Bacilex

• Approved Indications:
• Treatment of uncomplicated lower urinary tract infections (acute cystitis) caused by susceptible bacteria in adults and children.
• Treatment of acute uncomplicated pyelonephritis in some regions.
• Prophylaxis and treatment of urinary tract infections in select patient populations.
• Off-label/Clinically Accepted Uses:
• Management of urinary tract infections caused by multidrug-resistant Gram-negative bacteria when susceptibility is confirmed.
• Occasional off-label use in prostatitis under specialist supervision.

• Route: Oral administration.
• Adults:
• 400 mg twice daily (every 12 hours) for 5 to 7 days in uncomplicated urinary tract infections.
• For severe infections, dose and duration should be individualized by a healthcare professional.
• Pediatrics:
• Dose based on body weight, approximately 20 mg/kg/day divided into two doses.
• Elderly:
• No routine dose adjustment; monitor renal function and adjust if necessary.
• Renal impairment:
• Use caution and adjust dosing frequency in moderate to severe renal impairment.
• Hepatic impairment:
• No specific dose adjustments required.
• Duration:
• Typically 5 to 7 days, tailored to clinical response and infection severity.

Pivmecillinam is a prodrug rapidly converted in the gastrointestinal tract to the active compound mecillinam. Mecillinam is a beta-lactam antibiotic that selectively binds to penicillin-binding protein 2 (PBP2) in susceptible Gram-negative bacteria, inhibiting the synthesis of the bacterial cell wall by disrupting peptidoglycan cross-linking. This results in weakened cell walls, bacterial cell lysis, and death, particularly effective against Enterobacteriaceae such as Escherichia coli, the primary pathogen in urinary tract infections.

• Absorption: Well absorbed after oral administration; rapidly hydrolyzed to mecillinam. Peak plasma levels reached within 1–2 hours.
• Distribution: Distributes effectively to urinary tract tissues and urine; low plasma protein binding (~10–20%).
• Metabolism: Mecillinam undergoes minimal metabolism; pivmecillinam is hydrolyzed to mecillinam in the gut.
• Elimination: Primarily excreted unchanged by renal clearance (glomerular filtration and tubular secretion).
• Half-life: Approximately 1 hour for mecillinam.
• Onset: Rapid bactericidal activity after absorption.

• Pregnancy: FDA Pregnancy Category B — animal studies have not demonstrated risk; human data are limited. Use only if clearly needed.
• Lactation: Mecillinam is excreted in breast milk in small amounts; generally considered compatible with breastfeeding, but infant monitoring is advised.

• Beta-lactam antibiotic
• Penicillin subclass
• Amidopenicillin derivative

• Known hypersensitivity to pivmecillinam, mecillinam, other penicillins, or beta-lactam antibiotics.
• History of severe allergic reactions (anaphylaxis) to beta-lactams.
• Severe renal impairment without appropriate dose adjustment and monitoring.

• Risk of hypersensitivity reactions including anaphylaxis; discontinue immediately if such reactions occur.
• Monitor for signs of superinfection or Clostridium difficile-associated diarrhea.
• Use cautiously in patients with renal impairment; adjust dose accordingly.
• Avoid use in infections caused by mecillinam-resistant organisms.
• Caution in patients with a history of gastrointestinal diseases, especially colitis.

• Common:
• Gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal discomfort.
• Skin reactions including rash and pruritus.
• Serious (rare):
• Hypersensitivity reactions (e.g., angioedema, anaphylaxis).
• Clostridium difficile-associated diarrhea and pseudomembranous colitis.
• Hematologic abnormalities such as neutropenia or thrombocytopenia.
• Side effects are generally mild and reversible.

• May have decreased efficacy when coadministered with bacteriostatic antibiotics (e.g., tetracyclines).
• Probenecid may reduce renal elimination of mecillinam, increasing plasma concentrations.
• Minimal CYP450 involvement; low risk of metabolic drug interactions.
• Alcohol use should be cautious due to potential gastrointestinal side effects.

• Recommended as a first-line oral agent for uncomplicated urinary tract infections in many regions with low resistance rates.
• Increasing attention as a treatment option for infections with multidrug-resistant Gram-negative bacteria.
• No recent significant changes in dosing or approved indications.
• Ongoing surveillance for emerging resistance patterns is advised.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in tightly closed containers.
• Do not freeze.
• Keep out of reach of children.