Friday, September 14, 2007
Antibiotic resistance is the ability of a micro-organism to withstand the effects of an antibiotic. It is a specific type of drug resistance. Antibiotic resistance evolves naturally via natural selection through random mutation, but it could also be engineered. SOS response of low-fidelity polymerases can also cause mutation via a process known as programmed evolution. Once such a gene is generated, bacteria can then transfer the genetic information in a horizontal fashion (between individuals) by plasmid exchange. If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug.
Antibiotic resistance can also be introduced artificially into a micro-organism through transformation protocols. This can be a useful way of implanting artificial genes into the micro-organism.
The four main mechanisms by which micro-organisms exhibit resistance to antimicrobials are:
Drug inactivation or modification: e.g. enzymatic deactivation of Penicillin G in some penicillin-resistant bacteria through the production of β-lactamases.
Alteration of target site : e.g. alteration of PBP—the binding target site of penicillins—in MRSA and other penicillin-resistant bacteria.
Alteration of metabolic pathway: e.g. some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid.
Reduced drug accumulation: by decreasing drug permeability and/or increasing active efflux on the cell surface. Mechanisms
Staphylococcus aureus (colloquially known as "Staph aureus" or a Staph infection) is one of the major resistant pathogens. Found on the mucous membranes and the skin of around a third of the population, it is extremely adaptable to antibiotic pressure. It was the first bacterium in which penicillin resistance was found—in 1947, just four years after the drug started being mass-produced. Methicillin was then the antibiotic of choice, but has since been replaced by oxacillin due to significant kidney toxicity. MRSA (methicillin-resistant Staphylococcus aureus) was first detected in Britain in 1961 and is now "quite common" in hospitals. MRSA was responsible for 37% of fatal cases of blood poisoning in the UK in 1999, up from 4% in 1991. Half of all S. aureus infections in the US are resistant to penicillin, methicillin, tetracycline and erythromycin.
This left vancomycin as the only effective agent available at the time. However, VRSA (Vancomycin-resistant Staphylococcus aureus) was first identified in Japan in 1996, and has since been found in hospitals in England, France and the US. VRSA is also termed GISA (glycopeptide intermediate Staphylococcus aureus) or VISA (vancomycin insensitive Staphylococcus aureus), indicating resistance to all glycopeptide antibiotics.
A new class of antibiotics, oxazolidinones, became available in the 1990s, and the first commercially available oxazolidinone, linezolid, is comparable to vancomycin in effectiveness against MRSA. Linezolid-resistance in Staphylococcus aureus was reported in 2003.
CA-MRSA has now emerged as an epidemic that is responsible for rapidly progressive, fatal diseases including necrotizing pneumonia, severe sepsis and necrotizing fasciitis.
MRSA is acknowledged to be a human commensal and pathogen. MRSA has been found in cats, dogs and horses, where it can cause the same problems as it does in humans. Owners can transfer the organism to their pets and vice-versa, and MRSA in animals is generally believed to be derived from humans.
Currently, it is estimated that greater than 50% of the antibiotics used in the US are given to food animals (e.g. chickens, pigs and cattle) in the absence of disease. Antibiotic use in food animal production has been associated with the emergence of antibiotic resistant strains of bacteria including Salmonella, Campylobacter, Escherichia coli and Enterococcus, among others. There is substantial evidence from the US and European Union that these resistant bacteria cause antibiotic resistant infections in humans. The American Society for Microbiology (ASM), the American Public Health Association (APHA) and the American Medical Association (AMA) have called for substantial restrictions on antibiotic use in food animal production including an end to all non-therapeutic uses. The food animal and pharmaceutical industries have fought hard to prevent new regulations that would limit the use of antibiotics in food animal production. For example, in 2000 the US Food and Drug Administration (FDA) announced their intention to rescind approval for fluoroquinolone use in poultry production because of substantial evidence linking it to the emergence of fluoroquinolone resistant Campylobacter infections in humans. The final decision to ban fluoroquinolones from use in poultry production was not made until 5 years later because of challenges from the food animal and pharmaceutical industries. Today, there are two federal bills (S.742 and H.R. 2562) aimed at phasing out non-therapeutic antibiotics in US food animal production. These bills are endorsed by many public health and medical organizations including the American Nurses Association (ANA), the American Academy of Pediatrics (AAP), and the American Public Health Association (APHA).
The illegal use of amantadine to medicate poultry in the South of China and other parts of southeast Asia means that although the H5N1 (avian flu) strain that appeared in Hong Kong in 1997 was amantadine sensitive, the more recent strains have all been amantadine resistant. This seriously reduces the treatment options available to doctors in the event of an influenza pandemic.
Role of animals
Washing hands properly reduces the chance of getting infected or spreading infection. Thoroughly washing or avoiding raw foods such as fruits, vegetables, raw eggs, and undercooked meat can also reduce the chance of an infection. High risk activities include unprotected sex, especially homosexual sex between two men,
Phage therapy, an approach that has been extensively researched and utilized as a therapeutic agent for over 60 years, especially in the Soviet Union, is an alternative that might help with the problem of resistance. Phage Therapy was widely used in the United States until the discovery of antibiotics, in the early 1940's. Bacteriophages or "phages" are viruses that invade bacterial cells and, in the case of lytic phages, disrupt bacterial metabolism and cause the bacterium to lyse [destruct]. Phage Therapy is the therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections.
Until recently, research and development (R&D) efforts have provided new drugs in time to treat bacteria that became resistant to older antibiotics. That is no longer the case. The potential crisis at hand is the result of a marked decrease in industry R&D, government inaction, and the increasing prevalence of resistant bacteria. Infectious disease physicians are alarmed by the prospect that effective antibiotics may not be available to treat seriously ill patients in the near future.
The pipeline of new antibiotics is drying up. Major pharmaceutical companies are losing interest in the antibiotics market because these drugs may not be as profitable as drugs that treat chronic (long-term) conditions and lifestyle issues..
List of environment topics
Drug of last resort
Posted by iamyrfans at 9:59 AM