April 25, 2018 Edited by: Gregory K. Perry, PharmD, BCPS-AQID

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VOLUME FOUR; ISSUE 4 April 25, 2018 Edited by: Gregory K. Perry, PharmD, BCPS-AQID

InPHARMation Pharmacy and Therapeutics Committee Update April 25 th, 2018 Meeting The Pharmacy and Therapeutics Committee at Hendrick Medical Center is a Medical Staff Committee that meets the fourth Wednesday of each month with five physicians and one pharmacist serving as voting members. P and T is Medical Staff Committee. The current Chair of P and T is Charles W. Fuller, M.D. Drug Shortages: IV hydromorphone and IV morphine continue to experience supply issues. To date we have been able to assure a supply to cover patient care needs but it has been tight at times. We will continue to monitor the situation. P and T recommends that the medical staff minimize the use of these drugs if other alternatives are available (oral pain medications). Multi-Modal Pain Control: Effective January 1 st, 2018 The Joint Commission published Standard LD.04.03.13. This is the pain assessment and pain management, including safe opioid prescribing, is identified as an organizational priority for the hospital. One of the metrics is participating in the establishment of protocols and quality metrics. P and T would like to remind the medical staff that HMC does have a pain management protocol that physicians may elect to use. If you would like more information please contact Greg Perry. Antimicrobial Stewardship Committee (AMS) Update: Utilization Reports through November 2017 Overall utilization of antimicrobials as defined by the CDC/NHSN indicates Hendrick Medical Center is potentially using to many antibiotics. The SAAR for March 2018 was 1.272 for the system. The recommendation would be if you do not need therapy directed towards Pseudomonas aeruginosa then please avoid all anti-pseudomonal antibiotics if at all possible. The overall days of therapy per 1000 patient days represents a steady decline in antibiotic use over the past 12 months. If you would like to see a detailed report (Physician specific use, floor specific use, CDC specifics) please contact Greg Perry, PharmD, BCPS-AQID at gperry@hendrickhealth.org Always remember the premise of Antimicrobial Stewardship using the three R s. With this in mind please read the Antimicrobial Education of this month s newsletter. Very timely information. R = Right Drug. R = Right Dose. R = Right Duration of Therapy. InPHARMation 4/25/2018 1

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Antimicrobial Stewardship Education by Gregory K. Perry, PharmD, BCPS-AQID The MERINO Trial RCT Meropenem vs Piperacillin-Tazobactam for Definitive Treatment of BSI's Due to Ceftriaxone Non-susceptible Escherichia Coli and Klebsiella Spp. From clinicaltrials.gov. No randomized controlled trials (RCTs) have yet been performed comparing different treatment options for AmpC or ESBL-producing Enterobacteriaceae. During the last 10 years we have seen an exponentially increasing rate of carbapenem resistance worldwide, including Australia and New Zealand. The investigators urgently need data from well-designed RCTs to guide clinicians in the treatment of antibiotic resistant Gram-negative infections. The investigators face a situation where a commonly used antibiotic for these infections (meropenem) may be driving carbapenem resistance. For this reason, the investigators are seeking to compare a carbapenem-sparing regimen with a carbapenem for the treatment of these infections. Formal evaluation of safety and efficacy of generic antibiotics in the treatment of infection is of immense clinical and public health importance, and no formal trial has yet been conducted to address these issues. The international collaboration between teams of clinician researchers, some of whom are leaders in their field, makes it highly likely that the outcomes of this trial will have a significant impact on clinical practice. The investigators' hypothesis is that piperacillin/tazobactam (a carbapenem-sparing regimen) is noninferior to meropenem (a widely used carbapenem) for the definitive treatment of bloodstream infections due to third-generation cephalosporin non-susceptible E. coli or Klebsiella species. The hypothesis was NOT proven. Just the opposite. Meropenem was superior to piperacillin/tazobactam for ESBL/AmpC producing Escherichia Coli and Klebsiella Spp not only for blood stream infections but for all other subgroup analysis. We most certainly want to avoid any anti-pseudomonal antibiotics if we are not treating a Pseudomonas infection. Both pip/tazo and meropenem also cover Pseudomonas. The logical drug of choice would be ertapenem 1000 mg IVPB q24h. InPHARMation 4/25/2018 8

Let s look at the results from the MERINO trial overall primary results. Mortality Mortality at 30 days (Primary analysis) Mortality at 30 days (per-protocol analysis) Pip/Tazo Meropenem 12.3% 3.7% 10.6% 3.8% Let s look at the results from the sub-group analysis of the MERINO trial. Mortality E. coli (Primary ESBL is the TEM and CTX-M easier to handle) K. pneumoniae (Primary ESBL is the SHV more potent inhibitor) HAI Non-HAI UTI Non-UTI Immunocompromised Non-Immunocompromised Pip/Tazo 10.6% 23.1% 16.8% 8.3% 6.9% 18.8% 19.6% 9.6% Meropenem 4.2% 0 3.7% 3.6% 3.1% 4.8% 2.5% 4% Recommendation: If you have an ESBL producing (C and S shows ceftriaxone or cefotaxime resistance) Enterobacteriaceae infection (E. coli or Klebsiella Spp) please consider therapy with ertapenem (Invanz) 1000 mg every 24 hours. For deep seated/life threatening infection ertapenem 2000 mg every 24 hour has been advocated but is not the normal dose needed. Therapeutically Speaking Test Your Knowledge: InPHARMation 4/25/2018 A 55-year-old man has a medical history of acute prostatitis. He has had two episodes within the past year; both were treated with trimethoprim/sulfamethoxazole. Now, his symptoms have returned. His physician is considering therapy options for chronic prostatitis. Which one of the following is best to recommend for this patient? A. Cephalexin. B. Azithromycin. C. Amoxicillin. D. Levofloxacin. 9

Test Your Knowledge Answer: ANSWER D: Levofloxacin The fluoroquinolones are the preferred agents to treat prostatitis because of the high degree of distribution in the prostatic tissue (Answer D is correct). The other antibiotics are not associated with similar treatment outcomes. Ref: Schiller et al and Grabe et al. InPHARMation 4/25/2018 10