Usage
Ticarcillin is a semi-synthetic carboxypenicillin antibiotic primarily used to treat bacterial infections caused by gram-negative bacteria, including Pseudomonas aeruginosa. It is often used in combination with clavulanate potassium (as in Timentin) to broaden its spectrum of activity against bacteria that produce beta-lactamase enzymes, which would otherwise inactivate ticarcillin.
Its pharmacological classification is antibiotic, specifically a beta-lactam antibiotic within the penicillin subgroup.
Ticarcillin’s mechanism of action involves inhibiting bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This binding disrupts the cross-linking of peptidoglycans, essential components of the bacterial cell wall, leading to cell lysis and bacterial death.
Alternate Names
Ticarcillin is available under various brand names, most notably Ticar. When combined with clavulanate potassium, it is marketed under the brand name Timentin.
How It Works
Pharmacodynamics: Ticarcillin exerts its bactericidal effect by interfering with the final stage of bacterial cell wall synthesis. By binding to PBPs, which are enzymes involved in peptidoglycan cross-linking, ticarcillin prevents the formation of a stable cell wall, leading to bacterial cell death.
Pharmacokinetics: Administered intravenously or intramuscularly, Ticarcillin demonstrates time-dependent killing. Peak serum concentrations are achieved rapidly after intravenous administration. It is primarily excreted unchanged by the kidneys.
Mode of Action: Ticarcillin’s mode of action is through the inhibition of PBPs. These enzymes are responsible for the transpeptidation reaction that cross-links peptidoglycan strands, essential for cell wall integrity. Ticarcillin’s binding to PBPs disrupts this process, compromising cell wall stability and causing bacterial death.
Elimination: Ticarcillin is mainly eliminated via renal excretion, with a small amount metabolized by the liver. Dosage adjustments are required for patients with renal impairment.
Dosage
Standard Dosage
Adults:
For systemic and urinary tract infections: 3 grams intravenously every 4 to 6 hours. For gynecological infections: 200-300 mg/kg/day intravenously divided every 4 to 6 hours, depending on infection severity.
Children:
Dosing is weight-based: 200-300 mg/kg/day intravenously divided every 4 to 6 hours, adjusted for age and severity of infection. Safety and efficacy have not been established for infants under 3 months.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary due to age-related decline in renal function.
- Patients with Renal Impairment: Dose reduction and/or increased dosing intervals are necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: Caution is advised, although significant dosage adjustments are usually not required.
- Patients with Comorbid Conditions: Careful consideration is required; adjust dosage based on specific conditions.
Clinical Use Cases:
Dosage recommendations for specific clinical situations should be determined by the treating physician, considering the patient’s specific circumstances and the infection’s severity. The drug is often used empirically in critical care settings while awaiting culture results, but dosage should be adjusted accordingly once the causative organism and its susceptibility are determined.
Dosage Adjustments:
Dose adjustments are crucial in patients with renal impairment, based on creatinine clearance. Hepatic impairment generally does not necessitate major dose modifications, but close monitoring is recommended.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, pain at the injection site, rash, itching, headache.
Rare but Serious Side Effects:
Allergic reactions (including anaphylaxis), seizures, bleeding, low platelet counts, low white blood cell counts, kidney dysfunction, pseudomembranous colitis, hepatitis, jaundice.
Long-Term Effects:
Long-term use can lead to superinfections (like Clostridium difficile infection) or fungal infections.
Adverse Drug Reactions (ADR):
Severe allergic reactions, including anaphylaxis, Stevens-Johnson syndrome, interstitial nephritis, and hepatic dysfunction.
Contraindications
Hypersensitivity to ticarcillin, other penicillins, or clavulanate potassium.
Drug Interactions
Probenecid, aminoglycosides, anticoagulants (like warfarin), oral contraceptives, methotrexate.
Pregnancy and Breastfeeding
Pregnancy Category B. While animal studies have not shown harm, there are no adequate and well-controlled studies in pregnant women. Use only if clearly needed. Small amounts are excreted in breast milk. While generally considered safe, monitor the infant for potential effects, including diarrhea and thrush.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis.
- Side Effects: Nausea, vomiting, diarrhea, allergic reactions, bleeding, kidney dysfunction.
- Contraindications: Hypersensitivity to penicillin or clavulanate.
- Drug Interactions: Probenecid, aminoglycosides, anticoagulants.
- Pregnancy & Breastfeeding: Category B; use with caution.
- Dosage: 3g IV q4-6h (adults).
- Monitoring Parameters: Renal function, liver function, complete blood counts, signs of superinfection.
Popular Combinations
Ticarcillin is frequently combined with clavulanate potassium (Timentin) to enhance its efficacy against beta-lactamase producing bacteria.
Precautions
Carefully assess for penicillin allergy, monitor renal and hepatic function, observe for signs of superinfection, and monitor for bleeding tendencies.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ticarcillin?
A: For adults with systemic or urinary tract infections, the standard dose is 3 grams intravenously every 4 to 6 hours. Pediatric dosages are weight-based (200-300 mg/kg/day IV divided every 4-6 hours) and should be adjusted according to age and infection severity. Dosages may need adjustment in patients with renal impairment.
Q2: How is Ticarcillin administered?
A: Ticarcillin is administered intravenously or intramuscularly. Intravenous infusion should be given over 30 minutes.
Q3: What are the most common side effects of Ticarcillin?
A: The most common side effects include nausea, vomiting, diarrhea, pain at the injection site, skin rash, and itching.
A: Serious side effects requiring urgent medical attention include severe allergic reactions (anaphylaxis, skin reactions), seizures, bleeding, signs of kidney dysfunction, and pseudomembranous colitis.
Q5: Can Ticarcillin be used in pregnant or breastfeeding women?
A: Ticarcillin is a Pregnancy Category B drug. While animal studies have not shown fetal harm, its use during pregnancy requires careful consideration of the potential risks and benefits. Small amounts are excreted in breast milk. Though generally considered safe for breastfeeding mothers, infants should be monitored for diarrhea, thrush, and other potential side effects.
Q6: Does Ticarcillin interact with other medications?
A: Yes, Ticarcillin can interact with several medications, including probenecid (increases ticarcillin levels), aminoglycosides (increased risk of nephrotoxicity), anticoagulants (like warfarin, increased risk of bleeding), oral contraceptives (reduced efficacy), and methotrexate (increased methotrexate toxicity). It’s essential to inform the prescribing physician about all concomitant medications.
Q7: What is the mechanism of action of Ticarcillin?
A: Ticarcillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) in the bacterial cell wall. This disrupts the final stage of peptidoglycan synthesis, a crucial component of the cell wall, eventually leading to bacterial lysis and death.
Q8: How should Ticarcillin be used in patients with renal impairment?
A: Dosage adjustments are crucial for patients with renal impairment. The dose and/or dosing interval should be reduced based on the patient’s creatinine clearance.
Q9: Is Ticarcillin effective against Pseudomonas aeruginosa?
A: Yes, Ticarcillin has activity against Pseudomonas aeruginosa, which is one of its key clinical uses. However, the emergence of resistant strains necessitates susceptibility testing to guide appropriate therapy.
Q10: What type of antibiotic is Ticarcillin?
A: Ticarcillin is a beta-lactam antibiotic, specifically a carboxypenicillin. It belongs to the broader class of penicillins.
