Generic Name

Fosfomycin

Brand Names

Monophas, Fosfomycin Tromethamine, fosfomycin disodium) is a broad‑spectrum, first‑generation phosphonic acid antibiotic. It is available as oral powder for suspensions (often mixed with fruit juice) and as an intravenous formulation.

Mechanism

• Inhibits UDP‑N‑acetylglucosamine enolpyruvyl transferase (MurA): Precludes the first committed step of bacterial cell‑wall synthesis, creating a lethal “dead‑end” complex.
• Permeable to Gram‑positive and Gram‑negative bacteria, including drug‑resistant *Escherichia coli* and *Klebsiella pneumoniae*.
• Low potential for cross‑resistance with other β‑lactams or fluoroquinolones.

This single‑step blockade halts peptidoglycan polymerisation, causing rapid bacterial lysis.

Pharmacokinetics

• Oral: absorbed ~70 % by passive diffusion. Peak plasma concentration (Cmax) 4–8 µg/mL (within 90 min).
• Intravenous: linear pharmacokinetics; Cmax proportional to dose.
• Distribution: achieves high urinary concentrations (~1–2 x peak serum), excellent for urinary tract infections (UTIs). Limited CNS penetration (<2 % of serum).
• Elimination: predominantly renal (≈ 99 % unchanged drug).
• Half‑life: 2.8 h in patients with normal renal function; ~ 7–8 h in patients with severe renal impairment (requires dose adjustment).
• Protein binding: ≤ 10 %.

Indications

• Acute uncomplicated cystitis (single oral dose 3 g or 6 g).
• Complicated cystitis & pyelonephritis (IV: 400 mg every 6 h or 1 g q12h; oral: 3 g q24h).
• Invasive gram‑negative infections when susceptible: abdominal, biliary, and world‑wide *E. coli* isolates.
• Empiric therapy prior to culture data in UTIs with limited drug options (e.g., in ≥ 65 y or in patients with multiple comorbidities).
• Combination therapy in carbapenem‑resistant Enterobacteriaceae (CRE) or multidrug‑resistant (MDR) *Pseudomonas*.

Contraindications

• Contraindications
• Severe renal impairment (CrCl < 30 mL/min) without dose adjustment.
• Known hypersensitivity to fosfomycin or its excipients.
• Warnings
• Drug interaction: co‑administration with *clindamycin* or *penicillins* may increase serum levels; avoid.
• Pregnancy & Lactation: Category B; limited data—use only if benefits outweigh risks.
• Impaired renal function: dose adjustment required; monitor CrCl daily.

Dosing

• Oral: reconstitute powder in water or favorite juice; hold 10–15 min; sip slowly.
• IV: infuse over 30–60 min; can be added to standard infusion bags.

Adverse Effects

• Common
• Gastrointestinal: nausea, vomiting, abdominal cramps, diarrhea.
• Local: perineal or genital erythema (especially with urinary preparations).
• Serious
• Hypersensitivity: urticaria, angioedema.
• Electrolyte imbalances (especially with large IV doses).
• Severe neutropenia (rare, <0.1 %).
• Nephrotoxicity: minimal IV toxicity; monitor creatinine.

Monitoring

• Renal function: CrCl/serum creatinine at baseline, then 4–7 days; adjust dose accordingly.
• Clinical response: symptom resolution (<48 h).
• Microbiology: repeat culture if no response after 48 h or if clinical deterioration.
• Serum drug levels: not routine; important only in special populations (e.g., MDR infections).

Clinical Pearls

• “One‑dose wonders”: A 3 g or 6 g oral dose cures > 80 % of uncomplicated cystitis, making it ideal for patient adherence and reducing nosocomial resistance.
• Urine “bloom”: Because fosfomycin concentrates >10× serum in urine, it’s especially potent for lower UTIs; however, its lower plasma levels limit efficacy in bloodstream infections unless combined with other agents.
• Resistance vigilance: Resistance rates are currently < 5 % among *E. coli* in most regions; however, recent outbreaks in Europe of fosfomycin‑resistant *Enterobacter cloacae* emphasize the need for susceptibility testing before empiric use in severe infections.
• Combination soundness: In CRE or MDR *Pseudomonas*, fosfomycin acts synergistically with colistin or ceftazidime‑avibactam; consider adding it to reduce mortality and preserve last‑line agents.
• Drug‑interaction caution: To avoid elevated serum levels, never give fosfomycin concurrently with clindamycin or beta‑lactam antibiotics; even though the interaction is modest, both pharmacokinetics can overlap.

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• Key Takeaway: *Fosfomycin* remains a critical, rapid‑acting, single‑dose oral option for uncomplicated cystitis, and a valuable, broad‑spectrum adjunct in complicated UTIs and MDR gram‑negative bacterial infections—especially when renal function is preserved or appropriately dose‑adjusted.