Treatment alternatives for piperacillin/tazobactam, meropenem, linezolid, and daptomycin The goals of the FHS Antimicrobial Stewardship Program (ASP) are to optimize clinical outcomes associated with antimicrobial use while minimizing toxicities and adverse events of such therapy. Through appropriate antibiotic selection, dosing, and duration of therapy, our objective is to decrease the spread of antimicrobial resistance in the setting of limited new and projected pharmacologic agents coming to market. Cost containment will always be a secondary goal to ensuring excellent patient care.

However, many of the antimicrobial agents with the broadest spectra of activity also come with the greatest costs, both with regards to financial cost and the cost of growing antimicrobial resistance. It is imperative that all providers select an agent with the narrowest spectrum possible to decrease these consequences.

We have chosen to intensely focus on four antimicrobial agents that have been responsible for some of the greatest costs to our health system: piperacillin/tazobactam, meropenem, linezolid, and daptomycin.

Antibiotic Cost per Potential alternative agents Cost per day* day* Piperacillin/tazobactam IV 3.375 g Q8H (over 4 hr) $11.67 (generic for Zosyn®)

Pseudomonal coverage usually not necessary for Ampicillin/sulbactam IV 3 g IV Q6H $8.40 diabetic foot infections (unless patient is neutropenic, (if Pseudomonal coverage not required) post-op infection, or related to burn or nail puncture wound) or community-acquired intra-abdominal infections Ceftriaxone IV 2 g Q24H + Risk factors for Pseudomonas: ICU admission metronidazole IV 500 mg Q8H $5.22 within 90 days, chronic decubitus ulcers, increased age, length of mechanical ventilation, (if Pseudomonal coverage not required) immunocompromised, structural lung Amoxicillin/clavulanate PO 875 mg disease/bronchiectasis, repeated exacerbations of Q12H $1.80 COPD requiring frequent glucocorticoid and/or antibiotic use (if Pseudomonal coverage not required) Levofloxacin IV 750 mg Q24H Anaerobic coverage may not be necessary in $3.28 aspiration pneumonia (unless patient has poor oral (if anaerobic coverage not required) hygiene, periodontal disease or alcoholism) Levofloxacin PO 750 mg Q24H $0.36 Indications for anaerobes: vascular insufficiency, (if anaerobic coverage not required) abscesses, intra-abdominal infections Ceftriaxone IV 2 g IV Q24H (if neither Pseudomonal nor anaerobic $1.95 coverage required)

Updated by Ka Ning Jellison, PharmD Approved by ASP Committee, PT&T Last Revision Date September 2015

Antibiotic Cost per Potential alternative agents Cost per day* day* Meropenem IV1 g Q8H (over 3 hr) $23.31 (generic for Merrem®) Cefepime IV 2 g IV Q8H $17.40 Cephalosporins are considered as safe as may add metronidazole IV 500 mg Q8H if +$3.27 carbapenems in patients with penicillin allergy due anerobic coverage required to low risk for cross-reaction May consider any of the above alternatives for $0.36-$8.40 piperacillin/tazobactam Fosfomycin is useful for ESBL(+) and Enterococcus Fosfomycin 3 g PO x 1 faecalis UTI, but not useful for pyelonephritis or other (Enterococcus and ESBL+ E. Coli) $52.30- indications due to poor drug distribution or 3 g PO Q48H x 3 doses for $157 higher resistance (ESBL+ K. (1-3 doses) pneumonia) Linezolid IV 600 mg Q12H $84.98 (generic for Zyvox®) Multiple meta-analyses have failed to show superiority of linezolid over vancomycin for clinical Vancomycin IV success and mortality in pneumonia.1-2 RCT that did ~$20 can be effectively dose adjusted for renal (includes show clinical/ micro outcome superiority in MRSA dysfunction monitoring) HAP/HCAP failed to show mortality benefit.3

Ceftaroline may be used in patients with ABSSSI Ceftaroline 600 mg IV Q12H $216.66 including those caused by MRSA and CAP (not caused by MRSA) Linezolid PO 600 mg Q12H $158.62 (generic for Zyvox®) Doxycycline PO 100 mg Q12H $0.66 Consider alternate PO agents for MRSA coverage Minocycline PO 100 mg Q12H $0.92 with clinical improvement based on culture Bactrim DS PO 1-2 tabs Q12H $0.26-$0.52 susceptibility Clindamycin PO 450 mg Q8H  excellent bone, joint, and abscess $2.25 penetration  may increase risk for Clostridium difficile infection Daptomycin IV 4-6 mg/kg Q24H (Cubicin®) $0.71/mg no generic available

Often reserved for MRSA strains with vancomycin Vancomycin IV ~$20 MIC > 1 can be effectively dose adjusted for renal (includes dysfunction monitoring) See above for ceftaroline indications Linezolid 600mg Q12H IV $84.95 Linezolid 600mg Q12H PO $158.62 Ceftaroline 600 mg IV Q12H $216.66 *Cost per day assumes patient weight 80 kg, BMI > 30, and CrCl > 50 mL/min

Updated by Ka Ning Jellison, PharmD Approved by ASP Committee, PT&T Last Revision Date September 2015

1. Kalil AC, et al. Crit Care Med. 2010;38(9):1802 2. Walkey AJ, et al. Chest. 2011;139(5):1148. 3. Wunderink RG, et al. Clin Infect Dis. 2012;54(5):621. 4. Kanj, SS. Principles of antimicrobial therapy of Pseudomonas aeruginosa infections. In: UpToDate, Calderwood, SB (Ed), Bloom, A (Ed). 2015. 5. File, TM. Treatment of community-acquired pneumonia in adults who require hospitalization. In: UpToDate, Bartlett, JG (Ed), Thorner, AT (Ed). 2015. 6. Bartlett, J. Anaerobic bacterial infections. In: UpToDate, Calderwood, SB (Ed), Thorner, AR (Ed). 2015

Updated by Ka Ning Jellison, PharmD Approved by ASP Committee, PT&T Last Revision Date September 2015