Indications
Ceftazidime is indicated for the treatment of a variety of infections caused by susceptible bacteria. These include lower respiratory tract infections, skin and skin structure infections, urinary tract infections, bacterial septicemia, bone and joint infections, gynecologic infections, intra-abdominal infections (such as peritonitis), and central nervous system infections, including meningitis. Furthermore, in combination with avibactam, ceftazidime is used to treat infections caused by Gram-negative organisms, including complicated intra-abdominal infections (cIAI) when used with metronidazole, and complicated urinary tract infections (cUTI), including pyelonephritis, in patients three months and older. Additionally, it is used in the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients aged 18 years and above. To mitigate the risk of bacterial resistance and preserve its efficacy, ceftazidime should be used only for infections confirmed or strongly suspected to be caused by susceptible bacterial strains.
Pharmacodynamics
Ceftazidime is a semisynthetic, broad-spectrum, third-generation cephalosporin antibiotic that exerts a bactericidal effect by inhibiting enzymes responsible for bacterial cell-wall synthesis, primarily penicillin-binding protein 3 (PBP3). It is distinct among cephalosporins for its resistance to numerous β-lactamases and possesses a broad spectrum of activity against Gram-negative bacteria, notably Pseudomonas aeruginosa. However, its activity is less pronounced against Staphylococcus aureus and other Gram-positive bacteria when compared with first- and second-generation cephalosporins, and it also demonstrates low activity against anaerobes. Ceftazidime has confirmed efficacy against several clinically relevant Gram-negative bacteria, including Citrobacter spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Pseudomonas aeruginosa, and some Gram-positive bacteria such as Staphylococcus spp. and Streptococcus spp. Although there are in vitro data supporting its efficacy against other bacteria like Acinetobacter baumannii and Neisseria gonorrhoeae, clinical studies to substantiate its use for infections caused by these bacteria are lacking. While β-lactam antibiotics such as ceftazidime are generally well tolerated, there is a potential for serious acute hypersensitivity reactions, particularly in patients with known allergies to β-lactam antibiotics. Use of ceftazidime may also lead to overgrowth of non-susceptible organisms, potentially resulting in Clostridium difficile-associated diarrhea. The risk of serious neurological side effects, especially among patients with renal insufficiency, necessitates careful monitoring. Periodic susceptibility testing is advisable to ensure therapeutic effectiveness and to mitigate resistance development, with additional antibiotics considered as needed.
Absorption
Ceftazidime, when administered intravenously, achieves mean peak plasma concentrations (Cmax) ranging from 42 to 170 μg/mL for doses between 500 mg and 2 g, reaching these levels immediately after infusion. For an intramuscular administration of 1 g, the Cmax is achieved approximately one hour post-injection, measuring between 37 and 43 mg/L. Intramuscular administration of 500 mg and 1 g doses results in serum concentrations remaining above 4 μg/mL for six and eight hours, respectively. The pharmacokinetics of ceftazidime demonstrate linearity across the therapeutic dose range, evidenced by its Cmax and area under the curve (AUC) being directly proportional to the administered dose. In patients with normal renal function, ceftazidime administered intravenously at 1 or 2 g doses every eight hours over a 10-day period shows no evidence of accumulation.
Metabolism
Ceftazidime undergoes minimal metabolic transformation in the body.
Mechanism of Action
Ceftazidime, a semisynthetic third-generation cephalosporin, demonstrates broad-spectrum activity against a wide range of Gram-negative and select Gram-positive bacteria. Its primary mechanism of action involves the inhibition of penicillin-binding proteins (PBPs), which are integral to bacterial cell wall synthesis and maintenance. Ceftazidime effectively targets PBP3 in susceptible Gram-negative bacteria like Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, while also exhibiting weaker binding affinities to PBP1a/1b, PBP2, and, to a lesser extent, PBP4. In Staphylococcus aureus, it binds to PBP1, PBP2, and PBP3, though with reduced efficacy against PBP4. Furthermore, recent studies indicate that Ceftazidime can inhibit PBPs such as PonA1, PonA2, and PbpA in Mycobacterium abscessus. This targeted inhibition disrupts cell wall homeostasis, compromises bacterial cell integrity, and ultimately exerts a bactericidal effect.
