrobial Therapy Regimens Within a Healthcare System.

BACKGROUND: Local institutional guidelines and order sets were updated in June 2023 to recommend first-line cefoxitin monotherapy for the treatment of intra-amniotic infections (IAIs) and endometritis. This study evaluated the clinical impact of this change. METHODS: This was a retrospective, observational cohort study in an 11-campus health system comparing clinical outcomes of patients with chorioamnionitis, endometritis, or septic abortion receiving intravenous antimicrobial therapy before and after implementation of first-line cefoxitin monotherapy recommendations for the treatment of these infections. Primary outcome was a composite of serious clinical events postdelivery (ie, intensive care unit admission, death, hospital readmission related to IAI or endometritis within 30 days, additional surgery or procedures, or deep surgical site infection). Baseline characteristics between the pre- and post-cefoxitin groups were compared via Student's t tests for continuous variables and chi-square tests for categorical variables. Outcomes were evaluated via generalized linear modeling. RESULTS: A total of 472 patients were enrolled, 350 (74%) in the pre-cefoxitin group and 122 (26%) in the post-cefoxitin group. Groups were significantly different by race, healthcare payor, and hospital campus. Cefoxitin was rarely used in the pre-cefoxitin group (n = 2, <0.1%) and commonly used in the post-cefoxitin group (n = 112, 91.8%). After controlling for group differences, odds of experiencing serious clinical event postdelivery in the post-cefoxitin group were noninferior to those in the pre-cefoxitin group (adjusted odds ratio, .37; 95% CI, .17-.76; P = .010). CONCLUSIONS: Local institutional guidelines with predominant use of cefoxitin therapy were noninferior to traditional antimicrobial therapy regimens for the treatment of IAI.

Incidence and predictors of complications in Gram-negative bloodstream infection.

BACKGROUND: The incidence of metastatic complications in Gram-negative bloodstream infection (GN-BSI) remains undefined. This retrospective cohort study examines the incidence and predictors of complications within 90 days of GN-BSI. METHODS: Patients with GN-BSIs hospitalized at two Prisma Health-Midlands hospitals in Columbia, South Carolina, USA from 1 January 2012 through 30 June 2015 were included. Complications of GN-BSI included endocarditis, septic arthritis, osteomyelitis, spinal infections, deep-seated abscesses, and recurrent GN-BSI. Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine incidence and risk factors of complications, respectively. RESULTS: Among 752 patients with GN-BSI, median age was 66 years and 380 (50.5%) were women. The urinary tract was the most common source of GN-BSI (378; 50.3%) and Escherichia coli was the most common bacteria (375; 49.9%). Overall, 13.9% of patients developed complications within 90 days of GN-BSI. The median time to identification of these complications was 5.2 days from initial GN-BSI. Independent risk factors for complications were presence of indwelling prosthetic material (hazards ratio [HR] 1.73, 95% confidence intervals [CI] 1.08-2.78), injection drug use (HR 6.84, 95% CI 1.63-28.74), non-urinary source (HR 1.98, 95% CI 1.18-3.23), BSI due to S. marcescens, P. mirabilis or P. aeruginosa (HR 1.78, 95% CI 1.05-3.03), early clinical failure criteria (HR 1.19 per point, 95% CI 1.03-1.36), and persistent GN-BSI (HR 2.97, 95% CI 1.26-6.99). CONCLUSIONS: Complications of GN-BSI are relatively common and may be predicted based on initial clinical response to antimicrobial therapy, follow-up blood culture results, and other host and microbiological factors.

Evaluation of early clinical failure criteria in Enterococcus species bloodstream infection.

PURPOSE: Early clinical failure criteria (ECFC) were recently introduced to predict unfavorable outcomes in patients with Gram-negative bloodstream infections (BSI). ECFC include hypotension, tachycardia, tachypnea or mechanical ventilation, altered mental status, and leukocytosis evaluated at 72-96 h after BSI. The aim of this retrospective cohort study was to assess performance of ECFC in predicting 28-day mortality in Enterococcus species BSI. METHODS: Hospitalized adults with Enterococcus species BSI at Prisma Health hospitals from 1 January 2015 to 31 July 2018 were identified. Multivariate logistic regression was used to determine the association between ECFC and 28-day mortality. Area under the receiver operating characteristic (AUROC) curve was used to measure model discrimination. RESULTS: Among 157 patients, 28 (18%) died within 28 days of BSI. After adjustments in multivariate model, the risk of 28-day mortality increased in the presence of each additional ECFC (OR 1.6, 95% CI 1.2-2.3, p = 0.005). Infective endocarditis (OR 3.9, 95% CI 1.4-10.7, p = 0.01) was independently associated with 28-day mortality. AUROC curve of ECFC model in predicting 28-day mortality was 0.74 with ECFC of 2 identified as the best breakpoint. Mortality was 8% in patients with ECFC < 2 compared to 33% in those with ECFC ≥ 2 (p < 0.001). CONCLUSION: ECFC had good discrimination in predicting 28-day mortality in patients with Enterococcus species BSI. These criteria may have utility in future clinical investigations.

Role of Early De-escalation of Antimicrobial Therapy on Risk of Clostridioides difficile Infection Following Enterobacteriaceae Bloodstream Infections.

BACKGROUND: There is a paucity of data on the effect of early de-escalation of antimicrobial therapy on rates of Clostridioides difficile infection (CDI). This retrospective cohort study evaluated impact of de-escalation from antipseudomonal ß-lactam (APBL) therapy within 48 hours of Enterobacteriaceae bloodstream infections (BSIs) on 90-day risk of CDI. METHODS: Adult patients hospitalized for >48 hours for treatment of Enterobacteriaceae BSI at Palmetto Health hospitals in Columbia, South Carolina, from 1 January 2011 through 30 June 2015 were identified. Multivariable Cox proportional hazards regression was used to examine time to CDI in patients who received >48 hours or ≤48 hours of APBL for empirical therapy of Enterobacteriaceae BSI after adjustment for the propensity to receive >48 hours of APBL. RESULTS: Among 808 patients with Enterobacteriaceae BSI, 414 and 394 received >48 and ≤48 hours of APBL, respectively. Incidence of CDI was higher in patients who received >48 hours than those who received ≤48 hours of APBL (7.0% vs 1.8%; log-rank P = .002). After adjustment for propensity to receive >48 hours of APBL and other variables in the multivariable model, receipt of >48 hours of APBL (hazard ratio [HR], 3.56 [95% confidence interval {CI}, 1.48-9.92]; P = .004) and end-stage renal disease (HR, 4.27 [95% CI, 1.89-9.11]; P = .001) were independently associated with higher risk of CDI. CONCLUSIONS: The empirical use of APBL for >48 hours was an independent risk factor for CDI. Early de-escalation of APBL using clinical risk assessment tools or rapid diagnostic testing may reduce the incidence of CDI in hospitalized adults with Enterobacteriaceae BSIs.

Derivation of a quick Pitt bacteremia score to predict mortality in patients with Gram-negative bloodstream infection.

PURPOSE: This retrospective cohort study derived a "quick" version of the Pitt bacteremia score (qPitt) using binary variables in patients with Gram-negative bloodstream infections (BSI). The qPitt discrimination was then compared to quick sepsis-related organ failure assessment (qSOFA) and systemic inflammatory response syndrome (SIRS). METHODS: Hospitalized adults with Gram-negative BSI at Palmetto Health hospitals in Columbia, SC, USA from 2010 to 2013 were identified. Multivariate Cox proportional hazards regression was used to determine variables associated with 14-day mortality. RESULTS: Among 832 patients with Gram-negative BSI, median age was 65 years and 449 (54%) were women. After adjustments for age and Charleston comorbidity score, all five components of qPitt were independently associated with mortality: temperature < 36 °C [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.95-4.62], systolic blood pressure < 90 mmHg or vasopressor use (HR 2.40, 95% CI 1.37-4.13), respiratory rate ≥ 25/min or mechanical ventilation (HR 3.01, 95% CI 1.81-5.14), cardiac arrest (HR 5.35, 95% CI 2.81-9.43), and altered mental status (HR 3.99, 95% CI 2.44-6.80). The qPitt had higher discrimination to predict mortality [area under receiver operating characteristic curve (AUROC) 0.85] than both qSOFA (AUROC 0.77, p < 0.001) and SIRS (AUROC 0.63, p < 0.001). There was a significant difference in mortality between appropriate and inappropriate empirical antimicrobial therapy in patients with qPitt ≥ 2 (24% vs. 49%, p < 0.001), but not in those with qPitt < 2 (3% vs. 5%, p = 0.36). CONCLUSIONS: The qPitt had good discrimination in predicting mortality following Gram-negative BSI and identifying opportunities for improved survival with appropriate empirical antimicrobial therapy.

Risk factors for pneumonia due to beta-lactam-susceptible and beta-lactam-resistant Pseudomonas aeruginosa: a case-case-control study.

PURPOSE: This case-case-control study aims to identify clinical predictors for pneumonia due to Pseudomonas aeruginosa (PA) which is (1) susceptible to all routinely tested antipseudomonal beta-lactams (APBL-S) and (2) resistant to at least one antipseudomonal beta-lactam (APBL-R). METHODS: Hospitalized adults with acute bacterial pneumonia at Palmetto Health hospitals in Columbia, SC, USA from January 1, 2012 to April 15, 2014 were identified. Multivariate logistic regression was used to determine risk factors for pneumonia due to APBL-S PA and APBL-R PA. RESULTS: Among 326 unique patients, 119 had pneumonia due to APBL-S PA (cases), 44 due to APBL-R PA (cases) and 163 due to ceftriaxone-susceptible bacteria (controls). Bronchiectasis [odds ratio (OR) 5.7, 95% confidence intervals (CI) 1.3-39.2], interstitial lung disease (OR 6.2, 95% CI 1.5-42.6), prior airway colonization with APBL-S PA (OR 7.2, 95% CI 1.1-139.4) and recent exposure to both antipseudomonal beta-lactam (APBL; OR 2.2, 95% CI 1.1-4.5) and nonpseudomonal beta-lactams (OR 2.6, 95% CI 1.0-6.8) were independently associated with increased risk of APBL-S PA pneumonia. Bronchiectasis (OR 8.3, 95% CI 1.7-46.6), prior airway colonization with APBL-R PA (OR 14.9, 95% CI 2.0-312.9) and recent use of only APBL (OR 7.7, 95% CI 3.4-17.9) were predictors for APBL-R PA pneumonia. CONCLUSIONS: Stratification of hospitalized patients with pneumonia based on structural lung disease, prior airway colonization and recent antimicrobial exposure may improve empirical antimicrobial selection. Expansion of antimicrobial regimen from ceftriaxone to APBL or combination therapy is suggested in patients with risk factors for APBL-S or APBL-R PA, respectively.

Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections.

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 162 (68%) patients were women, and 137 (58%) patients had cUTI due to Escherichia coli Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR], 23.4; 95% confidence interval [CI], 8.2 to 76.8; P < 0.001) and within 3 to 12 months (aOR, 13.2; 95% CI, 3.1 to 68.4; P < 0.001) was independently associated with fluoroquinolone resistance compared to no prior use. The area under the receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRSs of ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI on the basis of the predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis.

Association between inappropriate empirical antimicrobial therapy and hospital length of stay in Gram-negative bloodstream infections: stratification by prognosis.

OBJECTIVES: The potential benefit from appropriate empirical antimicrobial therapy in patients with favourable prognosis at initial presentation with Gram-negative bloodstream infection (BSI) remains unclear. This retrospective cohort study examined the impact of inappropriate empirical antimicrobial therapy on hospital length of stay (HLOS) following Gram-negative BSI after stratification by predicted prognosis using the BSI mortality risk score (BSIMRS). METHODS: Hospitalized adults with first episodes of Gram-negative BSI from 1 January 2010 to 31 December 2013 at Palmetto Health Hospitals in Columbia, SC, USA were identified. Multivariate Cox proportional hazards regression was used to examine the association between inappropriate empirical antimicrobial therapy and HLOS overall and within each predefined BSIMRS category (<5 and ≥5). RESULTS: Among 830 unique patients with Gram-negative BSI, 469 and 361 had BSIMRS <5 and ≥5, respectively. Overall, the median age was 65 years, 448 (54%) were women, Escherichia coli (444; 53%) was the most common bloodstream isolate and 444 (53%) had a urinary source of infection. After adjustments in the multivariate model, BSIMRS (HR = 1.14 per point, 95% CI = 1.11-1.17, P < 0.001) and inappropriate empirical antimicrobial therapy (HR = 1.41, 95% CI = 1.07-1.91, P = 0.01) were independently associated with increased risk of remaining hospitalized following Gram-negative BSI. Median HLOS with appropriate and inappropriate empirical antimicrobial therapy was 7 and 10 days, respectively, in patients with BSIMRS <5 (P = 0.03) and 13 and 17 days, respectively, in those with BSIMRS ≥5 (P = 0.02). CONCLUSIONS: Inappropriate empirical antimicrobial therapy is associated with prolonged HLOS following Gram-negative BSI in patients with both good and guarded prognosis.

Optimal duration of antimicrobial therapy for uncomplicated Gram-negative bloodstream infections.

PURPOSE: Optimal antimicrobial treatment duration for Gram-negative bloodstream infection (BSI) remains unclear. This retrospective cohort study examined effectiveness of short (7-10 days) and long (>10 days) courses of antimicrobial therapy for uncomplicated Gram-negative BSI. METHODS: Hospitalized adults with uncomplicated Gram-negative BSI at Palmetto Health hospitals in Columbia SC, USA from January 1, 2010 to December 31, 2013 were identified. Multivariate Cox proportional hazards regression with propensity score adjustment was used to examine risk of treatment failure in the two groups. RESULTS: During the study period, 117 and 294 patients received short and long courses of antimicrobial therapy for uncomplicated Gram-negative BSI, respectively. Overall, the median age was 67 years, 258 (63%) were women, 282 (69%) had urinary source of infection, and 271 (66%) had BSI due to Escherichia coli. The median duration of antimicrobial therapy was 8.5 and 13.3 days in the short and long treatment groups, respectively. After adjustment for the propensity to use a short course of therapy, risk of treatment failure was higher in patients receiving short compared to long courses of antimicrobial agents (HR 2.60, 95% CI: 1.20-5.53, p = 0.02). Other risk factors for treatment failure included liver cirrhosis (HR 5.83, 95% CI: 1.89-15.02, p = 0.004) and immune compromised status (HR 4.30, 95% CI: 1.57-10.80, p = 0.006). Definitive antimicrobial therapy with intravenous or highly bioavailable oral agents was associated with reduced risk of treatment failure (HR 0.33, 95% CI: 0.14-0.73, p = 0.006). CONCLUSIONS: The current results support common clinical practice of 2 weeks of antimicrobial therapy for uncomplicated Gram-negative BSI.

Development of Institutional Guidelines for Management of Gram-Negative Bloodstream Infections: Incorporating Local Evidence.

Background: Appropriate empirical antimicrobial therapy is associated with improved outcomes of patients with Gram-negative bloodstream infections (BSI). Objective: Development of evidence-based institutional management guidelines for empirical antimicrobial therapy of Gram-negative BSI. Methods: Hospitalized adults with Gram-negative BSI in 2011-2012 at Palmetto Health hospitals in Columbia, SC, USA, were identified. Logistic regression was used to examine the association between site of infection acquisition and BSI due to Pseudomonas aeruginosa or chromosomally mediated AmpC-producing Enterobacteriaceae (CAE). Antimicrobial susceptibility rates of bloodstream isolates were stratified by site of acquisition and acute severity of illness. Retained antimicrobial regimens had predefined susceptibility rates ≥90% for noncritically ill and ≥95% for critically ill patients. Results: Among 390 patients, health care-associated (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.5-6.3] and hospital-acquired sites of acquisition (OR: 3.7, 95% CI: 1.6-8.4) were identified as risk factors for BSI due to P aeruginosa or CAE, compared with community-acquired BSI (referent). Based on stratified bloodstream antibiogram, ceftriaxone met predefined susceptibility criteria for community-acquired BSI in noncritically ill patients (95%). Cefepime and piperacillin-tazobactam monotherapy achieved predefined susceptibility criteria in noncritically ill (95% both) and critically ill patients with health care-associated and hospital-acquired BSI (96% and 97%, respectively) and critically ill patients with community-acquired BSI (100% both). Conclusions: Incorporation of site of acquisition, local antimicrobial susceptibility rates, and acute severity of illness into institutional guidelines provides objective evidence-based approach for optimizing empirical antimicrobial therapy for Gram-negative BSI. The suggested methodology provides a framework for guideline development in other institutions.

Prediction of Fluoroquinolone Resistance in Gram-Negative Bacteria Causing Bloodstream Infections.

Increasing rates of fluoroquinolone resistance (FQ-R) have limited empirical treatment options for Gram-negative infections, particularly in patients with severe beta-lactam allergy. This case-control study aims to develop a clinical risk score to predict the probability of FQ-R in Gram-negative bloodstream isolates. Adult patients with Gram-negative bloodstream infections (BSI) hospitalized at Palmetto Health System in Columbia, South Carolina, from 2010 to 2013 were identified. Multivariate logistic regression was used to identify independent risk factors for FQ-R. Point allocation in the fluoroquinolone resistance score (FQRS) was based on regression coefficients. Model discrimination was assessed by the area under receiver operating characteristic curve (AUC). Among 824 patients with Gram-negative BSI, 143 (17%) had BSI due to fluoroquinolone-nonsusceptible Gram-negative bacilli. Independent risk factors for FQ-R and point allocation in FQRS included male sex (adjusted odds ratio [aOR], 1.97; 95% confidence intervals [CI], 1.36 to 2.98; 1 point), diabetes mellitus (aOR, 1.54; 95% CI, 1.03 to 2.28; 1 point), residence at a skilled nursing facility (aOR, 2.28; 95% CI, 1.42 to 3.63; 2 points), outpatient procedure within 30 days (aOR, 3.68; 95% CI, 1.96 to 6.78; 3 points), prior fluoroquinolone use within 90 days (aOR, 7.87; 95% CI, 4.53 to 13.74; 5 points), or prior fluoroquinolone use within 91 to 180 days of BSI (aOR, 2.77; 95% CI, 1.17 to 6.16; 3 points). The AUC for both final logistic regression and FQRS models was 0.73. Patients with an FQRS of 0, 3, 5, or 8 had predicted probabilities of FQ-R of 6%, 22%, 39%, or 69%, respectively. The estimation of patient-specific risk of antimicrobial resistance using FQRS may improve empirical antimicrobial therapy and fluoroquinolone utilization in Gram-negative BSI.

Stratification of the impact of inappropriate empirical antimicrobial therapy for Gram-negative bloodstream infections by predicted prognosis.

The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (<5, 5 to 9, and ≥ 10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31; P = 0.02) and BSIMRS of ≥ 10 (aHR, 4.99; 95% CI, 1.09 to 22.87; P = 0.04) but not in those with BSIMRS of <5 (aHR, 3.34; 95% CI, 0.17 to 22.77; P = 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of <5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥ 10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥ 10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of <5) at initial presentation.

The prevalence of gram-negative bacteria with difficult-to-treat resistance and utilization of novel ß-lactam antibiotics in the southeastern United States.

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel ß-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design: Retrospective, multicenter, cohort. Setting: Ten hospitals in the southeastern United States. Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel ß-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel ß-lactams. Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel ß-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden. Conclusions: The overall prevalence of GNB with DTR and the use of novel ß-lactams remain low. However, the uptrend in the use of novel ß-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.

Optimization of Empirical Antimicrobial Therapy in Enterobacterales Bloodstream Infection Using the Extended-Spectrum Beta-Lactamase Prediction Score.

Clinical tools for the prediction of antimicrobial resistance have been derived and validated without examination of their implementation in clinical practice. This study examined the impact of utilization of the extended-spectrum beta-lactamase (ESBL) prediction score on the time to initiation of appropriate antimicrobial therapy for bloodstream infection (BSI). The quasi-experimental cohort study included hospitalized adults with BSI due to ceftriaxone-resistant (CRO-R) Enterobacterales at three community hospitals in Columbia, South Carolina, USA before (January 2010 to December 2013) and after (January 2014 to December 2019) implementation of an antimicrobial stewardship intervention. In total, 45 and 101 patients with BSI due to CRO-R Enterobacterales were included before and after the intervention, respectively. Overall, the median age was 66 years, 85 (58%) were men, and 86 (59%) had a urinary source of infection. The mean time to appropriate antimicrobial therapy was 78 h before and 46 h after implementation of the antimicrobial stewardship intervention (p = 0.04). Application of the ESBL prediction score as part of an antimicrobial stewardship intervention was associated with a significant reduction in time to appropriate antimicrobial therapy in patients with BSI due to CRO-R Enterobacterales. Utilization of advanced rapid diagnostics may be necessary for a further reduction in time to appropriate antimicrobial therapy in this population.

Clinical Utility and Cost Effectiveness of Long-Acting Lipoglycopeptides Used in Deep-Seated Infections among Patients with Social and Economic Barriers to Care.

The use of long-acting lipoglycopeptides (LaLGPs) in serious, deep-seated infections is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT). This is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients were matched 1:1 to those who received standard of care (SOC). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics beyond planned course within 90 days of initial infection. There was no difference in clinical failure between the two cohorts (22% vs. 30%; p = 0.491). Six patients in the SOC cohort left against medical advice (AMA) prior to completing therapy. Among those who did not leave AMA, receipt of LaLGPs resulted in a decreased hospital length of stay by an average of 13.6 days. The average total healthcare-related cost of care was USD 295,589 in the LaLGP cohort compared to USD 326,089 in the SOC cohort (p = 0.282). Receipt of LaLGPs may be a beneficial treatment option for patients with deep-seated infections and socioeconomic factors who are not candidates for oral transition or OPAT.

Impact of follow up blood cultures on outcomes of patients with community-onset gram-negative bloodstream infection.

BACKGROUND: The role of follow up blood cultures (FUBC) in the management of gram-negative bloodstream infection (GN-BSI) remains controversial. This retrospective cohort study examines the association between obtaining FUBC and mortality in GN-BSI. METHODS: Hospitalized adults with community-onset GN-BSI at Prisma Health-Midlands hospitals in South Carolina, USA from January 1, 2010 to June 30, 2015 were identified. Patients who died or were discharged from hospital within 72 h were excluded to minimize impact of survival and selection biases on results, respectively. Multivariate Cox proportional hazards regression was used to examine association between obtaining FUBC and 28-day all-cause mortality after adjustment for the propensity to obtain FUBC. FINDINGS: Among 766 patients with GN-BSI, 219 (28.6%) had FUBC obtained and 15 of 219 (6.8%) FUBC were persistently positive. Overall, median age was 67 years, 438 (57%) were women, 457 (60%) had urinary source of infection, and 426 (56%) had BSI due to Escherichia coli. Mortality was significantly lower in patients who had FUBC obtained than in those who did not have FUBC (6.3% vs. 11.7%, log-rank p = 0.03). Obtaining FUBC was independently associated with reduced mortality (hazards ratio 0.47, 95% confidence intervals: 0.23-0.87; p = 0.02) after adjustments for age, chronic comorbidities, acute severity of illness, appropriateness of empirical antimicrobial therapy, and propensity to obtain FUBC. INTERPRETATION: Improved survival in hospitalized patients with GN-BSI who had FUBC is consistent with the results of recent publications from Italy and North Carolina supporting utilization of FUBC in management of GN-BSI. FUNDING: This study had no funding source.

Change in Antimicrobial Use During COVID-19 Pandemic in South Carolina Hospitals: A Multicenter Observational Cohort Study.

OBJECTIVES: This retrospective cohort study examined the impact of the pandemic on antimicrobial use (AU) in South Carolina hospitals. METHODS: Antimicrobial use in days of therapy (DOT) per 1000 days-present was evaluated in 17 hospitals in South Carolina. Matched-pairs mean difference was used to compare AU during the pandemic (March-June 2020) with that during the same months in 2019 in hospitals that did and did not admit patients with COVID-19. RESULTS: There was a 6.6% increase in overall AU in the seven hospitals that admitted patients with COVID-19 (from 530.9 to 565.8; mean difference (MD) 34.9 DOT/1000 days-present; 95% CI 4.3, 65.6; P = 0.03). There was no significant change in overall AU in the remaining 10 hospitals that did not admit patients with COVID-19 (MD 6.0 DOT/1000 days-present; 95% CI -55.5, 67.6; P = 0.83). Most of the increase in AU in the seven hospitals that admitted patients with COVID-19 was observed in broad-spectrum antimicrobial agents. A 16.4% increase was observed in agents predominantly used for hospital-onset infections (from 122.3 to 142.5; MD 20.1 DOT/1000 days-present; 95% CI 11.1, 29.1; P = 0.002). There was also a 9.9% increase in the use of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents (from 66.7 to 73.3; MD 6.6 DOT/1000 days-present; 95% CI 2.3, 10.8; P = 0.01). CONCLUSION: The COVID-19 pandemic appears to drive overall and broad-spectrum antimicrobial use in South Carolina hospitals admitting patients with COVID-19. Additional antimicrobial stewardship resources are needed to curtail excessive antimicrobial use in hospitals to prevent subsequent increases in antimicrobial resistance and Clostridioides difficile infection rates, given the continuing nature of the pandemic.

Application of Standardized Antimicrobial Administration Ratio as a Motivational Tool within a Multi-Hospital Healthcare System.

The standardized antimicrobial administration ratio (SAAR) is a novel antimicrobial stewardship metric that compares actual to expected antimicrobial use (AU). This prospective cohort study examines the utility of SAAR reporting and inter-facility comparisons as a motivational tool to improve overall and broad-spectrum AU within a three-hospital healthcare system. Transparent inter-facility comparisons were deployed during system-wide antimicrobial stewardship meetings beginning in October 2017. Stakeholders were advised to interpret the results to foster competition and incorporate SAAR data into focused antimicrobial stewardship interventions. Student's t-test was used to compare mean SAARs in the pre- (July 2017 through October 2017) and post-intervention periods (November 2017 through June 2019). The mean pre-intervention SAARs for hospitals A, B, and C were 0.69, 1.09, and 0.60, respectively. Hospital B experienced significant reductions in SAAR for overall AU (from 1.09 to 0.83; p < 0.001), broad-spectrum antimicrobials used for hospital-onset infections (from 1.36 to 0.81; p < 0.001), and agents used for resistant gram-positive infections in the intensive care units (from 1.27 to 0.72; p < 0.001) after the interventions. The alignment of the SAAR across the health-system and sustained reduction in overall and broad-spectrum AU through implementation of inter-facility comparisons demonstrate the utility in the motivational application of this antimicrobial use metric.