Oral and Intravenous Fosfomycin for the Treatment of Complicated Urinary Tract Infections

Abstract

Oral fosfomycin is approved in Canada for the treatment of acute uncomplicated cystitis. Several studies have reported “off label” use of oral fosfomycin in the treatment of patients with complicated lower urinary tract infection (cLUTI). This review summarizes the available literature describing the use of oral fosfomycin in the treatment of patients with cLUTI. Collectively, these studies support the use of a regimen of 3 grams of oral fosfomycin administered once every 48 or 72 hours for a total of 3 doses for patients who have previously failed treatment with another agent, are infected with a multidrug-resistant (MDR) pathogen, or cannot tolerate first-line treatment due to intolerance or adverse effects. Additionally, a Phase 2/3 clinical trial, known as the ZEUS study, assessed the efficacy and safety of intravenous (IV) fosfomycin versus piperacillin-tazobactam in the treatment of patients with complicated upper urinary tract infection (cUUTI) or acute pyelonephritis (AP) including in patients with concomitant bacteremia. IV fosfomycin was reported to be noninferior to piperacillin-tazobactam in treating patients with cUUTI and AP; however, when outcomes were independently evaluated according to baseline diagnosis (i.e., cUUTI versus AP), IV fosfomycin was superior to piperacillin-tazobactam in the treatment of patients with cUUTI and demonstrated superior microbiological eradication rates, across all resistant phenotypes including extended-spectrum β-lactamase- (ESBL-) producing Escherichia coli and Klebsiella spp. and carbapenem-resistant (CRE), aminoglycoside-resistant, and MDR Gram-negative bacilli (primarily Enterobacterales). Based on the ZEUS study, IV fosfomycin dosed at 6 grams every 8 hours for 7 days (14 days in patients with concurrent bacteremia) appears to be a safe and effective therapeutic option in treating patients with upper urinary tract infections, particularly those with cUUTI caused by antimicrobial-resistant Enterobacterales.

Assessment of Bacterial Isolates from the Urine Specimens of Urinary Tract Infected Patient

“…Complicated UTIs are predisposed by underlying host characteristics such as spinal cord damage, catheterization, age, and diabetes mellitus as in Figure 3 . Less infectious uropathogens (which hardly cause illness in a healthy urinary system) can produce severe harm to aberrant urinary tract in complex UTIs [ 23 ]. In the elderly, studies have found links among Enterococci, Group B streptococcal bacteremia, and Candida, as well as problematic UTIs.…”

In Vitro Susceptibility of Multi-Drug Resistant Klebsiellapneumoniae Strains Causing Nosocomial Infections to Fosfomycin. A Comparison of Determination Methods

“…Except for urinary tract infections, monotherapy with i.v. fosfomycin is not recommended due to the risk of development of resistance [ 40 , 41 ]. A good safety profile of the agent allows for infusions in a wide dosage range.…”

“…An extensive literature presents i.v. fosfomycin as a viable treatment option for patients with systemic infections with Enterobacterales producing both ESBL and CPE [ 1 , 3 , 4 , 13 , 41 , 42 ]. As early as in 2010, Falagaset et al reported the satisfactory sensitivity of multidrug-resistant Klebsiella pneumoniae to fosfomycin [ 1 ].…”

Development and Validation of New Method for the Simultaneous Estimation of Ceftriaxone and Tazobactam Using Rp-HPLC

“…Ceftriaxone, commercialised under the trade name Rocephin, is a third-generation cephalosporin [1][2] antibiotic [3][4][5] used for the treatment of a range of bacterial infections. These include middle ear infections, endocarditis [6][7] , meningitis [8][9] , pneumonia [10][11] , bone and joint infections, intra-abdominal infections [12] , skin infections [13] , urinary tract infections [14] , gonorrhea [15] , and pelvic inflammatory [16] disease. It is also occasionally administered before surgery and after a bite wound to attempt to avoid infection.…”