Harrold Final Exam Drug Resistance Mechanisms

Penicillins and Cephalosporins Bacterial Resistance Mechanisms

Enymatic inactivation by beta-lactamases

Decreased affinity of transpeptidase for the drug

Abnormalities of autolysin activity by the bacteria

Inability to penetrate to the site of action in gram negative bacteria (more of a spectrum issue than resistance)

Colistimethate Bacterial Resistance Mechanisms

Alterations of the outer membrane of the bacterial cell

Decreased concentrations due to an efflux pump

Sulfonamides Bacterial Resistance Mechanisms

Decreased affinity of the target enzyme, dihydropteroate synthase, for the drug

Acquisition of an active efflux pump or mechanism

Development of an alternative metabolic pathway to produce either dihydropteroate or folic acid

Increased production/uptake of PABA

Fluoroquinolones Bacterial Resistance Mechanisms

Gene mutations of gyrA and/or gyrB enzymes hinder the binding of the drug to its binding site (does not affect normal enzyme function)

Aminoglycoside Bacterial Resistance Mechanisms

Acquisition of genes that alter the structure of the drug, decreasing its ability to bind to its target

• Three types of resistance genes:

  • Aminoacetyltransferases (adds acetyl group)

  • Phosphotransferases (adds phosphate)

  • Nucleotidyltransferases (adds adenosine)

Failure of the drug to be transported across the cytoplasmic membrane due to loss of outer membrane porins

Alteration of the ribosomal target sites through production of 16S rRNA methyltransferases

Upregulation of efflux pumps

Tetracycline Bacterial Resistance Mechanisms

Decreased accumulation as a result of either decreased transport into the bacterial cell or acquisition of an energy-dependent efflux pathway

Production of a ribosomal protection protein that displaces the drug from its target

Enzymatic inactivation of the drug

Macrolide Bacterial Resistance Mechanisms

Drug efflux by an active pump mechanism

Ribosomal protection by inducible or constitutive production of methylase enzymes (modifies the ribosomal target to decrease drug binding)

Hydrolysis of drug by esterases produced by enterobacteriaceae

Chloramphenicol Bacterial Resistance Mechanisms

Some bacteria acquire acetyl transferase enzymes that chemically inactivate the drug by preventing it from binding to its target

Oxazolidinones (-zolid) Bacterial Resistance Mechanisms

Altered binding site caused by mutations in chromosomal genes encoding 23S rRNA or ribosomal proteins (L3 and L4)