Meropenem

Meropenem belongs to the carbapenem family, a subgroup of the beta-lactams. It destroys bacteria, an action described as bactericidal, by blocking the construction of their wall. In practice, it binds to the penicillin-binding proteins (PBPs), in particular PBPs 2, 3 and 4 in Escherichia coli and Pseudomonas aeruginosa. These proteins assemble the envelope of the bacterium: by neutralising them, it prevents the bacterium from building its wall, which eventually gives way.

Two properties explain its broad range of action. It penetrates the wall of most Gram-positive and Gram-negative bacteria. It also stays stable against hydrolysis by most beta-lactamases, the enzymes that bacteria produce to deactivate beta-lactams. This resistance keeps it active where other antibiotics lose their activity.

Meropenem targets serious bacterial infections, most often managed in hospital. Its indications include complicated skin and soft tissue infections, complicated intra-abdominal infections, and bacterial meningitis in children from 3 months of age. Its broad spectrum lets it cover a wide variety of bacteria, which matters when the germ responsible has not yet been identified.

It is one of the reserve antibiotics, brought in when the infection is severe or when the bacteria resist other treatments. The choice of the molecule rests with the physician, who decides according to the infected site, the severity of the condition and the germ identified. This strategic place explains why it is not used for ordinary infections.

Meropenem is administered only intravenously, never by mouth. The usual schedule is one administration every 8 hours, that is three times a day. Each dose is given as an infusion of about 15 to 30 minutes, or as a slow injection, a bolus of 3 to 5 minutes. Because it is injected directly into the blood, taking it does not depend on meals, and its binding to plasma proteins stays low, around 2 %.

The close spacing of the doses is due to its pharmacology: its plasma half-life is close to one hour in adults with normal kidney function, so the concentration must be renewed often to remain effective between two doses. The treatment most often takes place in a hospital setting, under nursing supervision. It is not stopped on one’s own initiative, even when the symptoms improve, because stopping early favours relapse and resistance.

Clinical trials have quantified the frequency of adverse effects. The most common are anaemia in 5.5 % of patients, diarrhoea in 4.8 %, nausea or vomiting in 3.6 % and inflammation at the injection site in 2.4 %. Next come headache in 2.3 %, skin rash in 1.9 %, constipation in 1.4 % and itching in 1.2 %.

Laboratory abnormalities sometimes accompany the treatment. A drop in blood potassium may be seen, known as hypokalaemia, a decrease in platelets, a thrombocytopenia reported in patients with kidney failure without clinical bleeding, a rise in eosinophils and variations in the blood cell lines. These parameters are read on a blood test, which makes it possible to spot them and adjust the management.

The central nervous system calls for particular attention. Seizures and other neurological effects have been reported, with a seizure rate of 0.7 % in immunocompetent adults treated for infections located outside the central nervous system. This risk is concentrated in people with pre-existing neurological disorders, bacterial meningitis or kidney failure.

Like almost all antibiotics, meropenem can trigger diarrhoea linked to the bacterium Clostridium difficile, which takes advantage of the imbalance in the gut flora caused by the treatment. Its intensity varies greatly, from mild diarrhoea to a colitis that can become serious. Diarrhoea that persists or worsens, during or after the treatment, should be reported to the physician.

Two interactions call for vigilance. Combined with valproic acid or divalproex, two antiepileptics, meropenem causes their blood concentrations to fall, which can reopen the door to epileptic seizures: in this situation, an antibiotic other than a carbapenem is preferable. Probenecid, for its part, slows the renal excretion of meropenem and raises its concentrations, so this combination is not recommended.

Monitoring is organised around three areas. Kidney function is checked to adjust the dose, an adjustment needed as soon as creatinine clearance falls to 50 mL/min or less, because the kidney eliminates about 70 % of the dose unchanged within 12 hours. Added to this are neurological monitoring, because of the risk of seizures, and follow-up of the complete blood count and platelets during prolonged treatments.