Bacterial resistance to antibiotics

Resistance to antimicrobial agents is of concern as it is well known that bacterial resistance to antibiotics can develop. Many bacteria already derive some nonspecific resistance to biocides through morphological features such as thek cell wall. Bacterial populations present as part of a biofilm have achieved additional resistance owkig to the more complex and thicker nature of the biofilm. A system contaminated with a biofilm population can requke several orders of magnitude more chlorine to achieve control than unassociated bacteria of the same species. A second type of resistance is attributed to chemical deactivation of the biocide. This deactivation resistance to the strong oxidising biocides probably will not occur (27). 

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%. 

Lambert PA (2005) Bacterial resistance to antibiotics modified target sites. Adv Drug Deliv Rev 29 1471-1485... 

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. 

Several factors are known to influence biocidal activity these include the period of contact, biocide concentration, pH, temperature, the presence of oigartic matter and the nature and condition of the microorgartisms being treated. Bacterial resistance to antibiotics is a well-established phenomenon and has been widely studied for luar years. By contrast, the mechanisms of insusceptibility to non-antibiotic chemical agents are less well understood. 

Another problem is bacterial resistance to antibiotics. As doctors have treated people with the available antibiotics that medicinal chemistry devised in the past, they have selected for strains of bacteria that are resistant to those antibiotics. There is now a race against time by medicinal chemists to devise new antibiotics that will work against the resistant organisms. If we do not succeed, many bacterial infections that we thought had been cured will emerge again as major threats to our health and life. 

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... 

Bacterial resistance to antibiotics usually results from modification of a target site, enzymatic inactivation, or reduced uptake into or increased efflux from bacterial cells. 

Russell AD (1998) Mechanisms of bacterial resistance to antibiotics and biocides. Prog Med Chem 35, 133-197. 

Bacterial infections are a significant health risk for populations across the world. Bacteria pose a major treatment challenge because of their tendency to mutate and share mutations with other bacteria. Bacterial resistance to antibiotics is common, and new drugs are continuously being sought to replace those that have become less effective. 

Biologists have now observed hundreds of cases of natural selection, beginning with the well-known examples of bacterial resistance to antibiotics, insect resistance to DDT and HIV resistance to antiviral dmgs. Natural selection accounts for the resistance of fish and mice to predators by making them more camouflaged, and for the adaptation of plants to toxic minerals in the soil.32... 

Various mechanisms of bacterial resistance to antibiotics and biocides have been discussed. The question as to whether there is a link between resistance to chemotherapeutic drugs on the one hand and non-antibiotics on the other remains to be addressed. 

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 fact, both methylation and acetylation are very common as mechanisms of bacterial resistance to antibiotics - which suggests that these reactions may have protective functions in mammalian / human drag metabolism, too. 

Interestingly, reserpine does inhibit some types of ATP-dependent dmg extmsion transporters, both in eukaryotic and bacterial cells. Bacteriologists have become interested in this effect, since drug extmsion is an important means of bacterial resistance to antibiotics. 

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