Antimicrobials are valuable allies to effectively defeat bacterial infections in humans and animals. Their discovery is attributed to Alexander Fleming: in 1928 he noticed that mould contamination in some bacterial cultures (Penicillium Notatum) did not develop in the area surrounding the mould, probably because the mould secretes an antibacterial substance which he named penicillin. After that, many other molecules with similar properties were discovered or produced by synthesis . In the very short time (less than a century) since Fleming’s discovery, unfortunately, many bacteria have quickly developed antibiotic resistance, so that our “weapons” have lost most or all of their effectiveness. A specific bacteria strain can develop multiple resistance to many different antibiotics. Bacteria may become resistant by spontaneous changes of the bacteria’s genetic material (different genetic mutations yield different types of resistance), or by acquiring resistance genes from another bacterium (present on mobile genetic elements). A non pathogen strain can develop antibiotic resistance and transfer it to a pathogen one. Furthermore, resistance can be developed both, towards antibiotics and to biocidal products, such as disinfectants. This effect is mostly derived from the overuse and inappropriate use of antibiotics (and disinfectants), since one of the basic elements causing this resistance is the frequent exposure to a specific biocidal agent (especially at sub-lethal doses), as this exposure generates a selective pressure on bacterial populations. The excessive use of antibiotics in human therapies is often condemned, but actually this is just the tiny rip of the iceberg, The real problem comes from the intensive stock-breeding of productive livestock (including aquaculture, both of fish and crustacean). On the other hand, intensive stock-breeding is the sole production system which gives low-cost meat and other animal products, whereby this cost can be even lower than that of other fundamental food products, such as bread and vegetables. A recent comment published by the Indian press encourages reflection on the increased cost of onions: “If Indians can’t afford onions, let them eat chicken”, suggesting that in this country the cost of chicken has become lower than the one of onions. The close clustering of animals in intensive farming systems, and the often intolerable health and hygienic conditions they are kept, are ideal for the spread of infections from one animal to another.
Bacterial resistance
When these infections are treated with antibiotics (often identical or similar to those used in human medicine), some bacteria may develop an antibiotic resistance; and it is most likely that these “benefiting” bacteria are easily transferred from one animal to another, making the whole livestock “antibiotic resistant”. Also, the transfer of resistant bacteria from animals to people isn’t particularly difficult or unlikely: next to the classic risk category represented by veterinaries and people working in slaughterhouses and farms, carriers are rapidly spreading among the risk-free population: a demonstration that these bacteria may have been transferred during the handling and/or consumption of food of animal origin, such as meat. fish, crustaceans, eggs, milk and dairy products. In Italy, antibiotic resistance is far higher than in other countries, especially in northern Europe, where this problem has been given more attention during the past years. Over time, some Italian regions (as for instance Emilia Romagna, where farming and production of animal food represent an important share) have implemented a regional surveillance system: the overview of the first 10 years shows how since 2003 the higher antibiotic resistance – especially among Gram-negative micro-organisms, Klebsiella pneumoniae and Escherichia coli – has become extremely worrying, and in relentless growth. According to the European Center for Disease Control (ECDC), which coordinates the European Antimicrobial Resistance Surveillance System (EARS Net), the problem of antibiotic resistance is perceived as a major threat to public health, and already claims dozens of victims (taking over the victims of AIDS in many countries). A recent report of the European Food Safety Authority (EFSA) in cooperation with ECDC (“European Union Summary Report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2012”), points out that bacteria most frequently causing food-born infections, such as Salmonella, Campylobacter and E. coli, show significant resistance to common antimicrobials. When comparing specific antibiotics, the detected resistance reaches levels close to 50% of the tested samples: an alarming rate.
Growth Promoters
This confirms that the bacteria typically present in farmed livestock not only can develop resistance to antimicrobials, but they may be transferred to humans from animals (chicken, pig) and food. Even in North America there is a growing awareness on this issue, and the US Food and Drug Administration recently banned the use of several antimicrobials on farmed livestock in order to preserve their effectiveness in humans. Furthermore, in the United States antimicrobials are commonly used as “growth promoters”; this means that antibiotics are usually administered to farm animals as an animal feed additive over a period of time to improve their physiological performance, the average daily weight gain and the feed efficiency. As already stated, bacteria can easily disseminate fragments of genes encoding specific abilities (as for instance production of enzymes capable of disabling antibiotics). When a human enters in contact with an animal bearing resistant bacteria, or its potentially contaminated meats, these bacteria can transfer from the animal to the human and carry the resistance in the human microbiota (without any symptom), including possible pathogens that he may contract in future, with obvious difficulty of treating them. A particularly serious antimicrobial resistance, recently discovered in the enterobacteriaceae of farmed livestock, is the resistance to new antimicrobials, also called last-line antibiotics, used to treat difficult infections when all other antibiotics have been useless. For instance, carbapenemase-producing bacteria have been detected, enzymes capable of breaking down the carbapenem antibiotics: accepted by the World Health Organization (WHO), they make up an important group of antibiotics used for treating human infections, and play a critically important role in our antibiotic armamentarium. In fact, they are often used to treat infections that are resistant to other antibiotic classes. If even last-line antibiotics become ineffective, the treatment of specific infections will be impossible, and the individual who suffers such infection will find himself in the same situation as his ancestors in the first part of 1900, when antibiotics had not yet been discovered. MRSA is one of the most famous antibiotic resistant bacteria: methicillin-resistant Staphylococcus aureus. This Staphylococcus is a bacteria capable of growth in animal and human skin and soft tissues: Accoding to the ECDC about 30% of humans are asymptomatic nasal carriers, whereas in other subjects this bacteria can cause different types of infections in various body sites. MRSA, asymptomatically present in approx. 1-2% of humans (and in approx 25% of the humans working in contact with farmed livestock and their relatives) is a very difficult strain to defeat, since traditional beta-lactam antibiotics (i.e. derived from penicillin) have no effect, so that even common infections require long and difficult treatments, and in some cases can even lead to death. The paradox is that patients with MRSA infections often must be hospitalized, however, the most resistant MRSA strains are usually to be found in hospitals, since in an environment with increased use of disinfectants and antibiotics they become ultra-resistant and aggressive. Other particularly resistant MRSA strains are those present in farmed livestock, which are often treated with antibiotics. Before 2005, MRSA was detected in rare cases, although known for many decades (first detected in 1970): over the last years the occurrence of MRSA epidemic escalates at an alarming rate. MRSA (especially the CC398 strain) in Europe is widely distributed in about 50% pig farms and approx. 20% turkey farms: the animals are not necessarily sick, but the staphylococcus (MRSA or not) is often cause of, for instance, mastitis in milk cows. People living near farms or agricultural fields are more frequently colonized with MRSA. In organic farming systems, MRSA may be present, but at lower levels compared to conventional intensive farming systems. In fresh meat, MRSA is detected in a variable number of samples, ranging from 10 to 40% (alarming percentage, however lower compared to the Unites States). It can, hence, be deduced that MRSA can be transmitted to humans by the handling and/or consumption of meat, especially if no hygienic rules are followed while handling food. The last remark emphasizes the importance of implementing and maintaining improved hygiene practices at all stages of the food chain.
Literature
• BfR (Federal Institute for Risk Assessment, Germany), 2012. Questions and answers about methicillin-resistant Staphylococcus aureus (MRSA)
• Ministero della Salute, Dipartimento della Sanità Pubblica Veterinaria, della Sicurezza Alimentare e degli Organi Collegiali per la Tutela della Salute, 2011. Manuale di “Biosicurezza e uso corretto e razionale degli antibiotici in zootecnia”
• EFSA, 2010. The Community summary report on antimicrobial resistance in zoonotic agents from animals and food in the European Union in 2004–2007. EFSA Journal, 2010, 8(4):1309–1615
• WTM Jansen et al., 2006. Bacterial resistance: A sensitive issue – Complexity of the challenge and containment strategy in Europe. Drug Resistance Updates, 9:123-133
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• S. Langsrud et al, 2003. Bacterial disinfectant resistance – a challenge for the food industry. International Biodeterioration & Biodegradation, 51:283-290
• H.C. Wegener, 2003. Antibiotics in animal feed and their role in resistance development. Current Opinion in Microbiology, 6:439-445
• N. Rudholm, 2002. Economic implications of antibiotic resistance in a global economy. Journal of Health Economics, 21:1071-1083
• J.G. Salisbury et al., 2002. A risk analysis frame work for the long-term management of antibiotic resistance in food-producing animals – commentary. International Journal of Abtimicrobial Agents, 20:153:164
• H. Sorum and T.M. L’abée-Lund, 2002. Antibiotic resistance in food-related bacteria – a result of interfering with the global web of bacterial genetics. International Journal of Food Microbiology, 78:43-56
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By Rita Lorenzini
