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.

Burden of community-associated Clostridioides difficile infection in southeastern United States: a population-based study.

OBJECTIVES: This cross-sectional population-based study aims to determine overall incidence rate of Clostridioides difficile infection (CDI) in the State of South Carolina and provide an estimated cost of hospitalization due to community-associated CDI (CA-CDI). METHODS: All CDI cases in South Carolina were identified through National Healthcare Safety Network (NHSN) and the South Carolina Infectious Disease and Outbreak Network (SCION) from January 1, 2015 to June 30, 2016, excluding infants < 1 year of age. RESULTS: During the 18-month study period, 10,254 CDI events were identified in South Carolina residents with an overall incidence rate of 139/100,000 person-years. Over one-half of CDI cases were CA-CDI (5192; 51%) with an incidence rate of 71/100,000 person-years. Among patients with CA-CDI, 2127 (41%) required hospitalization with a median length of stay of 5 days. The annual burden of CA-CDI in South Carolina was estimated to be 9282 hospital days and $16,217,295 in hospitalization costs. CONCLUSION: The incidence rate of CA-CDI in South Carolina has surpassed both community-onset healthcare facility associated and hospital-onset CDI combined. The heavy burden of CA-CDI justifies dedication of public health resources to combat CDI in ambulatory settings, through antimicrobial stewardship initiatives.

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.

Intra-abdominal infections survival guide: a position statement by the Global Alliance For Infections In Surgery.

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs.