Antibiotic resistance

Main article: Antibiotic resistance

SEM depicting methicillin-resistant Staphylococcus aureus bacteria.
SEM depicting methicillin-resistant Staphylococcus aureus bacteria.

Use or misuse of antibiotics may result in the development of antibiotic resistance by the infecting organisms, similar to the development of pesticide resistance in insects. Evolutionary theory of genetic selection requires that as close as possible to 100% of the infecting organisms be killed off to avoid selection of resistance; if a small subset of the population survives the treatment and is allowed to multiply, the average susceptibility of this new population to the compound will be much less than that of the original population, since they have descended from those few organisms that survived the original treatment. This survival often results from an inheritable resistance to the compound that was infrequent in the original population, but became more frequent in the descendants.

Antibiotic resistance has become a serious problem in both the developed and underdeveloped nations. By 1984 half of the people with active tuberculosis in the United States had a strain that resisted at least one antibiotic.[citation needed] In certain settings, such as hospitals and some child-care locations, the rate of antibiotic resistance is so high that the usual, low-cost antibiotics are virtually useless for treatment of frequently seen infections. This leads to more frequent use of newer and more expensive compounds, which in turn leads to the rise of resistance to those drugs. A struggle to develop new antibiotics ensues, to prevent losing future battles against infection. To date, tuberculosis and pneumococcus are two prominent examples of once easily treated infections where drug-resistance has become a problem.
Points of attack on bacteria by antibiotics
Points of attack on bacteria by antibiotics

Another example of selection is Staphylococcus aureus ('golden staph'), which could be treated successfully with penicillin in the 1940s and 1950s. At present, nearly all strains are resistant to penicillin, and many are resistant to nafcillin, leaving only a narrow selection of drugs such as vancomycin useful for treatment. The situation is complicated by the fact that genes coding for antibiotic resistance can be transferred between bacteria via plasmids, making it possible for bacteria never exposed to an antibiotic to acquire resistance from those which have. The problem of antibiotic resistance is made more widespread when antibiotics are used to treat disorders in which they have no efficacy, such as the common cold or other viral complaints, and when they are used broadly as prophylaxis rather than treatment (as in, for example, animal feeds), because this exposes more bacteria to selection for resistance.

[edit] Resistance modifying agents

One solution to combat resistance currently being researched is the development of pharmaceutical compounds that would revert multiple antibiotic resistance. These so called resistance modifying agents may target and inhibit MDR mechanisms rendering the bacteria susceptible to antibiotics they were previously resistant to. These compounds targets include among others

* Efflux inhibition(Phe-Arg-β-naphthylamide)[19]
* Beta Lactamase inhibitors - Including Clavulanic acid and Sulbactam

[edit] Beyond antibiotics

The comparative ease of identifying compounds which safely cured bacterial infections was more difficult to duplicate in treatments of fungal and viral infections. Antibiotic research led to great strides in the knowledge of biochemistry, establishing large differences between the cellular and molecular physiology of the bacterial cell and that of the mammalian cell. This explained the observation that many compounds that are toxic to bacteria are non-toxic to human cells. In contrast, the basic biochemistries of the fungal cell and the mammalian cell are much more similar. This restricts the development and use of therapeutic compounds that attack a fungal cell, while not harming mammalian cells. Similar problems exist in antibiotic treatments of viral diseases. Human viral metabolic biochemistry is very closely similar to human biochemistry, and the possible targets of antiviral compounds are restricted to very few components unique to a mammalian virus.

Research into bacteriophages for use as antibiotics is presently ongoing. Several types of bacteriophage appear to exist that are specific for each bacterial taxonomic group or species.[citation needed] Research into bacteriophages for medicinal use is just beginning, but has led to advances in microscopic imaging.[20] While bacteriophages provide a possible solution to the problem of antibiotic resistance, there is no clinical evidence yet that they can be deployed as therapeutic agents to cure disease.

Phage therapy has been used in the past on humans in the US and Europe during the 1920s and 1930s, but these treatments had mixed results. With the discovery of penicillin in the 1940s, Europe and the US changed therapeutic strategies to using antibiotics. However, in the former Soviet Union phage therapies continued to be studied. In the Republic of Georgia, the Eliava Institute of Bacteriophage, Microbiology & Virology continues to research the use of phage therapy. Various companies and foundations in North America and Europe are currently researching phage therapies.[citation needed] However, phage are living and reproducing; concerns about genetic engineering in freely released viruses currently limit certain aspects of phage therapy.

Bacteriocins are also a growing alternative to the classic small-molecule antibiotics [21]. Different classes of bacteriocins have different potential as therapeutic agents. Small molecule bacteriocins (microcins, for example, and lantibiotics) may be similar to the classic antibiotics; colicin-like bacteriocins are more likely to be narrow-spectrum, demanding new molecular diagnostics prior to therapy but also not raising the specter of resistance to the same degree. One drawback to the large molecule antibiotics is that they will have relative difficulty crossing membranes and travelling systemically throughout the body. For this reason, they are most often proposed for application topically or gastrointestinally[22]. Because bacteriocins are peptides, they are more readily engineered than small molecules[23]. This may permit the generation of cocktails and dynamically improved antibiotics that are modified to overcome resistance.

Probiotics are another alternative that goes beyond traditional antibiotics by employing a live culture which may establish itself as a symbiont, competing, inhibiting, or simply interfering with colonization by pathogens. It may produce antibiotics or bacteriocins, essentially providing the drug in vivo and in situ, potentially avoiding the side effects of systemic administration.