By attaching to one or more of the penicillin-binding proteins, ticarcillin clavulanate potassium prevents the formation of bacterial cell walls (PBPs).

Ttreats the following infections:

• Bone and joint infections occurs due to:

  • beta-lactamase-producing isolates of Staphylococcus aureus.

• Endometritis caused by:

  • Beta-lactamase-producing isolates of Prevotella melaninogenicus,

  • Enterobacter species (including E. cloacae)

  • S. aureus

  • Klebsiella pneumoniae

  • Escherichia coli or

  • Staphylococcus epidermidis.

• Lower respiratory tract infections caused by:

  • Beta-lactamase-producing isolates of S. aureus

  • Haemophilus influenzae

  • Klebsiella species.

• Peritonitis occurs due to:

  • Beta-lactamase-producing isolates of E. coli,

  • K. pneumonia

  • Bacteroides fragilis group.

• Septicemia including bacteremia caused by:

  • Beta-lactamase-producing isolates of Klebsiella species

  • E. coli

  • S. aureus

  • Pseudomonas aeruginosa (or other Pseudomonas species).

• Skin and skin structure infections occurs due to:

  • beta-lactamase-producing isolates of S. aureus

  • Klebsiella species

  • E. coli.

• Complicated and uncomplicated Urinary tract infections occurs due to:

  • beta-lactamase-producing isolates of E. coli

  • Klebsiella species

  • P. aeruginosa (and other Pseudomonas species)

  • S. aureus

  • Citrobacter species

  • Enterobacter cloacae

  • Serratia marcescens

• Off Label Usage of Ticarcillin clavulanate potassium in Adults:

  • Intra-abdominal infections

  • Cystic fibrosis exacerbations

Ticarcillin clavulanate dose in Adults

• Ticarcillin clavulanate is a combination product
• Each 3.1 g dosage form contains 3 g ticarcillin disodium and 0.1 g clavulanic acid.

Dosage in the treatment of Gynecologic infections like endometritis:

• Moderate infections:

  • The maximum daily dose is 12 g of ticarcillin given intravenously in divided doses every 6 hours.

• Severe infections:

  • Every 4 hours, 300 mg/kg of ticarcillin is administered intravenously in divided doses.
  • The daily maximum dose is 18 g.

Systemic infections:

• <60 kg:

  • Divided doses of 200-300 mg/kg/day of ticarcillin are administered intravenously every 4–6 hours.
  • The daily maximum dose is 18 g.

• ≥60 kg:

  • 1 gm intravenously is given every 4-6 hours

Dosage in the treatment of Urinary tract infections:

• <60 kg:

  • Divided doses of 200-300 mg/kg/day of ticarcillin are administered intravenously every 4–6 hours.
  • The daily maximum dose is 18 g.

• ≥60 kg:

  • 1 gm intravenously is given every 4-6 hours

Off label Dosage for treating complicated mild to moderate community-acquired Intra-abdominal infection:

• 3.1 g is given every 6 hours for 4-7 days

Ticarcillin clavulanate dose in Children

General dosing for susceptible infection:

• Infants, Children, and Adolescents:

  • Mild to moderate infections:

    • Divided dosages of 200 mg/kg/day of ticarcillin are administered intravenously every six hours.
    • The daily dose cap is 12 g of ticarcillin.

  • Severe infections:

    • Manufacturer's labeling:
    • Split dosages of 300 mg/kg/day of ticarcillin are administered intravenously every four hours.

  • AAP recommendations:

    • Divided doses of 200-300 mg/kg/day of ticarcillin are administered intravenously every 4–6 hours.
    • The daily dose cap is 18 g of ticarcillin.

Dose in the treatment of Cystic fibrosis:

• Infants, Children, and Adolescents:
  • Higher doses have also been utilised, such as: 400 mg ticarcillin/kg/day intravenously administered in divided doses every 6 hours. split dosages of 400–750 mg of ticarcillin per kilogramme every six hours.

Ticarcillin clavulanate Pregnancy Risk Factor B

• Animal reproduction studies did not show any adverse events.
• Placenta can be crossed by Ticarcillin or Clavulanate
• Penicillin use by mothers has not been associated with an increase in the risk of side effects for fetus.
• For the treatment of postpartum gynecologic infections, including endometritis, brought on by susceptible microorganisms, ticarcillin/clavulanate is recommended.

Ticarcillin clavulanate potassium use during breastfeeding:

• Breast milk contains small amounts of ticarcillin, but it is not absorbed if taken orally.
• The manufacturer suggests that nursing mothers exercise caution when administering ticarcillinclavulanate.

Ticarcillin clavulanate dose in Renal disease:

• Loading dose:
  • 3.1 gms intravenously as a single dose, followed by maintenance dose according to creatinine clearance:

    • CrCl 30-60 mL/minute:

      • Give 2 g of ticarcillin component every 4 hours

    • CrCl 10-30 mL/minute:

      • Give 2 g of ticarcillin component every 8 hours

    • CrCl <10 mL/minute:

      • Give 2 g of ticarcillin component every 12 hours

    • CrCl <10 mL/minute with concomitant hepatic dysfunction:

      • Give 2 g of ticarcillin component every 24 hours

• Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days):

  • Dialyzable (20% to 50%):
    • 2 gms of ticarcillin component is given every 12 hours
    • It is supplemented with 3.1 g (ticarcillin/clavulanate) after each dialysis session.
    • Alternatively, give 2 g every 8 hours without a supplemental dose for deep-seated infections.
• Dosing is dependent on the assumption of 3 times/week, complete IHD sessions.

• Peritoneal dialysis (PD):

  • 1 g every 12 hours is given

• Continuous renal replacement therapy (CRRT) :

  • Drug clearance is highly dependent on the method of renal replacement, type of filter, and flow rate.
  • Appropriate dosing needs close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, and drug concentrations in relation to target trough (if appropriate).
  • The following are only general recommendations (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
    • CVVH:
      • a loading dose of 3.1g is given  followed by 2 g every 6-8 hours
    • CVVHD:
      • a loading dose of 3.1 g is given followed by 3.1 g every 6-8 hours
    • CVVHDF:
      • a loading dose of 3.1 g is given followed by 3.1 g every 6 hours
• Do not give in intervals exceeding every 8 hours.
• Clavulanate component is hepatically eliminated; which extends the dosing interval beyond 8 hours may result in loss of beta-lactamase inhibition.

Ticarcillin clavulanate dose in liver disease:

• With concomitant renal dysfunction (Clcr<10 mL/minute): 2 g of ticarcillin component is given every 24 hours.

Side effects of Ticarcillin clavulanate

• Cardiovascular:

  • Local Thrombophlebitis (With Iv Injection)

• Central Nervous System:

  • Confusion
  • Drowsiness
  • Headache
  • Seizure

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Electrolyte Disturbance
  • Hypernatremia
  • Hypokalemia

• Gastrointestinal:

  • Clostridioides (Formerly Clostridium) Difficile-Diarrhea
  • Diarrhea
  • Nausea

• Genitourinary:

  • Proteinuria (False Positive)

• Hematologic & Oncologic:

  • Bleeding Complication
  • Eosinophilia
  • Hemolytic Anemia
  • Positive Direct Coombs' Test (False Positive)

• Hepatic:

  • Hepatotoxicity
  • Increased Serum Alt
  • Increased Serum Ast
  • Jaundice

• Immunologic:

  • Jarisch Herxheimer Reaction

• Infection:

  • Fungal or bacterial Superinfection

• Renal:

  • Acute Interstitial Nephritis

• Miscellaneous:

  • Anaphylaxis

Contraindication to Ticarcillin clavulanate potassium Include:

• Hypersensitivity is a history of severe reactions (eg anaphylaxis or Stevens-Johnson syndrome) to ticarcillin or clavulanate.

Warnings and precautions

• Hypersensitivity reactions
  • Patients on penicillin therapy have experienced severe and sometimes fatal hypersensitivity reactions (anaphylactic)
  • This is especially true if they have a history beta-lactam hypersensitivity, sensitivity to multiple allergens or IgE-mediated reactions such as anaphylaxis, urticaria, or angioedema.
  • Asthmatic patients should be cautious.
• Bleeding disorders:
  • Bleeding disorders are more common in patients with significant renal impairment.
  • If bleeding or thrombocytopenia occurs, stop immediately.
• Hypokalemia
  • Hypokalemia has been observed
  • Monitor serum potassium for patients receiving prolonged therapy or who have a fluid or electrolyte imbalance.
• Superinfection
  • Long-term use may lead to fungal or bacterial superinfection, including pseudomembranous colitis and C.difficile-associated diarrhoea (CDAD).
  • CDAD was seen after more than two months of postantibiotic treatment.
• Heart failure (HF):
  • It could be challenging to use this medicine in HF patients due to high salt loading.
• Renal impairment
  • Adjusting the dosage is advised for patients with compromised renal function.
• Seizure disorders:
  • Patients with seizure disorders should be cautious. High levels of the drug, especially in the presence renal impairment, can increase the risk of seizures.

Monitor:

• During the initial dose, watch for anaphylactic symptoms and signs;
• serum electrolytes
• bleeding time
• periodic tests of renal, hepatic, and hematologic function

How to administer Ticarcillin clavulanate potassium?

Infuse intravenously over 30 minutes.

•  If combination penicillin/aminoglycoside therapy is needed in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be done.

Mechanism of action of Ticarcillin clavulanate potassium:

• A beta-lactam antibiotic, it prevents the formation of bacterial cell walls by attaching to one or more penicillin-binding proteins (PBPs)
• It blocks the final step of peptidoglycan synthesis in bacterial cell walls.
• Bacteria eventually lyse because of ongoing activity by cell wall autolytic enzymes (autolysins, murein hydrolases), while cell wall assembly becomes blocked.

Distribution:

• Ticarcillin is mainly distributed into the tissue, interstitial fluid, pleural fluid, and bile;
• low concentrations of ticarcillin distribute into the CSF but increase when meninges are inflamed.

Protein binding: Ticarcillin: almost 45%; Clavulanic acid: almost 25%

Metabolism: Clavulanic acid is metabolized via hepatic route

Half-life elimination:

• Neonates: Ticarcillin: 4.4 hours & Clavulanic acid: 1.9 hours
• Children (1 month to 9.3 years): Ticarcillin: 66 minutes & Clavulanic acid: 54 minutes

Adults:

• Ticarcillin: 66 - 72 minutes; 13 hours (in patients having renal failure)
• Clavulanic acid: 66 - 90 minutes; clavulanic acid does not affect the clearance of ticarcillin

Time to peak, plasma:

• Immediately after completion of a 30-minute infusion

Excretion:

• Children:
  • Ticarcillin: Via Urine (71% 50% as unchanged drug over 4 hours);
  • Clavulanic acid: Via Urine (50% as unchanged drug over 4 hours)
• Adults:  
  • Ticarcillin: Via Urine (60% to 70% as unchanged drug);
  • Clavulanic acid: Via Urine (35% to 45% as unchanged drug)

International Brands of Ticarcillin clavulanate potassium:

• Betabactyl
• Claventin
• Ticarcin
• Ticarnic
• Timentin

Ticarcillin clavulanate potassium brands in Pakistan:

Ticaclav (Inf: 3.2 gms: 4 vials - Rs.2040) -

Stallion