Sandra Walker

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

Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion.

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.

HIV and male circumcision--a systematic review with assessment of the quality of studies.

Introduction:Although HAART has led to a reduction in overall mortality among HIV-infected individuals, its impact on death from specific causes is unknown. Methods:Twenty-two cohorts of HIV-infected individuals with known dates of seroconversion are pooled in the CASCADE collaboration. Causes of death (COD) were categorized into three AIDS-related and seven non-AIDS-related causes. The unknown causes were assigned a separate category. The cumulative incidence for each COD was calculated in the presence of the other competing COD, for the pre-HAART and HAART eras. A multivariate regression analyses for the cumulative rate of progression to the different COD was performed. Results:A total of 1938 of 7680 HIV-seroconverters died. Pre-HAART, AIDS opportunistic infections (OI) was the most common COD, followed by unknown and HIV/AIDS-unspecified. In the HAART era, the cumulative incidence for all AIDS-related COD decreased, OI remaining the most important. Large reductions in death due to other infections and organ failure were seen. Cumulative death risk decreased in the HAART era for most causes. The effect of HAART was not the same for all risk groups. The cumulative risk of death from AIDS-related malignancies, OI and non-AIDS-related malignancies decreased significantly among homosexual men (MSM), whereas the risk of dying from (un)-intentional death increased significantly among injecting drug users (IDU). A non-significant increase in hepatitis/liver-related death was seen in MSM, IDU and haemophiliacs. Conclusion:Overall and cause specific mortality decreased following the introduction of HAART. OI remain the most common COD in the HAART era, suggesting that AIDS-related events will continue to be important in the future. Future trends in COD should be monitored using standardized guidelines.

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

This Cochrane systematic review assesses the evidence for an interventional effect of male circumcision in preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse. The review includes a comprehensive assessment of the quality of all 37 included observational studies. Studies in high-risk populations consisted of four cohort studies, 12 cross-sectional studies, and three case-control studies; general population studies consisted of one cohort study, 16 cross-sectional studies, and one case-control study. There is evidence of methodological heterogeneity between studies, and statistical heterogeneity was highly significant for both general population cross-sectional studies (chi(2)=132.34; degrees of freedom [df]=15; p<0.00001) and high-risk cross-sectional studies (chi(2)=29.70; df=10; p=0.001). Study quality was very variable and no studies measured the same set of potential confounding variables. Therefore, conducting a meta-analysis was inappropriate. Detailed quality assessment of observational studies can provide a useful visual aid to interpreting findings. Although most studies show an association between male circumcision and prevention of HIV, these results may be limited by confounding, which is unlikely to be adjusted for.

Mycoplasma genitalium Incidence, Organism Load, and Treatment Failure in a Cohort of Young Australian Women

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.

Identification of predictors of early infection in acute burn patients

BACKGROUND Mycoplasma genitalium (MG) is an emerging sexually transmitted infection (STI) that is potentially associated with reproductive tract sequelae in women. This study aimed to estimate MG incidence and treatment failure and provide estimates of organism load in infection. METHODS 1110 women aged 16-25 years were recruited from primary care clinics in Australia. Women were tested for MG at baseline, 6 months, and 12 months, and MG organism load was measured by quantitative polymerase chain reaction (PCR). MG-positive cases were screened for MG 23S ribosomal RNA (rRNA) gene point mutations shown to confer azithromycin resistance using high-resolution melt following PCR. RESULTS MG incidence rate was 1.3 per 100 person-years (n=14; 95% confidence interval [CI], .8-2.3); women reporting 3 or more sex partners in the last 12 months had an increased rate of incident infection (rate ratio [RR], 5.1; 95% CI, 1.3-19.6]). There were 3 cases of MG reinfection (0.8 per 100 person-years [95% CI, .1-.9]. Organism load was higher for prevalent than incident infection (P=.04). There were 3 cases of treatment failure (9.4% [95% CI, 2.0-25.0]); organism load was higher in cases with treatment failure than in successfully treated cases (P<.01). An MG 23S rRNA mutation was detected in 5 cases (3 cases of treatment failure and 2 successfully treated). CONCLUSIONS Although MG incidence was relatively low, testing should be recommended for women considered to be at increased risk based on sexual history. Our results also suggest that organism load might be important in azithromycin treatment failure.

Determinants of response to first HAART regimen in antiretroviral‐naïve patients with an estimated time since HIV seroconversion

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.

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

To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV‐1 seroconversion.

Optimizing initial vancomycin dosing in burn patients

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.

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

RATIONALE Burned patients have altered vancomycin pharmacokinetics necessitating adjusted dosing. Published initial dosing recommendations to target troughs of 15-20mg/L for this population are lacking. OBJECTIVE This study was conducted to develop initial vancomycin dosing recommendations based on the pharmacokinetics of vancomycin in acute burn patients. METHODS A retrospective chart review of 49 vancomycin treated burn patients was conducted. Mean pharmacokinetic parameters were determined and Monte Carlo Simulation was used to develop initial vancomycin dosing recommendations that target trough concentrations between 15 and 20mg/L. RESULTS Vancomycin pharmacokinetic parameters were significantly (p < 0.05) different for vancomycin levels obtained 48 h to 14 days after burn versus >14 days after burn. Monte Carlo simulation indicated that the most commonly used empiric dosing regimen (1g iv q12 h) attained targets with a probability of <10% in all burned patients. The probability of attaining targets was optimized to 20-25% by using 1.5 g iv q8 h, 1.75 g iv q8 h, 1g iv q6 h, 1.25g iv q6 h or 750 mg iv q4 h in patients 48 h to 14 days after burn and 1-1.25 g iv q8 h or 500 mg iv q4 h in patients >14 days after burn. CONCLUSIONS This study provides initial vancomycin dosing recommendations for burned patients 48 h to 14 days after burn and patients >14 days after burn. However, because of the heterogeneity in pharmacokinetics and the observation that vancomycin pharmacokinetics change with time after burn, monitoring of vancomycin serum concentrations is required to ensure targets are met and maintained.