Cefepime

Cefepime belongs to the cephalosporin family and acts in a bactericidal way: it does not merely slow bacteria down, it kills them. Its target is the wall that surrounds and protects every bacterium. This wall is made of peptidoglycan, a rigid mesh that the bacterium must build continuously in order to survive and divide. By attacking its manufacture, the antibiotic strikes a vital structure.

Inside the bacterium, cefepime binds to specific targets, the penicillin-binding proteins, abbreviated as PBPs. These are the proteins that assemble the peptidoglycan. By binding to them, the antibiotic blocks the construction of the wall, so that the bacterium, deprived of its solid envelope, can no longer withstand its own internal pressure and dies. Cefepime binds only weakly to blood proteins, around 20 %, and this proportion does not vary with the dose.

Cefepime is reserved for serious infections, often managed in hospital. It treats pneumonia, urinary tract infections including pyelonephritis, which affects the kidney itself, skin infections and complicated infections of the abdomen. In the latter case, it is combined with metronidazole to cover other bacteria that cefepime does not reach on its own.

It also holds a special place in neutropenic patients, whose immune defenses have collapsed, for example during chemotherapy. In these patients, a simple fever can herald a severe infection even before the microbe has been identified. Cefepime then serves as first-line empirical treatment, given quickly and with a broad spectrum, while the diagnosis is being clarified.

Cefepime is not swallowed. It is given only by injection: as an infusion into a vein over about 30 minutes, or as an injection into a muscle. The usual rhythm is one administration every 8 to 12 hours. There is therefore no tablet to take and no timing linked to meals: the care team manages the schedule and the regularity, which is never changed on one’s own initiative.

What happens to the drug in the body dictates a major precaution. Its half-life is short, about 2 hours in a healthy person, which justifies repeated doses. Above all, it is eliminated almost entirely by the kidney: nearly 85 % of the dose is found unchanged in the urine. When the kidneys work poorly, the drug builds up in the body, and the dose must be reduced to avoid toxic effects.

Most of cefepime’s effects remain uncommon and were quantified in the trials. In more than 3,000 North American patients, the most frequent abnormality was a positive Coombs test without hemolysis, in 16.2 %: a laboratory reaction that most often causes no blood disorder. A reaction at the injection site occurred in 3 % of patients, with phlebitis in 1.3 % of cases, and a skin rash in 1.1 %.

At the highest doses, 2 g every 8 hours, the figures rise a little: rash 4 %, diarrhea 3 %, nausea 2 %, then vomiting, itching, fever and headache around 1 %. On the laboratory side, a drop in phosphorus is seen in 2.8 % of patients, a rise in transaminases (ALT 2.8 %, AST 2.4 %), eosinophilia 1.7 % and coagulation tests that are sometimes prolonged (aPTT 1.6 %, prothrombin time 1.4 %). These abnormalities guide monitoring.

Two more serious situations deserve particular vigilance. The first is neurological: cases of encephalopathy, seizures and nonconvulsive status epilepticus have been reported, sometimes fatal. They mainly affect patients with kidney failure who received an unadjusted dose, which is a reminder of why adjustment to kidney function is central. Confusion, unusual drowsiness or abnormal movements should alert the care team.

The second situation concerns the intestine. Like any antibiotic, cefepime can upset the flora and promote Clostridioides difficile colitis, which ranges from simple diarrhea to pseudomembranous colitis, potentially fatal. This disorder can appear up to two months after the end of treatment. Persistent or severe diarrhea, even after the antibiotic is stopped, should therefore be reported without delay.

Certain combinations call for close monitoring. Combined with an aminoglycoside or with a powerful diuretic such as furosemide, cefepime increases the risk of kidney toxicity, which makes it necessary to check kidney function. Furthermore, like other cephalosporins, it can lower prothrombin activity, one of the pillars of coagulation. This risk grows in the event of kidney or liver failure, poor nutritional status or prolonged antibiotic treatment.

Laboratory monitoring is organized around these risks: kidney function, prothrombin time in fragile patients, with administration of vitamin K if necessary, and the Coombs test. One practical detail matters in the laboratory: cefepime can wrongly turn some urinary glucose tests positive, hence the preference for glucose oxidase methods. This framework of monitoring makes it possible to use the drug safely.