Chemotherapy of bacterial infections. Part II.

Antibiotics – after-effects:

Origin of drug resistance: intrinsic - inherent, natural acquired nongenetic -lack of active replication -loss of the specific target structure (L-forms) -infection ocurring at sites where antimicrobials are excluded or not active

genetic - chromosomal resistance: mutation  resistant mutants selection o stable o allow vertical transmission of resistance only (descending) o allow no horizontal transmission: not transferable from one bacterium to another o these genes cause intrinsic resistance

Macrolide-Lincosamide- Streptogramin Resistance The MLS group: macrolides, lincosamides and streptogramins (A and B); resistance - due to efflux, target modification, drug enzymatic modification. In staphs, erythromycin resistance is caused by the erm gene coding an enzyme which modifies the ribosome NONE of these antibiotics may bind to the ribosome. If the erm gene product is constitutively produced, testing will find the staph resistant to all of the MLS antibiotics. If the erm gene product is inducibly produced, it will only be expressed when the organism is exposed to a macrolide C 14 and C 15, but not C 16 and ketolides.

Acquired Resistance to Aminoglycosides mainly enzymatic drug modification Kan HC Gen HC - HLAR E. faecalis IntermediateIntermediateSynergy with B-lactam and Kan or Gen ResistantResistantNo synergy with B- lactam and Kan or Gen ResistantIntermediateNo synergy with B- lactam and Kan

Glycopeptide resistance GISA, VISA glycopeptide, vancomycin intermediate susceptible Staphylococcus aureus Enterococci have natural susceptibility to vancomycin, except E. casseliflavus and E. galinarum (natural resistance to vancomycin).vanAvanBvanC  vanA confers high level resistance to vancomycin  vanB confers moderate level resistance to vancomycin  vanC causes intrinsic vancomycin resistance in E. gallinarum and E. casseliflavus VRE (Vancomycin Resistant Enterococci) refers to E.fecalis or E.faecium, which are normally sensitive to vancomycin. Vancomycin resistance in these organisms is due to the acquisition of vanA or vanB.