The introduction of antibiotics into medical practice in the 1940s revolutionized man's ability to cure infectious diseases. Now after more than sixty years health practitioners around the world can no longer expect their choice of antibiotic to work. Health professionals are losing the fight against antibiotic-resistant 'super bugs' and few drugs are in development to counter this growing threat.

Resistance occurs as a result of antibiotic use, and we are using tonnes of antibiotics, and every time we use an antibiotic, either in food production or by prescription, we affect not just the person, but also all living organisms and all future organisms. The cavalier use of antibiotics has resulted in the progressive depletion of cost-effective agents from our armamentarium. A dangerous pattern has emerged in which, as a new antibiotic is introduced, there is a rampant overuse or misuse resulting in accelerated development of resistance.

Additionally antibiotics can make us sick. One may ask how could that be possible?. Well the answer is simple; all drugs come with adverse effects and antibiotics are no exception.

Antimicrobial agents are associated with side-effects, which are usually tolerated because the benefits outweigh the toxic effects. Clinicians know about these side effects but are likely to understand that additional adverse events, such as the overgrowth of resistant microorganisms can eventuate. Overgrowth itself can precipitate a secondary infection, which can be more difficult to treat. Resistant organisms then spread to other patients and the environment, and contribute to increasing antimicrobial resistance worldwide. Organisms exposed to antimicrobials undergo molecular changes that might enhance virulence. Enhanced pathogenicity would affect the patients, particularly if the organism is also multiply resistant.

But the habits of physicians seem difficult to change. Clinicians have a responsibility to select the correct antibiotic as soon as they diagnose infection, depending on proper culture and sensitivity tests, but lack of access to, or use of, appropriate diagnostic facilities, and slow or inaccurate diagnostic results encourage prescribers of antibiotics, to use them inappropriately. In particular, the lack of accurate tests at point-of-care, to achieve a rapid diagnosis, is a significant problem for many diseases and is an area in which future research could be very beneficial.

Empiric treatment of infections with a reasonably well-defined clinical presentation is more likely to be more appropriate than that of infections with undifferentiated presentation e.g. malaria presenting with fever alone. In this latter situation the differential diagnosis may be wide and therefore empiric treatment protocols will necessarily need to be broad - leading to a higher likelihood of unnecessary antimicrobial therapy.

I can estimate that in Iraq the barefoot doctors prescribe antimicrobials for 60% of all patients seen without diagnostic services. The occurrence of overgrowth, or superinfection, as a direct result of antibiotic consumption, is less well understood by prescribers. It is a travesty to refer to a fact that deaths from acute respiratory infections, diarrhoeal diseases, measles, AIDS, malaria and tuberculosis accounts for more
than 85% of the mortality from infection worldwide.

Resistance to first-line drugs in the pathogens causing these diseases ranges from zero to one hundred percent. In some instances resistance to second -and third line agents is seriously compromising treatment outcome.

Added to these major killers is the significant global burden of hospital - acquired (nosocomial) infections usually caused by resistant pathogens; the emerging problems of antiviral resistance and the increasing threats of drug resistance in parasite diseases such as African trypanosomiasis and leishmaniasis.

The massive increases in trade and human mobility brought about by globalisation, has enabled the rapid spread of infectious agents, including those that are drug resistant.

While richer countries, to a large extent, are still able to rely on the latest ANTIMICROBIALS to treat resistant infections, access to these life-saving drugs is often limited or totally absent in many parts of the world.

Prevention of infection should be the primary goal to improve health and to reduce the need for antimicrobial therapy. Where appropriate, vaccine uptake should be improved to achieve this.

I am very concerned about resistance and believe that every person on the planet should be concerned about it too but now we have a world in which a multiply resistant bacteria can be as dangerous as an inherently virulent one. This is likely to be true when an immune compromised patient, or one who is simply elderly and/or suffering from other chronic diseases encounters an opportunistic, drug insensitive organism, that would be otherwise totally benign.

One may ask what is antimicrobial resistance? Well resistance to antimicrobials is a natural biological phenomenon .The introduction of every antimicrobial agent into clinical practice has been followed by the detection in the laboratory of strains of microorganisms that are resistant, i.e. able to multiply in the presence of drug concentrations higher than the concentrations in humans receiving therapeutic doses. Such resistance may either be a characteristic associated with the entire species or emerge in strains of a normally susceptible species through mutation or gene transfer.

Resistance gene encodes various mechanisms, which allow microorganisms to resist the inhibitory effects of specific antimicrobials. All the antimicrobial agents have the potential to select drug-resistant subpopulations of microorganisms. With the widespread use of antimicrobials, the prevalence of resistance to each new drug has increased. The prevalence of resistance varies between geographical regions and over time, sooner or later, resistance emerges to every antimicrobial. While there is much evidence that support the view that the total consumption of antimicrobials is the critical factor in selecting resistance, the relationship between resistance and use is not a simple correlation. In particular, the relative contribution of mode of use (dose, duration of therapy, route of administration, dosage interval) as opposed to total consumption, is poorly understood. Paradoxically, under-use through lack of access, inadequate dosing, poor adherence and substandard antimicrobials may play as important a role as overuse.

There is a consensus, however, that the inappropriate use of antimicrobial agents does not achieve the desired therapeutic outcomes and are associated with the emergence of resistance. For this reason improving use is a priority if the emergence and spread of resistance is to be controlled. The WHO Global Strategy defines the appropriate use of antimicrobials as the cost effective use of antimicrobials which maximizes clinical therapeutic outcomes, while it minimizes both drug toxicity and the development of antimicrobial resistance. The choice of appropriate antimicrobial agent is straightforward when the causative pathogen(s) is/are are known, or can be presumed with some certainty from patient clinical presentation. However, in the absence of reliable microbiological diagnosis or when several pathogens may be responsible for the same disease presentation, empiric treatment, often with broad-spectrum antimicrobials, should be guided by national or local antimicrobial resistance surveillance data and treatment guidelines.

The reality is often far removed from this ideal. Surveillance of antimicrobial resistance is essential for providing information on the magnitude and trends in resistance and for monitoring for the effect of interventions. Modern techniques have enabled the development and applications of molecular methods to determine the presence of specific resistance genes in microbes. They are widely used to detect genotypic resistance in viruses such as HIV and HBV and, in the future, may form the basis of a system to monitor antiviral resistance. However, these molecular methods rely on sophisticated technology that is not available in many settings.

The solutions are inappropriate use of antimicrobials, through:

• educating patients and the general community on the appropriate use of antimicrobials.
  
• educating the patients on the importance of measures to prevent infections, such as immunisation, vector control, use of bednets, etc.
  
• educating patients on simple measures that may reduce transmission of infection in the household and the community, such as hand washing, food hygiene, etc.

Patient related factors that are thought to contribute to the problem include the followings:

• Patients misinterpretations: Many patients believe that most infections, regardless of aetiology, respond to antimicrobials and thus expect to receive A PRESCRIPTION FROM THEIR PHYSICIAN for any perceived infection.
  
• Also many patients believe that new and expensive medications are more efficacious than older agents; this belief is shared by some prescribers and dispensers and often results in the unnecessary use of the newer agents as well as of older agents in their class. Patients commonly misunderstand the pharmacological action of antimicrobial agents. In the Philippines, isoniazide is viewed as a (Vitamin for the lungs) and mothers purchase isoniazide syrup for children (with weak lungs) in the absence of documented tuberculosis. Patients also fail to recognize that many brand names may actually be the same antimicrobial resulting in the unnecessary of overstocking of some agents .For example, specific patients demands caused one pharmacy in south India to stock more than 75 of the 100 or so brands of co-trimaxazole available. Self medication with antimicrobial is often sited as a major factor contributing to drug resistance regardless as to whether the patient's illness will benefit from antimicrobial treatment, also self medicated antimicrobials are often inadequately dosed or may not contain adequate amounts of active drugs, especially if they are counterfeit drugs.
  
• Self medication.
  
• Advertising and promotion: direct-to-consumer advertising allows pharmaceutical manufacturers to market medicines directly to the public via television, radio, print media and the internet. Where permitted, this practice has "the potential to stimulate demand by playing on the consumer's relative lack of sophistication about the evidence supporting the use of one treatment over another" These advertising methods are apparently quite effective, since pharmacists are frequently able to guess the feature advertisements of the previous day 's television programmes based upon daily customer requests for specific medications.
  
• Poor adherence to dosage regimens: in the vast majority of studies, it was the lack of patient understanding and provider communication that led to more instances of non-adherence. Many methods have been used to ensure adherence to antimicrobial therapies. These include the fixed dose combinations to minimize the number of the tablets or capsules, special calendars, blister packing, DOT (directly observed therapy) for tuberculosis, other course-of-therapy packaging using symbols in labeling, and more simplified therapy.