A-Clox

Approved Indications:

• Treatment of infections caused by penicillinase-producing Staphylococcus aureus and other susceptible bacteria.
• Skin and soft tissue infections: Impetigo, cellulitis, abscesses, wound infections.
• Bone and joint infections: Osteomyelitis, septic arthritis.
• Respiratory tract infections: Pneumonia, bronchitis, sinusitis caused by susceptible staphylococci.
• Septicemia: Bacteremia due to penicillin-resistant staphylococci.
• Endocarditis: Staphylococcal endocarditis (as part of combination therapy or monotherapy depending on severity).
• Surgical prophylaxis: For patients at high risk of infection with penicillinase-producing staphylococci.

Clinically Accepted Off-label Uses:

• Other serious infections caused by penicillin-resistant staphylococci when susceptibility is confirmed.

• Adults:
• Oral: 250–500 mg every 6 hours (1–4 g/day), depending on infection severity.
• Parenteral (IV/IM): 1–2 g every 4–6 hours, depending on infection severity and patient condition.
• Pediatrics:
• Oral: 12.5–25 mg/kg every 6 hours (maximum 100 mg/kg/day).
• Parenteral: 50–100 mg/kg/day divided every 6 hours.
• Elderly: Same as adults; adjust based on renal function and clinical response.
• Renal Impairment: Dosage adjustment recommended in severe renal impairment; dosing interval may be increased.
• Hepatic Impairment: No specific dose adjustment needed, but monitor closely.
• Administration Routes: Oral (capsules, suspension), intramuscular injection, intravenous injection/infusion.
• For serious infections, parenteral administration is preferred initially, with switch to oral when appropriate.

Cloxacillin is a beta-lactam antibiotic of the penicillinase-resistant penicillin class. It exerts bactericidal activity by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) inside the bacterial cell wall, blocking the cross-linking of peptidoglycan chains necessary for cell wall strength and rigidity. Its molecular structure confers resistance to beta-lactamases (penicillinases) produced by certain staphylococci, allowing it to remain active against penicillin-resistant strains. This results in bacterial cell lysis and death.

• Absorption: Oral bioavailability is approximately 37–60%; reduced by food but clinically not significant. Parenteral administration leads to complete bioavailability.
• Distribution: Widely distributed into most body tissues and fluids, including bone, sputum, bile, and pleural fluid; poor penetration into cerebrospinal fluid unless meninges inflamed.
• Metabolism: Minimal hepatic metabolism.
• Elimination: Primarily excreted unchanged in urine by glomerular filtration and tubular secretion.
• Half-life: Approximately 30 minutes in patients with normal renal function.
• Onset of action: Rapid bactericidal effect after administration.

• Pregnancy: Category B — No evidence of risk in humans; animal studies show no harm. Use only if clearly needed.
• Lactation: Excreted in low concentrations into breast milk; generally considered safe during breastfeeding. Monitor infants for diarrhea or sensitization.

• Primary Class: Beta-lactam Antibiotic
• Subclass: Penicillinase-resistant Penicillin

• Known hypersensitivity to cloxacillin, penicillins, or any beta-lactam antibiotics.
• History of severe allergic reaction (anaphylaxis) to beta-lactams.
• Previous jaundice or hepatic dysfunction associated with cloxacillin use.

• Use cautiously in patients with a history of allergy to beta-lactams; anaphylaxis can be life-threatening.
• Monitor liver function tests during prolonged therapy; rare reports of hepatotoxicity and cholestatic jaundice.
• Adjust dose in severe renal impairment to prevent accumulation.
• Risk of superinfection with prolonged use, including fungal infections.
• Monitor for signs of Clostridium difficile-associated diarrhea.
• Observe injection site for thrombophlebitis (IV) or pain/swelling (IM).

Common:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal discomfort.
• Hypersensitivity reactions: Rash, urticaria.
• Injection site reactions: Pain, inflammation, phlebitis.

Serious (Rare):

• Anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
• Hepatotoxicity: Cholestatic jaundice, elevated liver enzymes.
• Hematologic: Neutropenia, thrombocytopenia, eosinophilia.
• Clostridium difficile-associated diarrhea (potentially severe).

• Probenecid: May increase plasma levels by inhibiting renal tubular secretion.
• Methotrexate: May reduce elimination leading to increased toxicity.
• Oral contraceptives: Potential reduced efficacy due to alteration of gut flora (theoretical).
• Other nephrotoxic drugs: Caution advised due to additive renal toxicity risks.
• No significant CYP450 involvement.

• Clinical guidelines continue to recommend cloxacillin as a first-line agent for methicillin-sensitive Staphylococcus aureus (MSSA) infections.
• Updated stewardship programs emphasize avoiding cloxacillin for MRSA infections, where alternatives like vancomycin or linezolid are preferred.
• No major changes in dosing; recommendations support switching from IV to oral therapy once clinical improvement occurs.

• Store oral formulations at 20°C to 25°C (68°F to 77°F), protected from moisture and light.
• Store injectable solutions refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze injectable forms.
• Reconstituted solutions for injection should be used promptly or stored refrigerated and discarded after 24 hours.
• Keep all formulations out of reach of children.