Ticarcillin/clavulanate

Antibiotic Class:

Beta-lactam/beta-lactamase inhibitor

Antimicrobial Spectrum:

Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E. coli, Pseudomonas aeruginosa

Mechanism of Action:

The beta-lactamase inhibitors are recognized as substrates for the beta-lactamases produced by bacteria. This allows the actual beta-lactams to attack the bacterial cell wall by binding to penicillin binding proteins

Pharmacodynamics:

Time dependent killer (Time > MIC)

Pharmacokinetics:

(of the clavulanic acid)

Dose 200mg: Cmax: 8.5-14.3 mcg/L; Protein binding: 20%; Volume of distribution: 0.16-0.25L/kg; Table 5

Adverse Effects:

No new adverse effects are seen as a result of adding beta-lactamase inhibitors to beta-lactam antibiotics. The adverse reactions would remain the same for the parent compound

Dosage:

IV: Complete listing on Table 6

Dosing in adults:

Mild/Moderate: 3.1g q6h

Severe: 3.1g q4h

Dosing in pediatrics:

Not indicated in children < 12 years of age

Table 8

Disease state based dosing:

Renal failure:  CrCl > 60mL/min: Standard dosing

                       CrCl 30-60mL/min: 2g q4h

                       CrCl 10-30mL/min: 2g q8h

                       CrCl <10mL/min: 2g q12h (q24h with hepatic dysfunction)

Hepatic failure:  Half-life may be increased in severe hepatic disease (See creatine clearance < 10mL/min)

Table 9

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 2g IV q6-8h

CVVHD (Continuous venovenous hemodialysis): 3.1g IV q6h

CVVHDF (Continuous venovenous hemodiafiltration) 3.1g IV q6h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.

Contraindications/Warnings/Precautions:

Precautions:  hypersensitivity to penicillins, history of gastrointestinal disease, particularly colitis, renal impairment

Drug Interactions:

Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine

Probenecid - increased ticarcillin levels

Pregnancy:

Category B: No evidence of risk in humans but studies inadequate

Monitoring Requirements:

Therapeutic:  Culture and sensitivities, serum levels, signs and symptoms of infection, white blood cell count

Toxic: Urinalysis, BUN, SCr, AST and ALT, skin rash, Neutropenia and leukopenia,

Brand names/Manufacturer: 

Timentin/GlaxoSmithKline