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Antimicrobial

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An antimicrobial is an agent that kills microorganisms or stops their growth.[1] Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. Agents that kill microbes are microbicidal, while those that merely inhibit their growth are called biostatic. 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.

The main classes of antimicrobial agents are disinfectants (non-selective agents, such as bleach), which kill a wide range of microbes on non-living surfaces to prevent the spread of illness, antiseptics (which are applied to living tissue and help reduce infection during surgery), and antibiotics (which destroy microorganisms within the body). The term "antibiotic" originally described only those formulations derived from living microorganisms but is now also applied to synthetic agents, such as sulfonamides or fluoroquinolones. The term also used to be restricted to antibacterials (and is often used as a synonym for them by medical professionals and in medical literature), but its context has broadened to include all antimicrobials. Antibacterial agents can be further subdivided into 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.[2]

History

Antimicrobial use has been common practice for at least 2000 years. Ancient Egyptians and ancient Greeks used specific molds and plant extracts to treat infection.[3]

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.[4] 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 within in microbiology also led to the development of many vaccines for life-threatening diseases such as anthrax and rabies.[5] 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.[6] In 1942, Howard Florey, Ernst Chain, and Edward Abraham utilized Fleming's work to purify and extract penicillin for medicinal uses earning them the 1945 Nobel Prize in Medicine.[7]

Chemical

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

Antibacterials

Main article: Antibiotics

Antibacterials are used to treat bacterial infections. Antibiotics are classified generally as beta-lactams, macrolides, quinolones, tetracyclines or aminoglycosides. Their classification within these categories depends on their antimicrobial spectra, pharmacodynamics, and chemical composition.[8] Prolonged use of certain antibacterials can decrease the number of enteric bacteria, which may have a negative impact on health. Consumption of probiotics and reasonable eating may help to replace destroyed gut flora. Stool transplants may be considered for patients who are having difficulty recovering from prolonged antibiotic treatment, as for recurrent Clostridioides difficile infections.[9][10]

The discovery, development and use of antibacterials during the 20th century has reduced mortality from bacterial infections. The antibiotic era began with the pneumatic application of nitroglycerine drugs, 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.[11] In parallel, there has been an alarming increase in antimicrobial resistance of bacteria, fungi, parasites and some viruses to multiple existing agents.[12]

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.[13]

Antifungals

Main article: Fungicide

Antifungals are used to kill or prevent further growth of fungi. In medicine, they are used as a treatment for infections such as athlete's foot, ringworm and thrush and work by exploiting differences between mammalian and fungal cells. Unlike bacteria, both fungi and humans are eukaryotes. Thus, fungal and human cells are similar at the molecular level, making it more difficult to find a target for an antifungal drug to attack that does not also exist in the host organism. Consequently, there are often side effects to some of these drugs. Some of these side effects can be life-threatening if the drug is not used properly.

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.

Antivirals

Main article: Antiviral drug

Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics, specific antivirals are used for specific viruses. They should be distinguished from viricides, which actively deactivate virus particles outside the body.

Many antiviral drugs are designed to treat infections by retroviruses, including HIV. Important antiretroviral drugs include the class of protease inhibitors. Herpes viruses, best known for causing cold sores and genital herpes, are usually treated with the nucleoside analogue acyclovir. Viral hepatitis is caused by five unrelated hepatotropic viruses (A-E) and may be treated with antiviral drugs depending on the type of infection. Some influenza A and B viruses have become resistant to neuraminidase inhibitors such as oseltamivir, and the search for new substances continues.

Antiparasitics

Main article: Antiparasitic

Antiparasitics are a class of medications indicated for the treatment of infectious diseases such as leishmaniasis, malaria and Chagas disease, which are caused by parasites such as nematodes, cestodes, trematodes and infectious protozoa. Antiparasitic medications include metronidazole, iodoquinol and albendazole.[8] Like all therapeutic antimicrobials, they must kill the infecting organism without serious damage to the host.

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.

Main articles: Antimicrobial properties of copper and Antimicrobial copper-alloy touch surfaces

Copper-alloy surfaces have natural intrinsic antimicrobial properties and can kill microorganisms such as E. coli and Staphylococcus.[14] The United States Environmental Protection Agency has approved the registration of 355 such antibacterial copper alloys. In addition to regular cleaning, antimicrobial copper alloys are being installed in some healthcare facilities and subway transit systems as a public hygienic measure.[15][16] Other heavy metal cations such as Hg2+ and Pb2+ have antimicrobial activities, but can be toxic.

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.[17]

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.[18][19] Active constituents include terpenoids and secondary metabolites. 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.[20] Barriers to increased usage in mainstream medicine include poor regulatory oversight and quality control, mislabeled or misidentified products, and limited modes of delivery.

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 in order 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.[21]

Antimicrobial pesticide products

The EPA monitors products, such as disinfectants/sanitizers for use in hospitals or homes, in order to ascertain efficacy.[22] 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.

Public health products regulated by the EPA are divided into three categories:[21]

  • Sterilizers (Sporicides): Eliminate all bacteria, fungi, spores, and viruses.
  • 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.
Antimicrobial pesticide safety

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 protective equipment, 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.[23]

Ozone

Main article: Ozone Applications

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, biogas plants, wastewater treatment plants, textile production, breweries, dairies, food and hygiene production, 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.

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.[24] 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.

Physical

Heat

Main articles: Dry heat sterilization and Moist heat sterilization

Both dry and moist heat are effective in eliminating microbial life. For example, jars used to store preserves such as jam can be sterilized by heating them in a 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.

Radiation

Foods are often irradiated to kill harmful pathogens.[25] Common sources of radiation used in food sterilization include cobalt-60 (a gamma emitter), electron beams and x-rays.[26] Ultraviolet light is also used to disinfect drinking water, both in small scale personal-use systems and larger scale community water purification systems.[27]

See also

References

  1. ^ "Antimicrobial". Merriam-Webster Online Dictionary. Archived from the original on 24 April 2009. Retrieved 2009-05-02.
  2. ^ "Antimicrobial Porous Media | Microbicidal Technology | Porex Barrier Technology". www.porex.com. Retrieved 2017-02-16.
  3. ^ M. Wainwright (1989). "Moulds in ancient and more recent medicine". Mycologist. 3 (1): 21–23. doi:10.1016/S0269-915X(89)80010-2.
  4. ^ Kingston W (June 2008). "Irish contributions to the origins of antibiotics". Irish Journal of Medical Science. 177 (2): 87–92. doi:10.1007/s11845-008-0139-x. PMID 18347757.
  5. ^ Ullmann, Agnes (23 Dec 2019). "Louis Pasteur | Biography, Inventions, Achievements, & Facts". Encyclopedia Britannica. Encyclopedia Britannica, inc. Retrieved 24 February 2020.
  6. ^ A. Fleming (1929). "On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to their use in the Isolation of B. influenzae". The British Journal of Experimental Pathology. 10 (3): 226–236.
  7. ^ "The Nobel Prize in Physiology or Medicine 1945". The Nobel Prize Organization.
  8. ^ a b Gilbert, David N.; Saag, Michael S. (2018). Sanford Guide to Antimicrobial Therapy (48th ed.). ISBN 978-1944272067.
  9. ^ Brandt LJ (Feb 2013). "American Journal of Gastroenterology Lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C. difficile infection". Am J Gastroenterol. 108 (2): 177–85. doi:10.1038/ajg.2012.450. PMID 23318479.
  10. ^ Kellermayer R (Nov 15, 2013). "Prospects and challenges for intestinal microbiome therapy in pediatric gastrointestinal disorders". World J Gastrointest Pathophysiol. 4 (4): 91–3. doi:10.4291/wjgp.v4.i4.91. PMC 3829459. PMID 24244876.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  11. ^ Ventola C. L. (2015). "The Antibiotic Resistance Crisis, Part 1: Causes and Threats". Pharmacy and Therapeutics. 40 (4): 277–283. PMC 4378521. PMID 25859123.
  12. ^ Tanwar J, Das S, Fatima Z, Hameed S (Jul 16, 2014). "Multidrug resistance: an emerging crisis". Interdiscip Perspect Infect Dis. 2014: 541340. doi:10.1155/2014/541340. PMC 4124702. PMID 25140175.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  13. ^ Committee on New Directions in the Study of Antimicrobial Therapeutics (2006). Challenges for the Development of New Antibiotics — Rethinking the Approaches. National Academies Press. NBK19843.
  14. ^ "Copper Touch Surfaces". Archived from the original on 2012-07-23. Retrieved 2011-09-27.
  15. ^ "Research Proves Antimicrobial Copper Reduces the Risk of Infections by more than 40%" (PDF) (Press release). Copper Development Association. Archived from the original (PDF) on 2011-09-19.[unreliable medical source?]
  16. ^ "Chilean Subway Protected with Antimicrobial Copper" (PDF) (Press release). Copper Development Association. 19 July 2011. Archived from the original (PDF) on 23 November 2011.[unreliable medical source?]
  17. ^ Mollazadeh-Moghaddam K, Arfan M, Rafique J, Rezaee S, Jafari Fesharaki P, Gohari AR, Shahverdi AR (2010). "The antifungal activity of Sarcococca saligna ethanol extract and its combination effect with fluconazole against different resistant Aspergillus species". Applied Biochemistry and Biotechnology. 162 (1): 127–33. doi:10.1007/s12010-009-8737-2. PMID 19685213.
  18. ^ A. Smith-Palmer; J. Stewart; L. Fyfe (1998). "Antimicrobial properties of plant essential oils and essences against five important food-borne pathogens". Letters in Applied Microbiology. 26 (2): 118–122. doi:10.1046/j.1472-765x.1998.00303.x. PMID 9569693.
  19. ^ Kalemba D, Kunicka A (May 2003). "Antibacterial and antifungal properties of essential oils". Curr Med Chem. 10 (10): 813–29. doi:10.2174/0929867033457719. PMID 12678685.
  20. ^ Cowan, Marjorie Murphy (1 October 1999). "Plant Products as Antimicrobial Agents". Clinical Microbiology Reviews. 12 (4): 564–582. doi:10.1128/CMR.12.4.564. ISSN 0893-8512. PMC 88925. PMID 10515903.
  21. ^ a b "Archived copy". Archived from the original on 2013-05-20. Retrieved 2013-05-05.{{cite web}}: CS1 maint: archived copy as title (link)
  22. ^ Sanders FT (2003). "The Role of the EPA in the Regulation of Antimicrobial Pesticides in the United States". Pesticide Outlook. 14 (2): 251–255. doi:10.1039/b314854h.
  23. ^ Centers for Disease Control Prevention (CDC) (May 14, 2010). "Acute antimicrobial pesticide-related illnesses among workers in health-care facilities – California, Louisiana, Michigan, and Texas, 2002–2007". MMWR Morb Mortal Wkly Rep. 59 (18): 551–6. PMID 20467413.
  24. ^ Prestinaci, Francesca; Pezzotti, Patrizio; Pantosti, Annalisa (October 2015). "Antimicrobial resistance: a global multifaceted phenomenon". Pathogens and Global Health. 109 (7): 309–318. doi:10.1179/2047773215Y.0000000030. ISSN 2047-7724. PMC 4768623. PMID 26343252.
  25. ^ "20467413". US EPA. Retrieved 28 October 2014.
  26. ^ "Irradiation of Food FAQ: What is the actual process of irradiation?". U.S. Centers for Disease Control and Prevention. Archived from the original on 20 April 2016. Retrieved 17 April 2016.
  27. ^ "UV Disinfection Drinking Water". Water Research Center. Retrieved 18 April 2016.
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