Overview:
Ceftazidime- A Cephalosporin, and Avibactam- A beta-lactamase inhibitor used to treat complicated intra-abdominal infections, complicated urinary tract infections, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia, which are caused by gram-negative microorganisms.
To prevent drug resistance and maintain effectiveness, Ceftazidime and Avibactam should be prescribed to treat infections strongly suspected to be caused by susceptible bacteria. Initial approval was done by the United States Food and Drug Administration (FDA) in the year 2015 as an injection for intravenous use. Later major changes were made in the year 2019.
What Are the Indications?
Complicated Intra-Abdominal Infections:
In adult and pediatric patients three months and older, Ceftazidime and Avibactam in combination with Metronidazole are used to treat complicated intra-abdominal infections caused by Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, Klebsiella oxytoca, Enterobacter cloacae, Citrobacter freundii complex, and Pseudomonas aeruginosa.
Complicated Urinary Tract Infections:
In adult and pediatric patients three months and older, Ceftazidime and Avibactam are used to treat complicated urinary tract infections caused by Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, Klebsiella oxytoca, Enterobacter cloacae, Citrobacter freundii complex, and Pseudomonas aeruginosa.
Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia:
In eighteen years and older patients, Ceftazidime and Avibactam are indicated for treating hospital-acquired pneumonia and ventilator-associated pneumonia caused by Enterobacter cloacae, Klebsiella pneumonia, Escherichia coli, Serratia marcescens, Proteus mirabilis, Haemophilus influenzae, and Pseudomonas aeruginosa.
What Is the Usage of the Drug?
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To reduce drug resistance and maintain effectiveness, Ceftazidime and Avibactam are used to treat infections strongly suspected to be caused by susceptible bacteria.
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Culture and susceptibility information should be considered in selecting antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may be considered.
For Patients:
What Is Ceftazidime and Avibactam?
It is the combination of two antibacterial drugs, Ceftazidime and Avibactam. They are effective against susceptible bacteria.
What Are the Indications?
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To treat urinary tract infections.
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To treat abdominal infections.
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To treat hospital-acquired infections.
What Are the Uses?
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To reduce drug resistance and maintain effectiveness, Ceftazidime and Avibactam are used to treat infections strongly suspected to be caused by susceptible bacteria.
What Is the Dosage Recommended?
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Recommended adult dosage is 2.5 grams.
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Recommended pediatric dosage for two to eighteen years is 62.5 mg/kg to a maximum of 2.5 grams. From six months to less than two years, the recommended dosage is 62.5 mg/kg. The recommended dosage is 50 mg/kg from three to less than six months.
What Are the Contraindications?
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Contraindicated for individuals with known hypersensitivity to Ceftazidime and Avibactam or other members of the cephalosporin class.
What Are the Adverse Effects?
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Hypersensitivity reactions.
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Diarrhea.
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Central nervous system reactions.
What Happens in Case of Overdosage?
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In case of overdose, the drug will be discontinued, and supportive treatment will be instituted.
How Is the Drug Supplied?
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Ceftazidime and Avibactam 2.5 grams for injection are supplied as a single dose in a clear glass vial containing Ceftazidime 2 grams and Avibactam 0.5 grams.
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It should be stored at 25°C and protected from light.
For Doctors:
What Is Ceftazidime and Avibactam?
Ceftazidime and Avibactam is an antibacterial drug that comprises semisynthetic Cephalosporin-Ceftazidime pentahydrate and the Beta-lactamase inhibitor Avibactam sodium for intravenous administration.
What Is the Dosage Form and Strength?
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Ceftazidime and Avibactam 2.5 grams for injection are supplied as a white to yellow sterile powder for the constitution in a sterile, clear glass vial, a single dose containing Ceftazidime 2 grams and Avibactam 0.5 grams.
What Is the Mechanism of Action?
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Ceftazidime is a Cephalosporin antibacterial drug effective against gram-positive and gram-negative bacteria.
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The bactericidal effect is mediated through binding with Penicillin-binding proteins.
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Avibactam is a non-Beta-lactamase inhibitor that inactivates certain Beta-lactamases that degrade Ceftazidime. (Avibactam will not decrease the Ceftazidime activity against Ceftazidime-susceptible organisms).
What Is the Usage of the Drug?
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To reduce drug resistance and maintain effectiveness, Ceftazidime and Avibactam are used to treat infections strongly suspected to be caused by susceptible bacteria.
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Culture and susceptibility information should be considered in selecting antibacterial therapy.
What Is the Recommended Dosage?
Recommended Dosage in Adult Patients:
The recommended dosage for adults eighteen years and older with creatinine clearance greater than 50 mL/min is 2.5 grams- Ceftazidime 2 grams and Avibactam 0.5 grams. The drug is administered every eight hours by intravenous infusion over two hours.
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Ceftazidime and Avibactam, combined with Metronidazole, treat complicated intra-abdominal infections for five to fourteen days. In contrast, the duration of treatment for complicated urinary tract infections and hospital-acquired pneumonia is seven to fourteen days.
Recommended Dosage in Pediatric Patients:
The recommended dosage for pediatric patients from two years to less than eighteen years with an estimated glomerular filtration rate greater than 50 mL/min/1.73 m square is 62.5 mg/kg- Ceftazidime 50 mg/kg and Avibactam- 12.5 mg/kg to a maximum of Ceftazidime 2 gm and Avibactam 0.5 gm.
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For pediatric patients from six months to less than two years, the recommended dose is 62.5 mg/kg.
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The recommended dose is 50 mg/kg for patients aged three months to under six months.
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The drug is administered every eight hours by intravenous infusion over two hours.
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Ceftazidime and Avibactam, combined with Metronidazole, treat complicated intra-abdominal infections for five to fourteen days. In contrast, the duration of treatment for complicated urinary tract infections is seven to fourteen days.
What Is the Recommended Dose for Patients With Renal Impairment?
For Adult Patients:
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For patients with estimated creatinine clearance of 31 to 50 mL/minute- the recommended dose is Ceftazidime and Avibactam 1.25 grams- intravenous route for every eight hours.
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For patients with estimated creatinine clearance of 16 to 30 mL/minute- the recommended dose is Ceftazidime and Avibactam 0.94 grams- intravenous route for every twelve hours.
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For patients with estimated creatinine clearance of 6 to 15 mL/minute, the recommended dose is Ceftazidime and Avibactam 0.94 grams- intravenous route every twenty-four hours.
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For patients with estimated creatinine clearance of less than or equal to 5 mL/minute- the recommended dose are Ceftazidime and Avibactam 0.75 grams- intravenous route for every forty-eight hours.
For Pediatric Patients:
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For patients with an estimated glomerular filtration rate of 31 to 50 mL/min/1.73m square- the recommended dose is Ceftazidime and Avibactam 31.25 mg/kg to a maximum of 1.25 grams every eight hours.
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For patients with an estimated glomerular filtration rate of 16 to 30 mL/min/1.73m square- the recommended dose is Ceftazidime and Avibactam 23.75 mg/kg to a maximum of 0.94 grams for every twelve hours.
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For patients with an estimated glomerular filtration rate of 6 to 15 mL/min/1.73m square- the recommended dose is Ceftazidime and Avibactam 23.75 mg/kg to a maximum of 0.94 grams for every twenty-four hours.
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For patients with an estimated glomerular filtration rate of less than or equal to 5 mL/min/1.73m square- the recommended dose is Ceftazidime and Avibactam 23.75 mg/kg to a maximum of 0.94 grams for every forty-eight hours.
How to Prepare the Solution for Administration?
Ceftazidime and Avibactam are supplied as a dry powder, which should be constituted and diluted using an aseptic technique before infusion.
Step 1: Constitute the powder with 10 mL of any of the following solutions- 0.9 % sodium chloride injection, USP, 5 % dextrose injection, USP, ringer lactate injection, USP, or all combinations of dextrose injection and sodium chloride injection, containing up to 2.5 % dextrose, and 0.45 % sodium chloride, USP.
Step 2: Should mix gently. The constituted solution should have approximate Ceftazidime- 167 mg/mL and Avibactam- 42 mg/mL. The final volume should be 12 mL (2.5 grams). Whereas pediatric doses weighing less than 40 kg should have the final volume of a concentrated solution of approximately 209 mg/mL (Ceftazidime- 167 mg/mL and Avibactam- 42 mg/mL). This solution must be diluted before intravenous infusion.
Step 3: Before infusion, dilute the withdrawn volume of constituted Ceftazidime and Avibactam solution in an infusion bag further with the above-used diluent to achieve a Ceftazidime concentration of 8 to 40 mg/mL and Avibactam of 2 to 10 mg/mL. If sterile water is used for a constitution, other appropriate constitution diluents are recommended for dilution.
Step 4: Should mix gently and ensure the contents get dissolved completely.
Step 5: Use the diluted solution in the infusion bag within twelve hours when stored at room temperature and twenty-four hours when stored under refrigeration at 2 to 8°C.
What Are the Compatible Drugs?
The Ceftazidime and Avibactam solution with a concentration of Ceftazidime 8 mg/mL and Avibactam 10 mg/mL are compatible with the more commonly used intravenous infusion fluids in infusion bags such as 0.9 % sodium chloride injection, USP, 5 % dextrose injection, USP, ringer lactate injection, USP, or all combinations of dextrose injection and sodium chloride injection, containing up to 2.5 % dextrose, and 0.45 % sodium chloride, USP.
How to Store the Constituted Solution?
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The constituted solution should not be held for longer than thirty minutes before transfer and dilution in an infusion bag.
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Following dilution, you should use the diluted solution in the infusion bag within twelve hours when stored at room temperature and twenty-four hours when stored under refrigeration at 2 to 8°C.
What Are the Contraindications?
Patients with known hypersensitivity to Ceftazidime and Avibactam-containing products.
What Are the Warnings and Precautions?
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In a phase 3 trial in adult patients, there is a decreased clinical response with baseline creatinine clearance of 30 to less than or equal to 50 mL/min.
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Hypersensitivity and skin reactions have been reported in patients receiving Beta-lactam antibacterial drugs.
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Before starting treatment with Ceftazidime and Avibactam, it is necessary to inquire about previous hypersensitivity reactions to other Cephalosporins, Penicillins, or Carbapenems.
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Should discontinue the drug in case any allergic reactions occur. Also, one should be cautious when given Penicillin or Beta-lactam.
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Clostridium difficile-associated diarrhea has been reported, which may range from mild to fatal colitis.
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In case of suspected diarrhea, the drug should be discontinued and should manage fluid and electrolyte balance, supplement protein intake, monitor antibacterial treatment, and institute surgical evaluation if required.
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Seizures, nonconvulsive status epilepticus, coma, asterixis, encephalopathy, neuromuscular excitability, and myoclonia have been reported in patients treated with Ceftazidime.
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Prescribing Ceftazidime and Avibactam in the absence of a strongly suspected bacterial infection increases the risk of the development of drug resistance.
What Are the Adverse Reactions?
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Hypersensitivity reactions.
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Clostridium difficile-associated diarrhea.
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Central nervous system reactions.
What Are the Drug Interactions?
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Probenecid- Decreases the elimination of Avibactam when co-administered.
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Laboratory test interactions- Ceftazidime administration gives a false-positive reaction for glucose in the urine with certain methods.
What Are the Uses in a Specific Population?
Pregnancy: There are no adequate data regarding the effects of Ceftazidime and Avibactam in pregnant women.
Lactation: There is no adequate data regarding the effects of Ceftazidime and Avibactam in lactating women.
Pediatric Use: The safety and effectiveness of pediatric patients from three months to under eighteen years of age have been reported.
Geriatric Use: The risk of adverse effects is greater in patients with decreased renal function, and dose adjustment should be based on renal function.
Renal Impairment: Dose adjustment should be based on renal function.
What Happens During Overdose?
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In case of overdose, discontinue Ceftazidime and Avibactam and institute general supportive treatment.
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Ceftazidime must be removed by hemodialysis.
What Is Pharmacodynamics?
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The unbound plasma concentration of Ceftazidime exceeds the Ceftazidime and Avibactam minimum inhibitory concentration against the infecting organisms.
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It is used to determine the efficacy of Avibactam in vitro and in vivo nonclinical methods.
What Is Pharmacokinetics?
Distribution: Ceftazidime and Avibactam have a low affinity toward human plasma protein binding.
Metabolism: Ceftazidime is eliminated as an unchanged drug, whereas Avibactam metabolism is not observed in human liver preparations.
Excretion: Both Ceftazidime and Avibactam are excreted by kidneys.
What Are the Clinical Trial Experiences?
In Adult Patients:
Complicated Intra-Abdominal Infections:
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Ceftazidime and Avibactam effects were evaluated in active-controlled clinical trials, which included two phase 2 trials and four phase 3 trials.
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The phase 3 trial included 529 patients treated with intravenous Ceftazidime and Avibactam 2.5 grams over 120 minutes every eight hours plus intravenous administration of 0.5 grams of Metronidazole over sixty minutes for every eight hours, and 529 patients were treated with Meropenem.
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The median age of patients was fifty years, and 22.5 % of patients were sixty-five years and older.
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Treatment discontinuation was done due to adverse reactions occurring in 2.6 % of patients, which includes dizziness and headache. And 5 % of patients have diarrhea, nausea, vomiting, and abdominal pain.
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In the phase 3 trial, death occurred in 2.5 % of patients who received Ceftazidime and Avibactam and Metronidazole and in 1.5 % of patients who received Meropenem.
Complicated Urinary Tract Infections:
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The phase 3 trial includes 511 adult patients treated with intravenous Ceftazidime and Avibactam 2.5 grams over 120 minutes every eight hours and 509 patients treated with Doripenem.
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The median age of patients was fifty-four years, and 30.70 % were sixty-five years or older.
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The most common adverse reactions are nausea, diarrhea, constipation, and upper abdominal pain.
Hospital-Acquired Bacterial Pneumonia:
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The phase 3 trial consists of 436 adult patients treated with intravenous Ceftazidime and Avibactam 2.5 grams over 120 minutes and 434 patients treated with Meropenem. The median age of patients was sixty-six years, and 54.1 % were sixty-five years or older.
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The death occurred in 9.6 % of patients who received Ceftazidime and Avibactam and 8.3 % who received Meropenem.
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The adverse reactions that occur are diarrhea, vomiting, and pruritus.
In Pediatric Patients:
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Intravenous Ceftazidime and Avibactam were studied with 128 pediatric patients aged three months to less than eighteen years.
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Safety data is obtained from the study.
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There were no deaths reported.
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The common adverse reactions include vomiting, diarrhea, rash, and infusion site phlebitis.
