Antimicrobial toxicity

Howard, R., Topical antimicrobial toxicity, Arch. Surg., March 1985, 120, 3, 267-270. 

W Lineaweaver, R Floward, D Soucy, S McMorris, J Freeman, C Crain, J Robertson, T Rumley. Topical antimicrobial toxicity. Arch Surg 120 267-270, 1985. 

Tetracyclines are produced by various Streptomyces strains and are extensively applied in human and veterinary medicine. They display a broad spectrum of antimicrobial activity in combination with low toxicity and can be applied orally. The most commonly prescribed tetracycline drugs are tetracycline itself and oxytetracycline, an oxygenated derivative, which are directly isolated from fermentation liquors, and doxycycline whose partial synthesis from oxy-... 

Sodium trichloroacetate [650-51-17, C2Cl202Na, is used as a herbicide for various grasses and cattails (2). The free acid has been used as an astringent, antiseptic, and polymerisation catalyst. The esters have antimicrobial activity. The oral toxicity of sodium trichloroacetate is quite low (LD q rats, 5.0 g/kg). Although very corrosive to skin, trichloroacetic acid does not have the skin absorption toxicity found with chloroacetic acid (28). 

Several antimicrobials have been banned or severely restricted by the EPA based on documented or suspected toxicity or environmental problems. Others have been discontinued in the face of testing costs required by the EPA reregistration program mandated by the Pederal Insecticide, Pungicide, and Rodenticide Act (PIPRA) of 1988 (10). Some of the significant products that have become obsolete are 2,4,5-trichlorophenol/P3 -5 3 -47, sodium... 

Ivermectin is the catalytic reduction product of avermectin, a macroHde containing a spiroketal ring system. Two other related antibiotics having significantly different stmctural features and biological properties, moxidectin and milbemycin oxime, were more recentiy introduced into the market. Although these compounds have no antimicrobial activity, they are sometimes referred to as antibiotics because they are derived from fermentation products and have very selective toxicities. They have potent activity against worms or helminths and certain ectoparasites such as mites and ticks. 

Both chloramphenicol and thiamphenicol cause reversible bone marrow suppression (9). The irreversible, often fatal, aplastic anemia, however, is only seen for chloramphenicol (9). This rare (1 in 10,000—45,000) chloramphenicol toxicity has been linked to the nitroaromatic function (1,9). Thiamphenicol, which is less toxic than chloramphenicol in regard to aplastic anemia, lacks potency as can be seen in Table 1, and thiamphenicol has never found much usage in the United States. An analogue of thiamphenicol having antimicrobial potencies equivalent to chloramphenicol was sought. Florfenicol (2) was selected for further development from a number of closely related stmctures. 

Antimicrobial Activity. The elfamycins antimicrobial specificity and lack of toxicity in animals can be explained in view of species-dependent specificity of elfamycin binding to EE-Tu. Inefficient cellular uptake or the presence of a nonresponding EE-Tu were cited as responsible factors for the natural resistance in Halohacterium cutiruhrum (67), Lactobaci//us brevis (68), and in actinomycetes (5,69). The low activity of elfamycins against S. aureus was also attributed to an elfamycin-resistant EE-Tu system (70). However, cross-resistance with other antibacterial agents has not been observed (71). 

Because of lower toxicity and high antimicrobial activity, the phenols having the greatest use in disinfections are o-phenylphenol (Dowicide 1) [90-43-7J, C 2H qO i9-benzyl-/)-chlorophenol (Santophen 1) [120-32-1J, C H CIO and -Z fZ-amylphenol [80-46-6] They possess similar general... 

Further developments have brought forth polymeric quats having antimicrobial properties (158—160). Different kinds of polyquats have been described with molecular weight from 2,000 to 60,000 (153). Polymeric quats have two characteristics that make them uniquely different from the monomeric quats. One is the absence of foaming, even at high concentrations. The other is their remarkably low toxicity in skin and eye irritation tests and... 

Whereas tests (186) indicated that ampholytes were effective in skin cleansing for preoperative use, for wound cleansing, and as an antiseptic in the oral cavity (187), as well as other medical appHcations, the food and beverage industries have proved to be the principal employers of these compounds. Ampholytes are used as sanitizers and disinfectants, not as food preservatives. Low toxicity, absence of skin irritation, and noncorrosiveness, along with antimicrobial activity, has given ampholytes acceptance in dairies, meat plants, and the brewing and soft drink industries. These disinfectants have been manufactured and distributed in Europe and Japan, but not in the United States. 

Relatively high levels of copper in pig diets can improve nutritional performance due to the antimicrobial effects in the gastrointestinal tract. However, if land is fertilized with dung from pigs and subsequently grazed by sheep, the sheep may suffer copper toxicity because of their increased susceptibility to copper compared with pigs. Similarly, pig diets would be unacceptable for sheep because of the high levels of copper therein. 

The phenomenon of bacterial resistance to antibiotics was already known by the pioneers of the era of antibiotics, like Paul Ehrlich, who coined the term selective toxicity as the basic principle of antimicrobial therapeutics, as well as Gerhard Domagk, the inventor of the sulfonamide drugs, and Sir Alexander Fleming, the discoverer of the penicillins. When penicillin G was introduced into clinical practice in 1944, as many as 5% of the isolates of Staphylococcus aureus were resistant to penicillin, while 5 years later the percentage was 50%. 

As is apparent from the above information, there is no ideal disinfectant, antiseptic or preservative. All chemical agents have their limitations either in terms of their antimicrobial activity, resistance to organic matter, stability, incompatibility, irritancy, toxicity or corrosivity. To overcome the limitations of an individual agent, formulations consisting of combinations of agents are available. For example, ethanol has been combined with chlorhexidine and iodine to produce more active preparations. The combination of chlorhexidine and cetrimide is also considered to improve activity. QACs and phenols have been combined with glutaraldehyde so that the same effect can be achieved with lower, less irritant concentrations of glutaraldehyde. Some... 

Examples of preservatives are phenylmercuric nitrate or acetate (0.002% w/v), chlorhexidine acetate (0.01 % w/v), thiomersal (0.01 % w/v) and benzalkorrium chloride (0.01 % w/v). Chlorocresol is too toxic to the comeal epithehum, but 8-hydroxyquinoline and thiomersal may be used in specific instances. The principal considerahon in relation to antimicrobial properties is the activity of the bactericide against Pseudomonas aeruginosa, a major source of serious nosocomial eye infections. Although benzal-konium chloride is probably the most active of the recommended preservatives, it cannot always be used because of its incompatibility with many compounds commonly used to treat eye diseases, nor should it be used to preserve eye-drops containing anaesthetics. Since benzalkonium chloride reacts with natural mbber, silicone or butyl rabber teats should be substituted. Since silicone mbber is permeable to water vapour, products should not be stored for more than 3 months after manufacture. As with all mbber components, the mbber teat should be pre-equilibrated with the preservative prior to... 

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