Development and validation of a screening tool for early identification of bloodstream infection in acute burn injury patients.

Background: Standard diagnostic criteria are not useful for identifying bloodstream infection in patients with an acute burn injury patients. The study objective was to develop and validate a tool using common laboratory, clinical, and patient parameters for early identification of bloodstream infection after acute burn injury (within 10 days after a burn).

Methods: We retrospectively and prospectively reviewed for tool development the hospital course of patients with an acute burn injury (n = 156) and validated the tool in different cohorts (retrospective [n = 26] and prospective [n = 90]).

Monte Carlo simulation evaluation of tigecycline dosing for bacteria with raised minimum inhibitory concentrations in non-critically ill adults.

Purpose: Tigecycline is one of few antibiotics active against multidrug-resistant bacteria; however, the assessment of dosing strategies to optimize its activity is needed. The purpose was to use Monte Carlo Simulation (MCS) to determine if safe tigecycline dosing options attaining breakpoints for pharmacokinetic/pharmacodynamic (PK-PD) targets in non-critically ill adults could be identified.

Methods: Publications that evaluated tigecycline dosing regimens and provided mean PK variables of interest (minimum 2 of: elimination rate constant or half-life and volume of distribution or clearance), with SDs, were included.

Using Prior Culture Results to Improve Initial Empiric Antibiotic Prescribing: An Evaluation of a Simple Clinical Heuristic.

Background: A patient's prior cultures can inform the subsequent risk of infection from resistant organisms, yet prescribers often fail to incorporate these results into their empiric antibiotic selection. Given that timely initiation of adequate antibiotics has been associated with improved outcomes, there is an urgent need to address this gap.

Methods: In order to better incorporate prior culture results in the selection of empiric antibiotics, we performed a pragmatic, prospective, hospital-wide intervention: (1) empiric antibiotic prescriptions were assessed for clinically significant discordance with the most recent methicillin-resistant Staphylococcus aureus (MRSA) surveillance swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and the most recent culture for a Gram-negative (GN) organism; and (2) if discordant, an antimicrobial stewardship pharmacist provided recommendations for alternative therapy.

Improving Decision Making in Empiric Antibiotic Selection (IDEAS) for Gram-negative Bacteremia: A Prospective Clinical Implementation Study.

Background: Timely selection of adequate empiric antibiotics has become increasingly difficult due to rising resistance rates and the competing desire to apply antimicrobial stewardship (AMS) principles. Individualized clinical prediction models offer the promise of reducing broad-spectrum antibiotic use and preserving/improving adequacy of treatment, but few have been validated in the clinical setting.

Methods: Multivariable models were used to predict the probability of susceptibility for gram-negative (GN) bacteria in bloodstream infections (bacteremia) to ceftriaxone, ciprofloxacin, ceftazidime, piperacillin-tazobactam, and meropenem.

Retrospective multicentre matched cohort study comparing safety and efficacy outcomes of intermittent-infusion versus continuous-infusion vancomycin.

Background: Patients with good renal function receiving intermittent-infusion vancomycin (IIV) may require total daily doses ≥4 g to achieve trough concentrations of 15-20 mg/L, increasing the risk of vancomycin-associated nephrotoxicity. Continuous-infusion vancomycin (CIV) may be associated with a lower risk of vancomycin-associated nephrotoxicity compared with IIV, but studies comparing safety of both dosing strategies are lacking.

Objectives: To compare the risk of nephrotoxicity with CIV versus IIV when target concentration ranges were the same with both dosing modalities.

Development and validation of a screening tool for early identification of bloodstream infection in older patients - a retrospective case-control study.

Background: Delayed diagnosis of bloodstream infection (BSI) occurs in > 20% of older patients, with misdiagnosis in 35%. Our objective was to develop and validate a clinically useful screening tool to identify older patients with a high probability of having a BSI.

Methods: Hospitalized patients > 80 years old with BSI (n = 105/group) were evaluated for the tool development in this retrospective matched case-controlled study (learn cohort).

Impact of a Comprehensive Antimicrobial Stewardship Program on Institutional Burden of Antimicrobial Resistance: A 14-Year Controlled Interrupted Time-series Study.

Background: Antimicrobial resistance (AMR) constitutes an international public health threat widely believed to result from excessive antimicrobial use (AMU). Numerous authorities have recommended antimicrobial stewardship programs (ASPs) to curb the selection of AMR, but there is a lack of data confirming this benefit.

Methods: A controlled interrupted time-series study spanning 14 years was performed to assess impact of a comprehensive hospital-based ASP that included pharmacist-led audit and feedback on institutional AMR.

Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation - a retrospective study.

Background: Although aminoglycosides are routinely used in neonates, controversy exists regarding empiric dosing regimens. The objectives were to determine gentamicin pharmacokinetics in neonates, and develop initial mg/kg dosing recommendations that optimized target peak and trough concentration attainment for conventional and extended-interval dosing (EID) regimens.

Methods: Patient demographics and steady-state gentamicin concentration data were retrospectively collected for 60 neonates with no renal impairment admitted to a level III neonatal intensive care unit.

Development, evaluation and validation of a screening tool for late onset bacteremia in neonates - a pilot study.

Background: Clinical and laboratory parameters can aid in the early identification of neonates at risk for bacteremia before clinical deterioration occurs. However, current prediction models have poor diagnostic capabilities. The objective of this study was to develop, evaluate and validate a screening tool for late onset (> 72 h post admission) neonatal bacteremia using common laboratory and clinical parameters; and determine its predictive value in the identification of bacteremia.

Fluoroquinolone Antibiotic Prophylaxis to Prevent Post-Traumatic Bacterial Infectious Endophthalmitis: Using Monte Carlo Simulation to Evaluate the Probability of Success.

Patients with open globe injuries routinely receive fluoroquinolone (FQ) prophylaxis to prevent bacterial infectious endophthalmitis. Owing to the rarity of this infection, there is an absence of clinical trials evaluating optimal prophylactic FQ dosing. To address this knowledge gap, we conducted a Monte Carlo simulation (MCS)-based study to identify the FQ dosing option(s) that optimize pharmacokinetic-pharmacodynamic FQ target attainment against common bacterial pathogens implicated in post-traumatic bacterial infectious endophthalmitis (PTBIE).

The impact of vancomycin trough concentrations on outcomes in non-deep seated infections: a retrospective cohort study.

Background: Guidelines recommending vancomycin trough concentrations > 10 mg/L in non-deep seated infections are based on expert opinion. The objective of this study was to evaluate patients with non-deep seated infections treated with short-course vancomycin to determine whether there were differences in outcomes with trough concentrations of ≤10 mg/L (low) versus > 10 mg/L (high).

Methods: A retrospective cohort study of patients hospitalized between March 10, 2010 and December 31, 2015 who received ≤14 days of vancomycin to treat a non-deep seated infection and had at least one steady state trough concentration was completed.

Prophylactic Antimicrobial Therapy for Acute Aspiration Pneumonitis.

Background: Prophylactic antimicrobial therapy is frequently prescribed for acute aspiration pneumonitis, with the intent of preventing the development of aspiration pneumonia. However, few clinical studies have examined the benefits and harms of this practice.

Methods: A retrospective cohort study design was used to compare outcomes of patients with aspiration pneumonitis who received prophylactic antimicrobial therapy with those managed with supportive care only during the initial 2 days following macroaspiration.

Steady-State Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis Patients: Brief Report.

Steady-state pharmacokinetics of oral ciprofloxacin in 3 continuous cycling peritoneal dialysis (CCPD) outpatients given ciprofloxacin 750 mg b.i.d.

A prospective study evaluating tobramycin pharmacokinetics and optimal once daily dosing in burn patients.

Background: Once-daily aminoglycoside dosing (ODA) is used in most patient populations to optimize antibacterial activity and reduce toxicity. Unfortunately, burn patients are excluded from ODA due to concerns over altered pharmacokinetics resulting in a shortened half-life and low peak aminoglycoside concentrations. Retrospective studies suggest that ODA may be appropriate if higher milligram/kilogram doses are used.

Point-of-Care β-Lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation.

Background: β-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point of care.

Methods: We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at 3 hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving nonpreferred therapy due to severity of their reported allergy.

Elimination of Screening Urine Cultures Prior to Elective Joint Arthroplasty.

Discontinuing routine processing of screening urine cultures prior to elective joint arthroplasty resulted in substantial reduction in urine cultures ordered and antimicrobial prescriptions for asymptomatic bacteriuria, without any significant impact on incidence of prosthetic joint infection. This simple change would be scalable across institutions with potential for significant healthcare savings.

Antibiotic Use and Need for Antimicrobial Stewardship in Long-Term Care.

Background: Antimicrobial stewardship may be important in long-term care facilities because of unnecessary or inappropriate antibiotic use observed in these residents, coupled with their increased vulnerability to health care-associated infections.

Objectives: To assess antibiotic use in a long-term care facility in order to identify potential antimicrobial stewardship needs.

Methods: A retrospective descriptive study was conducted at the Veterans Centre, a long-term care facility at Sunnybrook Health Sciences Centre, Toronto, Ontario.

Impact of hospital length of stay on the distribution of Gram negative bacteria and likelihood of isolating a resistant organism in a Canadian burn center.

Rationale: The impact of hospital length of stay (LOS) on the distribution and susceptibility of Gram negative bacteria (GNB) causing infection in burn patients remains unexplored. Knowledge of causative pathogens is important in guiding empiric antibiotic therapy.

Objectives: To characterize the distribution of GNB causing infection and to identify changes in susceptibility with LOS in a tertiary care burn center.

Outcomes in Documented Pseudomonas aeruginosa Bacteremia Treated with Intermittent IV Infusion of Ceftazidime, Meropenem, or Piperacillin-Tazobactam: A Retrospective Study.

Background: Pseudomonas aeruginosa, one of the leading causes of nosocomial gram-negative bloodstream infections, is particularly difficult to treat because of its multiple resistance mechanisms combined with a lack of novel antipseudomonal antibiotics. Despite knowledge of time-dependent killing with ß-lactam antibiotics, most hospitals in Canada currently administer ß-lactam antibiotics by intermittent rather than extended infusions.

Objectives: To determine clinical outcomes, microbiological outcomes, total hospital costs, and infection-related costs for patients with P.

Point prevalence survey of antimicrobial utilization in a Canadian tertiary-care teaching hospital.

Objectives: Inappropriate antimicrobial use can promote antimicrobial resistance, which is associated with increased patient morbidity and mortality. Identifying the pattern of antimicrobial use can provide data from which targeted antimicrobial stewardship interventions can be made. The primary objective was to identify the prevalence of antimicrobial use at a tertiary care teaching hospital with both acute and long-term care patients.

Lessons from audit and feedback of hospitalized patients with bacteriuria.

We sought to prevent the initiation of antimicrobial therapy for asymptomatic bacteriuria (ASB) by providing audit and feedback of newly reported positive urine cultures to test whether this could empower providers to leave ASB untreated. Despite success in providing feedback before antibiotics could be initiated in most cases, these recommendations only reduced treatment duration, without affecting antibiotic initiation. This study highlights the limitations of educational initiatives in overcoming engrained beliefs about bacteriuria even when advice is provided in real time.

Identifying barriers to medication discharge counselling by pharmacists.

Background: Medication errors may occur more frequently at discharge, making discharge counselling a vital facet of medication reconciliation. Discharge counselling is a recognized patient safety initiative for which pharmacists have appropriate expertise, but data are lacking about the barriers to provision of this service to adult inpatients by pharmacists.

Objectives: To determine the proportion of eligible patients who received discharge counselling, to quantify perceived barriers preventing pharmacists from performing discharge counselling, and to determine the relative frequency of barriers and associated time expenditures.

Hospital-wide rollout of antimicrobial stewardship: a stepped-wedge randomized trial.

Our objective was to rigorously evaluate the impact of an antimicrobial stewardship audit-and-feedback intervention, via a stepped-wedge randomized trial. An effective intensive care unit (ICU) audit-and-feedback program was rolled out to 6 non-ICU services in a randomized sequence. The primary outcome was targeted antimicrobial utilization, using a negative binomial regression model to assess the impact of the intervention while accounting for secular and seasonal trends.

Determination of vancomycin pharmacokinetics in neonates to develop practical initial dosing recommendations.

Variability in neonatal vancomycin pharmacokinetics and the lack of consensus for optimal trough concentrations in neonatal intensive care units pose challenges to dosing vancomycin in neonates. Our objective was to determine vancomycin pharmacokinetics in neonates and evaluate dosing regimens to identify whether practical initial recommendations that targeted trough concentrations most commonly used in neonatal intensive care units could be determined. Fifty neonates who received vancomycin with at least one set of steady-state levels were evaluated retrospectively.

Determination of tobramycin pharmacokinetics in burn patients to evaluate the potential utility of once-daily dosing in this population.

The objective was to determine the pharmacokinetics of tobramycin in critically ill adult burn patients and evaluate a variety of milligram per kilogram (mg/kg) total body weight (TBW) regimens to determine whether practical initial once-daily administration recommendations to attain desired plasma levels could be identified. A retrospective study was conducted in 58 eligible patients who received tobramycin and had at least one set of steady-state levels from which pharmacokinetic parameters could be determined using standard first-order pharmacokinetic equations. Classification and Regression Tree analysis was used to identify whether tobramycin clearance changed with time postburn.