The Rotation of Disinfectants Principle: True or False? - Pharmaceutical Technology

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The Rotation of Disinfectants Principle: True or False?
The author defines sanitizers, disinfectants, and antibiotics, and examines the question of whether the rotation of disinfectants is scientifically warranted.

Pharmaceutical Technology
Volume 33, Issue 2, pp. 58-71

CHX at concentrations ≥ 20 μg/mL kills bacteria and yeasts (33). Reduced susceptibility to CHX among gram-positive bacteria is somewhat uncommon but has been reported in S. aureus (34). Conversely, gram-negative bacteria such as E. coli, Salmonella enteritica, Proteus mirabilis, Providencia stuartii, P. aeruginosa, B. cepacia, and S. marcescens (24, 35–39) have frequently shown reduced susceptibility to CHX and, in some cases, resistance at use concentrations. MICs as high as 1600 μg/mL have been reported, especially with strains of Providencia species (40).

Several gram-negative bacteria can be acclimatized to grow at low concentrations of CHX. They sometimes can thrive at or near use concentrations. One example is P. aeruginosa, which was exposed to 5 μg/mL of CHX. As a consequence of the exposure, the bacteria's MIC increased within six days from < 10 to 70 μg/mL (37). A second example is P. stutzeri, which reached a MIC of 50 μg/mL after 12 days of exposure to CHX (37). Wild strains of P. aeruginosa, K. pneumoniae, and A. baumannii grew at 1% CHX, which is within the recommended use concentration as an antibacterial agent.

Benzalkonium chloride (BKC). At low concentration in gram-positive bacteria (e.g., Listeria monocitogenes), BKC works by disrupting the membrane potential and pH gradient across the cellular membrane. At high concentration, BKC completely inhibits acidification and respiration and depletes adenosine triphosphate pools (41). In its mode of action, BKC resembles an antibiotic more than a disinfectant.

Several bacteria have exhibited reduced susceptibility to BKC, either because of intrinsic tolerance or by adaptation. Research indicates that efflux pumps are the major mechanism of adaptation of gram-positive bacteria such as S. aureus, L. monocitogenes, and other species of staphylococci. A strain of P. aeruginosa with resistance to BKC was shown to have defective porins. Hydrophilic molecules of low molecular weight usually can enter microorganisms by means of porins. P. aeruginosa may possess porins that do not function as do those in other bacteria.

A strain of B. cepacia showed a remarkable tolerance to BKC. This strain was isolated from a solution used as a cleansing or germicidal agent for catheters preserved with 0.05% BKC. The B. cepacia strain survived for 14 years in this solution. The strain's tolerance increased in increments of 0.5% to 16% BKC. The bacteria used BKC as a substrate for growth (42).

Development of resistance to disinfectants

True resistance or tolerance to common disinfectants such as chlorine, hydrogen peroxide, iodine, IPA and EA, phenol, and FA has not been documented. Logically, this must be the case because these disinfeectants attack microorganisms in various ways. True resistance or tolerance to antibiotic-like disinfectants (e.g., BKC, CHX, and TLN), however, has been documented empirically and experimentally (23–26, 29–30, 35–39, 42). These disinfectants, along with similar chemical agents, more closely resemble antibiotics than they do common disinfectants. On balance, their modes of action are basically the same as those of antibiotics. Bacteria can therefore develop resistance or tolerance to these agents.

One important mechanism of intrinsic reduced susceptibility and resistance or tolerance to antibiotic-like disinfectants and antibiotics in gram-negative bacteria and mycobacteria is the impermeability of the outer membrane or cell wall to these substances. In addition, many research studies have revealed that efflux pumps, at times with uncommonly wide specificity, contribute to the intrinsic resistance of gram-negative bacteria by removing agents such as detergents, antibiotics, and dyes from the cell (24, 25, 29, 30). An additional mechanism entails using enzymes to degrade harmful substances such as disinfectants and antibiotics. These enzymes can be intra- or extracytoplasmic. Another mechanism is the formation of biofilms. The other known mechanisms, which only apply to antibiotic-like disinfectants and antibiotics, are the modification of the target sites and substitution of susceptible metabolic pathways.


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