Ceftazidime

Ceftazidime belongs to the beta-lactam family, and more precisely to the third-generation cephalosporins. At the heart of its molecule, a beta-lactam ring binds to bacterial enzymes called penicillin-binding proteins, the PBPs. These enzymes normally carry out transpeptidation, the step that cross-links peptidoglycan, the rigid mesh that forms the bacterial wall. By blocking this reaction, ceftazidime prevents the bacterium from building and repairing its wall, which eventually gives way. The effect is bactericidal: the bacterium dies.

Among the third-generation cephalosporins, ceftazidime stands out for its activity against Pseudomonas aeruginosa, a Gram-negative organism that is often difficult to treat. It also retains its efficacy in the presence of many beta-lactamases, the enzymes that some bacteria produce to destroy antibiotics. This stability explains its action across a wide range of Gram-negative bacteria.

Ceftazidime treats infections caused by susceptible bacteria. It has no effect on viral infections such as the common cold or the flu, against which no antibiotic works. The doctor therefore reserves it for situations where a bacterial organism is suspected or identified, and where that organism falls within its spectrum.

Its main asset remains coverage of Gram-negative bacteria, particularly Pseudomonas aeruginosa, which many other antibiotics cannot control. Its resistance to many beta-lactamases makes it a useful option against organisms that inactivate older molecules. The choice rests on the type of infection and, when it is available, on the antibiogram.

Ceftazidime is not taken by mouth. It is given intravenously, into a vein, or intramuscularly, into a muscle, usually every 8 or 12 hours. There is therefore no link with meals, and unless the doctor says otherwise, the patient keeps their usual diet during treatment. The decisive point is to follow the schedule to the end: ceftazidime should be continued until the prescription is finished, even if you feel better, because stopping too early or skipping doses may leave the infection incompletely treated and encourage bacterial resistance.

Pharmacologically, ceftazidime acts quickly and briefly: its plasma half-life is about 1.9 hours after intravenous administration, which justifies repeated injections during the day. It binds little to blood proteins, less than 10 percent, and therefore circulates largely in free form. The liver does not transform it: it is eliminated almost exclusively by the kidney, through glomerular filtration, and 80 to 90 percent of the dose is found unchanged in the urine within 24 hours. This renal elimination explains the attention given to kidney function.

The effects reported in trials generally remain uncommon. At the injection site, phlebitis or inflammation affects about 1 patient in 69. On the skin and general condition, itching, a rash or fever occur in about 2 percent of patients. On the digestive side, diarrhoea concerns about 1 patient in 78 and nausea about 1 in 156. Persistent or severe diarrhoea should be reported without delay.

Abnormalities sometimes appear on blood tests: eosinophilia in about 1 patient in 13, a positive Coombs test without haemolysis in about 1 in 23, thrombocytosis in about 1 in 45, as well as transient rises in liver enzymes, AST, ALT, LDH, GGT and alkaline phosphatase. Like almost all antibiotics, ceftazidime can also cause Clostridioides difficile diarrhoea, sometimes up to two months after treatment is stopped: diarrhoea that occurs later should not be neglected.

Cephalosporins can lower prothrombin activity, a key clotting protein. Now this protein, like several clotting factors, depends on vitamin K to be active. The nutrition-type effect documented with ceftazidime therefore passes through this vitamin, by way of the clotting factors that need it.

This risk is not the same for everyone. Monitoring is recommended in the most exposed patients: kidney or liver failure, poor nutritional status, prolonged antimicrobial treatment. In them, a supply of vitamin K may be indicated. Food, rich in green vegetables and fermented foods, remains a simple way to maintain this intake day to day.

Several combinations call for caution. The risk of kidney toxicity increases when ceftazidime is combined with aminoglycosides or with potent diuretics such as furosemide. Chloramphenicol can oppose the action of beta-lactams, including ceftazidime. Finally, it can distort certain urine glucose tests based on copper reduction, Clinitest, Benedict’s solution or Fehling’s solution, by giving false positives: enzymatic glucose-oxidase tests are preferable.

Laboratory follow-up is organised mainly around the kidney. Renal function must be monitored and the dosage adjusted in case of renal failure, because an accumulation of the product exposes the patient to neurotoxicity: seizures, non-convulsive status epilepticus, encephalopathy, or even coma. This monitoring becomes all the more important when ceftazidime is combined with an aminoglycoside or a potent diuretic, situations that together weigh on the kidney.