Fosfomycin

# Fosfomycin ## Overview Fosfomycin is a phosphonic acid derivative antibiotic with broad-spectrum bactericidal activity, including activity against ESBL-producing and MDR organisms. Available as fosfomycin trometamol (oral) and fosfomycin disodium (IV). ## Primary Indications - **Oral (trometamol)**: Uncomplicated lower urinary tract infection (UTI); acute cystitis in women; prophylaxis before transrectal prostate biopsy. - **IV**: Complicated UTIs, pyelonephritis, septicemia; often used in combination for MDR gram-negative infections (e.g., *Pseudomonas*, *Klebsiella*, *Acinetobacter*). ## Adult Dosing - **Oral (UTI)** : 3 g single dose (one sachet) on an empty stomach. - **IV (complicated infections)** : 4–8 g IV divided every 8 hours (typically 4 g q8h). For serious MDR infections, up to 8 g every 8 hours may be used (check local guidelines). Administer IV over 30–60 minutes or as a 4-hour extended infusion. ## Pediatric Dosing - **Oral (UTI; ≥6 years)** : 2 g single dose (body weight not routinely adjusted per initial data; some protocols adjust by weight as 75–100 mg/kg, max 3 g). Use only if benefit clearly outweighs risk in children <6 years. - **IV (off-label, limited data)** : Usually 100–200 mg/kg/day divided every 8 hours (max 8 g/day). Exact dosing is not universally established; consult pediatric infectious diseases. ## Dose Adjustments - **Renal impairment (oral)** : CrCl ≥10 mL/min: 3 g single dose. CrCl <10 mL/min: not recommended for single-dose oral (insufficient data for oral accumulation). - **Renal impairment (IV)** : eGFR 30–59: 4–6 g q12h. eGFR <30 or dialysis: 4 g q24–48h (monitor levels). Exact protocols vary; adjust per local guidance. - **Hepatic impairment**: No adjustment required. ## Contraindications - Hypersensitivity to fosfomycin. - Severe renal impairment (CrCl <10 mL/min) for the oral formulation (single dose not substantiated; avoid). - IV formulation: caution in severe renal impairment; adjust dose. ## Adverse Effects - **Common**: Diarrhea (oral), nausea, dysgeusia, headache; injection site pain (IV). - **Serious**: Hypersensitivity (rare), *Clostridioides difficile* diarrhea; IV: hypernatremia (high sodium content – see Pearls), hypokalemia; dose-related renal toxicity (rare). - **Other**: Vaginitis, abdominal distension. ## Key Drug Interactions - **Metoclopramide**: Decreases fosfomycin absorption – avoid co-administration; separate by 2–3 hours if necessary. - **Antacids/calcium salts**: May bind and reduce oral absorption – avoid taking together. - **Aminoglycosides/loop diuretics**: Potential additive nephrotoxicity (IV use). - **Anticoagulants**: Limited data; IV high sodium may affect fluid balance – monitor in decompensated patients. ## Monitoring - Baseline renal function (serum Cr, eGFR) – especially for IV therapy and repeated doses. - Serum sodium, potassium, chloride (IV: due to sodium load – see Pearls). - Clinical response: 48–72h (oral UTI); culture and sensitivities for complicated infections. ## Clinical Pearls - **IV fosfomycin contains 14.4 mmol (330 mg) sodium per gram** – a 4 g dose = 57.6 mmol Na (~1,320 mg). Caution in heart failure, hypertension, or fluid overload. - **Oral bioavailability** ~35%; must be taken on an empty stomach (2h before or after food). - Single oral dose UTI is generally well tolerated; do not repeat without re-culture. - Always combine IV fosfomycin with another active agent for serious infections to prevent resistance. - Fosfomycin is not reliably active against *Acinetobacter baumannii*; check local susceptibility patterns. --- *This information is a clinical summary and is not a substitute for professional judgment. Always verify current prescribing information (e.g., manufacturer’s label, local guidelines) before use.*