AZTREONAM AVIBACTAM 1,5 g/0,5 g PFIZER

Indications

• Complicated intra-abdominal infections
• Complicated urinary tract infections
• Nosocomial pneumonia
• Infections caused by resistant strains of bacteria

Dosage

Children: Refer to BNF for Children for appropriate paediatric dosing information, tailored to the child's age, weight, and specific clinical condition.

Adults: Refer to BNF for specific adult dosing guidelines based on the type of infection and patient factors. Typically, it is used in conjunction with ceftazidime, following specific protocols.

Mechanism of action

Avibactam inactivates specific β-lactamases, including Ambler class A β-lactamases, class C, and some class D β-lactamases, through a unique covalent and reversible mechanism. This action protects ceftazidime from degradation, allowing it to remain effective against β-lactamase-producing strains. Avibactam effectively reaches the bacterial periplasm, achieving concentrations sufficient to restore the activity of ceftazidime against resistant strains.

Pharmacodynamics

Avibactam works synergistically with ceftazidime to enhance its antibacterial effect against β-lactamase-producing organisms. Its ability to inhibit β-lactamases increases the overall efficacy of treatment regimens involving ceftazidime, particularly in infections caused by multidrug-resistant bacteria.

Pharmacokinetics

Avibactam is administered intravenously and reaches therapeutic concentrations in the bloodstream and in the periplasm of bacteria. It exhibits a linear pharmacokinetic profile, with a volume of distribution and clearance that support its use in combination therapy. The half-life and elimination pathways are consistent with its classification and therapeutic use.

Pregnancy

There is limited data on the use of avibactam in pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether avibactam is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at 20 to 25 degrees Celsius. Protect from light and moisture.

Indications

• Severe gram-negative infections
• Pseudomonas aeruginosa infections
• Haemophilus influenzae infections
• Neisseria meningitidis infections

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: 1 g every 8 hours, or 2 g every 12 hours.

Mechanism of action

Aztreonam inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins, leading to cell lysis and death.

Pharmacodynamics

Aztreonam exhibits time-dependent bactericidal activity against susceptible Gram-negative bacteria. Its antibacterial spectrum is limited to certain aerobic bacteria, providing an effective option for infections caused by these pathogens.

Pharmacokinetics

Aztreonam is administered via intravenous injection or infusion, with peak plasma concentrations achieved shortly after administration. It is primarily eliminated by the kidneys, with a half-life that varies based on renal function.

Adverse effects

• Allergic reactions
• Nausea
• Diarrhea
• Rash

Precautions

• Use with caution in patients with renal impairment
• Not effective against Gram-positive bacteria
• Should not be used alone for blind treatment

Pregnancy

Use only if clearly needed; safety not established.

Breast-feeding

Minimal risk; monitor infant for adverse effects.

Storage

Store in a cool, dry place; reconstituted solutions should be used promptly.

Formulations

• Powder for solution for infusion

Mechanism of action

Avibactam is a non-β lactam β-lactamase inhibitor that inactivates some β-lactamases (Ambler class A β-lactamases, including Klebsiella pneumoniae carbapenemases, Ambler class C and some Ambler class D β-lactamases) by a unique covalent and reversible mechanism, and protects ceftazidime from degradation by certain β-lactamases. Avibactam rapidly reaches the periplasm of bacteria at high enough concentrations to restore activity of ceftazidime against ceftazidime-resistant, β-lactamase-producing strains. Avibactam does not decrease the activity of ceftazidime against ceftazidime­ susceptible organisms.

Mechanism of action

The bactericidal action of aztreonam results from the inhibition of bacterial cell wall synthesis due to a high affinity of aztreonam for penicillin binding protein 3 (PBP3). By binding to PBP3, aztreonam inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that aztreonam interferes with an autolysin inhibitor.

Pharmacodynamics

Aztreonam is a monocyclic beta-lactam antibiotic (a monobactam) originally isolated from <i>Chromobacterium violaceum</i>. Aztreonam exhibits potent and specific activity in vitro against a wide spectrum of gram-negative aerobic pathogens including <i>Pseudomonas aeruginosa</i>. It has no useful activity against gram-positive bacteria or anaerobes, but has very broad spectrum against gram-negative aerobes, including <i>Pseudomonas aeruginosa</i>. This has given it the nickname "the magic bullet for aerobic gram-negative bacteria". Aztreonam, unlike the majority of beta-lactam antibiotics, does not induce beta-lactamase activity and its molecular structure confers a high degree of resistance to hydrolysis by beta-lactamases (such as penicillinases and cephalosporinases) produced by most gram-negative and gram-positive pathogens; it is, therefore, usually active against gram-negative aerobic microorganisms that are resistant to antibiotics hydrolyzed by beta-lactamases. It is active against many strains that are multiply-resistant to other antibiotics, such as certain cephalosporins, penicillin, and aminoglycosides. Aztreonam maintains its antimicrobial activity over a pH range of 6 to 8 in vitro, as well as in the presence of human serum and under anaerobic conditions.