The May issue of Clinical Microbiology and Infection published a review by French researchers to discuss the theoretical and clinical aspects of the administration of β-lactam antibiotics by continuous infusion.

The concept of using PI β-lactam antibiotics is based on the pharmacodynamics of this class of antimicrobial agents. Unlike aminoglycosides and fluoroquinolones having a dose-dependent activity, the bactericidal activity of β-lactams depends on the time of exposure of the antibiotic. The main parameter determining the clinical effectiveness of β-lactam antibiotics is the period of time during which the concentration of the drug at the site of infection exceeds its minimum inhibitory concentration (MIC) relative to the pathogen (t is greater than the MIC). The results of various studies in vivo have shown that this time interval should represent at least 30 to 40% of the total dosing interval, regardless of where the focus of the 'infection. This interval increases with the patient's initial serious condition (neutropenia, cystic fibrosis, stay in the intensive care unit and the intensive care unit), and also depends on the type of infectious agent (longer in infections caused by Pseudomonas aeruginosa, Gram-positive cocci).

For the eradication of certain types of microorganisms (for example, Pseudomonas aeruginosa), it is necessary to maintain the concentration of the antibiotic in the blood serum several (4-5) times higher than the MIC of this antibiotic against the pathogen. The severity of the disease, the presence of neutropenia, the location of the focus of infection and the sensitivity of the microorganism also affect this parameter.

The number of studies on the efficacy of PI β-lactam antibiotics is limited. In clinical situations, this technique has been used mainly in several patient categories: patients in the intensive care and intensive care unit, patients with neutropenia and cystic fibrosis. In almost all studies, the equal clinical efficacy of continuous infusion and conventional intravenous administration has been demonstrated, and only one has shown slightly higher PI efficacy. At the same time, in all studies, the pharmacodynamic advantages of PI, guaranteeing the achievement of the maximum indicator t greater than MPC or t greater than 4x MPC, were noted.

Despite the fact that there are still no convincing data from clinical studies proving the superiority of PI β-lactam antibiotics compared to their traditional administration, certain arguments militate in favor of the introduction by continuous infusion. The main advantages of PI are the possibility of obtaining an optimal pharmacodynamic profile, a more precise dose selection in patients with altered or difficult to predict pharmacokinetic parameters, a therapeutic correction according to certain pharmacodynamic parameters (residual concentration of drug in blood serum), relative ease of administration, prevention of overdoses.

One of the most important benefits of PI is to reduce the risk of resistant strains. Unlike PI, the traditional method of administering antibiotics is accompanied by a decrease in the concentration of the drug in the blood between injections, which can theoretically contribute to the selection of strains resistant to antibiotics, and the keeping the concentration of β-lactams in the plasma at a constantly high level prevents the appearance of resistant microorganisms.

To optimize the administration of β-lactam antibiotics by PI, the authors propose to use the initial loading dose of the drug to reach its bactericidal concentration from the first minutes of treatment. Monitoring the concentration of β-lactam antibiotic in the plasma 5 hours after the start of administration makes it possible to adjust the dose and to individualize the treatment of the infection in the patients.

According to the researchers, cefepime can be considered as the optimal β-lactam antibiotic for administration by PI. Its spectrum of activity is broader compared to the third generation cephalosporins, it penetrates faster through the membrane of gram-negative bacteria, has a greater affinity for penicillin-binding proteins, is less sensitive to he action of β-lactamases (mainly the chromosomal β-lactamases of the mutants repressed in a stable manner), is stable for a long time in various solutions. With cefepime, the risk of antibiotic resistance in microorganisms is lower than with other cephalosporins.

The review authors proposed the following regimen for cefepime during PI in adult patients, suitable for most clinical situations: bolus administration of a loading dose of 2 g followed by an infusion of 4 g / day. with dose adjustment, if necessary, based on the determination of the serum antibiotic concentration.