Hospitals in India have a high burden of infections in their intensive care units (ICU) and general wards, many of which are resistant to antibiotic treatment, according to a report by Global Antibiotic Resistance Partnership (GARP) – India Working Group and Centre for Disease Dynamics, Economics and Policy (CDDEP). The 2011 GARP report, Situation Analysis: Antibiotic Use and Resistance in India, also states that a large proportion of these hospital-acquired infections (HAI) are preventable with increased infection control measures.

Research on hospital infections in India reveals several concerning trends. In Indian ICUs, the rate of vancomycin-resistant enterococcus (VRE), a dangerous hospital infection, is five times the rate in the rest of the world. Rates of methicillin-resistant Staphylococcus aureus in Indian ICUs are also high, with one study finding over 80 per cent of S. aureus samples testing positive for resistance to methicillin and closely related antibiotics.

Antibiotic resistant infections are difficult, and sometimes impossible, to treat. They lead to longer hospital stays, increased treatment costs, and in some cases, death. The GARP research estimates that of the approximately 190,000 neonatal deaths in India each year due to sepsis – a bacterial infection that overwhelms the bloodstream – over 30 per cent are attributable to antibiotic resistance. Antibiotic resistant hospital infections can be especially deadly because antibiotics are used intensely in hospitals compared with the community, and frequent use drives the development of highly resistant bacteria.

Organisms causing hospital infections in India are similar to those around the world, with S. aureus and P. aeruginosa among the most common disease-causing pathogens. A prospective study of 71 burn patients at Post Graduate Institute of Medical Education and Research (PGIMER) in Chandigarh found that up to 59 patients (83 per cent) had hospital-acquired infections: 35 per cent of pathogens isolated from wounds and blood were S. aureus, 24 per cent were P. aeruginosa, and 16 per cent were ?-haemolytic streptococci.

Another six-month study conducted in 2001 of the intensive care units (ICUs) at All India Institute of Medical Sciences (AIIMS) in New Delhi, found that 140 of 1,253 patients (11 per cent) had 152 hospital-acquired infections, where P. aeruginosa made up 21 per cent of isolates, 23 per cent were S. aureus, 16 per cent Klebsiella spp., 15 per cent Acinetobacter baumannii and 8 per cent Escherichia coli. Further, a study of 493 patients in a tertiary teaching hospital in Goa also found that 103 people (21 per cent) developed 169 infections.

“A large proportion of these hospital infections are easily preventable with increased hospital infection control, including stepping up hygiene practices, such as frequent hand-washing,” says Dr Ramanan Laxminarayan, Director of CDDEP and vice president for research and policy at the Public Health Foundation of India.

In India, however, hospitals often do not follow infection control practices, and this leads to the spread of disease. In response to the growing burden of HAIs in India, GARP is issuing several key recommendations that aim at reducing the prevalence of HAIs, including increased hand-washing, use of isolation rooms for infected patients, increased availability and uptake of diagnostic tests, reminders to limit catheter use, and use of gloves and gowns. The ministry of health and family welfare task force also recommends that all hospitals create an infection control plan, committee and team.

“Surveillance of antibiotic resistance, combined with tracking physician prescribing patterns, can be the foundation of successful infection control programmes in hospitals. But surveillance is a challenge in many places, where microbiology laboratories and trained staff may be unavailable,” says Dr Laxminarayan.

Infection control committees may also be met with uncooperative hospital staff and administrators. “The greatest challenge is to empower infection control committees and make hospital staff aware of their activities and recommendations,” adds Dr Ramanan Laxminarayan.

Hospital acquired infections (HAI) are far more common in India than in western countries. This occurs at the alarming rate of one infection per four hospital visits compared to one in ten for a European country and one in twenty for the United States. At a rate this high, and due to the potential infection for immunocompromised patients, this could be a large contributing factor to the spread of disease in India.

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Hygiene routines are already in place for Indian hospitals. Standards have been set and there are rules to follow. Many of these HAIs are common despite this. This implies that infections are occurring not through absence of set rules, but through non-compliance to the rules that are already in place.

A recent study finds that the rates of hospital-acquired infections and antimicrobial resistance were markedly higher in India than those reported by the CDC in the U.S.
A large number of patients who go to hospitals come back with something more serious. According to the World Health Organisation, at any given time over 1.4 million people across the globe suffer from a nosocomial or hospital-acquired infection (HAI). HAIs account for 2 million cases and about 80,000 deaths a year.

The first step to combat this situation is to improve hygiene practices and implement standard operating procedures at each step, according to the president of the International Nosocomial Infection Control Consortium (INICC), Victor D. Rosenthal, who has been studying the problem for several decades.

This viewpoint has been acknowledged by the World Health Organization (WHO). Knowledge of the pathophysiology of infectious diseases has been enhanced by world leading research stemming from many countries. The spreading of antimicrobial resistance amongst many diseases has become a top priority in recent years. Yet still infections occur through what amounts to negligence of hygiene rules. To combat this the WHO has focused on the “Clean Care is Safer Care” campaign, focusing on the basics of hand hygiene.

“Most HAIs are caused due to [a] lack of compliance with infection control guidelines, such as hand hygiene, [and] use of outdated technology,” he says. The most common types of HAIs are bloodstream infection, pneumonia, urinary tract infection and surgical site infections.

A re-assessment of hygiene strategy and the means to enforce standards from the ground up may be the best potential strategy to address the situation. It has been found that a large number of the infections stem from medical devices such as mechanical ventilators and catheters. Again this relates to a lack of hygiene associated with the device, with suggestions that different, potentially outdated, devices are often used in Indian hospitals and so often will not adhere to modern standards.

A study conducted by Dr Victor Rosenthal published by the International Nosocomial Infection Control Consortium (INICC) assessed the rates of device associated infections across 40 Indian hospitals compared to a number of other countries. These studies were conducted on patients in intensive care units (ICUs).

The findings indicate that 7.92 central line-associated bloodstream infections occurred per 1,000 central line-days, 10.6 catheter-associated urinary tract infections per 1,000 urinary catheter-days and a ventilator-associated pneumonia rate of 10.4 per 1,000 mechanical ventilator-days.

Many of those in intensive care will be in severely weakened states, potentially on antibiotics for other conditions. Conditions such as pneumonia may be life threatening under these circumstances . Also of concern is the fact that many of the HAIs are immune to antibiotics, this contributes to the spread of antibiotic immunity, with the potential to transfer the associated genes to other, potentially more lethal diseases if co-infection occurs.

Dr Rosenthal warns against the overuse of antibiotics to address the problem “The misuse and excess use of antibiotics increase resistance. The approach should be to prevent infections and in the process bring down the HAI rate together with bacterial resistance, rather than waiting for infections and then treating them with antibiotics.”. It is perhaps this “catch up” mentality that allows the infections to flourish.

The WHO present a strong case for an overhaul of the hygiene system from the ground up, preventing the spread of infection rather than treating it when it occurs.

Key findings
A study published in 2015 by the INICC led by Dr. Rosenthal, studied the rate of device-associated infection rates in 40 hospitals from 20 Indian cities over a 10-year period from 2004. The study, which collected data from 236,700 intensive care unit (ICU) patients for 970,713 bed-days, found that rates of HAIs and antimicrobial resistance were markedly higher in India than the rates reported by the Centers for Disease Control and Prevention, the leading national public health institute in the United States.

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The study found an incidence rate of 7.92 central line-associated bloodstream infections per 1,000 central line-days, 10.6 catheter-associated urinary tract infections per 1,000 urinary catheter-days and a ventilator-associated pneumonia rate of 10.4 per 1,000 mechanical ventilator-days in adult ICUs. The study reports that these high rates could reflect “the typical ICU situation in hospitals in India”.

“In India, adherence to practice bundles is irregular, hospital accreditation is not mandatory, and some of the technology applied is different from that of high-income countries. This situation is further emphasised by the fact that administrative and financial support in public hospitals is insufficient to fund full infection control programmes, which invariably results in extremely low nurse-to-patient staffing ratios — which have proved to be highly connected to high HAI rates in ICUs — and hospital overcrowding,” reads the study.

Issue of overcrowding
Acknowledging India’s serious problem of overcrowding of hospitals which leads to many basic hygiene processes being given the go by, Dr. Rosenthal says limited manpower is an important risk factor. “Having one nurse for three beds in an ICU is an important risk factor. With limited resources, there are limitations on providing a good enough manpower, proper guidelines, proper training, proper education, good behaviour, and right technology,” he explains.

Today more than ever, pathologists are constantly in “catching up” mode trying to counter microorganisms rapidly mutating and adapting to existing known methods of treatment. And the persons most susceptible to infection are those whose immune system is already compromised, say after a surgery or a prolonged visit to the hospital.

Referring to the overuse of antibiotic drugs, Dr. Rodenthal sounds a sharp warning to the overuse of antibiotics: “The misuse and excess use of antibiotics increase resistance. The approach should be to prevent infections and in the process bring down the HAI rate together with bacterial resistance, rather than waiting for infections and then treating them with antibiotics.”

Hospital Infection Solution In India
A Bengaluru firm has become India’s first to receive the international CARB-X grant to develop antibiotics to treat hospital-acquired infections. #KhabarLive explains why this is important.

What is CARB-X, and why was it instituted?

CARB-X, or Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, is a public-private international partnership, which was set up in 2016 to focus on innovations to improve diagnosis and treatment of drug-resistant infections. It grew out of President Barack Obama’s 2015 Combating Antibiotic Resistant Bacteria (CARB) initiative, and is funded by the London-based biomedical research charity Wellcome Trust, and the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services.

“The partnership provides a new, collaborative approach to speed research, development and delivery of new antibiotics, vaccines, diagnostics, and other innovative products to address the urgent global problem of drug-resistant bacterial infections,” Kevin Outterson, Executive Director of CARB-X and Professor of Law at Boston University told #KhabarLive in an interview.

CARB-X is headquartered at BU Law, and will provide grants up to $ 455 million (over Rs 2,900 crore) over a five-year period to firms across the globe for antibiotics R&D. Two sets of funding, covering 18 projects in six countries, were announced on March 30 and July 25 this year. All CARB-X funding so far is focused on projects to address the most resistant “Gram-negative” bacteria.

So, what are Gram-negative bacteria?

Bacteria are classified as Gram-positive and Gram-negative, based on a structural difference in their cell walls that is detectable through a staining technique developed in 1884 by the Danish bacteriologist Hans Christian Gram. Gram-negative bacteria are responsible for 20-25% of infections, and are multi drug resistant — which is the ability of bacteria to defend themselves against drugs that try to kill them.

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Antibiotic resistance has become a global crisis that threatens the management of infections, both in the community and in hospital practice. The major reasons are the indiscriminate use of antibiotics, including against viral infections, especially in countries like India where they are commonly available over the counter; their prolonged use in patients admitted to hospitals; and their abuse in animal husbandry as growth promoters. Cheaper antibiotics such as penicillin, tetracycline or co-trimoxazole can often no longer cure an infection, and high-end ones like third- and fourth-generation cephalosporin and carbapenem are commonly used, doctors in India believe. In hospital critical care units, more than 50% organisms are now resistant even to these drugs.

Technically, antibiotic resistance is a subset of antimicrobial resistance (AMR), which is a wider category that covers resistance in all microorganisms — bacteria, parasites, viruses and fungi — to drugs. But as antibiotics (drugs against bacteria) are the commonest antimicrobials, the two terms are often used interchangeably. Some 700,000 people die of resistant infections every year globally, a number that is estimated to rise to 10 million by 2050.

OK, but is there a reason for India to be particularly interested in CARB-X and AMR?

One, India, because of its sheer numbers, poor literacy and awareness, and lax controls over medical practices, is on the frontlines of the global AMR public health crisis. A 2015 WHO multi-country survey recorded “widespread public misunderstanding” about antibiotic use in India, and Health Minister J P Nadda, in April 2016, flagged antimicrobial resistance as a “serious threat to global public health”. As per the National Action Plan on Antimicrobial Resistance (NAP-AMR), the crude mortality from infectious diseases in India is 417 per 100,000, and India is among countries with the highest burden of bacterial infections.

Two, an Indian company, Bangalore-based Bugworks Research, has received an Initial fund of $ 2.6 million (about Rs 16.6 crore) for its work on a new class of antibiotics to fight what is known as the “ESKAPE” group of pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). “ESKAPE pathogens are considered the leading cause of nosocomial (hospital-born) and hospital acquired infections throughout the world. Most of these strains are multidrug resistant isolates, and treatment of these infections is one of the greatest challenges in clinical practice,” co-founder of Bugworks Research, Santanu Datta, told #KhabarLive.

And how do independent experts see projects like CARB-X?

Professor Balaji Veeraraghavan, Head, Clinical Microbiology, Christian Medical College and Hospital, Vellore, told #KhabarLive: “In the recent past, no new antibiotics have been approved for clinical use. Regardless of ongoing efforts to develop new agents, government and private sectors must be alert and promote drug development. It is of supreme importance to have more initiatives like CARB-X for the development of new antimicrobial agents. This would ultimately reduce the ever-increasing gap between rising antimicrobial resistance and declining rates of the discovery of new agents.”

Professor Pallab Ray of the Department of Microbiology, PGIMER, Chandigarh, said initiatives like CARB-X are required not only at the global level, but in India as well. “There is no dearth of data on AMR, there are policies in most hospitals, declarations on how to take the bull by its horns. What we lack is an administrative structure to implement it. The need of the day is programmes to implement the control measures empowered by administrative control and legislative binding on every user of antibiotics,” he said.

Several Ministers signed a ‘Delhi Declaration’ to strategise together to contain AMR. Specific objectives of the plan include the “prevention of emergence and spread of resistant bacteria through infection prevention and control, optimised use of antibiotics in all sectors, and enhanced investments for AMR activities, research and innovations”.

The plan also aims to enable monitoring and evaluation (M&E) of the implementation of NAP-AMR based on the M&E framework. #KhabarLive


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