Imipenem

Imipenem is an antibiotic from the carbapenem family, a subgroup of the beta-lactams. Its bactericidal action comes from inhibiting the synthesis of the bacterial cell wall. It binds to penicillin-binding proteins, the PBPs, enzymes that assemble peptidoglycan, the framework that gives the wall its rigidity. Its strongest affinity is for several of these proteins. The lethal effect stems from binding to PBP 2 and 1B, which blocks transpeptidation, the step that locks the wall’s mesh together. Deprived of this framework, the bacterium can no longer withstand its own internal pressure and dies.

The medicine combines imipenem with cilastatin, which has no antibacterial activity of its own. Cilastatin inhibits dehydropeptidase-I in the kidney, the enzyme that would otherwise break down imipenem, and thereby maintains active urinary concentrations. Imipenem also shows strong stability against beta-lactamases, both the penicillinases and the cephalosporinases produced by Gram-positive and Gram-negative bacteria. This resistance to bacterial defense enzymes broadens its spectrum of action.

Imipenem-cilastatin treats serious bacterial infections. The indications cover the lower respiratory tract, urinary, intra-abdominal and gynecological infections, septicemia, bone and joint infections, skin and soft tissue infections, as well as endocarditis. This wide range corresponds to a broad-spectrum antibiotic, reserved for situations where the infection is severe or difficult to treat.

Its use most often takes place in a hospital setting, sometimes when other antibiotics are not enough or the germ is resistant. The medicine is not indicated for meningitis: its diffusion and profile are not suited to that location. The choice of imipenem therefore addresses a specific infection, identified by the doctor, and is not a first-line prescription for common infections.

Imipenem-cilastatin is given by intravenous infusion, never as a rapid direct injection into the vein. A 500 mg dose is infused over 20 to 30 minutes, a 1000 mg dose over 40 to 60 minutes, generally every 6 to 8 hours. An intramuscular administration every 12 hours exists for certain forms. The rhythm of the infusions is set by the care team and closely monitored during treatment.

Because the medicine is given by injection, it does not interact with meals: the usual diet continues, unless the doctor advises otherwise. The plasma half-life is about one hour for both imipenem and cilastatin, and close to 70 percent of imipenem is recovered in the urine within ten hours. The regularity of the doses keeps the antibiotic at an effective level. The treatment is not shortened or interrupted on one’s own initiative, even if the signs of infection ease, because stopping early promotes relapse and resistance.

In adults, the adverse effects reported in clinical trials and their frequencies are as follows: phlebitis or thrombophlebitis at the infusion site in 3.1 percent of cases, nausea 2.0 percent, diarrhea 1.8 percent, vomiting 1.5 percent, skin rash 0.9 percent, fever 0.5 percent, seizures 0.4 percent and hypotension 0.4 percent. Digestive disorders and the local venous reaction are among the most frequently reported effects.

The risk of seizures depends on the individual context. In infants from birth to 3 months, they were reported with a frequency of 5.9 percent, well above the 0.4 percent in adults, and central nervous system involvement is among the monitored effects. Severe diarrhea, with watery or bloody stools, may also occur up to two months, or even longer, after the treatment is stopped: this antibiotic-associated colitis calls for urgent medical advice.

Several combinations call for caution. With valproic acid or divalproex, imipenem-cilastatin causes the valproate concentration to fall below the therapeutic threshold, which exposes the person to breakthrough seizures: the combination is not advised. Generalized seizures have been reported with ganciclovir, whose concomitant use should be avoided unless the benefit outweighs the risk. Probenecid, for its part, increases the plasma concentrations and lengthens the half-life of imipenem, so that giving them together is not recommended.

The treatment is accompanied by laboratory monitoring. The trials showed electrolyte variations: a drop in serum sodium, a rise in potassium and chloride. Elevations of liver enzymes are also seen, ALT, AST, alkaline phosphatase and bilirubin, along with eosinophilia, a Coombs test that may become positive, as well as a rise in urea and creatinine. These parameters justify regular blood tests, which make it possible to adjust care and to monitor the kidney and the liver.