ANTIBIOTIC MICROBIAL RESISTANCE IN MAN & ANIMALS
India is among the nations with the highest burden of bacterial infections. An estimated 410 000 children aged 5 years or less die from pneumonia in India annually; accounting for almost 25% of all child deaths in India. The crude mortality from infectious diseases in India today is 417 per 100 000 persons. Consequently, the impact of AMR is likely to be higher in the Indian setting. AMR is a major public health concern in India. The emergence of resistance is not limited to the older and more frequently used classes of drugs. There has also been a rapid increase in resistance to the newer and more expensive drugs, like carbapenems. Available data indicates rising rates of AMR across multiple pathogens of clinical importance. An indicator of the rising tide of AMR in India is the rapidly increasing proportion of isolates of Staphylococcus aureus that are resistant to methicillin. In 2008, about 29% of isolates were of methicillinresistant Staphylococcus aureus (MRSA), and by 2014, this had risen to 47%. In contrast, countries that have established effective antibiotic stewardship and/or infection prevention and control programmes, the proportion of MRSA isolates has been decreasing. The burden of AMR in livestock and food animals has been poorly documented in India. Aside from sporadic, small, localized studies, evidence that can be extrapolated to the national level is lacking. Given that there are few regulations against the use of antibiotics for non-therapeutic purposes in India, with no stringent implementation protocols even when there are regulations, the emergence of AMR from antibiotic overuse in the animal sector is likely to be an unmeasured burden in India. Drug resistant bacteria have been isolated from dairy cattle as early as the 1970s. One of the most common clinical issues encountered in dairy farms is mastitis, which maybe sub-clinical or overtly symptomatic. Commonly thought to be a disease of production, milk from mastitic cows and buffaloes has been shown to contain a wide range of bacteria, with a wide spectrum of resistance against commonly used antibiotics. In some cases, multi-drug resistant bacteria have been seen to co-infect animals suffering from mastitis. As with the dairy sector, there is limited evidence available on the exact amount of antibiotics consumed within the poultry industry, and the various indications for which the medications were prescribed. In many cases, since the antibiotics are given as a growth promoter through the premixed feed, which comes with added antibiotics, it is difficult to estimate exactly the dose or the consumption levels of antibiotics in the poultry sector. Individual studies have consistently shown that bacteria isolated from animals or seafood has high levels of resistance. The legislative conditions regulating the aquaculture processes are different from those in the poultry or the dairy industry. The Food Safety and Standards Authority of India (FSSAI) has placed an extensive ban on the use of antibiotics and several pharmacologically active substances in fisheries. Also, in contrast to the poultry industry where many of the commercially available pre-mixed feeds come with antibiotics added, none of the feed in the fisheries sector contain antibiotics. These drugs can, of course, be added to the feeds separately by the farmers. Compared to the poultry and dairy sector, antibiotic resistance has been scrutinized more closely in the aquaculture sector. Due to the existence of stringent legislative provisions to contain the inappropriate and non-therapeutic use of antibiotics, it is expected that the problem of AMR in the aquaculture sector should be smaller compared to the dairy or poultry sectors. However, in a recent study that examined over 250 samples, it was seen that multi-drug resistant bacteria were isolated from over two-thirds of the samples. There exists a large body of evidence that comprises of studies investigating the resistance profiles of bacteria isolated from both sick and healthy cattle. However, these studies cannot be compiled to obtain a representative picture of the problem at the national level. Driven by local contexts, these studies can at best provide a rough overview of the magnitude of the problem of drug resistance in bacteria, but for obtaining a more comprehensive and holistic understanding, it is imperative to have a broad based surveillance system in place.
AMR situation in India —-
A combination of factors – rising incomes, unregulated access to antibiotics, including overthe-counter sale as well as sale without prescription or with invalid prescription; and perverse financial incentives for providers to prescribe antibiotics, often driven by patient demand and expectations – have played a major role in the emergence of AMR in India. The issue of AMR drew global attention through the controversy of the nomenclature of the New Delhi Metallo-beta-lactamase-1 (NDM-1), and has since received a lot of attention as a major public health concern. All the factors like the high burden of bacterial infections, poor sanitary and hygiene conditions and the increasing proportion of intensive animal farming, especially in small holder settings with minimal oversight and quality control makes emergent AMR a cause of special concern in the country. The problem is no longer restricted to the clinical or hospital setting, and is now emerging as a wider concern involving the animal/food/livestock sector, as well as environmental contamination as a source for the spread of resistance genes and antibiotic residues promoting selection pressure
It was first noted in the 1940s that addition of small doses of antibiotics to the feed led to an increased rate of weight gain and a better “feed-conversion ratio” in animals. This led to the practice of non-therapeutic use of antibiotics either for prophylaxis or metaphylaxis (timely mass medication of a group of animals to eliminate or minimize an expected outbreak of disease), and for growth promotion. Over the years, it has been seen that with improving environments in which animals are reared and with the adoption of good agricultural norms, the effect of antibiotic growth promoters (AGPs) has become progressively smaller. However, in countries where animals are reared in unhygienic or unsanitary environments, which make them more prone to suffer from infectious diseases, antibiotics still have a role to play in growth promotion. The use of sub-therapeutic doses of antibiotics for this purpose has been widely viewed to be a driver for the emergence of AMR in countries with intensive animal farming where the use of antibiotics for growth promotion is not prohibited or controlled legally . The burden of AMR in livestock and food animals has been poorly documented in India. Aside from sporadic, small, localized studies, evidence that can be extrapolated to the national level is lacking. Given that there are few regulations against the use of antibiotics for non-therapeutic purposes in India, with no stringent implementation protocols even when there are regulations, the emergence of AMR from antibiotic overuse in the animal sector is likely to be an unmeasured burden in India. India does not have a surveillance system that accounts for use and/or consumption of antibiotics in the animal/food/livestock sector. If the data from USA are indicative, then it is likely that a large proportion of the total antibiotic consumption may actually be accounted for through the livestock sector. According to a report issued by the US Food and Drug Administration (FDA), in 2011, 13.6 million kg of antibiotics were sold for use in food-producing animals in the United States, accounting for almost 80% of all the antibiotics sold or distributed in the country . In 2012, India manufactured about a third of the total antibiotics produced globally. Hence, it is likely that the consumption patterns and emerging AMR through antibiotic use in the livestock sector is an important target for policy-makers.
Antibiotic use: Cattle —
The detection of antibiotic residues in milk and dairy products has been the main approach for estimating the use of antibiotic use in dairy cattle, followed by non-compliance with withholding periods to allow the drug to be completely metabolised before initiating milking. A survey conducted by the National Dairy Research Institute (NDRI) identified that the most commonly used antibiotics in cattle were – tetracycline, oxytetracycline, gentamicin, ampicillin, amoxicillin, cloxacillin, and penicillin due to their lower costs . Use of enrofloxacin, lincomycin, streptomycin and chloramphenicol was also common when veterinarians treated for clinical conditions. More recent studies have shown that the most common indication for using antibiotics in dairy cattle is mastitis, and the preferred antibiotics include beta-lactams and streptomycin . This was supported by findings from Delhi, where similar trends were observed as beta-lactam antibiotic residues were detected from 11% of milk samples . Although antibiotic residues in milk are an indicator that the animal had been provided with antibiotic drugs in the recent past, there is no way to elicit information on the indication for which the medication was given, who prescribed it, what duration the medication was given for, what dosage the medication was given in, and whether the use of antibiotics in that particular instance was justified or not. Hence, in the absence of more robust antibiotic consumption surveillance, it is difficult to elicit data on antibiotic consumption specific to the dairy industry
Antibiotic use: Poultry —
As with the dairy sector, there is limited evidence available on the exact amount of antibiotic consumed within the poultry industry, and what were the various indications for which the medications were prescribed. In many cases, since the antibiotic is given as a growth promoter through the premixed feed, which comes with added antibiotics, it is difficult to exactly estimate the dose or the consumption levels of antibiotics in the poultry sector. In a study where samples of chicken meat were drawn from the Delhi National Capital Region, it was seen that 40% of the samples contained the residues of one or more antibiotics and 17% of the samples contained more than one antibiotic residue in the meat . With the market for chicken meat growing at a rate of 10% per annum, intensification of poultry rearing is the way to keep up with the demand, and may further increase the use of antibiotics as growth promoters.
Antimicrobial resistance:
Antimicrobial resistance: Cattle
Antimicrobial Resistance (AMR): A Global Threat to Livestock and Human Health
Drug resistant bacteria have been isolated from dairy cattle as early as the 1970s. A high level of AMR was reported from Shiga toxin-producing E. coli isolated from calves with diarrhoea in Gujarat and the Kashmir Valley . All of the strains from Gujarat were resistant to at least three antibiotics, and almost half were resistant to eight or more of the 11 antibiotics tested. Resistance was ubiquitous for kanamycin and cephalexin and was above 50% for seven of the antibiotics tested One of the most common clinical issues encountered on dairy farms is mastitis, which may be subclinical or overtly symptomatic. Commonly thought to be a disease of production, milk from mastitic cows and buffaloes have been shown to contain a wide range of bacteria, with a wide spectrum of resistance against commonly used antibiotics. In some cases, MDR bacteria have been seen to co-infect animals suffering from mastitis . One study identified that almost all samples drawn from 105 sick cows showed bacteria that were resistant to ampicillin, carbenicillin and/or oxacillin . MRSA has also been isolated from the samples of milk drawn from cows suffering from mastitis . In a recent study, almost 13% of the milk samples exhibited the presence of MRSA. These samples were significantly more resistant to other groups of antibiotics than other bacteria that were also seen in the same samples . In this study, none of the isolated MRSA were seen to be resistant to vancomycin; however, recently the first report on the presence of vancomycin resistant Staphylococcus aureus (VRSA) in bovine and caprine milk has been published, indicating the rapidly growing issue of AMR . Recent studies have shown that samples drawn from mastitic cows also contained E. coli which carried the multi-resistant NDM-1 gene and other samples, which contained E. coli with ESBL genes . Bovine source milk, especially from those animals suffering from mastitis, has been observed to have high levels of resistant bacteria. In a study conducted in eastern India, it was seen that 20% of the isolates demonstrated resistance to imipenem; samples were positive for plasmidmediated quinolone resistance genes (qnrS). The samples also contained ESBL and AmpC type beta lactamase producing MDR Klebsiella pneumoniae . There exists a large body of evidence, which comprises of studies investigating the resistance profiles of bacteria isolated from both sick and healthy cattle. However, these studies do not provide a representative picture of the problem at the national scale, for which it is imperative to have a broad based surveillance system in place.
Poultry—-
There are gaps in the surveillance system monitoring antibiotic resistance in animals in India. However, individual studies have consistently shown that bacteria isolated from animals or seafood have high levels of resistance. It has been seen that for certain groups of antibiotics, Staphylococcus and Pasteurella multocida isolated from poultry may have up to 100% resistance A 2009 study reveals that a majority of isolates from poultry were resistant to at least one antibiotic, the highest rates being against streptomycin (75%) and erythromycin (57%). Resistance was also greater than 40% for kanamycin, ampicillin, tobramycin, and rifampicin, which were largely used for non-therapeutic purposes, the most important one of them being growth promotion . Salmonella isolated from eggs, has been shown to be resistant to multiple groups of antibiotics . A recent study found significant differences in the resistance profiles of broiler farms vs. layer farms1 in the Punjab region of northern India, with drug resistance being far more common in broiler operations. Broiler farms ranged from twice as likely to more than twenty times as likely to harbour resistant E. coli, and prevalence of multi-drug resistance was much higher (94% in broiler farms vs. 60% in layers). ESBL prevalence in broiler farms was also higher at 87% vs. 42% among layers. Independent broiler operations had overall higher rates of resistant E. coli, while contracted layer farms (not independent) had higher prevalence of ESBL producers (7). The first systematic study of MDR ESBL-producing E. coli in Indian poultry and cattle found 18 of 316 E. coli isolates sampled in Odisha to be ESBL producers. All ESBL-producing strains emerged as a single lineage through phylogenetic analysis and were resistant to cephalosporins and monobactam, as well as a host of other antibiotics(40). A more recent study from backyard layers has found high rates of resistance against chloramphenicol, ciprofloxacin, gentamicin, levofloxacin, norfloxacin and oxytetracycline
Historically, AMR has not received adequate focus and attention in India. However, recent trends clearly illustrate the growing political commitment at the highest levels to have a cogent response in place that can provide the necessary gravitas for nation-wide surveillance and stewardship for containment of AMR. Efforts are also being made to incorporate the One Health approach into these plans. WHO’s framework for National Action Plans is a template that can aid in systematically addressing AMR containment in India and make it comparable to global efforts. On 27 September 2016, MoHFW notified three governance mechanisms – an intersectoral coordination committee, a technical advisory group and a core working group on AMR. The recent UNGA declaration is an opportunity for the technical leadership in India to leverage the current conducive policy environment.
Dr.Shanker Singh, TVO, Galudih, Jamshedpur.
Reference-On request..
