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Intrinsic Resistance

Intrinsic resistance is the innate ability of a bacterial species to resist activity of a particular antimicrobial agent through its inherent structural or functional characteristics, which allow tolerance of a particular drug or antimicrobial class.  This can also be called “insensitivity” since it occurs in organisms that have never been susceptible to that particular drug. Such natural insensitivity can be due to:

  • lack of affinity of the drug for the bacterial target
  • inaccessibility of the drug into the bacterial cell
  • extrusion of the drug by chromosomally encoded active exporters
  • innate production of enzymes that inactivate the drug


Table 2.2 Examples of intrinsic resistance and their respective mechanisms (From Forbes et al., 1998, Giguere et al., 2006)





Anaerobic bacteria


Lack of oxidative metabolism to drive uptake of aminoglycosides

Aerobic bacteria


Inability to anaerobically reduce drug to its active form

Gram-positive bacteria

Aztreonam (a beta-lactam)

Lack of penicillin binding proteins (PBPs) that bind and are inhibited by this beta lactam antibiotic

Gram-negative bacteria


Lack of uptake resulting from inability of vancomycin to penetrate outer membrane

Klebsiella spp.

Ampicillin (a beta-lactam)

Production of enzymes (beta-lactamases) that destroy ampicillin before the drug can reach the PBP targets

Stenotrophomonas. maltophila

Imipenem (a beta-lactam)

Production of enzymes (beta lactamases) that destroy imipenem before the drug can reach the PBP targets.

Lactobacilli and Leuconostoc


Lack of appropriate cell wall precursor target to allow vancomycin to bind and inhibit cell wall synthesis

Pseudomonas aeruginosa

Sulfonamides, trimethoprim, tetracycline, or chloramphenicol

Lack of uptake resulting from inability of antibiotics to achieve effective intracellular concentrations



Lack of sufficient oxidative metabolism to drive uptake of aminoglycosides

All cephalosporins

Lack of PBPs that effectively bind and are inhibited by these beta lactam antibiotics


Clinical implications: Intrinsic Resistance

Knowledge of the intrinsic resistance of a pathogen of concern is important in practice to avoid inappropriate and ineffective therapies. For bacterial pathogens which are naturally insensitive to a large number of classes of antimicrobials, such as Mycobacterium tuberculosis and Pseudomonas aeruginosa, this consideration can pose a limitation in the range of options for treatment and thus consequently further increase the risk for emergence of acquired resistance.



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