Antiseptic Resistance: What Do We Know and What Does It Mean?

Clinical Laboratory Science, Summer 2005 by Sheldon, Albert T Jr

Biocides (antiseptics, disinfectants, preservatives, sterilants) are used in clinical medicine as intervention strategies that prevent the dissemination of nosocomial pathogens. Biocides are also used for personal hygiene and to prevent cross-contamination of food-borne pathogens in homes, restaurants, day care centers, and nursing homes. However, laboratory evidence has emerged suggesting that the mechanism of nonsusceptibility to biocides may counter-select for resistance to antibiotics. Nature conserves successful survival strategies. Using existing mechanisms of resistance to antibiotics and their means of dissemination, microorganisms have adopted this same survival strategy for biocide nonsusceptibility. These mechanisms are intrinsic in nature or are acquired. The consequences to biocide efficacy in the clinical setting are probably not significant from the biocide perspective. But, the selective pressure biocides exert on bacterial populations that have mechanisms of resistance similar to those to antibiotics or that are also substrates for antibiotic resistance is of concern.

ABBREVIATIONS: CM = cytoplasmic membrane; LPS = lipopolysaccharides; MRSA = methicillin-resistant Staphylococcus aureus; OM = outer membrane; PG = peptidoglycan; PMF = proton motive force; RND = resistance-nodulation-division.

INDEX TERMS: biocide, biofilm, efflux, mechanism of action.

Clin Lab Sci 2005;18(3):181

LEARNING OBJECTIVES

1. Identify the mechanism of action and targets of antiseptics.

2. Discuss the mechanisms of resistance to antiseptics.

3. Describe the intrinsic and acquired mechanisms of antiseptic nonsusceptibility.

4. Discuss the mechanisms used to disseminate resistant determinants of antiseptics.

Semmelweis's mandate that physicians wash examining fingers with chlorine to prevent puerperal (childbed) fever provided the scientific evidence to justify the use of biocides in the practice of medicine.1 Biocides (antiseptics, disinfectants, preservatives, and sterilants) are now an integral component in the practice of clinical medicine and serve primarily to prevent the dissemination of nosocomial pathogens in the hospital environment.2 Antiseptics are used as surgical hand scrubs, healthcare personnel hand washes, preoperative skin preparations, and total body washes. Biocides are also used in vascular catheter-care site preparation and are impregnated into catheters to prevent catheter related blood stream infections.3-5 Disinfectants are used to decontaminate or sterilize medical instruments and patient care items, while preservatives are used to prevent the growth of organisms in multi-use medical products, although not always successfully.5,7 Biocides are also used in homes, restaurants, day care centers, and nursing homes for personal hygiene and to prevent cross-contamination of food-borne pathogens.8,9 Intended use of biocides in these settings are not unlike those in the clinical setting: to prevent the dissemination of potential pathogens. However, as with antibiotics, increased use of biocides may contribute to the emergence and/or selection of pathogens less susceptible to biocides and resistant to antibiotics.10,11 These observations suggest that antiseptics and antibiotics have common mechanisms of action and possible resistance.

The present article discusses the mechanisms by which biocides exert their biological effect, mechanisms that influence their biological activity, and the possible consequences of these mechanisms in the clinical setting. Although the use of biocides in homes, restaurants, day care centers, and nursing homes is not discussed, the principles discussed regarding the use of biocides in clinical environments are generally applicable to the other environments since their strategic use is the same: the prevention of the dissemination of pathogens.12-14

BIOCIDE MECHANISMS OF ACTION

Biocide mechanisms of action are determined using the same methods used in the evaluation of the action of antibiotics. These methods include evaluation of the effects on intracellular components such as interactions with macromolecules and their biosynthetic processes, inhibition of oxidative phosphorylation, and interference with enzymes and electron transport. They also include effects upon membranes such as microscopic examination of cells exposed to biocides; effects on model membranes; and examination of uptake, lysis, and leakage of intracellular components.15 Since the methods used to assess the mechanism of action include evaluation of their effects on the membrane and intracellular components, these targets are used ill our discussion. Although the antimicrobial spectrum of activity and efficacy of biocides is well documented, complete characterization of their mechanisms of action, especially at low concentrations, is lacking. Detailed discussions of the mechanisms of action of biocides are presented elsewhere.15,16

The cell wall of gram-positive bacteria is composed of a cytoplasmic membrane (CM), which overlies the cytoplasm and a thick peptidoglycan (PG) outer layer. Gram-negative bacteria add an outer membrane (OM), composed of lipopolysaccharides (LPS), lipoproteins, and proteins, separated from the CM by a periplasmic space.17