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Introduction

Antibiotic resistance is one of the most serious global threats to the treatment of infectious diseases [1]. Antibiotics are critical in the fight against infectious disease caused by bacteria and other microbes. Antimicrobial chemotherapy is a leading cause for the rise of average life expectancy. Antimicrobial resistance — when germs change in a way that reduces or eliminates the effectiveness of drugs to treat them — is a growing global problem. One part of the problem is that bacteria and other microbes that cause infections are remarkably resilient and have developed several ways to resist antibiotics and other antimicrobial drugs. Another part of the problem is due to increasing use, and misuse, of existing antibiotics in human and veterinary medicine and in agriculture. Workers exposed may be at risk of contracting serious and possibly fatal infections that are not treatable.

Although the general community is at risk, some occupations pose higher risks to the workers. This, however, is dependent on the type of bacteria involved. Chapter 3, reviewing the most important types of antibiotic resistant bacteria, gives a brief description of the occupations with increased risk for each type of bacteria. From a sectoral point of view, the main occupational groups exposed are treated in chapter 4.

Mechanisms of resistance to antibiotics

Resistance to antibiotics can be a natural process – bacteria are naturally resistant to some antibiotics. For example, benzyl penicillin has very little effect on most microorganisms that can be found in the human digestive system. Other bacteria have developed resistance to antibiotics that were already once used to treat them. For example, Staphylococcus aureus is now almost always resistant to benzyl penicillin, while in the past, this infection was controlled by penicillin. These mechanisms of resistance to antibiotics can be of two types – the genetic and the biological. Genetic mutation occurs and causes a change in the bacterial DNA, and the bacterium becomes resistant to antibiotics. Biological mechanisms can be summarized to antibiotic destruction or antibiotic transformation. This destruction or transformation occurs when the bacteria produces one or more enzymes that chemically degrade or modify the antimicrobial making them inactive against the bacteria. Evidence also began to accumulate that bacteria could pass genes for drug resistance between strains and even between species. For example, antibiotic-resistance genes of staphylococci are carried on plasmids that can be exchanged with Bacillus, Streptococcus and Enterococcus providing the means for acquiring additional genes and gene combinations. Some are carried on transposons, segments of DNA that can exist either in the chromosome or in plasmids [2].

The most serious problem is that some bacteria have become resistant to almost all available antibiotics. These bacteria are able to cause serious disease and this is a major public health problem as well as an occupational risk for people exposed to these bacteria.

The most important types of multiple drug resistant micro-organisms

Methicillin/oxacillin-resistant Staphylococcus aureus

Methicilin/oxacilin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality worldwide. MRSA are often sub-categorized as Hospital-Associated MRSA (HA-MRSA) or Community-Associated MRSA (CA-MRSA), depending upon the circumstances of acquiring disease [3]. MRSA infection can cause severe health problems in health care workers that may lead to long-term incapacity. People occupationally exposed to livestock (animal farming, food industry, butchers, slaughterhouse workers, animal and veterinary laboratory workers) are under risk of nasal colonization (a process by which species of microorganisms spread into the area of the nasal mucous membrane with successful integration) with MRSA strains. Risk factors for community acquired infection also include intravenous drug use, previous antimicrobial therapy, serious illnesses, transmission from environmental surfaces by airborne route, bioaerosols in working areas. Especially for CA-MRSA a well known environment with increased risk for infection are crowded places with limited hygiene. Prisons, security and police staff and social workers may be at risk.

Vancomycin-resistant enterococci

The incidence of infection caused by multiple resistant enterococci remains lower nowadays, although several outbreaks have been reported in transplant and intensive care units. About 2­5% of the population in Europe are intestinal carriers of vancomycin resistant E faecium, acquired from food [4]. The biggest risk of vancomycin-resistant enterococci (VRE) is for hospital workers (especially direct patient contact and contact to faecal material lead to highly increased risk), agriculture, food industry, and waste and waste water treatment workers.

Bacteria containing extended-spectrum beta-lactamases (which are resistant to cephalosporins and monobactams)

Extended-spectrum beta-lactamase (ESBL) – producing Gram-negative bacteria. Known risk factors for colonization and/or infection with organisms harbouring ESBLs include admission to an intensive care unit, recent surgery, instrumentation, prolonged hospital stay and antibiotic exposure, especially to extended-spectrum beta-lactam antibiotics. Use of extended-spectrum antibiotics promotes the emergence of ESBL producing strains. The resistance plasmids can then be transferred to other bacteria, not necessarily of the same species, conferring resistance to them [5]. The most common risk of ESBL is for health care workers with direct patient contact; especially with contact to body fluids typically in intensive care units, elderly homes, and similar kind of places. This is a strongly growing problem which in many countries now is the major cause of bacterial infection in hospitals. Especially the fact that certain ESBL bacteria are resistant to nearly all known antibiotics makes this a very serious threat to patients, their families, as well as the health care workers.

Penicillin-resistant microorganisms

Multiple antibiotic resistances to useful classes of antibiotics, including penicillin, cephalosporin, and amino glycosides, has gradually increased among a number of Gram negative hospital pathogens, especially Streptococcus pneumonia, Klebsiella pneumonia, Entero­bacter, Pseudomonas aeruginosa, ESBL bacteria nearly always are resistant against penicillin as well. Epidemic and endemic infections caused by these multiple resistant strains followed intense antibiotic use in many hospitals, particularly in intensive care units. In many cases, epidemic strains of these Gram negative bacilli shows resistance to nearly all available antibacterial drugs and causes serious nosocomial infections – such as pneumonia and bacteraemia – which are associated with increased mortality [6]. When caring for patients, health care workers are exposed to the same risk of being infected through inhaled bioaerosols in which there could be penicillin-resistant microorganisms ( Bioaerosols and occupational safety and health).

Multi-drug resistant Mycobacterium tuberculosis

Tuberculosis (TB) is caused by a mycobacterium. Mycobacterium tuberculosis (MTB) is the most common bacterial agent responsible for TB, however, M. bovis, M. microti canetti, and M. africanum can also result in TB. Drug-resistant tuberculosis has been recognised since about the 1940s, with the rapid emergence of streptomycin resistance unless a combination of drugs was used. Drug-resistant TB can be said to exist when treatment with a drug suppresses the growth of some bacilli (susceptible to that drug) but permits multiplication of pre-existing drug-resistant organisms. “Multidrug-resistant TB” (MDRTB) is resistant to both isoniazid and rifampicin. All drug-resistant TB cases are made up of strains that are: resistant to isoniazid or streptomycin (monoresistant), resistant to isoniazid and streptomycin (double resistant), resistant to isoniazid, streptomycin and rifampicin (triple resistant), resistant to isoniazid, streptomycin, rifampicin and ethambutol (quadruple resistant).

It is estimated that there are 300,000 cases of MDRTB in the world and most exist where HIV is spreading most rapidly, 79% of MDRTBs are super strains (for example, resistant to three or four first-line drugs), TB patients in Eastern Europe and the former Soviet Union are 10 times more likely to have MDRTB [7]. People who have an increased chance of contact with MDRTB include the following groups of staff: health care workers, prison and police officers, veterinary workers and others. Social workers and teachers might also be at a low level risk in some areas of Eastern European, however currently there are no research results to substantiate this.

The main occupationally exposed groups

Agriculture, livestock, food industry

Drugs used by people are not the only source of antibiotics in the environment – antibiotics can be found in dairy, pig, poultry and factory farms (agricultural sector). These antibiotics find their way into municipal water systems then they run off from housing facilities and contaminate streams and groundwater. So it's a double hit: we get antibiotics in our food and drinking water, and by waste and wastewater promotes bacterial resistance. In the agrifood industry – in cattle, poultry and hog farming, fish farming, honeybee hives – these agents are used as growth promoters. Some estimates suggest that antibiotic use in animals and fish is at least 1000-fold greater in terms of absolute tonnage compared with use in humans [8].

The potential public health risks related to the use of antibiotics in pig and other factory farms include the contamination of food with residues of antibiotics, release of antibiotics residues into the environment, the selection for antibiotic resistant bacteria, and an occupational exposure of farmers and other agricultural workers to antibiotics. The selection for resistant bacteria is the main problem followed by farm workers who acquire infections which can potentially spread the resistant bacteria in the community as well.

There is substantial evidence that antimicrobial use in food-animal production contributes to the burden of antimicrobial resistant diseases in human populations through food borne routes of exposureAntimicrobial-resistant bacteria have been detected in animal wastes, animal bedding, air both inside and downwind of animal feeding operations, in groundwater near animal feeding operations, and in consumer meat and poultry products. Additional pathways likely exist through exposure to contaminated environmental media in and around animal production facilities as well as contact with animals in the occupational setting. Occupational epidemiology studies of European broiler farmers and turkey farmers, as well as broiler and turkey slaughterhouse workers, indicated that these populations were at increased risk of colonization with antimicrobial-resistant E. coli and Enterococcus because of their occupational exposure to these animals [9]. People occupationally exposed to livestock are under risk of nasal colonization with MRSA strains. In the Netherlands, the prevalence of MRSA in pig farmers was estimated to be 29% compared to about 0.1% in general population. In the USA, however, the exposure of pig farmers to MRSA is much lower [10].

Health care

As a result of a wide use of antibiotics for human health and veterinary purposes, not only for therapy but also for animal growth promotion, some bacteria and other microorganisms have developed resistance to one or more anti-microbial agents. This process is also part of the natural microbial evolution, but the increase of such organisms in the last years is due to the continuous misuse of antibiotics. A very well known example of such an organism is the methicillin/oxacillin - or multi-resistant Staphyloccoccus aureus (MRSA), which is the most common cause of hospital-acquired – or so-called nosocomial infections (pneumonia, chronic bronchitis, purulent skin diseases, etc.). Therapeutic difficulties in the treatment of such infections lead to a longer duration of illness and higher mortality [11]. Hospitals and intensive care units are an important breeding ground for the development and spread of antibiotic resistant bacteria. This is the consequence of exposing to heavy antibiotic use a high density patient population in frequent contact with healthcare staff (health service sector). Among pathogens causing hospital infections, Gram positive cocci have become predominant. This trend is related to these pathogens' capacity for accumulating antibiotic resistance [12]. The ways of antibiotic resistant bacteria transmission in hospitals can be contact with contaminated hands of hospital staff, the contact with contaminated surfaces such as door handles, the contact with contaminated equipment, and direct contact with patient and/or contact with patient`s body fluids (faeces, saliva, wound fluids) which are the major sources of infectious material.

Laboratories

Laboratories are a very special working environment that may increase a risk of infectious disease to staff in or near them. Laboratory workers have an important role to play in the care of infected patients, preventing further transmission of microorganisms, and reducing the epidemic. Laboratory staff can be working with all groups of biological agents for diagnostic, research and teaching purposes. A larger number of cases of infection occur in research laboratories than in clinical laboratories because they are working with live cultures. Laboratory staff is estimated to be more likely than the general public to develop tuberculosis. Tuberculosis has emerged as a significant public health issue that has become further complicated by the appearance of multiple drug-resistant strains.

Working areas with air conditioning systems and high humidity

Many biological agents are communicated via air, such as exhaled bacteria or toxins of mouldy grain [13]. Rushed construction and poorly designed air-conditioning systems present serious problems with air conditioning system. The equipment is unable to dry the air properly. The early recorded outbreaks or epidemics of Legionnaires’ disease were related to hospitals or health centres, hotels, shopping centres, meat packing plants, garment industries, office buildings, food stores, car manufacturing plants, and even nuclear power stations [14]. The most common bacterium which breeds in air-conditioning systems and in water tanks and fittings is Legionella pneumophila, but there can be other drug-resistant microorganisms (germs, moulds, spores, fungi), including, for example, MRSA.

Waste water treatment

Along with total microbial concentration, the concentration of antibiotic-resistant bacteria varies throughout the wastewater treatment process. The percentage of antibiotic-resistant bacteria increases with secondary (usually biologic) treatment, but decreases with tertiary treatments such as ultraviolet radiation or chlorination. MRSA can survive for as many as 14 days in aquatic environments, both saline and non-saline. Several types of antibiotic-resistant bacteria occur in higher numbers in wastewater than in the natural environment, but in general, S. aureus occurs at low levels in both surface water and wastewater [15],[16].

Prevention

In order to effectively address the risk of global epidemics affecting workers and the general public, networking and sharing information between public health, including epidemic hygiene, and occupational health are essential. Good knowledge of the transmission chain (reservoir – transmission route/vector - entrance point into the host) is essential to implement effective prevention measures at early stages of the chain. These measures should be in compliance with the EU legislation. They are also necessary to avoid the spread of an infection to non-affected areas e.g. by infected workers who come into contact with uninfected materials, animals or people, such as breeders, transport personnel, workers at slaughterhouses, veterinarians or culling personnel, or by contaminated travellers [17]. Measures to stop the spread of drug resistant microorganisms and the contamination of workers, include the improvement of work organisation, regular cleaning of the work premises, use of safety-engineered sharp instruments, appropriate handling of clinical waste and thorough hand washing [18].

If the exposure is not avoidable, it should be kept to a minimum by limiting the number of workers who are exposed, and reducing their exposure time. The control measures must be tailored to the working process, and the workers must be well trained to follow safe working practices [19]. People who have an increased chance of contact with drug-resistant microorganisms ( risk management for dangerous substances) in an occupational setting are also recommended to have their health check routinely assessed when starting work and then periodically. The employer also has the responsibility to provide the workers with information and [[OSH training |training to enable them to recognise the hazards and to follow safe working procedures, to make risk assessment that identifies the hazards in workplace and evaluates the risks posed by these hazards. Good housekeeping, hygienic working procedures and use of relevant warning signs are key elements of safe and healthy working conditions. In some cases preventive measures may include vaccinations to workers most at risk [20].

The most important ways to prevent antibiotic resistance are to minimise unnecessary prescribing of antibiotics, a good personal hygiene, such as hand washing before and after contact with contaminated surfaces and the appropriate use of disinfectants, the use of barrier equipment such as glovesgownsmasks and goggles. Guidance is available for hand washing policies, especially for the (health) care professions [21],[22]. A recent WHO campaign (SAVE LIVES: Clean Your Hands) reiterated its importance for the prevention of antimicrobial resistance, contamination and the protection of health care workers. Specific guidance is also available for disinfection and sterilization and other hygienic measures for these sectors.

The most important organisational measures to prevent antibiotic resistance and transmission in hospitals are isolation of patients, regular cleaning, and disposable equipment.

Prevention of infection among health care professionals, working in tuberculosis research laboratory, requires appropriate safeguards. Laboratory staff, while processing infectious materials has to be educated about the protection from potentially infectious aerosols, which can be prevented. Proper usage of primary (biological cabinets, PPE, appropriate work clothing) and secondary barriers (e.g. limiting access) in contagious areas through the regular use of good laboratory practices is important in controlling the risk of laboratory-acquired infection. Based on the activities performed in the laboratory, different levels of containment are essential. Procedures involving manipulation of liquid suspension containing infectious materials needs to be done in the Bio-safety cabinets. For effective and absolute containment of potentially lethal infection, Mycobacteriology research laboratorines need to be upgraded as Bio-Safety level III facility which ensures absolute containment of turbulent air currents inside the laboratory besides adhering to the international standards [23].

To prevent transmission of antibiotic resistant bacteria at work places and, more generally, in community, it is recommended to wash hands before and after food handling, going to the toilet and changing nappies, to cover nose and mouth when coughing and sneezing, to use tissues to blow or wipe nose, not to spit, to stay at home if feeling unwell, not to send children to child care or school if they are unwell, to take the entire course of prescribed antibiotics, to avoid use of products which can contain antibiotics, or are antibacterial or antimicrobial, unless advised to do so by health professional.

References

[1] Conly, J., ‘Antimicrobial resistance in Canada’, CMAJ, Vol. 167, No 8, 2002, pp. 885-891. Available at: http://www.cmaj.ca/content/167/8/885.full.pdf+html

[2] Jacoby, G.A., Munoz-Price, L.S., ‘The new b-lactamases’, N Engl J Med, Vol. 352, 2005, pp. 380–391. Available at: http://www.nejm.org/doi/pdf/10.1056/NEJMra041359

[3] Todar's Online Textbook of Bacteriology. Retrieved 25 April 2012, from: http://textbookofbacteriology.net/resantimicrobial_2.html

[4] Struelens, M.J., ‘The epidemiology of antimicrobial resistance in hospital acquired infections: problems and possible solutions’, BMJ, Vol. 317, 1998, pp. 652-654. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113836/pdf/652.pdf

[5] Todar's Online Textbook of Bacteriology. Retrieved 25 April 2012, from: http://textbookofbacteriology.net/resantimicrobial_2.html

[6] Struelens, M.J., ‘The epidemiology of antimicrobial resistance in hospital acquired infections: problems and possible solutions’, BMJ, Vol. 317, 1998, pp. 652-654. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113836/pdf/652.pdf

[7] WHO/IUATLD ‘Global Project on Anti-tuberculosis Drug Resistance Surveillance (1999-2002)’, Anti-tuberculosis drug resistance in the world: Report Number 3, 2004. Available at: http://www.who.int/tb/publications/who_htm_tb_2004_343/en/index.html

[8] WHO/IUATLD ‘Global Project on Anti-tuberculosis Drug Resistance Surveillance (1999-2002)’, Anti-tuberculosis drug resistance in the world: Report Number 3, 2004. Available at: http://www.who.int/tb/publications/who_htm_tb_2004_343/en/index.html

[9] Price, L.B., et all, ‘Elevated Risk of Carrying Gentamicin-Resistant Escherichia coli among U.S. Poultry Workers’, Environmental Health Perspectives, Vol. 115, No 12, 2007, pp. 1738-1742. Available at: http://ehp03.niehs.nih.gov/article/info:doi/10.1289/ehp.10191

[10] Dutkiewicz, J., et all, ‘Biological agents a occupational hazards – selected issues’, Annals of Agricultural and Environmental Medicine, Vol. 18, No 2, 2011, pp. 286-293. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22216801

[11] Kosk-Bienko, J., ‘OSH risks related to global epidemics and drug-resistant micro-organisms’, EU-OSHA – European Agency for Safety and Health at Work, 2007. Available at: http://osha.europa.eu/en/seminars/occupational-risks-from-biological-agents-facing-up-the-challenges/speech-venues/speeches/osh-risks-related-to-global-epidemics-and-drug-resistant-micro-organisms

[12] Struelens, M.J., ‘The epidemiology of antimicrobial resistance in hospital acquired infections: problems and possible solutions’, BMJ, Vol. 317, 1998, pp. 652-654. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113836/pdf/652.pdf

[13] EU-OSHA – European Agency for Safety and Health and Work, E-fact 41 – Biological agents, 2003. Available at: http://osha.europa.eu/en/publications/factsheets/41

[14] Sas, K., ‘Legionella and Legionnaires’ disease: a policy overview’, EU-OSHA – European Agency for Safety and Health at Work, 2011. Available at: http://osha.europa.eu/en/publications/literature_reviews/legionella-policy-overview.pdf

[15] Araújo C, et al., Vancomycin-resistant enterococci from Portuguese wastewater treatment plants. J Basic Microbiol. 2010 Dec;50(6):605-9.

[16] Goldstein, R.E.R., ‘Evaluation of antibiotic-resistant bacteria in tertiary treated wastewater, reclaimed wastewater used for spray irrigation, and resulting occupational exposures’, Thesis, 2010. Retrieved 25 April 2012, from: http://drum.lib.umd.edu/bitstream/1903/10484/1/Goldstein_umd_0117N_11346.pdf

[17] Kosk-Bienko, J., ‘OSH risks related to global epidemics and drug-resistant micro-organisms’, EU-OSHA – European Agency for Safety and Health at Work, 2007. Available at: http://osha.europa.eu/en/seminars/occupational-risks-from-biological-agents-facing-up-the-challenges/speech-venues/speeches/osh-risks-related-to-global-epidemics-and-drug-resistant-micro-organisms

[18] EU-OSHA – European Agency for Safety and Health and Work (2007). Expert forecast on Emerging Biological Risks related to Occupational Safety and Health. European risk observatory report. Available at: http://osha.europa.eu/en/publications/reports/7606488

[19] EU-OSHA – European Agency for Safety and Health and Work, E-fact 41 – Biological agents, 2003. Available at: http://osha.europa.eu/en/publications/factsheets/41

[20] EU-OSHA – European Agency for Safety and Health and Work, E-fact 41 – Biological agents, 2003. Available at: http://osha.europa.eu/en/publications/factsheets/41

[21] Hand Hygiene in Outpatient and Home-based Care and Long-term Care Facilities, World Health Organization 2012, available at http://www.who.int/gpsc/5may/hh_guide.pdf

[22] WHO Guidelines on Hand Hygiene in Health Care, World Health Organisation 2009. Available at: https://www.who.int/publications-detail-redirect/9789241597906

[23] Challu, V.K., ‘Safety in TB research laboratory’, NTI Bulletin, Vol. 41, No 3&4, 2005, pp. 97-100. Available at: http://medind.nic.in/nac/t05/i3/nact05i3p97.pdf9

Further reading

Levy, S.B., Marshall, B., `Antibacterial resistance worldwide: causes, challenges and responses`, Nat Med, No 10(Suppl), 2004, pp. S122–S129.

WHO - World Health Organization, Antimicrobial resistance, Fact sheet No. 194. Retrieved on 5 December 2012, from: March 2012.

EU-OSHA – European Agency for Safety and Health and Work, E-fact 53 – Risk assessment for biological agents. Available at: [23]

EU-OSHA - European Agency for Safety and Health at Work 2009. Biological agents and pandemics: review of the literature and national policies. Available at: [24]

CDC pages on veterinary safety and health, [25]

Do Bugs Need Drugs? A Community Program for Wise Use of Antibiotics, Workplace/Occupational Health, including training materials, available at [26]

CDC pages and guidelines for Disinfection and Sterilization in Healthcare Facilities, 2008, available at [27]

Guidelines for Prevention and Control of Infections Due to Antibiotic-Resistant Organisms, Florida Department of Health Division of Disease Control, Bureau of Epidemiology, March 2010. Available at: [28]

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Gediminas Vilkevicius

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