Antibiotics and Antibiotic Resistance

The level of antibiotic resistance of the gut flora of pigs has been found to be influenced by factors other than the inclusion of antibiotics in the diet such factors include the herd environment, history and the opportunity for cross-contamination. 

Cross-contamination between animal species may be a factor in the spread of resistance. Flint and Stewart showed that a rumen strain (46/5) of the Gram 

Cansunar, A. J. Richardson, G. Wallace and C. S. Stewart, FEMS Microbiol. Lett., 1990,70,157. 

Oi skov and F. Orskov, in Molecular Pathogenesis of Gastrointestinal Infections, ed. T. Wadsti oin, P. FI. Makela, A.-M. Svennerholm and FI. Wolf-Watz, Plenum, New York, 1991, pp. 49-53. 

Drugs and Dietary Additives, Their Use in Animal Production 

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Baquero F, Martinez JL, Canton R (2008) Antibiotics and antibiotic resistance in water environments. Curr Opin Biotechnol 19(3) 260-265... 

Kim S, Aga DS (2007) Potential ecological and human health impacts of antibiotics and antibiotic-resistant bacteria from waste water treatment plants. J Toxicol Environ Health B CritRev 10(8) 559-573... 

Bugg TDH and Walsh CT (1992) Intracellular steps of bacterial cell wall peptidoglycan biosynthesis enzymology, antibiotics, and antibiotic resistance. Nat Prod Rep 9, 199-215. 

Bugg TDH, Walsh CT. intracellular sreps of bacterial cell wall pepiidoglycan biosynthesis. Entymology, antibiotics and antibiotic resistance. Nat Prod Rep 1992 6 199-215. 

Kim, S., and D. S. Aga. Potential Ecological and Human Health Impacts of Antibiotics and Antibiotic-Resistant Bacteria from Wastewater Treatment Plants. Journal of Toxicology and Environmental Health, Part B Critical Reviews 10 (2007) 559-73. 

Tolypomycin Y (48) shows strong antibacterial activity against gram-positive bacteria and Neisseriagonorrheae. When adininistered by subcutaneous, intraperitoneal, and intravenous routes, tolypomycin Y is effective in mice infected with Staphylococcus aureus Streptococcuspyrogenes and Diplococcuspneumoniae. Cross-resistance is observed with rifampicia but not with other antibiotics. Resistance to tolypomycin Y develops rapidly. The bioactivity of tolypomycin R... 

Preventive medicine through vaccination continues to be the most cost-effective pubHc health practice, even with the drastic advance in modern medicine. Mass vaccination programs have eradicated smallpox from the earth. The World Health Organization (WHO) has a major campaign underway to eradicate poHo by the year 2000. The development of vaccines has saved millions of Hves and prevented many more from suffering. However, there are stiU many diseases without effective vaccines, such as malaria. With the recent emergence of antibiotic-resistance strains and exotic vimses, an effective vaccine development program becomes a top priority of pubHc health poHcy. 

Bacteria produce chromosomady and R-plasmid (resistance factor) mediated P-lactamases. The plasmid-mediated enzymes can cross interspecific and intergeneric boundaries. This transfer of resistance via plasmid transfer between strains and even species has enhanced the problems of P-lactam antibiotic resistance. Many species previously controded by P-lactam antibiotics are now resistant. The chromosomal P-lactamases are species specific, but can be broadly classified by substrate profile, sensitivity to inhibitors, analytical isoelectric focusing, immunological studies, and molecular weight deterrnination. Individual enzymes may inactivate primarily penicillins, cephalosporins, or both, and the substrate specificity predeterrnines the antibiotic resistance of the producing strain. Some P-lactamases are produced only in the presence of the P-lactam antibiotic (inducible) and others are produced continuously (constitutive). 

One approach to combating antibiotic resistance caused by P-lactamase is to inhibit the enzyme (see Enzyme inhibition). Effective combinations of enzyme inhibitors with P-lactam antibiotics such as penicillins or cephalosporins, result in a synergistic response, lowering the minimal inhibitory concentration (MIC) by a factor of four or more for each component. However, inhibition of P-lactamases alone is not sufficient. Pharmacokinetics, stability, ability to penetrate bacteria, cost, and other factors are also important in determining whether an inhibitor is suitable for therapeutic use. Almost any class of P-lactam is capable of producing P-lactamase inhibitors. Several reviews have been pubUshed on P-lactamase inhibitors, detection, and properties (8—15). 

Antibiotic Resistance. Figure 1 According to Bush, Jacoby and Medeiros [2] four molecular classes of (3-lactamases can be discriminated based upon biochemical and molecular features. Classes 1, 2, and 4 included serine-proteases, while metallo enzymes are included in class 3. The substrate spectrum varies between different subclasses and the corresponding genes can be part of an R-plasmid leading to a wider distribution or are encoded chromosomally in cells of specific species. 

The glucocorticoids are contraindicated in patients widi serious infections, such as tuberculosis and fungal and antibiotic-resistant infections. 

Numerous studies confirmed ubiquity of several antibiotics (i.e., ofloxacin, trimethoprim, roxythromycin, and sulfamethoxazole) in sewage influent, though at low ng level [8, 13, 14]. However, even at very low concentrations they can have significant ecotoxicological effects in the aquatic and terrestrial compartment [15, 16]. Indiscriminate or excessive use of antibiotics has been widely blamed for the appearance of so-called super-bugs that are antibiotic-resistant. It is of crucial importance to control their emissions into the environment through more cautious utilization and monitoring outbreaks of dmg-resistant infections. 

P. acnes is an anaerobic diphteroid that populates the androgen-stimulated sebaceous follicles and is a normal constituent of the cutaneous microflora even if acne is not infectious, the commensal P. acnes acts in acne pathogenesis. Three pieces of evidence support the role of P. acnes in acne 1) higher counts of P. acnes in individuals with acne than in those without acne 2) correlation between the reduction of P. acnes counts and the clinical improvement of the disease and 3) correlation between development of acne and presence of antibiotic-resistant P. acnes organisms. P. acnes products mediate the formation of comedones and contribute to their rupture, leading to extrusion of... 

Bacterial plasmids are small, circular, duplex DNA molecules whose natural function is to confer antibiotic resistance to the host cell. Plasmids have several properties that make them extremely useful as cloning vectors. They exist as single or multiple copies within the bacterium and replicate independently from the bacterial DNA. The complete DNA sequence of many plasmids is known hence, the precise location of restriction enzyme... 

For many years, it was thought that binary fission was the only method of reproduction in bacteria, but it is now known that there are three methods of reproduction in which genetic exchange can occur between pairs of cells, and thus a form of sexual reproduction is exhibited. These processes are transformation, conjugation and transduction. Further details ofthese processes as they affect antibiotic resistance will be found in Chapter 9. 

Bacterial resistance to antibiotics has been recognized since the first drugs were introduced for clinical use. The sulphonamides were introduced in 1935 and approximately 10 years later 20% of clinical isolates of Neisseria gonorrhoeae had become resistant. Similar increases in sulphonamide resistance were found in streptococci, coliforms and other bacteria. Penicillin was first used in 1941, when less than 1 % of Staphylococcus aureus strains were resistant to its action. By 1947,3 8% of hospital strains had acquired resistance and currently over 90% of Staph, aureus isolates are resistant to penicillin. Increasing resistance to antibiotics is a consequence of selective pressure, but the actual incidence of resistance varies between different bacterial species. For example, ampicillin resistance inEscherichia coli, presumably under similar selective pressure as Staph, aureus with penicillin, has remained at a level of 30-40% for mai years with a slow rate of increase. Streptococcus pyogenes, another major pathogen, has remained susceptible to penicillin since its introduction, with no reports of resistance in the scientific literature. Equally, it is well recognized that certain bacteria are unaffected by specific antibiotics. In other words, these bacteria have always been antibiotic-resistant. 

Antibiotic resistance is classified into two broad types intrinsic and acquired. 

Acquired resistance. This occurs when bacteria which were previously susceptible become resistant, usually, but not always, after exposure to the antibiotic concerned. Intrirrsic resistance is always chromosomally mediated, whereas acquired resistance may occirr by mutations in the chromosome or by the acquisition of genes coding for resistance ftom an external source normally via a plasmid or transposon. Both types are clinically important and can result in treatment failure, although acquired resistance is more of a threat in the spread of antibiotic resistance (Russell Chopra 1996). 

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