Resistant Bacteria: What are the Facts?

March 1, 2001

Resistant Bacteria: What are the Facts?

By Rhonda D. Jones, BS, RM

Theemergence of antibiotic-resistant bacteria linked with the overuse and misuse ofantibiotics has become a legitimate public health concern. Scientists, infectioncontrol practitioners, epidemiologists, consumers, and regulators have askedwhether there might be similar effects from the use of other antimicrobialingredients such as those contained in disinfectants, antiseptics, andsanitizers.1 Unlike antibiotics, current scientific evidence does notdemonstrate a link between the use of antimicrobial-biocidal products and theemergence of biocide or antibiotic resistance.2,3 However, there areimportant differences between antibiotics and disinfecting cleaning products orantiseptics that need to be understood. In this article, the "FrequentlyAsked Questions" format is used to explain a problem that has beenexacerbated 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 resistancemight also manifest itself with other antibacterial agents such as those used indisinfectants, sanitizers, and antiseptics.4,5 Because antibioticresistance is at least partly due to over-use of antibiotics, one response is touse antibiotics less often and only when absolutely necessary. The same actionshould not be taken with disinfectants and sanitizers, as restricting their usemay do more harm than good. Antibiotics are different and work by differentmechanisms. Antibiotics typically have a single target and a very specific modeof action, thus interacting with a microbe similar to a lock and key to achieveits microbicidal action, whereas biocides have multiple targets and modes ofaction.6 Antibiotics and biocides are as different from one anotheras 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 thatinhibit 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 toperform their function. Just as minor changes in a lock make a key useless, asingle mutation in an organism can make it resistant to an antibiotic.Penicillin is a good example. Widespread use began circa 1945, and resistancewas detected within a decade. Conversely, many antiseptics and disinfectantshave been used for over 100 years without loss of effectiveness.6

Q: Is a highly specific cellular target the only reason why bacteriabecome resistant to antibiotics?

A: No. There is another important factor that influences the "lock andkey" mechanism. Because antibiotics are used on live people, there is anupper limit to the concentration that can be used without harming the patient.This level is often close to the minimum inhibitory concentration (MIC). The MICis the lowest concentration of an agent that will inhibit the organism. Forantibiotics, the MIC correlates to the appropriate therapeutic dose. If anorganism adapts such that it tolerates a concentration of the antibiotic that isslightly 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 correlateor 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 theirattack. They oxidize, denature, or attack in multiple ways. This makes thedevelopment of resistance much more difficult and would certainly require morethan a single mutation. Furthermore, since they are used on inanimate surfacesrather than in vivo, the biocidal agents in disinfectants are used atconcentrations that exceed the MIC by a factor of 100-10,000 or more. Thus, adecrease in susceptibility by a factor of 2 or 3, while very important to anantibiotic, would be of little relevance to the effectiveness of a disinfectant.2,3,6In the analogy, if you use a sledge hammer to open a door, minor changes in thelock will not make much difference to the effectiveness of the hammer.

Q: Genetic changes that result in antibiotic resistance have beendemonstrated. Is the same true for antibacterial/antimicrobial/biocidal agents?

A: Bleach and phenolics have been used since the 1800s, and quaternaryammonium compounds since at least 1935.7 The many decades and highvolumes of use have provided ample opportunity for bacteria to adaptgenetically; however, disinfectant failure due to genetic adaptation has notbeen reported.2 In contrast, the evolution of antibiotic-resistantbacteria rendered penicillin therapeutically useless within a decade of itsintroduction.6 In addition, germicides have been shown to be equallyeffective 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 oursurroundings.8-11

Q: What about biofilm and other ways bacteria resist attack byantimicrobials?

A: It is easy to confuse intrinsic and extrinsic resistance or reducedsusceptibility. Intrinsic resistance is the result of a natural or"built-in" characteristic of a strain or species, such as, thepermeability barriers exhibited by mycobacteria, Gram negative bacteria, andspores. Extrinsic or acquired resistance is the result of the acquisition of newgenetic information or mutation of the existing genome, for example, whenplasmids carrying the genes for antibiotic resistance are acquired by abacterium. Lack of reports about an increase in acquired resistance todisinfectants and sanitizers does not mean that bacteria lack a means of evadingthese products. The ability of bacteria to form a biofilm (e.g., toiletbowl slime) is a good example. Effectively, the bacteria immerse themselves in aprotective "castle" that the biocidal agent may not be able topenetrate although the bacteria themselves may be just as susceptible.Interestingly, this scenario is more likely to result from lack of cleaning ordisinfecting 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 resultedin development of genetically adapted resistance on the part of bacteria.2More importantly, there is ample evidence that hands are a major vector in thetransmission of bacteria. Thus, antiseptics play an important role as part of aninfection control program designed to reduce pathogen transmission.12

Rhonda D. Jones is the president of Scientific and RegulatoryConsultants, 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.

Terminology

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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