Julie Ann Justo

Antibiotic lock therapy: review of technique and logistical challenges

Antibiotic lock therapy (ALT) for the prevention and treatment of catheter-related bloodstream infections is a simple strategy in theory, yet its real-world application may be delayed or avoided due to technical questions and/or logistical challenges. This review focuses on these latter aspects of ALT, including preparation information for a variety of antibiotic lock solutions (ie, aminoglycosides, beta-lactams, fluoroquinolones, folate antagonists, glycopeptides, glycylcyclines, lipopeptides, oxazolidinones, polymyxins, and tetracyclines) and common clinical issues surrounding ALT administration. Detailed data regarding concentrations, additives, stability/compatibility, and dwell times are summarized. Logistical challenges such as lock preparation procedures, use of additives (eg, heparin, citrate, or ethylenediaminetetraacetic acid), timing of initiation and therapy duration, optimal dwell time and catheter accessibility, and risks of ALT are also described. Development of local protocols is recommended in order to avoid these potential barriers and encourage utilization of ALT where appropriate.

Clinical Risk Score for Prediction of Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae in Bloodstream Isolates

OBJECTIVE To develop a risk score to predict probability of bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE). DESIGN Retrospective case-control study. SETTING Two large community hospitals. PATIENTS Hospitalized adults with Enterobacteriaceae BSI between January 1, 2010, and June 30, 2015. METHODS Multivariate logistic regression was used to identify independent risk factors for ESBLE BSI. Point allocation in extended-spectrum β-lactamase prediction score (ESBL-PS) was based on regression coefficients. RESULTS Among 910 patients with Enterobacteriaceae BSI, 42 (4.6%) had ESBLE bloodstream isolates. Most ESBLE BSIs were community onset (33 of 42; 79%), and 25 (60%) were due to Escherichia coli. Independent risk factors for ESBLE BSI and point allocation in ESBL-PS included outpatient procedures within 1 month (adjusted odds ratio [aOR], 8.7; 95% confidence interval [CI], 3.1-22.9; 1 point), prior infections or colonization with ESBLE within 12 months (aOR, 26.8; 95% CI, 7.0-108.2; 4 points), and number of prior courses of β-lactams and/or fluoroquinolones used within 3 months of BSI: 1 course (aOR, 6.3; 95% CI, 2.7-14.7; 1 point), ≥2 courses (aOR, 22.0; 95% CI, 8.6-57.1; 3 points). The area under the receiver operating characteristic curve for the ESBL-PS model was 0.86. Patients with ESBL-PSs of 0, 1, 3, and 4 had estimated probabilities of ESBLE BSI of 0.7%, 5%, 24%, and 44%, respectively. Using ESBL-PS ≥3 to indicate high risk provided a negative predictive value of 97%. CONCLUSIONS ESBL-PS estimated patient-specific risk of ESBLE BSI with high discrimination. Incorporation of ESBL-PS with acute severity of illness may improve adequacy of empirical antimicrobial therapy and reduce carbapenem utilization. Infect Control Hosp Epidemiol 2017;38:266-272.

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

ABSTRACT 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.

Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections

There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for <14 days at Palmetto Health Hospitals in Columbia, SC, from 1 January 2010 through 31 December 2013 and discharged on oral antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, <75%). Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine treatment failure. Among the 362 patients, high, moderate and low bioavailability oral antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines.

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.

Differential effect of prior β-lactams and fluoroquinolones on risk of bloodstream infections secondary to Pseudomonas aeruginosa

OBJECTIVE This retrospective case-control study examines risk factors for bloodstream infections (BSI) due to Pseudomonas aeruginosa (PSA). METHODS Hospitalized adults with Gram-negative BSI at Palmetto Health from 2010 to 2015 were identified. Multivariate logistic regression was used to examine PSA BSI risk factors. RESULTS Seventy and 910 patients with PSA and Enterobacteriaceae BSI, respectively, were included. Prior use of β-lactams (adjusted odds ratio [aOR] 3.9, 95% confidence intervals [CI]: 2.3-6.9), but not fluoroquinolones (aOR 1.0, 95% CI: 0.4-2.2), was a risk factor for PSA BSI. Immune compromised status (aOR 3.7, 95% CI: 2.0-6.7), respiratory source (aOR 4.4, 95% CI: 2.1-8.9), and prolonged hospitalization (aOR 1.9, 95% CI: 1.1-3.5), were predictors of PSA BSI. CONCLUSIONS Determination of class of previously used antibiotics among other clinical variables helps identify patients at risk of PSA BSI and offers opportunities to optimize empirical antimicrobial therapy.

Association between chronic hemodialysis and bloodstream infections caused by chromosomally mediated AmpC-producing Enterobacteriaceae

BACKGROUND The combination of inherent antimicrobial resistance and high mortality after bloodstream infections (BSIs) caused by chromosomally mediated AmpC-producing Enterobacteriaceae (CAE) emphasizes the importance of identifying patients at risk of BSI because of these bacteria. This retrospective case-control study examines chronic hemodialysis among other risk factors for BSI caused by CAE. METHODS Hospitalized adults with Enterobacteriaceae BSI from January 1, 2010-June 30, 2014, at 2 large community hospitals in the Southeastern United States were identified. Multivariate logistic regression was used to examine risk factors for CAE BSI. RESULTS Among 831 Enterobacteriaceae bloodstream isolates, 106 (13%) met the phenotypic definition of CAE. Enterobacter spp accounted for 47% (50/106) of CAE BSIs. Chronic hemodialysis was an independent risk factor for CAE BSI (adjusted odds ratio [aOR], 2.34; 95% confidence interval [CI], 1.21-4.44). Other predictors of CAE BSI included nosocomial acquisition (aOR, 1.72; 95% CI, 1.02-2.87) and exposure to β-lactam antibiotics within the last 30 days (aOR, 2.39; 95% CI, 1.37-4.14). CONCLUSIONS To our knowledge, this is the first study to demonstrate an increased risk of CAE BSI in patients with end-stage renal disease undergoing chronic hemodialysis. This highlights the importance of effective infection prevention and antimicrobial stewardship interventions in hemodialysis clinics. Further studies to examine the impact of antibiotics on intestinal microbiota and rates of CAE colonization in this patient population are warranted.

Cumulative Effect of an Antimicrobial Stewardship and Rapid Diagnostic Testing Bundle on Early Streamlining of Antimicrobial Therapy in Gram-Negative Bloodstream Infections

ABSTRACT The use of rapid diagnostic tests (RDTs) enhances antimicrobial stewardship program (ASP) interventions in optimization of antimicrobial therapy. This quasi-experimental cohort study evaluated the combined impact of an ASP/RDT bundle on the appropriateness of empirical antimicrobial therapy (EAT) and time to de-escalation of broad-spectrum antimicrobial agents (BSAA) in Gram-negative bloodstream infections (GNBSI). The ASP/RDT bundle consisted of system-wide GNBSI treatment guidelines, prospective stewardship monitoring, and sequential introduction of two RDTs, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and the FilmArray blood culture identification (BCID) panel. The preintervention period was January 2010 through December 2013, and the postintervention period followed from January 2014 through June 2015. The postintervention period was conducted in two phases; phase 1 followed the introduction of MALDI-TOF MS, and phase 2 followed the introduction of the FilmArray BCID panel. The interventions resulted in significantly improved appropriateness of EAT (95% versus 91%; P = 0.02). Significant reductions in median time to de-escalation from combination antimicrobial therapy (2.8 versus 1.5 days), antipseudomonal beta-lactams (4.0 versus 2.5 days), and carbapenems (4.0 versus 2.5 days) were observed in the postintervention compared to the preintervention period (P < 0.001 for all). The reduction in median time to de-escalation from combination therapy (1.0 versus 2.0 days; P = 0.03) and antipseudomonal beta-lactams (2.2 versus 2.7 days; P = 0.04) was further augmented during phase 2 compared to phase 1 of the postintervention period. Implementation of an antimicrobial stewardship program and RDT intervention bundle in a multihospital health care system is associated with improved appropriateness of EAT for GNBSI and decreased utilization of BSAA through early de-escalation.

Preventing the Post-Antibiotic Era by Training Future Pharmacists as Antimicrobial Stewards

Antimicrobials enable modern medicine, but their efficacy is a limited resource. In the past 20 years, antimicrobial development has slowed dramatically while antimicrobial resistance continues to rise. In response to this, there has been an increased focus on strategically managing antimicrobial use with an approach called “antimicrobial stewardship.” Antimicrobial stewardship programs have been endorsed by health systems, professional societies, regulators, and government. These programs have been shown to reduce antimicrobial use, slow the growth of antimicrobial resistance, and improve patient outcomes. This commentary will discuss recent mandates for antimicrobial stewardship, compare current approaches to teaching infectious diseases pharmacotherapy with the skills and knowledge required for antimicrobial stewardship, and provide recommendations for and examples of best practices in training student pharmacists to become antimicrobial stewards.

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.