Τόμος 6 (1988) – Τεύχος 4 – Άρθρο 2- Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 6 (1988) – Issue 4 – Article 2 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

6: 215-226 (1988)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

6: 215-226 (1988)

Resistance describes the condition in which invading microbial cells are invulnerable to the chemotherapeutic agent. It may be inherent (or natural), i.e. the drug is not interfering with some pro­cess essential for a particular pathogen due to its natural make-up (e.g. Gram-negative bacteria and methicillin), and acquired, i.e., in the presence of the antibiotics, the inva­ding cell alters its genetic structure to pro­duce a resistant phenotype by natural sele­ction of particular mutants. There may be transfer of genetic material (DNA which codes for a particular phenotype) by release to and uptake from the environment (trans­formation), by the intermediation of a bacte­riophage (transduction) or by a resistance transfer factor (RTF, conjugation). The geno­type having modified, bacteria may be resi­stant to antimicrobial drugs through 7 main phenotypic mechanisms: (a) changes in the target site resulting in lowering the drug ‘s affinity for its ribosomal binding site by loss or other alteration of the S12 protein of the 30S subunit (e.g. streptomycin), of the L4 or L12 protein of the 50S subunit (e.g. erythromycin), of the 16 protein of the 50 S subunit (e.g. chloramphenicol); (b) reduction in cellular permeability to antibiotic, so that it cannot enter to exert its effects (e.g. streptomycin with the tubercle bacillus; sulphonamides, beta-lactams or tetracycli­nes with other organisms); (c) conversion of an active drug to a non-toxic derivative-inactivation (e.g. penicillins by β-lactamase or amidase; streptomycin by adenyl transfe­rase; chloramphenicol by acetyl transfera­se); (d) increased production of a biochemi­cal intermediate that is competitively anta­gonised by a drug (e.g. sulfonamide and PABA); (e) bypass of an antibiotic-sensitive step; (f) increased levels of inhibited enzymes; (g) production of modified alloste­ric enzymes.

1. Δ.Δ. Bαρώνος: Ιατρική Φαρμακολογiα, 5η έκδοση, σελ. 496. Εκδόσεις Γ.K. Παρισιάνος, Αθήνα, 1987
2. Brumfitt, W., Hamilton-Miller, J.M.T.: Principles and practice of antimicrobial chemotherapy. In: Drugs Treat­ment (T.M. Speight, ed.), 3rd ed.. p. 1207, Auckland, 1987
3. Sande, M.A., Mandell, G.L.: Chemotherapy of microbial diseases. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 7th ed., p. 1068, 1097, 1117, 1140, 1153, 1172, 1180
4. L.F. Bryan (ed.): Antimicrobial Drug Resistance. Academic Press, London, 1984
5. Wehrli, W.: Rifampin: mechanisms of action and resistan­ce. Rev. Infect. Dis. 5 (Suppl.): 5407 (1983)