Can fosfomycin be used to treat multidrug-resistant Pseudomonas cystitis?

From the Guidelines

Fosfomycin can be used to treat multidrug-resistant Pseudomonas cystitis, but it is not considered a first-line option for this specific pathogen. When treating multidrug-resistant Pseudomonas urinary tract infections, fosfomycin should be used based on susceptibility testing results 1. The typical dosing for uncomplicated cystitis is 3 grams of fosfomycin tromethamine powder dissolved in water as a single dose, though for multidrug-resistant Pseudomonas, multiple doses (such as every 48-72 hours for 3 doses) may be necessary for adequate treatment. Before prescribing fosfomycin, urine culture and susceptibility testing should be performed to confirm that the Pseudomonas strain is susceptible to fosfomycin, as resistance rates vary. Fosfomycin works by inhibiting bacterial cell wall synthesis through a unique mechanism different from beta-lactams, which explains why some multidrug-resistant organisms may remain susceptible to it. However, clinical success rates for Pseudomonas infections are generally lower than for other common urinary pathogens like E. coli, so close follow-up and potentially combination therapy with another antibiotic might be necessary in severe or complicated cases. Some studies suggest that fosfomycin may be used in combination with other antibiotics for the treatment of multidrug-resistant Pseudomonas infections 1. It is essential to note that the use of fosfomycin should be guided by local resistance patterns and susceptibility testing results, as well as clinical experience and patient-specific factors. In general, the use of fosfomycin for multidrug-resistant Pseudomonas cystitis should be considered on a case-by-case basis, taking into account the severity of the infection, the patient's underlying health status, and the potential risks and benefits of treatment.

Some key points to consider when using fosfomycin for multidrug-resistant Pseudomonas cystitis include:

• Fosfomycin should be used based on susceptibility testing results 1
• The typical dosing for uncomplicated cystitis is 3 grams of fosfomycin tromethamine powder dissolved in water as a single dose
• Multiple doses may be necessary for adequate treatment of multidrug-resistant Pseudomonas
• Close follow-up and potentially combination therapy with another antibiotic may be necessary in severe or complicated cases
• The use of fosfomycin should be guided by local resistance patterns and susceptibility testing results, as well as clinical experience and patient-specific factors.

It is also important to consider the potential risks and benefits of treatment with fosfomycin, including the risk of adverse effects and the potential for the development of resistance. Overall, fosfomycin can be a useful option for the treatment of multidrug-resistant Pseudomonas cystitis, but its use should be guided by careful consideration of the individual patient's needs and circumstances.

From the FDA Drug Label

Fosfomycin tromethamine granules for oral solution is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis. The following in vitro data are available, but their clinical significance is unknown entrations (MIC’s) of 64 mcg/mL or less against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of fosfomycin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials: Aerobic gram-negative microorganisms Citrobacter diversus Citrobacter freundii Enterobacter aerogenes Klebsiella oxytoca Klebsiella pneuomoniae Proteus mirabilis Proteus vulgaris Serratia marcescens Pseudomonas is not listed as a susceptible microorganism.

Fosfomycin is not indicated for the treatment of multidrug-resistant Pseudomonas cystitis. The FDA drug label does not provide sufficient information to support the use of fosfomycin for this specific indication 2 2.

From the Research

Fosfomycin for Multidrug-Resistant Pseudomonas Cystitis

• Fosfomycin is a bactericidal antibiotic with a broad-spectrum activity, including multidrug-resistant Gram-negative bacteria 3.
• The efficacy of fosfomycin against Pseudomonas aeruginosa urinary tract infections has been studied in a dynamic in vitro bladder infection model, which showed that simulated treatment with oral fosfomycin was ineffective despite high urinary concentrations and repeated daily doses for 7 days 4.
• However, fosfomycin has been shown to be effective against multidrug-resistant Pseudomonas aeruginosa infections in clinical studies, with a susceptibility rate of >90% in some studies 5.
• A systematic review of microbiological, animal, and clinical studies found that fosfomycin could have a role as a therapeutic option against multidrug-resistant Pseudomonas aeruginosa infections 5.
• Fosfomycin has also been studied in a Phase 2/3 randomized trial for the treatment of complicated urinary tract infection, including acute pyelonephritis, and was found to be effective and well-tolerated 6.

Treatment Options for Multidrug-Resistant Pseudomonas Cystitis

• Treatment options for urinary tract infections caused by multidrug-resistant Pseudomonas spp. include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, and fosfomycin 7.
• Fosfomycin can be used in combination with other antimicrobial agents to treat multidrug-resistant Pseudomonas aeruginosa infections, and has been shown to be synergistic with beta-lactams, aminoglycosides, and ciprofloxacin 5.
• The use of fosfomycin for the treatment of multidrug-resistant Pseudomonas cystitis should be guided by susceptibility testing and clinical experience, and should be used in accordance with local resistance patterns and treatment guidelines 7.