Resistant Bacteria: What are the Facts?
By Rhonda D. Jones, BS, RM
The emergence of antibiotic-resistant bacteria linked with the overuse and misuse of antibiotics has become a legitimate public health concern. Scientists, infection control practitioners, epidemiologists, consumers, and regulators have asked whether there might be similar effects from the use of other antimicrobial ingredients such as those contained in disinfectants, antiseptics, and sanitizers.1 Unlike antibiotics, current scientific evidence does not demonstrate a link between the use of antimicrobial-biocidal products and the emergence of biocide or antibiotic resistance.2,3 However, there are important differences between antibiotics and disinfecting cleaning products or antiseptics that need to be understood. In this article, the "Frequently Asked Questions" format is used to explain a problem that has been exacerbated by confusion over terms such as "antimicrobial" and "antibiotic."
Q: Why all the fuss?
A: The concern has been expressed that the problem of antibiotic resistance might also manifest itself with other antibacterial agents such as those used in disinfectants, sanitizers, and antiseptics.4,5 Because antibiotic resistance is at least partly due to over-use of antibiotics, one response is to use antibiotics less often and only when absolutely necessary. The same action should not be taken with disinfectants and sanitizers, as restricting their use may do more harm than good. Antibiotics are different and work by different mechanisms. Antibiotics typically have a single target and a very specific mode of action, thus interacting with a microbe similar to a lock and key to achieve its microbicidal action, whereas biocides have multiple targets and modes of action.6 Antibiotics and biocides are as different from one another as trying to open a door with a key versus a sledge hammer.
Q: What are antibiotics and how do they work?
A: By definition, antibiotics are substances produced by one organism that inhibit the growth of another organism. They have specific cellular targets, e.g., a particular site on an enzyme, into which they fit like a key into a lock to perform their function. Just as minor changes in a lock make a key useless, a single mutation in an organism can make it resistant to an antibiotic. Penicillin is a good example. Widespread use began circa 1945, and resistance was detected within a decade. Conversely, many antiseptics and disinfectants have been used for over 100 years without loss of effectiveness.6
Q: Is a highly specific cellular target the only reason why bacteria become resistant to antibiotics?
A: No. There is another important factor that influences the "lock and key" mechanism. Because antibiotics are used on live people, there is an upper limit to the concentration that can be used without harming the patient. This level is often close to the minimum inhibitory concentration (MIC). The MIC is the lowest concentration of an agent that will inhibit the organism. For antibiotics, the MIC correlates to the appropriate therapeutic dose. If an organism adapts such that it tolerates a concentration of the antibiotic that is slightly above the achievable therapeutic level, then it is often described as "resistant." However, it would be more accurate to describe that as "decreased susceptibility." For biocides, the MIC does not correlate or predict the effective concentration of a product.2
Q: Why are disinfectants and sanitizers like sledge hammers?
A: Biocides used in disinfectants and sanitizers are not specific in their attack. They oxidize, denature, or attack in multiple ways. This makes the development of resistance much more difficult and would certainly require more than a single mutation. Furthermore, since they are used on inanimate surfaces rather than in vivo, the biocidal agents in disinfectants are used at concentrations that exceed the MIC by a factor of 100-10,000 or more. Thus, a decrease in susceptibility by a factor of 2 or 3, while very important to an antibiotic, would be of little relevance to the effectiveness of a disinfectant.2,3,6 In the analogy, if you use a sledge hammer to open a door, minor changes in the lock will not make much difference to the effectiveness of the hammer.
Q: Genetic changes that result in antibiotic resistance have been demonstrated. Is the same true for antibacterial/antimicrobial/biocidal agents?
A: Bleach and phenolics have been used since the 1800s, and quaternary ammonium compounds since at least 1935.7 The many decades and high volumes of use have provided ample opportunity for bacteria to adapt genetically; however, disinfectant failure due to genetic adaptation has not been reported.2 In contrast, the evolution of antibiotic-resistant bacteria rendered penicillin therapeutically useless within a decade of its introduction.6 In addition, germicides have been shown to be equally effective against antibiotic-resistant bacterial strains (e.g., MRSA, VRE, PRSP) and strains exhibiting renewed virulence (e.g., E. coli 0157). Biocides are crucial to reducing the reservoir of such pathogens in our surroundings.8-11
Q: What about biofilm and other ways bacteria resist attack by antimicrobials?
A: It is easy to confuse intrinsic and extrinsic resistance or reduced susceptibility. Intrinsic resistance is the result of a natural or "built-in" characteristic of a strain or species, such as, the permeability barriers exhibited by mycobacteria, Gram negative bacteria, and spores. Extrinsic or acquired resistance is the result of the acquisition of new genetic information or mutation of the existing genome, for example, when plasmids carrying the genes for antibiotic resistance are acquired by a bacterium. Lack of reports about an increase in acquired resistance to disinfectants and sanitizers does not mean that bacteria lack a means of evading these products. The ability of bacteria to form a biofilm (e.g., toilet bowl slime) is a good example. Effectively, the bacteria immerse themselves in a protective "castle" that the biocidal agent may not be able to penetrate although the bacteria themselves may be just as susceptible. Interestingly, this scenario is more likely to result from lack of cleaning or disinfecting rather than excessive use of a biocide.2,6
Q: Is this also true for hand sanitizers?
A: Similarly, there is no evidence that use of hand sanitizers has resulted in development of genetically adapted resistance on the part of bacteria.2 More importantly, there is ample evidence that hands are a major vector in the transmission of bacteria. Thus, antiseptics play an important role as part of an infection control program designed to reduce pathogen transmission.12
Rhonda D. Jones is the president of Scientific and Regulatory Consultants, Inc. in Columbia City, Ind. She would like to acknowledge Sean G. Dwyer, PhD, manager, Chemical Technology and Support, S. C. Johnson & Sons, Inc. for his assistance during the preparation of this manuscript.
For more information, visit the website at www.srcconsultants.com.
For a complete list of references visit, www.infectioncontroltoday.com.
Acquired resistance: Decreased susceptibility or insusceptibility that is the result of genetic changes in a cell due to mutation or the acquisition of extra chromosomal genetic material.
Antimicrobial agent: Any agent that kills or inhibits the growth of microbes.
Antibiotic: A synthetic or naturally derived organic chemical substance that prevents or inhibits the growth of microorganisms, used most often at low concentrations in the treatment of infectious diseases of man, animals, and plants.
Antimicrobial/Antibacterial Soap: A soap or surfactant containing an antimicrobial or antibacterial agent.
Antiseptic: A substance applied topically to living tissue that prevents or inhibits the growth of microorganisms.
Disinfectant: A substance that destroys or eliminates a specific species of infectious or other public health microorganism, but not necessarily bacterial spores, in the inanimate environment.1
Intrinsic resistance: A natural property of an organism resulting in decreased susceptibility.
Plasmid: A mobile, extra chromosomal piece of DNA that is able to replicate within a bacterial cell.
Resistance: A decrease in susceptibility or a lack of susceptibility of a microbe toward an agent.
Resistant: Something that exhibits resistance.
Sanitizer: A substance that reduces the bacterial population in the inanimate environment by significant numbers but does not destroy or eliminate all bacteria or other microorganisms.13
Susceptibility: Describes the degree to which a target organism is affected by an agent. Susceptibility can be measured through a number of standard methods, including broth dilution, agar dilution, or zone of inhibition determinations.
Tolerance: A phenotypic change (i.e., physical change) in the susceptibility of a microbe in a particular setting.
Tolerant: Something that exhibits tolerance.
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