Meta Description:
Ceftazidime and Avibactam is a powerful antibiotic combination used to treat multidrug-resistant Gram-negative bacterial infections, including complicated intra-abdominal infections, urinary tract infections, and hospital-acquired pneumonia. Learn its uses, mechanism of action, dosage, side effects, precautions, and FAQs in this detailed medical article.
Introduction
Ceftazidime and Avibactam is a combination antibacterial agent developed to combat multidrug-resistant Gram-negative bacteria. Ceftazidime is a third-generation cephalosporin antibiotic, while Avibactam is a non-Ξ²-lactam Ξ²-lactamase inhibitor. This combination is particularly effective against pathogens that produce extended-spectrum Ξ²-lactamases (ESBLs), AmpC enzymes, and some carbapenemases such as Klebsiella pneumoniae carbapenemase (KPC). It is widely used in hospitals and intensive care settings for severe infections that are difficult to treat with conventional antibiotics.
Indications and Medical Uses
Ceftazidime and Avibactam is approved for the treatment of the following conditions in adults and pediatric patients (β₯3 months):
Complicated Intra-abdominal Infections (cIAI): Often used in combination with metronidazole to cover anaerobic organisms.
Complicated Urinary Tract Infections (cUTI), including Pyelonephritis: Effective against multidrug-resistant Gram-negative organisms.
Hospital-acquired Pneumonia (HAP) and Ventilator-associated Pneumonia (VAP): Indicated for severe nosocomial infections.
Bacteremia Associated with the Above Infections: Used when bloodstream infections occur as a complication of cIAI, cUTI, or HAP/VAP.
This combination is considered a critical reserve antibiotic in many hospital stewardship programs due to its broad activity against resistant pathogens.
Mechanism of Action
Ceftazidime: A third-generation cephalosporin that exerts its bactericidal effect by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs).
Avibactam: A Ξ²-lactamase inhibitor that does not possess intrinsic antibacterial activity, but protects ceftazidime from degradation by Ξ²-lactamases produced by resistant bacteria. Avibactam inhibits a wide range of enzymes, including Class A (e.g., KPC), Class C (AmpC), and some Class D enzymes.
Together, the combination restores ceftazidimeβs activity against resistant Gram-negative organisms, making it highly effective for difficult-to-treat infections.
Dosage and Administration
Formulation: Intravenous (IV) infusion
Adult Dosage:
2.5 g (2 g ceftazidime + 0.5 g avibactam) IV every 8 hours, infused over 2 hours.
Treatment Duration: Typically 5β14 days depending on infection site and clinical response.
Renal Impairment: Dose adjustment is required in patients with creatinine clearance <50 mL/min.
Pediatric Patients (β₯3 months): Dosage is weight-based, typically 62.5 mg/kg (50 mg ceftazidime + 12.5 mg avibactam) every 8 hours.
Note: Therapy should be guided by local resistance patterns and culture results whenever possible.
Side Effects
Ceftazidime and Avibactam are generally well tolerated, but some adverse reactions may occur:
Nausea and vomiting
Diarrhea
Headache
Hypokalemia
Elevated liver enzymes (AST/ALT)
Rash or hypersensitivity reactions
Seizures (rare, usually in patients with renal dysfunction)
Any severe allergic reaction or neurological symptoms should be promptly evaluated.
Precautions and Warnings
Hypersensitivity: Contraindicated in patients with known hypersensitivity to cephalosporins or Ξ²-lactamase inhibitors.
Renal Impairment: Dose adjustment is mandatory; monitor renal function throughout therapy.
Superinfections: Prolonged use may lead to Clostridioides difficile-associated diarrhea.
Antibiotic Stewardship: Should be reserved for confirmed or strongly suspected multidrug-resistant infections to reduce resistance development.
Pregnancy and Lactation: Limited human data; use only if potential benefit outweighs risk.
Drug Interactions
Aminoglycosides: May have additive nephrotoxic effects; use with caution.
Loop Diuretics: Can increase risk of nephrotoxicity.
Probenecid: May increase serum concentrations of avibactam.
No significant cytochrome P450 interactions are known.
Frequently Asked Questions (FAQs)
Q1: What type of bacteria does Ceftazidime & Avibactam target?
It is active against multidrug-resistant Gram-negative bacteria, including Enterobacterales and Pseudomonas aeruginosa producing Ξ²-lactamases.
Q2: Is it effective against carbapenem-resistant organisms?
Yes, especially against KPC-producing Enterobacterales. However, it is not effective against metallo-Ξ²-lactamase producers (e.g., NDM, VIM).
Q3: How is it administered?
It is given intravenously, typically every 8 hours over a 2-hour infusion.
Q4: Can it be used in children?
Yes, for patients β₯3 months, with weight-based dosing.
Q5: Should it be used empirically?
Preferably not. It should be reserved for documented or strongly suspected resistant infections based on culture data and local resistance patterns.
Conclusion
Ceftazidime and Avibactam represent a critical advancement in the fight against multidrug-resistant Gram-negative bacterial infections. Their synergistic mechanism provides robust coverage against pathogens resistant to many other antibiotics. However, due to its importance in antimicrobial stewardship, this combination should be used judiciously under medical guidance. Proper dosing, monitoring, and infection control practices are essential to preserve its clinical effectiveness.
