Cloxacillin

Usage

• Cloxacillin is prescribed for bacterial infections caused by susceptible, penicillinase-producing staphylococci. These infections can include skin and soft tissue infections (SSTIs), respiratory tract infections (e.g., pneumonia), bone and joint infections (e.g., osteomyelitis), urinary tract infections, bacteremia, endocarditis, and meningitis. It is effective against methicillin-susceptible Staphylococcus aureus (MSSA) but not methicillin-resistant S. aureus (MRSA).
• Pharmacological classification: Antibiotic, specifically a penicillinase-resistant penicillin.
• Mechanism of action: Cloxacillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This binding interferes with the cross-linking of peptidoglycans, essential components of the bacterial cell wall, leading to cell wall instability and bacterial lysis. Its resistance to penicillinase allows it to remain effective against bacteria that produce this enzyme, which would otherwise inactivate many penicillins.

Alternate Names

• No widely recognized alternate names exist for cloxacillin itself. However, it belongs to the group of isoxazolyl penicillins.
• Brand names: Cloxapen, Dry Clox, Tegopen, Orbenin, Prostaphlin-A, M-CLOX, Clodax. (Note: Brand names can vary regionally.)

How It Works

• Pharmacodynamics: Cloxacillin exerts its bactericidal effect by disrupting bacterial cell wall synthesis, as described in the mechanism of action. This leads to cell death and controls the infection.

• Pharmacokinetics:

  • Absorption: Absorption is incomplete and variable following oral administration, improved when taken on an empty stomach (1-2 hours before meals).
  • Distribution: Distributes widely throughout the body, achieving therapeutic concentrations in various tissues and fluids. Penetration into the cerebrospinal fluid (CSF) is limited unless the meninges are inflamed. Crosses the placental barrier. Approximately 94% protein-bound.
  • Metabolism: Minimally metabolized.
  • Elimination: Primarily excreted unchanged in the urine via glomerular filtration and tubular secretion. Some biliary excretion occurs.

• Mode of action: Cloxacillin’s mode of action involves irreversible binding to and inhibition of PBPs, specifically those involved in the transpeptidation reaction of bacterial cell wall synthesis. This inhibition disrupts the final cross-linking step of peptidoglycan synthesis, leading to cell wall weakness and eventual lysis of the bacterial cell.

• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Cloxacillin primarily acts through enzyme inhibition (PBPs).

Dosage

Standard Dosage

Adults:

• Oral: 250-500 mg every 6 hours. For severe infections, doses up to 1 g every 6 hours may be used. Maximum daily dose: 6 g. Administer 1-2 hours before meals.
• IV: 500 mg - 2 g every 6 hours. For severe infections: 2 g every 4 hours. Maximum daily dose: 12 g.
• IM: 500 mg - 1g every 4-6 hours.

Children:

• Oral:
  • <1 year: Safety and efficacy not established.

  • = 1 year: 50-100 mg/kg/day divided every 6 hours. Maximum daily dose: 4 g.

• IV/IM:
  • Neonates (<=7 days):
    • <2 kg: 25 mg/kg every 12 hours.

    • =2 kg: 25 mg/kg every 8 hours.

  • Infants (7-28 days):
    • <2 kg: 25 mg/kg every 8 hours.

    • =2 kg: 25 mg/kg every 6 hours.

  • Children >1 month : 25 to 50 mg/kg every 6 hours. Maximum single dose: 2g
• Administer 1-2 hours before meals.

Special Cases:

• Elderly Patients: Closely monitor renal function. No specific dose adjustments are typically needed unless renal impairment is present.
• Patients with Renal Impairment: Dose adjustment may be required in cases of severe renal impairment (consult specific product or local treatment guidelines).
• Patients with Hepatic Dysfunction: No specific dose adjustments are typically recommended.
• Patients with Comorbid Conditions: Closely monitor for drug interactions and adjust treatment accordingly.

Clinical Use Cases

• Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Dosing should be guided by the severity of the infection and adjusted based on patient response and clinical context. High doses (e.g., 2 g every 4 hours IV) are often used in severe infections.

Dosage Adjustments

• Dose modifications are necessary for patients with renal impairment, especially those with severely reduced creatinine clearance. Consult specific guidelines for recommendations.

Side Effects

Common Side Effects

• Nausea, vomiting, diarrhea, abdominal discomfort, flatulence, mouth sores.

Rare but Serious Side Effects

• Allergic reactions (ranging from rash to anaphylaxis), interstitial nephritis, hepatitis, cholestatic jaundice, neutropenia, agranulocytosis, thrombocytopenia, Clostridioides difficile-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment).

Long-Term Effects

• With prolonged high doses, potential for hematological disorders, renal dysfunction, and hepatic dysfunction.

Adverse Drug Reactions (ADR)

• Anaphylaxis, severe skin reactions (e.g., Stevens-Johnson syndrome), drug-induced liver injury.

Contraindications

• Known hypersensitivity to cloxacillin, penicillin, or cephalosporins.

Drug Interactions

• Bacteriostatic antibiotics: Tetracyclines, macrolides (e.g., erythromycin), and sulfonamides can antagonize the bactericidal action of cloxacillin.
• Oral contraceptives: Cloxacillin can reduce the effectiveness of oral contraceptives.
• Methotrexate: Cloxacillin can decrease methotrexate clearance, leading to increased toxicity.
• Probenecid: Probenecid reduces renal excretion of cloxacillin, increasing serum levels.
• Warfarin: Cloxacillin can potentiate the anticoagulant effects of warfarin.
• Live vaccines (e.g., typhoid): Cloxacillin can reduce the efficacy of these vaccines.
• Other: Aminoglycosides (incompatible in solution). Fusidic acid, khat, guar gum.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (Animal studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. Use only if clearly needed).
• Fetal risks: No documented teratogenic effects, but use with caution.
• Breastfeeding: Cloxacillin is excreted in breast milk in small amounts. Monitor the nursing infant for gastrointestinal side effects. Generally considered safe, but use with caution.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to PBPs.
• Side Effects: Common: nausea, vomiting, diarrhea. Serious: allergic reactions, interstitial nephritis, hepatitis.
• Contraindications: Hypersensitivity to penicillins or cephalosporins.
• Drug Interactions: Tetracyclines, macrolides, sulfonamides, oral contraceptives, methotrexate, probenecid, warfarin.
• Pregnancy & Breastfeeding: Category B; generally considered safe but use with caution.
• Dosage: Adults: 250-500 mg PO q6h or 500mg -2g IV q6h; Children: 50-100 mg/kg/day divided q6h (oral); Neonates: dose adjusted by weight.
• Monitoring Parameters: Renal function, liver function tests (LFTs), complete blood count (CBC) during prolonged therapy. Monitor for signs of hypersensitivity.

Popular Combinations

• No commonly recommended or established combination therapies exist with cloxacillin. Combination therapy is usually not necessary as cloxacillin has a fairly broad spectrum of activity against susceptible organisms.

Precautions

• General Precautions: Assess for allergies to penicillins and cephalosporins. Monitor renal and hepatic function, especially with prolonged high-dose therapy. Assess for signs and symptoms of superinfection (e.g., CDAD).
• Specific Populations: As noted above in the special cases section.
• Lifestyle Considerations: Alcohol may exacerbate gastrointestinal side effects. No specific dietary restrictions are usually necessary.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Cloxacillin?

A: The dosage varies depending on the patient’s age, the severity of the infection, and the route of administration. See the detailed dosage section above for specific recommendations.

Q2: What infections is Cloxacillin used to treat?

A: Cloxacillin is primarily used to treat infections caused by susceptible, penicillinase-producing staphylococci, such as skin and soft tissue infections, pneumonia, osteomyelitis, and endocarditis.

Q3: Is Cloxacillin effective against MRSA?

A: No, cloxacillin is not effective against MRSA. It is only effective against methicillin-susceptible Staphylococcus aureus (MSSA).

Q4: What are the most common side effects of Cloxacillin?

A: The most common side effects are gastrointestinal, including nausea, vomiting, diarrhea, and abdominal discomfort.

Q5: Are there any serious side effects to be aware of?

A: Yes. Serious side effects, though rare, can include allergic reactions (including anaphylaxis), interstitial nephritis, and hepatitis.

Q6: Can Cloxacillin be used during pregnancy and breastfeeding?

A: Cloxacillin is generally considered safe to use during pregnancy and breastfeeding, but it should be used with caution and only if clearly needed. It is classified as Pregnancy Category B.

Q7: What are the important drug interactions with Cloxacillin?

A: Significant drug interactions can occur with bacteriostatic antibiotics (tetracyclines, macrolides, sulfonamides), oral contraceptives, methotrexate, probenecid, and warfarin.

Q8: How should Cloxacillin be administered?

A: Cloxacillin can be administered orally, intravenously (IV), or intramuscularly (IM). Oral administration should be on an empty stomach (1-2 hours before meals) for optimal absorption. IV administration is preferred for severe infections. IM is less common than IV.

Q9: Should the dose of Cloxacillin be adjusted for patients with renal impairment?

A: Dose adjustment may be necessary for patients with severe renal impairment. Consult specific guidelines for recommendations.

Q10: What should be monitored in patients receiving Cloxacillin?

A: Monitor renal function, liver function tests (LFTs), and complete blood counts (CBC), especially during prolonged, high-dose therapy. Also, closely monitor for any signs of hypersensitivity reactions.