Ceftazidime and avibactam

Ceftazidime and avibactam is a combination antibiotic medication used in the treatment of a variety of bacterial infections, particularly those that are difficult to treat due to antibiotic resistance. This combination includes ceftazidime, a third-generation cephalosporin antibiotic, and avibactam, a non-β-lactam β-lactamase inhibitor. The addition of avibactam to ceftazidime protects ceftazidime from degradation by β-lactamase enzymes produced by certain bacteria, thereby extending its spectrum of activity.

Indications

Ceftazidime and avibactam is indicated for the treatment of adult patients with complicated intra-abdominal infections (Intra-abdominal infections), complicated urinary tract infections (Urinary tract infection), including pyelonephritis, and hospital-acquired pneumonia (Hospital-acquired pneumonia), including ventilator-associated pneumonia. It is also used for the treatment of infections caused by Gram-negative bacteria that are resistant to carbapenem antibiotics in patients with limited or no alternative treatment options.

Mechanism of Action

Ceftazidime acts by inhibiting the synthesis of the bacterial cell wall, leading to cell lysis and death. Avibactam enhances the activity of ceftazidime by inhibiting certain β-lactamase enzymes (such as Klebsiella pneumoniae carbapenemase (KPC), certain oxacillinases (OXA), and extended-spectrum β-lactamases (ESBLs)), which some bacteria produce to inactivate cephalosporins and other β-lactam antibiotics.

Pharmacokinetics

The combination is administered intravenously. Both ceftazidime and avibactam are primarily excreted unchanged in the urine. The half-life of ceftazidime is approximately 2 hours, and the half-life of avibactam is approximately 2.7 hours.

Adverse Effects

Common adverse effects include nausea, vomiting, diarrhea, and allergic reactions. Less frequently, it may cause changes in liver function tests, thrombocytopenia, and neutropenia. As with all antibiotics, the use of ceftazidime and avibactam can lead to Clostridium difficile-associated diarrhea.

Drug Interactions

Ceftazidime and avibactam should be used with caution in patients receiving strong inhibitors of renal tubular secretion, as these can increase the concentration of ceftazidime and avibactam, potentially leading to toxicity.

Resistance

The development of bacterial resistance to ceftazidime-avibactam, although less common due to the presence of avibactam, remains a concern. Continuous surveillance and appropriate use of this antibiotic combination are essential to minimize the risk of resistance development.

Conclusion

Ceftazidime and avibactam represent an important option in the treatment of difficult-to-treat infections due to resistant Gram-negative bacteria. Its use should be guided by bacterial susceptibility patterns and in the context of an overall antimicrobial stewardship program.