Marion Elligsen

Impact of antimicrobial stewardship in critical care: a systematic review

OBJECTIVES To evaluate the current state of evidence for antimicrobial stewardship interventions in the critical care unit. METHODS We performed a systematic search of OVID MEDLINE, Embase and Cochrane electronic databases from 1996-2010. Studies were included if they involved any experimental intervention to improve antimicrobial utilization in the critical care setting. RESULTS Thirty-eight studies met the inclusion criteria, of which 24 met our quality inclusion criteria. The quality of research was poor, with only 3 randomized controlled trials, 3 interrupted time series and 18 (75%) uncontrolled before-and-after studies. We identified six intervention types: studies of antibiotic restriction or pre-approval (six studies); formal infectious diseases physician consultation (five); implementation of guidelines or protocols for de-escalation (two); guidelines for antibiotic prophylaxis or treatment in intensive care (two); formal reassessment of antibiotics on a pre-specified day of therapy (three); and implementation of computer-assisted decision support (six). Stewardship interventions were associated with reductions in antimicrobial utilization (11%-38% defined daily doses/1000 patient-days), lower total antimicrobial costs (US

Audit and Feedback to Reduce Broad-Spectrum Antibiotic Use among Intensive Care Unit Patients A Controlled Interrupted Time Series Analysis

5-10/patient-day), shorter average duration of antibiotic therapy, less inappropriate use and fewer antibiotic adverse events. Stewardship interventions beyond 6 months were associated with reductions in antimicrobial resistance rates, although this differed by drug-pathogen combination. Antibiotic stewardship was not associated with increases in nosocomial infection rates, length of stay or mortality. CONCLUSIONS More rigorous research is needed, but available evidence suggests that antimicrobial stewardship is associated with improved antimicrobial utilization in the intensive care unit, with corresponding improvements in antimicrobial resistance and adverse events, and without compromise of short-term clinical outcomes.

Identification of predictors of early infection in acute burn patients

OBJECTIVE We aimed to rigorously evaluate the impact of prospective audit and feedback on broad-spectrum antimicrobial use among critical care patients. DESIGN Prospective, controlled interrupted time series. SETTING Single tertiary care center with 3 intensive care units. PATIENTS AND INTERVENTIONS A formal review of all critical care patients on their third or tenth day of broad-spectrum antibiotic therapy was conducted, and suggestions for antimicrobial optimization were communicated to the critical care team. OUTCOMES The primary outcome was broad-spectrum antibiotic use (days of therapy per 1000 patient-days; secondary outcomes included overall antibiotic use, gram-negative bacterial susceptibility, nosocomial Clostridium difficile infections, length of stay, and mortality. RESULTS The mean monthly broad-spectrum antibiotic use decreased from 644 days of therapy per 1,000 patient-days in the preintervention period to 503 days of therapy per 1,000 patient-days in the postintervention period (P < .0001); time series modeling confirmed an immediate decrease (± standard error) of 119 ± 37.9 days of therapy per 1,000 patient-days (P = .0054). In contrast, no changes were identified in the use of broad-spectrum antibiotics in the control group (nonintervention medical and surgical wards) or in the use of control medications in critical care (stress ulcer prophylaxis). The incidence of nosocomial C. difficile infections decreased from 11 to 6 cases in the study intensive care units, whereas the incidence increased from 87 to 116 cases in the control wards (P = .04). Overall gram-negative susceptibility to meropenem increased in the critical care units. Intensive care unit length of stay and mortality did not change. CONCLUSIONS Institution of a formal prospective audit and feedback program appears to be a safe and effective means to improve broad-spectrum antimicrobial use in critical care.

Hospital-wide Rollout of Antimicrobial Stewardship: A Stepped-Wedge Randomized Trial

Burn patients are at high risk for infections; however, common indicators of infection are unreliable in this population and can lead to unnecessary use of antibiotics. The study objective was to determine if predictors of early infection in adult acute burn patients are identified to provide clinicians with a practical tool to aid in the diagnosis of infection, thereby minimizing unnecessary exposure to antimicrobials. A retrospective chart review of all adult acute burn injury patients admitted over a 1 year period to the burn centre at Sunnybrook Health Sciences Centre was conducted. Early infection was defined as one that occurred within the first 10 days after injury and in accordance with American Burn Association guidelines. Those without infection were compared to patients with infection generally and also to patients with sepsis specifically. The period prevalence of early infection and sepsis in our patients was 50% (56/111) and 16% (18/111), respectively. It was determined that heart rate ≥110 bpm, systolic blood pressure ≤100 mmHg and intubation were the best predictors of sepsis (p<0.05); and fraction of inhaled oxygen >25% and maximum temperature ≥39 °C were the best predictors of infection (p<0.05). This pilot project identified significant predictors of early infection and sepsis in acute burns and will be validated in a prospective study.

Duration of antibiotic therapy for critically ill patients with bloodstream infections: A retrospective cohort study.

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. The intervention was successfully transitioned, with high volumes of orders reviewed, suggestions made, and recommendations accepted. Among patients meeting stewardship review criteria, the intervention was associated with a large reduction in targeted antimicrobial utilization (-21%, P = .004); however, there was no significant change in targeted antibiotic use among all admitted patients (-1.2%, P = .9), and no reductions in overall costs and microbiologic outcomes. An ICU day 3 audit-and-feedback program can be successfully expanded hospital-wide, but broader benefits on non-ICU wards may require interventions earlier in the course of treatment.

Impact of infection with extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella species on outcome and hospitalization costs

BACKGROUND The optimal duration of antibiotic treatment for bloodstream infections is unknown and understudied. METHODS A retrospective cohort study of critically ill patients with bloodstream infections diagnosed in a tertiary care hospital between March 1, 2010 and March 31, 2011 was undertaken. The impact of patient, pathogen and infectious syndrome characteristics on selection of shorter (≤10 days) or longer (>10 days) treatment duration, and on the number of antibiotic-free days, was examined. The time profile of clinical response was evaluated over the first 14 days of treatment. Relapse, secondary infection and mortality rates were compared between those receiving shorter or longer treatment. RESULTS Among 100 critically ill patients with bloodstream infection, the median duration of antibiotic treatment was 11 days, but was highly variable (interquartile range 4.5 to 17 days). Predictors of longer treatment (fewer antibiotic-free days) included foci with established requirements for prolonged treatment, underlying respiratory tract focus, and infection with Staphylococcus aureus or Pseudomonas species. Predictors of shorter treatment (more antibiotic-free days) included vascular catheter source and bacteremia with coagulase-negative staphylococci. Temperature improvements plateaued after the first week; white blood cell counts, multiple organ dysfunction scores and vasopressor dependence continued to decline into the second week. Among 72 patients who survived to 10 days, clinical outcomes were similar between those receiving shorter and longer treatment. CONCLUSION Antibiotic treatment durations for patients with bloodstream infection are highly variable and often prolonged. A randomized trial is needed to determine the duration of treatment that will maximize cure while minimizing adverse consequences of antibiotics.

Predictive Utility of Prior Positive Urine Cultures

BACKGROUND Extended-spectrum β-lactamase (ESBL)-producing bacteria are important sources of infection; however, Canadian data evaluating the impact of ESBL-associated infection are lacking. AIM To determine whether patients infected with ESBL-producing Escherichia coli or Klebsiella species (ESBL-EcKs) exhibit differences in clinical outcome, microbiological outcome, mortality, and/or hospital resource use compared to patients infected with non-ESBL-producing strains. METHODS A retrospective case-control study of 75 case patients with ESBL-EcKs matched to controls infected with non-ESBL-EcKs who were hospitalized from June 2010 to April 2013 was conducted. Patient-level cost data were provided by the institutions business office. Clinical data were collected using the electronic databases and paper charts. FINDINGS Median infection-related hospitalization costs per patient were greater for cases than controls (C

Determination of Vancomycin Pharmacokinetics in Neonates To Develop Practical Initial Dosing Recommendations

10,507 vs C

Utility of prior screening for methicillin-resistant Staphylococcus aureus in predicting resistance of S. aureus infections

7,882; median difference: C

Patient Characteristics and Outcomes of Outpatient Parenteral Antimicrobial Therapy: A Retrospective Study

3,416; P = 0.04). The primary driver of increased costs was prolonged infection-related hospital length of stay (8 vs 6 days; P = 0.02) with patient location (ward, ICU) and indirect care costs (including costs associated with infection prevention and control) as the leading cost categories. Cases were more likely to experience clinical failure (25% vs 11%; P = 0.03), with a higher all-cause mortality (17% vs 5%; P = 0.04). Less than half of case patients were prescribed appropriate empiric antimicrobial therapy, whereas controls received adequate initial treatment in nearly all circumstances (48% vs 96%; P < 0.01). CONCLUSION Patients with infection caused by ESBL-EcKs are at increased risk for clinical failure and mortality, with additional cost to the Canadian healthcare system of C