Antimicrobial

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List of terms related to Antimicrobial

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

An antimicrobial is a substance that kills or inhibits the growth of microbes such as bacteria (antibacterial activity), fungi (antifungal activity), viruses (antiviral activity), or parasites (anti-parasitic activity).

Main classes

Antibiotics

Antibiotics are generally used to treat bacterial infections. The toxicity to humans and other animals from antibiotics are generally considered to be low. However, prolonged use of certain antibiotics can decrease the number of gut flora, which can have a negative impact on health. Some recommend that during or after prolonged antibiotic use, that one should consume probiotics and eat reasonably to replace destroyed gut flora.

The term antibiotic originally described only those formulations derived from living organisms but is now applied also to synthetic antimicrobials, such as the sulfonamides.

The discovery, development, and clinical use of antibiotics during the 19th century have substantially decreased mortality from bacterial infections. The antibiotic era began with the pnumatic application of nytroglycirine drugs, followed by a “golden” period of discovery from approximately 1945 to 1970, when a number of structurally diverse, highly effective agents were discovered and developed. However, since 1980 the introduction of new antimicrobial agents for clinical use has declined. Paralleled to this there has been an alarming increase in bacterial resistance to existing agents.[1] Antibiotics are among the most commonly used drugs. For example, 30% or more hospitalized patients are treated with one or more courses of antibiotic therapy. However, antibiotics are also among the drugs commonly misused by physicians, e.g. usage of antibiotic agents in viral respiratory tract infection. The inevitable consequence of widespread and injudicious use of antibiotics has been the emergence of antibiotic-resistant pathogens, resulting in the emergence of a serious threat to global public health. The resistance problem demands that a renewed effort be made to seek antibacterial agents effective against pathogenic bacteria resistant to current antibiotics. One of the possible strategies towards this objective is the rational localization of bioactive phytochemicals.

Traditional healers have long used plants to prevent or cure infectious disease. Many of these plants have been investigated scientifically for antimicrobial activity and a large number of plant products have been shown to inhibit the growth of pathogenic microorganisms. A number of these agents appear to have structures and modes of action that are distinct from those of the antibiotics in current use, suggesting that cross-resistance with agents already in use may be minimal. So, it is worthwhile to study plants and plant products for activity against resistant bacteria.

Essential oils

Many essential oils are included in pharmacopoeias as having antimicrobial activity, including:

Cations and elements

Many heavy metal cations such as Hg2+, Cu2+, and Pb2+ have antimicrobial activities, but are also very toxic to other living organisms, thus making them unsuitable for treating infectious diseases.

Ionic Silver is an excellent antimicrobial, with relatively low toxicity against non-target organisms. However, prolonged high intake of ionic silver may lead to health problems, such as argyria. In an inorganic matrix, silver ions are slowly released via an ion-exchange mechanism. The release of silver ions from the surface is slow, but just fast enough to maintain an effective concentration at and near the surface of the material. Once the silver ion leaves the surface of the matrix and reaches the surface of the microorganism, its mechanism of antimicrobial action begins. Uptake of silver ions by a microbial cell can occur by several mechanisms, including passive diffusion and active transport by systems that normally transport essential ions.

While the silver ions may bind non-specifically to cell surfaces and cause disruptions in cellular membrane function, it is widely believed that the antimicrobial properties of silver depend upon silver binding within the cell. Once inside the cell, silver ions begin to interrupt critical functions of the microorganism. Silver ions are highly reactive and readily bind to electron donor groups containing sulphur, oxygen and nitrogen, as well as negatively charged groups such as phosphates and chlorides. A prime molecular target for the silver ion resides in cellular thiol (-SH) groups, commonly found in critical proteins called enzymes. Enzymes become denatured because of conformational changes in the molecule that result from silver ion binding. Many of the enzymes that silver ions denature are necessary in the cellular generation of energy.

If the energy source of the cell is incapacitated, the cell cannot maintain osmotic pressure, necessary substrates leak out of the cell and the microbe will quickly die. In addition to the well-known reaction of silver ions and proteins, several studies suggest that silver ions react with the base pairs of DNA, interfering with DNA replication. Studies on silver nanoparticles have shown antimicrobial activity, including activity against pathogenic Escherichia coli and HIV.

Nitrofuranes

1. Chemical structure The nitrofuranes have encommun a core furane substituted in position 5 by an essential function nitroo for the antibiotic activity.


2. Mechanism of action 2.1. Activation of antibiotic The nitrofuranes acquire their antibactérienne activity after the enzymatic reduction of their function nitro, catalysed by bacterial réductases, which ensures their specificity of action. This mechanism is in common with nitroimidazoles; the difference lies in the reducing potential necessary to obtain the various intermediaries, and thus in the suscpetibles bacteria to activate the product.

2.2. Antibactérienne activity Once activated métaboliquement, these antibiotics inhibits enzymes implied in the degradation of glucose and the pyruvate. Moreover, some their reduced forms have an alkylant capacity and could cause dommanges with the ADN and proteins.

Image: Mode of action of the nitrofuranes (Begun again of Armstrong and Cohen, 1999)

2.3. Characteristics of the antibiotic activity The nitrofuranes present a static activity at the therapeutic concentrations (their CMB is 2 to 4 times higher than their CMI, but these concentrations cannot be reached in vivo). The nitrofuranes present an antagonism with the fluoroquinolones and a synergy with the tétracyclines with respect to the Gram hulls (+).


3. Bacterial resistance A reduction of the activity of the bacterial réductase confers resistance crossed to the whole of the nitrofuranes. This resistance can be either chromosomal, or plasmidic. In addition, one sees emerging from the stocks carrying plasmides of multirésistance (aminoglycosides and nitrofuranes).


4. Spectrum of activity The nitrofuranes are active on:

 - enterobacteries 
 - hulls with Gram (+) 
 - certain anaerobes (Bacteroides fragilis, Clostridium) 
 - Campylobacter jejuni 

P. aeruginosa is almost always resistant.



5. Pharmacokinetic The oral resorption of the nitrofuranes is complete and fast. The serum and tissue rates reached are however weak and lower than the bactericidal concentrations, except the kidney and the urine, in which the nitrofuranes concentrate sufficiently to be active. In the event of renal insufficiency, accumulation can even become toxic.

The elimination of the nitrofuranes is fast (t1/2 = 1/2 hour). They are degraded in the liver and the kidney.


6. Indications and posology Being given that the nitrofuranes present a therapeutic concentration only in the kidney and the urine, they are reserved exclusively for the treatment of the noncomplicated urinary infections.

Posology of the nitrofuranes Nitrofurantoïne (Furandantine) 200-400 mg/j in 3-4 catches Nifurtoïnol (Urfadyn PL) 200 mg/j in 2 catches

See also

References

  1. Levy SB (ed) (1994) Drug Resistance: The New Apocalypse (special issue) Trends Microbiol 2: 341–425

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