Optimizing Cefazolin Prophylaxis in Obstetrical Patients with Reported Beta-Lactam Allergy Undergoing Cesarean Delivery.

OBJECTIVES: Evaluate the impact of an allergy history-guided algorithm for optimizing perioperative cefazolin use in patients with reported beta-lactam allergy undergoing cesarean delivery. METHODS: The Allergy Clarification for Cefazolin Evidence-based Prescribing Tool (ACCEPT) was developed through consensus by allergists, anesthesiologists, and infectious diseases specialists, and implemented over a 2-month period (December 1, 2018, to January 31, 2019). A segmented regression on monthly cefazolin use was conducted during the baseline (January 1 to November 30, 2018) and intervention (February 1 to December 31, 2019) periods to evaluate the impact of ACCEPT on the monthly use of perioperative cefazolin in patients with reported beta-lactam allergy undergoing cesarean delivery. The frequency of perioperative allergic reactions and surgical site infections was collected during both periods. RESULTS: Of the 3128 eligible women who underwent a cesarean delivery, 282 (9%) reported a beta-lactam allergy. The most common beta-lactam allergens were penicillin (64.3%), amoxicillin (16.0%), and cefaclor (6.0%). The most frequently reported allergic reactions were rash (38.1%), hives (21.4%), and unknown (11.6%). Use of cefazolin increased from 52% (baseline) to 87% during the intervention period. Segmented regression analysis confirmed a statistically significant increase following implementation (incidence rate ratio 1.62, 95% CI 1.19-2.21, P = 0.002). There was 1 perioperative allergic reaction in the baseline period and 2 during the intervention period. Cefazolin use remained high (92%) 2 years after algorithm implementation. CONCLUSIONS: Implementation of a simple allergy history-guided algorithm in obstetrical patients with reported beta-lactam allergy resulted in a sustained increase in perioperative cefazolin prophylaxis.

Introducing the Escalation Antibiogram: A Simple Tool to Inform Changes in Empiric Antimicrobials in the Nonresponding Patient.

BACKGROUND: Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among nonresponding patients. METHODS: Using gram-negative bacteremia as an exemplar condition, we sought to introduce the concept of an escalation antibiogram. Among episodes of gram-negative bacteremia between 2017 and 2020 from 6 hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type. RESULTS: Among 6577 gram-negative bacteremia episodes, the likelihood of coverage was ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates, piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, P < .0001), ciprofloxacin (63.0%, P < .0001), ertapenem (73.4%, P < .0001), tobramycin (80.1%, P < .0001), gentamicin (82.8%, P < .0001), meropenem (94.3%, P < .0001), and amikacin (97.1%, P < .0001). Trimethoprim-sulfamethoxazole was the second-ranked agent in the meropenem escalation antibiogram (49.6%) and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals. CONCLUSIONS: Escalation antibiograms can be generated to inform empiric treatment changes in nonresponding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected gram-negative bacteremia.

Improving Intrapartum Group B Streptococcus Prophylaxis in Patients with a Reported Penicillin or Cephalosporin Allergy: A Quality Improvement Project.

OBJECTIVE: To evaluate the impact of a standardized allergy-guided approach to Group B Streptococcus (GBS) prophylaxis in pregnant women with reported penicillin or cephalosporin allergy. METHODS: This interrupted time-series analysis included obstetric patients requiring GBS prophylaxis who reported penicillin or cephalosporin allergies. Patients were divided into baseline (April 1, 2019 to July 21, 2020) and intervention (July 22, 2020 to July 31, 2021) groups. The primary outcome was prophylaxis appropriateness, based on antibiotic type, nature of reaction, and cross-reactivity risk. Secondary outcomes included type of prophylaxis received and antibiotic-related adverse events. RESULTS: The study included 88 patients in the baseline period and 52 patients in the intervention period. Appropriate prophylaxis increased from 47% (41/88) to 85% (44/52), with the segmented regression model confirming a statistically significant increase over time (incidence rate ratio 1.57; 95% CI 1.02-2.43, P = 0.04, slope coefficient 1.06/month; 95% CI 1.01-1.10, P = 0.01). Penicillin and cefazolin use increased from 61% (54/88) to 87% (45/52) in the intervention period (P = 0.002), and no hypersensitivity reactions occurred during this period. CONCLUSIONS: Implementation of standardized allergy-guided prophylaxis safely improved appropriate ß-lactam antibiotic use in obstetric patients requiring GBS prophylaxis who reported penicillin and cephalosporin allergies.

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.

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.

Long-Term Sustainability and Acceptance of Antimicrobial Stewardship in Intensive Care: A Retrospective Cohort Study.

OBJECTIVES: To evaluate long-term uptake of an antimicrobial stewardship audit-and-feedback program along with potential predictors of stewardship suggestions and acceptance across a diverse ICU population. DESIGN: A retrospective cohort study. SETTING: An urban, academic medical institution. PATIENTS: Patients admitted to an ICU who received an antimicrobial stewardship program suggestion between June 2010 and September 2019. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The antimicrobial stewardship program provided 7,749 antibiotic assessments over the study period and made a suggestion to alter therapy in 2,826 (36%). Factors associated with a higher likelihood of receiving a suggestion to alter therapy included shorter hospital length of stay prior to antimicrobial stewardship program review (odds ratio 1.15 for ≤ 5 d; 95% CI 1.00-1.32), admission to cardiovascular (1.37; 1.06-1.76) or burn surgery (1.88; 1.50-2.36) versus general medicine, and preceding duration of antibiotic use greater than 5 days (1.33; 1.10-1.60). Assessment of aminoglycosides (2.91; 1.85-4.89), carbapenems (1.93; 1.54-2.41), and vancomycin (2.71; 2.19-3.36) versus ceftriaxone was more likely to result in suggestions to alter therapy. The suggestion acceptance rate was 67% (1,895/2,826), which was stable throughout the study period. Admission to a level 3 ICU was associated with higher likelihood of acceptance of suggestions (1.50; 1.14-1.97). Factors associated with lower acceptance rates were admission to burn surgery (0.64; 0.45-0.91), treatment of pneumonia (0.64; 0.42-0.97 for community-acquired and 0.65; 0.44-0.94 for ventilator-acquired), unknown source of infection (0.66; 0.48-0.92), and suggestion types of "narrow spectrum" (0.65; 0.45-0.94), "change formulation of antibiotic" (0.42; 0.27-0.64), or "change agent of therapy" (0.63; 0.40-0.97) versus "change of dose". CONCLUSIONS: An antimicrobial stewardship program implemented over a decade resulted in sustained suggestion and acceptance rates. These findings support the need for a persistent presence of audit-and-feedback over time with more frequent suggestions to alter potentially nephrotoxic agents, increased efforts toward specialized care units, and further work approaching infectious sources that are typically treated without pathogen confirmation and identification.

Impact of the Allergy Clarification for Cefazolin Evidence-based Prescribing Tool on Receipt of Preferred Perioperative Prophylaxis: An Interrupted Time Series Study.

Implementation of a perioperative allergy and antibiotic assessment tool in patients with reported beta-lactam allergy resulted in a pronounced and sustained increase in perioperative cefazolin use. This intervention could result in improved efficiencies surrounding perioperative antibiotic administration and possible reductions in surgical site infection rates.

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.

Voriconazole prophylaxis in leukemic patients: A retrospective single-center study.

BACKGROUND: Invasive fungal infections commonly occur in acute myeloid and lymphoblastic leukemia patients receiving chemotherapy. In these patients with acute leukemia, posaconazole prophylaxis is recommended; however, voriconazole may be a less costly alternative. OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of voriconazole prophylaxis in acute leukemia patients. METHODS: A retrospective chart review of inpatients at Sunnybrook Health Sciences Centre between 2005 and 2017 was completed. Hospitalized adult acute leukemia patients who received voriconazole prophylaxis (cases) were compared to patients who received fluconazole or no prophylaxis during chemotherapy (controls). Statistical analyses comparing baseline characteristics, safety, and efficacy outcomes between the study cohorts were completed. A posaconazole literature-based weighted mean risk was compared to the voriconazole risk of invasive fungal infection identified in this study. RESULTS: Of 490 acute myeloid leukemia or acute lymphoblastic leukemia patients, 83 controls and 92 cases were eligible. Case patients received an average of 24.4 ± 10.8 days of voriconazole prophylaxis. The incidence of proven or probable invasive fungal infections with voriconazole was 3.3% (3/92) versus 7.2% (6/83) in the control cohort (p > 0.05) and was comparable to the literature reported weighted incidence of invasive fungal infection with posaconazole (2.4 ± 2.1%; 95% CI 1.3%-3.4%; p > 0.05). Voriconazole was well tolerated by patients (91%; 84/91; seven discontinued due to asymptomatic elevated liver function tests). CONCLUSIONS: Voriconazole prophylaxis was found to be safe, effective, and comparable to literature-based efficacy data for risk of invasive fungal infection with posaconazole antifungal prophylaxis in patients with acute leukemia undergoing chemotherapy and could represent a significant cost advantage.

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.

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.

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

Outpatient parenteral antimicrobial therapy (OPAT) is a safe and effective alternative to hospitalization for many patients with infectious diseases. The objective of this study was to describe the OPAT experience at a Canadian tertiary academic centre in the absence of a formal OPAT program. This was achieved through a retrospective chart review of OPAT patients discharged from Sunnybrook Health Sciences Centre within a one-year period. Between June 2012 and May 2013, 104 patients (median age 63 years) were discharged home with parenteral antimicrobials. The most commonly treated syndromes included surgical site infections (33%), osteoarticular infections (28%), and bacteremia (21%). The most frequently prescribed antimicrobials were ceftriaxone (21%) and cefazolin (20%). Only 56% of the patients received follow-up care from an infectious diseases specialist. In the 60 days following discharge, 43% of the patients returned to the emergency department, while 26% required readmission. Forty-eight percent of the return visits were due to infection relapse or treatment failure, and 23% could be attributed to OPAT-related complications. These results suggest that many OPAT patients have unplanned health care encounters because of issues related to their infection or treatment, and the creation of a formal OPAT clinic may help improve outcomes.

Predictive utility of prior positive urine cultures.

BACKGROUND: A patient's prior urine cultures are often considered when choosing empiric antibiotic therapy for a suspected urinary tract infection. We sought to evaluate how well previous urine cultures predict the identity and susceptibility of organisms in a patient's subsequent urine cultures. METHODS: We conducted a multinational, multicenter, retrospective cohort study, including 22 019 pairs of positive urine cultures from 4351 patients across 2 healthcare systems in Toronto, Ontario, and Chicago, Illinois. We examined the probability of the same organism being identified from the same patient's positive urine culture as a function of time elapsed from the previous positive urine specimen; in cases where the same organism was identified we also examined the likelihood of the organism exhibiting the same or better antimicrobial susceptibility profile. RESULTS: At 4-8 weeks between cultures, the correspondence in isolate identity was 57% (95% confidence interval [CI], 55%-59%), and at >32 weeks it was 49% (95% CI, 48%-50%), still greater than expected by chance (P < .001). The susceptibility profile was the same or better in 83% (95% CI, 81%-85%) of isolate pairs at 4-8 weeks, and 75% (95% CI, 73%-77%) at >32 weeks, still greater than expected by chance (P < .001). Despite high local rates of ciprofloxacin resistance in urine isolates across all patients (40%; 95% CI, 39.5%-40.5%), ciprofloxacin resistance was <20% among patients with a prior ciprofloxacin sensitive organism and no subsequent fluoroquinolone exposure. CONCLUSIONS: A patient's prior urine culture results are useful in predicting the identity and susceptibility of a current positive urine culture. In areas of high fluoroquinolone resistance, ciprofloxacin can be used empirically when prior urine culture results indicate a ciprofloxacin-susceptible organism and there has been no history of intervening fluoroquinolone use.

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. 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.

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. Mean pharmacokinetic values were determined using first-order pharmacokinetic equations, and Monte Carlo simulation was used to evaluate initial dosing recommendations for target trough concentrations of 15 to 20 mg/liter, 5 to 20 mg/liter, and ≤20 mg/liter. Monte Carlo simulation revealed that dosing by mg/kg of body weight was optimal where intermittent dosing of 9 to 12 mg/kg intravenously (i.v.) every 8 h (q8h) had the highest probability of attaining a target trough concentration of 15 to 20 mg/liter. However, continuous infusion with a loading dose of 10 mg/kg followed by 25 to 30 mg/kg per day infused over 24 h had the best overall probability of target attainment. Initial intermittent dosing of 9 to 15 mg/kg i.v. q12h was optimal for target trough concentrations of 5 to 20 mg/liter and ≤20 mg/liter. In conclusion, we determined that the practical initial vancomycin dose of 10 mg/kg vancomycin i.v. q12h was optimal for vancomycin trough concentrations of either 5 to 20 mg/liter or ≤20 mg/liter and that the same initial dose q8h was optimal for target trough concentrations of 15 to 20 mg/liter. However, due to large interpatient vancomycin pharmacokinetic variability in neonates, monitoring of serum concentrations is recommended when trough concentrations between 15 and 20 mg/liter or 5 and 20 mg/liter are desired.

Weighted-incidence syndromic combination antibiograms to guide empiric treatment of critical care infections: a retrospective cohort study.

INTRODUCTION: Empiric antimicrobial selection for critical care infections must balance the need for timely adequate coverage with the resistance pressure exerted by broadspectrum agents. We estimated the potential of weighted incidence syndromic combination antibiograms (WISCAs) to improve time to adequate coverage for critical care infections. In contrast to traditional antibiograms, WISCAs display the likelihood of coverage for a specific infectious syndrome (rather than individual pathogens), and also take into account the potential for poly-microbial infections and the use of multi-drug regimens. METHODS: Cases of ventilator-associated pneumonia (VAP) and catheter-related bloodstream infection (CRBSI) were identified over three years using stringent surveillance criteria. Based on the susceptibility profile of the culprit pathogens, we calculated the WISCA percentages of infections that would have been adequately covered by common antimicrobial(s). We then computed the excess percentage coverage offered by WISCA regimens compared to the actual antimicrobials administered to patients by 12 h, 24 h, and 48 h from culture collection. RESULTS: Among 163 patients with critical care infection, standard practice only resulted in adequate coverage of 35% of patients by 12 h, 52% by 24 h, and 75% by 48 h. No WISCA mono-therapy regimen offered greater than 85% adequate overall coverage for VAP and CRBSI. A wide range of dual therapy regimens would have conferred greater than 90% adequate coverage, with excess coverage estimated to be as high as +56%, +42% and +18% at 12 h, 24 h and 48 h, respectively. We did not detect a decrease in mortality associated with early adequate treatment, and so could not estimate potential downstream benefits. CONCLUSIONS: WISCA-derived empiric antimicrobial regimens can be calculated for patients with intensive care unit (ICU)-acquired infections, and have the potential to reduce time to adequate treatment. Prospective research must confirm whether implementation of WISCA prescribing aids facilitate timely adequate treatment and improved ICU outcomes.

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

BACKGROUND: Screening for methicillin-resistant Staphylococcus aureus (MRSA) is intended to reduce nosocomial spread by identifying patients colonized by MRSA. Given the widespread use of this screening, we evaluated its potential clinical utility in predicting the resistance of clinical isolates of S. aureus. METHODS: We conducted a 2-year retrospective cohort study that included patients with documented clinical infection with S. aureus and prior screening for MRSA. We determined test characteristics, including sensitivity and specificity, of screening for predicting the resistance of subsequent S. aureus isolates. RESULTS: Of 510 patients included in the study, 53 (10%) had positive results from MRSA screening, and 79 (15%) of infecting isolates were resistant to methicillin. Screening for MRSA predicted methicillin resistance of the infecting isolate with 99% (95% confidence interval [CI] 98%-100%) specificity and 63% (95% CI 52%-74%) sensitivity. When screening swabs were obtained within 48 hours before isolate collection, sensitivity increased to 91% (95% CI 71%-99%) and specificity was 100% (95% CI 97%-100%), yielding a negative likelihood ratio of 0.09 (95% CI 0.01-0.3) and a negative predictive value of 98% (95% CI 95%-100%). The time between swab and isolate collection was a significant predictor of concordance of methicillin resistance in swabs and isolates (odds ratio 6.6, 95% CI 1.6-28.2). INTERPRETATION: A positive result from MRSA screening predicted methicillin resistance in a culture-positive clinical infection with S. aureus. Negative results on MRSA screening were most useful for excluding methicillin resistance of a subsequent infection with S. aureus when the screening swab was obtained within 48 hours before collection of the clinical isolate.