Antimicrobial

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Microbicide
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An antimicrobial is an agent that kills

fungi. They can also be classified according to their function. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.[2]

The main classes of antimicrobial agents are

bactericidal agents, which kill bacteria, and bacteriostatic agents, which slow down or stall bacterial growth. In response, further advancements in antimicrobial technologies have resulted in solutions that can go beyond simply inhibiting microbial growth. Instead, certain types of porous media have been developed to kill microbes on contact.[3] Overuse or misuse of antimicrobials can lead to the development of antimicrobial resistance.[4]

History

Antimicrobial use has been common practice for at least 2000 years.

molds and plant extracts to treat infection.[5]

In the 19th century, microbiologists such as Louis Pasteur and Jules Francois Joubert observed antagonism between some bacteria and discussed the merits of controlling these interactions in medicine.[6] Louis Pasteur's work in fermentation and spontaneous generation led to the distinction between anaerobic and aerobic bacteria. The information garnered by Pasteur led Joseph Lister to incorporate antiseptic methods, such as sterilizing surgical tools and debriding wounds into surgical procedures. The implementation of these antiseptic techniques drastically reduced the number of infections and subsequent deaths associated with surgical procedures. Louis Pasteur's work in microbiology also led to the development of many vaccines for life-threatening diseases such as anthrax and rabies.[7] On September 3, 1928, Alexander Fleming returned from a vacation and discovered that a Petri dish filled with Staphylococcus was separated into colonies due to the antimicrobial fungus Penicillium rubens. Fleming and his associates struggled to isolate the antimicrobial but referenced its therapeutic potential in 1929 in the British Journal of Experimental Pathology.[8] In 1942, Howard Florey, Ernst Chain, and Edward Abraham used Fleming's work to purify and extract penicillin for medicinal uses earning them the 1945 Nobel Prize in Medicine.[9]

Chemical

Selman Waksman, who was awarded the Nobel Prize in Medicine for developing 22 antibiotics—most notably Streptomycin

Antibacterials

Antibacterials are used to treat

Stool transplants may be considered for patients who are having difficulty recovering from prolonged antibiotic treatment, as for recurrent Clostridioides difficile infections.[11][12]

The discovery, development and use of antibacterials during the 20th century have reduced mortality from bacterial infections. The antibiotic era began with the therapeutic application of sulfonamide drugs in 1936, followed by a "golden" period of discovery from about 1945 to 1970, when a number of structurally diverse and highly effective agents were discovered and developed. Since 1980, the introduction of new antimicrobial agents for clinical use has declined, in part because of the enormous expense of developing and testing new drugs.[13] In parallel, there has been an alarming increase in antimicrobial resistance of bacteria, fungi, parasites and some viruses to multiple existing agents.[14]

Antibacterials are among the most commonly used drugs and among the drugs commonly misused by physicians, for example, in viral respiratory tract infections. As a consequence of widespread and injudicious use of antibacterials, there has been an accelerated emergence of antibiotic-resistant pathogens, resulting in 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 antibacterials. Possible strategies towards this objective include increased sampling from diverse environments and application of metagenomics to identify bioactive compounds produced by currently unknown and uncultured microorganisms as well as the development of small-molecule libraries customized for bacterial targets.[15]

Antifungals

Antifungals are used to kill or prevent further growth of

side effects to some of these drugs. Some of these side effects can be life-threatening if the drug is not used properly.[16]

As well as their use in medicine, antifungals are frequently sought after to control indoor mold in damp or wet home materials. Sodium bicarbonate (baking soda) blasted on to surfaces acts as an antifungal. Another antifungal solution applied after or without blasting by soda is a mix of hydrogen peroxide and a thin surface coating that neutralizes mold and encapsulates the surface to prevent spore release. Some paints are also manufactured with an added antifungal agent for use in high humidity areas such as bathrooms or kitchens. Other antifungal surface treatments typically contain variants of metals known to suppress mold growth e.g. pigments or solutions containing copper, silver or zinc. These solutions are not usually available to the general public because of their toxicity.[17]

Antivirals

Antiviral drugs are a class of medication used specifically for treating

viricides, which actively deactivate virus particles outside the body.[18]

Many antiviral drugs are designed to treat infections by

B viruses have become resistant to neuraminidase inhibitors such as oseltamivir, and the search for new substances continues.[19]

Antiparasitics

Antiparasitics are a class of medications indicated for the treatment of infectious diseases such as

iodoquinol and albendazole.[10] Like all therapeutic antimicrobials, they must kill the infecting organism without serious damage to the host.[20]

Broad-spectrum therapeutics

Broad-spectrum therapeutics are active against multiple classes of pathogens. Such therapeutics have been suggested as potential emergency treatments for

better source needed
]

Non-pharmaceutical

A wide range of chemical and natural compounds are used as antimicrobials.

Organic acids and their salts are used widely in food products, e.g. lactic acid, citric acid, acetic acid, either as ingredients or as disinfectants. For example, beef carcasses often are sprayed with acids, and then rinsed or steamed, to reduce the prevalence of Escherichia coli.[22]

Heavy metal cations such as Hg2+ and Pb2+ have antimicrobial activities, but can be toxic. In recent years, the antimicrobial activity of coordination compounds has been investigated.[23][24][25][26]

Traditional herbalists used plants to treat infectious disease. Many of these plants have been investigated scientifically for antimicrobial activity, and some 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.[27]

Copper

Copper-alloy surfaces have natural intrinsic antimicrobial properties and can kill microorganisms such as E. coli and Staphylococcus.[28][29] The United States Environmental Protection Agency approved the registration of antimicrobial copper alloy surfaces for use in addition to regular cleaning and disinfection to control infections.[29][30] Antimicrobial copper alloys are being installed in some healthcare facilities and subway transit systems as a public hygienic measure.[29] Copper nanoparticles are attracting interest for the intrinsic antimicrobial behaviors.[31]

Essential oils

Many essential oils included in herbal pharmacopoeias are claimed to possess antimicrobial activity, with the oils of bay, cinnamon, clove and thyme reported to be the most potent in studies with foodborne bacterial pathogens.[32][33] Coconut oil is also known for its antimicrobial properties.[34] Active constituents include terpenoids and secondary metabolites.[35][36] Despite their prevalent use in alternative medicine, essential oils have seen limited use in mainstream medicine. While 25 to 50% of pharmaceutical compounds are plant-derived, none are used as antimicrobials, though there has been increased research in this direction.[37] Barriers to increased usage in mainstream medicine include poor regulatory oversight and quality control, mislabeled or misidentified products, and limited modes of delivery.[38]

Antimicrobial pesticides

According to the U.S. Environmental Protection Agency (EPA), and defined by the Federal Insecticide, Fungicide, and Rodenticide Act, antimicrobial pesticides are used to control growth of microbes through disinfection, sanitation, or reduction of development and to protect inanimate objects, industrial processes or systems, surfaces, water, or other chemical substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, algae, or slime.[39] The EPA monitors products, such as disinfectants/sanitizers for use in hospitals or homes, to ascertain efficacy.[40] Products that are meant for public health are therefore under this monitoring system, including products used for drinking water, swimming pools, food sanitation, and other environmental surfaces. These pesticide products are registered under the premise that, when used properly, they do not demonstrate unreasonable side effects to humans or the environment. Even once certain products are on the market, the EPA continues to monitor and evaluate them to make sure they maintain efficacy in protecting public health.[41]

Public health products regulated by the EPA are divided into three categories:[39]

  • Disinfectants: Destroy or inactivate microorganisms (bacteria, fungi, viruses,) but may not act as sporicides (as those are the most difficult form to destroy). According to efficacy data, the EPA will classify a disinfectant as limited, general/broad spectrum, or as a hospital disinfectant.
  • Sanitizers: Reduce the number of microorganisms, but may not kill or eliminate all of them.
  • Sterilizers (Sporicides): Eliminate all bacteria, fungi, spores, and viruses.
Antimicrobial pesticide safety

Antimicrobial pesticides have the potential to be a major factor in drug resistance.[42] Organizations such as the World Health Organization call for significant reduction in their use globally to combat this.[43] According to a 2010 Centers for Disease Control and Prevention report, health-care workers can take steps to improve their safety measures against antimicrobial pesticide exposure. Workers are advised to minimize exposure to these agents by wearing personal protective equipment such as gloves and safety glasses. Additionally, it is important to follow the handling instructions properly, as that is how the EPA has deemed them as safe to use. Employees should be educated about the health hazards and encouraged to seek medical care if exposure occurs.[44]

Ozone

Ozone can kill microorganisms in air, water and process equipment and has been used in settings such as kitchen exhaust ventilation, garbage rooms, grease traps,

pharmaceutical industries, bottling plants, zoos, municipal drinking-water systems, swimming pools and spas, and in the laundering of clothes and treatment of in–house mold and odors.[45][46]

Antimicrobial scrubs

Antimicrobial scrubs can reduce the accumulation of odors and stains on scrubs, which in turn improves their longevity. These scrubs also come in a variety of colors and styles. As antimicrobial technology develops at a rapid pace, these scrubs are readily available, with more advanced versions hitting the market every year.[47] These bacteria could then be spread to office desks, break rooms, computers, and other shared technology. This can lead to outbreaks and infections like MRSA, treatments for which cost the healthcare industry $20 billion a year.

Halogens

Elements such as chlorine, iodine, fluorine, and bromine are nonmetallic in nature and constitute the halogen family. Each of these halogens have a different antimicrobial effect that is influenced by various factors such as pH, temperature, contact time, and type of microorganism. Chlorine and iodine are the two most commonly used antimicrobials. Chlorine is extensively used as a disinfectant in the water treatment plants, drug, and food industries. In wastewater treatment plants, chlorine is widely used as a disinfectant. It oxidizes soluble contaminants and kills bacteria and viruses. It is also highly effective against bacterial spores. The mode of action is by breaking the bonds present in these microorganisms. When a bacterial enzyme comes in contact with a compound containing chlorine, the hydrogen atom in that molecule gets displaced and is replaced with chlorine. This thus changes the enzyme function which in turn leads to the death of the bacterium. Iodine is most commonly used for sterilization and wound cleaning. The three major antimicrobial compounds containing iodine are alcohol-iodine solution, an aqueous solution of iodine, and iodophors. Iodophors are more bactericidal and are used as antiseptics as they are less irritating when applied to the skin. Bacterial spores on the other hand cannot be killed by iodine, but they can be inhibited by iodophors. The growth of microorganisms is inhibited when iodine penetrates into the cells and oxidizes proteins, genetic material, and fatty acids. Bromine is also an effective antimicrobial that is used in water treatment plants. When mixed with chlorine it is highly effective against bacterial spores such as S. faecalis.[48]

Alcohols

Alcohols are commonly used as disinfectants and antiseptics. Alcohols kill vegetative bacteria, most viruses and fungi. Ethyl alcohol, n-propanol and isopropyl alcohol are the most commonly used antimicrobial agents.[49] Methanol is also a disinfecting agent but is not generally used as it is highly poisonous. Escherichia coli, Salmonella, and Staphylococcus aureus are a few bacteria whose growth can be inhibited by alcohols. Alcohols have a high efficiency against enveloped viruses (60–70% ethyl alcohol) 70% isopropyl alcohol or ethanol are highly effective as an antimicrobial agent. In the presence of water, 70% alcohol causes coagulation of the proteins thus inhibiting microbial growth. Alcohols are not quite efficient when it comes to spores. The mode of action is by denaturing the proteins. Alcohols interfere with the hydrogen bonds present in the protein structure. Alcohols also dissolve the lipid membranes that are present in microorganisms.[50][51] Disruption of the cell membrane is another property of alcohols that aid in cell death. Alcohols are cheap and effective antimicrobials. They are widely used in the pharmaceutical industry.  Alcohols are commonly used in hand sanitizers, antiseptics, and disinfectants.

Phenol and Phenolic compounds

Phenol also known as carbolic acid was one of the first chemicals which was used as an antimicrobial agent. It has high antiseptic properties. It is bacteriostatic at concentrations of 0.1%–1% and is bactericidal/fungicidal at 1%–2%. A 5% solution kills anthrax spores in 48 hr.

packing materials however.) Ihloff and Kalitzki 1961 find a small but measurable amount remains in the skin of fruits processed in this manner.[54]
: 193 

Aldehydes

They are highly effective against bacteria, fungi, and viruses.  Aldehydes inhibit bacterial growth by disrupting the outer membrane. They are used in the disinfection and sterilization of surgical instruments. Being highly toxic they are not used in antiseptics. Currently, only three aldehyde compounds are of widespread practical use as disinfectant biocides, namely glutaraldehyde, formaldehyde, and ortho-phthalaldehyde (OPA) despite the demonstration that many other aldehydes possess good antimicrobial activity.[55] However, due to its long contact time other disinfectants are commonly preferred.

Physical

Heat

Microorganisms have a minimum temperature, an optimum, and a maximum temperature for growth.

conventional oven. Heat is also used in pasteurization, a method for slowing the spoilage of foods such as milk, cheese, juices, wines and vinegar. Such products are heated to a certain temperature for a set period of time, which greatly reduces the number of harmful microorganisms. Low temperature is also used to inhibit microbial activity by slowing down microbial metabolism.[59]

Radiation

Foods are often

electron beams and X-rays.[62] Ultraviolet light is also used to disinfect drinking water, both in small-scale personal-use systems and larger-scale community water purification systems.[63]

Desiccation

Desiccation is also known as dehydration.  It is the state of extreme dryness or the process of extreme drying. Some microorganisms like bacteria, yeasts and molds require water for their growth. Desiccation dries up the water content thus inhibiting microbial growth. On the availability of water, the bacteria resume their growth, thus desiccation does not completely inhibit bacterial growth. The instrument used to carry out this process is called a desiccator. This process is widely used in the food industry and is an efficient method for food preservation. Desiccation is also largely used in the pharmaceutical industry to store vaccines and other products.[64]

Antimicrobial surfaces

Antimicrobial surfaces are designed to either inhibit the ability of microorganisms to grow or damaging them by chemical (copper toxicity) or physical processes (micro/nano-pillars to rupture cell walls). These surfaces are especially important for the healthcare industry.[65] Designing effective antimicrobial surfaces demands an in-depth understanding of the initial microbe-surface adhesion mechanisms. Molecular dynamics simulation and time-lapse imaging are typically used to investigate these mechanisms.[66]

Osmotic pressure

Osmotic pressure is the pressure required to prevent a solvent from passing from a region of high concentration to a region of low concentration through a semipermeable membrane.  When the concentration of dissolved materials or solute is higher inside the cell than it is outside, the cell is said to be in a hypotonic environment and water will flow into the cell.[56]When the bacteria is placed in hypertonic solution, it causes plasmolysis or cell shrinking, similarly in hypotonic solution, bacteria undergoes plasmotysis or turgid state. This plasmolysis and plasmotysis kills bacteria because it causes change in osmotic pressure.[67]

See also

References

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