Oxacillin
Oxacillin
Generic Name
Oxacillin
Mechanism
- β‑lactam ring binds penicillin-binding proteins (PBPs), particularly PBP2a, inhibiting transpeptidase activity.
- Blocks cross‑linking of peptidoglycan chains, weakening the bacterial cell wall → lysis.
- Bulky side chain (methyl‑piperazyl group) protects the β‑lactam ring from penicillinase (β‑lactamases) produced by resistant staphylococci.
- Activity is time‑dependent; effective when drug concentrations remain above the MIC for a significant portion of the dosing interval.
Pharmacokinetics
- Route: Only intravenous (IV) administration; oral absorption is negligible (<5 % bioavailability).
- Distribution: Widely distributed in plasma, interstitial fluid, and infected tissues (e.g., skin, bones, joints). Penetrates urine and synovial fluid at therapeutic levels.
- Protein binding: ~15 %.
- Metabolism: Minimal hepatic metabolism; primarily renal excretion unchanged.
- Half‑life: ~1 h (IV); prolonged in renal impairment (up to 2–3 h).
- Clearance: 30–35 mL/min in adults; reduced by renal dysfunction.
Indications
| Infection | Typical site | Susceptibility |
| Staphylococcus aureus (penicillinase‑resistant) | Skin & soft tissue, suppurative osteomyelitis, septic arthritis, pyogenic bone infections | Susceptibility testing required |
| Endocarditis | Infective | For susceptible isolates |
| Bacterial pneumonia | Lower respiratory tract | For susceptible *S. aureus* |
| Other invasive Staphylococcal infections | Any | Susceptibility confirmed |
> *Note:* Not effective against MRSA, *Streptococcus pyogenes*, or many gram‑negative organisms.
Contraindications
- Hypersensitivity to penicillins or anaphylaxis.
- Severe renal impairment (eGFR <30 mL/min): dose adjustment required.
- Pregnancy & lactation: Category B; caution advised; no compelling evidence of harm, but use only if benefits outweigh risks.
- Known glucose‑6‑phosphate dehydrogenase (G6PD) deficiency: risk of hemolysis.
- History of drug‑induced liver injury.
- Concurrent use with other β‑lactams: additive risk of hypersensitivity reactions.
Dosing
| Population | Dose | Frequency | Duration |
| Adults (≥ 50 kg) | 1 g IV | every 6 h (q6h) | 7–14 days (varies) |
| Children (1–12 yrs) | 25–50 mg/kg IV | every 6 h | 7–14 days |
| Renal impairment (CrCl 30–49 mL/min) | 0.5–1 g IV | every 6–8 h | Adjust per drug levels |
| Severe renal impairment (CrCl 15–29 mL/min) | 0.5 g IV | every 8 h | Adjust per drug levels |
| Note: Set the dose to the nearest 0.5 g (0.5, 1, 1.5 g). Do not** administer orally.
Adverse Effects
| Adverse Effect | Frequency | Management |
| Gastrointestinal: nausea, vomiting, diarrhea, abdominal cramps | Common | Prophylactic antiemetics; dose adjustment |
| Skin reactions: rash, urticaria, erythema multiforme | Common | Stop drug if rash develops; steroids for severe reaction |
| Allergic reactions: anaphylaxis | Rare | Immediate cessation; epinephrine, antihistamines, steroids |
| Hepatotoxicity: elevated LFTs, cholestasis | Rare | Monitor LFTs; discontinue if ALT/AST >5× ULN |
| Hematologic: leukopenia, neutropenia, thrombocytopenia, hemolytic anemia | Rare | CBC monitoring; consider G6PD screening |
| Drug‑induced immune hemolysis | Rare | Fasting glucose‑6‑phosphate dehydrogenase check |
| Renal: microscopic hematuria (rare) | Rare | Monitor urinalysis; adjust dose if CrCl↓ |
Monitoring
- Renal function: Serum creatinine, eGFR on days 1, 7, 14.
- Liver enzymes: ALT, AST baseline, days 7 and 14 (or sooner if symptoms).
- Complete blood count (CBC): baseline, every 3 days for first 2 weeks, then weekly.
- Signs of hypersensitivity: monitor for anaphylaxis symptoms during infusion; pre‑medicate high‑risk patients if appropriate.
- Therapeutic drug monitoring (TDM): rarely required; consider if severe infection or impaired clearance.
Clinical Pearls
- Oxacillin ≠ β‑lactam generalist: Only treat *penicillinase‑resistant* *S. aureus*; confirm susceptibility before therapy.
- Intravenous route is mandatory – oral forms are ineffective.
- Take advantage of the 6‑hour dosing interval for outpatient parenteral antimicrobial therapy (OPAT) programs—use extended‑interval dosing if renal function permits.
- Avoid concomitant high‑dose ampicillin or amoxicillin/sulbactam when possible; overlapping β‑lactam therapy may increase hypersensitivity risks without added benefit.
- G6PD deficiency alert: Patients with hemolytic disorders may develop hemolysis; pre‑screening helps prevent catastrophic anemia.
- Severe infections (e.g., endocarditis, osteomyelitis): Extend duration to 14 days or more; ensure source control and culture data guide therapy.
- Renal impairment: Adjust the interval (q8h) rather than the dose; this helps maintain adequate trough levels without excessive accumulation.
> Quick reference: 1 g IV q6h in adults for penicillinase‑resistant *S. aureus* – adjust for renal function; no oral alternative.
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• References for Study:
1. Antimicrobial guidelines (IDSA) – *Staphylococcal infections* 2024.
2. Pharmacology Textbook, 12th ed. – Penicillins and β‑lactamases.
3. Clinical Microbiology Reviews – Penicillinase‑resistant *S. aureus* characteristics.
*(Ensure to keep up‑to‑date with local antibiogram patterns before prescribing.)*