Antimicrobials · Urinary Tract Antiseptics
The facts most likely to be tested
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Fosfomycin is a first-line treatment for uncomplicated acute cystitis in non-pregnant women.
The mechanism of action involves the irreversible inhibition of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), blocking the first step of peptidoglycan synthesis.
Fosfomycin is administered as a single-dose oral powder packet, which enhances patient compliance.
The drug achieves high concentrations in the urine while maintaining low systemic absorption, making it ideal for lower urinary tract infections.
Fosfomycin maintains efficacy against many multidrug-resistant organisms, including extended-spectrum beta-lactamase (ESBL) producing *E. coli*.
Resistance to fosfomycin typically occurs via mutations in the GlpT or UhpT transport proteins, which prevent the drug from entering the bacterial cytoplasm.
Fosfomycin is not indicated for the treatment of pyelonephritis or systemic infections due to insufficient tissue penetration in the kidneys.
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A 24-year-old female presents to the urgent care clinic with a 2-day history of dysuria, urinary frequency, and suprapubic tenderness. She has no fever, flank pain, or costovertebral angle tenderness. Urinalysis reveals positive nitrites and leukocyte esterase. Her medical history is significant for a mild allergy to sulfonamides. She is otherwise healthy and not pregnant.
Which of the following is the most appropriate single-dose antibiotic therapy for this patient?
Fosfomycin
The patient has uncomplicated cystitis, and fosfomycin is a preferred first-line, single-dose agent that avoids the use of sulfonamides or fluoroquinolones.
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High yield triage
Classification
Phosphonic acid derivative. Cell wall synthesis inhibitor.
Indications
Uncomplicated cystitis.
Mechanism of Action
Inhibits MurA enzyme, blocking peptidoglycan synthesis.
Side Effects
Diarrhea, headache, vaginitis.
Contraindications / Monitoring
Hypersensitivity. No routine monitoring required.
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Mechanism of Action
Fosfomycin irreversibly inhibits the MurA enzyme (UDP-N-acetylglucosamine enolpyruvyl transferase). This prevents the formation of N-acetylmuramic acid, the essential precursor for peptidoglycan cell wall synthesis. By blocking this early step, it exerts a bactericidal effect against both Gram-positive and Gram-negative pathogens.
Unique Properties
It is a small molecule with high tissue penetration in the bladder. It maintains activity against many multidrug-resistant organisms, including ESBL-producing *E. coli*.
Indications
Indicated as a single-dose therapy for uncomplicated cystitis in women. It is not effective for pyelonephritis or systemic infections due to poor tissue distribution outside the urinary tract.
Pharmacokinetics
Excreted unchanged in the urine, achieving high concentrations that persist for up to 48 hours. It does not require dose adjustment for renal impairment or hepatic dysfunction.
Side Effects & Adverse Events
Common adverse effects include diarrhea, nausea, and headache. Patients may also report vaginitis due to alteration of local flora. Anaphylaxis and angioedema are rare but serious hypersensitivity reactions.
Contraindications
Known hypersensitivity to fosfomycin or any component of the formulation. It is not indicated for the treatment of pyelonephritis or perinephric abscess due to insufficient systemic drug levels.
Monitoring
No routine laboratory monitoring is required for a single-dose regimen. Assess for resolution of dysuria, frequency, and urgency symptoms post-treatment.
Clinical Pearls
Consider as a first-line alternative for uncomplicated cystitis when patients have allergies to nitrofurantoin or TMP-SMX. Remember the one-and-done dosing strategy for board questions.