Antibiotic Resistance
Ever since the advent of penicillin by Alexander Fleming, antibiotics have played a pivotal role in combating against the various bacterial infections which affect the human race (Lewis, 1995). Most of the World War 2 veterans owe their lives to the timely use of antibiotics. These antibiotics have revamped the way medicine is practiced. We now have ways to address and combat the issue of infection at almost all the areas that it involves. Bacteria are divided into gram positive and gram negative along with being either acid fast bacilli. The various bacteria which are present on the human body can be classified as either commensals or infectious agents. The commensals or the normally occurring bacteria present on the body are naturally harmless, but their growth if disturbed might lead to disorders. The disorders might consist of a simple oral thrush to pseudo membranous colitis, depending upon the degree and extent of the damage to the normal commensular organisms. Bacteria may use the lysogenic pathway which may enable them to complete their life cycles. This is then responsible for the destruction of the host cells.
Of the plethora of problems facing physicians the question of antibiotic resistance is a constant threat and it is the cause of concern for the millions of scientists working around the globe .Bacteria are said to be resistant to an antibiotic if their growth is not inhibited by the maximal level of that antibiotic that can be tolerated by the host. Some organisms are inherently resistant to an antibiotic. However microbial species that are normally responsive to a particular drug may develop more virulent, resistant strains through spontaneous mutation or acquired resistance and selection. Some of these strains may become resistant to more than one antibiotic. Antimicrobial drugs can be classified in a number of ways, either by their chemical structure, their mechanism of action or by their activity against several different types of organisms.
Before discussing as to what causes antibiotic resistance it would be prudent to delve on the fact as to how the antibiotics act to combat bacterial infections. Antibiotics are either bacteristatic or bactericidal on the basis of their mechanism of action. What does this signify, it means that the drug might kill the bacteria altogether or may cause its cell division to stall. The complete eradication of bacteria is desirable in some areas while in others the most questions is to stop its growth and in such cases we have the two different classes of antibiotics.
Along with antibiotics comes the resistance of bacteria to these antibiotics and comes the question of antibiotic resistance. The scare of antibiotic resistance has risen ever since these drugs have been prescribed on a day to day basis.
There are four major mechanisms which lead to bacterial resistance : 1 ) Bacteria produce enzymes that inactivate the drug egg Beta lactamases can inactivate penicillin’s by cleaving the beta lactam ring (2) Bacteria synthesize modified targets against which the drug has no effect eg mutant proteins can act to counter the effect of streptomycin (3) Bacteria may decrease their permeability such that an effective intracellular concentration of drug is not achieved ( 4) Bacteria actively export drugs using a multi drug resistance pump. (Anderson, 2005)
Most drug resistance is due to a genetic change in the organism. These and other mechanisms act to simulate the various procedures whereby which a bacteria produces a resistance to an antibiotic. Hospital acquired resistance is due to the nosocomial infections. The recent scare of MRSA or methicillin resistant staphylococcus aureus in UK hospitals has provided sufficient food for thought.
The various bacterial strains present in the hospital environment account for the multitude of resistant strains being produced. Wide spread use of antibiotic use is responsible for this menace. Common among them are staphylococcus aureas and enteric organisms such as E- coli and pseudomonas aureginosa. Hospital strains are resistant to multiple antibiotics .The answer to these problems lies in the newly developed drugs such as vancomycin and Chloramphenicol , which have been developed with the aim of adopting to a new line of drugs which may combat infections which are not been addressed by the antibiotics being used in the daily practice .
The hospital acquired infections can be prevented by limiting the stay in the hospital and not using unspecific antibiotics as prophylaxis, rather the patients who are preoperative need to be assessed regularly and those who are fit otherwise should not be prescribed antibiotics unnecessarily. Certain clinical situations require the use of antibiotics for the prevention rather than treatment of infections. Because the indiscriminate use of antimicrobial agents can result in bacterial resistance and super infection, prophylactic use is restricted to clinical situations in which the benefits outweigh the risks. The duration of prophylaxis is dictated by the duration of the risk of infection. (Todar, 2002)
The other mechanism of acquiring resistance encompasses either chromosome mediated resistance or plasmid mediated resistance. Of the non genetic basis of resistance includes the fact that the bacteria can be walled off within an abscess cavity which the drug cannot penetrate effectively, or the bacteria can be in a resting state.
In some cases organisms that would be killed by penicillin can loose their cell wall and serve as protoplasts and become insensitive to cell wall active drug, if a wrong antibiotic is prescribed then it may also presumably show that the bacteria are resistant to the used antibiotic, when in fact it is just not being combated by the proper antibiotic.
Some examples of major bacterial species and the drugs against which they have developed resistance include in case of gram positive cocci, Staphylococcus aureus, streptococcus pneumonia and enterococcus feacalis, which have developed resistance against penicillin. Then in the category of gram negative cocci Neisseria gonorrhea has also developed resistance against penicillin-G, in case of gram negative rods Haemophilis influenza has developed resistance to ampicillin, while pseudomonas and enterobacteriacae have acquired resistance against beta lactam antibiotics and aminoglycosides (Lewinson, 2004).
Another group which has developed resistance is that of mycobacterium i.e. tuberculosis, which is the reason of failure of therapy in case of a case of tuberculosis. These are some of the examples of the bacteria which have acquired resistance against the major antibiotics. According to a study by the methicillin resistant staphylococcus is a source of constant threat to hospital authorities. In case of UK this has resulted in an outbreak. In the US due to the strict practices of culture and sensitivity tests this has been controlled to a large extent but the problem can resurface if appropriate control measures are not undertaken.
Speaking of tuberculosis, which used to be a major killer disease and is still affecting millions around the globe in the third world countries, the issue of drug resistance is of major concern. The DOTS or directly observed treatment strategy, initiated by WHO in the developing countries is a step to safeguard against the development of drug resistant strains of tuberculosis (Davidson, 2005). A total of 4 drugs are used in combinations for duration of 6-9 months depending upon the condition and compliance is ensured by the nurse providing the dosage.
This leads us to the question of the link between compliance and drug resistance. What really happens is that if a drug is taken in meager amounts or if it is not taken in the correct dosage then it is rendered harmless for the bacteria and bacteria in turn develop resistance against it. The same is the concept of using several drugs at a time, in this way there is a less chine of development of resistance because a backup drug is always there to ensure eradication of the bacteria in case the first drug fails to control the infection.
In case the first line drugs fail then there is the possibility of using a second array or generation of drugs. In this manner the chances of a resistance developing against any drug is lessened to a considerable extent. But the problem is that the adverse effects or complications may arise too e.g. hypersensitivity may develop or toxicity and worst of all super infections. Now how can this problem be addressed, the core of the problem lies in not giving too much attention to the cases of infection when they first appear and haphazardly prescribing antibiotics.
It is generally observed that the general practitioners tend to give broad spectrum antibiotics to their patients when they first come to them for a minor ailment. This rampant use of antibiotics is one of the reasons of development of resistance. What the protocol demands is the investigation of every case on the lines of methodical approach. This involves careful screening through tests and then referral for the culture and sensitivity report.
What is basically a culture and sensitivity report? It consists of an agar plate on which antibiotics are present covering a small area. Several antibiotics are present, now a culture which grows on the medium when subjected to an antibiotic it is sensitive to results in an area of either decreased or no growth. This helps in pointing out the specific antibiotic to which an organism is resistant. The results are commonly reported as minimum inhibitory concentration, which is defined as the lowest concentration of drug that inhibits the growth of the organism.
The MIC is determined by inoculating the organism isolated from the patient into a series of tubes or cups containing 2-fold dilutions of the drug. After inoculation at 35 degrees centigrade for 18 hours, the lowest concentration of the drug that prevents visible growth is the MIC. A second method of determining antibiotic sensitivity is the disc diffusion method, in which disks impregnated with various antibiotics are placed on the surface of an agar plate that has been inoculated with the organism isolated from the patient. After incubation at 35 degrees for 18 hours, the diameter of the zone of inhibition is determined. The size of inhibition is measured with standards to determine the sensitivity of the organism to the drug.
Reports obtained or cultivated in this manner provide the physician a guideline for the correct use of the antibiotics. In case of pediatric practice there are certain rules and guidelines which govern the use of antibiotics such as in case of tachycardia or fast breathing a child is evaluated according to certain parameters. Only if a child falls within the category of pneumonia is he prescribed antibiotics. And that too are prescribed according to the culture and sensitivity report.
Until the report is pending generally a broad spectrum antibiotic is started, but only after confirming that the child has got bacterial infection is an antibiotic prescribed. The use of combination antibiotics has stepped in to solve this problem of drug resistance.
In most cases the single best antimicrobial agent should be selected for use because this minimizes the side effects; however there are several instances in which two or more drugs are commonly given. In order to treat serious infection before the organism is known, In order to achieve a synergistic inhibitory effect against certain organisms and to prevent the emergence of resistant organisms (Richard, n.d.).
Two drugs can interact in one of several ways. They may be indifferent to each other or there may be a synergistic effect, in which the effect of the two drugs together is significantly more than that of a single drug alone. A synergistic effect can result from a variety of mechanisms e.g. the combination of Ampicillin and Clavaluic acid results in the action against gram positive bacteria as well as beta lactamase producing microbials as well.
This results in the prescription of a single dose which is sufficient to combat the infection causative organisms .It should be kept in mind that a bacteristatic antibiotic is not prescribed along with a bactericidal antibiotic as this might result in an antagonism and there would be no effect what so ever of the drug prescription.
According to an article (Anderson, 2005) the increased prevalence of antibiotic resistance is an outcome of evolution. It has also been stressed that the improvement in the public health measures a go a long way in prevention against infection. Here comes the vital point of prevention, which is the basis of modern medicine. This is what around which the public health system evolves. Prevention of an infection in the first place is our guaranteed guard against any bacterial invasion.
The effective and timely use of vaccine has also been advocated as a means to combat bacterial infections. Now one of the questions is that if Vancomycin resistant bacteria are also a constant threat and measures need to be adopted to cultivate safe drug practice among physicians. Physicians and pharmaceutical industries together can combat this menace of antibiotic resistance in a very positive manner. The need is to address this problem on a broader spectrum and to rationalize the use of antibiotics. This is the only chance before we have to face an era where we will need to find new ways to combat infection instead of the trusted and time tested use of antibiotics.
Antibiotic resistance is to be avoided by following the principles of health management (Barbara E. Murray, 1994). Whereby it is mandatory to enforce steps to find the problem, assess the problem and alleviate the problem. Modern pharmaceutical companies are constantly striving to make their utmost effort in the manufacture of antibiotics. Careful planning and integration is vital if we desire that this issue be addressed amicably. Most cases of diarrhea among children are caused by a virus, termed as the rota virus, thus there is no use what so ever in prescribing any antibiotic.
The future lies in expanding the horizons of our intellect and to look beyond what we term as possible, but we need to bear in mind the ethical issues , the broadening gap between the developed and the under privileged . The scope of modern technological advancements is quite broad and everyday new antibiotics are emerging which offer hope to the millions of people around the globe in search for the cure of the bacterial infections. Being able to comprehend the true potential of these advancements and being able to use them for the betterment of mankind along with improving the quality and not merely the quantity of life is what can be considered the ultimate reward.
References
Barbara Murray, (1994) Antimicrobial resistance, M.D., of the University of Texas Medical School at Houston, New England Journal of Medicine
Kenneth Teodar, (2002) Bacterial resistance to antibiotics
http://Textbookofbacteriology.Net/Resantimicrobial.Html
Accessed, July 24, 2007
Davidson’s Principles and practice of medicine 19th edition (pg147-164)
Kevin Anderson, (2005) Is bacterial resistance an example of evolutionary change
www.Trueorigin.Org/Bacteria01.Asp Accessed, July 24, 2007
Warren Lewinson, (2004) Microbiology and Immunology (pg 54-75)
Richard Howland, (n.d.) Pharmacology, Lippincot Illustrated reviews 3rd edition (pg 341-350)
Riki Lewis, (1995) The Rise of Antibiotic-Resistant Infections
http://Www.Fda.Gov/Fdac/Features/795_Antibio Accessed, July 24, 2007
