Education And Debate

The origins and molecular basis of antibiotic resistance

BMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7159.657 (Published 05 September 1998) Cite this as: BMJ 1998;317:657
  1. Peter M Hawkey, professor
  1. Department of Microbiology, and Antimicrobial Research Centre, University of Leeds, Leeds LS2 9JT

    We frequently refer to bacteria as being resistant to antibiotics, but rarely do we consider what that means. Even the most resistant bacterium can be inhibited or killed by a sufficiently high concentration of antibiotic; patients, however, would not be able to tolerate the high concentration required in some cases. Bacterial species vary tremendously in their susceptibility to an antibiotic — for example, most strains of Streptococcus pneumoniae in Britain are inhibited by 0.01 mg/l of benzylpenicillin (the minimum inhibitory concentration), whereas for Escherichia coli 32-64 mg/l are required to inhibit growth, a level which cannot be achieved in the human body. This introduces the concept of clinical resistance, which is dependent on outcome and is all too often ignored. Clinical resistance is a complex concept in which the type of infecting bacterium, its location in the body, the distribution of the antibiotic in the body and its concentration at the site of infection, and the immune status of the patient all interact.

    Summary points

    • Antibiotic resistance should be defined in terms of clinical outcomes, not laboratory methods

    • Resistance occurs by means of four main mechanisms — more than one may be present in a single bacterium

    • Resistance mechanisms have probably evolved from genes present in organisms producing antibiotics

    • Resistance genes occur not only in bacteria that carry disease but also in commensal bacteria, to which we are continuously exposed and which are found in food, the environment, and animals

    • The plethora of genetic mechanisms for evolution and reassortment of antibiotic resistance genes ensures that useful genes will be disseminated rapidly

    • Action must be taken to slow the rate of evolution and spread of antibiotic resistance genes, in which the biggest single factor is the amount of antibiotics used in human medicine and agriculture

    Mechanisms of antibiotic resistance in bacteria

    The many mechanisms that bacteria exhibit to protect …

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