Cefuroxime (axetil)

Cefuroxime axetil is an antibiotic in the beta-lactam family, more precisely a second-generation cephalosporin. Its action is bactericidal: it kills bacteria rather than merely slowing their growth. The core of the molecule, the beta-lactam ring, binds to enzymes in the bacterial wall called penicillin-binding proteins, or PBPs. By binding to them, it blocks transpeptidase, the enzyme that assembles the wall.

The bacterial wall is made of peptidoglycan, a rigid mesh whose strands must be linked together, a process called cross-linking, in order to hold. By blocking transpeptidase, cefuroxime prevents this cross-linking: the bacterium can no longer build or repair its wall, and it eventually lyses. One asset of this molecule is its stability against certain beta-lactamases, the enzymes that some bacteria produce to destroy beta-lactams. Cefuroxime remains active where older antibiotics are broken down.

Cefuroxime axetil covers a wide range of common infections of the respiratory tract and the ear, nose and throat: pharyngitis and tonsillitis, acute otitis media, acute maxillary sinusitis, and acute exacerbations of chronic bronchitis. It also treats uncomplicated skin infections and uncomplicated urinary tract infections. The spectrum chosen targets the most likely organisms depending on the site of infection.

Two more specific indications complete the list: uncomplicated gonorrhoea and early Lyme disease, at the erythema migrans stage, the skin lesion that appears after a tick bite. The choice of antibiotic depends on the suspected organism, the affected site and the patient’s condition. It is the doctor who determines the indication and sets the dose.

The cefuroxime axetil tablet is better absorbed with a meal. On an empty stomach, its absolute bioavailability is 37%; taken after food, it rises to 52%. Taking the tablet during or just after a meal therefore markedly increases the amount of antibiotic that passes into the blood.

Cefuroxime is eliminated quickly: its mean half-life is 1.2 to 1.3 hours. To maintain an effective concentration throughout the day, it is usually taken twice a day, at regular intervals. It should not be stopped on one’s own as soon as one feels better: completing the prescribed course limits the risk of relapse and of selecting resistant bacteria.

With the usual multiple-dose regimens, the most frequent effects involve the digestive tract: diarrhoea in about 4% of people, nausea and vomiting in 3%. Then come eosinophilia, that is a rise in a type of white blood cell, in 1%, and transient elevations of liver enzymes: AST in 2%, ALT in 2%, LDH in 1%. These laboratory abnormalities generally resolve after the end of treatment.

Treatment of early Lyme disease, which is longer with a 20-day course, is accompanied by higher frequencies: diarrhoea in 10.6%, Jarisch-Herxheimer reaction in 5.6%, vaginitis in 5.4%. The Jarisch-Herxheimer reaction is a temporary worsening of symptoms at the start of treatment, linked to the massive destruction of bacteria. It is not an allergy and resolves on its own within one to two days.

Like any broad-spectrum antibiotic, cefuroxime does not target only the bacteria responsible for the infection: it also alters the gut flora. Yet part of the body’s vitamin K, vitamin K2 or menaquinone, is made in the gut by these bacteria, which convert the vitamin K1 provided by the diet. By disrupting the flora, an antibiotic can in theory reduce this production. This link is plausible, but it has not been specifically quantified for cefuroxime.

Certain cephalosporins that carry an N-methyl-thiotetrazole or NMTT side chain, such as cefotetan, cefamandole, cefmetazole, cefoperazone and moxalactam, interfere with vitamin K metabolism and can cause hypoprothrombinaemia and bleeding. Cefuroxime does not have this NMTT chain. A prolongation of prothrombin time, or Quick time, has been reported after marketing, in pharmacovigilance, without a quantified frequency.

Two interactions are worth knowing. Probenecid slows the renal elimination of cefuroxime: it increases its area under the curve by 50% and its maximum concentration by 21%, so the combination is not recommended. Conversely, medicines that reduce stomach acidity decrease the absorption of cefuroxime axetil. It is better to take it at least 1 hour before or 2 hours after an antacid, and to avoid H2 blockers as well as proton pump inhibitors.

Cefuroxime is eliminated essentially by the kidneys: about 50% of the dose is found unchanged in the urine within 12 hours. Kidney function therefore governs the dose adjustment, and it is checked in case of renal impairment. Monitoring also covers digestive tolerance and, if needed, liver enzymes. Any severe or prolonged diarrhoea during or after treatment should be reported to the doctor.