Antibiotics (Properties, Administration, Interactions) - Posokhova K.A., Viktorov O.P. 2005

Penicillins

Depending on the method of production and THE SPECTRUM OF antimicrobial activity, penicillin drugs can be divided into the following groups:

I. Natural (biosynthetic) Penicillins: benzylpenicillin (penicillin G), phenoxymethylpenicillin (penicillin V), benzylpenicillin procaine (procaine benzylpenicillin), bicillin-1 (benzathine benzylpenicillin), bicillin-3, bicillin-5.

II. Semisynthetic penicillins:

1) antistaphylococcal penicillinase-resistant penicillins - isoxazolyl penicillins (oxacillin, cloxacillin, dicloxacillin, flucloxacillin, nafcillin, methicillin);

2) broad-spectrum penicillins - aminopenicillins (ampicillin and its derivatives - amoxicillin, pivampicillin, bacampicillin, talampicillin, etc.);

3) antipseudomonal penicillins - carboxypenicillins (carbenicillin, ticarcillin);

4) antipseudomonal penicillins - ureidopenicillins (azlocillin, mezlocillin, piperacillin, carindacillin, apalcillin, sulbenicillin, carfecillin);

5) amidinopenicillins (mecillinam - amidinocillin and its derivatives);

6) beta-lactamase inhibitor-combined penicillins - «protected» penicillins (amoxicillin/clavulanate, ampicillin/sulbactam, ticarcillin/clavulanate, piperacillin/tazobactam).

MECHANISM OF ACTION. The antimicrobial effect of all beta-lactam Antibiotics, and penicillins in particular, is based on their ability to bind to transpeptidases and Carboxypeptidases (known as penicillin-binding Proteins, or PBPs). These Enzymes catalyze a critical step in the synthesis of peptidoglycan, the primary structural component of The Cell wall in both gram-positive and gram-negative microorganisms. Disruption of peptidoglycan synthesis renders the bacterial membrane unable to withstand the osmotic gradient between the intracellular environment and the extracellular milieu, causing the Bacteria to swell and lyse. Consequently, beta-lactam antibiotics exert their bactericidal effect specifically on actively multiplying microorganisms, as this is when new cell wall assembly takes place. The activity of beta-lactam antibiotics is determined by several key factors: the degree of affinity for various types of PBPs; The ability to penetrate the outer structures of microorganisms and enter host Cells; and resistance to Hydrolysis by beta-lactamases. The capsule and peptidoglycan layer of gram-positive microorganisms do not impede the penetration of beta-lactams to PBPs. However, in gram-negative bacteria, these agents can only cross the lipopolysaccharide membrane via porin channels. The poor intracellular penetration of beta-lactams into host cells explains their ineffectiveness against intracellular pathogens such as Chlamydia, Legionella, Brucella, and Rickettsia. Mycoplasmas, which lack peptidoglycan in their cell walls, exhibit intrinsic resistance to beta-lactam antibiotics. The comparative susceptibility of microorganisms to penicillins is presented in Table 4.

Class="center">Table 4. Comparative susceptibility of microorganisms to penicillins (S. N. Kozlov, L. S. Strachunsky, 2000; with modifications)