Ticarcillin / Clavulanate
Ticarcillin/clavulanate (Timentinยฎ) is a powerful, injectable **extended-spectrum penicillin** (anti-pseudomonal penicillin) combined with a **beta-lactamase inhibitor**. * **Expanded Spectrum:** The addition of clavulanate protects ticarcillin from enzymatic degradation, extending its efficacy against beta-lactamase-producing strains of *E. coli*, *Pasteurella* spp., *Staphylococcus* spp., *Klebsiella*, and *Proteus*. * **Clinical Pearl:** It is particularly valued in veterinary medicine for its efficacy against *Pseudomonas aeruginosa* and is often reserved for severe, hospital-acquired infections, sepsis, or bacteremia. * **Alternative Uses:** While primarily a systemic hospital drug, it is frequently compounded into an otic preparation for the adjunctive treatment of stubborn *Pseudomonas* ear infections in dogs.
Mechanism: **Ticarcillin** is a bactericidal beta-lactam antibiotic: * Binds to specific **Penicillin-Binding Proteins (PBPs)** (such as transpeptidases and carboxypeptidases) located inside the bacterial cytoplasmic membrane. * Inhibits bacterial cell wall mucopeptide synthesis โ creates an osmotically unstable spheroplast โ leads to cell lysis and death. **Clavulanate Potassium** is a "suicide inhibitor": * Competitively and irreversibly binds to **beta-lactamase enzymes** (including types II, III, IV, V, and staphylococcal penicillinases). * Prevents these enzymes from hydrolyzing the beta-lactam ring of ticarcillin, thereby restoring and expanding its antimicrobial spectrum. * *Note:* Type I beta-lactamases (often associated with *E. coli*, *Enterobacter*, and *Pseudomonas*) are generally not inhibited by clavulanic acid.
Dosing by species
- Sepsis ยท 40-50 mg/kg ยท IV ยท q6-8h ยท Dosed on the basis of ticarcillin content
- Pseudomonas sepsis/bacteremia ยท 40 mg/kg ยท IV ยท q6h ยท Dosed on the basis of ticarcillin content
- Resistant Pseudomonas infections ยท 50 mg/kg ยท IV or IM ยท 4 times daily ยท May need more frequent dosing or constant rate infusion for resistant infections
- Susceptible infections ยท 15-50 mg/kg ยท IV, IM or SC ยท q6-8h ยท Dosed on the basis of ticarcillin content
- Serious systemic infections ยท 15-25 mg/kg followed by CRI at 7.5-15 mg/kg/h ยท IV ยท CRI ยท As directed ยท Initial bolus followed by continuous rate infusion
- Pseudomonas otitis (adjunct) ยท 0.25-0.5 ml of a 100 mg/ml injectable ticarcillin solution ยท topical ยท q8h ยท As directed ยท Instil into the affected ear
- Susceptible infections ยท 50 mg/kg ยท IV ยท q6h ยท Dosed on the basis of ticarcillin content
- Neonatal septicemia (Foals) ยท 40-60 mg/kg ยท IV or IM ยท q8h ยท Dosed on the basis of ticarcillin content
- Susceptible infections (Foals) ยท 50 mg/kg ยท IV or IM ยท q6-8h ยท Dosed on the basis of ticarcillin content
- Intrauterine infusion ยท 3-6 grams with a minimum of 200 mL of saline ยท Intrauterine ยท every 4-6 h ยท Mares need to be treated frequently in order to maintain drug concentrations above MIC.
Routes of administration
Contraindications
- Documented hypersensitivity to penicillins or other beta-lactam antibiotics
- Known hypersensitivity to penicillins or other beta-lactam antibiotics
Adverse effects
- Hypersensitivity reactions (allergic reactions)
- Platelet dysfunction and bleeding (especially at high doses or with renal impairment)
- CNS effects including headache, giddiness, hallucinations, and seizures (at high doses)
- Pain at intramuscular (IM) injection sites
- Phlebitis or local vein irritation (IV administration)
- Antibiotic-associated diarrhea or colitis
- Nausea
- Diarrhoea
- Skin rashes
Drug interactions
- Aminoglycosides (e.g., amikacin, gentamicin, tobramycin) ยท In vitro synergy against certain bacteria; however, penicillins can chemically inactivate aminoglycosides in vitro and in vivo (especially in renal failure or at massive doses). Do not mix in the same syringe or IV line.
- Probenecid ยท Reduces renal tubular secretion of ticarcillin, maintaining higher systemic levels for a longer duration (does not affect clavulanate elimination).
- Warfarin ยท Increased risk of bleeding due to potential ticarcillin-induced platelet dysfunction; use with caution.
- Heparin ยท Increased risk of bleeding due to potential ticarcillin-induced platelet dysfunction; use with caution.
- Aminoglycosides (e.g., gentamicin) ยท Mutual inactivation if mixed in the same syringe. However, there is significant synergism in vivo against Pseudomonas when administered separately. ยท major
Monitoring
- Clinical efficacy (resolution of clinical signs, WBC count, fever)
- Renal function (in patients with pre-existing impairment)
- Signs of bleeding or CNS abnormalities (if on high doses)
- Clinical signs of infection resolution
- Renal function (in prolonged use)
- Signs of hypersensitivity or adverse gastrointestinal effects
Overdose
A single inadvertent overdose is unlikely to cause significant morbidity. However, very high dosages of parenteral penicillins (especially in patients with underlying renal disease) have induced **CNS effects** (hallucinations, headaches, seizures) and alterations in **platelet function** leading to bleeding.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.