β-lactams
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penicillins
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cephalosporins
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carbapenems
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monobactams
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Interference with bacterial cell wall synthesis |
Production of β-lactamases or extended-spectrum β-lactamases (ESBLs), which hydrolyze and inactivate drug
Change/down-regulation of porins (access points throughbacterial cell membrane,), prohibiting drug entry
Change in configuration of Penicillin binding site (such as encoded by mecA gene in MRSA)
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Glycopeptides
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Interference with bacterial cell wall synthesis |
MRSA: accumulation of cell wall fragments which thicken wall and are capable of binding vancomycin extracellularly; change to several metabolic pathways
Enterococcus and MRSA: acquisition of genes which alters peptide synthesis, reducing glycopeptide affinity
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Macrolides, Chloramphenicol, Clindamycin, Quinupristin-dalfopristin, Linezolid |
Inhibition of protein synthesis- bind to 50S ribosomal subunit |
Multi-drug efflux pump systems which pump drug out of cell
Prevention of leader single amino acid substitutions in the chromosomal dihydrofolate reductase peptide synthesis, stopping transcriptional or translational attenuation
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Aminoglycosides, Tetracyclines |
Inhibition of protein synthesis- bind to 30S ribosomal subunit |
Expression of aminoglycoside-modifying enzymes
Prevention of leader peptide synthesis, stopping transcriptional or translational attenuation
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Fluoroquinolones |
Interference with bacterial DNA synthesis |
Upregulating production of enzymes inactivating the antimicrobial agent
Mutations in DNA gyrase and topoisomerase enzymes involved in RNA production
Drug efflux pump systems which pump drug out of cell
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Rifampin |
Interference with bacterial RNA synthesis |
Mutation or duplication of drug target, modification cell permeability |
Trimethoprim-sulfamethoxazole |
Inhibition of metabolism (bacterial folate synthesis) |
Single amino acid substitutions in the chromosomal dihydrofolate reductase (as in S. pneumoniae) leading to decreased binding of drug |
Polymixins, Daptomycin |
Disruption of bacterial membrane structure |
Mutations altering cell surface charge |