Ceftazidime + avibactam

Intravenous
Complicated intra-abdominal infections
Adult: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion In combination with metronidazole, and with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 2 g/0.5 g 8 hourly via infusion over 2 hours for 5-14 days.
Child: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion In combination with metronidazole, and with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 3-<6 months 0.04 g/0.01 g/kg 8 hourly; 6 months to <18 years 0.05 g/0.0125 g/kg 8 hourly, up to Max of 2 g/0.5 g. All doses are given via infusion for over 2 hours. Treatment duration: 5-14 days. Treatment recommendations may vary among countries and individual products (refer to local detailed product guideline).
Renal impairment: Adult: CrCl is estimated using Cockcroft-Gault formula. ESRD including patients on haemodialysis: 0.75 g/0.1875 g 48 hourly via infusion over 2 hours after the haemodialysis session on haemodialysis days. Child: CrCl is estimated using Schwartz bedside formula. 2-<18 years ESRD including patients on haemodialysis: 0.01875 g/0.00475 g/kg 48 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours after the haemodialysis session on haemodialysis days; CrCl 6-15 mL/min/1.73 m²: 0.01875 g/0.00475 g/kg 24 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 16-30 mL/min/1.73 m²: 0.01875 g/0.00475 g/kg 12 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 31-50 mL/min/1.73 m²: 0.025 g/0.00625 g/kg 8 hourly (Max: 1 g/0.25 g) via infusion over 2 hours.

CrCl (ml/min)	Dosage Recommendation
6-15	Adult: 0.75 g/0.1875 g 24 hourly via infusion over 2 hours.
16-30	Adult: 0.75 g/0.1875 g 12 hourly via infusion over 2 hours.
31-50	Adult: 1 g/0.25 g 8 hourly via infusion over 2 hours.

Reconstitution: Reconstitute vial labelled as 2 g ceftazidime/0.5 g avibactam with 10 mL sterile water for inj to prepare a concentration of 167.3 mg/mL ceftazidime and 41.8 mg/mL avibactam (volume of entire contents is approx 12 mL). Further dilute the reconstituted solution by transferring the appropriately calculated volume of reconstituted solution in an infusion bag containing 0.9% NaCl solution, 5% dextrose in water, combination of 0.45% NaCl and 2.5% dextrose, or Lactated Ringer's solution to attain a final concentration of 8-40 mg/mL ceftazidime and 2-10 mg/mL avibactam. Total time interval when starting the reconstitution and completing the IV infusion preparation must not exceed 30 minutes.

Intravenous
Complicated urinary tract infections
Adult: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion For cases including pyelonephritis: In combination with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 2 g/0.5 g 8 hourly via infusion over 2 hours for 5-10 days, may be increased to 14 days in patients with bacteraemia. Total duration of treatment may include IV doses, followed by appropriate oral therapy.
Child: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion For cases including pyelonephritis: In combination with antibacterial drug active against Gram-positive pathogens (when these are known or suspected to contribute to the infection): 3-<6 months 0.04 g/0.01 g/kg 8 hourly; 6 months to <18 years 0.05 g/0.0125 g/kg 8 hourly, up to Max of 2 g/0.5 g. All doses are given via infusion for over 2 hours. Treatment duration: 5-14 days. Total duration of treatment may include IV doses, followed by appropriate oral therapy. Treatment recommendations may vary among countries and individual products (refer to local detailed product guideline).
Renal impairment: Adult: CrCl is estimated using Cockcroft-Gault formula. ESRD including patients on haemodialysis: 0.75 g/0.1875 g 48 hourly via infusion over 2 hours after the haemodialysis session on haemodialysis days. Child: CrCl is estimated using Schwartz bedside formula. 2-<18 years ESRD including patients on haemodialysis: 0.01875 g/0.00475 g/kg 48 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours after the haemodialysis session on haemodialysis days; CrCl 6-15 mL/min/1.73 m²: 0.01875 g/0.00475 g/kg 24 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 16-30 mL/min/1.73 m²: 0.01875 g/0.00475 g/kg 12 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 31-50 mL/min/1.73 m²: 0.025 g/0.00625 g/kg 8 hourly (Max: 1 g/0.25 g) via infusion over 2 hours.

CrCl (ml/min)	Dosage Recommendation
6-15	Adult: 0.75 g/0.1875 g 24 hourly via infusion over 2 hours.
16-30	Adult: 0.75 g/0.1875 g 12 hourly via infusion over 2 hours.
31-50	Adult: 1 g/0.25 g 8 hourly via infusion over 2 hours.

Reconstitution: Reconstitute vial labelled as 2 g ceftazidime/0.5 g avibactam with 10 mL sterile water for inj to prepare a concentration of 167.3 mg/mL ceftazidime and 41.8 mg/mL avibactam (volume of entire contents is approx 12 mL). Further dilute the reconstituted solution by transferring the appropriately calculated volume of reconstituted solution in an infusion bag containing 0.9% NaCl solution, 5% dextrose in water, combination of 0.45% NaCl and 2.5% dextrose, or Lactated Ringer's solution to attain a final concentration of 8-40 mg/mL ceftazidime and 2-10 mg/mL avibactam. Total time interval when starting the reconstitution and completing the IV infusion preparation must not exceed 30 minutes.

Intravenous
Hospital-acquired pneumonia
Adult: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion For cases including ventilator-associated pneumonia: In combination with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 2 g/0.5 g 8 hourly via infusion over 2 hours for 7-14 days.
Child: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion For cases including ventilator-associated pneumonia: In combination with antibacterial drug(s) active against Gram-positive pathogens and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 3-<6 months 0.04 g/0.01 g/kg 8 hourly; 6 months to <18 years 0.05 g/0.0125 g/kg 8 hourly, up to Max of 2 g/0.5 g. All doses are given via infusion for over 2 hours. Treatment duration: 7-14 days. Treatment recommendations may vary among countries and individual products (refer to local detailed product guideline).
Renal impairment: Adult: CrCl is estimated using Cockcroft-Gault formula. ESRD including patients on haemodialysis: 0.75 g/0.1875 g 48 hourly via infusion over 2 hours after the haemodialysis session on haemodialysis days. Child: CrCl is estimated using Schwartz bedside formula. 2-<18 years ESRD including patients on haemodialysis: 0.01875 g/0.00475 g/kg 48 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours after the haemodialysis session on haemodialysis days; CrCl 6-15 mL/min/1.73 m²: 0.01875 g/0.00475 g/kg 24 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 16-30 mL/min/1.73 m²: 0.01875 g/0.00475 g/kg 12 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 31-50 mL/min/1.73 m²: 0.025 g/0.00625 g/kg 8 hourly (Max: 1 g/0.25 g) via infusion over 2 hours.

CrCl (ml/min)	Dosage Recommendation
6-15	Adult: 0.75 g/0.1875 g 24 hourly via infusion over 2 hours.
16-30	Adult: 0.75 g/0.1875 g 12 hourly via infusion over 2 hours.
31-50	Adult: 1 g/0.25 g 8 hourly via infusion over 2 hours.

Reconstitution: Reconstitute vial labelled as 2 g ceftazidime/0.5 g avibactam with 10 mL sterile water for inj to prepare a concentration of 167.3 mg/mL ceftazidime and 41.8 mg/mL avibactam (volume of entire contents is approx 12 mL). Further dilute the reconstituted solution by transferring the appropriately calculated volume of reconstituted solution in an infusion bag containing 0.9% NaCl solution, 5% dextrose in water, combination of 0.45% NaCl and 2.5% dextrose, or Lactated Ringer's solution to attain a final concentration of 8-40 mg/mL ceftazidime and 2-10 mg/mL avibactam. Total time interval when starting the reconstitution and completing the IV infusion preparation must not exceed 30 minutes.

Intravenous
Bacteraemia
Adult: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion For cases associated with or suspected to be associated with complicated intra-abdominal infections, complicated UTI, or hospital-acquired pneumonia (HAP): 2 g/0.5 g 8 hourly via infusion over 2 hours. Treatment duration may vary according to the site of infection.
Renal impairment: Adult: CrCl is estimated using Cockcroft-Gault formula. ESRD including patients on haemodialysis: 0.75 g/0.1875 g 48 hourly via infusion over 2 hours after the haemodialysis session on haemodialysis days.

CrCl (ml/min)	Dosage Recommendation
6-15	Adult: 0.75 g/0.1875 g 24 hourly via infusion over 2 hours.
16-30	Adult: 0.75 g/0.1875 g 12 hourly via infusion over 2 hours.
31-50	Adult: 1 g/0.25 g 8 hourly via infusion over 2 hours.

Reconstitution: Reconstitute vial labelled as 2 g ceftazidime/0.5 g avibactam with 10 mL sterile water for inj to prepare a concentration of 167.3 mg/mL ceftazidime and 41.8 mg/mL avibactam (volume of entire contents is approx 12 mL). Further dilute the reconstituted solution by transferring the appropriately calculated volume of reconstituted solution in an infusion bag containing 0.9% NaCl solution, 5% dextrose in water, combination of 0.45% NaCl and 2.5% dextrose, or Lactated Ringer's solution to attain a final concentration of 8-40 mg/mL ceftazidime and 2-10 mg/mL avibactam. Total time interval when starting the reconstitution and completing the IV infusion preparation must not exceed 30 minutes.

Intravenous
Susceptible Gram-negative infections
Adult: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion For cases due to aerobic organisms in patients with limited treatment options: In combination with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 2 g/0.5 g 8 hourly via infusion over 2 hours. Treatment duration may vary depending on the severity of the infection, pathogen(s), and clinical response of the patient.
Child: Available preparation: Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion For cases due to aerobic organisms in patients with limited treatment options: In combination with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 3-<6 months 0.04 g/0.01 g/kg 8 hourly; 6 months to <18 years 0.05 g/0.0125 g/kg 8 hourly, up to Max of 2 g/0.5 g. All doses are given via infusion for over 2 hours. Treatment duration may vary depending on the severity of the infection, pathogen(s), and clinical and bacteriological progress of the patient. Treatment recommendations may vary among countries and individual products (refer to local detailed product guideline).
Renal impairment: Adult: CrCl is estimated using Cockcroft-Gault formula. ESRD including patients on haemodialysis: 0.75 g/0.1875 g 48 hourly via infusion over 2 hours after the haemodialysis session on haemodialysis days. Child: CrCl is estimated using Schwartz bedside formula. 2-<18 years ESRD including patients on haemodialysis: 0.01875 g/0.00475 g/kg 48 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours after the haemodialysis session on haemodialysis days; CrCl 6-15 mL/min/1.73 m²: 0.01875 g/0.00475 g/kg 24 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 16-30 mL/min/1.73 m²: 0.01875 g/0.00475 g/kg 12 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 31-50 mL/min/1.73 m²: 0.025 g/0.00625 g/kg 8 hourly (Max: 1 g/0.25 g) via infusion over 2 hours.

CrCl (ml/min)	Dosage Recommendation
6-15	Adult: 0.75 g/0.1875 g 24 hourly via infusion over 2 hours.
16-30	Adult: 0.75 g/0.1875 g 12 hourly via infusion over 2 hours.
31-50	Adult: 1 g/0.25 g 8 hourly via infusion over 2 hours.

Reconstitution: Reconstitute vial labelled as 2 g ceftazidime/0.5 g avibactam with 10 mL sterile water for inj to prepare a concentration of 167.3 mg/mL ceftazidime and 41.8 mg/mL avibactam (volume of entire contents is approx 12 mL). Further dilute the reconstituted solution by transferring the appropriately calculated volume of reconstituted solution in an infusion bag containing 0.9% NaCl solution, 5% dextrose in water, combination of 0.45% NaCl and 2.5% dextrose, or Lactated Ringer's solution to attain a final concentration of 8-40 mg/mL ceftazidime and 2-10 mg/mL avibactam. Total time interval when starting the reconstitution and completing the IV infusion preparation must not exceed 30 minutes.

Hypersensitivity to ceftazidime, avibactam, any other cephalosporins, or severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other β-lactam antibacterial (e.g. carbapenems, monobactams, penicillins).

Patient with history of non-severe hypersensitivity reaction to penicillins, monobactams or carbapenems. Children. Renal impairment. Pregnancy and lactation. Patient Counselling This drug may cause dizziness, if affected, do not drive or operate machinery. Monitoring Parameters Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Assess patient's history of hypersensitivity reactions to ceftazidime, other cephalosporins, or any other type of β-lactam antibiotic prior to treatment initiation. Obtain renal function at baseline in all patients and at least daily in those with changing renal function. Monitor for signs and symptoms of anaphylaxis (during initial dose), serious skin reactions, and seizures or other neurologic activity, particularly in renally impaired patients.

Significant: Bacterial or fungal superinfection (prolonged use), severe neurological reactions (e.g. asterixis, encephalopathy, neuromuscular excitability, myoclonus, seizures, non-convulsive status epilepticus, coma). Blood and lymphatic system disorders: Eosinophilia, thrombocytopenia, thrombocytosis. Gastrointestinal disorders: Abdominal pain, vomiting, nausea, diarrhoea, dysgeusia. General disorders and administration site conditions: Infusion site thrombosis or phlebitis, pyrexia. Infections and infestations: Candidiasis including oral or vulvovaginal candidiasis. Investigations: Increased ALT, AST, blood alkaline phosphatase, gamma-glutamyltransferase, and blood lactate dehydrogenase. Metabolism and nutrition disorders: Hypokalaemia. Nervous system disorders: Dizziness, headache. Psychiatric disorders: Anxiety. Renal and urinary disorders: Acute kidney injury, nephrolithiasis, renal impairment. Skin and subcutaneous tissue disorders: Pruritus, urticaria, maculopapular rash.
Potentially Fatal: Serious hypersensitivity reactions, including anaphylactoid reactions and severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms); Clostridioides difficile-associated diarrhoea, pseudomembranous colitis.

Symptoms: Neurological sequelae including encephalopathy, convulsions, and coma. Management: May perform haemodialysis or peritoneal dialysis to reduce serum levels of ceftazidime.

Ceftazidime: Concomitant use of high dose cephalosporins and nephrotoxic agents (e.g. aminoglycosides, potent diuretics) may have adverse effects on renal function. Avibactam: Elimination of avibactam may be altered by probenecid.

Ceftazidime: May lead to positive direct antiglobulin test (DAGT) or Coombs' test which may interfere with blood cross-matching and/or cause drug-induced immune haemolytic anaemia. May cause false-positive urinary glucose test with copper reduction methods (e.g. Benedict's solution, Fehling's solution, Clinitest^®).

Ceftazidime, a 3rd generation cephalosporin, binds to 1 or more penicillin-binding proteins (PBPs) which inhibits the final transpeptidation step of bacterial peptidoglycan cell wall synthesis, thus resulting in bacterial cell lysis and death. Avibactam is a reversible non β-lactam β-lactamase inhibitor with minimal intrinsic antibacterial activity; however, it has the potential to enhance the activity of ceftazidime against β-lactamase-producing bacteria. It acts by forming a covalent adduct with the enzyme that is stable to hydrolysis.
Distribution: Ceftazidime: Widely distributed throughout body tissues and fluids; therapeutic concentrations are achieved in the CSF when meninges are inflamed. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: Mean: 18.1 L (single dose); 17 L (multiple dose). Plasma protein binding: Approx 10%. Avibactam: Volume of distribution: Mean: 23.2 L (single dose); 22.2 L (multiple dose). Plasma protein binding: 5.7-8.2%.
Metabolism: Not metabolised.
Excretion: Terminal elimination half-life: Approx 2 hours. Ceftazidime: Via urine (approx 80-90% as unchanged drug within 24 hours). Avibactam: Via urine (approx 97%); bile (<1%); faeces (<0.25%).

Intravenous: Store intact vials between 15-30°C. Protect from light. Solutions after further dilution in 0.9% NaCl, 5% dextrose in water, combination of 0.45% NaCl and 2.5% dextrose, or Lactated Ringer's solution are stable for up to 12 hours at room temperature (≤25°C) and up to 24 hours when stored between 2-8°C.

Cephalosporins

J01DD02 - ceftazidime ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.