Intravenous Fosfomycin (ZTI-01) for the Treatment of Complicated Urinary Tract Infections (cUTI) Including Acute Pyelonephritis (AP): Results from a Multi-center, Randomized, Double-Blind Phase 2/3 Study in Hospitalized Adults (ZEUS)

Kaye, Keith S.; Rice, Louis B.; Dane, Aaron; Stus, V.P.; Sagan, Olexsiy; Fedosiuk, Elena; Das, Anita; Skarinsky, David; Eckburg, Paul B.; Ellis-Grosse, Evelyn J.

doi:10.1093/ofid/ofx163.1375

Cited by 13 publications

(10 citation statements)

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“…Grabein et al also reported that, in general, intravenous fosfomycin demonstrated a favorable safety profile, with only mild adverse effects (e.g., mild hypokalemia due to high sodium load with administration of fosfomycin disodium) not requiring discontinuation of therapy [ 49 ]. Other reviews and studies have reported similar conclusions [ 13 , 15 , 16 , 51 , 52 , 59 ].…”

Section: Intravenous Fosfomycin: Clinical Trials and Clinical Utilsupporting

confidence: 70%

“…In that review, the pooled estimate for resistance development during fosfomycin therapy was 3.4% (95% CI: 1.8–5.1%) [ 49 ]. Nonetheless, given that resistance to fosfomycin has the potential to develop in vivo when it is used as monotherapy, convention dictates that fosfomycin be administered as a component of combination therapy with one or more other antimicrobial agents when used for systemic therapy, except for the treatment of complicated urinary tract infections where it may be used as monotherapy [ 15 , 50 , 51 ].…”

Section: Fosfomycin: Resistance Mechanisms and Prevalence Of Resismentioning

confidence: 99%

“…The lack of nephrotoxicity of fosfomycin in patients suffering from parenchymal renal infection, together with the antibacterial spectrum of fosfomycin (i.e., includes enteric Gram-negative bacilli), suggests reliable efficacy in the treatment of these infections [ 68 ]. Several reviews of studies have suggested that fosfomycin is in association with favorable outcomes (versus comparators) when treating with MDR Gram-negative bacterial infections, predominantly urinary tract infections [ 16 , 51 – 53 , 60 ].…”

Section: Intravenous Fosfomycin: Clinical Trials and Clinical Utilmentioning

confidence: 99%

“…More recently, in 2017, the ZEUS study, a multicentered, randomized, double-blind phase II/III study of hospitalized patients with complicated urinary tract infections or pyelonephritis received a 1-h infusion of 6 g fosfomycin every 8 h (18 g total daily dose) or a 1-h infusion of 4.5 g piperacillin-tazobactam every 8 h (13.5 g total daily dose) for 7 days [ 51 ]. Patients with concurrent bacteremia received 14 days of treatment.…”

Section: Intravenous Fosfomycin: Clinical Trials and Clinical Utilmentioning

confidence: 99%

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Intravenous Fosfomycin: An Assessment of Its Potential for Use in the Treatment of Systemic Infections in Canada

Zhanel

Karlowsky

2018

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Fosfomycin is a bactericidal agent that inhibits cell wall synthesis using a mechanism of action distinct from β-lactams or other antimicrobial agents. It is a broad-spectrum agent that is frequently active against antimicrobial-resistant bacterial pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Enterobacteriaceae, and some isolates of MDR Pseudomonas aeruginosa. Intravenous fosfomycin has been prescribed for a wide variety of infections in many countries for >40 years. It is most frequently used in combination with other antimicrobial agents (e.g., β-lactams, carbapenems, and aminoglycosides) and has an excellent safety profile, including in neonates and children, even with long-term administration (weeks). Fosfomycin achieves extensive tissue distribution including difficult to reach compartments such as aqueous humor, vitreous humor, abscess fluid, and CSF. Available data, to date, suggest no clinically relevant pharmacological interactions between fosfomycin and other agents, including drugs, stimulants, or food. Intravenous fosfomycin's role in therapy in Canada is likely as an agent used alone or in combination for complicated urinary tract infections in hospitalized patients as well as hospitalized patients with MDR infections who have not responded to first-, and potentially, second-line antimicrobials or in patients who cannot tolerate (due to adverse effects) first- and second-line antimicrobials.

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Section: Intravenous Fosfomycin: Clinical Trials and Clinical Utilsupporting

confidence: 70%

Section: Fosfomycin: Resistance Mechanisms and Prevalence Of Resismentioning

confidence: 99%

Section: Intravenous Fosfomycin: Clinical Trials and Clinical Utilmentioning

confidence: 99%

Section: Intravenous Fosfomycin: Clinical Trials and Clinical Utilmentioning

confidence: 99%

See 2 more Smart Citations

Intravenous Fosfomycin: An Assessment of Its Potential for Use in the Treatment of Systemic Infections in Canada

Zhanel

Karlowsky

2018

Canadian Journal of Infectious Diseases and Medical Microbiolog

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“…The most appropriate dosing schedules range from 4 g every 6 to 8 h to up to 8 g every 8 h (129,130). For monotherapy, the drug has been tested as empirical therapy (6 g every 8 h) in an RCT of cUTI, including pyelonephritis; a preliminary report of the trial showed that fosfomycin met the noninferiority criteria against piperacillin-tazobactam for overall success (131). It is also being tested compared to ceftriaxone or meropenem as targeted therapy in an RCT of bacteremic UTI due to multidrug-resistant E. coli (132).…”

Section: Fosfomycinmentioning

confidence: 99%

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

et al. 2018

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Therapy of invasive infections due to multidrug-resistant (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producing (CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.

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Uso actual de la fosfomicina: del laboratorio a la práctica clínica

Candel

2019

Enfermedades Infecciosas y Microbiología Clínica

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Intravenous Fosfomycin (ZTI-01) for the Treatment of Complicated Urinary Tract Infections (cUTI) Including Acute Pyelonephritis (AP): Results from a Multi-center, Randomized, Double-Blind Phase 2/3 Study in Hospitalized Adults (ZEUS)

Cited by 13 publications

References 0 publications

Intravenous Fosfomycin: An Assessment of Its Potential for Use in the Treatment of Systemic Infections in Canada

Intravenous Fosfomycin: An Assessment of Its Potential for Use in the Treatment of Systemic Infections in Canada

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

Uso actual de la fosfomicina: del laboratorio a la práctica clínica

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