Cefotaxime

Cefotaxime is a third-generation cephalosporin. It is a bactericidal antibiotic, which means it kills the bacterium rather than simply slowing its multiplication. Its action targets the bacterial wall, the rigid envelope that protects the cell and gives it its shape. By disrupting the building of this wall, it leaves the bacterium unable to withstand its internal pressure, and the cell eventually bursts.

In detail, cefotaxime binds to bacterial enzymes called penicillin-binding proteins, or peptidoglycan transpeptidases. These enzymes normally carry out the cross-linking of peptidoglycan, that is, the weaving of the mesh that makes up the wall. Once they are blocked, the wall no longer holds and the bacterium dies. In the body, the molecule is converted into desacetyl-cefotaxime, a metabolite that is also active and works in synergy with the parent molecule. Given intravenously, cefotaxime crosses the blood-brain barrier, the boundary that protects the brain, which explains its value in meningitis.

Cefotaxime covers a broad range of bacterial infections. It treats pneumonia and other lower respiratory tract infections, gonorrhoea, meningitis, as well as abdominal, gynaecological, skin, bone and joint infections. It also acts on urinary tract infections and on bloodstream infections. This wide spectrum makes it a treatment of choice for situations that are often severe and managed in hospital.

Resistance remains the main obstacle to its effectiveness. Some bacteria produce enzymes called beta-lactamases, capable of hydrolysing the molecule and neutralising it before it can act. Others modify their penicillin-binding proteins, the very target of the drug, so that it no longer attaches to them. This is why cefotaxime is reserved for documented or strongly suspected bacterial infections, never for a viral infection against which it would have no effect.

Cefotaxime is given only by injection, intravenously or intramuscularly, from a powder reconstituted just before use. There is no oral form, tablet or syrup, so the question of taking it with or apart from meals does not arise. The treatment is most often given by a healthcare professional. An intravenous injection should never last less than three minutes, in order to avoid reactions linked to too rapid an administration.

The dosing schedule is tight: cefotaxime is given every six to eight hours, for example two grams every six to eight hours in severe infections. This rhythm is explained by its short elimination half-life, of about one hour, which causes blood concentrations to fall quickly. After 500 mg or 1 g intramuscularly, peak serum levels reach 11.7 and 20.5 micrograms per millilitre respectively. Taking the doses regularly maintains an effective concentration throughout treatment, which must be carried through to the end even when symptoms improve, and never stopped on one’s own initiative.

The adverse effects of cefotaxime are for the most part uncommon. Local reactions at the injection site, such as inflammation, affect about 4.3 % of patients. Hypersensitivity reactions, with rash, itching, fever or eosinophilia, concern about 2.4 % of patients. Gastrointestinal disorders, colitis, diarrhoea, nausea or vomiting, occur in about 1.4 % of the people treated. Below the 1 % mark are drops in certain white blood cells, neutropenia and leukopenia, headaches and transient rises in liver enzymes.

One signal deserves particular vigilance: Clostridioides difficile diarrhoea. It has been reported with almost all antibacterials, including cefotaxime, because they upset the balance of the intestinal flora. Loose or bloody stools, accompanied by cramps or fever, call for medical advice without delay. This picture may appear during treatment or in the weeks following its discontinuation.

Two combinations require attention. Probenecid reduces the clearance of cefotaxime by about 50 %, which increases its blood concentrations and may strengthen its effects. Aminoglycosides, another family of antibiotics, can potentiate the toxicity of cefotaxime for the kidney when they are given together: it is then recommended to separate the injections and to monitor kidney function.

Follow-up therefore largely concerns the kidney. The dose must be reduced when creatinine clearance drops below 20 mL/min/1.73 m², and kidney function is monitored in the elderly as well as in people with renal impairment. A final point concerns salt: cefotaxime is a sodium salt and provides about 50.5 mg, or 2.2 mEq, of sodium per gram of active ingredient. This load is taken into account at high doses or in a person on a low-sodium diet.