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

A microorganism can use any of the above mechanisms or a combination of them. These mechanisms are not new to microorganisms and do not result from the use of disinfectants and antibiotics. Evolution provides microorganisms with the necessary tools to survive in hostile environments. Microorganisms have struggled for food and survival for billion of years. Humans have unwittingly selected the fittest microorganisms through the overuse and abuse of antibiotics and antibiotic-like disinfectants.

Cross-resistance (i.e., tolerance to a toxic substance as a result of exposure to a similarly acting substance) has been proven only for the antibiotic-like disinfectants. Mutant strains of S. aureus that were resistant to BKC showed a higher resistance than their parent strains to various ß-lactam antibiotics and to ofloxacin, a quinolone (43). One strain of Salmonella typhimurium that developed resistance to CHX also became resistant to erythromycin and BKC (24). In the same study, another strain of Salmonella developed a high degree of cross-resistance to other antibiotics and biocides.

Adaptive cross-resistance to BKC, amikacin, and tobramycin also has been documented (44). Exposure of a P. aeruginosa strain susceptible to TLN resulted in a multidrug-resistant bacteria at high frequencies (45). Because of gene mutations, the strain hyperexpressed an efflux-pump system. The MICs of tetracycline, trimethoprim, erythromycin, and gentamicin for the mutants were increased by as much as 500 times. The MIC of ciprofloxacin, a quinolone, was increased 94 times.

Antibiotics

In contrast to disinfectants, antibiotics are substances that are selectively toxic for bacteria. Bactericidal antibiotics kill them, and bacteriostatic antibiotics inhibit their growth without harm to the patient. These substances must act on targets found in bacteria, not in the patient. This characteristic distinguishes antibiotics from disinfectants. Antibiotics work best in conjunction with a healthy immune system to kill infecting bacteria in the host (46).

For antibiotics to be effective, the MIC or MBC must be reached at the site of infection. The pharmacological properties of the antibiotic influence the route and dose to achieve a successful concentration at the site of infection. Antibiotics are divided into several classes, each with its own mode of action. This article only discusses the major classes of antibiotics that are active against bacteria because they provide a good example for comparison with disinfectants.

Antibiotics that bind to the 30S ribosomal subunit. Aminoglycosides. The most common aminoglycosides are streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin, and neomycin, which are bactericidal. They are active against many gram-negative and some gram-positive bacteria, but resistance to them is common.

Their mode of action is twofold. The initial site of action is the outer membrane (OM). Antibiotic molecules create crevices in the OM, resulting in leakage of intracellular contents and enhanced antibiotic uptake (47, 48). Their quick damage to the OM probably contributes to aminoglycosides' bactericidal activity. Second, aminoglycosides irreversibly bind to the 30S ribosomal subunit and freeze the 30S initiation complex (30S–mRNA–tRNA) so that no further initiation can occur (49).

Aminoglycoside resistance results from production of aminoglycoside-modifying enzymes, reduced uptake or decreased cell permeability, and alterations at the ribosomal binding sites. Most resistance to aminoglycosides is caused by bacterial inactivation by intracellular enzymes (50, 51).

Tetracyclines. Tetracycline and doxycycline, the most common examples, are bacteriostatic. Tetracycline's mode of action is to reversibly bind to the 30S ribosome and inhibit the binding of aminoacyl-t-RNA to the 70S ribosome. Tetracyclines' spectrum of activity is broad, but resistance is common. Resistance occurs through ribosomal protection and efflux pumps.

Ribosomal protection results from minor changes in the ribosome that prevent the drug from binding to it and stop the production of new proteins. The bacteria can thus continue as if the drug were not there (52, 53). The second form of resistance, efflux pumps, is especially common in gram-negative bacteria. As the drug enters the cell through its porins, efflux pumps pump it out of the cell (54, 55). Again, the bacterium behaves as if the drug was not present. The net result is that the drug does not inhibit protein production. Cross-resistance, resulting from these two mechanisms, to all of the drugs in the tetracycline class is widespread.


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