I. Antibacterial Resistance

209 Pages·2013·11.57 MB·English

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TABLE OF CONTENTS
LIST OF FIGURES .........…………......…………….............................. V
LIST OF TABLES .............…………………………….......................... VI
LIST OF APPENDICES ...................................................................... VII
LIST OF ABBREVIATIONS & ACRONYMS ...................................... IX
DEFINITIONS ..................................................................................... XI
AGRADECIMENTOS .......................................................................... XIV
ABSTRACT ...............……………………………….............................. XV
RESUMO ...............……………………………….................................. XVI
STRUCTURE OF DISSERTATION .................................................... XVII
INTRODUCTION ...……………………………….................................. 1
OBJECTIVES ..................................................................................... 5
I. General Objective .................……………….……….…………………...... 6
II. Specific Objectives ....……..........………….……….…………………...... 6
LITERATURE REVIEW ...................................................................... 7
Chapter I : The Big Picture on Antibacterial Resistance ............... 8
I. Antibacterial Resistance ....……………….……….…………………...... 9
1. Why is Antibacterial Resistance a Public Health Concern? …...................... 9
2. Origins of Antibacterial Resistance ............................................................... 10
3. Types of Antibacterial Resistance ................................................................. 11
4. Antibacterial Modes of Action and Resistance Mechanisms …..................... 12
4.1. Inhibition of Cell Wall Synthesis ....................................................................... 14
4.2. Inhibition of Protein Synthesis .......................................................................... 16
4.3.Inhibition of Metabolic Pathways & Interference with Nucleic Acid Metabolism 18
5. Genetics of Antibacterial Resistance Transfer ……....................................... 20
6. Pharmacodynamics and Pharmacokinetics of Antibacterials ........................ 24
6.1. Time-dependent vs. Concentration-dependent Bacterial Decimation …........... 27
7. Laboratory Detection of Antibacterial Resistance …….................................. 28
7.1. Antibacterial Susceptibility Breakpoints ............................................................ 28
7.2. Definitions of Susceptibility Categories ............................................................. 29
7.3. Organizations that Set Breakpoints .................................................................. 30
7.4. The Nature of Minimum Inhibitory Concentrations …........................................ 31
7.5. Test Methods in Antibacterial Resistance Detection …..................................... 34
7.5.1. Broth Dilution Methods ........................................................................................ 34
7.5.2. Disk Diffusion Method …...................................................................................... 35
7.5.3. Antibacterial Gradient Diffusion Method .............................................................. 36
7.5.4. Automated Antibacterial Susceptibility Testing Systems .................................... 37
7.5.5. Current Test Methods and Future Directions ...................................................... 38
II. The Use of Antibacterials ..……………….……….……...….................. 39
8. The Use of Antibacterial Agents in Human Populations ……........................ 39
8.1. The Relationship Between Antibacterial Use and Resistance ……................... 39
8.2. Critically Important Antibacterials for Human Medicine ……............................. 40
8.3. The Current Use of Antibacterials in Europe ……............................................. 41
8.4. The Current Use of Antibacterials in Portugal …............................................... 46
9. The Use of Antibacterials in Animal Husbandry …........................................ 48
9.1. Definitions of Antibacterial Use ......................................................................... 49
9.2. Pharmacodynamics and Pharmacokinetics of Antibacterial Use in Animal
Husbandry …..................................................................................................... 50
9.3. Regulation and Authorization of Antibacterial Use in the EU ............................ 51
9.4. The Current Use of Antibacterials in Europe .................................................... 52
9.5. The Current Use of Antibacterials in Portugal ................................................... 55
9.6. Applications of Antibacterials in Animal Husbandry Operations …................... 58
9.6.1. Antibacterial Use in Dairy Production Systems ................................................... 59
III. Dissemination and Transfer of Resistant Bacteria and Resistance
Genes from Animals to Humans ........................................................ 63
10. Sources and Routes for ABR Dissemination and Transfer ........................... 64
11. Bacteria of Public Health Concern ................................................................ 66
11.1. Foodborne Pathogens (Salmonella & Campylobacter) …............................... 66
11.2. Indicator (Commensal) Organisms ...............…............................................... 69
11.2.1. Enterococci ….......................…....................................................................... 70
11.2.2. Escherichia coli ….........................…............................................................... 73
11.3. Other Gram-negative Bacteria ........................................................................ 76
11.4. Staphylococcus aureus ........…....................................................................... 76
11.5. Streptococcus pneumoniae …..............…....................................................... 79
IV. Response to the Increasing Burden of ABR: Control Strategies
and Interventions – The One Health Approach ............................. 80
12. Surveillance Systems to Track Antibacterial Use and Resistance ................ 81
12.1 Surveillance of Antibacterial Resistance …...................................................... 82
12.2 Surveillance of Antibacterial Usage ….............................................................. 83
12.3 Combined Surveillance …................................................................................ 83
13. Reducing Antibacterial Use in Humans ......................................................... 84
13.1 Promoting Rational Antibacterial Use …........................................................... 84
13.2 Infection Prevention and Control in Health-Care Facilities …........................... 85
13.3 Fostering Innovation ........................................................................................ 85
14. Reducing Antibacterial Use in Animal Husbandry ......................................... 87
14.1 Regulations to Restrict the Use of Antibacterials in Food-Producing Animals 87
14.2 Financial Incentives …...................................................................................... 90
14.3 Prudent use Guidelines and Education ........................................................... 90
14.4 Improving Animal Health .................................................................................. 90
14.5 Improving Hygiene in Food Production ............................................................ 91
14.6 Applying Advances in Data Management Technology …................................. 91
Chapter II: Antibacterial Resistance of Mastitis Pathogens .........
92
I. Mastitis in Dairy Production Operations .....................……………....... 93
1. Introduction …................................................................................................ 93
2. Mastitis Pathogens ….................................................................................... 95
3. Current Approaches for Mastitis Diagnosis ................................................... 97
II. Mastitis Antibacterial Therapy and the Use of Susceptibility
Profiles for Treatment Decisions ...................................…………….... 98
4. Assessing Efficacy …..................................................................................... 98
5. Pharmacological Considerations …............................................................... 101
6. Susceptibility Testing for Mastitis Pathogens …............................................ 102
6.1. Determination and Validation of Susceptibility Breakpoints for Mastitis

Pathogens ......................................................................................................... 102
6.1.1. Limited Availability of MIC Values for Mastitis Pathogens .................................. 103
6.1.2. Incomplete PK/PD Data for Lactating Dairy Cows .............................................. 103
6.1.3. Inadequate Number of Field Studies Validating Susceptibility Breakpoints ........ 103
6.2. Test Methods …................................................................................................. 104
6.2.1. Milk Dilution Method ............................................................................................ 104
6.3. Guidance for Antibacterial Selection Using Susceptibility Test Results and
MIC Values ....................................................................................................... 106
6.3.1. Validity of Developing a ‘‘Herd Profile’’ for Susceptibility .................................... 106
6.3.2. Validity of Selecting the Antibacterial with the Lowest In Vitro MIC Value .......... 106
6.3.3. Validity of Assumption that all Antibacterials Within a Class have Identical MIC
Values ................................................................................................................. 107
6.3.4. Effect of Milk on MIC Values ............................................................................... 107
6.3.5. Deleterious Effects of Antibacterials on Normal Mammary Defense
108
Mechanisms ........................................................................................................
6.3.6. Distribution of Antibacterials in an Inflamed Mammary Gland ............................ 108
7. Calculation of Antibacterial Dosage …........................................................... 109
III. Resistance Patterns of Mastitis Pathogens ........................................ 112
8.Trends on Resistance Patterns Over Time in Response to Antibacterial
112
Usage ............................................................................................................
MATERIALS & METHODS ................................................................... 115
I. Criteria for Selection of Cases …….......................…………………...... 116
II. Sample Collection and Microbiology …….............…………………..... 116
III. In vitro Antibacterial Susceptibility Testing …....…………………..... 117
IV. Tested Antibacterials ....................……….……….…………………...... 117
V. Selection of Pathogens ..................…..……….…………………........... 117
VI. Data Analysis ............................………….……….…………………....... 118
RESULTS ............................................................................................. 119
DISCUSSION ....................................................................................... 128
I. Novelty Aspects of this Study …….......................…………………...... 129
II. Antibacterial Resistance Pattern and Trend Analysis ……............... 129
III. Data Analysis …....…………………....................................................... 132
IV. Limitations of the Study ....................……….……….…………............ 133
V. Improvement Suggestions for Future Similar Research .................. 134
VI. Further Research Ideas and Recommendations .............................. 134
CONCLUSIONS ................................................................................... 136
REFERENCES ..................................................................................... 139
APPENDICES ….................................................................................. i - xl
LIST OF FIGURES
Figure 1: Broad depiction of major ABR mechanisms ..................................................................................................................................... 13
Figure 2: Protein synthesis. Aminoacyl-tRNA molecules are formed in the cytoplasm and bind to the cognate triplicate codon of mRNA at
the ribosome. Peptide bond formation links the new amino acid to the growing polypeptide chain. The ribosome migrates to free the A site
17
for the next aminoacyl-tRNA molecule and the cycle repeats until a stop codon is encountered and translation is terminated ......................
Figure 3: Activity of protein synthesis inhibitors. Schematic of the bacterial ribosome and the sites of action of select antibacterials that
inhibit polypeptide biosynthesis ........................................................................................................................................................................ 18
Figure 4: Schematic of multiple antibacterial resistance accumulation on a plasmid ...................................................................................... 22
Figure 5: Schematic representation of the complexity of interactions between patient, pathogen and antibacterial agent ............................. 25
Figure 6: Concentration-versus-time curve with MIC superimposed and pharmacokinetic and pharmacodynamic markers .......................... 26
Figure 7: MIC distributions for four microorganism-antibacterial pairs. In each case, the wild type appears as the log-normally distributed
population at the lower MICs. COWT – calculated wild-type cutoff value ........................................................................................................... 33
Figure 8: A broth microdilution susceptibility panel containing 98 reagent wells and a disposable tray inoculator ......................................... 35
Figure 9: Antibacterial susceptibility testing by disk diffusion. On this agar plate, a bacterial isolate is tested for resistance to each of four
different antibacterials ....................................................................................................................................................................................... 36
Figure 10: Antibacterial susceptibility testing by E-Test. On this agar plate, a bacterial isolate is tested for resistance to a specific
antibacterial ....................................................................................................................................................................................................... 37
Figure 11: Vitek® 2 System – BioMérieux, France ........................................................................................................................................... 38
Figure 12: Total outpatient antibacterial use in 2009 in Europe ....................................................................................................................... 42
Figure 13: Boxplotted distribution of outpatient antibacterial use between 1999 and 2009 among the participating European countries ...... 42
Figure 14: Trends of total outpatient antibacterial use in Europe from 1997 to 2009. Dark bars correspond to the year 2009 ....................... 44
Figure 15: Outpatient antibacterial use in 2009 subdivided into the major antibacterial classes according to ATC classification ................... 44
Figure 16: Hospital use of antibacterials for systemic use in 2009 (N= 22 countries) ..................................................................................... 46
Figure 17: Distribution of antibacterial classes in ambulatory (A) and hospital (B) care sectors in Portugal in 2009 .................................... 47
Figure 18: Trends of antibacterial usage in ambulatory care sector in Portugal .............................................................................................. 47
Figure 19: Annual antibacterial/antimicrobial use for human and veterinary practice in Denmark .................................................................. 48
Figure 20: PCU (in 1.000 tons) of the major food-producing animal species in 2009, by country ................................................................... 53
Figure 21: Proportion of US dairy operations in 2007 that treated cows with any antibacterial for the main diseases/disorders .................... 59
Figure 22: Proportion of US adult dairy cows treated with antibacterials for the main diseases/disorders in 2007 ......................................... 60
Figure 23: Proportion of preweaned and weaned heifers treated with antibacterials in 2007 for the main diseases/disorders ...................... 60
Figure 24: Possible routes of transmission of antibacterial-susceptible or -resistant gastrointestinal pathogens or normal intestinal flora
between animals and humans .......................................................................................................................................................................... 64
Figure 25: Reservoirs of ABR bacteria causing human infections. Schematic overview of some of the most important ABR pathogens and
the overlap between the different reservoirs ..................................................................................................................................................... 65
Figure 26: Trend and number of reported confirmed human campylobacteriosis cases by month, in the EU and EEA/EFTA countries,
2006–09 ............................................................................................................................................................................................................ 66
Figure 27: Trend and number of reported confirmed human salmonellosis cases by month, in the EU and EEA/EFTA countries, 2006–09 67
Figure 28: (A) E. faecalis: trends of high-level resistance to aminoglycosides by country, 2007–2010. (B) E. faecium: Trends of resistance
to vancomycin by country 2007–2011 .............................................................................................................................................................. 71
Figure 29: S. aureus: Trends of resistance to methicillin (MRSA) by country, 2007–2011 .............................................................................. 78
Figure 30: ECDC promotional One Health poster ............................................................................................................................................ 80
Figure 31: Discovery timeline of new antibacterial classes (1930s to 2000s) .................................................................................................. 86
Figure 32: Macrolide use and resistance among enterococci in swine, Denmark ........................................................................................... 88
Figure 33: Cephalosporin resistance in poultry industry in Quebec, Canada .................................................................................................. 89
Figure 34: Reduction in antibacterial use after the introduction of vaccination in aquaculture in Norway ....................................................... 91
Figure 35: Sliding scale for contagious and environmental origin of mastitis pathogens, based on insights from molecular epidemiology .... 95
Figure 36: Concentration-versus-time curve for drug concentration in milk and plasma ................................................................................. 109

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Balbino M. Rocha, 2013 V
LIST OF TABLES
Table 1: Estimated annual burden due to selected antibacterial-resistant bacteria in EU-Member States, Iceland and Norway, 2007 .......... 9
Table 2: Evolution of resistance to major antibacterials .......….……....…………….......................................................................................... 10
Table 3: Mechanisms of action of main antibacterial agents ........….……....…………….................................................................................. 12
Table 4: Mechanisms of ABR ….......………...........….……....……………......................................................................................................... 13
Table 5: World organizations with published breakpoints ….....................................………...........….……....………….................................... 31
Table 6: Summary of the antibacterial classes included in the three categories of Critically Important Antimicrobials for Human Medicine 41
Table 7: Outpatient antibacterial use in 2009 subdivided into the major antibacterial classes according to ATC classification …................... 43
Table 8: Hospital use of antibacterials for systemic use in 2009 (N= 22 countries) ….......………...........….……............................................. 45
Table 9: Total sales of veterinary antibacterial agents (active ingredient) and PCU (1000 tons) in eight European countries (Switzerland
not included) ….......………...........….……....……………................................................................................................................................... 52
Table 10: Sales normalized by PCU (mg/PCU) for the years 2005-2009 ….......……...........….……....…………….......................................... 53
Table 11: Difference between 2009 and 2005 sales, expressed as tons of active ingredient and as mg/PCU, for eight European countries
(Switzerland not included) ….......……...........….……....……………................................................................................................................. 54
Table 12: Total 2010 sales of veterinary antibacterial agents (active ingredient, in tons and %) by antibacterial class in Portugal …............ 56
Table 13: Distribution of active ingredients (in tons) in each animal species, in Portugal in 2010 ….......……................................................. 57
Table 14: Distribution of the antibacterial dosage forms in each animal species, in Portugal in 2010 ….......……........................................... 58
Table 15: Examples of diseases on the different food-producing animal species including organ, pathogen and type of treatment …........... 62
Table 16: Salmonella serotypes most frequently reported from human salmonellosis cases in the EU and EEA/EFTA countries and
percentage change, 2008-09 …........................................................................................................................................................................ 67
Table 17: Number of invasive E. faecalis and E. faecium isolates and proportion of high-level aminoglycoside-resistant E. faecalis and
vancomycin-resistant E. faecium (%R), including 95% CI, reported per country in 2011 ................................................................................. 70
Table 18: Number and proportion of invasive E. coli isolates resistant to aminopenicillins, 3rd-generation cephalosporins, fluoroquinolones,
aminoglycosides and multi-drug resistant (%R), including. 95% CI, reported per country in 2011 .................................................................. 74
Table 19: Number of invasive E. coli isolates resistant to 3rd-generation cephalosporins (CREC) and proportion of ESBL-positive
(%ESBL) among these isolates, as ascertained by the participating laboratories in 2011 ............................................................................... 74
Table 20: Overall resistance and resistance combinations among invasive E. coli isolates tested against aminopenicillins,
fluoroquinolones, 3rd-generation cephalosporins and aminoglycosides (n= 49847) in Europe, 2011 ............................................................... 75
Table 21: Number and proportion of invasive S. aureus isolates resistant to methicillin (MRSA) and rifampin (RIF), including 95% CI,
reported per country in 2011 ….......……...........….……....……........................................................................................................................ 77
Table 22: ABR surveillance networks for common bacterial pathogens in the WHO Regions …..................................................................... 82
Table 23: Prevalence of mastitis pathogens in dairy herds from Northwestern Portugal, between 2005 and 2008 ........................................ 96
Table 24: Current SCC measuring methods and alternatives for detection of mastitis .................................................................................... 98
Table 25: Summary of three-compartment model to target mastitis pathogens ............................................................................................... 101
Table 26: MIC data for several bacterial isolates from mastitic milk samples from the MAHDL, 1999-2001 ................................................... 111
Table 27: Conclusions from short- to long-term studies on the effect of antibacterials on resistance of mastitis pathogens worldwide ......... 113
Table 28: Antibacterial agents used for susceptibility testing of 47,413 bacterial pathogen isolates obtained from dairy cow milk samples
and submitted for bacterial culture between January 2004 and September 2012 ............................................................................................ 120
Table 29: Number of major bacterial pathogens isolated along the study period (2004-2012) ........................................................................ 120
Table 30: Results of resistance in antibacterial susceptibility testing, by antibacterial agent, of major mastitis bacterial pathogens .............. 121
Table 31: Results of logistic regression analysis to determine, for the isolated bacterial pathogens, whether the percentage of isolates
resistant to the various antibacterial agents changed with year ....................................................................................................................... 122
Table 32: S. aureus resistance proportions, among each tested antibacterial agent, along each tested year (n = 28,126 isolates) .............. 123
Table 33: S. agalactiae resistance proportions, among each tested antibacterial agent, along each tested year (n = 4,589 isolates) ........... 123
Table 34: S. uberis resistance proportions, among each tested antibacterial agent, along each tested year (n = 5,799 isolates) .................. 124
Table 35: S. dysgalactiae resistance proportions, among each tested antibacterial agent, along each tested year (n = 1,231 isolates) ....... 125
Table 36: Enterococcus spp. resistance proportions, among each tested antibacterial agent, along each tested year (n = 979 isolates) ..... 125
Table 37: E. coli resistance proportions, among each tested antibacterial agent, along each tested year (n = 5,916 isolates) ...................... 126
Table 38: K. pneumoniae resistance proportions, among each tested antibacterial agent, along each tested year (n = 773 isolates) ........... 127
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Balbino M. Rocha, 2013 VI
LIST OF APPENDICES
Appendix 1:
Table 39: Summary of some of the pertinent literature on the ABR of S. aureus isolated in milk from cows with mastitis worldwide ............. ii
Table 40: Summary of some of the pertinent literature on the ABR of CNS isolated in milk from cows with mastitis worldwide ..................... iii
Table 41: Summary of some of the pertinent literature on the ABR of environmental Streptococcus sp. isolated in milk from cows with iv
mastitis worldwide .............................................................................................................................................................................................
Table 42: Summary of some of the pertinent literature on the ABR of E. coli isolated in milk from cows with mastitis worldwide .................. v
Table 43: Summary of some of the pertinent literature on the ABR of other Gram-negative bacteria (besides E. coli) isolated in milk from vi
cows with mastitis worldwide ............................................................................................................................................................................
Table 44: Summary of some of the pertinent literature on the ABR of S. uberis and S. dysgalactiae isolated in milk from cows with mastitis vii
worldwide ..........................................................................................................................................................................................................
Table 45: Summary of some of the pertinent literature on the ABR of S. agalactiae, esculin-positive Streptococcus sp. and Enterococcus viii
spp. isolated in milk from cows with mastitis worldwide ....................................................................................................................................

Appendix 2:
Figure 36: Resistance proportions of S. aureus isolates, among each tested antibacterial agent, along each tested year (2004-2012) ....... ix
Figure 37: Resistance proportions of S. aureus isolates, among each tested antibacterial agent, along each tested year. Asterisks
represent statistically significant changes (p<0.05) .......................................................................................................................................... x
Figure 38: Resistance proportions of S. agalactiae isolates, among each tested antibacterial agent, along each tested year (2004-2012) .. xi
Figure 39: Resistance proportions of S. agalactiae isolates, among each tested antibacterial agent, along each tested year. Asterisks
represent statistically significant changes (p<0.05) .......................................................................................................................................... xii
Figure 40: Resistance proportions of S. uberis isolates, among each tested antibacterial agent, along each tested year (2004-2012) ......... xiii
Figure 41: Resistance proportions of S. uberis isolates, among each tested antibacterial agent, along each tested year. Asterisks
represent statistically significant changes (p<0.05) .......................................................................................................................................... xiv
Figure 42: Resistance proportions of S. dysgalactiae isolates, among each tested antibacterial, along each tested year (2004-2010) ........ xv
Figure 43: Resistance proportions of S. dysgalactiae isolates, among each tested antibacterial agent, along each tested year. Asterisks
represent statistically significant changes (p<0.05) .......................................................................................................................................... xvi
Figure 44: Resistance proportions of Enterococcus spp. isolates, among each tested antibacterial, along each tested year (2004-2010) ... xvii
Figure 45: Resistance proportions of Enterococcus spp. isolates, among each tested antibacterial agent, along each tested year.
Asterisks represent statistically significant changes (p<0.05) ........................................................................................................................... xviii
Figure 46: Resistance proportions of E. coli isolates, among each tested antibacterial agent, along each tested year (2004-2012) ............. xix
Figure 47: Resistance proportions of E. coli isolates, among each tested antibacterial agent, along each tested year. Asterisks represent
statistically significant changes (p<0.05) ........................................................................................................................................................... xx
Figure 48: Resistance proportions of K. pneumoniae isolates, among each tested antibacterial agent, along each tested year (2004-2012) xxi
Figure 49: Resistance proportions of K. pneumoniae isolates, among each tested antibacterial agent, along each tested year. Asterisks
represent statistically significant changes (p<0.05) .......................................................................................................................................... xxii
Table 46: SPSS outputs for logistic regression analysis to determine, for the S. aureus isolates, whether the percentage of isolates
resistant to the various antibacterial agents changed throughout the study period .......................................................................................... xxiii
Table 47: SPSS outputs for logistic regression analysis to determine, for the S. agalactiae isolates, whether the percentage of isolates
resistant to the various antibacterial agents changed throughout the study period .......................................................................................... xxiv
Table 48: SPSS outputs for logistic regression analysis to determine, for the S. uberis isolates, whether the percentage of isolates
resistant to the various antibacterial agents changed throughout the study period .......................................................................................... xxv
Table 49: SPSS outputs for logistic regression analysis to determine, for the S. dysgalactiae isolates, whether the percentage of isolates
resistant to the various antibacterial agents changed throughout the study period .......................................................................................... xxvi
Table 50: SPSS outputs for logistic regression analysis to determine, for the Enterococcus spp. isolates, whether the percentage of
isolates resistant to the various antibacterial agents changed throughout the study period ............................................................................. xxvii
Table 51: SPSS outputs for logistic regression analysis to determine, for the E. coli isolates, whether the percentage of isolates resistant
to the various antibacterial agents changed throughout the study period ......................................................................................................... xxviii
Table 52: SPSS outputs for logistic regression analysis to determine, for the K. pneumoniae isolates, whether the percentage of isolates
resistant to the various antibacterial agents changed throughout the study period .......................................................................................... xxix
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Balbino M. Rocha, 2013 VII
Appendix 3:
Article under submission for publication in international journal:
Rocha, B.; Mendonça, D.; Niza-Ribeiro, J. (2013) "Trends in Antibacterial Resistance of Major Bovine Mastitis Pathogens in Portugal" ...... xxx

Appendix 4:
Slide presentation of short communication presented by the author:
"Evolução de Padrões de Resistência a Antibióticos em Agentes Etiológicos da Mastite Bovina em Portugal". II Conferência Anual do
Conselho Português de Saúde do Úbere (CPSU). Santarém, Portugal – February 23rd, 2013 ....................................................................... xxxviii

Appendix 5:
Poster presentation:
Rocha, B., Mendonça, D., Niza-Ribeiro, J. (2013). “Evolução de Padrões de Resistência a Antibióticos em Agentes Etiológicos da Mastite
Bovina em Portugal”. XV Jornadas da Associação Portuguesa de Buiatria. Ílhavo, Portugal – May 24th to 26th, 2013 ................................... xl

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Balbino M. Rocha, 2013 VIII
LIST OF ABBREVIATIONS & ACRONYMS
GCREC – E. coli isolates resistant to 3rd-generation cephalosporins
3
ABR – Antibacterial Resistance
AI - Active Ingredient
AMP – Ampicillin
ATC – Anatomical Therapeutic Chemical (Classification System)
ATCC – American Type Culture Collection
AUC – Area under the (concentration–time) curve
AUG – Amoxicillin/Clavulanic acid
AHVLA – Animal Health and Veterinary Laboratories Agency
bp – Base pair
BSAC – British Society for Antimicrobial Chemotherapy
BTSCC – Bulk tank somatic cell count
CATs – Chloramphenicol acetyltransferases
CDS-AST – CDS disk diffusion method - Australia
CFP – Cefoperazone
CFU – Colony Forming Unit
CI – Confidence Interval
CLSI – The Clinical and Laboratory Standards Institute
CM – Clinical Mastitis
C – Peak concentration
max
CN – Gentamicin
CO – Calculated wild-type cutoff value
WT
CSF – Cerebrospinal fluid
CSN - Coagulase-negative staphylococci
CVMP – Committee for Medicinal Products for Veterinary Use
DDD – Defined Daily Dose
DGAV – Direção Geral de Alimentação e Veterinária
DID – Defined Daily Doses per 1000 inhabitants per day
DIN – Deutsches Institut für Normung
DNA – Deoxyribonucleic Acid
EARS-Net – The European Antimicrobial Resistance Surveillance Network
EEA – European Economic Area
EFTA – European Free Trade Association
EMA – European Medicines Agency
ESAC-Net – European Surveillance of Antimicrobial Consumption Network
ESBL – Extended Spectrum β-Lactamase
ESVAC – European Surveillance of Veterinary Antimicrobial Consumption Project
EU – European Union
EU-MS – European Union Member State
EUCAST – European Committee of Antimicrobial Susceptibility Testing
FAO – Food and Agriculture Organization of the United Nations
HACCP – Hazard Analysis and Critical Control Point
HHPM – Herd Health and Production Management
HGT – Horizontal gene transfer
IMI – Intramammary Infection
IMM – Intramammary
IS – Insertion sequence
ISCR1 – Insertion sequence common regions
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Balbino M. Rocha, 2013 IX