1. Stubenrauch, James M. senior editor


What if more prudent antibacterial use isn't always enough to prevent the spread of resistance?


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The mutations that make bacteria resistant to antibiotics reduce the organisms' overall fitness. This "fitness cost" means that the energy spent on defending against antimicrobial medications makes the bacterium less competitive in other ways.


Efforts to slow the emergence of resistance through more prudent antibiotic use are rooted in the assumption that, in the absence of antibiotics, these resistant, less-fit bacteria will be unable to compete with sensitive but highly fit bacterial strains and will die off. Eventually, as this line of thinking goes, the bacterial population will revert to its original antibiotic-sensitive state. But what if this assumption isn't always correct?


A growing body of evidence suggests that, at least in some cases, other mutations occur in resistant bacteria, helping them compensate for the fitness costs of resistance.1 These resistant bacteria achieve an intermediate level of overall fitness and are better able to compete with antibiotic-sensitive strains. When this occurs, resistant strains of bacteria can survive even in the absence of antibiotics.


One implication of these findings is that, even with better prescribing practices and treatment compliance, it may be difficult to prevent resistant strains of bacteria from spreading. And even bacteria that haven't acquired resistance to antibiotics can contribute to treatment failure.


Noninherited resistance, or resistance because of phenotypic characteristics, is less well known and understood than acquired resistance, but recent research indicates that it too may be a significant factor in some treatment failures.2, 3


Even when an infection is successfully treated with an antibiotic, the medication plays only a supportive role in effecting a cure. Many other factors of the host, such as age, general health, and genetic characteristics, also come into play. Likewise, in treatment failure, factors such as the host's immune response may be more determinative of the outcome than the damage done directly by bacterial toxins.


Bacteria that are genetically sensitive to a given antibiotic can still survive in its presence, depending on the physiologic state of the bacterial cells and the physical structure of the bacterial population. For example, bacteria are usually most susceptible to antibiotics while they divide, and some bacterial cells may not be dividing or may reproduce too slowly to be affected by the medication. In other cases, a growing mass of bacteria can form a structure called a biofilm, in which some bacterial cells can be embedded too deeply to be reached by the diffusing antibiotic. Therefore, noninherited resistance may well prolong infections, make infections more difficult to treat, and promote acquired resistance.


For more on these topics, see the work of Emory University biologist Bruce R. Levin:


James M. Stubenrauch, senior editor




1. Levin BR, et al. Compensatory mutations, antibiotic resistance and the population genetics of adaptive evolution in bacteria. Genetics 2000;154(3):985-97. [Context Link]


2. Levin BR, Rozen DE. Non-inherited antibiotic resistance. Nat Rev Microbiol 2006;4(7):556-62. [Context Link]


3. Levin BR. Microbiology. Noninherited resistance to antibiotics. Science 2004;305(5690):1578-9. [Context Link]