Veena Venugopalan

Impact of an antimicrobial stewardship initiative on time to administration of empirical antibiotic therapy in hospitalized patients with bacteremia

PURPOSE The impact of an antimicrobial stewardship initiative on time to first antibiotic dose and clinical outcomes in bacteremic patients was evaluated. METHODS A single-center, retrospective study was conducted for adult inpatients who received antibiotics before and after implementation of a rapid administration of antimicrobials by an infectious diseases specialist (RAIDS) protocol. Patients admitted to an inpatient service from June to October 2011 (pre-RAIDS protocol) and from December 2011 to February 2012 (post-RAIDS protocol) were eligible for inclusion if (1) they were age 18 years or older, (2) their infection occurred two or more days after hospital admission, and (3) they had a blood culture growing an organism other than common skin contaminants (i.e., coagulase-negative staphylococci, Bacillus species). The primary outcome was the time to the first antibiotic dose (TFAD), defined as the time that elapsed from a positive blood culture result to administration of the first empirical antimicrobial dose. RESULTS A total of 111 bacteremic patients were included in the analysis. Implementation of the RAIDS protocol led to significantly faster antibiotic order entry, verification, and administration of empirical antibiotics in patients with bacteremia. The median TFAD was approximately 8 hours faster in the post-RAIDS group than in the pre-RAIDS group (9:09 hr:min versus 1:23 hr:min, p < 0.001). Patients in the post-RAIDS group had a significant reduction in infection-related mortality (p = 0.047), though all-cause 30-day mortality was similar. CONCLUSION Early notification of an infectious diseases pharmacist about positive blood cultures using the RAIDS protocol led to increased appropriateness of empirical drug selection and a dramatic reduction in the administration of antibiotics and was associated with decreased infection-related mortality.

Preparing Students to Enter the Race for Postgraduate Training

Purpose: Exposure of pharmacy students to postgraduate training prior to clinical practice is currently endorsed by national professional organizations. To meet this goal, colleges and schools of pharmacy are developing residency preparation programs. In this descriptive report, we review published studies of curricular activities and structured programs from academic institutions across the United States aimed at preparing students for residency training and promoting postgraduate education. Additionally, we discuss our experience developing a residency preparation program at Touro College of Pharmacy (TCOP). Summary: A literature search yielded 15 residency preparation programs. While the format, content, and length of programs varied, there were common components such as curriculum vitae critique, mock interviews, and focused sessions on the residency application process. At TCOP, a 5-themed residency preparation workshop series was implemented during the third and fourth academic year. The workshops were modeled after existing programs and included several of the core components. One feature unique to the TCOP program was the addition of multiple mock interviews. Conclusion: The growing focus on residency training has led to increased competition among applicants. To better prepare students for this rigorous application and interview process, development of structured residency preparation programs, similar to TCOP’s, should be encouraged.

Training a Drug to Do New Tricks: Insights on Stability of Meropenem Administered as a Continuous Infusion

Background: The antibiotic armamentarium used to combat multi-drug resistant organisms (MDROs) include carbapenems. Continuous infusion (CI) dosing is frequently employed to maximize beta-lactam efficacy; however, use of meropenem CI has been limited due to concerns with product instability. Objective: The primary objective of this study was to quantify meropenem serum concentrations to reflect drug stability when administered as CI over 8- or 12-h exchanges. In addition, a stability experiment was performed to further establish meropenem integrity over 12 h. The secondary objectives were to assess the ability of meropenem to achieve target pharmacokinetic/pharmacodynamic (PK/PD) exposures relative to the minimum inhibitory concentration (MIC) of the pathogen, and to determine clinical cure. Methods: This was a retrospective, observational study on use of CI meropenem (infused either over 8- or 12- h) at a 1% concentration. The stability experiment was conducted on 1% meropenem at room temperature. Results: In 22 patients, a median meropenem daily dose of 6 g/day (range 2-6 g/day) resulted in a median serum concentration of 17.8 mg/L (interquartile range, 9.3-27.8 mg/L). In 95% of cases, meropenem delivered as CI resulted in free drug concentrations at or above the MIC of the pathogen for the entire dosing interval. Clinical cure was achieved in 80% of patients included in this review. The stability experiment revealed negligible drug degradation at the end of the 12-h dosing interval. Conclusions: The data from this study provides compelling evidence for the use of meropenem as CI utilizing either a 12- or 8-h exchange process.

Use of an Anti-Infective Medication Review Process at Hospital Discharge to Identify Medication Errors and Optimize Therapy:

Background: Medication reconciliation is a major patient safety concern, and the impact of a structured process to evaluate anti-infective agents at hospital discharge warrants further review. Objective: The aim of this study was to (1) describe a structured, multidisciplinary approach to review anti-infectives at discharge and (2) measure the impact of a stewardship-initiated antimicrobial review process in identifying and preventing anti-infective-related medication errors (MEs) at discharge. Methods: A prospective study to evaluate adult patients discharged on anti-infectives was conducted from October 2013 to May 2014. The antimicrobial stewardship program (ASP) classified interventions on anti-infective regimens into predefined ME categories. Results: Forty-five patients who were discharged on 59 anti-infective prescriptions were included in the study. The most common indications for anti-infective regimens at discharge were pneumonia (22%, n = 10), bacteremia (18%, n = 8), and skin and soft tissue infections (16%, n = 7). An ME was identified in 42% (n = 19/45) of anti-infective regimens. Seventy percentage of ASP team recommendations were accepted which resulted in an avoidance of MEs in 68% (n = 13/19) of patients with an ME prior to discharge. Conclusion: This study describes the outcomes of a stewardship-initiated review process in preventing MEs at discharge. Developing a systematic process for a multidisciplinary ASP team to review all anti-infectives can be a valuable tool in preventing MEs at hospital discharge.

Assessing antimicrobial stewardship initiatives: Clinical evaluation of cefepime or piperacillin/tazobactam in patients with bloodstream infections secondary to AmpC-producing organisms

Management of micro-organisms harbouring AmpC β-lactamases remains challenging. Carbapenems are often considered first-line agents. Due to growing concern regarding carbapenem-resistant Enterobacteriaceae, integrating non-carbapenem treatment strategies is being explored for these pathogens. The primary objective of this study was to evaluate clinical outcomes in patients with bacteraemia secondary to AmpC-producing organisms treated with cefepime or piperacillin/tazobactam (TZP). A retrospective study of adult patients receiving cefepime or TZP for the treatment of AmpC -producing organisms with positive cefoxitin screen (i.e. Citrobacter, Enterobacter or Serratia spp. along with cefoxitin resistance) isolated from blood cultures was conducted. The primary endpoint was clinical cure at end of therapy (EOT). Secondary endpoints included microbiological eradication, frequency of susceptibility changes following treatment, and 7- and 30-day all-cause mortality. Clinical cure at EOT was 87.1%, with 93.2% of patients achieving microbiological eradication. The 7- and 30-day mortality rates were 3.8% and 10.6%, respectively. Organism susceptibility was exceptionally high, with minimum inhibitory concentrations (MICs) of ≤2 μg/mL in 90% of patients treated with cefepime (n = 108). Selection for resistance to third-generation cephalosporins or primary antimicrobial therapy was infrequent at 6.1% (8/132). In conclusion, use of cefepime or TZP for management of AmpC bloodstream infections was associated with clinical and microbiological cure with infrequent selection for resistance.

SCAN: A novel approach for vancomycin time-out

To the Editor—Approximately 30%–50% of antimicrobials prescribed in hospitals are either inappropriate or unnecessary. The Joint Commission (TJC), Centers for Disease Control (CDC), and Infectious Diseases Society of America (IDSA) in partnership with the Society of Healthcare Epidemiology (SHEA) have all issued performance elements for antimicrobial stewardship programs (ASP). One core element in these standards is use of a systematic process for evaluating the need for treatment after a set period of time, most often referred to as “antibiotic time-out.” Although there is unanimous agreement that use of prospective strategies to evaluate antibiotic treatment is essential, little guidance on how to best integrate an antibiotic time-out process into clinical practice exists. We present an innovative approach to perform vancomycin time-out in a hospital setting.

Impact of an Extended Infusion Beta-lactam Strategy on Outcomes in Critically Ill Patients with Pseudomonas Infections

Abstract Background Pseudomonas aeruginosa (PSA) is frequently associated with nosocomial infections resulting in significant morbidity and mortality. High MICs in MDR strains highlights the need to maximize antibiotic exposure with the goal of improving patient outcomes. For β-lactams, optimal efficacy is achieved when free drug concentrations are above the MIC for ~ 40–60% of the dosing interval. Unfortunately, due to significant pharmacokinetic variability in the critically ill, achieving this target with standard intermittent infusions (II) is challenging, resulting in preference for extended (EI) or continuous infusion strategies. Additional data in patients with PSA infections are needed to understand the association between infusion strategy and clinical outcome. Methods A single-center, retrospective chart review. Adult patients with positive respiratory or blood cultures for PSA treated with cefepime or piperacillin/tazobactam managed in an ICU from January 2012 to May 2016 were included. Primary endpoint was clinical cure (CC) at end of therapy (EOT) between patients receiving EI or II. Secondary endpoints included microbiologic eradication (ME), 28-day mortality, length of ICU and hospital stay, and effect of baseline kidney function on clinical cure. Results Eighty-three patients were included in the analysis. Patient characteristics were well matched except for a higher frequency of malignancy in the EI arm (P = 0.02). CC was achieved in an overwhelming majority of EI patients compared with II (89.2% vs. 69.6%, P = 0.031). Further, patients with normal renal function (CrCL ≥ 60; P = 0.02) or APACHE II ≥ 17 (P = 0.04) receiving II experienced higher failure rates. In multivariate analysis, use of II associated with 4-fold higher incidence of clinical failure (OR 4.5 [1.3–16.3]). For other secondary endpoints, ME was observed in 73% of EI vs. 65% of II (P = 0.44) and 28-day mortality was observed in 13% of patients in both arms (P = 0.94). No significant differences were observed with other secondary variables. Conclusion Use of an EI strategy in critically ill patients with PSA infections improves CC. Further, EI benefitted those patients with normal to augmented renal clearance suggesting that improved exposure may play a role in clinical outcomes. Disclosures K. Klinker, The Medicines Company: Scientific Advisor, Consulting fee.