EpistemisFosfomycin and Nitrofurans
Fosfomycin and nitrofurantoin are urinary antiseptics with an excellent safety profile, ideal for the outpatient management of acute uncomplicated cystitis caused by multidrug-resistant enterobacteria.
Mechanism
💊 Generic and Commercial NamesFosfomicina Trometamol (Monurol), Fosfomicina Sódica (Fosfocina), Nitrofurantoína (Furantoína).
🔬 Pharmacological GroupAntisépticos urinarios de curso estrecho. Inhibidores de la síntesis de pared en fase temprana (Fosfomicina) y destructores multiorgánicos (Nitrofurantoína).
Mechanism of Action
Su selectividad se basa en su rápida eliminación activa por la vía urinaria:
- Inhibición de la enzima MurA de Fosfomicina: Es un análogo estructural de la fosfoenolpiruvato (PEP). Se une de forma covalente e irreversible al residuo de cisteína (Cys-115) del sitio activo de la enzima citoplasmática UDP-N-acetilglucosamina enolpiruvil transferasa (MurA). Al bloquear esta enzima, impide la síntesis de ácido UDP-N-acetilmurámico (precursor metabólico básico del peptidoglicano bacteriano de curso temprano), inhibiendo la síntesis de la pared en su fase inicial.
- Disrupción Genómica Multiorgánica de Nitrofurantoína: Es reducida intracelularmente por enzimas flavoproteínas bacterianas (nitrofurano reductasas) a intermediarios químicos altamente reactivos y radicales libres que dañan de forma no específica proteínas ribosomales, bloquean la traducción proteica bacteriana, e inducen roturas masivas en las dobles hebras de ADN celular cromosómico. Al poseer múltiples mecanismos de acción dirigidos de forma simultánea, el desarrollo de resistencia por bacterias comunes es sumamente infrecuente.
Pharmacokinetics
Key Pharmacokinetics
| Parameter | Fosfomycin Trometamol (Oral) | Nitrofurantoin (Microcrystalline) |
|---|---|---|
| Routes of Administration | Oral (trometamol) or IV (sodium - hospital doses). | Exclusively Oral. Its gastric absorption improves significantly in the presence of food. |
| Dural absorption | Moderate oral bioavailability (~34-40%), trometamol increases gastric absorption. Tmax of 2 hours. | Moderate oral bioavailability (~50-60%), undergoes rapid systemic clearance. |
| Distribution and Tissues | Very hydrophilic. Confined to the extracellular space. Excellent in kidney, prostate and dural urinary parenchyma. | Low systemic distribution. Rapid plasma clearance; does not reach effective levels in lung or systemic tissue (high UTI). |
| Urinary Excretion and Concentration | Massive unaltered renal excretion (40% of the oral dose) through pure glomerular filtration. Reaches extraordinary urinary concentrations (>100 mcg/mL) that persist bactericidal for 36-48 hours. | 40% unaltered renal excretion through glomerular filtration and active secretion. Urine concentration higher than the bacterial MIC. |
| Half-life (t1/2) | 4.0 to 6.0 hours in plasma. | Very short, 30 to 60 minutes. |
Antimicrobial Spectrum
- Fosfomycin: Excellent bactericidal activity against Gram-positive (MRSA, VRE) and Gram-negative multidrug-resistant ESBL and AmpC producers (such as ESBL-producing E. coli from the community).
- Nitrofurantoin: Excellent spectrum of low urinary course against E. coli(including most ESBL producers), enteric Gram-positive cocci (susceptible streptococci and enterococci). It is not active against Pseudomonas aeruginosa or Proteus mirabilis.
Indicators and dose
Dosage and Adjustment
- Fosfomycin Trometamol (uncomplicated low UTI): 3 g orally in a single dose for healthy adults (a second sachet of 3 g can be repeated after 48 hours in complex cases).
- Nitrofurantoin (uncomplicated low UTI): 100 mg every 12 hours orally for 5 to 7 consecutive days.
- Adjustment in Kidney Failure:
- Clcr < 30 mL/min: Nitrofurantoin is absolutely contraindicated. Oral Fosfomycin Trometamol loses efficacy due to reduced dural clearance, preferring management with systemic course alternatives.
Security
Contraindications and ADRs
- Contraindications: Moderate to severe kidney failure; glucose-6-phosphate dehydrogenase deficiency; end of pregnancy (weeks 38-42 due to risk of neonatal hemolytic anemia).
- Adverse Effects (ADR):
- Uselessness of Nitrofurantoin in Renal Failure: If the glomerular filtration rate falls below 30 mL/min, nitrofurantoin is not adequately filtered into the urine, which causes two direct clinical problems:
- Analgesic ineffectiveness due to urinary concentrations lower than the MIC of the pathogen.
- Systemic plasma accumulation that drastically increases the risk of toxicity.
- Acute and Chronic Pulmonary Fibrosis: Acute transient immune-mediated pulmonary toxicity (fever, progressive dyspnea, eosinophilia in sputum), or irreversible cumulative chronic fibrosing course in prolonged treatments greater than 6 months.
- Hepatotoxicity: Chronic autoimmune hepatitis or transaminasitis.
- Uselessness of Nitrofurantoin in Renal Failure: If the glomerular filtration rate falls below 30 mL/min, nitrofurantoin is not adequately filtered into the urine, which causes two direct clinical problems:
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Antimicrobial and Infectious
- Cluster
- Urinary Antiseptics and Early Wall Inhibitors