Lucas Schulz

Addition of ceftaroline to daptomycin after emergence of daptomycin-nonsusceptible Staphylococcus aureus during therapy improves antibacterial activity.

ABSTRACT Antistaphylococcal beta-lactams enhance daptomycin activity and have been used successfully in combination for refractory methicillin-resistant Staphylococcus aureus (MRSA) infections. Ceftaroline possesses MRSA activity, but it is unknown if it improves the daptomycin potency comparably to other beta-lactams. We report a complex patient case of endocarditis who was treated with daptomycin in combination with ceftaroline, which resulted in clearance of a daptomycin-nonsusceptible strain. An in vitro pharmacokinetic/pharmacodynamic model of renal failure was used to simulate the development of daptomycin resistance and evaluate the microbiologic effects of daptomycin plus ceftaroline treatment. Combination therapy with daptomycin and ceftaroline restored daptomycin sensitivity in vivo and resulted in clearance of persistent blood cultures. Daptomycin susceptibility in vitro was increased in the presence of either ceftaroline or oxacillin. Daptomycin at 6 mg/kg of body weight every 48 h was bactericidal in the model but resulted in regrowth and daptomycin resistance (MIC, 2 to 4 μg/ml) with continued monotherapy. The addition of ceftaroline at 200 mg every 12 h after the emergence of daptomycin resistance enhanced bacterial killing. Importantly, daptomycin plus ceftaroline as the initial combination therapy produced rapid and sustained bactericidal activity and prevented daptomycin resistance. Both in vivo- and in vitro-derived daptomycin resistance resulted in bacteria with more fluid cell membranes. After ceftaroline was added in the model, fluidity was restored to the level of the initial in vivo isolate. Daptomycin-resistant isolates required high daptomycin exposures (at least 10 mg/kg) to optimize cell membrane damage with daptomycin alone. Ceftaroline combined with daptomycin was effective in eliminating daptomycin-resistant MRSA, and these results further justify the potential use of daptomycin plus beta-lactam therapy for these refractory infections.

Use of Electronic Health Records and Clinical Decision Support Systems for Antimicrobial Stewardship

Electronic health records (EHRs) and clinical decision support systems (CDSSs) have the potential to enhance antimicrobial stewardship. Numerous EHRs and CDSSs are available and have the potential to enable all clinicians and antimicrobial stewardship programs (ASPs) to more efficiently review pharmacy, microbiology, and clinical data. Literature evaluating the impact of EHRs and CDSSs on patient outcomes is lacking, although EHRs with integrated CDSSs have demonstrated improvements in clinical and economic outcomes. Both technologies can be used to enhance existing ASPs and their implementation of core ASP strategies. Resolution of administrative, legal, and technical issues will enhance the acceptance and impact of these systems. EHR systems will increase in value when manufacturers include integrated ASP tools and CDSSs that do not require extensive commitment of information technology resources. Further research is needed to determine the true impact of current systems on ASP and the ultimate goal of improved patient outcomes through optimized antimicrobial use.

The Use of Best Practice Alerts with the Development of an Antimicrobial Stewardship Navigator to Promote Antibiotic De-escalation in the Electronic Medical Record

OBJECTIVE Develop a clinical decision support tool comprised of an electronic medical record alert and antimicrobial stewardship navigator to facilitate antimicrobial stewardship. DESIGN We analyzed alerts targeting antimicrobial de-escalation to assess the effectiveness of the navigator as a stewardship tool. The alert provides antimicrobial recommendations, then directs providers to the navigator, which includes order management, relevant patient information, evidence-based clinical information, and bidirectional communication capability. SETTING Academic, tertiary care medical center with an electronic medical record. INTERVENTION Alerts containing stewardship recommendations and immediate access to the navigator were created. RESULTS  Antibiotic use and response data were collected 1 day before stewardship recommendation via the best practice alert (BPA) tool and 1 day after the BPA tool response. A total of 1,285 stewardship BPAs were created. Two hundred and forty-four (18.9%) of the BPAs were created and acted upon within 72 hours for the purpose of de-escalation: 169 (69%) were accepted, 30 (12%) were accepted with modification, and 45 (18%) were rejected. Statistically significant decreases in total antibiotic use as well as in use of broad-spectrum (anti-methicillin-resistant Staphylococcus aureus and anti-pseudomonal) agents occurred when accepted recommendations were compared with rejected recommendations. CONCLUSIONS We describe the successful development of a clinical decision support tool to perform prospective audit and feedback comprised of an alert and navigator system featuring evidence-based recommendations and clinical and educational information. We demonstrate that this tool improves antibiotic use through our example of de-escalation.

Can the antibiogram be used to assess microbiologic outcomes after antimicrobial stewardship interventions? A critical review of the literature.

Hospitals are implementing antimicrobial stewardship programs (ASPs) in response to national guidelines to improve the use and to extend the utility of antiinfective drugs. An often implied purpose of ASPs is to curb or reverse the emergence of resistant bacteria. Because antibiotic use causes antibiotic resistance, there is a natural tendency to link local measures of antibiotic use to local measures of bacterial resistance, and the hospital antibiogram is a readily available measure of resistance. We performed a literature review to identify published reports that used hospitalwide and unit‐specific antibiograms to assess the relationship of ASP interventions to changes in resistance. Eight studies were identified and reviewed. The relationship between hospital antibiotic use and resistance is complex, and the existing literature has several limitations. Furthermore, the antibiogram itself is neither designed nor well suited to reflect changes in hospital antimicrobial drug use. The literature on the effectiveness of ASPs in reducing resistance continues to emerge, but at this time the antibiogram bears an inconsistent relationship with changes in hospital antibiotic use and cannot be recommended to reliably evaluate an ASP intervention. Interrupted time series analysis is a superior strategy to assess the effect of an ASP intervention on bacterial resistance, but it is not widely used because of its complexity and greater data requirements. Nevertheless, before ASP efforts can be convincingly demonstrated to have a favorable impact on resistance, a more sophisticated approach that links drug use to resistance should become a priority, at least for hospitals that have sufficient resources.

Stress Ulcer Prophylaxis: Reducing Non-Indicated Prescribing after Hospital Discharge

Background: Gastric acid suppressant medications used as stress ulcer prophylaxis (SUP) in the intensive care unit (ICU) are often prescribed inappropriately after discharge. We present tools to reduce the use and cost of non-indicated SUP. Objective: To reduce the non-indicated use of SUP after hospital discharge originally started in the ICU, using an education intervention and pharmacist-led medication reconciliation on patient care rounds and at hospital discharge. Methods: In a retrospective medical record review using a historic control, 356 consecutively admitted patients to the medical/surgical ICU at the University of Wisconsin Hospital were assessed for the appropriate use of SUP at admission to the ICU, at transfer to a general care unit, and at hospital discharge. The education intervention involved teaching both the medical and pharmacist staff about indications for SUP using a memorandum and a pocket guide. Pharmacists also conducted medication reconciliation during daily patient care rounds and at discharge to justify medication use. The outcome of this study is the percentage of patients prescribed non-indicated gastric acid suppressants at hospital discharge. This outcome is compared to a previous study conducted at our hospital. Results: Of 356 eligible patients, 308 (86.5%) received SUP while in the ICU. Thirty-nine (11%) were given continuing SUP after discharge from the hospital, of which 31 (8.7%) had no clear indication. This was a 64.3% reduction from the 24.4% found in the prior study (p < 0.0001). Conclusions: Educational materials that guide prescribing, pharmacist interaction on patient care rounds, and pharmacist-conducted medication reconciliation significantly reduced the prescribing of non-indicated gastric acid suppressant medications after hospital discharge.

Daptomycin Dosing Based on Ideal Body Weight versus Actual Body Weight: Comparison of Clinical Outcomes

ABSTRACT Daptomycin use at our institution changed to ideal body weight dosing based on a published analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. Patients were treated for documented Enterococcus species, Staphylococcus aureus, or coagulase-negative Staphylococcus infections, including bloodstream, intraabdominal, skin and soft tissue, urinary, and bone. There was no statistically significant difference in clinical success between the groups (88.9% for actual body weight compared to 89.1% for ideal body weight, P = 0.97). After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups. Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all patients and types of infections and organisms.

Pharmacist participation in infection prevention: An innovative approach to monitoring compliance with the Five Moments for Hand Hygiene in a large academic medical center

Using pharmacy residents as covert observers, we evaluated compliance with hand hygiene and contact precautions among 101 unique health care workers on entrance, exit, and inside rooms of patients with known or suspected Clostridium difficile infection. Overall compliance rates with hand hygiene upon entering and exiting patient rooms were 63.4% and 69.3%, respectively. However, there was a lack of hand hygiene inside patient rooms for the observed opportunities.

Compatibility of cefepime and vancomycin during simulated Y-site administration of prolonged infusion.

PURPOSE The physical and chemical compatibility of cefepime and vancomycin at concentrations typically used in prolonged-infusion cefepime infusions was assessed. METHODS Samples from a typical Y-site configuration of standard-infusion vancomycin and prolonged-infusion cefepime were collected at various time points during the simulated 4-hour infusion. Samples were analyzed by visual inspection, spectrophotometry, and high-performance liquid chromatography (HPLC). Infusion antibiotics were reconstituted in pairwise combinations of 0.9% sodium chloride injection and 5% dextrose injection to determine the effects of solvent selection on stability. Infusion simulations were performed in triplicate without light protection under fluorescent lighting at room temperature (22.5 °C). Experimental replicates were not run simultaneously but on sequential days due to the considerable time (~12 hours) required to analyze samples obtained from a single infusion simulation and the known time-dependent instability of reconstituted cefepime beyond 24 hours. Physical stability was assessed visually for evidence of particulate formation, haze, precipitation, color change, and gas evolution. Samples were also assessed spectrophotometrically at 600 nm at the time of collection and 24 hours after collection. RESULTS Cefepime was compatible with vancomycin at the concentrations tested. The solvent selected (0.9% sodium chloride or 5% dextrose) to reconstitute either antibiotic had no impact on compatibility. Solutions were indistinguishable from positive and negative controls (heat-degraded cefepime and freshly reconstituted cefepime, respectively) at all time points assessed in terms of visual clarity, spectrophotometric absorbance, and HPLC recovery. CONCLUSION Cefepime and vancomycin were physically and chemically compatible during simulated Y-site administration of prolonged-infusion cefepime.

Stability of Sodium Nitroprusside and Sodium Thiosulfate 1:10 Intravenous Admixture:

Purpose Thiosulfate has been shown to reduce the risk of cyanide toxicity during nitroprusside administration. Admixtures containing both agents may provide a safe and effective alternative to more expensive agents used to reduce blood pressure in the critically ill patient. This study determined the physical and chemical stability of a 1:10 nitroprusside:thiosulfate admixture, stored up to 48 hours. The economic consequences of a shift toward using thiosulfate and nitroprusside, and away from higher cost alternatives, are considered. Methods Seven samples of 50 mg nitroprusside and 500 mg thiosulfate were prepared and stored away from light, at room temperature, and in a refrigerator prepared in D5W and NS. Each sample was analyzed via a novel high-performance liquid chromatographic (HPLC) method at time 0, 8, 24, and 48 hours. The method was tested and passed specifications for linearity, reproducibility, and accuracy. A visual inspection by 9 licensed pharmacists was used to demonstrate physical stability. A cost evaluation comparing nitroprusside and thiosulfate to alternative agents was completed. Results The concentration of both nitroprusside and thiosulfate remain greater than 95% of the initial concentration through 48 hours. Physical compatibility was confirmed in all samples tested through 72 hours. Conclusion The combination of nitroprusside and thiosulfate is chemically and physically stable as a single compounded dose for up to 48 hours when stored at room temperature and protected from light. The admixture represents an inexpensive option to other higher cost alternatives such as nicardipine or clevidipine.

Top 1% of Inpatients Administered Antimicrobial Agents Comprising 50% of Expenditures: A Descriptive Study and Opportunities for Stewardship Intervention.

OBJECTIVE To characterize the top 1% of inpatients who contributed to the 6-month antimicrobial budget in a tertiary, academic medical center and identify cost-effective intervention opportunities targeting high-cost antimicrobial utilization. DESIGN Retrospective cohort study. PATIENTS Top 1% of the antimicrobial budget from July 1 through December 31, 2014. METHODS Patients were identified through a pharmacy billing database. Baseline characteristics were collected through a retrospective medical chart review. Patients were presented to the antimicrobial stewardship team to determine appropriate utilization of high-cost antimicrobials and potential intervention opportunities. Appropriate use was defined as antimicrobial therapy that was effective, safe, and most cost-effective compared with alternative agents. RESULTS A total of 10,460 patients received antimicrobials in 6 months; 106 patients accounted for