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Category: Bacterial Pathogenesis
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Antimicrobial Resistance in Bacteria of Animal Origin comprehensively examines the current research on antimicrobial resistance in the main veterinary and zoonotic pathogens, including resistance to disinfectants and metals used in agriculture. Providing a broad overview from a global perspective, this new volume is an important reference for students, researchers, public health experts, veterinarians, and anyone with an interest in resistant bacteria in animals.
Written by experts in the field of antimicrobial resistance, the early chapters provide information on modes of action of antibiotics and mechanisms of bacterial resistance, in addition to exploring the history of antimicrobial use in agriculture. Several chapters are devoted to examination of antimicrobial resistance in specific bacteria, including: the family Pasteurellaceae, species of Campylobacter, pathogenic Escherichia coli, staphylococci, steptococci, and Enterococcus. Also detailed are phenotypic and molecular methods for susceptibility testing, regulatory mechanisms for usage of antibiotics, and methods for monitoring drug usage and resistance.
Electronic Only, 441 pages, illustrations, index.
This introductory chapter is an overview of targets for antimicrobial action and mechanisms of bacterial resistance combined with information on the nature of antibacterial drugs, their classification, and their usage in animals. On the basis of the target microorganism, drugs are classified as antiviral, antibacterial, antifungal, and antiparasitic. There are numerous definitions of bacterial resistance, which are based on different criteria (genetic, biochemical, microbiological, and clinical) and do not necessarily overlap. The two most commonly used definitions are based on microbiological (in vitro resistance) and clinical (in vivo resistance) criteria. Multiresistant clinical strains of Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica serovar Enteritidis, and Staphylococcus aureus display in vivo mutation rates that are 1,000-fold higher than in other members of these species. There are important differences in the use of antibacterial agents in humans and animals, in particular food animals. Bacteria have developed various mechanisms to neutralize the action of antibacterial agents. The most widespread are enzymatic drug inactivation, modification or replacement of the drug target, active drug efflux, and reduced drug uptake.
The introduction of antimicrobial drugs into agriculture shortly after the Second World War caused a revolution in the treatment of many diseases of food animals. A broad overview of key features of the history of antimicrobial drug usage in food animals is given, which traces developments from the preantibiotic era to the present day, where there are highly arguable fears that we are moving into the "postantibiotic" era. The majority of antimicrobial drugs used in animals belong to a small number of major classes, and only one new class of antimicrobial drugs, fluoroquinolones has been introduced for food animal use in the last 30 years. Improvements in understanding of the microbiology of infectious diseases acquired from animals were less important, but also critical, forces in the reexamination of antimicrobial usage in agriculture. Ready access to the ‘’miracle drugs’’ by medicine and agriculture, coupled with the ability of chemists to alter existing drugs or develop new ones to counter resistance, led to the expectation that the preantibiotic era was to become a folk memory marked only on mossy gravestones. The new technologies of recombinant DNA, diagnostic DNA microarrays, genomics, proteomics, and combinatorial chemistry hold considerable promise for the development of new, possibly pathogen-targeted, antimicrobial drugs.
Antimicrobial susceptibility tests (ASTs) provide essential information that guides the veterinarian in selecting the most appropriate agent. In 1993 the National Committee for Clinical Laboratory Standards (NCCLS) formed the Subcommittee on Veterinary Antimicrobial Susceptibility Testing (V-AST) with the task of developing veterinary-specific AST standards. This group decided that rather than attempt to address all uses of antimicrobial agents in veterinary medicine, such as growth promotion, prophylaxis, and extralabel usage, it would limit its efforts to therapeutic uses in systemic diseases. The veterinary diagnostic laboratory can select from several different methodologies for antimicrobial susceptibility testing of veterinary pathogens, with most laboratories using either the agar disk diffusion method (ADD) or the broth microdilution MIC method. Regardless of the test method selected, the routine conduct of quality control (QC) testing is an essential component of the AST. In order for AST to be clinically relevant to the clinician, individual test results must be reported in an accurate, timely fashion. The development of test methods for additional veterinary pathogens such as Haemophilus parasuis from swine needs to be addressed, as well as the continued development of veterinary-specific interpretive criteria for older, generic agents. At present, a standardized method for susceptibility testing of Campylobacter spp. has been developed, but no interpretive criteria for these organisms or other enteric pathogens are available.
The combination of molecular characterization of resistant strains with precise identification of the antibiotic resistance gene(s) or mutation(s) and the genetic elements involved in the dissemination of these genes is an effective approach in the control of the spread of antibiotic resistance. Molecular methods also help to determine the location of the gene and to differentiate between horizontal gene transfer and clonal spread. This chapter describes polymerase chain reaction (PCR) and microarray analysis in detail, and specifies applications of these methods in the investigation of antibiotic-resistant strains. Numerous PCR assays for the detection of antibiotic resistance genes have been developed and the development of microarrays for the simultaneous detection of a large number of these genes and the genetic elements involved in their dissemination is in progress. The implementation of molecular methods in routine analysis can be achieved only when it is supported by the proper validation of the methods and the availability of the necessary controls, reference strains, and educated personnel. The molecular characterization of antibiotic-resistant strains can help to identify atypical resistant strains, describe new outbreak strains at an early stage, elucidate the epidemiology of resistant strains at a genotypic level, and explain the processes leading to the selection of resistant and virulent strains. In addition, molecular methods can allow proper risk assessment with respect to the use of antimicrobial substances. If the transcriptional and translational expression of antibiotic resistance genes can be better understood, molecular methods may replace phenotypic measurements.
This chapter reviews current concepts of dosage optimization to achieve optimal therapeutic effect with minimal resistance. As Schentag and Schentag have emphasized, the most important contribution of the pharmacologist to the resistance debate will be to design dosage schedules that minimize opportunities for its development. A given population of mixed microorganisms may comprise many subpopulations with different levels of susceptibility to antibiotics. In addition, for a given bacterial species genetic variation can confer resistance to one or more antimicrobial drugs of a given class, e.g., aminoglycosides, penicillins, or fluoroquinolones. The chapter briefly reviews categories of antimicrobial drugs and their pharmacokinetic (PK) and pharmacodynamic (PD) properties. For the majority of infections, the free (non-protein-bound) concentration in plasma is the best predictor of concentration in the biophase, as most infections are extracellular. However, when an anatomical or pathological barrier exists, lipid solubility is an important determinant of penetration of drug to the infection site. In addition, there are for some drugs (e.g., macrolides and ketolides) and some situations (e.g., biofilms) additional complications. However, ex vivo studies in the laboratory suggested two potentially important differences between marbofloxacin and danofloxacin investigated against a calf pathogen. The ultimate goal of population PK-PD analysis is to design dosage regimens that take account of animal or group characteristics.
Nowadays, antimicrobial agents are among the most frequently used therapeutics in human and veterinary medicine. Resistance to antimicrobial agents can be subdivided into two basic types of resistance, intrinsic resistance and acquired resistance. Resistance to ß-lactam antibiotics is mainly due to inactivation by ß-lactamases and decreased ability to bind to penicillin-binding proteins (PBPs) in both gram-positive and gram-negative bacteria, but may also be based on decreased uptake of ß-lactams due to permeability barriers or increased efflux via multidrug transporter systems. Different types of multidrug transporters mediating resistance to tetracycline in addition to resistance to a number of structurally unrelated compounds are described, for instance, in Escherichia coli, Salmonella, and P. aeruginosa. Plasmids, genomic islands, transposons, gene cassettes, and integrons are spread vertically during the division of the host cell, but can also be transferred horizontally between bacteria of the same or different species and genera via transduction, conjugation and mobilization, or transformation. The development of antimicrobial resistance—by either mutations, generation of new resistance genes, or acquisition of resistance genes already present in other bacteria—is a complex process that involves different mechanisms. Due to the usage of all types of antimicrobial substances for selection of resistant bacteria, prudent use of the antimicrobial agents is strongly recommended in both human and veterinary medicine, as well as in food animal production, to retain the efficacy of antimicrobial agents for the control of bacterial infections in animals.
Metal resistance measurements of bacteria in the laboratory are calculated either in milligrams of metal per liter of medium or in millimolar units (millimoles per liter). Little has been done to determine MIC distributions of metals for bacterial populations under standardized conditions. One study tested populations of Salmonella, E. coli, Staphylococcus aureus, Staphylococcus hyicus, Enterococcus faecalis, and Enterococcus faecium isolated from Danish food animals for their tolerance to copper sulfate and zinc chloride in Mueller-Hinton media at either pH 7 (copper sulfate) or pH 5.5 (zinc chloride). Heavy metal homeostasis versus resistance is a complicated balancing act between maintaining a full supply of cells with essential trace elements on one hand and protection against accumulation of toxic metal concentrations on the other. The use of copper as a feed supplement to poultry and pigs could therefore shift the bacterial populations toward increased levels of these potential pathogens in the guts of the animals. A more critical issue is the maintenance of antibiotic resistance genes by increasing the selective pressure of the bacterial populations through coselection by metals. Some studies do establish a direct link between copper, zinc, and arsenic resistance and resistance to antibiotics. In these cases, the metal resistance mechanism has the potential to select for resistance to antibiotics through coselection, when the bacterial host is exposed to selective concentrations of the metal, for instance, copper and streptomycin resistance transferred together in a conjugation study on P. syringae pv. syringae..
Disinfectants are used extensively in animal husbandry, hospital and food industry. Particularly important in the food industry is the inactivation of bacteria attached to surfaces and at low temperatures, both conditions where bacterial tolerance to disinfectants can be enhanced. Concerns about possible antibiotic and disinfectant cross-resistance are discussed in “Potential for Selection of Resistant Strains”. Gram-negative bacteria are generally less susceptible to disinfectants than gram-positive bacteria, presumably due to the reduced permeability of the double membrane. Mutants of various bacterial species (S.enteric serovar Typhimurium, E.coli, and S.aureus) with reduced susceptibility to triclosan can be selected in vitro after exposure to sublethal concentrations of the compound. The inherent resistance of gram-negative bacteria to antibacterial agents and disinfectants is often attributed to poor permeability of the cell to these agents. The MICs of disinfectants for most bacteria are normally greatly below the concentrations used in practice. A recent study demonstrated differences between the hand flora isolated from “homemakers” and intensive care nurses. A key difference between the two groups was the increased hand hygiene practiced by the nurses, and it is possible that disinfectant exposure has contributed to the differences in flora observed in this study. Cleaning prior to disinfection is important in order to remove organic material and other contaminants that might interfere with disinfectant activity.
This chapter focuses on issues relating to antimicrobial resistance in some of the more commonly encountered anaerobic bacterial pathogens of animals. Most of the available data on specific antimicrobial resistance relate to Clostridium perfringens type A, causing necrotic enteritis in broiler chickens, and to Brachyspira hyodysenteriae, causing swine dysentery. Some Clostridium species are essentially nonpathogenic; others, such as C. perfringens, may act as opportunistic pathogens, occasionally causing disease; and others are classified as major pathogens. Recently, in vitro development of resistance to coumermycin A1 in B. hyodysenteriae was reported. The resistance was associated with single-nucleotide mutations in the gyr(B) gene. Coumarins are not used for treatment of infections with Brachyspira spp. and this study was performed to evaluate this resistance as a selective marker for genetic studies. Recently, three different mutations in the ribosomal protein L3 gene and six mutations in the 23S rRNA gene that are associated with tiamulin resistance in B. hyodysenteriae and B. pilosicoli were described. Early studies on the in vitro susceptibility of 18 U.S. strains of D. nodosus indicated that penicillin was the most effective antimicrobial, followed by cefamandole, clindamycin, tetracycline, chloramphenicol, erythromycin, cefoxitin, tylosin, nitrofurazone, tinidazole, and dihydrostreptomycin.
This chapter focuses on the prevalence of antimicrobial resistance phenotypes among Escherichia coli isolates associated with enteric and systemic colibacillosis in minor species, cattle, pigs, and poultry, as well as bovine mastitis and uterine and urinary tract infections in companion animals. Antimicrobial resistance phenotypes among avian pathogenic E. coli recovered from diseased turkeys are similar to those reported from chickens. Fluoroquinolones are highly efficacious antimicrobial agents commonly used in human medicine. This class of drugs has also been approved for certain bacterial diseases in animals, including acute bovine respiratory disease and avian colibacillosis. Resistance to narrow-spectrum cephalosporins and tetracyclines among E. coli isolates may be due to their use for intramammary treatment for clinical mastitis in dairy cows. Treatment in grower-finisher rations was significantly associated with resistance to ampicillin, spectinomycin, sulfisoxazole, and tetracycline. Nineteen percent of swine E. coli isolates were also shown to possess class 1 integrons bearing gene cassettes conferring resistance primarily to trimethoprim and streptomycin. Plasmids containing the oqxAB genes yielded high resistance to olaquindox as well as chloramphenicol in E. coli. Diarrhea associated with E. coli infection is responsible for high rates of morbidity and mortality in goat kids and lambs. Antimicrobials are essential tools of disease management regimens in food and companion animals worldwide. The most commonly used antimicrobial drugs in food and companion animals are from five major classes: β-lactams, tetracyclines, aminogylcosides, macrolides, and sulfonamides.
This chapter focuses mainly on the genera Pasteurella, Mannheimia, Actinobacillus, Haemophilus, and Histophilus, for which sufficient data on antimicrobial susceptibility and the detection of resistance genes are currently available. A study in Germany, investigating the susceptibility of bovine isolates of P. multocida and M. haemolytica collected in 1999 to spectinomycin and comparator agents, showed that none of the 302 isolates tested were resistant to florfenicol, cefquinome, or ceftiofur, and only 6.5% of the P. multocida and 1.4% of the M. haemolytica isolates were classified as resistant to spectinomycin. The chapter provides an overview of the current knowledge of resistance genes and resistance mediating mutations so far detected in bacteria of the genera Pasteurella, Mannheimia, Actinobacillus, and Haemophilus. Molecular analysis of isolates of Pasteurella, Mannheimia and Actinobacillus revealed that antimicrobial resistance genes were associated with plasmids in many cases. The examples given in the chapter illustrate that Pasteurella, Mannheimia, Actinobacillus, and Haemophilus have obviously acquired a number of resistance genes from other gram-negative or maybe even gram-positive bacteria. Knowledge of the location and colocation of the resistance genes on mobile genetic elements as well as the conditions for their coselection and persistence will be valuable for veterinarians and will assist them in selecting the most efficacious antimicrobial agents for the control of isolates of the family Pasteurellaceae.
This chapter reviews the summarized data on susceptibility patterns and prevalence and epidemiology of resistance for the most clinically relevant staphylococcal and streptococcal pathogens in animals. The chapter focuses mainly on resistance in Staphylococcus aureus, Staphylococcus hyicus, and Staphylococcus intermedius. The first isolation of methicillin resistant Staphylococcus aureus (MRSA) from a veterinary specimen was reported from bovine mastitis in Belgium by Devriese et al. in 1972. The presence of other resistance genes and mechanisms has not been examined in streptococci of animal origin. Antimicrobial agents are most often used to control infections caused by these two groups of bacteria. The continuous monitoring of staphylococci and streptococci from animal infections is an essential prerequisite for early detection of new trends in the development of resistance to antimicrobials commonly used to control these infections. However, standardized procedures need to be made available for unambiguous species identification and for in vitro susceptibility testing, and such procedures also need to be applied by researchers in this field to make the results of susceptibility testing more comparable. More knowledge about the ability of certain subtypes to acquire resistance, together with the development of means to control such clones, could perhaps provide new means of controlling the increase in resistance.
In the 1970s several reports of drug resistance in fish pathogens from Japanese fish farms linked antibiotic resistance to fish farming. In this report, the devastating effect of acquired sulfonamide resistance in the treatment of furunculosis was demonstrated in clinical trials. A. salmonicida strains from Norway, including 10 isolates of sulfonamide-resistant atypical strains representing the various groups of a typical A. salmonicida isolated in Norway, were screened for occurrence of class 1 integrons and sulfonamide resistance genes. In this study A. salmonicida isolates from Switzerland, Finland, France, Japan, Scotland, and the United States were also studied. The study also characterized a third R plasmid of about 70 kb found in two A. hydrophila isolates in 1974 in the United States. It is also of particular interest that one of the R plasmids of E. tarda is very similar to the R plasmids of P. damselae subsp. piscicida. Infections with multiple-drug-resistant V. anguillarum occurred in farmed ayu in Japan in 1973. Several studies demonstrate transfer of R plasmids from fish pathogens to E. coli recipients. In many ways, fish pathogens represent possible intermediate vectors for shipping antibiotic resistance genes between the environment and human beings for further recombination.
The main species that cause infections in animals belongs to the genera Mycoplasma and Ureaplasma. In veterinary medicine the most commonly used antimicrobial agents are fluoroquinolones, macrolides, tetracyclines, and tiamulin. Susceptibility testing for Mycoplasma can, as for all other bacterial species, be performed by agar or broth dilution or disk diffusion. Susceptibility testing of mycoplasmas requires special media because of their slow growth and fastidious medium requirements. Worldwide, there have been very few reports on the antimicrobial susceptibility of the different Mycoplasma species. M. synoviae is intrinsically resistant to erythromycin and flumequin. Most studied strains are susceptible to josamycin, spiramycin, lincomycin, tylosin, tilmicosin, tiamulin, danofloxacin, and enrofloxacin. The genetic background for resistance has been studied only with mycoplasmas causing infections in humans. A high frequency of tetracycline resistance has been reported in several Mycoplasma species. Quinolones interfere with DNA replication by binding to DNA gyrase or topoisomerase IV. Resistance to quinolones is caused mainly by mutations in the genes encoding DNA gyrase or topoisomerase IV. Mutations at positions 83, 87, and 119 in gyrA have been frequently found to be associated with quinolone resistance in several gram-negative bacterial species, whereas changes at positions 81 and 84 seem to be infrequently found. There are only a very limited number of reports on the antimicrobial susceptibility of the different Mycoplasma species pathogenic for animals, and there is an obvious need for standardization of methods and interpretation.
This chapter describes the occurrence and mechanisms of resistance in some of the bacterial species and some of the problems in susceptibility testing of these bacteria. Actinobaculum suis seems to be susceptible to penicillin, ampicillin, ceftiofur, tetracyclines, macrolides, lincosamides, pleuromutilins, chloramphenicol, florfenicol, and spectinomycin but intrinsically resistant to the fluoroquinolones, aminoglycosides, and sulfamethoxazole-trimethoprim (co-trimoxazole or SXT). Antimicrobial agents used in food animal production are excreted in active forms in feces and urine, which subsequently are spread on fields. Resistance to SXT might be emerging in Brucella. There have been only a limited number of studies on the antimicrobial susceptibility of Burkholderia mallei and Burkholderia pseudomallei. Most studies have found that Corynebacterium pseudotuberculosis shows reduced susceptibility or resistance to aminoglycoside. Susceptibility testing of Erysipelothrix rhusiopathiae has been performed as both agar and broth dilution using normal nonsupplemented medium. Most early studies on growth and susceptibility testing of Leptospira were performed using different media supplemented with serum. Susceptibility testing of Listeria spp. can be performed as for all other gram-positive bacterial species. Numerous bacterial species can cause infections in animals and humans or function as reservoirs for antimicrobial resistance genes. Some of the resistance genes found in rarely isolated pathogens are also well known from the more important pathogens. Thus, this emphasizes that all bacterial species to some extent share the same gene pool.
This chapter provides a review of prevalence and trends of resistance in Campylobacter jejuni and Campylobacter coli isolated from humans in different parts of the world and a more thorough description of the mechanisms of resistance, origin, spread, and clinical consequences of resistance. Aminoglycosides exhibit rapid and significant bactericidal effects in vitro and should initially be included for the treatment of Campylobacter bacteremia in patients who appear very ill. The only mechanism of chloramphenicol resistance identified in Campylobacter occurs through modification of chloramphenicol by chloramphenicol acetyltransferase, which prevents its binding to the ribosome. The majority of contacts between Tet(O) and the ribosome are mediated by the rRNA, and one interaction with ribosomal protein S12. Most of the antimicrobials used in veterinary medicine are tetracyclines and macrolides, which result in high and continuous selective pressure for the animal-colonizing bacteria, ultimately resulting in the acquisition of antimicrobial resistance genes. Investigation into the mechanisms of action of antimicrobials, as well as the transfer of resistance determinants, is necessary to gain effective control of antimicrobial resistance. Epidemiological and microbiological studies show that poultry is the most important source for quinolone-susceptible and quinolone-resistant Campylobacter infections in humans. Trends over time for macrolide resistance show stable low rates in most countries, and macrolides should remain the drug class of choice for C. jejuni and C. coli enteritis.
Epidemiologic data of a study of a multistate outbreak of food-borne salmonellosis due to resistant Salmonella enterica serovar Newport carrying a common ampicillin and tetracycline resistance plasmid, strongly associated hamburger meat originating from a single farm in South Dakota. Similarly, an outbreak study reported by a group used antimicrobial resistance and plasmid profiling to trace chloramphenicol-resistant serovar Newport from the incriminated hamburger meat back through the abattoir and to the dairy farm from which the meat was derived. As with many bacterial pathogens, antimicrobial resistance in nontyphoidal Salmonella spp. is an international problem. Resistance associated with integrons has been studied extensively and is common in many multiple-drug resistance (MDR) Salmonella serovars. An outbreak of quinolone-resistant DT104 in Denmark, originating in swine, resulted in 11 hospitalizations and the death of 2 patients due to therapeutic failure. The majority of Salmonella AmpC β-lactamases belong to the CMY gene family, whose sequence similarity suggests an origin in Citrobacter freundii. Food is an important vehicle for the national and international transmission of antimicrobial-resistant bacteria and antimicrobial resistance genes from food animals to humans. As food is distributed worldwide, attempts to control the spread of antimicrobial resistance must be approached internationally, in order to reduce or eliminate contamination by antimicrobial-resistant Salmonella at the primary production site.
This chapter focuses on the presence of virulence and antimicrobial resistance genes in enterococci of animal origin and the possible spread of resistance between the animal and human reservoir, probably through the food chain. Some species, such as Enterococcus gallinarum and E. casseliflavus, are motile. At least 23 distinct Enterococcus species are recognized and new species continue to be identified. The defined species have been separated into five groups on the basis of acid formation in mannitol and sorbose broths and hydrolysis of arginine. Identification of the different Enterococcus species can be done by conventional physiological tests, by commercial systems, or by molecular methods. The major natural habitat of organisms appears to be the gastrointestinal tract of animals and humans, where they make up a significant portion of the normal aerobic gut flora. Some Enterococcus species are host specific, while others are more broadly distributed. The emergence of antimicrobial resistance represents the greatest threat to the treatment of human enterococcal infections. The chapter also focuses on the antimicrobial resistance selected for animals that can be transferred to humans, causing treatment failures. Tetracycline resistance is probably the most common resistance phenotype in enterococci from food. Enterococci have an ability to become resistant to antimicrobials. The role of enterococci in disease raises valid concerns regarding their safety for use in foods or as probiotics. If Enterococcus strains are selected for use as starter or probiotic cultures, ideally such strains should harbor no virulence determinants and should be susceptible to clinically relevant antibiotics.
This chapter reviews the clinical and public health consequences of antimicrobial drug resistance in bacteria transferred from food animals to humans. To address the clinical importance of animal-related antimicrobial drug resistance, one must review how resistant bacteria may be a cause of increased morbidity and mortality. The chapter discusses the significance of increased transmission as a result of the unrelated use of antimicrobial agents to which a pathogen is resistant. It further covers reduced efficacy of treatment and increased virulence from a public health perspective, i.e., by summarizing observational studies that address the clinical and public health consequences of animal-related resistance. The food chain contains an abundance of antimicrobial drug-resistant pathogens, including Salmonella and Campylobacter. There is growing evidence that this has significant public health consequences. Mitigation of antimicrobial resistance in food-borne bacteria such as Salmonella and Campylobacter will likely benefit human health.
The origin of acquired antimicrobial resistance is in general believed to be adoption of resistance genes from antimicrobial-producing organisms and/or nucleotide changes in housekeeping genes. This chapter provides a brief overview of the putative origins of some of the most important antimicrobial resistance determinants and some of the genetic mechanisms. The actual origin of antimicrobial resistance genes is unknown, but environmental microbes, including the natural producers of antimicrobial substances, are believed to be important primary sources. The ß-lactamases are believed to have evolved from enzymes involved in cell wall biosynthesis. The main mechanism of resistance to aminoglycosides is enzymatic inactivation. Comparison of the DNA and deduced amino acid sequence of the erm genes from macrolide producing organisms and macrolide-resistant bacteria strongly suggests that the origin of macrolide resistance is macrolide-synthesizing organisms. Resistance to tetracyclines is mediated either by genes encoding ribosomal protection proteins (RPPs) or efflux pumps. Food animals and pets produce large amounts of waste products, which may contain many pathogenic bacteria, antimicrobial-resistant bacteria, and resistance genes. Human waste contains large amounts of antimicrobial-resistant bacteria and resistance genes. Such waste is normally treated to avoid transmission of pathogenic bacteria.
Registration of Veterinary Medicinal Products ( VICH) has been very successful in harmonizing product quality, human food safety, environmental risk assessment, and efficacy requirements, and those guidelines are highlighted in this chapter. There is general agreement within the scientific community that the development of resistant, human-pathogenic bacteria results primarily from the direct use of antimicrobial agents in humans but also from acquisition of resistant organisms or resistance factors from animal and environmental sources. The direct public health concern is that use of antimicrobials in food-producing animals may contribute to the development or dissemination of antibiotic-resistant zoonotic organisms that may contaminate food products at the time of slaughter and subsequently be transmitted to humans. The indirect effect is where animals are treated with antimicrobials and commensal bacteria develop resistance that may be passed to human-pathogenic bacteria. Licensing and approval of antimicrobials for use in animals, particularly food-producing animals, is a complex process involving considerations of efficacy, target animal safety, environmental safety, and human safety, including antimicrobial resistance. The approval process strives to ensure that the products are effective and safe and to manage the risks of adverse effects from their use. After veterinary drugs are licensed and marketed, surveillance is undertaken to ensure the continued safety and efficacy of the products.
This chapter evaluates the usefulness and limitations of the various sources of input data, discusses how usage should be expressed in order to comply with the various purposes of monitoring, and presents examples on the application of data obtained through various monitoring programs. Data on antimicrobial drug usage collected from veterinarians and farmers may give information about dosage schemes and usage per species, per age group, by indication, and at herd level. Data on antimicrobial drug usage could also be collected by the use of questionnaires to veterinarians or farmers. Ideally, all antimicrobial ingredients and classes of antimicrobials used in animals should be included in a monitoring program on antimicrobial drug usage. Conversion of aggregate usage data to defined daily dose (DDD) may thereby create over- or underestimates of usage. The prescribed daily doses (PDDs) for veterinary antimicrobials may be calculated from prescriptions, questionnaires, or information obtained from veterinarians’ invoices. Usage of antimicrobials in selected food producing animal species should, if possible, be calculated to express doses per number of animal species and per age group, e.g., weaning pigs. In order to examine the selective pressure exerted by the various antimicrobial growth promoters (AGPs) or coccidiostat feed additives (CFAs), the proportional use of the different feed additives may be expressed as amounts of feed (in weight) containing an AGP or a CFA per 1,000 animals per time period.
This chapter reviews information relevant to the design and scope of antimicrobial resistance monitoring and surveillance programs for animals and food, with emphasis on program purposes and methods. The chapter describes some of the essential features of existing monitoring and surveillance programs in various countries around the world. It shows how these programs have been useful in improving understanding of resistance and its relation to antimicrobial use and other factors, guiding public policy, and measuring the impact of interventions on antimicrobial resistance in bacteria from animals, food, and humans. The major methodological considerations for the monitoring program include the types of samples to be collected, sampling strategies, species of bacteria, antimicrobials for susceptibility testing, data collection and analysis, and reporting of results. Comprehensive monitoring of antimicrobial resistance in animals in the context of animal and human health covers the entire farm-to-fork continuum. The Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM) has been active in developing new approaches for the preapproval assessment of antimicrobial resistance risks from antimicrobials used in animals. The Japanese Veterinary Antimicrobial Resistance Monitoring (JVARM) program examines the susceptibility of bacteria from food-producing animals to antimicrobial agents. Most programs focus on pathogenic bacteria or Salmonella, but some also report data on resistance in indicator bacteria isolated from healthy animals. Knowledge about antimicrobial resistance should be combined with knowledge regarding the usage of antimicrobial agents for different food animal species, which also should be performed on an internationally comparable basis.
The purpose of risk assessment is to help a manager better understand the risks (and opportunities) being faced and to evaluate the options available for their control. The chapter describes some antimicrobial resistance risk assessments that have been completed. The Food and Drug Administration (FDA) wanted to produce a model that was based on reliable data. The FDA deemed that the risk assessment had quantitatively demonstrated that the resistance in question presented a risk to human health, and subsequently moved to withdraw use of the antimicrobial. The major strengths of the model were its mathematical simplicity, its reliance on mostly federally collected data, its very limited set of assumptions, and the ease with which it could be updated as new data became available. The data problems underlined the difficulties of evaluating even relatively simple model parameters for antimicrobial risk assessments. The FDA’s quantitative risk analysis model was successful in that it provided robust information from which the FDA was able to make an important decision. A key to the successful involvement of risk assessment in decision making is the neutrality of the risk assessor. There is, unfortunately, a growing trend in published antimicrobial resistance risk assessments that are clearly selective about their sources or manipulate a risk assessment model to produce the desired answer. The FDA guidance takes an essentially qualitative approach to evaluating drugs for approval and continued use.
The antimicrobial agents are among the most important medical discoveries of the 20th century and are unique in the respect that their usage might itself lead them to become useless. It is very difficult to estimate the true human health risk associated with the use of antimicrobial agents for animals, since it involves estimation of selection for resistance to different compounds; the spread of clones, plasmids, and genes through the food chain; and the consequences of human infections with different bacterial species that are resistant to different antimicrobial agents. Several international bodies and conferences have addressed the need to have concrete and common approaches in order to control the global emergence of antimicrobial resistance. In 2000, the World Health Organization issued global principles for the containment of antimicrobial resistance in animals intended for food. In most countries it is now required that pharmaceutical companies perform postmarketing monitoring of antimicrobial resistance. International meetings and conferences have pointed to the need for more data through monitoring of the occurrence of resistance in different reservoirs. Antimicrobials are essential for the sake of both human and animal health. Antimicrobial-free production of food animals, as is currently attempted in organic production, is seemingly associated with so many welfare problems that it will become a viable production method only for a minor market.
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At A Glance
Antimicrobial Resistance in Bacteria of Animal Origin comprehensively examines the current research on antimicrobial resistance in the main veterinary and zoonotic pathogens, including resistance to disinfectants and metals used in agriculture. Providing a broad overview from a global perspective, this new volume is an important reference for students, researchers, public health experts, veterinarians, and anyone with an interest in resistant bacteria in animals.
Written by experts in the field of antimicrobial resistance, the early chapters provide information on modes of action of antibiotics and mechanisms of bacterial resistance, in addition to exploring the history of antimicrobial use in agriculture. Several chapters are devoted to examination of antimicrobial resistance in specific bacteria, including: the family Pasteurellaceae, species of Campylobacter, pathogenic Escherichia coli, staphylococci, streptococci, and Enterococcus. Also detailed are phenotypic and molecular methods for susceptibility testing, regulatory mechanisms for usage of antibiotics, and methods for monitoring drug usage and resistance.
Description
This is a timely publication on a current issue of human and animal socioeconomic significance -- antimicrobial agents commonly used for prophylactic and therapeutic indications in animals. It presents comprehensive data from international experts from Europe, Australia, and the U.S.
Purpose
The book details a systematic analysis of mechanisms of action and the genesis of antimicrobial resistance at the cultural and molecular level including elements of the epidemiology of resistance acquisition and transfer. The impact of indiscriminate and suboptimal use of antimicrobial agents is discussed well, particularly in veterinary therapeutics and prophylaxis.
Audience
The scope of the book means it does not adequately address use of related compounds in human healthcare delivery, but readers can garner sufficient background to extrapolate veterinary data to the human health situation and vice versa.
Features
The authors remind readers that antimicrobial use is ancient, as shown by the Egyptian cover photograph. However, there are no major contributors from third world countries where antimicrobial resistance could have an enormous impact of global significance. This is a major oversight, considering the high level of epidemics likely to occur in third world countries where antimicrobial agents would be indicated and from where antimicrobial resistance could spread to the rest of the world through trade and tourism. Unfortunately, this book may not be affordable in those countries. Hopefully it will be available online sometime in the near future.
Assessment
Regardless, this book is recommended for public libraries, private collections, veterinary and medical institutions, and regulatory agencies. It is also a useful resource for research and policy formulation. Experiences gained from Scandinavian countries are a shining example of how antimicrobial resistance can be controlled through rational antimicrobial use. Close to 20 percent of the contributors are directly or indirectly associated with Scandinavian countries.
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Reviewer: Ibulaimu KAKOMA, DVM PHD (University of Illinois College of Veterinary Medicine)
Review Date: Unknown
©Doody’s Review Service