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Fact Sheet No 194May 1998 ANTIMICROBIAL RESISTANCEAntimicrobial agents (antibiotics and related medicinal products) are among the wonder drugs of the twentieth century. They have transformed our ability to treat many infectious diseases that were previously killers. However, through massive and increasing use of antimicrobials in humans, animals, fish and in agriculture, a resistance problem has been created that is rapidly moving to the forefront of public health concerns.CausesMicrobes (bacteria, fungi, parasites and viruses) are responsible for infectious diseases and antimicrobial agents (such as penicillin, erythromycin, and many others) have been developed to combat the spread and severity of many infections. However, the use of these agents for any infection, real or feared, in any dose and over any time period, forces microbes to adapt or die (”selective pressure”). The microbes which survive are those that carry genes for resistance to antimicrobial agents and, in the medical setting, a resistant microbe is one which is not killed by an antimicrobial agent after a standard course of treatment. Antimicrobial agents are also used in agriculture such as livestock and crop production, as well as in fish farming and to treat and control animal diseases and enhance growth and yield. All these uses increase the total selective pressure exerted on the microbial world and encourage the emergence of resistance.Factors that favour the spread of resistanceBacteria are particularly efficient at enhancing the effects of resistance, not only because of their ability to multiply very rapidly but also because they can transfer their resistance genes to other strains. Resistant microbes can spread easily from person to person. Thus in hospitals and health care facilities, where there is intensive use of antimicrobials, and many sick and susceptible people gathered together, spread of resistant bacteria (such as Staphylococcus) is common. Overcrowding and poor hygiene and sanitation also facilitate the spread of resistant organisms (such as those that cause typhoid, tuberculosis, respiratory infections and pneumonia).The enormous increase in international travel in recent years means that individuals may be exposed to resistant microbes in one country and carry them to other countries, where resistance can then spread. For example, resistant strains of gonorrhoea that originated in Asia and Africa, have now spread throughout the world.The widespread use of antimicrobials for disease control and growth promotion in animals has been paralleled by an increase in resistance in those bacteria (such as Salmonella and Campylobacter) that can spread from animals, often through food, to cause infections in humans.Detection of resistanceResistance in bacteria is most commonly detected during standard laboratory investigations to establish the cause of a patient’s infection and the best choice of treatment. Detection depends on the collection of specimens from the patient, and on the availability of laboratory facilities for isolation, identification and susceptibility testing of the infecting microbe. This takes time and money and thus is often foregone. In consequence, resistance may not be detected until a course of treatment fails to cure a patient’s infection. By this time it may be too late. Consequences of resistanceInfections caused by resistant microbes fail to respond to treatment, resulting in prolonged illness and greater risk of death. Treatment failures also lead to longer periods of infectivity. This increases the numbers of infected people moving in the community, augmenting opportunities for spread of resistance and exposing the general population to the risk of contracting infection with resistant strains. Prolonged illness increases the costs of treatment, both the direct costs for additional laboratory tests, treatment, hospitalization, and the indirect costs due to loss of income or time away from family. When infections become resistant to ‘first-line’ antimicrobials, treatment has to be switched to ’second-line’ agents which are almost always more costly and may have to be given by injection instead of by mouth. In many countries the high cost of newer second-line antimicrobials means that they are unavailable to the majority of the population and many infections become effectively untreatable. Containment of antimicrobial resistanceAntimicrobial resistance is not an infectious disease, like smallpox or poliomyelitis, that we can eradicate. It is a natural response of microbes to exposure to antimicrobial agents. Therefore the approach has to be one of containment, aiming to reduce the rate of emergence and spread of resistance. In order to contain the threat of antimicrobial resistance, it is important to determine the magnitude and trends of resistance and to define the relative importance of different contributing factors, such as therapeutic, behavioural, economic and social, and health system factors, and veterinary and agricultural misuse. Based on this understanding it should be possible to develop effective methods to contain antimicrobial resistance in different settings.In particular, much needs to be done to reduce overuse and inappropriate use. For example, there is an often unjustified faith in the ‘healing power’ of antimicrobials. Physicians feel pressured by patient expectations of treatment and prescribe antimicrobials even in the absence of appropriate indications. Moreover, the vast majority of patients, especially outside hospital, are prescribed antimicrobials without the doctor knowing exactly the cause of the infection, and in many countries antimicrobials can easily be purchased in pharmacies and markets without a prescription. Patients often comply poorly with the prescriptions; they forget or interrupt their treatment prematurely or may be unable to afford a full course, thereby creating an ideal environment for microbes to adapt rather than be killed. In some countries, low quality antibiotics (poorly formulated or manufactured, counterfeited or expired) are still sold and used for self-medication or prophylaxis.WHO’s ProgrammeThrough its antimicrobial resistance monitoring (ARM) activities, WHO assists developing countries, through the provision of training, quality assurance, laboratory reagents and computer software (WHONET), to detect and monitor resistance by establishing laboratory-based surveillance networks. WHO also sponsors national policy workshops which aim to improve collaboration between decision-makers in developing strategies for monitoring resistance and improving rational use of antimicrobials, including educational programmes for prescribers and users. A WHO global information bank on ARM will include databases on resistant microbes and resistance surveillance networks and will serve to make information available to governments, health care institutions, professional societies, the media and the lay public. Other ARM activities include identifying human medical resistance problems resulting from antimicrobial use in livestock production and improving resistance monitoring in foodborne bacteria. Through the Division of Emerging and other Communicable Diseases Surveillance and Control (EMC), which coordinates WHO’s ARM activities, and the Division of Child Health and Development (CHD), the Division of the Action Programme for Essential Drugs (DAP) and the Division of Drug Management and Policies (DMP), WHO is working to develop and implement a global strategy for the containment of antimicrobial resistance._______________For further information, journalists can contact Health Communications and Public Relations, WHO, Geneva. Telephone (41 22) 791 4458. Fax (41 22) 791 4858. E-Mail: info@who.ch All WHO Press Releases, Fact Sheets and Features as well as other information on this subject can be obtained on Internet on the WHO home page http://www.who.ch/

? WHO/OMS, 1998 | Concept

Agent Zone Inhibition Diameters(nearest whole mm) Equivalent MIC (mg/L)


Penicillin(10U) *=26 27-46 *=47 *=2.0 0.13-1.0 *=0.06

Tetracycline(30 mcg) *=30 31-37 *=38 *=2.0 0.5-1.0 *=0.25

Spectinomycin(100 mcg) *=15 16-17 *=18 *=128.0 64.0 *=32.0

Cefoxitin(30 mcg) *=23 24-27 *=28 *=8.0 4.0 *=2.0

Ceftriaxone*(30 mcg) *=35 *=0.25

Cefixime*(5 mcg) *=31 *=0.25

Ciprofloxacin**(5 mcg) *=29 30-35 *=36 *=1.0 0.13-0.5 *=0.06

Ofloxacin**(5 mcg) *=24 25-30 *=31 *=2.0 0.5-1.0 *=0.

An antibiotic is any substance that inhibits or kill certain microorganisms. Antibiotics can be either bactericidal or bacteriostatic, meaning they either kill already grown bacteria, or they inhibit the growth of growing bacteria. They accomplish this end in many different ways, some affect cell walls, some the cytoplasmic membrane, and some affect an enzyme involved in nucleic acid synthesis. Some affect only gram-positive or gram-negative bacteria, while some affect both. The antibiotic we worked with, Tetracycline, inhibits protein synthesis by binding to the ribosomes and preventing the tRNA from docking at the “A” site. This prevents protein synthesis and will kill the cell.

Antibiotic Resistance: Resistance to antibiotics develops in bacteria in the following way. In many types of bacteria there are a small number of cells which contain genes that are resistant to certain antibiotics. When a small dose of antibiotics is applied to a colony of bacteria, all the cells not resistant are killed or inhibited, while the resistant cells remain strong. The resistant cells then proceed to thrive and multiply, passing down their resistance to their offspring. In addition, these bacteria spread their resistant traits to other, previously non-resistant cells through the methods mentioned above (transformation and conjugation), thus eventually affecting the entire colony.

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