Oxacillin

BRAND NAMES

• Bactocill (most well-known brand name for oxacillin sodium) 

• Prostaphlin (older/less commonly used historical brand in some markets)

MECHANISM OF ACTION

Oxacillin is a beta-lactam antibiotic belonging to the penicillinase-resistant penicillin class. It acts by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs) located on the inner bacterial cell membrane. This binding blocks the transpeptidation step required for cross-linking peptidoglycan chains, which is essential for maintaining cell wall strength and stability. As a result, the bacterial cell wall becomes weak and unable to withstand osmotic pressure, leading to cell lysis and bacterial death. Oxacillin is resistant to beta-lactamase enzymes, making it particularly effective against penicillinase-producing strains of Staphylococcus aureus.

PHARMACOKINETICS

Absorption

Oxacillin is poorly absorbed from the gastrointestinal tract and is therefore not suitable for oral use. It is mainly given by intravenous or intramuscular routes to ensure effective 
systematic levels.

Distribution

Oxacillin has a relatively small volume of distribution, approximately 0.2–0.3 L/kg. This indicates that the drug is largely confined to the extracellular fluid rather than extensively distributing into tissues. Its high plasma protein binding further limits free distribution into body compartments.

Metabolism

Oxacillin is partially metabolized in the liver into inactive metabolites, but most of the drug remains unchanged. Hepatic metabolism is minimal, and the parent drug accounts for most of the antibacterial activity.

Elimination

Oxacillin is primarily eliminated through the kidneys, with a large portion excreted unchanged in the urine via glomerular filtration and active tubular secretion. A smaller amount is excreted in bile. Its elimination half-life is short, requiring frequent dosing to maintain therapeutic levels.

PHARMACODYNAMICS

Oxacillin is a beta-lactam antibiotic that exhibits time-dependent bactericidal activity, meaning its effectiveness depends on the duration that drug concentrations remain above the minimum inhibitory concentration (MIC). It acts by binding to penicillin-binding proteins (PBPs) and inhibiting bacterial cell wall synthesis, leading to cell lysis and death. It is most effective against actively dividing bacteria, particularly penicillinase-producing Staphylococcus aureus.

ADMINISTRATION

Oxacillin is administered parenterally, mainly through intravenous (IV) infusion or intramuscular (IM) injection, because it is poorly absorbed from the gastrointestinal tract. IV administration is preferred in serious infections to achieve rapid and reliable therapeutic levels. It is usually given in divided doses at regular intervals to maintain effective plasma concentrations, and dosage is adjusted based on the severity of infection and patient condition.

DOSAGE AND STRENGTH

Oxacillin is commonly available as injection formulations of 250 mg, 500 mg, 1 g, and 2 g vials for intravenous (IV) or intramuscular (IM) use. The usual adult dose for moderate to severe infections is 1–2 g IV every 4–6 hours, depending on the severity and site of infection. In severe infections such as endocarditis, higher or more frequent dosing may be required under strict medical supervision. Dosage should always be adjusted based on renal and hepatic function as well as clinical response.

DRUG INTERACTIONS

Oxacillin may interact with drugs like probenecid, which increases its levels by reducing renal excretion. It can also reduce the effectiveness of oral contraceptives and may interfere with bacteriostatic antibiotics, lowering its activity.

FOOD INTERACTIONS

Oxacillin has reduced absorption when taken with food. Therefore, it is recommended to administer it on an empty stomach (if given orally), although it is mainly used parenterally where food does not affect its absorption.

CONTRAINDICATIONS

Oxacillin is contraindicated in patients with a known hypersensitivity to penicillins or other beta-lactam antibiotics, as it may cause severe allergic reactions including anaphylaxis. It should also be avoided in individuals with a history of serious hypersensitivity reactions to cephalosporins due to possible cross-reactivity.

SIDE EFFECTS

• Nausea

• Vomiting

• Diarrhea

• Stomach pain

• Rash or itching

• Injection site pain

• Fever

• Joint pain

• Yeast infections

• Increased liver enzymes

• Allergic reactions (rash, swelling, breathing difficulty)

• Severe diarrhea (possible Clostridioides difficile infection)

• Liver problems (jaundice, dark urine)

• Kidney issues (reduced urine, swelling)

• Unusual bleeding or bruising

OVER DOSE

Overdose may cause nausea, vomiting, diarrhea, stomach pain, confusion, seizures (rare), and kidney problems. Immediate medical attention is required, and treatment is supportive with stopping the drug and giving fluids.

TOXICITY

Oxacillin toxicity is rare but may cause nausea, vomiting, diarrhea, rash, kidney problems, electrolyte imbalance, and in severe cases seizures or allergic reactions. It mainly affects the kidneys and nervous system in high doses or overdose situations. Immediate medical care is required if toxicity is suspected.