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Usage Criteria for Fosfomycin In Fosfomycin Suggested Usage in ESBL+ and Enterococcus UTI Fosfomycin is useful for UTI, but NOT useful for pyelonephritis 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 antibiotics 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, pregnancy, ≥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 ertapenem is the preferred agent for ESBL+ organisms and IV vancomycin 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 amoxicillin 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 meropenem 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 Escherichia coli-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 piperacillin-tazobactam 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. .
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