Usage
- Clavulanic acid + ticarcillin is prescribed for a variety of bacterial infections, including lower respiratory tract infections, urinary tract infections, bone and joint infections, skin and soft tissue infections, gynecological infections, and infections caused by Pseudomonas aeruginosa and Stenotrophomonas maltophilia.
- Pharmacological classification: Beta-lactam antibiotic combined with a beta-lactamase inhibitor.
- Mechanism of action: Ticarcillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to bacterial cell death. Clavulanic acid, a beta-lactamase inhibitor, protects ticarcillin from degradation by beta-lactamase enzymes produced by some bacteria, thus extending ticarcillin’s antibacterial spectrum.
Alternate Names
- Co-ticarclav
- Brand Names: Timentin
How It Works
- Pharmacodynamics: Ticarcillin exerts bactericidal activity by disrupting bacterial cell wall synthesis. Clavulanic acid itself has little antibacterial activity but enhances the effect of ticarcillin by inhibiting beta-lactamases.
- Pharmacokinetics: Administered intravenously or intramuscularly. Ticarcillin is well distributed in body tissues and fluids. It crosses the placenta and enters breast milk in small amounts. Primarily eliminated unchanged by the kidneys. Clavulanic acid is also well distributed and undergoes significant hepatic metabolism. Both components achieve peak plasma concentrations immediately after a 30-minute infusion.
- Mode of action: Ticarcillin binds to PBPs, specifically inhibiting transpeptidases and carboxypeptidases involved in peptidoglycan synthesis, a crucial component of the bacterial cell wall.
- Receptor binding/enzyme inhibition: Ticarcillin inhibits PBPs. Clavulanic acid inhibits beta-lactamase enzymes.
- Elimination pathways: Ticarcillin is primarily excreted renally. Clavulanic acid is significantly metabolized by the liver, with some renal excretion.
Dosage
Standard Dosage
Adults:
- 3.1 grams (containing 3 grams ticarcillin and 100 mg clavulanic acid) every 4 to 6 hours intravenously. Maximum dose: 18 g/day.
Children (≥ 3 months):
- 200-300 mg ticarcillin/kg/day IV divided every 4-6 hours.
- Neonates (0-28 days): refer to specialized neonatal dosing guidelines.
Special Cases:
- Elderly Patients: Dosage adjustment generally not required unless renal function is impaired.
- Patients with Renal Impairment: Dose adjustments are necessary based on creatinine clearance. A loading dose of 3.1 grams is typically followed by adjusted maintenance doses.
- Patients with Hepatic Dysfunction: Dosage adjustment may be necessary with concomitant renal impairment.
- Patients with Comorbid Conditions: Individualized dosing may be required based on specific comorbidity.
Clinical Use Cases
Dosing recommendations for specific clinical situations often follow the standard adult or pediatric dosages, adjusted as needed based on severity of infection and renal function. Consultation with an infectious disease specialist is recommended in complex cases.
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Standard or adjusted dosages are typically used based on the infection’s severity and the patient’s condition.
Dosage Adjustments
Dose modifications are crucial for patients with renal impairment and should be based on creatinine clearance. Consult specific guidelines for detailed recommendations and adjustments based on dialysis modality.
Side Effects
Common Side Effects
- Diarrhea, nausea, vomiting, abdominal discomfort
- Rash, pruritus, urticaria
- Pain, swelling, phlebitis at injection site
- Headache
Rare but Serious Side Effects
- Anaphylaxis
- Clostridium difficile-associated diarrhea (CDAD)
- Seizures (particularly in patients with renal impairment or high doses)
- Hepatitis, cholestatic jaundice
- Bleeding disorders (particularly in renally impaired patients)
Long-Term Effects
- Superinfection (fungal or bacterial) with prolonged use.
Adverse Drug Reactions (ADR)
- Anaphylaxis (requires immediate intervention)
Contraindications
- Hypersensitivity to penicillins, cephalosporins, or clavams.
Drug Interactions
- Probenecid decreases renal excretion of ticarcillin.
- May reduce efficacy of oral contraceptives.
- Aminoglycosides (synergistic effect).
- Anticoagulants (increased bleeding risk).
- Methotrexate (decreased excretion, increased toxicity risk).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B
- Ticarcillin and clavulanate cross the placenta. Use only if clearly needed and benefits outweigh risks.
- Excreted in breast milk (ticarcillin in small amounts). Use with caution during breastfeeding; monitor infant for signs of diarrhea or thrush.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis, extended spectrum by beta-lactamase inhibition.
- Side Effects: Diarrhea, nausea, rash, injection site reactions; rarely anaphylaxis, seizures, hepatitis.
- Contraindications: Hypersensitivity to penicillins or beta-lactam antibiotics.
- Drug Interactions: Probenecid, oral contraceptives, aminoglycosides, anticoagulants.
- Pregnancy & Breastfeeding: Category B; use with caution.
- Dosage: Adults: 3.1 g IV q4-6h; Children: 200-300 mg/kg/day IV divided q4-6h; adjust for renal impairment.
- Monitoring Parameters: Renal function, liver function, electrolytes, bleeding time.
Popular Combinations
- Aminoglycosides (gentamicin, tobramycin) for synergistic effect against certain bacteria, especially Pseudomonas aeruginosa.
Precautions
- Hypersensitivity reactions.
- CDAD.
- Seizures (especially with renal impairment).
- Bleeding complications.
- Superinfections.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Clavulanic Acid + Ticarcillin?
A: Adults: 3.1 g IV every 4-6 hours. Children: 200-300 mg ticarcillin/kg/day IV divided every 4-6 hours. Dosages should be adjusted for patients with renal impairment.
Q2: What are the common side effects?
A: Common side effects include diarrhea, nausea, rash, and injection site reactions.
Q3: What are the serious side effects?
A: Rare but serious side effects include allergic reactions (including anaphylaxis), Clostridium difficile-associated diarrhea, and seizures.
Q4: Can it be used during pregnancy or breastfeeding?
A: It is a Pregnancy Category B drug. Use during pregnancy and breastfeeding only if the potential benefit justifies the potential risk to the fetus or infant.
Q5: What are the major drug interactions?
A: Significant drug interactions include probenecid, oral contraceptives, aminoglycosides, and anticoagulants.
Q6: How is it administered?
A: Clavulanic acid + ticarcillin is administered via intravenous infusion over 30-60 minutes.
Q7: What infections does it treat?
A: It’s used to treat a broad range of bacterial infections, including respiratory, urinary tract, bone and joint, skin, gynecological, and infections caused by Pseudomonas aeruginosa.
Q8: What should be monitored during treatment?
A: Renal function, liver function tests, electrolytes (especially potassium), and signs of bleeding should be monitored.
Q9: Is dose adjustment needed for renal impairment?
A: Yes, dosage adjustment is crucial for patients with renal impairment, and specific guidelines should be consulted.
Q10: Is it effective against beta-lactamase producing bacteria?
A: Yes, the clavulanic acid component inhibits beta-lactamases, thus extending the effectiveness of ticarcillin against these resistant bacteria.
