Bacterial resistance, acquired

Resistance to Tetracyclines. The tetracyclines stiU provide inexpensive and effective treatment for several microbial infections, but the emergence of acquired resistance to this class of antibiotic has limited their clinical usehilness. Studies to define the molecular basis of resistance are underway so that derivatives having improved antibacterial spectra and less susceptibiUty to bacterial resistance may be developed. Tetracyclines are antibiotics of choice for relatively few human infections encountered in daily clinical practice (104), largely as a result of the emergence of acquired tetracycline-resistance among clinically important bacteria (88,105,106). Acquired resistance occurs when resistant strains emerge from previously sensitive bacterial populations by acquisition of resistance genes which usually reside in plasmids and/or transposons (88,106,107). Furthermore, resistance deterrninants contained in transposons spread to, and become estabUshed in, diverse bacterial species (106). 

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. 

Bacterial resistance to biocides (Table 13.2) is usually considered as being of two types (a) intrinsic (innate, natural), a natural property of an organism, or (b) acquired, either by chromosomal mutation or by the acquisition of plasmids or transposons. Intrinsic resistance to biocides is usually demonstrated by Gram-negative bacteria, mycobacteria and bacterial spores whereas acquired resistance can result by mutation or, more frequently, by the acquisition of genetic elements, e.g. plasmid- (or transposon-) mediated resistance to mercury compounds. Intrinsic resistance may also be exemplified by physiological (phenotypic) adaptation, a classical example of which is biofilm production. 

Table 13.2 Intrinsic and acquired bacterial resistance to biocides... 

Erythromycin has efficacy similar to tetracycline, but it induces higher rates of bacterial resistance. Resistance may be reduced by combination therapy with benzoyl peroxide. Erythromycin can be used for patients who require systemic antibiotics but cannot tolerate tetracyclines, or those who acquire bacterial resistance to tetracyclines. The usual dose is 1 g/day with meals to minimize GI intolerance. 

Bacterial resistance to antibiotics is an emerging public health crisis. The prevalence of pathogens resistant to currently available antibiotics continues to grow annually. Two million patients in the U.S. acquire an infection during a hospital stay and approximately 90,000 of these patients die each year as a result of the infection [1]. More than 70% of hospital-acquired infections are now resistant to... 

DNA transfer of drug resistance Of particular clinical concern is resistance acquired due to DNA transfer from one organism to another. Resistance properties are usually encoded in extrachro-mosomal R factors (plasmids). These may enter cells by processes such as transduction (phage-mediated), transformation or, most importantly, bacterial conjugation. 

Bacterial resistance to antibiotics and biocides is essentially of two types, intrinsic and acquired. Whilst the latter is of greater significance clinically with antibiotics, specific examples of intrinsic resistance to both antibiotics, e.g. mycobacteria, and biocides (e.g. mycobacteria, Gram-negative bacteria, spores) are also of importance. 

In general terms, bacterial resistance to antibacterial agents can be considered as being either intrinsic (innate, a natural property) or acquired, for example, by mutation or by the acquisition of a plasmid or transposon (jumping gene) [105]. Resistance to mercury [103, 122-125] and to other cations and anions [103, 122, 123, 125] is well characterized. The mechanisms involved in resistance to some metals, including silver, are summarized in Table 7.1. 

Acquired bacterial resistance to the tetracyclines has become widespread in animal populations and has severely reduced the usefulness of these drugs. Resistance to the tetracyclines results from plasmid-mediated mechanisms that prevent the active transport of the drug into the bacterial cell or increase the efflux of drug from the bacterial cell. 

MECHANISMS OF BACTERIAL RESISTANCE TO PENICILLINS AND CEPHALOSPORINS A sensitive strain may acquire resistance by mutations that decrease the affinity of PBPs for the antibiotic. Because /5-lactam antibiotics inhibit many different PBPs, their affinity for several PBPs must decrease to confer resistance. Methidllin-resistant S. aureus are resistant via acquisition of an additional high-molecular-weight PBP (via a transposon) with a very low affinity for all /5-lactam antibiotics this mechanism is responsible for methicillin resistance in the coagu-lase-negative staphylococci. 

Trimethoprim frequently is used as a single agent clinically for the oral treatment of uncomplicated urinary tract infections caused by susceptible bacteria (predominantly community acquired Escherichia coli and other Gram-negative rods). It is, however, most commonly used in a 1 5 fixed concentration ratio with the sulfonamide sulfamethoxazole (Bactrim, Septra). This combination is not only synergistic in vitro but also is less likely to induce bacterial resistance than either agent alone. It is rationalized that microorganisms not... 

Infections caused by antibiotic-resistant bacteria expose an important risk to human health around the world. These bacteria are very resistant to traditional antibiotics owing to acquired resistance, inadequate diffusion and intracellular inactivation. Therefore, the development of novel antimicrobial materials with high protection and antibacterial activity, which lack bacterial resistance, is critical. 

Antimicrobial resistance traits are genetically coded and can either be intrinsic or acquired. Intrinsic resistance is due to innately coded genes which create natural insensitivity to a particular antibiotic. Innate resistance is normally expressed by virtually all strains of that particular bacterial species. Acquired resistance is gained by previously susceptible bacteria either through mutation or horizontally obtained from other bacteria possessing such resistance via transformation, transduction, or conjugation. Acquired resistance is limited to subpopulations of a particular bacterial species and may result from selective pressure exerted by antibiotic usage. 

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