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]). The Pearson correlation identified independent variables associated with bloodstream infection (P < .1) in the development cohort that were then analyzed using binary logistic regression to identify the simplest model (P < .05; adjusted odds ratio >1). Classification and regression tree analysis was used to identify tool parameter breakpoints. Performance metrics were completed to evaluate and validate the tool. RESULTS: The best model (P < .05) was: Ln [odds of bloodstream infection] = -96.749 + 3.230 (platelet volatility) + 2.235 (max temperature [°C]) + 0.339 (% full burn) + 0.242 (% partial burn) + 0.045 (max heart rate [bpm]), with a threshold probability categorizing bloodstream infection of >48%. The sensitivity, specificity, accuracy, false positive rate, false negative rate, and positive (+) and negative (-) likelihood ratios of the tool in the developmental cohort (n = 156) were 89%, 98%, 96%, 2%, 11%, 53, and 0·11, respectively; and in the prospective validation cohort (n = 90 were 91%, 90%, 90%, 10%, 9%, 9, and 0·1, respectively (n = 90). CONCLUSION: The validated bloodstream infection screening tool in patients with acute burn injury has excellent predictive ability to assist in the identification of patients for whom blood cultures should be requested.

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. The impact was analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic, tertiary care institution. RESULTS: Clinically significant discordance was identified 99 times in the preintervention period and 86 times in the intervention period. The proportion of patients that received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = .01). The median time to concordant therapy was shorter in the intervention group than the control group (25 vs 55 hrs, respectively; P < .001; adjusted hazard ratio = 1.95 [95% confidence interval {CI}, 1.37-2.77; P < .001]). The median duration of unnecessary vancomycin therapy was reduced by 1.1 days (95% CI, .5-1.6 days; P < .001). CONCLUSIONS: This intervention improved prescribing, with a shorter time to concordant therapy and an increased proportion of patients receiving empiric therapy concordant with prior culture results. The use of unnecessary vancomycin was also reduced.

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. Weighted mean (±SDs) for each PK parameter were determined. Food and Drug Administration minimum inhibitory concentration (MIC) tigecycline breakpoints for susceptible (MIC ≤ 2 µg/mL), intermediate (MIC 4 µg/mL), and resistant (MIC ≥ 8 µg/mL) Enterobacteriaceae were used. MCS probability distributions for PK-PD target attainment of AUC for total tigecycline plasma concentration from 0 to 24 h following an intravenous dose (AUCtotal, 0-24h) to MIC ratios of ≥ 18, 7, and 4.5 were generated, with success defined as ≥ 80% probability of target attainment at a given MIC. RESULTS: Ten studies (n = 442) were eligible. Tigecycline 150 mg IV q12h for ward patients with resistant bacteria up to a MIC of 0.48, 1, and 2 µg/mL for an AUCtotal, 0-24h/MIC target attainment of 18, 7, and 4.5, respectively, may be appropriate. CONCLUSION: Bacterial infections with tigecycline MICs ≥ 0.48-2 µg/mL, depending on AUCtotal, 0-24h/MIC target, may require treatment with alternate antibiotics due to target attainment failure.

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. The models were combined with existing resistance-prediction methods to generate optimized and individualized suggestions for empiric therapy that were provided to prescribers by an AMS pharmacist. De-escalation of empiric antibiotics and adequacy of therapy were analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic tertiary care institution. RESULTS: Episodes of bacteremia (n = 182) were identified in the preintervention and postintervention (n = 201) periods. Patients who received the intervention were more likely to have their therapy de-escalated (29 vs 21%; aOR = 1.77; 95% CI, 1.09-2.87; P = .02). The intervention also increased the proportion of patients who were on the narrowest adequate therapy at the time of culture finalization (44% in the control and 55% in the intervention group; aOR = 2.04; 95% CI, 1.27-3.27; P = .003). Time to adequate therapy was similar in the intervention and control groups (5 vs 4 hours; P = .95). CONCLUSIONS: An AMS intervention, based on individualized predictive models for resistance, can influence empiric antibiotic selections for GN bacteremia to facilitate early de-escalation of therapy without compromising adequacy of antibiotic coverage.

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. METHODS: A retrospective multicentre matched cohort study of admitted patients between 1 January 2010 and 31 December 2016 was completed. Adult patients who received ≥48 h of vancomycin with at least one steady-state vancomycin concentration were eligible. The primary outcome was to compare the rates of nephrotoxic risk and renal injury, defined by the RIFLE criteria, between CIV and IIV. RESULTS: Of 2136 patients who received vancomycin during the study period, 146 CIV patients were eligible and matched to 146 IIV patients. After adjustment of potential confounders, CIV was found to have a lower odds of developing nephrotoxic risk (OR 0.42, 95% CI 0.21-0.98, P = 0.025) and renal injury (OR 0.19, 95% CI 0.05-0.59, P = 0.004). CONCLUSIONS: CIV is associated with a lower odds of nephrotoxicity compared with IIV when targeting the same concentration range and should be an alternative dosing strategy for patients who will receive prolonged therapy or require >4 g/day to achieve therapeutic levels.

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). The tool was validated in different retrospectively matched case and control patients > 80 years old (n = 120/group) and 65 to 79 years old (n = 250/group) (test cohort). Binary logistic regression was used to develop a screening tool using laboratory and clinical parameters that were significantly associated with BSI (P < 0.05; adjusted odds ratio (OR) > 1); and Classification and Regression Tree (CART) analysis was used to identify parameter breakpoints. Performance metrics were used to evaluate and validate the tool. RESULTS: The significant parameters associated with BSI were maximum temperature (Tmax)(> 37.55C)(OR = 42.575), neutrophils (> 7.95)(OR = 1.923), a change in level of consciousness (LOC) (Yes = 1, No = 0)(OR = 1.571), blood urea nitrogen (BUN)(> 10.05)(OR = 1.359), glucose (> 7.35)(OR = 1.167), albumin (< 33.5)(OR = 1.038) and alanine aminotransferase (ALT) (> 19.5)(OR = 1.005). The optimal screening tool [Ln (odds of BSI) = - 150.299 + 3.751(Tmax) + 0.654(neutrophils) + 0.452(change in LOC) + 0.307(BUN) + 0.154(glucose) + 0.038(albumin) + 0.005(ALT)] had favorable performance metrics in the learn and test cohorts (sensitivity, specificity and accuracy of 95% in the learn cohort and 77, 89, and 81% in the total test cohort); and performed better than using only temperature and neutrophil count. CONCLUSIONS: The validated tool had high predictive value which may improve early identification and management of BSI in older patients.

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. Patient-level microbiologic and AMU data were obtained from October 2002 to September 2016. Poisson regression models were used to identify changes in the incidence and trend of hospital-acquired (HA) antibiotic-resistant organisms (AROs) and multidrug-resistant organisms (MDROs). Changes in community-acquired (CA)-ARO, CA-MDRO, and inpatient AMU were assessed as controls and process outcomes. RESULTS: Statistically significant shifts in AMU, HA-ARO, and HA-MDRO trends coinciding with ASP implementation were observed, corresponding with a 9% reduction in HA-ARO burden (incidence rate ratio [IRR], 0.91 [95% confidence interval {CI}, .83-.99]; P = .03) and a 13% reduction in HA-MDRO burden (IRR, 0.87 [95% CI, .73-1.04]; P = .13) in the intervention period. In contrast, CA-ARO and CA-MDRO incidence continued to rise, with 40% (IRR, 1.40 [95% CI, 1.28-1.54]; P < .0001) and 68% (IRR, 1.68 [95% CI, 1.57-1.82]; P < .0001) increases in burden found, respectively. CONCLUSIONS: Implementation of a comprehensive ASP resulting in reduced AMU was associated with a significant reduction in institutional AMR, even though community AMR increased during the same period. These results confirm that ASPs play an important role in the fight against 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. Mean pharmacokinetics were calculated and multiple linear regression was performed to determine significant covariates of clearance (L/h) and volume of distribution (L). Classification and regression tree (CART) analysis identified breakpoints for significant covariates. Monte Carlo Simulation (MCS) was used to determine optimal dosing recommendations for each CART-identified sub-group. RESULTS: Gentamicin clearance and volume of distribution were significantly associated with weight at gentamicin initiation. CART-identified breakpoints for weight at gentamicin initiation were: ≤ 850 g, 851-1200 g, and > 1200 g. MCS identified that a conventional dose of gentamicin 3.5 mg/kg given every 48 h or an EID of 8-9 mg/kg administered every 72 h in neonates weighing ≤ 850 g, and every 24 and 48 h, respectively, in neonates weighing 851-1200 g, provided the best probability of attaining conventional (peak: 5-10 mg/L and trough: ≤ 2 mg/L) and EID targets (peak:12-20 mg/L, trough:≤ 0.5 mg/L). Insufficient sample size in the > 1200 g neonatal group precluded further investigation of this weight category. CONCLUSIONS: This study provides initial gentamicin dosing recommendations that optimize target attainment for conventional and EID regimens in neonates weighing ≤ 1200 g. Prospective validation and empiric dose optimization for neonates > 1200 g is needed.

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. METHODS: A retrospective chart review of neonates admitted to a neonatal intensive care unit (NICU) between March 1, 2012 and January 14, 2015 and a prospective evaluation of all neonates admitted between January 15, 2015 and March 30, 2015 were completed. Neonates with late-onset bacteremia (> 72 h after NICU admission) were eligible for inclusion in the bacteremic cohort. Bacteremic patients were matched to non-infected controls on several demographic parameters. A Pearson's Correlation matrix was completed to identify independent variables significantly associated with infection (p < 0.05, univariate analysis). Significant parameters were analyzed using iterative binary logistic regression to identify the simplest significant model (p < 0.05). The predictive value of the model was assessed and the optimal probability cut-off for bacteremia was determined using a Receiver Operating Characteristic curve. RESULTS: Maximum blood glucose, heart rate, neutrophils and bands were identified as the best predictors of bacteremia in a significant binary logistic regression model. The model's sensitivity, specificity and accuracy were 90, 80 and 85%, respectively, with a false positive rate of 20% and a false negative rate of 9.7%. At the study bacteremia prevalence rate of 51%, the positive predictive value, negative predictive value and negative post-test probability were 82, 89 and 11%, respectively. CONCLUSION: The model developed in the current study is superior to currently published neonatal bacteremia screening tools. Validation of the tool in a historic data set of neonates from our institution will be completed.

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

Purpose: 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). Methods: Weighted mean pharmacokinetic parameters and standard deviations for ciprofloxacin, levofloxacin, and moxifloxacin were calculated from published studies in healthy volunteers. The incidence and FQ susceptibility profiles for the most common bacteria causing PTBIE were extracted from the literature. MCS was used to determine the cumulative fraction of response (CFR) for 5 FQ dosing options to determine the probability of attaining pathogen-specific target 24-hour area under the curve to minimum inhibitory concentration ratios in the vitreous humor of the eye against the 4 most common causative bacteria seen in PTBIE. Results: Moxifloxacin 400 mg po daily (M400) achieved the highest CFR (72%). Levofloxacin dosing options achieved CFRs between 54% and 63%. Ciprofloxacin dosing options achieved CFRs between 28% and 35%. Conclusion: M400 optimized the likelihood of prophylactic success in the prevention of PTBIE, and based on the study findings, M400 is predicted to optimize the probability of success compared with ciprofloxacin and levofloxacin dosing options currently endorsed by expert opinion.

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. Patient data for the low versus high trough cohorts were compared using appropriate statistical tests and binary logistic regression was used to identify factors associated with clinical outcome. RESULTS: Of 2098 patients screened, 103 (5%) met inclusion criteria. Baseline characteristics between cohorts were not different. Clinical cure was not different between the low (42/48 [88%]) and high trough (48/55 [87%]) cohorts (p > 0.99) and vancomycin trough concentration was not associated with clinical outcome (p = 0.973). More patients in the high trough group had dosing changes (7/48 [15%] vs. 22/55 [40%], p = 0.0046), with approximately three times more dose adjustments per patient (0.17 vs. 0.55, p = 0.0193). No signal for increased vancomycin resistance associated with vancomycin troughs was identified. CONCLUSIONS: No difference in clinical or microbiological outcomes based on vancomycin trough concentrations were observed in patients with non-deep seated infections treated with vancomycin for ≤14 days. Targeting higher vancomycin trough concentrations of > 10 mg/L may be associated with increased workload with no corresponding benefit in clinical or microbiological outcomes in these patients.

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. The primary outcome was in-hospital mortality within 30 days. Secondary outcomes included transfer to critical care and antimicrobial therapy received between days 3 and 14 following macroaspiration including escalation of therapy and antibiotic-free days. Results: Among 1483 patients reviewed, 200 met the case definition for acute aspiration pneumonitis, including 76 (38%) who received prophylactic antimicrobial therapy and 124 (62%) who received supportive management only. After adjusting for patient-level predictors, antimicrobial prophylaxis was not associated with any improvement in mortality (odds ratio, 0.9; 95% confidence interval [CI], 0.4-1.7; P = .7). Patients receiving prophylactic antimicrobial therapy were no less likely to require transfer to critical care (5% vs 6%; P = .7) and subsequently received more frequent escalation of antibiotic therapy (8% vs 1%; P = .002) and fewer antibiotic-free days (7.5 vs 10.9; P < .0001). Conclusions: Prophylactic antimicrobial therapy for patients with acute aspiration pneumonitis does not offer clinical benefit and may generate antibiotic selective pressures that results in the need for escalation of antibiotic therapy among those who develop aspiration pneumonia.

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. for 5 doses was determined. Mean steady-state maximum serum concentration and half-life were 4.4 ± 1.5 mg/L and 10.3 ± 2.6 hours, respectively. Mean maximum dialysate concentration in the daytime long dwell and overnight continuous cycling dwell were 7.4 ± 1.2 mg/L and 3.3 ± 1.2 mg/L, respectively. Oral ciprofloxacin 750 mg b.i.d. may be reasonable for bloodstream and peritoneal infections caused by susceptible bacteria in CCPD patients.

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. However, no prospective clinical trials in burn patients exist to confirm these findings. OBJECTIVE: To determine the adequacy of once daily tobramycin dosed at 10mg/kg in adult burn patients. METHODS: This prospective single dose pharmacokinetic clinical trial was conducted at the Ross Tilley Burn Centre. Patients with a total burn surface area (TBSA) of <20% and creatinine clearance ≥50mL/min were eligible. A first-order one compartment model was used to determine the pharmacokinetic profile from 3 or 5 tobramycin levels over a 24h period per patient. Monte Carlo simulation (MCS) was performed to determine the probability of target level attainment. RESULTS: The mean percent TBSA, partial, and full thickness burn were 10%, 6%, and 4%, respectively. Nine of the ten patients recruited achieved peak concentrations of ≥20mg/L (mean of 29.4±5.7mg/L) and all patients had a trough level ≤0.5mg/L. The mean half-life, volume of distribution, and clearance were 2.58h, 0.33L/kg, and 7.40L/h, respectively. The MCS determined probability of attaining target peak concentrations with the 10mg/kg dose was 97%, which almost doubled that predicted with the usual 7mg/kg dose. CONCLUSION: Burn patients with adequate renal function and <20% TBSA are candidates for ODA. Tobramycin half-life was similar to healthy, non-burn patients. The larger than normal volume of distribution supports the use of the higher empiric dose of 10mg/kg total body or adjusted weight in non-obese and obese patients, respectively, with further dose adjustment based on therapeutic drug monitoring.

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

Background: ß-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. The primary outcome was the proportion of patients receiving the preferred ß-lactam therapy. Results: Of 827 patients with reported ß-lactam allergy over 15 months, ß-lactam therapy was preferred among 632 (76%). During baseline periods, 50% (124/246) received preferred ß-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (P = .02), which improved further to 81% (313/386) upon provision of BLAST (P < .001) without any increase in incidence of adverse drug reactions (4% vs 3%; P = .4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred ß-lactam therapy (95% confidence interval, 2.4-8.2; P < .0001). Conclusions: The use of BLAST at the point of care across 3 hospital ASPs resulted in greater use of preferred ß-lactam therapy without increasing the risk of adverse drug reactions. Longer-term studies are needed to better assess the safety and clinical impact of this ASP intervention.

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.

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. METHODS: A retrospective review of all admissions to the Ross Tilley Burn Centre at Sunnybrook Health Sciences Centre with clinical cultures yielding GNB (duplicates excluded) between March 12, 2010 to July 17, 2013 was completed. Positive cultures were categorized into 5 clinically relevant time periods (in days) based on specimen collection date relative to the patient's date of admission: 0-7, 7-14, 14-21, 21-28, >28. Chi-square for proportions was used to compare the time periods. RESULTS: The proportion of patients with clinical cultures for P. aeruginosa increased with hospital LOS (0-7 days: 8% vs. >28 days: 55%; p<0.05). Conversely, clinical cultures for H. influenzae occurred primarily within the first 7 days of hospitalization (0-7 days: 36% vs. >28 days: 0.7%; p<0.05). Enterobacteriaceae isolation was highest between 7 and 14 days of hospitalization (7-14 days: 62% vs. >28 days: 38%; p<0.05). Antibiotic resistance was directly proportional to hospital LOS (% patients with multidrug resistant GNB increased from 6% [LOS 0-7 days] to 44% [LOS>28 days]; p<0.05). CONCLUSIONS: This study provides objective data documenting changes in species and resistance patterns of GNB causing infection in patients admitted to a burn center as a function of hospital LOS; which may support delaying the use of broad spectrum antibiotics (e.g. carbapenems and beta-lactam/beta-lactamase inhibitors) in clinically stable patients.

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. All residents taking one or more antibiotics (n = 326) were included as participants. Antibiotic-use data for patients residing in the facility between April 1, 2011, and March 31, 2012, were collected and analyzed. RESULTS: Totals of 358 patient encounters, 835 antibiotic prescriptions, and 193 positive culture results were documented during the study period. For 36% (302/835) of antibiotic prescriptions, the duration was more than 7 days. Cephalosporins (30%; 251/835) and fluoroquinolones (28%; 235/835) were the most frequently prescribed antibiotic classes. Urine was the most common source of samples for culture (60%; 116/193). CONCLUSIONS: Characteristics of antimicrobial use at this long-term care facility that might benefit from further evaluation included potentially excessive use of fluoroquinolones and cephalosporins and potentially excessive duration of antibiotic use for individual patients.

CONTEXTE: La gérance des antibiotiques peut s'avérer importante au sein des établissements de soins de longue durée à cause d'une utilisation inutile ou inappropriée des antibiotiques chez les résidents de ces établissements et de leur vulnérabilité aux infections nosocomiales. OBJECTIFS: Évaluer l'utilisation des antibiotiques dans un établissement de soins de longue durée afin de déterminer si une gérance des antimicrobiens peut être nécessaire. MÉTHODES: Une étude descriptive rétrospective a été réalisée au Veterans Centre, un établissement de soins de longue durée au sein du Sunnybrook Health Sciences Centre, à Toronto en Ontario. Tous les résidents prenant au moins un antibiotique (n = 326) ont été admis à l'étude. Des données sur les antibiothérapies pour des patients résidant dans l'établissement entre le 1er avril 2011 et le 31 mars 2012 ont été recueillies et analysées. RÉSULTATS: Pendant l'étude, on a consigné en tout 358 séjours de patients, 835 prescriptions d'antibiotiques et 193 résultats positifs de culture. Pour 36 % (302/835) des prescriptions d'antibiotiques, le traitement était de plus de 7 jours. Les céphalosporines (30 % [251/835]) et les fluoroquinolones (28 % [235/835]) étaient les antibiotiques les plus souvent prescrits. Les cultures étaient le plus souvent obtenues à partir d'urines (60 % [116/193]). CONCLUSIONS: L'utilisation possiblement excessive de fluoroquinolones et de céphalosporines ainsi que la durée potentiellement exagérée des antibiothérapies font partie des caractéristiques de l'emploi des antimicrobiens dans cet établissement de soins de longue durée qui pourraient mériter de plus amples évaluations.

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. aeruginosa bacteremia who received intermittent IV administration of antipseudomonal ß-lactam antibiotics in a tertiary care institution. METHODS: For this retrospective descriptive study, data were collected for patients who were admitted between March 1, 2005, and March 31, 2013, who had P. aeruginosa bacteremia during their admission, and who received at least 72 h of treatment with ceftazidime, meropenem, or piperacillin-tazobactam. Clinical and microbiological outcomes were determined, and total and infection-related hospital costs were calculated. RESULTS: A total of 103 patients were included in the analysis, of whom 79 (77%) experienced clinical cure. In addition, bacterial eradication was achieved in 41 (87%) of the 47 patients with evaluable data for this outcome. Twenty-eight (27%) of the 103 patients died within 30 days of discontinuation of antipseudomonal ß-lactam antibiotic therapy. The median total cost of the hospital stay was $121 718, and the median infection-related cost was $29 697. CONCLUSIONS: P. aeruginosa bacteremia is a clinically significant nosocomial infection that continues to cause considerable mortality and health care costs. To the authors' knowledge, no previous studies have calculated total and infection-related hospital costs for treatment of P. aeruginosa bacteremia with intermittent infusion of antipseudomonal ß-lactam antibiotics, with characterization of cost according to site of acquisition of the infection. This study may provide important baseline data for assessing the impact of implementing extended-infusion ß-lactam therapy, antimicrobial stewardship, and infection control strategies targeting P. aeruginosa infection in hospitalized patients.

CONTEXTE: La bactérie Pseudomonas aeruginosa, l'une des principales causes des bactériémies nosocomiales à Gram négatif, est particulièrement difficile à traiter, parce qu'elle possède de nombreux mécanismes de résistance et qu'il n'y a pas de nouveaux antibiotiques anti-Pseudomonas. Bien que l'on sache que l'effet bactéricide des ß-lactamines est fonction du temps, la plupart des hôpitaux au Canada administrent actuellement ces antibiotiques par perfusions intermittentes plutôt que prolongées. OBJECTIFS: Déterminer quels sont les résultats cliniques, les résultats microbiologiques, les coûts totaux d'hospitalisation et ceux liés à l'infection seule pour les patients atteints d'une bactériémie à P. aeruginosa ayant reçu des ß-lactamines anti-Pseudomonas par perfusion intermittente dans un établissement de soins tertiaires. MÉTHODES: Pour la présente étude rétrospective descriptive, on a recueilli des données sur des patients hospitalisés entre le 1er mars 2005 et le 31 mars 2013, qui étaient atteints d'une bactériémie à Pseudomonas aeruginosa, et qui ont reçu au moins 72 heures de traitements par ceftazidime, méropenem ou pipéracilline-tazobactam. Les résultats cliniques et microbiologiques ont été déterminés, et les coûts totaux d'hospitalisation et ceux liés à l'infection ont été calculés. RÉSULTATS: En tout, 103 patients ont été retenus pour l'analyse. Parmi eux, 79 (77 %) ont joui d'une guérison clinique. De plus, une éradication bactérienne a été obtenue chez 41 (87 %) des 47 patients ayant des données évaluables pour ce résultat. Vingt-huit (27 %) des 103 patients sont décédés dans les trente jours suivant la fin de l'antibiothérapie par ß-lactamines anti-Pseudomonas. Le coût total médian du séjour à l'hôpital était de 121 718 $ et le coût médian lié à l'infection était de 29 697 $. CONCLUSIONS: La bactériémie à Pseudomonas aeruginosa est une infection nosocomiale cliniquement significative. Elle demeure à ce jour une cause importante de mortalité et une source considérable de coûts de soins de santé. À la connaissance des auteurs, aucune étude antérieure n'a calculé les coûts totaux d'hospitalisation et ceux liés à l'infection pour le traitement de la bactériémie à Pseudomonas aeruginosa par perfusion intermittente de ß-lactamines anti-Pseudomonas, en caractérisant ces coûts selon le site de transmission de l'infection. Cette étude pourrait fournir d'importantes données de référence pour évaluer l'effet de la mise en place du traitement par perfusion prolongée de ß-lactamines, d'une gestion responsable des antimicrobiens et de stratégies de prévention des infections qui visent l'infection à P. aeruginosa chez les patients hospitalisés.

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. METHODS: A point prevalence study was conducted on July 19th, 2012. Data on antimicrobial utilization, indication for prescribing, duration of therapy, and frequency of infectious disease or antimicrobial stewardship consultations were collected using a customized integrated stewardship database (SPIRIT) and prospective chart review. RESULTS: One or more antimicrobial agents were ordered in 31% and 4% of acute care and long-term care patients, respectively. Respiratory and urinary tract infections were the most common indication for antimicrobial therapy in both acute and long-term care. About 25% of surgical prophylaxis orders were prescribed for greater than 24h. CONCLUSION: This prospective point prevalence survey provided important baseline information on antimicrobial use within a large tertiary care teaching hospital and identified potential targets for future antimicrobial stewardship initiatives. A multi-center point prevalence survey should be considered to identify patterns of antimicrobial use in Canada and to establish the first steps toward international antimicrobial surveillance.