Resistance selection pressure

Approximately a third of patients who attend their GP with a sore throat want or expect a prescription for antibiotics. There is evidence to suggest that prescribing antibiotics increases re-attendance rates for further episodes of sore throat and exposes patients to side-effects. Indiscriminate use of antibiotics also increases antibiotic resistance selection pressure (National Prescribing Centre, 2003). 

Step 1. Determine the lightest weight of casing to resist collapse pressure for a setting depth of 12,000 ft. Because the maximum collapse pressure is (12,000)(0.52) = 6,240 psi, select N-80, 29-lb/ft casing with collapse pressure resistance of 7,020 psi. (Note assumed safety factor for collapse = 1.0.) This is Section 1. 

Short replication cycles that may be completed within a few hours, a large amount of viral progeny from one infected host-cell, as well as the general inaccuracy of viral nucleic acid polymerases result in an evolution occurring in fast motion, allowing rapid adaptation of viruses to selective pressures (see chapter by Boucher and Nijhius, this volume). Generalizing, it can be stated that any effective antiviral therapy will lead to the occurrence of resistance mutations. A well studied example... 

As explained in Chapter 1, the toxicity of natural xenobiotics has exerted a selection pressure upon living organisms since very early in evolutionary history. There is abundant evidence of compounds produced by plants and animals that are toxic to species other than their own and which are nsed as chemical warfare agents (Chapter 1). Also, as we have seen, wild animals can develop resistance mechanisms to the toxic componnds prodnced by plants. In Anstralia, for example, some marsupials have developed resistance to natnrally occnrring toxins produced by the plants upon which they feed (see Chapter 1, Section 1.2.2). 

It is only very recently that organic componnds synthesized by humans have begun to exert a selection pressure upon natural populations, with the consequent emergence of resistant strains. Pesticides are a prime example and will be the principal subject of the present section. It should be mentioned, however, that other types of biocides (e.g., antibiotics and disinfectants) can produce a similar response in microbial populations that are exposed to them. 

Interestingly, it appears that earlier selective pressure by dichlorodiphenyl trichloroethene (DDT) raised the frequency of kdr genes in the population before pyrethroids came to be used. Thus, some pyrethroid resistance already existed before these insecticides were applied in the field. 

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. 

Resistance to quinolones by efflux has been described in Staph, aureus and Proteus mirabilis. This gene has been designated nor A in Staph, aureus and is homologous to membrane transport proteins coupled to the electromotive force. These proteins have the ability to remove small amounts of quinolone from cells normally and nor A may have arisen as a result of mutations under selective pressure from quinolone use, resulting in a transport protein with increased affinity for these agents. 

The function of DMEs is also thought to include the detoxification of dietary products and the evolution of plant metabolites, including drugs [11]. The selective forces responsible for the maintenance of different alleles in different populations may include the fact that one allele may enable improved rates of implantation, improved prenatal growth and development, improved postnatal health in response to dietary or environmental selective pressures or improved resistance to bacteria, viruses or parasites [11, 14]. Allele frequencies may also reflect ethnic dietary differences that have evolved over thousands of years [15]. 

We have, therefore, been able to indirectly assess the importance of three factors involved in chlorinated alicyclic insecticide resistance in mosquitofish disposition, metabolism and target site sensitivity. In a highly polluted environment in which mosquitofish have been placed under severe selective pressures by chronic exposure to insecticides, the system of metabolism appears to be of little significance in resistance the... 

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