Antibiotic Resistance: A fiery crisis
Dr. Kamal Kishor*, Dr. Neha Shukla, Dr. Sheikh Uzma and Dr. Amit Singh Vishen
Department of Veterinary Pharmacology and Toxicology
Khalsa College of Veterinary & Animal Science, Amritsar- Punjab
*Corresponding author: Dr. Kamal Kishor, Assistant Professor,
Email ID- kamal3928kishor@gmail.com
Introduction
In 2016, the World Health Organization named antibiotic resistance. “One of the biggest threats to global health, food security and development.” Antibiotics are medicine used to prevent and treat bacterial infection. Antibiotic resistance occurs when bacteria change in response to the use of these medicines. Antibiotic resistance is one of the biggest threats to global health, food security and development today. Antibiotic resistance can affect anyone of any age, in any country. Growing infections such as pneumonia, tuberculosis and gonorrhea are becoming harder to treat as the antibiotics used to treat them become less effective. Antibiotic resistance is raising too dangerously high levels in all parts of world. Antibiotic resistance is endangering the efficacy of antibiotics. More recently molecular detection methods have demonstrated that resistant bacteria in farm animals reach consumers through meat products. Antibiotic resistance is on the rise with millions of deaths every year.
Antibiotic resistance
Antibiotic resistance is the ability of bacteria to resist the effect of antibiotics, bacteria survives and continues to multiply causing more harm. According to WHO antibiotic resistance as a microorganism’s resistance to an antimicrobial drug that was once able to treat an infection by that microorganism. Microbes resistant to multiple antimicrobials are called multidrug resistant or sometime superbugs. Increase in resistance of gram negative bacteria is faster than gram positive bacteria mainly due to mobile genes on plasmids which can readily spread through bacterial population.
Mechanism of action
Important mechanisms of antibiotic action against bacterial Cells:
Inhibition of Cell Wall Synthesis (most common mechanism), Inhibition of Protein Synthesis (Translation), Alteration of Cell Membranes, Inhibition of Nucleic Acid Synthesis, Antimetabolite activity, Enzymatic inhibition, Alteration of bacterial membranes, Outer membrane permeability, Inner membrane permeability, Altered ribosomal target sites, altered cell wall precursor targets and altered target enzymes.
The germs are treated with antibiotics as only few are drug resistant. Antibiotics kill bacteria causing the illness as well as good bacteria protecting the body from infection. The drug resistant bacteria are now allowed to grow and take over, some bacteria give their drug resistance to other bacteria, causing more problems. Some bacteria can “neutralize” an antibiotic by changing it in a way that makes it harmless. Others have learned how to pump an antibiotic back outside of the bacteria before it can do any harm. Some bacteria can change their outer structure so the antibiotics have no way to attach to the bacteria, it is designed to kill.
Types of antibiotic resistance
- Natural resistance: Some bacteria are inherently insensitive to a particular antibiotic naturally. Escherichia coli bacteria are naturally resistant to benzyl penicillin unable to penetrate cell wall. Gram positive bacteria are usually susceptible to some antibiotics which are ineffective against gram negative bacteria and vice versa.
- Acquired resistance: Previously sensitive bacteria become resistant to an antibiotic known as acquired resistance. Indiscriminate use of antibiotics and genetic change promote acquired resistance.
Causes of antibiotic resistance
Antibiotic resistant bacteria can spread to family members, schoolmates and coworkers and may threaten young community. Antibiotic resistant bacteria are often more difficult to kill and more expensive to treat in some cases the antibiotic resistant infection can lead to serious disability or even death. Over and misuse of antibiotics can promote the development of antibiotic resistant bacteria as well as lack of new drug development by the pharmaceutical industry due to reduced economic incentives and challenging regulatory requirement. Every time a person takes antibiotics sensitive bacteria are killed but resistant bacteria are left to grow and multiply. Repeated use of antibiotics can increase the number of drug resistance bacteria. Sub-inhibitory and sub-therapeutic antibiotic concentration can promote the development of antibiotic resistance by supporting genetic alterations such as change in gene expression and horizontal gene transfer and mutagenesis changes in antibiotic induced gene expression can increase virulence while increased mutagenesis and horizontal gene transfer promote antibiotic resistance and spread. The antibiotics used in livestock are ingested by human when they consume food.
More recently molecular detection methods have demonstrated that resistant bacteria in farm animals reach consumers through meat. The transfer of resistant bacteria to humans by farm animals was first noted more than 35 years ago, when rate of antibiotic resistance where found in the intestinal flora of both farm animals and farmers. Resistant bacteria transmitted to human through food supply. The agricultural use of antibiotics also effect environmental micro-biome up to 90 per cent of the antibiotics given to livestock are excreted in urine and stool then widely dispersed through fertilizers, groundwater and surface runoff. Genetic and genomic use of studies of waste water treatment plants has shown that they are rich reservoir of r genes and resistant organisms, such treatment plant established for the common good have become the common bad. Erythromycin was early introduced as an alternate to penicillin for the treatment of staphylococcus aureus in Boston city hospital in the early 1950 it was completely withdrawn after less than a year same was observed with chlortetracycline and chloramphenicol. Antibiotic use in animals as therapeutic, prophylactic, metaphylatic and growth promotion all are responsible for causing antibiotic resistance. NDM-1 is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. NDM-1 was first detected in a Klebsiella pneumonia isolate from a Swedish patient of Indian origin in 2008 later detected in bacterial in India, Pakistan, UK, Canada and Japan. According to A. Lancet, NDM-1 is New Delhi is metallo-beta-lactamase-1 originated in India.
Antibiotic resistant bacteria
Among gram positive pathogen a global pandemic of resistant are Staphylococcus aureus Enterococcus species and Vencomycin- resistant enterococci. The global spread of drug resistance among common respiratory pathogens including Streptococcus pneumonia and Mycobacterium tuberculosis is epidemics. Gram negative pathogens are particularly worrisome because they are becoming resistant to nearly all the antibiotic drugs. Staphylococcus aureus (methicillin as resistant S.aureus) , Streptococcus pyogenes, Streptococcus pneumonia, Enterococcus faecalis, Pseudomonas aeruginosa, Clostridium dificle, carbapenem – resistant Enterobacteriaceae, multidrug resistant Acinetobacter, Campylobacter, Salmonella, Escherichia coli, Mycobacterium tuberculosis and Neisseria gonorrhoeae etc.
Impact of antibiotic resistance on humans and animals
Antibiotic resistance has been called animals world’s most pressing public health problems it can cause illness that were once easily treatable with antibiotics to become dangerous infection prolonging suffering for children and adults. Antibiotic resistance lead to higher medical cost, prolonged stay and increased mortality. When infection can no longer be treated by first line antibiotics more expensive medicines must be used for longer duration of illness and treatment, often in hospitals, increases heath care cast as well as the economic burden on families and societies. The achievements of modern medicine are at risk due to antibiotic resistance. Organ transplantation, chemotherapy and surgeries such as caesarean sections become much more dangerous without effective antibiotics for the prevention and treatment of infections. Increased human mortality, increased human morbidity, reduced efficacy of related antibiotics used in humans, increased human healthcare costs, increased potential for carriage and dissemination. NDM-1 is a gene that makes bacteria resistant to beta-lactam antibiotics. Superbugs – Micro-organisms resistant to the major therapies used to treat them first detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin in 2008. From August to November 2009, 22 isolates carrying NDM-1 were found in Mumbai. In May 2010, a case of infection with Escherichia coli expressing nin June 2010 CDC stated that U.S. isolates were from patients who received recent medical care in India. In July 2010, three cases from Chennai of blandm-1 carrying Acinetobacter baumannii. A multi-national team reported 44 isolates with NDM-1 in Chennai and 26 in Haryana.
The NDM-1 encoding gene is located on different large plasmids, a 180-kb plasmid for Klebsiella pneumoniae and 140-kb plasmid for Escherichia coli. NDM-1 transfer through air, through moisture and transfer through contact. Symptoms due to NDM-1 are urinary tract infections, sepsis, pneumonia and wound infections.
The Indian Health Ministry has disputed the conclusion of the August 2010 Lancet study. In January 2011, the editor of The Lancet acknowledged that naming it NDM-1 was an “error. Detection of superbug and NDM-1 by- a significantly elevated MIC of a carbapenem, VITEK 2 AST cards and Etest accurately provide MIC results to specific carbapenem. Advanced Expert System™ (AES) analyzes the antimicrobial susceptibility pattern of each organism. Etest, an agar gradient method, provides mics for slow growing and fastidious organisms. Zooanthroponosis may be associated with NDM-1. Escherichia coli and Klebsiella spp, carrying NDM-1 can cause infections in many different species.
Prevention of antibiotic resistance
Never skip dose or stop taking an antibiotic early unless your healthcare professional tells you to do so. Never take an antibiotic for a viral infections like- cold or flu. Never pressure your healthcare professional to prescribe antibiotics. Never save antibiotic for next time you get sick. Never take antibiotic prescribed for someone else. Ask your healthcare professional about vaccines recommended for you and your family to prevent infection. Prescribing an antibiotic are only when it is likely to benefit the patient. Prescribing an antibiotic that targets the particular bacteria which cause illness. Educate the patient never take any antibiotic at any time. FDA released a proposed rule in December 2013 to require manufactures to submit data supporting the efficacy and safety of antibacterial soaps and washes. Take antibiotics only when the clinical indications are clear do not use antibiotics if the disease is not infectious, untreatable or self limiting. First prefer narrow spectrum antibiotics, broad spectrum antibiotics prefers when a narrow spectrum drug is not effective against organisms. Prevent infection by regularly washing hands, preparing food hygienically, avoiding close contact with sick people and keeping vaccination up to date. Do not use antibiotics for growth promotion or to prevent disease. A global action plan of WHO on antibiotic resistance including antibiotic resistance was enclosed at the world health assembly in May 2015. Proper large scale disposal of toxic waste, metals, disinfectant, biocide and residues of manufacturing processes, the amount of noxious xenobiotics released in to the biosphere are inestimable. Follow alternating therapy is a proposed in which two or three antibiotics are taken in a rotation. Parasite resistance to anthelmintics starts with the first report on phenothiazine resistance in 1957 and second report against Thiabendazole in 1964 Haemonchus contortus, first nematode to develop resistance against the different anthelmintics.
Conclusion
Rapidly emerging resistant bacteria threaten the extra ordinary health benefits that have been achieved with antibiotics.The crises is global reflecting the worldwide overuse of these drugs and lack of development of new antibiotics agents by pharmaceutical companies to adverse the challenge. Antibiotic resistance infections are plays a substantial health and economic burden on the Indian health care system and population. A WHO report released April 2014 state this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Since the last third of the 20th century antibiotics have been used extensively in animal husbandry. In 2013, 80 per cent of antibiotics used in US were used in animals and only 20 per cent in humans, in 1997 half were used in humans and half in animals. Coordinated efforts to implement new policies, new research efforts and pursue steps to manage the crises are greatly needed. Netherland and Scandinavia have successfully reduced resistance level because of lowest rate of antibiotics prescription. Germany and Sweden also have lower prescription rate. No reliable alternative are in pipe line. Most of alternative are at the level of lab. Reliability of alternative is questionable. For near future we have to rely only on antibiotics. Efforts in India for prevention of antibiotic resistance- are India Clean-Indian clinical epidemiology network and IIMAR-Indian initiative for management of antibiotic resistance. In March 2008 with WHO support by a consortium of NGOS are INSAR-SEARO- Indian network for surveillance of antibiotic resistance. Networks of 20 laboratories are in the private as well as public sector across the country. GARP- India working group is global antibiotic resistance partnership. Network on hospital acquired infections.
