No

Antibiotic, Penicillin

Treatment of infections of lower respiratory tract, urinary tract, skin and skin structures, bone and joint, and septicemia caused by susceptible organisms. Clavulanate expands activity of ticarcillin to include beta-lactamase producing strains of S. aureus, H. influenzae, Bacteroides species, and some other gram-negative bacilli

B

Known hypersensitivity to ticarcillin, clavulanate, or any penicillin

Not approved for use in children <12 years of age; use with caution and modify dosage in patients with renal impairment; use with caution in patients with a history of allergy to cephalosporins and in patients with CHF due to high sodium load

Percentage unknown: Convulsions, confusion, drowsiness, fever, rash, electrolyte imbalance, hemolytic anemia, positive Coombs' reaction, bleeding, thrombophlebitis, myoclonus, acute interstitial nephritis, hypersensitivity reactions, anaphylaxis, Jarisch-Herxheimer reaction

Symptoms of overdose include neuromuscular hypersensitivity, seizures

Many beta-lactam containing antibiotics have the potential to cause neuromuscular hyperirritability or convulsive seizures. Hemodialysis may be helpful to aid in the removal of the drug from the blood, otherwise most treatment is supportive or symptom directed.

Decreased effect:

Tetracyclines may decrease penicillin effectiveness

Aminoglycosides physical inactivation of aminoglycosides in the presence of high concentrations of ticarcillin

Decreased effectiveness of oral contraceptives

Increased effect:

Probenecid may increase penicillin levels

Neuromuscular blockers may increase duration of blockade

Potential toxicity in patients with with mild to moderate renal dysfunction

Aminoglycosides synergistic efficacy

Increased bleeding risk with large I.V. doses and anticoagulants

Reconstituted solution is stable for 6 hours at room temperature and 72 hours when refrigerated; for I.V. infusion in NS is stable for 24 hours at room temperature, 7 days when refrigerated or 30 days when frozen; after freezing, thawed solution is stable for 8 hours at room temperature; for I.V. infusion in D₅W solution is stable for 24 hours at room temperature, 3 days when refrigerated or 7 days when frozen; after freezing, thawed solution is stable for 8 hours at room temperature; darkening of drug indicates loss of potency of clavulanate potassium; incompatible with sodium bicarbonate, aminoglycosides

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Distribution: Low concentrations of ticarcillin distribute into the CSF and increase when meninges are inflamed, otherwise widely distributed

Protein binding:

Ticarcillin: 45% to 65%

Clavulanic acid: 9% to 30% removed by hemodialysis

Metabolism: Clavulanic acid is metabolized in the liver

Half-life:

Clavulanate: 66-90 minutes

Ticarcillin: 66-72 minutes in patients with normal renal function; clavulanic acid does not affect the clearance of ticarcillin

Elimination: 45% excreted unchanged in urine, whereas 60% to 90% of ticarcillin excreted unchanged in urine

I.V.:

Children >60 kg and Adults: 3.1 g (ticarcillin 3 g plus clavulanic acid 0.1 g) every 4-6 hours; maximum: 24 g/day

Urinary tract infections: 3.1 g every 6-8 hours

Dosing adjustment in renal impairment:

Cl_cr 30-60 mL/minute: Administer 2 g every 4 hours or 3.1 g every 8 hours

Cl_cr 10-30 mL/minute: Administer 2 g every 8 hours or 3.1 g every 12 hours

Cl_cr <10 mL/minute: Administer 2 g every 12 hours

Moderately dialyzable (20% to 50%)

Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Dose as for Cl_cr 10-50 mL/minute

Observe signs and symptoms of anaphylaxis during first dose

Positive Coombs' test, false-positive urinary proteins

May cause drowsiness or confusion; penicillins reported to cause apprehension, illusions, hallucinations, depersonalization, agitation, insomnia, and encephalopathy

None reported

No information available to require special precautions

Prolonged use of penicillins may lead to development of oral candidiasis

This medication will be administered I.V. or I.M. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may reduce nausea or dry mouth. Maintain good oral and vaginal hygiene to reduce incidence of opportunistic infection. If diabetic, drug may cause false tests with Clinitest® urine glucose monitoring; use of glucose oxidase methods (Clinistix®) or serum glucose monitoring is preferable. This drug may interfere with oral contraceptives; an alternate form of birth control should be used. Report persistent diarrhea or abdominal pain (do not use antidiarrhea medication without consulting prescriber), fever, chills, unhealed sores, bloody urine or stool, muscle pain, mouth sores, difficulty breathing, or skin rash.

Draw sample for culture and sensitivity prior to first dose if possible

Infusion, premixed (frozen): Ticarcillin disodium 3 g and clavulanate potassium 0.1 g (100 mL)

Powder for injection: Ticarcillin disodium 3 g and clavulanate potassium 0.1 g (3.1 g, 31 g)

Begue P, Quiniou F, Quinet B, "Efficacy and Pharmacokinetics of Timentin® in Paediatric Infections," J Antimicrob Chemother, 1986, 17(Suppl C):81-91.

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Itokazu GS and Danziger LH, "Ampicillin-Sulbactam and Ticarcillin-Clavulanic Acid: A Comparison of Their In Vitro Activity and Review of Their Clinical Efficacy," Pharmacotherapy, 1991, 11(5):382-414.

Reed MD, Yamashita TS, and Blumer JL, "Pharmacokinetic-Based Ticarcillin/Clavulanic Acid Dose Recommendations for Infants and Children," J Clin Pharmacol, 1995, 35(7):658-65.

Stutman HR and Marks MI, "Review of Pediatric Antimicrobial Therapies," Semin Pediatr Infect Dis, 1991, 2:3-17.

Wright AJ, "The Penicillins," Mayo Clin Proc, 1999, 74(3):290-307.