What is the effectiveness of Fosfomycin (an antibiotic) against Enterococcus (a type of bacteria)?

From the Guidelines

Fosfomycin is recommended as a treatment option for uncomplicated urinary tract infections caused by Vancomycin-resistant Enterococci (VRE) at a dose of 3 grams orally as a single dose, but only when susceptibility is confirmed and other preferred options are not suitable. According to the most recent and highest quality study available 1, fosfomycin may be considered for uncomplicated urinary tract infections due to VRE. The study recommends a single dose of fosfomycin 3 g PO for uncomplicated urinary tract infections due to VRE, with a weak recommendation and very low quality of evidence (2D).

Some key points to consider when using fosfomycin for VRE infections include:

• Fosfomycin has variable susceptibility patterns against enterococci overall, with generally poor efficacy against Enterococcus faecium 1.
• The limited efficacy of fosfomycin against enterococci is due to its mechanism of action, which inhibits cell wall synthesis by interfering with phosphoenolpyruvate transferase, but enterococci often possess intrinsic or acquired resistance mechanisms that reduce fosfomycin's effectiveness against these organisms.
• For serious enterococcal infections, standard treatment regimens typically include ampicillin (2 grams IV every 4-6 hours) for susceptible strains, or vancomycin (15-20 mg/kg IV every 8-12 hours) for resistant strains, often combined with gentamicin for synergy in endocarditis or other severe infections.
• High dose daptomycin at 8e12 mg/kg daily may be used to treat VRE-BSI, with a weak recommendation and low quality of evidence (2C) 1.
• Tigecycline is recommended as a drug of choice for intra-abdominal infections caused by VREs, with a weak recommendation and very low quality of evidence (2D) 1.

It is essential to note that the evidence for fosfomycin's use in VRE infections is limited, and its effectiveness may vary depending on the specific strain and infection site. Therefore, fosfomycin should only be used when susceptibility is confirmed, and other preferred options are not suitable. Additionally, the treatment duration and dosage may need to be individualized based on the patient's clinical response and infection site.

From the FDA Drug Label

Fosfomycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Aerobic gram-positive microorganisms 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-positive microorganisms Enterococcus faecium

Fosfomycin is effective against Enterococcus faecalis. However, its effectiveness against Enterococcus faecium is unknown due to limited clinical trials.

• Enterococcus faecalis: Fosfomycin has been shown to be active against this microorganism.
• Enterococcus faecium: The safety and effectiveness of fosfomycin in treating clinical infections due to this microorganism has not been established in adequate and well-controlled clinical trials 2. Fosfomycin tromethamine granules for oral solution is indicated for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis 2.

From the Research

Fosfomycin versus Enterococcus

• Fosfomycin is an established treatment for uncomplicated urinary tract infections (UTIs), including those caused by Enterococcus species 3.
• The susceptibility of Enterococcus species to fosfomycin has been evaluated in several studies, with varying results:
  • One study found that the minimum inhibitory concentration (MIC) of fosfomycin for Enterococcus faecalis was 32-64 μg/mL, and for Enterococcus faecium was 64-128 μg/mL 4.
  • Another study found that the MIC50 and MIC90 values for fosfomycin against Enterococcus faecalis were 4 and 64 μg/mL, respectively, and against Enterococcus faecium were 16 and 128 μg/mL, respectively 5.
• Fosfomycin has been shown to be effective against Enterococcus species in vitro, including vancomycin-resistant Enterococcus (VRE) 4, 5.
• The use of fosfomycin for the treatment of Enterococcal UTIs is supported by several studies, including one that found that fosfomycin was effective in promoting suppression of regrowth (>3 log10 kill) in the majority of isolates 4.
• However, the optimal dose and duration of fosfomycin treatment for Enterococcal UTIs have not been established, and emerging resistance is a concern 6, 7.

Mechanism of Action and Resistance

• Fosfomycin inhibits the MurA enzyme involved in peptidoglycan synthesis, which is a critical component of the bacterial cell wall 3.
• Resistance to fosfomycin can occur through various mechanisms, including mutations in the MurA enzyme and the presence of efflux pumps 7.
• The use of fosfomycin in combination with other antibiotics may help to prevent the development of resistance 6.

Clinical Implications

• Fosfomycin may be a useful treatment option for Enterococcal UTIs, particularly in cases where other antibiotics are not effective or are contraindicated 4, 5.
• However, the use of fosfomycin should be guided by susceptibility testing and clinical experience, and the development of resistance should be monitored closely 6, 7.