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Flexible technologies and smart clothing for citizen medicine, home healthcare, and disease prevention
Improvement of the quality and efficiency of healthcare in medicine, both at home and in hospital, is becoming more and more important for patients and society at large. As many technologies (micro technologies, telecommunication, low-power design, new textiles, and flexible sensors) are now available, new user-friendly devices can be developed to enhance the comfort and security of the patient. As clothes and textiles are in direct contact with about 90% of the skin surface, smart sensors and smart clothes with noninvasive sensors are an attractive solution for home-based and ambulatory health monitoring. Moreover, wearable devices or smart homes with exosensors are also potential solutions. All these systems can provide a safe and comfortable environment for home healthcare, illness prevention, and citizen medicine
WHAT ARE YOUR VIEWS ON BUNDLE CLOTHINGS?
Symptoms of Diseases contagious from clothing
The list of signs and symptoms mentioned in various sources for Diseases contagious from clothing includes the 1 symptoms listed below:
- Symptoms can vary considerably depending on the particular disease involved
Diseases contagious from clothing: Related Conditions
Research the causes of these diseases that are similar to, or related to, Diseases contagious from clothing:
Types of Diseases contagious from clothing:
Types of Diseases contagious from clothing:- Amebic dysentery
- Dysentery
- Genital warts
- Gonorrhea
- Impetigo
- Pubic lice
- Scabies
- Tinea
- Vaginal candidiasis
- Yaws
Primary Cause of Diseases contagious from clothing
The primary cause of Diseases contagious from clothing is the result:
- of transmission of an infectious agent by another person by one or more of the following: saliva, air, cough, fecal-oral route, surfaces, blood, needles, blood transfusions, sexual contact, mother to fetus, etc.
Diseases contagious from clothing: Related Medical Conditions
Hand mouth and foot disease
German measeles
Diseases contagious from clothing: Causes and Types
Causes of Types of Diseases contagious from clothing: Review the cause informationfor the various types of Diseases contagious from clothing:
Symptoms of Diseases contagious from clothing
Symptoms can vary considerably depending on the particular disease involved.
About misdiagnosis: When checking for a misdiagnosis of Diseases contagious from clothing or confirming a diagnosis of Diseases contagious from clothing, it is useful to consider what other medical conditions might be possible misdiagnoses or other alternative conditions relevant to diagnosis. These alternate diagnoses of Diseases contagious from clothing may already have been considered by your doctor or may need to be considered as possible alternative diagnoses or candidates for misdiagnosis of Diseases contagious from clothing. For a general overview of misdiagnosis issues for all diseases, see Overview of Misdiagnosis.
China Burns Old Clothing Donated From Abroad to Avoid 'Foreign Diseases'
PEKING — In one of the most bizarre public exhibitions in recent Chinese history, soldiers piled up more than 20 tons of used clothing from abroad and torched the hand-me-downs with flame throwers.
As the smoke spiraled upward at a garbage disposal site in the Haidian district of western Peking, a crowd--specially assembled for the Nov. 12 occasion--cheered, television cameras recorded the event for the evening news broadcasts, and a deputy mayor delivered a speech.
During the next two weeks, officially sponsored burnings of used foreign clothing were reported in at least two other Chinese cities. Throughout the fall, Chinese newspapers have been warning the public not to buy or sell second-hand clothes from overseas or from Hong Kong and Macao.
Chinese officials usually describe the actions as general public health measures. Su Shifang, vice minister of China's general administration of customs, explained in September that a ban on importing used clothes was necessary "to prevent epidemic diseases from being introduced to China."
Many foreign analysts here believe that the real objective is to keep AIDS--acquired immune deficiency syndrome--out of the country
WHAT ARE YOUR VIEWS ON BUNDLE CLOTHINGS?
there are many kind of bundles out there, local and also international.. there's clothing which consists of t-shirts and blouse, jeans, stuffed toys, shoes and even bed sheets and curtains.. some are still in great shape, some aren't so good and full of stains.. some were genuinely given away, some were stolen from them, mostly shoes.. there's so many kind of bundles..
personally, I have been to a few bundle places in Alor Setar.. hey, I'm no rich snobby girl who's all high up in the clouds spending her parents money on expensive clothes ftw, I'm just a simple girl who has no source of income, yet.. now, the bundle place I went sells really freaking cheap clothes,RM1 per piece.. you read me right, RM1 ftw! but here's the catch, you have to dive in tonnes and tonnes of clothes to find the nicest clothing.. there are some nice ones on racks, but they cost more, usually RM5 and above, so I'd rather swim in clothes than pay more, thank you very much..
you might think I'm gross or whatever, but I don't really care.. cause the bundle shop offers really pretty clothes, from overseas, namely from Korea and Japan.. you know how trendy and fashionable chicks over there are, what is not in fashion over there now, is fashionable here in Malaysia.. skirts are mostly everywhere, but you can find leather jackets, mini skirts, jeans, and also nice shirts, not forgetting dresses to die for.. hey, they're still in good shape, just not wanted by their previous owner..
okay, I get it, bundle clothing is not hygienic, it's full of germs and it's not clean.. this I agree with you, but only before you wash the clothes.. personally when I buy bundle clothes, I soak them inside hot water to kill the germs.. then I wash them using detergent, like how you wash normal clothing.. I don't mix them with my other clothes, I only wash bundle clothing together.. anyway, check out some of the clothes I picked out at the bundle so time back, which I don't wear anymore and is selling..
BUNDLE AND BECOME TO HEALTH ISU
Written by Sade Oguntola.Wednesday, 14 September 2011
For many people, second-hand goods market has become the best way out of the present economic difficulties. For those who do buy fairly used second-hand clothes, experts caution on health hazards that buying these clothes popularly referred
Nkechi Amadi, 23, a student of The Polytechnic Ibadan, was initially hesitant of comments from her friends when she mentioned that her aunty who trades in fairly used clothes popularly called Okirika, bend-down boutique or bend-down select was the instrument to her new wardrobe. Looking prim and proper in a pink lacy blouse and jeans pants, with a shoe to match, her friends could hardly believe that such beautiful blouses and shoes at low costs were sold at second-hand clothes shops.
MosNkechi, like Asabi Adekola, a secretary in a private firm, also sees nothing wrong in people patronising markets where second-hand shoes and bags are sold. In fact, “most of the second-hand goods last longer than the new ones and they are a bit cheaper. You will also get value for your money
Mostt of the times, I get pure leather shoes and bags while the new ones are made with inferior leather,” she said.
That sales are booming in markets where second-hand items are sold is an understatement. In most of the markets for second-hand goods, there is always a rush by customers. Yaba, Katangua and Aswani are the biggest markets for second-hand clothes. All classes of people who want to dress corporate patronise these sale joints. Items readily available in these markets are clothing’s, shoes, towels, bedspreads, belts, under wears, bags and trinkets.
But not all items shipped to many developing countries are necessarily used items. Some of them cannot be sold in their countries of production because they come out with minor factory defects. It could just be that a button hole is missing. Some clothes were also donations by the manufacturing companies either to humanitarian organisations like the Red Cross, refugees and orphanage but the goods end up being cornered by business conscious people.
In the past years, second-hand clothes were synonymous with poverty; the rich and middle class bought their clothes from boutiques and stores. But today, the reverse is the case. Both the middle class and the low income earners have practically adjusted their budgets and are now visiting these markets. Unfortunately, the reality of life is that second-hand markets is the saving grace for some people who despite the global economic recession wants to feel good or dress their children like their peers with affluence.
Ironically, medical and environmental experts continue to worry about the harmful effects of these used items, even though people cannot be stopped patronising second-hand wears. “It is difficult trying to stop people buying these clothes and shoes, especially when these are people that do not have enough resources to buy clothes that are new and, of course, want to get clothed and look good,” stated Dr Adeola Fowotade, a consultant clinical virologist at the University College Hospital (UCH), Ibadan, Oyo State.
According to her, “some people buy these fairly used second-hand clothes for their children because they want them to dress well just like their peers. So just as there are tokunbo cars, so are tokunbo wears and there is nothing that we can do about it. It is just another thing we have to accept and play safe in the face of the situation.”
But second-hand goods do carry a few health risks such as infestations from scabies, mites, lice, and fungi. For instance, transmission of lice can occur through infected clothing, bedding and furniture. While many of these germs can survive away from a human host for two to four days, ringworms remain contagious for a much longer period.
According to the medical expert, “whatever illness the person that wore the cloth had before his or her death could most likely be transmitted to the buyer, especially if it is a disease that can be transmitted to the new buyer through body fluids like sweat.”
“Actually a lot of diseases can be contracted through buying these clothes; it is just like sharing clothes. Many diseases could be transferred through contact such as scabies, ringworm and all sorts of skin infections. If such a new buyer wore the underwear of another person that had a sexually transmitted disease like gonorrhea, such stand the risk of contracting the infection due to contact with infected body fluids.”
Nonetheless, Dr Fowotade stated that individuals can reduce their risk of contracting diseases from second-hand goods by not trying them out before washing them. “It is not the best to try it on first to be sure whether it fits or not before washing. It should be discouraged as much as possible. Rather, they should buy the clothes, soak and wash them inside hot water with active detergent before spreading in the sun to kill any germ that might be on such clothes. It is also important to iron such clothes to further reduce the danger of contracting any disease from the clothing.”
However, Dr Fowotade discouraged buying second hand underwear and brassieres. ”In my own opinion, second-hand underwear should be banned. It does not make sense. We have cheap underwear in the market that almost anyone can afford to buy,” she declared.
Dr Debo Oresanya, President, Nigerian Association of Dermatologist, declared that all fairly used clothes either bought as second-hand, gotten from charity or brought newly from the shop should be washed and ironed before they were worn.
According to him, “obviously, once any clothe is washed and ironed before wearing, it is safe to be worn.” These clothes are made in different parts of the world, kept in boxes; pass through many hands before they are then purchased at the shop. They can easily be infested with parasites.
Dr Oresanya, who declared that without proper cleaning, second hand undergarments can spread diseases, said it was not a good idea for people to buy second-hand underwear.
However, for those who do buy used shoes, it is best to leave such out in the sun for several days before wearing. But items that cannot be washed such as toys, pillows and delicates can be dry cleaned, sealed in a plastic bag for five days or placed on high heat in a tumble dryer for 10 minutes
Destruction of Lice in Clothing by hot and cold Air
J. R. Busvinea1
a1 Entomologist, Ministry of Health.
The most suitable methods of disinfecting clothing and bedding depend upon circumstances, such as the extent and importance of the pest infestation, the numbers to be treated and the facilities available. This paper describes investigations of heat and cold for killing lice which were undertaken with an eye to very different situations, viz., the heat treatment of bedding in London air-raid shelters and the possible use of winter cold in Eastern Europe during post-war relief. Nevertheless, the problems have one thing in common; the inherent difficulty of heat transference through clothing and bedding.
Second hand clothes could spread skin diseases
By Mar 1, 2011 - 14:30
KABUL (): For many poor people in the Afghan capital, the second-hand clothes market provides an affordable option to keep warm in winter.
But doctors are warning that wearing unwashed clothes may cause skin diseases. econd-hand clothes are sold all over the capital, in shops and on hand carts. The demand goes up during the winter months when the temperatures can drop to below freezing and only a few Afghans are lucky enough to have the simple wood-burning stove in their homes.
Ramazan, 38, a father of four, bought second-hand winter clothes for his 3-year-old child from a hand cart near Pamir Cinema in Kabul city. Asked why he did not buy new clothes for his child, he replied he did not have the money to do so.
"I am a labourer and have a low income. I have to purchase second-hand clothes. Unless the clothes are very dirty, we don’t wash them. I did not know that wearing second-hand clothes could cause skin diseases,” he said.
Ramazan said that he and his children often get sick and he did not know the reason for it. People who wear second-hand clothes must wash or disinfect the items before they wear them or they may suffer from different kinds of skin diseases, Dr. Abdul Matin Baha, a dermatologist at Maiwand Hospital in Kabul, said.
Diseases like dermatitis, scabies and fungal diseases can be passed on by wearing unwashed second-hand clothes, he said, advising that clothes be washed with warm water and disinfectant and ironed on both sides.
Used shoes and sandals can also carry skin diseases, and should be washed with warm water and disinfectant, Baha said. Clothes which come into direct contact with the skin, such as underwear, can be the most dangerous if they are not disinfected well.
Baha advised paying more attention to the washing of these types of garments. Mehro 55, who was buying sweaters for her 9-year old daughter said she could not afford to buy new clothes for her children.
She has nine children and her husband is a hand cart vendor. "We are poor, we have to buy used clothing," she said.
“These clothes may cause disease but the winter weather is also dangerous,” she said.
The price of a second-hand sweater is between 40 afgnanis ($0.80) to 70 afghanis, while at the store such an item can cost 300 afghanis, she said. "Two months ago, one of my children got an itchy rash all over his body. When we took him to the doctor he said it was due to wearing used clothing," she said.
Mir Hassan 42, who sells second-hand clothes near Pamir Cinema said they do not wash the clothes before selling them. According to him, they buy second-hand clothes from traders in the Chindawol or Mandawi area, and then they sell them on.
Most of their customers are poor, he said. “Prices will increase if the traders wash and disinfect the clothes and then people cannot afford to buy them,” he said. Faiz Mohammad, 25, who sells children’s used sweaters in Kabul’s city centre, said most of his customers are poor and cannot afford to buy new clothes.
"The weather is very cold and most of our clients are poor; therefore, they have to buy used clothes, and they put them on their children unwashed." Most of the used clothes, including sweaters, coats, shirts, under wear, socks, boots, shoes and sandals are imported from European countries, the United States and Canada, according to traders.
Mohammad Qasim Sahebi, a doctor at Jamhoriat Hospital, also said certain bacteria and infections could be spread by second-hand clothes. The bacteria on the clothes are very resistant and so unless the garments are treated, the germs will remain and cause skin diseases, he said. Sahebi advised storing the clothes for 48 hours in a cold area, then washing them with disinfectant and warm water and using a hot iron on both sides. He said the media division of the Ministry of Public Health should advise people on how to treat second-hand clothes to avoid the spread of skin diseases.
Dr. Mohammad Hakim Satar, deputy chief of the environmental health department, acknowledged his department had not done anything to promote better treatment of used clothing. His department was more involved in the field of air pollution, food safety and safe drinking water, he said.
![Second-hand clothing shops are becoming popular across Yemen because of lower prices. [Faisal Darem/Al-Shorfa]](http://al-shorfa.com/shared/images/2010/12/20/101220-feature-3-photo-650_416.jpg)
Despite health warnings, used clothing shops gain popularity in Yemen
Adel Sabri, 33, is keen to pay a monthly visit to used clothes markets in Sanaa where he finds "good quality and stylish clothes of international brands at low prices". Adel said that his family is also "keen on buying these clothes because they are better than the new clothes imported from China, which are in many cases of low quality", and that he finds all the winter and summer clothes he wants.
Second-hand clothing markets have spread across Yemeni cities. They specialise in the resale of used European-made clothes. These are in great demand because of their high quality and exceedingly cheap prices.
Fayez al-Bakari, owner of a used clothing shop in downtown Sanaa, told Al-Shorfa that he has been working in this profession "for 20 years and that it has evolved significantly and provides clothes of genuine international brands at cheap prices, as one can buy a 400 dollar jacket for an average price of 15 dollars".
Al-Bakari added that "the markets for selling this kind of clothing have proliferated due to the increase in customers who avoid buying new clothes and opt instead to buy cheap but genuine articles".
Fayez al-Hijra, who has been also working in this trade for the past 10 years told Al-Shorfa that he "washes and disinfects these clothes before selling them so that they show their real value", adding that he sells only suits, jackets and dresses and that his clients are both male and female.
"The economic factor inherent in the low prices and high quality of these clothes help them gain the confidence of consumers, especially when the market is flooded with brand-new but counterfeit clothes," he said.
Economic expert Abdul Aziz Thabet says that the popularity of these clothes in Yemen is due to "the weak purchasing power of the Yemenis".
"The prices of these products are commensurate with the purchasing power of citizens," he said. "Consumer numbers [for these clothes] are growing in light of the drop in income. The consumer finds in these clothes high quality and very cheap prices compared to clothes sold by the dealers and merchants of new clothes."
Thabet said that this trade augments the economic downturn in addition to "resulting in many medical conditions as a result of not sterilising and washing the clothes either by merchants or by consumers who do not know enough about these clothes and the importance of cleaning them before use".
Dr Nabil al-Najjar, a dermatologist at As-Sabine Hospital in Sanaa, told Al-Shorfa that "used clothes carry fungi and skin diseases and cause allergic reactions and skin rashes in some cases".
Najjar said that used clothing should be "well washed, disinfected and pressed upon purchase in order to avoid their negative effects".
General Manager of Consumer Protection in the Ministry of Industry and Trade Mahmoud al-Nakeeb said that second-hand clothes are sometimes "declared new and therefore allowed to enter the country," adding that the ministry will issue directives to prevent these clothes from entering the markets.
CUBA. Reports from Cienfuegos, Casilda, and Santa Cruz del Sur
Studies on Ringworm Funguses with Reference to Public Health Problems *
Lee Bonar, and Alice Domsler Dreyer
Read More: http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.22.9.909
BUNDLE
THE CONTROL OF MICROBIAL GROWTH
Introduction
In the 19th century, surgery was risky and dangerous, and patients undergoing even the most routine operations were at very high risk of infection. This was so because surgery was not performed under aseptic conditions. The operating room, the surgeon's hands, and the surgical instruments were laden with microbes, which caused high levels of infection and mortality.Surgeons in the mid-1800s often operated wearing their street clothes, without washing their hands. They frequently used ordinary sewing thread to suture wounds, and stuck the needles in the lapels of their frock coats in between patients. Surgical dressings were often made up of surplus cotton or jute from the floors of cotton mills. It was against this background that French scientist Louis Pasteur demonstrated that invisible microbes caused disease.
Louis Pasteur
Pasteur's work influenced the English surgeon Joseph Lister, who applied Pasteur's germ theory of disease to surgery, thus founding modern antiseptic surgery. To disinfect, Lister used a solution of carbolic acid (phenol), which was sprayed around the operating room by a handheld sprayer.
Joseph Lister
19th Century surgery using Lister’s carbolic acid sprayer.
It was clear that Lister's techniques were effective in increasing the rates of surviving surgery, but his theories were controversial because many 19th century surgeons were unwilling to accept something they could not see. Also, perhaps another reason that surgeons were slow to pick up on Lister's methods was the fact that during surgery they were required to breathe an irritating aerosol of phenol.
Control of Microbial Growth
The control of microbial growth is necessary in many practical situations, and significant advances in agriculture, medicine, and food science have been made through study of this area of microbiology.
"Control of microbial growth", as used here, means to inhibit or prevent growth of microorganisms. This control is affected in two basic ways: (1) by killing microorganisms or (2) by inhibiting the growth of microorganisms. Control of growth usually involves the use of physical or chemical agents which either kill or prevent the growth of microorganisms. Agents which kill cells are called cidal agents; agents which inhibit the growth of cells (without killing them) are referred to as static agents. Thus, the term bactericidalrefers to killing bacteria, and bacteriostatic refers to inhibiting the growth of bacterial cells. A bactericide kills bacteria, a fungicide kills fungi, and so on.
In microbiology, sterilization refers to the complete destruction or elimination of all viable organisms in or on a substance being sterilized. There are no degrees of sterilization: an object or substance is either sterile or not. Sterilization procedures involve the use of heat, radiation or chemicals, or physical removal of cells.
Methods of Sterilization
Heat: most important and widely used. For sterilization one must consider the type of heat, and most importantly, the time of application and temperature to ensure destruction of all microorganisms. Endospores of bacteria are considered the most thermoduric of all cells so their destruction guarantees sterility.
Incineration: burns organisms and physically destroys them. Used for needles, inoculating wires, glassware, etc. and objects not destroyed in the incineration process.
Boiling: 100o for 30 minutes. Kills everything except some endospores. To kill endospores, and therefore sterilize a solution, very long (>6 hours) boiling, or intermittent boiling is required (See Table 1 below).
Autoclaving (steam under pressure or pressure cooker)
Autoclaving is the most effective and most efficient means of sterilization. All autoclaves operate on a time/temperature relationship. These two variables are extremely important. Higher temperatures ensure more rapid killing. The usual standard temperature/pressure employed is 121ºC/15 psi for 15 minutes. Longer times are needed for larger loads, large volumes of liquid, and more dense materials. Autoclaving is ideal for sterilizing biohazardous waste, surgical dressings, glassware, many types of microbiologic media, liquids, and many other things. However, certain items, such as plastics and certain medical instruments (e.g. fiber-optic endoscopes), cannot withstand autoclaving and should be sterilized with chemical or gas sterilants. When proper conditions and time are employed, no living organisms will survive a trip through an autoclave.
Schematic diagram of a laboratory autoclave in use to sterilize microbiological culture medium. Sterilization of microbiological culture media is is often carried out with the autoclave. When microbiological media are prepared, they must be sterilized and rendered free of microbial contamination from air, glassware, hands, etc. The sterilization process is a 100% kill, and guarantees that the medium will stay sterile unless exposed to contaminants.
An autoclave for use in a laboratory or hospital setting.
Why is an autoclave such an effective sterilizer? The autoclave is a large pressure cooker; it operates by using steam under pressure as the sterilizing agent. High pressures enable steam to reach high temperatures, thus increasing its heat content and killing power. Most of the heating power of steam comes from its latent heat of vaporization. This is the amount of heat required to convert boiling water to steam. This amount of heat is large compared to that required to make water hot. For example, it takes 80 calories to make 1 liter of water boil, but 540 calories to convert that boiling water to steam. Therefore, steam at 100º C has almost seven times more heat than boiling water.
Moist heat is thought to kill microorganisms by causing denaturation of essential proteins. Death rate is directly proportional to the concentration of microorganisms at any given time. The time required to kill a known population of microorganisms in a specific suspension at a particular temperature is referred to as thermal death time (TDT). Increasing the temperature decreases TDT, and lowering the temperature increases TDT. Processes conducted at high temperatures for short periods of time are preferred over lower temperatures for longer times.
Environmental conditions also influence TDT. Increased heat causes increased toxicity of metabolic products and toxins. TDT decreases with pronounced acidic or basic pHs. However, fats and oils slow heat penetration and increase TDT. It must be remembered that thermal death times are not precise values; they measure the effectiveness and rapidity of a sterilization process. Autoclaving 121ºC/15 psi for 15 minutes exceeds the thermal death time for most organisms except some extraordinary sporeformers.
Dry heat (hot air oven): basically the cooking oven. The rules of relating time and temperature apply, but dry heat is not as effective as moist heat (i.e., higher temperatures are needed for longer periods of time). For example 160o/2hours or 170o/1hour is necessary for sterilization. The dry heat oven is used for glassware, metal, and objects that won't melt.
Irradiation: usually destroys or distorts nucleic acids. Ultraviolet light is commonly used to sterilize the surfaces of objects, although x-rays, gamma radiation and electron beam radiation are also used.
Ultraviolet lamps are used to sterilize workspaces and tools used in microbiology laboratories and health care facilities. UV light at germicidal wavelengths (two peaks, 185 nm and 265 nm) causes adjacent thymine molecules on DNA to dimerize, thereby inhibiting DNA replication (even though the organism may not be killed outright, it will not be able to reproduce). However, since microorganisms can be shielded from ultraviolet light in fissures, cracks and shaded areas, UV lamps should only be used as a supplement to other sterilization techniques.
An ultraviolet sterilization cabinet.
Gamma radiation and electron beam radiation are forms of ionizing radiation used primarily in the health care industry. Gamma rays, emitted from cobalt-60, are similar in many ways to microwaves and x-rays. Gamma rays delivered during sterilization break chemical bonds by interacting with the electrons of atomic constituents. Gamma rays are highly effective in killing microorganisms and do not leave residues or have sufficient energy to impart radioactivity.
Electron beam (e-beam) radiation, a form of ionizing energy, is generally characterized by low penetration and high-dose rates. E-beam irradiation is similar to gamma radiation in that it alters various chemical and molecular bonds on contact. Beams produced for e-beam sterilization are concentrated, highly-charged streams of electrons generated by the acceleration and conversion of electricity.
e-beam and gamma radiation are for sterilization of items ranging from syringes to cardiothoracic devices.
Filtration involves the physical removal (exclusion) of all cells in a liquid or gas. It is especially important for sterilization of solutions which would be denatured by heat (e.g. antibiotics, injectable drugs, amino acids, vitamins, etc.). Portable units can be used in the field for water purification and industrial units can be used to "pasteurize" beverages. Essentially, solutions or gases are passed through a filter of sufficient pore diameter (generally 0.22 micron) to remove the smallest known bacterial cells.
This water filter for hikers and backpackers is advertised to "eliminate Giardia, Cryptosporidium and most bacteria." The filter is made from 0.3 micron pleated glass fiber with a carbon core.
A typical set-up in a microbiology laboratory for filtration sterilization of medium components that would be denatured or changed by heat sterilization. The filter is placed (aseptically) on the glass platform, then the funnel is clamped and the fluid is drawn by vacuum into a previously sterilized flask. The recommended size filter that will exclude the smallest bacterial cells is 0.22 micron.
Chemical and gas
Chemicals used for sterilization include the gases ethylene oxide and formaldehyde, and liquids such as glutaraldehyde. Ozone, hydrogen peroxide and peracetic acid are also examples of chemical sterilization techniques are based on oxidative capabilities of the chemical.
Ethylene oxide (ETO) is the most commonly used form of chemical sterilization. Due to its low boiling point of 10.4ºC at atmospheric pressure, EtO) behaves as a gas at room temperature. EtO chemically reacts with amino acids, proteins, and DNA to prevent microbial reproduction. The sterilization process is carried out in a specialized gas chamber. After sterilization, products are transferred to an aeration cell, where they remain until the gas disperses and the product is safe to handle.
ETO is used for cellulose and plastics irradiation, usually in hermetically sealed packages. Ethylene oxide can be used with a wide range of plastics (e.g. petri dishes, pipettes, syringes, medical devices, etc.) and other materials without affecting their integrity.
ETO is used for cellulose and plastics irradiation, usually in hermetically sealed packages. Ethylene oxide can be used with a wide range of plastics (e.g. petri dishes, pipettes, syringes, medical devices, etc.) and other materials without affecting their integrity.
An ethylene oxide sterilization gas chamber.
Ozone sterilization has been recently approved for use in the U.S. It uses oxygen that is subjected to an intense electrical field that separates oxygen molecules into atomic oxygen, which then combines with other oxygen molecules to form ozone.
Ozone is used as a disinfectant for water and food. It is used in both gas and liquid forms as an antimicrobial agent in the treatment, storage and processing of foods, including meat, poultry and eggs. Many municipalities use ozone technology to purify their water and sewage. Los Angeles has one of the largest municipal ozone water treatment plants in the world. Ozone is used to disinfect swimming pools, and some companies selling bottled water use ozonated water to sterilize containers.
An ozone fogger for sterilization of egg surfaces. The system reacts ozone with water vapors to create powerful oxidizing radicals. This system is totally chemical free and is effective against bacteria, viruses and hazardous microorganisms which are deposited on egg shells.
An ozone sterilizer for use in the hospital or other medical environment.
Low Temperature Gas Plasma (LTGP) is used as an alternative to ethylene oxide. It uses a small amount of liquid hydrogen peroxide (H2O2), which is energized with radio frequency waves into gas plasma. This leads to the generation of free radicals and other chemical species, which destroy organisms.
An LTGP sterilizer that pumps vaporized H2O2 into the chamber.
Non Sterilizing Methods to Control Microbial Growth
Many physical and chemical technologies are employed by our civilization to control the growth of (certain) microbes, although sterility may not the desired end-point. Rather, preventing spoilage of food or curing infectious disease might be the desired outcome.
Applications of Heat
The lethal temperature varies in microorganisms. The time required to kill depends on the number of organisms, species, nature of the product being heated, pH, and temperature. Autoclaving, which kills all microorganisms with heat, is commonly employed in canning, bottling, and other sterile packaging procedures. This is an ultimate form of preservation against microbes. But, there are some other uses of heat to control growth of microbes although it may not kill all organisms present.
Boiling: 100o for 30 minutes (more time at high altitude). Kills everything except some endospores. It also inactivates viruses. For the purposes of purifying drinking water, 100o for five minutes is a "standard" in the mountains" though there have been some reports that Giardia cysts can survive this process. Longer boiling might be recommended for Mississippi River water the closer to the Gulf.
Pasteurization is the use of mild heat to reduce the number of microorganisms in a product or food. In the case of pasteurization of milk, the time and temperature depend on killing potential pathogens that are transmitted in milk, i.e., staphylococci, streptococci, Brucella abortus and Mycobacterium tuberculosis. But pasteurization kills many spoilage organisms, as well, and therefore increases the shelf life of milk especially at refrigeration temperatures (2°C).
Milk is usually pasteurized by heating, typically at 63°C for 30 minutes (batch method) or at 71°C for 15 seconds (flash method), to kill bacteria and extend the milk's usable life. The process kills pathogens but leaves relatively benign microorganisms that can sour improperly stored milk.
During the process of ultrapasteurization, also known as ultra high-temperature (UHT) pasteurization, milk is heated to temperatures of 140 °C. In the direct method, the milk is brought into contact with steam at 140°C for one or two seconds. A thin film of milk falls through a chamber of high-pressure steam, heating the milk instantaneously. The milk is flash cooled by application of a slight vacuum, which serves the dual purpose of removing excess water in the milk from condensing steam. In the indirect method of ultrapasteurization, milk is heated in a plate heat exchanger. It takes several seconds for the temperature of the milk to reach 140°C, and it is during this time that the milk is scalded, invariably leading to a burned taste. If ultrapasteurization is coupled with aseptic packaging, the result is a long shelf life and a product that does not need refrigeration.
During the process of ultrapasteurization, also known as ultra high-temperature (UHT) pasteurization, milk is heated to temperatures of 140 °C. In the direct method, the milk is brought into contact with steam at 140°C for one or two seconds. A thin film of milk falls through a chamber of high-pressure steam, heating the milk instantaneously. The milk is flash cooled by application of a slight vacuum, which serves the dual purpose of removing excess water in the milk from condensing steam. In the indirect method of ultrapasteurization, milk is heated in a plate heat exchanger. It takes several seconds for the temperature of the milk to reach 140°C, and it is during this time that the milk is scalded, invariably leading to a burned taste. If ultrapasteurization is coupled with aseptic packaging, the result is a long shelf life and a product that does not need refrigeration.
Table 1. Recommended use of heat to control bacterial growth
| Treatment | Temperature | Effectiveness |
| Incineration | >500o | Vaporizes organic material on nonflammable surfaces but may destroy many substances in the process |
| Boiling | 100o | 30 minutes of boiling kills microbial pathogens and vegetative forms of bacteria but may not kill bacterial endospores |
| Intermittent boiling | 100o | Three 30-minute intervals of boiling, followed by periods of cooling kills bacterial endospores |
| Autoclave and pressure cooker (steam under pressure) | 121o/15 minutes at 15# pressure | kills all forms of life including bacterial endospores. The substance being sterilized must be maintained at the effective T for the full time |
| Dry heat (hot air oven) | 160o/2 hours | For materials that must remain dry and which are not destroyed at T between 121o and 170o Good for glassware, metal, not plastic or rubber items |
| Dry heat (hot air oven) | 170o/1 hour | Same as above. Note increasing T by 10 degrees shortens the sterilizing time by 50 percent |
| Pasteurization (batch method) | 63o/30 minutes | kills most vegetative bacterial cells including pathogens such as streptococci, staphylococci and Mycobacterium tuberculosis |
| Pasteurization (flash method) | 72o/15 seconds | Effect on bacterial cells similar to batch method; for milk, this method is more conducive to industry and has fewer undesirable effects on quality or taste |
| Ultrapasteurization (direct method) | 140o/2 seconds | Effect on most bacterial cells is lethal. For milk, this method creates a product with relatively long shelf life at refrigeration temperatures. |
Low temperature (refrigeration and freezing): Most organisms grow very little or not at all at 0oC. Perishable foods are stored at low temperatues to slow rate of growth and consequent spoilage (e.g. milk). Low temperatures are not bactericidal. Psychrotrophs, rather than true psychrophiles, are the usual cause of food spoilage in refrigerated foods. Although a few microbes will grow in supercooled solutions as low as minus 20oC, most foods are preserved against microbial growth in the household freezer.
Drying (removal of H2O): Most microorganisms cannot grow at reduced water activity (Aw < 0.90). Drying is often used to preserve foods (e.g. fruits, grains, etc.). Methods involve removal of water from product by heat, evaporation, freeze-drying, and addition of salt or sugar.
Irradiation (UV, x-ray, gamma radiation): destroys microorganisms as described under "sterilization". Many spoilage organisms are readily killed by irradiation.
In some parts of Europe, fruits and vegetables are irradiated to increase their shelf life up to 500 percent. The practice has not been accepted in the U.S. UV light can be used to pasteurize fruit juices by flowing the juice over a high intensity ultraviolet light source. UV systems for water treatment are available for personal, residential and commercial applications and may be used to control bacteria, viruses and protozoan cysts.
The FDA has approved irradiation of poultry and pork to control pathogens, as well as foods such as fruits, vegetables, and grains to control insects, and spices, seasonings, and dry enzymes used in food processing to control microorganisms. Food products are treated by subjecting them to radiation from radioactive sources, which kills significant numbers of insects, pathogenic bacteria and parasites.
According to the FDA, irradiation does not make food radioactive, nor does it noticeably change taste, texture, or appearance. Irradiation of food products to control food-borne disease in humans has been generally endorsed by the United Nation's World Health Organization and the American Medical Association. Two important Disease-causing bacteria that can be controlled by irradiation include Escherichia coli 0157:H7 and Salmonella species.
Control of microbial growth by chemical agents
Antimicrobial agents are chemicals that kill or inhibit the growth microorganisms. Antimicrobial agents include chemical preservatives and antiseptics, as well as drugs used in the treatment of infectious diseases of plants and animals. Antimicrobial agents may be of natural or synthetic origin, and they may have a static or cidal effect on microorganisms.
Types of antimicrobial agents
Antiseptics: microbicidal agents harmless enough to be applied to the skin and mucous membrane; should not be taken internally. Examples include alcohols, mercurials, silver nitrate, iodine solution, alcohols, detergents.
Disinfectants: agents that kill microorganisms, but not necessarily their spores, but are not safe for application to living tissues; they are used on inanimate objects such as tables, floors, utensils, etc. Examples include, hypochlorites, chlorine compounds, lye, copper sulfate, quaternary ammonium compounds, formaldehyde and phenolic compounds.
Common antiseptics and disinfectants and their uses are summarized in Table 2. Note: disinfectants and antiseptics are distinguished on the basis of whether they are safe for application to mucous membranes. Often, safety depends on the concentration of the compound.
Table 2. Common antiseptics and disinfectants
| Chemical | Action | Uses |
| Ethanol (50-70%) | Denatures proteins and solubilizes lipids | Antiseptic used on skin |
| Isopropanol (50-70%) | Denatures proteins and solubilizes lipids | Antiseptic used on skin |
| Formaldehyde (8%) | Reacts with NH2, SH and COOH groups | Disinfectant, kills endospores |
| Tincture of Iodine (2% I2 in 70% alcohol) | Inactivates proteins | Antiseptic used on skin Disinfection of drinking water |
| Chlorine (Cl2) gas | Forms hypochlorous acid (HClO), a strong oxidizing agent | Disinfect drinking water; general disinfectant |
| Silver nitrate (AgNO3) | Precipitates proteins | General antiseptic and used in the eyes of newborns |
| Mercuric chloride | Inactivates proteins by reacting with sulfide groups | Disinfectant, although occasionally used as an antiseptic on skin |
| Detergents (e.g. quaternary ammonium compounds) | Disrupts cell membranes | Skin antiseptics and disinfectants |
| Phenolic compounds (e.g. carbolic acid, lysol, hexylresorcinol, hexachlorophene) | Denature proteins and disrupt cell membranes | Antiseptics at low concentrations; disinfectants at high concentrations |
| Ethylene oxide gas | Alkylating agent | Disinfectant used to sterilize heat-sensitive objects such as rubber and plastics |
| Ozone | Generates lethal oxygen radicals | Purification of water, sewage |
Preservatives: static agents used to inhibit the growth of microorganisms, most often in foods. If eaten they should be nontoxic. Examples are calcium propionate, sodium benzoate, formaldehyde, nitrate and sulfur dioxide. Table 3a and 3b are lists of common preservative and their uses.
Table 3a. Some common preservatives added to processed foods
Salt - retards bacterial growth. Not good for blood pressure.
Nitrates - can be found in some cheeses, adds flavor, maintains pink color in cured meats and prevents botulism in canned foods. Can cause adverse reactions in children, and potentially carcinogenic.
Sulfur Dioxide and Sulfites - are used as preservatives and to prevent browning in alcoholic beverages, fruit juices, soft drinks, dried fruits and vegetables. Sulfites prevent yeast growth and also retard bacterial growth in wine. Sulfites may cause asthma and hyperactivity. They also destroy vitamins.
Benzoic Acid and Sodium Benzoate - are used to preserve oyster sauce, fish sauce, ketchup, non-alcoholic beverages, fruit juices, margarine, salads, confections, baked goods, cheeses, jams and pickled products. They have also been found to cause hyperactivity.
Propionic Acid and Propionates - used in bread, chocolate products, and cheese for lasting freshness.
Sorbic Acid and Sorbates - prevent mold formation in cheese and flour confectioneries
Table 3b. Common food preservatives and their uses
| Preservative | Effective Concentration | Uses |
| Propionic acid and propionates | 0.32% | Antifungal agent in breads, cake, Swiss cheeses |
| Sorbic acid and sorbates | 0.2% | Antifungal agent in cheeses, jellies, syrups, cakes |
| Benzoic acid and benzoates | 0.1% | Antifungal agent in margarine, cider, relishes, soft drinks |
| Sodium diacetate | 0.32% | Antifungal agent in breads |
| Lactic acid | unknown | Antimicrobial agent in cheeses, buttermilk, yogurt and pickled foods |
| Sulfur dioxide, sulfites | 200-300 ppm | Antimicrobial agent in dried fruits, grapes, molasses |
| Sodium nitrite | 200 ppm | Antibacterial agent in cured meats, fish |
| Sodium chloride | unknown | Prevents microbial spoilage of meats, fish, etc. |
| Sugar | unknown | Prevents microbial spoilage of preserves, jams, syrups, jellies, etc. |
| Wood smoke | unknown | Prevents microbial spoilage of meats, fish, etc. |
Chemotherapeutic agents (synthetic antibiotics): antimicrobial agents of synthetic origin useful in the treatment of microbial or viral disease. Examples are sulfonilamides, isoniazid, ethambutol, AZT, nalidixic acid and chloramphenicol. Note that the microbiologist's definition of a chemotherapeutic agent requires that the agent be used for antimicrobial purpose and excludes synthetic agents used for therapy against diseases that are not of microbial origin. Hence, pharmacology distinguishes the microbiologist's chemotherapeutic agent as a "synthetic antibiotic".
Antibiotics: antimicrobial agents produced by microorganisms that kill or inhibit other microorganisms. This is the microbiologist's definition. A more broadened definition of an antibiotic includes any chemical of natural origin (from any type of cell) which has the effect to kill or inhibit the growth of other types cells. Since most clinically-useful antibiotics are produced by microorganisms and are used to kill or inhibit infectious Bacteria, we will follow the classic definition. Note also (above), pharmacologists refer to any antimicrobial chemical used in the treatment of infectious disease as as antibiotic.
Three bacterial colonies growing on this plate secrete antibiotics that diffuse into the medium and inhibit the growth of a mold.
Antibiotics are low molecular-weight (non-protein) molecules produced as secondary metabolites, mainly by microorganisms that live in the soil. Most of these microorganisms form some type of a spore or other dormant cell, and there is thought to be some relationship (besides temporal) between antibiotic production and the processes of sporulation. Among the molds, the notable antibiotic producers are Penicillium and Cephalosporium, which are the main source of the beta-lactam antibiotics (penicillin and its relatives). In the Bacteria, the Actinomycetes, notably Streptomyces species, produce a variety of types of antibiotics including the aminoglycosides (e.g. streptomycin), macrolides (e.g. erythromycin), and the tetracyclines. Endospore-forming Bacillus species produce polypeptide antibiotics such as polymyxin and bacitracin. The table below (Table 4) is a summary of the classes of antibiotics and their properties including their biological sources.
Semisynthetic antibiotics are molecules produced my a microbe that are subsequently modified by an organic chemist to enhance their antimicrobial properties or to render them unique for a pharmaceutical patent.
Table 4. Classes of antibiotics and their properties
| Chemical class | Examples | Biological source | Spectrum (effective against) | Mode of action | |
| Beta-lactams (penicillins and cephalosporins) | Penicillin G, Cephalothin | Penicillium notatum andCephalosporium species | Gram-positive bacteria | Inhibits steps in cell wall (peptidoglycan) synthesis and murein assembly | |
| Semisynthetic penicillin | Ampicillin, Amoxycillin | Gram-positive and Gram-negative bacteria | Inhibits steps in cell wall (peptidoglycan) synthesis and murein assembly | ||
| Clavulanic Acid | Clavamox is clavulanic acid plus amoxycillin | Streptomyces clavuligerus | Gram-positive and Gram-negative bacteria | Suicide inhibitor of beta-lactamases | |
| Monobactams | Aztreonam | Chromobacter violaceum | Gram-positive and Gram-negative bacteria | Inhibits steps in cell wall (peptidoglycan) synthesis and murein assembly | |
| Carboxypenems | Imipenem | Streptomyces cattleya | Gram-positive and Gram-negative bacteria | Inhibits steps in cell wall (peptidoglycan) synthesis and murein assembly | |
| Aminoglycosides | Streptomycin | Streptomyces griseus | Gram-positive and Gram-negative bacteria | Inhibit translation (protein synthesis) | |
| Gentamicin | Micromonospora species | Gram-positive and Gram-negative bacteria esp. Pseudomonas | Inhibit translation (protein synthesis) | ||
| Glycopeptides | Vancomycin | Streptomyces orientales | Gram-positive bacteria, esp. Staphylococcus aureus | Inhibits steps in murein (peptidoglycan) biosynthesis and assembly | |
| Lincomycins | Clindamycin | Streptomyces lincolnensis | Gram-positive and Gram-negative bacteria esp. anaerobic Bacteroides | Inhibits translation (protein synthesis) | |
| Macrolides | Erythromycin | Streptomyces erythreus | Gram-positive bacteria, Gram-negative bacteria not enterics, Neisseria, Legionella, Mycoplasma | Inhibits translation (protein synthesis) | |
| Polypeptides | Polymyxin | Bacillus polymyxa | Gram-negative bacteria | Damages cytoplasmic membranes | |
| Bacitracin | Bacillus subtilis | Gram-positive bacteria | Inhibits steps in murein (peptidoglycan) biosynthesis and assembly | ||
| Polyenes | Amphotericin | Streptomyces nodosus | Fungi | Inactivate membranes containing sterols | |
| Nystatin | Streptomyces noursei | Fungi (Candida) | Inactivate membranes containing sterols | ||
| Rifamycins | Rifampicin | Streptomyces mediterranei | Gram-positive and Gram-negative bacteria, Mycobacterium tuberculosis | Inhibits transcription (eubacterial RNA polymerase) | |
| Tetracyclines | Tetracycline | Streptomyces species | Gram-positive and Gram-negative bacteria, Rickettsias | Inhibit translation (protein synthesis) | |
| Semisynthetic tetracycline | Doxycycline | Gram-positive and Gram-negative bacteria, Rickettsias Ehrlichia, Borrelia | Inhibit translation (protein synthesis) | ||
| Chloramphenicol | Chloramphenicol | Streptomyces venezuelae | Gram-positive and Gram-negative bacteria | Inhibits translation (protein synthesis) |
Antimicrobial Agents Used in the Treatment of Infectious Disease
The modern era of antimicrobial chemotherapy began following Fleming's discovery in 1929 of the powerful bactericidal substance penicillin, and Domagk's discovery in 1935 of synthetic chemicals (sulfonamides) with broad antimicrobial activity. In the early 1940's, spurred partially by the need for antibacterial agents in WW II, penicillin was isolated, purified and injected into experimental animals, where it was found to not only cure infections but also to possess incredibly low toxicity for the animals. This fact ushered into being the age of antibiotic chemotherapy and an intense search for similar antimicrobial agents of low toxicity to animals that might prove useful in the treatment of infectious disease. The rapid isolation of streptomycin, chloramphenicol and tetracycline soon followed, and by the 1950's, these and several other antibiotics were in clinical usage.
The most important property of a clinically-useful antimicrobial agent, especially from the patient's point of view, is its selective toxicity, i.e., the agent acts in some way that inhibits or kills bacterial pathogens but has little or no toxic effect on the animal taking the drug This implies that the biochemical processes in the bacteria are in some way different from those in the animal cells, and that the advantage of this difference can be taken in chemotherapy.
Antibiotics may have a cidal (killing) effect or a static (inhibitory) effect on a range of microbes. The range of bacteria or other microorganisms that are affected by a certain antibiotic is expressed as its spectrum of action. Antibiotics effective against procaryotes which kill or inhibit a wide range of Gram-positive and Gram-negative bacteria are said to be broad spectrum . If effective mainly against Gram-positive or Gram-negative bacteria, they are narrow spectrum. If effective against a single organism or disease, they are referred to as limited spectrum.
Kinds of Antimicrobial Agents and their Primary Modes of Action
1. Cell wall synthesis inhibitors Cell wall synthesis inhibitors generally inhibit some step in the synthesis of bacterial peptidoglycan. Generally they exert their selective toxicity against eubacteria because human cells lack cell walls.
Beta lactam antibiotics Chemically, these antibiotics contain a 4-membered beta lactam ring. They are the products of two groups of fungi, Penicillium and Cephalosporium molds, and are correspondingly represented by the penicillins and cephalosporins. The beta lactam antibiotics inhibit the last step in peptidoglycan synthesis, the final cross-linking between between peptide side chains, mediated by bacterial carboxypeptidase and transpeptidase enzymes. Beta lactam antibiotics are normally bactericidal and require that cells be actively growing in order to exert their toxicity.
Natural penicillins, such as Penicillin G or Penicillin V, are produced by fermentation of Penicillium chrysogenum. They are effective against streptococcus, gonococcus and staphylococcus, except where resistance has developed. They are considered narrow spectrum since they are not effective against Gram-negative rods.
Semisynthetic penicillins first appeared in 1959. A mold produces the main part of the molecule (6-aminopenicillanic acid) which can be modified chemically by the addition of side chains. Many of these compounds have been developed to have distinct benefits or advantages over penicillin G, such as increased spectrum of activity (e.g. effectiveness against Gram-negative rods), resistance to penicillinase or effectiveness when administered orally. Amoxycillin and Ampicillin have broadened spectra against Gram-negatives and are effective orally; Methicillin is penicillinase-resistant.
Clavulanic acid is a chemical sometimes added to a semisynthetic penicillin preparation. Thus, amoxycillin plus clavulanate is clavamox or augmentin. The clavulanate is not an antimicrobial agent. It inhibits beta lactamase enzymes and has given extended life to penicillinase-sensitive beta lactams.
Although nontoxic, penicillins occasionally cause death when administered to persons who are allergic to them. In the U.S. there are 300 - 500 deaths annually due to penicillin allergy. In allergic individuals the beta lactam molecule attaches to a serum protein which initiates an IgE-mediated inflammatory response.
Cephalolsporins are beta lactam antibiotics with a similar mode of action to penicillins that are produced by species of Cephalosporium. The have a low toxicity and a somewhat broader spectrum than natural penicillins. They are often used as penicillin substitutes, against Gram-negative bacteria, and in surgical prophylaxis. They are subject to degradation by some bacterial beta-lactamases, but they tend to be resistant to beta-lactamases from S. aureus.
Chemical structure of some Beta Lactam antibiotics.
Bacitracin is a polypeptide antibiotic produced by Bacillus species. It prevents cell wall growth by inhibiting the release of the muropeptide subunits of peptidoglycan from the lipid carrier molecule that carries the subunit to the outside of the membrane. Teichoic acid synthesis, which requires the same carrier, is also inhibited. Bacitracin has a high toxicity which precludes its systemic use. It is present in many topical antibiotic preparations, and since it is not absorbed by the gut, it is given to "sterilize" the bowel prior to surgery.
2. Cell membrane inhibitors disorganize the structure or inhibit the function of bacterial membranes. The integrity of the cytoplasmic and outer membranes is vital to bacteria, and compounds that disorganize the membranes rapidly kill the cells. However, due to the similarities in phospholipids in bacterial and eucaryotic membranes, this action is rarely specific enough to permit these compounds to be used systemically. The only antibacterial antibiotic of clinical importance that acts by this mechanism is Polymyxin, produced by Bacillus polymyxa. Polymyxin is effective mainly against Gram-negative bacteria and is usually limited to topical usage. Polymyxins bind to membrane phospholipids and thereby interfere with membrane function. Polymyxin is occasionally given for urinary tract infections caused by Pseudomonas that are gentamicin, carbenicillin and tobramycin resistant. The balance between effectiveness and damage to the kidney and other organs is dangerously close, and the drug should only be given under close supervision in the hospital.
3. Protein synthesis inhibitors Many therapeutically useful antibiotics owe their action to inhibition of some step in the complex process of translation. Their attack is always at one of the events occurring on the ribosome rather than the stage of amino acid activation or attachment to a particular tRNA. Most have an affinity or specificity for 70S (as opposed to 80S) ribosomes, and they achieve their selective toxicity in this manner. The most important antibiotics with this mode of action are the tetracyclines,chloramphenicol, the macrolides (e.g. erythromycin) and the aminoglycosides (e.g. streptomycin).
The aminoglycosides are products of Streptomyces species and are represented by streptomycin, kanamycin, tobramycin and gentamicin. These antibiotics exert their activity by binding to bacterial ribosomes and preventing the initiation of protein synthesis. Aminoglycosides have been used against a wide variety of bacterial infections caused by Gram-positive and Gram-negative bacteria. Streptomycin has been used extensively as a primary drug in the treatment of tuberculosis. Gentamicin is active against many strains of Gram-positive and Gram-negative bacteria, including some strains of Pseudomonas aeruginosa. Kanamycin is active at low concentrations against many Gram-positive bacteria, including penicillin-resistant staphylococci. Gentamicin andTobramycin are mainstays for treatment of Pseudomonas infections. An unfortunate side effect of aminoglycosides has tended to restrict their usage: prolonged use is known to impair kidney function and damage to the auditory nerves leading to deafness.
The chemical structure of tobramycin.
The tetracyclines consist of eight related antibiotics which are all natural products of Streptomyces, although some can now be produced semisynthetically. Tetracycline, chlortetracycline and doxycycline are the best known. The tetracyclines are broad-spectrum antibiotics with a wide range of activity against both Gram-positive and Gram-negative bacteria. The tetracyclines act by blocking the binding of aminoacyl tRNA to the A site on the ribosome. Tetracyclines inhibit protein synthesis on isolated 70S or 80S (eucaryotic) ribosomes, and in both cases, their effect is on the small ribosomal subunit. However, most bacteria possess an active transport system for tetracycline that will allow intracellular accumulation of the antibiotic at concentrations 50 times as great as that in the medium. This greatly enhances its antibacterial effectiveness and accounts for its specificity of action, since an effective concentration cannot be accumulated in animal cells. Thus a blood level of tetracycline which is harmless to animal tissues can halt protein synthesis in invading bacteria.
The tetracyclines have a remarkably low toxicity and minimal side effects when taken by animals. The combination of their broad spectrum and low toxicity has led to their overuse and misuse by the medical community and the wide-spread development of resistance has reduced their effectiveness. Nonetheless, tetracyclines still have some important uses, such as in the treatment of Lyme disease.
The chemical structure of tetracycline.
Chloramphenicol has a broad spectrum of activity that exerts a bacteriostatic effect. It is effective against intracellular parasites such as the rickettsiae. Unfortunately, aplastic anemia, which is dose related, develops in a small proportion (1/50,000) of patients. Chloramphenicol was originally discovered and purified from the fermentation of a Streptomyces, but currently it is produced entirely by chemical synthesis. Chloramphenicol inhibits the bacterial enzyme peptidyl transferase thereby preventing the growth of the polypeptide chain during protein synthesis.
Chloramphenicol is entirely selective for 70S ribosomes and does not affect 80S ribosomes. Its unfortunate toxicity towards the small proportion of patients who receive it is in no way related to its effect on bacterial protein synthesis. However, since mitochondria originated from procaryotic cells and have 70S ribosomes, they are subject to inhibition by some of the protein synthesis inhibitors including chloroamphenicol. This likely explains the toxicity of chloramphenicol. The eucaryotic cells most likely to be inhibited by chloramphenicol are those undergoing rapid multiplication, thereby rapidly synthesizing mitochondria. Such cells include the blood forming cells of the bone marrow, the inhibition of which could present as aplastic anemia. Chloramphenicol was once a highly prescribed antibiotic and a number of deaths from anemia occurred before its use was curtailed. Now it is seldom used in human medicine except in life-threatening situations (e.g. typhoid fever).
The chemical structure of chloroamphenicol.
The Macrolides is a family of antibiotics whose structures contain large lactone rings linked through glycoside bonds with amino sugars. The most important members of the group are erythromycin and azithromycin. Erythromycin is active against most Gram-positive bacteria, Neisseria, Legionella and Haemophilus, but not against the Enterobacteriaceae. Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. Binding inhibits elongation of the protein by peptidyl transferase or prevents translocation of the ribosome or both. Macrolides are bacteriostatic for most bacteria but are cidal for a few Gram-positive bacteria.
The chemical structure of erythromycin.
4. Effects on Nucleic Acids Some chemotherapeutic agents affect the synthesis of DNA or RNA, or can bind to DNA or RNA so that their messages cannot be read. Either case, of course, can block the growth of cells. The majority of these drugs are unselective, however, and affect animal cells and bacterial cells alike and therefore have no therapeutic application. Two classes of nucleic acid synthesis inhibitors which have selective activity against procaryotes and some medical utility are quinolones andrifamycins.
Quinolones are broad-spectrum agents that rapidly kill bacteria and are well absorbed after oral administration. Nalidixic acid and ciprofloxacin belong to this group. They act by inhibiting the activity of bacterial DNA gyrase, preventing the normal functioning of DNA. Bacterial DNA exists in a supercoiled form and the enzyme DNA gyrase, a topoisomerase, is responsible for introducing negative supercoils into the structure. Humans possess DNA gyrase but it is structurally distinct from the bacterial enzyme and remains unaffected by the activity of quinolones. Overuse of these drugs in certain situations is selecting quinolone resistant mutants and these may threaten the long term use of such compounds.
The chemical structure of nalidixic acid.
Some quinolones penetrate macrophages and neutrophils better than most antibiotics and are thus useful in treatment of infections caused by intracellular parasites. However, the main use of nalidixic acid is in treatment of lower urinary tract infections (UTI). The compound is unusual in that it is effective against several types of Gram-negative bacteria such as E. coli, Enterobacter aerogenes, K. pneumoniae and species which are common causes of UTI. It is not usually effective against Pseudomonas aeruginosa, and Gram-positive bacteria are resistant. However, a fluoroquinolone, Ciprofloxacin (Cipro) was recently recommended as the drug of choice for prophylaxis and treatment of anthrax.
The chemical structure of ciprofloxacin.
The rifamycins are the products of Streptomyces. Rifampicin is a semisynthetic derivative of rifamycin that is active against Gram-positive bacteria (including Mycobacterium tuberculosis) and some Gram-negative bacteria. Rifampicin acts quite specifically on eubacterial RNA polymerase and is inactive towards RNA polymerase from animal cells or towards DNA polymerase. The antibiotic binds to the beta subunit of the polymerase and apparently blocks the entry of the first nucleotide which is necessary to activate the polymerase, thereby blocking mRNA synthesis. It has been found to have greater bactericidal effect against M.tuberculosis than other anti-tuberculosis drugs, and it has largely replaced isoniazid as one of the front-line drugs used to treat the disease, especially when isoniazid resistance is indicated. It is effective orally and penetrates well into the cerebrospinal fluid and is therefore useful for treatment of tuberculosis meningitis, as well as meningitis caused by Neisseria meningitidis.
The chemical structure of rifampicin.
5. Competitive Inhibitors The competitive inhibitors are mostly all synthetic chemotherapeutic agents. Most are "growth factor analogs", chemicals which are structurally similar to a bacterial growth factor but which do not fulfill its metabolic function in the cell. Some are bacteriostatic and some are bactericidal.Sulfonamides were introduced as chemotherapeutic agents by Domagk in 1935, who showed that one of these compounds (prontosil) had the effect of curing mice with infections caused by beta-hemolytic streptococci. Chemical modifications of the compound sulfanilamide gave compounds with even higher and broader antibacterial activity. The resulting sulfonamides have broadly similar antibacterial activity, but differ widely in their pharmacological actions. Bacteria which are almost always sensitive to the sulfonamides include Streptococcus pneumoniae, beta-hemolytic streptococci and E. coli. The sulfonamides have been extremely useful in the treatment of uncomplicated UTI caused by E. coli, and in the treatment of meningococcal meningitis (because they cross the blood-brain barrier). The most useful sulfonamides are sulfanilamide, Gantrisin and Trimethoprim.
The sulfonamides are inhibitors of the bacterial enzymes required for the synthesis of tetrahydrofolic acid (THF), the vitamin form of folic acid essential for 1-carbon transfer reactions. Sulfonamides are structurally similar to para aminobenzoic acid (PABA), the substrate for the first enzyme in the THF pathway, and they competitively inhibit that step. Trimethoprim is structurally similar to dihydrofolate (DHF) and competitively inhibits the second step in THF synthesis mediated by the DHF reductase. Animal cells do not synthesize their own folic acid but obtain it in a preformed fashion as a vitamin. Since animals do not make folic acid, they are not affected by these drugs, which achieve their selective toxicity for bacteria on this basis.
Sulfanilamide is similar in structure to para-aminobenzoic acid (PABA), an intermediate in the biosynthetic pathway for folic acid. Sulfanilamide can competitively inhibit the enzyme that has PABA as it's normal substrate by competitively occupying the active site of the enzyme.
Three additional synthetic chemotherapeutic agents have been used in the treatment of tuberculosis: isoniazid (INH), para-aminosalicylic acid (PAS), and ethambutol. The usual strategy in the treatment of tuberculosis has been to administer a single antibiotic (historically streptomycin, but now, most commonly, rifampicin is given) in conjunction with INH and ethambutol. Since the tubercle bacillus rapidly develops resistance to the antibiotic, ethambutol and INH are given to prevent outgrowth of a resistant strain. It must also be pointed out that the tubercle bacillus rapidly develops resistance to ethambutol and INH if either drug is used alone. Ethambutol inhibits incorporation of mycolic acids into the mycobacterial cell wall. Isoniazid has been reported to inhibit mycolic acid synthesis in mycobacteria and since it is an analog of pyridoxine (Vitamin B6) it may inhibit pyridoxine catalyzed reactions as well. Isoniazid is activated by a mycobacterial peroxidase enzyme and destroys several targets in the cell. PAS is an anti-folate. PAS was once a primary anti-tuberculosis drug, but now it is a secondary agent, having been largely replaced by ethambutol.
The chemical structure of isoniazid.
Bacterial resistance to antibiotics
Penicillin became generally available for treatment of bacterial infections, especially those caused by staphylococci and streptococci, about 1946. Initially, the antibiotic was effective against all sorts of infections caused by these two Gram-positive bacteria. Resistance to penicillin in some strains of staphylococci was recognized almost immediately. (Resistance to penicillin today occurs in as many as 80% of all strains of Staphylococcus aureus). Surprisingly, Streptococcus pyogenes (Group A strep) have not fully developed resistance to penicillin and it remains a reasonable drug of choice for many types of streptococcal infections. Natural penicillins have never been effective against most Gram-negative pathogens (e.g. Salmonella, Shigella, Bordetella pertussis, Yersinia pestis, Pseudomonas) with the notable exception of Neisseria gonorrhoeae. Gram-negative bacteria are inherently resistant because their vulnerable cell wall is protected by an outer membrane that prevents permeation of the penicillin molecule.
The period of the late 1940s and early 1950s saw the discovery and introduction of streptomycin, chloramphenicol, and tetracycline, and the age of antibiotic chemotherapy came into full being. These antibiotics were effective against the full array of bacterial pathogens including Gram-positive and Gram-negative bacteria, intracellular parasites, and the tuberculosis bacillus. However, by 1953, during a Shigella outbreak in Japan, a strain of the dysentery bacillus was isolated which was multiple drug resistant, exhibiting resistance to chloramphenicol, tetracycline, streptomycin, and the sulfanilamides. There was also evidence mounting that bacteria could pass genes for multiple drug resistance between strains and even between species. It was also apparent thatMycobacterium tuberculosis was capable of rapid development of resistance to streptomycin which had become a mainstay in tuberculosis therapy.
By the 1960's it became apparent that some bacterial pathogens were developing resistance to antibiotic-after-antibiotic, at a rate faster than new antibiotics could be brought to market. A more conservative approach to the use of antibiotics has not been fully accepted by the medical and agricultural communities, and the problems of emerging multiple-drug resistant pathogens still loom. The most important pathogens to emerge in multiple drug resistant forms so far have been Mycobacterium tuberculosis andStaphylococcus aureus.
The basis of bacterial resistance to antibiotics
An antibiotic sensitivity test performed on an agar plate. The discs are seeded with antibiotics planted on the agar surface. Interpretation of the size of the bacterial "zones of inhibition" relates to the possible use of the antibiotic in a clinical setting. The organism is resistant to the antibiotics planted on the plate at 5 o'clock and 9 o'clock.
Bacterial resistance to an antimicrobial agent may be due to some innate property of the organism or it may due to acquisition of some genetic trait as described below.
Inherent (Natural) Resistance - Bacteria may be inherently resistant to an antibiotic. For example, a streptomycete may have some natural gene that is responsible for resistance to its own antibiotic; or a Gram-negative bacterium has an outer membrane that establishes a permeability barrier against the antibiotic; or an organism lacks a transport system for the antibiotic; or it lacks the target or reaction that is hit by the antibiotic.
Acquired Resistance - Bacteria can develop resistance to antibiotics, e.g. bacterial populations previously-sensitive to antibiotics become resistant. This type of resistance results from changes in the bacterial genome. Acquired resistance is driven by two genetic processes in bacteria: (1) mutation and selection (sometimes referred to as vertical evolution); (2) exchange of genes between strains and species (sometimes called horizontal evolution or horizontal gene transmission).
Vertical evolution is strictly a matter of Darwinian evolution driven by principles of natural selection: a spontaneous mutation in the bacterial chromosome imparts resistance to a member of the bacterial population. In the selective environment of the antibiotic, the wild type (non mutants) are killed and the resistant mutant is allowed to grow and flourish. The mutation rate for most bacterial genes is approximately 10-8. This means that if a bacterial population doubles from 108 cells to 2 x 108 cells, there is likely to be a mutant present for any given gene. Since bacteria grow to reach population densities far in excess of 109 cells, such a mutant could develop from a single generation during 15 minutes of growth.
Horizontal gene transmission (HGT) is the acquisition of genes for resistance from another organism. For example, a streptomycete has a gene for resistance to streptomycin (its own antibiotic), but somehow that gene escapes and gets into E. coli orShigella. Or, more likely, some bacterium develops genetic resistance through the process of mutation and selection and then donates these genes to some other bacterium through one of several processes for genetic exchange that exist in bacteria.
Bacteria are able to exchange genes in nature by three processes: conjugation, transduction and transformation. Conjugation involves cell-to-cell contact as DNA crosses a sex pilus from donor to recipient. During transduction, a virus transfers the genes between mating bacteria. In transformation, DNA is acquired directly from the environment, having been released from another cell. Genetic recombination can follow the transfer of DNA from one cell to another leading to the emergence of a new genotype (recombinant). It is common for DNA to be transferred as plasmids between mating bacteria. Since bacteria usually develop their genes for drug resistance on plasmids (called resistance factors [R-factors] or resistance transfer factors [RTFs]), these genetic elements play heavily in the of spread drug resistance to other strains and species during genetic exchange processes.
The combined effects of fast growth rates, high populations of cells, genetic processes of mutation and selection, and the ability to exchange genes, account for the extraordinary rates of adaptation and evolution that can be observed in the bacteria. For these reasons bacterial adaptation (resistance) to the antibiotic environment seems to take place very rapidly in evolutionary time: bacteria evolve fast!
The medical problem of bacterial drug resistance
Obviously, if a bacterial pathogen is able to develop or acquire resistance to an antibiotic, then that substance becomes useless in the treatment of infectious disease caused by that pathogen (unless the resistance can somehow be overcome with secondary measures). So as pathogens develop resistance, we must find new (different) antibiotics to fill the place of the old ones in treatment regimes. Hence, natural penicillins have become useless against staphylococci and must be replaced by other antibiotics; tetracycline, having been so widely used and misused for decades, has become worthless for many of the infections where it once worked as a "wonder drug".
Not only is there a problem in finding new antibiotics to fight old diseases (because resistant strains of bacteria have emerged), there is a parallel problem to find new antibiotics to fight new diseases. In the past two decades, many "new" bacterial diseases have been discovered (Legionnaire's disease, gastric ulcers, Lyme disease, toxic shock syndrome, "skin-eating" streptococci). We are only now able to examine patterns of susceptibility and resistance to antibiotics among new pathogens that cause these diseases. Broad patterns of resistance exist in these pathogens, and it seems likely that we will soon need new antibiotics to replace the handful that are effective now against these bacteria, especially as resistance begins to emerge among them in the selective environment antibiotic chemotherapy.
Alternatives to Antibiotics
Phage therapy is the therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections. Phage therapy is an alternative to antibiotics being developed for clinical use by research groups in Eastern Europe and the U.S. After having been extensively used and developed mainly in former Soviet Union countries for about 90 years, phage therapies for a variety of bacterial and poly microbial infections are now becoming available on an experimental basis in other countries, including the U.S. The principles of phage therapy have potential applications not only in human medicine, but also in dentistry, veterinary science, food science and agriculture.An important benefit of phage therapy is derived from the observation that bacteriophages are much more specific than most antibiotics that are in clinical use. Theoretically, phage therapy is harmless to the eucaryotic host undergoing therapy, and it should not affect the beneficial normal flora of the host. Phage therapy also has few, if any, side effects, as opposed to drugs, and does not stress the liver. Since phages are self-replicating in their target bacterial cell, a single, small dose is theoretically efficacious. On the other hand, this specificity may also be disadvantageous because a specific phage will only kill a bacterium if it is a match to the specific subspecies. Thus, phage mixtures may be applied to improve the chances of success, or clinical samples can be taken and an appropriate phage identified and grown.
Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics, particularly in the country of Georgia. They are reported to be especially successful where bacteria have constructed a biofilm composed of a polysaccharide matrix that antibiotics cannot penetrate.
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