AURIZEF 1,0 g

Indications

• Bacterial infections
• Complicated urinary tract infections
• Hospital-acquired pneumonia
• Sepsis
• Febrile neutropenia
• Prophylaxis for transurethral resection of the prostate
• Intra-abdominal infections
• Acute exacerbations of chronic obstructive pulmonary disease

Dosage

Children: Child: 1 g

Adults: 1 g every 8 hours, or 2 g once daily for severe infections, with a maximum of 9 g per day depending on the clinical scenario.

Mechanism of action

Ceftazidime works by inhibiting the synthesis of the bacterial cell wall. Specifically, it binds to penicillin-binding proteins (PBPs), predominantly PBP3, thus interfering with the cross-linking of peptidoglycan layers in the bacterial cell wall. This disruption leads to cell lysis and death, making ceftazidime bactericidal against susceptible organisms.

Pharmacodynamics

As a semisynthetic cephalosporin, ceftazidime is particularly resistant to certain beta-lactamases, which enhances its effectiveness against a range of Gram-negative bacteria. Its bactericidal action is primarily due to the inhibition of cell wall synthesis, particularly against bacteria such as Escherichia coli and Pseudomonas aeruginosa. While it is effective against many Gram-negative pathogens, it is less effective against Gram-positive bacteria.

Pharmacokinetics

Ceftazidime is well absorbed when administered intravenously, with a distribution volume of approximately 0.3 to 0.5 L/kg. It is primarily eliminated by the kidneys, with a half-life of about 1.5 to 2 hours in individuals with normal renal function. Dosing adjustments are necessary in patients with renal impairment to prevent accumulation.

Adverse effects

• Thrombocytosis
• Cellulitis
• Erysipelas
• Thrombophlebitis
• Fungal infection
• Acute kidney injury
• Coma
• Encephalopathy
• Jaundice
• Lymphocytosis
• Myoclonus
• Neurological effects
• Paraesthesia
• Seizure
• Taste altered
• Tremor

Precautions

• Caution in patients with severe hepatic impairment
• Caution in renal impairment, dose adjustments may be necessary

Pregnancy

Not known to be harmful.

Breast-feeding

Present in milk in low concentration, but appropriate to use.

Storage

Store at room temperature, protect from light. Reconstituted solutions should be used promptly.

Formulations

• 500 mg powder for solution for injection
• 1 g powder for solution for injection
• 2 g powder for solution for injection

Dosage

Children: Refer to the specific drug formulation and clinical guidelines for appropriate dosing. Pediatric doses should be carefully calculated based on the active ingredient and the child's age and weight.

Adults: Refer to the specific drug formulation and clinical guidelines for appropriate dosing. Doses can vary widely based on the active ingredient and its clinical application.

Mechanism of action

Pentahydrate forms do not have a specific mechanism of action, as they are typically salts or hydrates of other active compounds. The effectiveness depends on the active ingredient associated with the pentahydrate form, which may engage in various biochemical interactions in the body to exert therapeutic effects. Generally, the release of the active drug from its hydrated form can influence its absorption and subsequent pharmacological activity.

Pharmacodynamics

The pharmacodynamics of pentahydrate forms is determined by their active ingredients. The hydration state can affect the dissolution rate, which in turn influences the onset of action and overall efficacy. Hydrated forms can improve solubility in biological fluids, leading to enhanced absorption and bioavailability in certain cases. The specific pharmacological action, such as receptor binding or enzyme inhibition, will depend on the drug itself rather than the pentahydrate status.

Pharmacokinetics

The pharmacokinetics of pentahydrate forms is influenced by the solubility and stability of the drug. Generally, a hydrated form may result in increased dissolution rates, promoting better absorption in the gastrointestinal tract. The extent and rate of absorption can vary based on the specific pentahydrate and its active ingredient. Distribution, metabolism, and excretion will depend on the nature of the drug itself, including its half-life and the pathways involved in its elimination from the body.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the risk.

Breast-feeding

Caution is advised. It is unknown if pentahydrate is excreted in human milk.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Indications

• Hypokalemia
• Potassium depletion
• Certain types of arrhythmias
• Prevention of hypokalemia in patients receiving diuretics

Dosage

Children: Refer to established guidelines or consult the BNF for Children for specific dosing recommendations.

Adults: Refer to established guidelines or consult the BNF for specific dosing recommendations.

Mechanism of action

Potassium ions play a crucial role in cellular physiology. They are essential for maintaining the resting membrane potential of cells and are involved in the generation of action potentials in excitable tissues such as neurons and muscle cells. The influx and efflux of potassium ions across cell membranes are critical for normal cardiac and neuromuscular function.

Pharmacodynamics

Potassium functions as an essential intracellular cation, influencing various physiological processes. It helps regulate heart rhythm, muscle contraction, and nerve impulses. An adequate potassium level is necessary to prevent muscle weakness, paralysis, and arrhythmias. The relationship between potassium levels and these physiological functions is tightly controlled by renal function and dietary intake.

Pharmacokinetics

Potassium is absorbed primarily in the gastrointestinal tract. Following absorption, it is distributed throughout the body's tissues, with approximately 98% of the body's potassium found intracellularly. The kidneys play a critical role in regulating potassium levels by excreting excess potassium in urine. The half-life of potassium in the body can vary significantly based on renal function, dietary intake, and cellular demands.

Pregnancy

There is insufficient data on the safety of pentapotassium during pregnancy. It should only be used if the benefits outweigh the risks.

Breast-feeding

It is not known if pentapotassium is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Mechanism of action

The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan. Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as "penicillin-binding proteins" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal. Ceftazidime is a semisynthetic third-generation cephalosporin with broad activity against numerous Gram-negative and some Gram-positive bacteria. Like other β-lactam antibiotics, ceftazidime exhibits its bactericidal effect primarily through direct inhibition of specific PBPs in susceptible bacteria. _In vitro_ experiments in Gram-negative bacteria such as _Escherichia coli_, _Pseudomonas aeruginosa_, _Acinetobacter baumannii_, and _Klebsiella pneumoniae_ suggest that ceftazidime primarily binds to PBP3, with weaker binding to PBP1a/1b and PBP2 as well; although binding to other PBPs, such as PBP4, is detectable, the concentrations required are much greater than those achieved clinically. Similarly, ceftazidime showed binding to _Staphylococcus aureus_ PBP 1, 2, and 3 with a much lower affinity for PBP4. Recent data for _Mycobacterium abcessus_ suggest that ceftazidime can inhibit PonA1, PonA2, and PbpA at intermediate concentrations.

Pharmacodynamics

Ceftazidime is a semisynthetic, broad-spectrum, third-generation cephalosporin antibiotic that is bactericidal through inhibition of enzymes responsible for cell-wall synthesis, primarily penicillin-binding protein 3 (PBP3). Among cephalosporins, ceftazidime is notable for its resistance to numerous β-lactamases and its broad spectrum of activity against Gram-negative bacteria, including _Pseudomonas aeruginosa_. However, it is less active than first- and second-generation cephalosporins against _Staphylococcus aureus_ and other Gram-positive bacteria and also has low activity against anaerobes. Ceftazidime has confirmed activity against 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 including _Staphylococcus_ spp. and _Streptococcus_ spp. There are also _in vitro_ data for ceftazidime efficacy against a wide variety of other bacteria, such as _Acinetobacter baumannii_ and _Neisseria gonorrhoeae_, but no clear clinical studies to support the use of ceftazidime for infections caused by these bacteria. Although β-lactam antibiotics like ceftazidime are generally well tolerated, there remains a risk of serious acute hypersensitivity reactions, which is higher in patients with a known allergy to ceftazidime or any other β-lactam antibiotic. As with all antibiotics, ceftazidime may result in the overgrowth of non-susceptible organisms and potentially serious effects including _Clostridium difficile_-associated diarrhea (CDAD); CDAD should be considered in patients who develop diarrhea and, in confirmed cases, supportive care initiated immediately. Ceftazidime is primarily renally excreted such that high and prolonged serum concentrations can occur in patients with renal insufficiency, leading to seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia. Treatment may lead to the development or induction of resistance with a risk of treatment failure. Periodic susceptibility testing should be considered, and monotherapy failure may necessitate the addition of another antibiotic such as an aminoglycoside. Cephalosporin use may decrease prothrombin activity, which may be improved by exogenous vitamin K. Inadvertent intra-arterial administration of ceftazidime may result in distal necrosis.