Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species.

OBJECTIVES: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. METHODS: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. RESULTS: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis. CONCLUSIONS: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

Effects of a Remote Antimicrobial Stewardship Program on Antimicrobial Use in a Regional Hospital System.

While antimicrobial stewardship programs (ASPs) are well established at most large medical centers, small or rural facilities often do not have the same resources; therefore, different methods must be developed to start or expand ASPs for these hospitals. The purpose of this quality improvement study was to describe the implementation of a pharmacist-led remote ASP and assess the effect on antimicrobial use. Antimicrobial use in days of therapy per 1000 patient days (DOT/1000 PD) was compared between the six months before and after remote ASP implementation. Changes in system-wide, facility-specific, and target antimicrobial use were evaluated. Pharmacist interventions, acceptance rates, and number of times infectious disease (ID) physician assistance was sought were also tracked. System-wide antimicrobial use was 4.6% less in the post-implementation time period than in the pre-implementation time period, with vancomycin, piperacillin/tazobactam, and fluoroquinolones having the greatest reductions in use. Ninety-one percent of interventions made during the post-implementation period were accepted. ID physician review was requested 38 times, and direct ID physician intervention was required six times. Remote ASPs delivered from a central facility to serve a larger system may reduce antimicrobial use, especially against targeted agents, with minimal increase in ID physician workload.

Implementation of a Post-Surgical, Multimodal Analgesia Pain Management Order Set in Opioid-Naive Patients.

BACKGROUND: Perioperative pain management guidelines recommend using multimodal analgesia to improve pain control while reducing opioids administered. The primary objective of this study was to assess whether implementing multimodal analgesia on general surgery postoperative pain management order sets would reduce opioid quantities postoperatively. METHODS: Opioid-naive patients undergoing nonemergent general surgery procedures were evaluated before and after order set revision. The primary outcome was the total quantity of inpatient opioids administered. The secondary outcomes were inpatient naloxone administration, patient-reported pain scores, and opioid quantities prescribed at discharge. RESULTS: The average daily opioid consumption was less each postoperative day (POD) after implementing the revised postsurgical multimodal analgesia pain management order set. On POD 1 and POD 2, average opioid consumption was 53.6 and 47.9 oral morphine equivalents (OME) before the multimodal analgesia order set, respectively, compared with 21.2 and 21.4 OME after, respectively (p < 0.01 and p < 0.01, respectively). Average daily opioid consumption through POD 3 was 60.6 OME before and 21.14 OME after the revision. Average daily pain scores were similar on POD 0, 1, and 2 before and after (3.2, 2.8, and 2.4 compared with 2.8, 3.1, and 2.7, respectively; p = 0.09, 0.33, and 0.12, respectively). On POD 3, pain scores were higher in the postorder set group (2.8 compared with 1.9; p < 0.01), but this was considered clinically insignificant. Average daily pain score through POD 3 was 2.6 before implementation compared with 2.8 after implementation. Neither group required naloxone administration. CONCLUSION: Using perioperative multimodal analgesia reduces opioid consumption without increasing pain scores.

Evaluation of a standardized daptomycin dosing nomogram.

PURPOSE: Implementation of a standardized daptomycin dosing protocol in a community teaching hospital to determine potential cost savings, effectiveness, and safety is presented. METHODS: A retrospective review of randomly selected patients receiving daptomycin therapy from October 2013 to January 2014 was performed to establish a preimplementation patient control group. A specific time for preparing daptomycin in the i.v. room was used based on a standardized administration time of 4 p.m. Reconstituted doses were stored for up to 48 hours in the refrigerator in plastic syringes. All daptomycin doses were given by rapid i.v. administration. For all patients who received daptomycin, the protocol specified that a baseline creatine phosphokinase level be evaluated within 24 hours of the start date and on day 3, day 7, and weekly thereafter until daptomycin therapy was completed or discontinued. RESULTS: The most frequent indications for daptomycin use preimplementation and postimplementation were related to catheter use or persistent bacteremia and skin and soft tissue infections. Through the implementation of the standardized dosing nomogram and optimization of i.v. room workflow, the amount of waste decreased by 21,500 mg and generated a savings of $13,845 over the course of the four-month study period, which can be extrapolated to $41,535 annually. The infection cure rate at completion of therapy was 56.7% in the preimplementation population compared with 70.0% in the postimplementation population. Daptomycin was well tolerated at the standardized doses used in the study. CONCLUSION: Implementation of a standardized dosing nomogram reduced the amount of daptomycin wasted and resulted in cost savings. The standardized dosing nomogram did not impair the rate of clinical effectiveness or cause adverse events.

Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial.

Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of >15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of >15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, gender, race, dose, length of therapy, use of other nephrotoxins (including contrast media), intensive care unit (ICU) residence, episodes of hypotension, and comorbidities. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a ≥ 50% increase from the baseline for two consecutive measurements. MICs of vancomycin for the MRSA isolates were also determined. A total of 288 patients were studied between February 2008 and June 2010, with approximately one-half having initial trough concentrations of ≥ 15 mg/ml. Nephrotoxicity was observed for 42 patients (29.6%) with trough concentrations >15 mg/ml and for 13 (8.9%) with trough concentrations of ≤ 15 mg/ml. Multivariate analysis revealed vancomycin trough concentrations of >15 mg/ml and race (black) as risk factors for nephrotoxicity in this population. Vancomycin trough concentrations of >15 mg/ml appear to be associated with a 3-fold increased risk of nephrotoxicity.