Antimicrobial resistance – a wake up call

The development of antimicrobial drugs in the 20th century was among the greatest developments of the medical history as it changed the outlook of treatment of infectious diseases. Antimicrobial drugs are widely prescribed; in India antibiotics constitute 16 per cent of the drug market while in UK, antibiotics accounted for 19 per cent of the expenditure in secondary health care.

Millions of lives were saved and many are still being saved by the use of these drugs. Within few decades of their use/misuse, there is a major problem arising with their use that is development of resistance – many micro-organisms are developing resistance to the antimicrobial drugs. We are fast approaching the pre-antibiotic era, where we are losing the effect of existing antimicrobials and new antimicrobial drugs are not coming.

Globally, the development of resistance among the pathogens causing communicable diseases, is a matter of grave concern, the scenario is no different in our country. The fact that resistance has developed to even newer drugs like carbapenems, is a major cause of concern.

In country like India we find that there are well laid guidelines for the appropriate use of antimicrobials in various health programs that are being run at the national level like: RNTCP, National AIDS control programme, etc. While for other infections like diarrheas, typhoid fever, respiratory infections where clear cut guidelines are not there, the use of antimicrobials varies among the physicians and hospitals. In India practically all the antimicrobials are available over the counter- it may be for human consumption, animal or for agriculture use. This has led to the widespread (mis)use of the drugs leading to development of resistance. Of particular concern are the multidrug resistant bacteria, e.g. E. coil, Pseudomonas, Klebsiella pneumoniae, MRSA (methicillin-resistant Staphylococcus aureus), penicillin-resistant Streptococcus pneumoniae, VRE(vancomycin-resistant Enterococcus), and extensively drug-resistant Mycobacterium tuberculosis.

Most of the antimicrobial drugs act by one or more of the following mechanisms:

• Interference with cell wall synthesis
• Disorganizing of the cell membrane
• Inhibition of protein synthesis
• Interference with nucleic acid synthesis/ functioning
• Inhibition of a metabolic pathway

To achieve the above effect the antimicrobial drugs must:
1.    Reach inside the bacteria
2.    Bind with the target site/enzyme.

It was mentioned by Alexander Fleming that “There is probably no chemotherapeutic drug to which in suitable circumstances the bacteria cannot react by in some way acquiring ‘fastness’ [resistance].”Resistance develops because micro-organisms develop mechanisms to:

• Inactivate the drug(by disrupting the chemical structure of drug – e.g. Penicillinase or by modifying the chemical structure of the drug – e.g. chloramphenicol, inactivated by acetylation).
• The target site/enzyme is altered ( enzyme has reduced affinity for the antibacterial drug or an altered organelle of the microorganism with decreased antimicrobial -binding properties (e.g. erythromycin and bacterial ribosomes).
• The drug is effluxed out of the cytoplasm (e.g. tetracycline).
  

This is achieved by either development of Spontaneous mutation in the bacteria (these resistant strains are get selected in the bacterial population by elimination of sensitive strains by the antimicrobial drugs) or Transmission of genes from other organisms. Transmission of genes from other organisms is more common and is a serious problem. Genes responsible for resistance (sometimes to a group of many antibiotics simultaneously - MDR) are transferred by Plasmids by the way of conjugation, transformation or by bacteriophage.

Problems galore
Globally the problem of antimicrobial resistance has increased tremendously in the last decade. Some strains of resistant bacteria like MRSA, vancomycin-resistant enterococci (VRE) and coliforms that produce 'extended spectrum beta-lactamases' are mostly restricted to patients admitted in hospitals. Other resistant strains of bacteria like penicillin-resistant Streptococcus pneumoniae and multi drug resistant Mycobacterium tuberculosis infect the persons in the community. All the evidence points to the fact the outcome in the patients having infection with drug resistant organisms is worse when compared to patients having infection with susceptible strains. The hospital stay and cost of the therapy is also more.

Reasons for antimicrobial resistance in India
Limiting the development of resistance

• Though many guidelines are available that should be followed to limit this serious problem, a few general principles says:
• No indiscriminate use of antimicrobials should be there. Indication, dose and duration of treatment should be proper.
• Antimicrobial combinations must be used when prolonged therapy is there e.g. tuberculosis.
• Strict no to antimicrobials to coughs and colds and viral sore throats.
• Monitoring the resistance pattern in hospital or community should be a routine procedure and prescribing pattern should be altered as required.
• Newer antimicrobials should not be the first choice while prescribing. If organism show sensitivity to older antimicrobials, it should be preferred- it may limit the development of resistance to the newer drug. The services of the microbiologist must be sought.
  

Challenges
No doubt, containing the development of resistance is a big challenge. Solution lies in educating the medical professionals as well as society about the gravity of the problem. One must understand the fact that micro-organisms are better equipped by the nature to adapt to the adversity than human beings, considering their number and multiplication rate. We cannot eliminate them with use of drugs. We have to learn to coexist with them. More stress should be on improving the hygiene. Old saying ‘prevention is better than cure’ is to be stressed. The rate of infections in the Europe is low not due to use of antimicrobial drugs but due to better hygiene in the society in the general. Simple habit of proper hand wash can decrease the incidence of infections in the society and more so in the hospital set up. This can bring down the requirement of antimicrobials and spread of MDR resistant organisms. A lot needs to be regulated at the government level. It should be clear who can prescribe antimicrobials & under which situation which drug can be prescribed. Pharmaceutical companies have to own the responsibility and at least antimicrobial drugs should be kept above the profits- remember ‘more we use then more we lose them’. It is a very precious asset and with proper use we can preserve it for future generations and responsibility has to be taken by everybody.