Nick Daneman

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

Meta-Analysis of Antibiotics and the Risk of Community-Associated Clostridium difficile Infection

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.

Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis.

ABSTRACT The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

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

BACKGROUND Many meta-analyses have shown reductions in infection rates and mortality associated with the use of selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) in intensive care units (ICUs). These interventions have not been widely implemented because of concerns that their use could lead to the development of antimicrobial resistance in pathogens. We aimed to assess the effect of SDD and SOD on antimicrobial resistance rates in patients in ICUs. METHODS We did a systematic review of the effect of SDD and SOD on the rates of colonisation or infection with antimicrobial-resistant pathogens in patients who were critically ill. We searched for studies using Medline, Embase, and Cochrane databases, with no limits by language, date of publication, study design, or study quality. We included all studies of selective decontamination that involved prophylactic application of topical non-absorbable antimicrobials to the stomach or oropharynx of patients in ICUs, with or without additional systemic antimicrobials. We excluded studies of interventions that used only antiseptic or biocide agents such as chlorhexidine, unless antimicrobials were also included in the regimen. We used the Mantel-Haenszel model with random effects to calculate pooled odds ratios. FINDINGS We analysed 64 unique studies of SDD and SOD in ICUs, of which 47 were randomised controlled trials and 35 included data for the detection of antimicrobial resistance. When comparing data for patients in intervention groups (those who received SDD or SOD) versus data for those in control groups (who received no intervention), we identified no difference in the prevalence of colonisation or infection with Gram-positive antimicrobial-resistant pathogens of interest, including meticillin-resistant Staphylococcus aureus (odds ratio 1·46, 95% CI 0·90-2·37) and vancomycin-resistant enterococci (0·63, 0·39-1·02). Among Gram-negative bacilli, we detected no difference in aminoglycoside-resistance (0·73, 0·51-1·05) or fluoroquinolone-resistance (0·52, 0·16-1·68), but we did detect a reduction in polymyxin-resistant Gram-negative bacilli (0·58, 0·46-0·72) and third-generation cephalosporin-resistant Gram-negative bacilli (0·33, 0·20-0·52) in recipients of selective decontamination compared with those who received no intervention. INTERPRETATION We detected no relation between the use of SDD or SOD and the development of antimicrobial-resistance in pathogens in patients in the ICU, suggesting that the perceived risk of long-term harm related to selective decontamination cannot be justified by available data. However, our study indicates that the effect of decontamination on ICU-level antimicrobial resistance rates is understudied. We recommend that future research includes a non-crossover, cluster randomised controlled trial to assess long-term ICU-level changes in resistance rates. FUNDING None.

IDENTIFICATION OF A PROGENITOR OF THE CTX-M-9 GROUP OF EXTENDED-SPECTRUM BETA-LACTAMASES FROM KLUYVERA GEORGIANA ISOLATED IN GUYANA

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.

Delirium after elective surgery among elderly patients taking statins

ABSTRACT Chromosomal β-lactamase genes (blaKLUY) from six Kluyvera georgiana strains isolated in Guyana were cloned and expressed in Escherichia coli. KLUY-1 exhibited 100% amino acid identity with the extended-spectrum β-lactamase CTX-M-14. We also show that a 2.7-kb Kluyvera chromosomal region exhibits 99% nucleotide identity to a portion of In60 that includes blaCTX-M-9.

Reducing Antimicrobial Therapy for Asymptomatic Bacteriuria Among Noncatheterized Inpatients: A Proof-of-Concept Study

Background: Postoperative delirium after elective surgery is frequent and potentially serious. We sought to determine whether the use of statin medications was associated with a higher risk of postoperative delirium than other medications that do not alter microvascular autoregulation. Methods: We conducted a retrospective cohort analysis of 284 158 consecutive patients in Ontario aged 65 years and older who were admitted for elective surgery. We identified exposure to statins from outpatient pharmacy records before admission. We identified delirium by examining hospital records after surgery. Results: About 7% (n = 19 501) of the patients were taking statins. Overall, 3195 patients experienced postoperative delirium; the rate was significantly higher among patients taking statins (14 per 1000) than among those not taking statins (11 per 1000) (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.15–1.47, p < 0.001). The increased risk of postoperative delirium persisted after we adjusted for multiple demographic, medical and surgical factors (OR 1.28, 95% CI 1.12–1.46) and exceeded the increased risk of delirium associated with prolonging surgery by 30 minutes (OR 1.20, 95% CI 1.19–1.21). The relative risk associated with statin use was somewhat higher among patients who had noncardiac surgery than among those who had cardiac surgery (adjusted OR 1.33, 95% CI 1.16–1.53), and extended to more complicated cases of delirium. We did not observe an increased risk of delirium with 20 other cardiac or noncardiac medications. Interpretation: The use of statins is associated with an increased risk of postoperative delirium among elderly patients undergoing elective surgery.

The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study

This proof-of-concept study demonstrates that no longer routinely reporting urine culture results from noncatheterized medical and surgical inpatients can greatly reduce unnecessary antimicrobial therapy for asymptomatic bacteriuria without significant additional laboratory workload. Larger studies are needed to confirm the generalizability, safety, and sustainability of this model of care.

The Economic Impact of Clostridium difficile Infection: A Systematic Review

Background Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. Methodology/Principal Findings We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. Conclusions/Significance Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Use of a structured panel process to define quality metrics for antimicrobial stewardship programs.

Objectives:With Clostridium difficile infection (CDI) on the rise, knowledge of the current economic burden of CDI can inform decisions on interventions related to CDI. We systematically reviewed CDI cost-of-illness (COI) studies.Methods:We performed literature searches in six databases: MEDLINE, Embase, the Health Technology Assessment Database, the National Health Service Economic Evaluation Database, the Cost-Effectiveness Analysis Registry, and EconLit. We also searched gray literature and conducted reference list searches. Two reviewers screened articles independently. One reviewer abstracted data and assessed quality using a modified guideline for economic evaluations. The second reviewer validated the abstraction and assessment.Results:We identified 45 COI studies between 1988 and June 2014. Most (84%) of the studies were from the United States, calculating costs of hospital stays (87%), and focusing on direct costs (100%). Attributable mean CDI costs ranged from