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Common Mechanisms of Antibiotic Resistance

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Mechanism	Example
Decreased outer membrane permeability	Loss of outer membrane D2 porin in imipenem-resistant Pseudomonas aeruginosa
Enzymatic inactivation	Production of beta-lactamases that inactivate penicillins in penicillin-resistant Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli Production of aminoglycoside-inactivating enzymes in gentamicin-resistant enterococci
Changes in target	Decreased affinity of penicillin-binding proteins for beta-lactam antibiotics (eg, in methicillin-resistant Staphylococcus aureus [MRSA] and Streptococcus pneumoniae with reduced penicillin susceptibility) Decreased affinity of methylated ribosomal RNA target for macrolides, clindamycin, and quinupristin in MLSB-resistant Decreased affinity of methylated ribosomal RNA target for macrolides, clindamycin, and quinupristin in MLSB-resistantS. aureus Decreased affinity of altered cell wall precursor for vancomycin (eg, in Decreased affinity of altered cell wall precursor for vancomycin (eg, inEnterococcus faecium) Decreased affinity of DNA gyrase for fluoroquinolones in fluoroquinolone-resistant S. aureus
Increased antibiotic efflux pump	Increased efflux of tetracycline, macrolides, Increased efflux of tetracycline, macrolides,clindamycin, or fluoroquinolones (eg, in S. aureus)
Bypass of antibiotic inhibition and target overproduction	Development of bacterial mutants that can subsist on products (eg, thymidine) present in the environment, not just products synthesized within the bacteria or may overproduce the drug target, thus minimizing its effects on that pathway (eg, in certain bacteria exposed to trimethoprim/sulfamethoxazole)Development of bacterial mutants that can subsist on products (eg, thymidine) present in the environment, not just products synthesized within the bacteria or may overproduce the drug target, thus minimizing its effects on that pathway (eg, in certain bacteria exposed to trimethoprim/sulfamethoxazole)
MLSB = macrolide, lincoside, streptogramin B.