Lentis/Antibiotics in India

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Introduction[edit]

Antibiotic resistance is the decrease in drug effectiveness toward bacteria which hinders the ability to cure infections. While this is a global phenomenon, its epicenter is in India as it has easy access to strong antibiotics without prescription or diagnosis. A study by Princeton University found between 2000 and 2010, India consumed the most antibiotics in the world, with China the second consumer, followed by the United States.[1] India has been affected the most due to recent changing social factors such as rapid economic growth and rising incomes which have not translated to improvements in water, sanitation, and public health but have increased patient expectations to receive prescriptive care from their doctors.

Origin and Background[edit]

In 2009, A Swedish national fell ill with an antibiotic-resistant bacterial infection that he acquired in New Delhi, India. None of the regular antibiotics were able to treat his infection which was determined to be Klebsiella pneumoniae, one of the most frequent causes of pneumonia in hospitalized patients. His specific strain contained an irregular gene now referred to as New Delhi metallo-beta-lactamase 1 (NDM-1), after the city where this superbug is thought to have originated. This bacteria is resistant to almost all antibiotics.[2] NDM-1 has traveled fast: by 2015, strains had appeared in more than 70 countries in all regions of the world.[3]

Countries from which NDM-positive bacteria have been reported. Triangles indicate an epidemiological link to the Indian subcontinent.[3]

Antibiotic Resistance[edit]

Bacteria are single-celled organisms that live in and around the human body. Antibiotics fight bacteria by killing the cells or making it hard for them to grow and multiply. These drugs have no effects on viruses.

Antibiotic resistance occurs when bacteria change to reduce the effectiveness of a drug or chemical. This is caused by the overuse or misuse of antibiotics which kills sensitive bacteria but cannot kill resistant bacteria. Repeated use of antibiotics and sub-lethal doses increases the number of drug resistant bacteria.[4] Too low of a dose is not typically an error by the doctor, but more often caused by patients discontinuing their medication when symptoms fade instead of completing the entire course.

Mechanism[edit]

Antibiotics work by inhibiting DNA replication and thus multiplication of bacteria. Bacteria can become resistant by either a genetic mutation or accepting antimicrobial resistant genes from other bacteria. The resistance occurs in one of three ways; mutation, destruction or efflux. In mutation, the part of the bacteria that replicates itself becomes unaffected by the antimicrobial. In destruction, a protein in the bacteria kills the antimicrobial before it can kill the replication proteins of the bacteria. In efflux, there is a channel in the cell of the bacteria that eject the antimicrobial when it enters.[5] The resistant bacteria then multiply or share their genes with other bacteria, promoting antibiotic resistance.[4]

Resistance Statistics in India[edit]

In India, nearly a quarter of patients infected with bacteria carrying NDM-1 die.[6]

India has the highest rates of resistance to nearly every drug available to treat it. Strains of E. coli tested in labs are more than 80 percent resistant to three common drug types, and there are high levels of antimicrobial resistance to broad-spectrum antibiotics like fluoroquinolones and third- generation cephalosporins.[7] Dr. J V Divatia, professor of anesthesia at Tata Memorial Hospital in Mumbai says Carbapenem resistance levels are increasing, in some cases up to 60% compared to 5% in Europe. Carbapenems are considered last-resort antibiotics, used for infections that are resistant to first-, second- and even third-line antibiotics. This led hospitals in India to use colistin, the last antibiotic available in the world which was brought back from a 40-year exile due to toxicity in 2005, to treat an increasing number of infections resistant to other high-end antibiotics. Reports from 2014 show colistin resistance is up to 5% in New Delhi hospitals. Colistin is often a patient's last hope for survival.[8]

Different antibiotics' resistance to E. Coli in India. [9]

Factors Influencing Antibiotic Resistance Rise in India[edit]

High Burden of Disease[edit]

The mortality rate of infectious diseases in India is 416.75 per 100,000 persons.[10] The Ministry of Health in India is responsible for handling public health outbreaks but lacks the appropriate public health infrastructure. Control of tuberculosis, visceral leishmaniasis, and malaria has been inadequate. Other highly infectious diseases are not in the process of being systemically controlled.[11]

Human Bacteria Transfer[edit]

Resistant bacteria can spread either through humans or livestock. Humans can create antibiotic resistant bacteria in their gut and spread them in hospitals, nursing homes, or the general community either directly or indirectly.

Environmental Bacteria Transfer[edit]

Resistant bacteria can travel through animals, water, and food. Livestock, like humans, can develop antibiotic resistant bacteria in their gut. This bacteria can get in fertilizer or water via the animal feces and then can be ingested by humans. Meat that is not handled or cooked properly also carries risk.

Easy access to Antibiotics[edit]

Antibiotics are easily accessible without a prescription, especially in rural areas. Pharmacies are often sites of primary health care; it is common for people to seek the advice of pharmacists and untrained medicine shop attendants. Ready access to restricted pharmaceuticals promotes a popular health culture wherein people engage in self-diagnosis, retain and reuse old prescriptions, acquire antibiotics at early stages of the illness to avoid future symptoms, and put off seeing a medical practitioner until their medications fail.[12]

Medical Store in rural Matiana, India[13]

Rising Incomes[edit]

India has become the fifth largest economy through enhanced industrial output and technological development. Rapid economic growth and rising incomes have fueled the scale up in antibiotic use because patients have increased expectations to receive medication when requested. These rising incomes, however, have not been translated into better sanitation or public health. Increased incomes coupled with the availability of over the counter prescription drugs has contributed to the overuse of antibiotics and has increased the drug resistant gene pool.[14]

Low Vaccination Rates[edit]

Vaccination can reduce antibiotic use and slow the spread of resistance. The current Indian National Immunization Program indicates only 75 percent of children in India are fully vaccinated.[15]

Pollution[edit]

There are no standards or monitoring of antibiotic residues in pharmaceutical industrial pollution. The antibiotic resistance gene (NDM-1) has been identified in several major rivers in India.[16] Wastewater treatment plants serving antibiotic manufacturing facilities also spread the resistant genes.[17]

Participants in Rising Antibiotic Resistance[edit]

Indian Government as Critics[edit]

In August 2010, the Lancet Journal of Infectious Disease published an article warning against the resistant gene NDM-1 and its "alarming potential to spread". It warned against undergoing surgery in India. [18]

The Indian Health Ministry refuted the Lancet journal as "unfair" stating that their hospitals are safe for treatment.[19] The Indian government believed the naming of NDM-1 was a plot against the country's medical tourism industry. Congress party's Jayanthi Natarajan said the report was a "wrong propaganda against the country". She added "When India is emerging as a medical tourism destination, this type of news is unfortunate and may be a sinister design of multi-national companies".[20] India's medical tourism industry is still growing rapidly and is estimated to be worth hundreds of millions of dollars.

The Indian government banned bacteria samples being taken to Britain and Scandinavia for further research after NDM-1 was first named. Ramanan Laxminarayan, a New Delhi-based director for the CDDEP, stated that "instead of dealing with this new healthcare issue, they got caught up in irrelevant details like the naming of NDM-1”.[21]

Patient Expectations[edit]

Patients in India often consult doctors convinced that they have infections and are unwilling to leave without a prescription. "There is an extremely powerful urge to please a patient and to alleviate his or her anxieties, so doctors think, 'It can't hurt'." claims surgeon Dr. Ramesh Punjani. [21] This increases pressure on physicians who might not otherwise prescribe antibiotics in certain situations. "It's a question of social norms," says Laxminarayan.[22]

To test patient ignorance, a survey was administered to 773 high school students in Goa, India. 67 percent were unaware of antibiotic resistance, 49 percent had misconceptions about bacteria, thinking that they caused cold and flu, 19 percent self-medicated with antibiotics, and 57 percent stop taking antibiotics when symptoms alleviated. These practices expose bacteria to nonlethal doses of the drug, giving them a chance to develop immunity.[23] Before 2015, India did not educate their citizens about the dangers of antibiotic overuse. [21]

Physician Behaviors[edit]

In 2010, researchers interviewed Indian doctors who said that when dealing with uncertainty about whether an infection is bacterial or viral, they defer to antibiotics. Time and money often prevents medical tests to confirm the cause. Doctors in both private and public sectors say that patients demand antibiotics, especially if they have received these drugs before. Often, patients request a prescription because they have already spent money consulting the doctor and would like a tangible return. Physicians in the private sector face competition. An unidentified physician in 2010 stated “if I don't give antibiotics and a patient goes to another physician or to chemist who prescribes antibiotic and he gets cured. You lose a patient”.[24]

In public hospitals, physicians have less time per patient and often do not perform a full history. One doctor recognized the issue of antibiotic overuse saying "frankly speaking we have to move patients fast and we can't really argue so much. We have only two minutes per patient". Physicians prescribe antibiotics to save time. This is worse in overcrowded hospitals. [24]

Medical Schools[edit]

The Indian medical curriculum teaching of infectious diseases to undergraduate and post graduate students. According to Abdul Ghafur, an Infectious Disease Consultant in Chennai, India, an MD General Medicine candidate can clear his or her examination without reading the chapter on infectious diseases and antibiotic usage. [25]

Hospitals[edit]

There is a lack of importance placed on resistance prevention in government hospitals. Few hospitals in India have infectious diseases and infection control specialists. The majority of private and corporate hospitals are in denial, either purposefully or due to ignorance. Dr. Ghafur says he has "come across many hospital administrators in India claiming zero infection in their hospitals. It is sad to say that many of these hospitals do not have the necessary microbiology laboratory support or trained infection control specialists to look for resistance. The claim of zero infection is in fact an innocent advertisement of the lack of necessary infection control infrastructure in that hospital". [25]

Pharmacists[edit]

A study of pharmacies in Mumbai, India found that pharmacies are typically managed by untrained attendants. Their primary sources of knowledge are medical representatives and salespersons. The market also favors the growth of small drug shops that are enticed by the incentives of pharmaceutical companies to push their products. The competition created by these stores leads pharmacy owners to allow restricted medications to be bought over the counter. [26]

Present State[edit]

World Health Organization Response[edit]

The WHO has declared antimicrobial resistance as a public health concern and has commissioned infection prevention and control programs (IPC) in India in order to contain it. In 2015, the WHO conducted a survey that revealed widespread public misunderstanding of antibiotics. Education of medical, veterinary and agricultural professionals as well as antibiotic stewardship have been identified as key to reducing the provider side of antibiotic overuse. The Ministry of Health and Family Welfare has been working towards incorporate the WHO’s National Action Plan framework into its efforts.[27]

Indian Government Response[edit]

Chennai Declaration[edit]

On August 24, 2012, a joint meeting of medical societies met in Chennai, India to begin addressing the problem of antibiotic resistance in India. The symposium resulted in the Chennai Declaration which detailed a list of objectives to address in the coming years.[28]

Objectives:[29]

  • Regulate over the counter sale of antibiotics
  • Monitor in-hospital antibiotic usage
  • Establish an autonomous antibiotic policy accreditation agency (APAA)
  • Step up infection control facilities in hospitals
  • National advisory board to prepare guidelines for infection prevention and antimicrobial stewardship in India
  • Regulate antibiotic usage in veterinary practice
  • Clinical research to explore existing options to treat infections due to MDR gram negative bacteria
  • Curriculum changes in medical schools
  • Recruit hospitals to join an national antibiotic resistance monitoring network
  • Encourage research to develop new molecules
  • Gain active contribution of medical societies
  • Introduce online modules on antibiotic usafe
  • Publish articles on tackling resistance in medical journals
  • Use media to advertise against misuse
  • Gain help from non-governmental organizations (NGOs) to increase awareness in schools and clubs
  • Measures to improve public sanitation
  • Standardize hospital accreditation agencies’ protocols
  • Step up microbiology lab facilities


Prescription Regulation[edit]

In 2014, the government started requiring prescriptions for 24 types of antibiotics, known as the Schedule H list. These prescriptions must be sold in specially marked boxes. As of 2015, there were no published evaluations or indications that this has been successful in reducing antibiotic consumption in India. It is difficult to regulate the sale of antibiotics, and the true extent of their prevalence is unknown. [30]

Global Impact[edit]

Steps have been taken to curb antibiotic resistance, but patients are still at risk. In January 2017, a woman from Reno, Nevada died from a rare bacterial infection that she picked up in India where she had been treated for a leg fracture and hip infection. The bacterium was resistant to 26 antibiotics.[31]

Number of volunteers who picked up a superbug after travels. 7/8 travelers to India picked up ESBL-producing bacteria.[32]

Conclusion[edit]

The story of NDM-1’s origin and rapid spread demonstrates the need for local, national, and global actions to preserve the effectiveness of antibiotics. Globalism has increased human access to all regions of the world, but there are medical risks associated with global travel. The occurrence of resistant micro-organisms in one part of the world now can have a major impact on the efficacy of antimicrobial therapy in other regions. Antibiotics, starting with the discovery of Penicillin in 1928, were once thought to be miracle healers, but their success is contingent on human management. Now, they are a contributing factor to rising death rates from infection in patients across the world. More education and a deeper appreciation for harmful practices associated with antibiotic use needs to be implemented to reduce this problem. This shows how social factors can alter the science behind medicine. Further work is needed to extend the examination beyond India and compare different cultures' attitudes and behaviors.

References[edit]

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