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Home , Fosfomycin, Tazobactam

Suggested Usage in ESBL+ and Enterococcus UTI

 Fosfomycin is useful for UTI, but NOT useful for or other indications due to poor drug distribution. o Due to high cost ($157 per dose), use is limited to ESBL+ and resistant enterococcus UTI (traditional agents are preferred for less resistant infections unless confirmed allergies are present) o Sensitivities are not readily available at most institutions. Literature suggests the following: . ESBL+ E.coli: >95% susceptible . ESBL+ K. pneumonia: 80-93% susceptible . Enterococcus (including VRE) : >95% susceptible . SNF residents should be expected to have lower susceptibilities. o Outcomes are better for uncomplicated UTI vs. complicated UTI . One study found a clinical cure rate of 100% for uncomplicated VRE UTI vs 76% for complicated VRE UTI o FHS hospitals will stock at least 1 fosfomycin dose o FHS outpatient pharmacies will stock 3 doses of fosfomycin o Beta-lactam are not reliable treatment options for ESBL+ organisms even if they are reported as sensitive

Definition of complicated UTI: UTI in the presence of an anatomic abnormality, a functional abnormality, or urinary catheter.  Factors that may increase risk of failing therapy: diabetes, , ≥7 days of symptoms before seeking care, hospital-acquired infection, renal failure, urinary tract obstruction, presence of catheter/stent/nephrostomy tube, recent urinary tract instrumentation, functional abnormality

Fosfomycin for OUTPATIENT UTI (Not for use in pyelonephritis)  For patients returning to facilities that are able to provide IV infusions is the preferred agent for ESBL+ organisms and IV is preferred for enterococcus.  Uncomplicated ESBL+/enterococcus UTI: o Enterococcus (including VRE) and ESBL+ E.coli: 1st line oral agent . Dose: 3 grams PO x1 o ESBL+ K. pneumonia: Increase dose to 3 grams po q48hrs x3 doses due to higher resistance  Complicated UTI: 2nd line agent for complicated UTI caused by resistant enterococcus (i.e. resistant to or confirmed amoxicillin allergy), ESBL+ E.coli, and ESBL+ K. Pneumoniae. Recommend requesting fosfomycin E-test on the sample to confirm sensitivity. o IV ertapenem is 1st line treatment for E.coli and K. Pneumoniae (unless resistant). IV vancomycin is 1st line agent for enterococcus (unless resistant) o Fosfomycin dose: 3 grams PO q48hrs x3 doses

Fosfomycin for INPATIENT UTI (Not for use in pyelonephritis)  Uncomplicated UTI: o Enterococcus (e.g. VRE): 1st line oral agent if amoxicillin and nitrofurantoin are resistant or not appropriate (i.e. fosfomycin can be used in place of linezolid). . Dose: 3 grams PO x1 o ESBL+ E.coli: Consider as oral alternative if is not appropriate, or if patient has inpatient status solely to receive IV antitibiotics (i.e. if patient can be discharged after fosfomycin dose) . Dose: 3 grams PO x1 o ESBL+ K. Pneumoniae: Consider as 2nd-3rd line oral agent if meropenem cannot be used . Dose: 3 grams PO q48hrs x3 doses  Complicated UTI: o Consider as 2nd line oral agent (failure rates are higher with complicated infection). Recommend requesting fosfomycin E-test on the sample to confirm sensitivity. . Dose: 3 grams PO q48hrs x3 doses

References:

 Arias, C., Contreras, G., & Murray, B. (n.d.). Management of multidrug-resistant enterococcal infections. Clinical Microbiology and Infection, 555-562.  Allerberger, F. (1999). In-vitro activity of fosfomycin against vancomycin-resistant enterococci. Journal of Antimicrobial Chemotherapy, 211-217  Shrestha, N., Chua, J., Tuohy, M., Wilson, D., Procop, G., Longworth, D., ... Hall, G. (2003). Antimicrobial Susceptibility of Vancomycin-Resistant Enterococcus faecium: Potential Utility of Fosfomycin. Scandinavian Journal of Infectious Diseases, 12-14  Pullukcu, H., Tasbakan, M., Sipahi, O., Yamazhan, T., Aydemir, S., & Ulusoy, S. (n.d.). Fosfomycin in the treatment of extended spectrum beta-lactamase-producing -related lower urinary tract infections. International Journal of Antimicrobial Agents, 62-65.  Falagas, et.al. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta- lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis. 2010 Jan;10(1):43-50  Chislet, et.al Fosfomycin susceptibility among extended-spectrum-β-lactamase-producing Escherichia coli in Nottingham, UK. Journal of Antimicrobial Chemotherapy Volume 65, Issue 5. Pp. 1076-1077.  Harada Y, Morinaga Y, Kaku N, et al. In vitro and in vivo activities of - and meropenem at different inoculum sizes of ESBL-producing Klebsiella pneumoniae. Clin Microbiol Infect. 2014;  Prakash V, Lewis JS, Herrera ML, Wickes BL, Jorgensen JH. Oral and parenteral therapeutic options for outpatient urinary infections caused by enterobacteriaceae producing CTX-M extended-spectrum beta- lactamases. Antimicrob Agents Chemother. 2009;53(3):1278-80.