Is fosfomycin (antibiotic) safe to use during the third trimester of pregnancy?

Safety of Fosfomycin Use During the Third Trimester of Pregnancy

Fosfomycin is safe to use during the third trimester of pregnancy and is an appropriate first-line treatment option for urinary tract infections in pregnant women.

Evidence Supporting Safety in Pregnancy

Fosfomycin has demonstrated a favorable safety profile throughout pregnancy, including the third trimester:

• According to the FDA drug label, animal reproduction studies with fosfomycin tromethamine did not show teratogenic effects in pregnant rats at doses up to 9 times the human dose 1
• A large observational study analyzing data from 5,362 pregnancies confirmed the safety of fosfomycin use during pregnancy, with no significant differences in pregnancy outcomes such as gestational age, neonatal weight, Apgar scores, or pregnancy complications between women who took fosfomycin and those who did not 2
• A 2023 comparative study using the EFEMERIS database (including 2,724 pregnant women exposed to fosfomycin) found no increased risk of major congenital anomalies after first-trimester exposure to fosfomycin compared to other antibiotics or no antibiotic exposure 3

Efficacy for UTIs in Pregnancy

Fosfomycin is not only safe but also highly effective for treating UTIs during pregnancy:

• A study examining bacterial profiles in pregnant women with UTIs found fosfomycin to be highly effective against common urinary pathogens across all trimesters:

  • 98-99% sensitivity for E. coli
  • 88-89% sensitivity for Klebsiella species
  • 93-100% sensitivity for Enterococcus species 4

• The researchers concluded that fosfomycin should be considered "the most adequate first-line treatment regimen due to high sensitivity to the drug, ease of use and safety for use in pregnancy" 4

Advantages of Fosfomycin in Pregnancy

Fosfomycin offers several practical advantages for treating UTIs in pregnant women:

• Single-dose treatment (3g packet mixed in water)
• High urinary concentration and prolonged activity
• Minimal systemic absorption, reducing fetal exposure
• Low risk of bacterial resistance
• Convenient administration improving compliance 5, 6

Clinical Recommendations

When treating UTIs in pregnant women in the third trimester:

1. Fosfomycin 3g as a single oral dose is an appropriate first-line option

2. Alternative safe antibiotics during pregnancy include:

   • Penicillins (e.g., amoxicillin)
   • Cephalosporins (e.g., cephalexin)
   • Nitrofurantoin (though avoid near term due to risk of hemolytic anemia in G6PD-deficient infants) 7, 5

3. Avoid during pregnancy:

   • Trimethoprim-sulfamethoxazole (especially in third trimester due to risk of kernicterus) 7
   • Fluoroquinolones
   • Tetracyclines 5

Important Considerations

• Obtain urine culture before and after treatment to confirm appropriate antibiotic selection and cure 1
• Patients should be informed that symptoms typically improve within 2-3 days after taking fosfomycin 1
• Physiologic changes in pregnancy (increased glomerular filtration rate, increased total body volume) may affect antibiotic pharmacokinetics, but fosfomycin's single-dose regimen helps mitigate these concerns 5

Fosfomycin represents an excellent balance of safety, efficacy, and convenience for treating UTIs in the third trimester of pregnancy, with substantial evidence supporting its use in this population.