Samuel J. Borgert

Clinical and economic impact of antimicrobial stewardship interventions with the FilmArray blood culture identification panel.

The purpose of this study was to evaluate the impact of the FilmArray Blood Culture Identification (BCID) Panel on the management of patients with blood cultures growing gram positive cocci and Candida. We retrospectively compared clinical and economic outcomes between patients during the BCID testing period and a matched historical control group before BCID testing was introduced. A total of 84 BCID patients were matched to 252 historical controls. BCID identification of coagulase negative staphylococci contaminants resulted in shorter post-culture length of stay (P < 0.008) and saved roughly

Beyond Vancomycin: The Tail of the Lipoglycopeptides

30,000 per 100 patients tested. The BCID led to shorter duration of empirical vancomycin for patients with contaminated blood cultures (P = 0.005) and methicillin-susceptible Staphylococcus aureus bacteremia (P < 0.001). Patients with vancomycin-resistant enterococcal bacteremia received active therapy earlier than historical controls (P = 0.047). The BCID, coupled with antimicrobial stewardship intervention, was a cost effective tool to improve patient care.

Time to Positivity of Blood Cultures Supports Antibiotic De-escalation at 48 Hours

PURPOSE The purpose of this comparative review is to provide clinical information on the semisynthetic lipoglycopeptides (telavancin, oritavancin, and dalbavancin) for the management of gram-positive infections. METHODS A PubMed search was conducted using the following terms: telavancin, dalbavancin, and oritavancin. Clinical trials evaluating pharmacokinetic properties, pharmacodynamic properties, clinical efficacy, and safety profiles were included in the review. FINDINGS The lipoglycopeptides are approximately 4- to 8-fold more potent than vancomycin against gram-positive organisms, including activity against vancomycin-intermediate or vancomycin-resistant strains of Staphylococcus and Enterococcus species. In addition, oritavancin maintains activity against Enterococcus species harboring vanA operon. Clinical trial data revealed equal efficacy to vancomycin in the management of acute bacterial skin and skin structure infections and, in the case of telavancin, hospital-acquired pneumonia. A benefit of oritavancin and dalbavancin is that a full course of therapy consists of a single- or 2-dose regimen, respectively. These agents are well tolerated with similar adverse event rates to vancomycin. Telavancin requires a thorough assessment before initiation of therapy to minimize the risk of acute kidney injury and teratogenicity. IMPLICATIONS The lipoglycopeptides enhance the antibiotic gram-positive armamentarium at a time when methicillin-resistant Staphylococcus aureus prevalence and overall resistance is at an all-time high. These agents serve to fill different clinical roles in the management of gram-positive infections. On the basis of the available data, telavancin should be considered a plausible agent for the management of gram-positive organisms when patients do not respond or develop adverse effects to vancomycin. Dalbavancin and oritavancin are new therapeutic options, and their potency and pharmacokinetic properties may provide benefit over existing therapies. Clinical trial data indicate that patients with signs or symptoms of skin and skin structure infections may be successfully treated using 1 or 2 doses of these agents. Eliminating the need for inpatient admission, central catheter placement, and/or daily outpatient parenteral antibiotic therapy is a major advance in treatment of skin and skin structure infections. This strategy may reduce costs associated with resource utilization and iatrogenic morbidity, resulting in overall improvements in care.

Detection of Neisseria meningitidis from Negative Blood Cultures and Cerebrospinal Fluid with the FilmArray Blood Culture Identification Panel

Background: Appropriate de-escalation of empirical antimicrobial therapy is a fundamental component of antimicrobial stewardship. Concern for the late detection of bloodstream pathogens may undermine early streamlining efforts and subject patients to protracted courses of nonessential therapy. Objective: To quantify the prevalence of bacterial bloodstream infection (BSI) detection after more than 48 hours of culture incubation. We also assessed the impact of antimicrobial therapy delivered prior to blood sample collection. Methods: We retrospectively evaluated time to blood culture positivity (TTP) in adult patients at an academic tertiary care hospital. Microbiology reports were reviewed to identify the TTP for the first positive blood culture bottle for each episode of BSI occurring from February 1, 2011, to July 31, 2011. Isolates were classified as true pathogens or contaminants. Blood culture results after 48 hours of incubation were compared with results after 120 hours of incubation. Results: The median TTP of 416 monomicrobial BSIs and 210 contamination episodes was 13.7 and 24.4 hours, respectively (P < .001). The median TTPs in those who received and did not receive prior antibiotics were 17.0 and 12.8 hours, respectively (P < .001). By 48 hours, 98% of aerobic Gram-positive and Gram-negative BSIs were detected. Culture results at 48 hours were 97% sensitive and had a negative predictive value of 99.8%. Conclusion: Few true BSIs are detected after more than 48 hours of culture incubation. Clinicians may adjust empirical antibiotic coverage at this time with little risk for subsequent bacterial pathogen detection.

Evaluation of an Interactive Educational Model to Enhance AntimicrobialStewardship at an Academic Medical Center

ABSTRACT The FilmArray blood culture identification (BCID) panel is a rapid molecular diagnostic test approved for use with positive blood culture material. We describe a fatal case of meningococcemia with central nervous system (CNS) involvement detected using the BCID test with culture-negative blood and cerebrospinal fluid.

Ampicillin for the treatment of complicated urinary tract infections caused by vancomycin resistant enterococcus spp (VRE): a single-center university hospital experience

Purpose: Employee education and professional development within a pharmacy department is vital for increasing job satisfaction and optimizing quantity and quality of interventions. Frontline pharmacists have a unique opportunity to intervene at the time of verification to prevent initiation of inappropriate antibiotics, avoid adverse reactions and toxicities from unnecessary agents, decrease risk for secondary infections, and lower selection pressure for antimicrobial resistance. Methods: In an attempt to strengthen knowledge surrounding Antimicrobial Stewardship Program (ASP) practices at an academic medical center, an IRB-approved, prospective, non-randomized pilot educational program focused on urinary tract infections (UTIs) was developed for frontline pharmacy personnel with order verification duties. The goal of this program was to provide an interactive, case-based learning experience for pharmacists to improve their ability to make interventions on antimicrobials prescribed for UTI. Results: Over half of pharmacists surveyed felt a lack of knowledge prohibited them from making interventions on UTI antimicrobials. Eighty-three percent of pharmacists desired to learn more about UTI treatment. After the CE lecture, pharmacists had a better perception of knowledge with significantly increased confidence and satisfaction in their understanding of UTI. Test scores assessing pharmacists’ ability to make an intervention regarding appropriate antimicrobial treatment of UTI nearly doubled. Scores also significantly increased in pathogenesis and overall categories. Conclusion: An interactive educational program focused on practical areas for intervention increased knowledge and confidence of frontline pharmacists. Involvement of these pharmacists extends the ASP footprint within our healthcare system.

Impact of the Cyp2c19 genotype on voriconazole exposure in adults with invasive fungal infections.

Vancomycin-resistant enterococci (VRE) are a common cause of urinary tract infections (UTIs) and are typically multidrug resistant, including ampicillin. This retrospective study evaluated outcomes of 84 adult patients hospitalized between January 2007 and December 2015 with ampicillin- and vancomycin-resistant enterococcus isolates causing UTI and treated with ampicillin. Treatment response was classified as clinical cure and microbiological eradication. Clinical cure was achieved in 88.1% (74/84) of patients. In patients with follow-up cultures, microbiological eradication was achieved in 86% (50/58) of patients. Cure rates were similar in patients with indwelling urinary catheters (n = 45) receiving catheter exchange/removal (90.47%; 19/21) versus catheter retention (87.5%; 21/24). Presence of co-morbidities, such as diabetes and chronic kidney disease, were not associated with increased risk of treatment failure. Immunocompromised patients achieved lower cure rates of 78.1% (25/32) compared with 94.2% (49/52) among those without immune impairment (P = 0.038). Presence of an underlying urinary tract abnormality was also associated with a lower cure rate of 71.4% (15/21) compared with 93.7% (59/63) in those without urinary tract abnormalities (P = 0.0135). Overall cure rates remained high in all groups providing good evidence to support ampicillin for the treatment of complicated UTI caused by ampicillin- and vancomycin-resistant enterococci.

Measuring quality metrics to identify and monitor antimicrobial stewardship program quality improvement efforts.

Objectives Voriconazole, a first-line agent for the treatment of invasive fungal infections (IFIs), is metabolized by CYP2C19. A significant proportion of patients fail to achieve therapeutic trough concentrations with standard weight-based voriconazole dosing, placing them at increased risk for treatment failure, which can be life threatening. We sought to test the association between the CYP2C19 genotype and subtherapeutic voriconazole concentrations in adults with IFIs. Patient and methods Adults receiving weight-based voriconazole dosing for the treatment of IFIs were genotyped for the CYP2C19*2, *3, and *17 polymorphisms, and CYP2C19 metabolizer phenotypes were inferred. Steady-state voriconazole trough plasma concentrations and the prevalence of subtherapeutic troughs (<2 mg/l) were compared between patients with the CYP2C19*17/*17 (ultrarapid metabolizer, UM) or *1/*17 (rapid metabolizer, RM) genotype versus those with other genotypes. Logistic regression, adjusting for clinical factors, was performed to estimate the odds of subtherapeutic concentrations. Results Of 70 patients included (mean age 52.5±18 years), 39% were RMs or UMs. Compared with patients with the other phenotypes, RMs/UMs had a lower steady-state trough concentration (4.26±2.2 vs. 2.86±2.3, P=0.0093) and a higher prevalence of subtherapeutic troughs (16 vs. 52%, P=0.0028), with an odds ratio of 5.6 (95% confidence interval: 1.64–19.24, P=0.0044). Conclusion Our findings indicate that adults with the CYP2C19 RM or UM phenotype are more likely to have subtherapeutic concentrations with weight-based voriconazole dosing. These results corroborate previous findings in children and support the potential clinical utility of CYP2C19 genotype-guided voriconazole dosing to avoid underexposure in RMs and UMs.

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

Quality Improvement Efforts Author(s): David J. Guervil, PharmD; Kenneth P. Klinker, PharmD; Nicole T. Reardon, PharmD, BCPS; Hassan M. Alnuaimat, MD; Samuel J. Borgert, PharmD; Reuben Ramphal, MD Source: Infection Control and Hospital Epidemiology, Vol. 35, No. 1 (January 2014), pp. 101103 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/674403 . Accessed: 07/01/2014 16:28

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

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.