Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 9: Polymyxins: colistin

[EN] The specific concentrations of colistin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels of colistin in feed that showed to have an effect on growth promotion/increased yield were reported. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these antimicrobialsSIThe BIOHAZ Panel, leading Panel in charge of the adoption of the scientific opinion and assessment of Term of Reference 1 (ToR1, antimicrobial resistance) wishes to thank the following for the support provided to this scientific output: EFSA Panel on Animal Health and Welfare (AHAW Panel), who supported ToR1 assessments development and endorsement of those sections under their remit (animal production, main use of antimicrobials); EFSA Panel for Additives and Products or Substances used in Animal Feed (FEEDAP), in charge of the assessment and endorsement of ToR2, and providing advice and data needed for ToR1 assessments; European Medicines Agency (EMA), who was represented by an external expert and EMA secretariat as members of the Working Group (WG); Valeria Bortolaia, who was member of the WG until 17 April 2020; EFSA staff members: Angelica Amaduzzi, Gina Cioacata, Pilar Garc ıa-Vello, Michaela Hempen, Rita Navarrete, Daniel Plaza and Anita Radovnikovic; EMA staff members: Barbara Freischem, Zoltan Kunsagi, Nicholas Jarrett, Jordi Torren, and Julia F abrega (currently EFSA staff). The BIOHAZ Panel wishes also to acknowledge the EMA Committee for Medicinal Products for Veterinary Use (CVMP) and their expert

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 6: Macrolides: tilmicosin, tylosin and tylvalosin

[EN] The specific concentrations of tilmicosin, tylosin and tylvalosin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield, were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for tilmicosin and tylosin, whilst for tylvalosin no suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these three antimicrobialsSIThe BIOHAZ Panel, leading panel in charge of the adoption of the scientific opinion and assessment of Term of Reference 1 (ToR1, antimicrobial resistance) wishes to thank the following for the support provided to this scientific output: EFSA Panel on Animal Health and Welfare (AHAW Panel), who supported ToR1 assessments development and endorsement of those sections under their remit (animal production, main use of antimicrobials); EFSA Panel for Additives and Products or Substances used in Animal Feed (FEEDAP), in charge of the assessment and endorsement of ToR2, and providing advice and data needed for ToR1 assessments; European Medicines Agency (EMA), who was represented by an external expert and EMA secretariat as members of the Working Group (WG); Valeria Bortolaia, who was member of the WG until 17 April 2020; EFSA staff members: Angelica Amaduzzi, Gina Cioacata, Pilar Garc ıa-Vello, Michaela Hempen, Rita Navarrete, Daniel Plaza and Anita Radovnikovic; EMA staff members: Barbara Freischem, Zoltan Kunsagi, Nicholas Jarrett, Jordi Torren, and Julia F abrega (currently EFSA staff). The BIOHAZ Panel wishes also to acknowledge the EMA Committee for Medicinal Products for Veterinary Use (CVMP) and their expert

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 3: Amprolium

[EN] The specific concentrations of amprolium in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC for amprolium, it was not possible to conclude the assessment. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels of amprolium in feed that showed to have an effect on growth promotion/increased yield were reported. The lack of antibacterial activity at clinically relevant concentrations for amprolium suggests that further studies relating to bacterial resistance are not a priority.SI: The BIOHAZ Panel, leading Panel in charge of the adoption of the scientific opinion and assessment of Term of Reference 1 (ToR1, antimicrobial resistance) wishes to thank the following for the support provided to this scientific output: EFSA Panel on Animal Health and Welfare (AHAW Panel), who supported ToR1 assessments development and endorsement of those sections under their remit (animal production, main use of antimicrobials); EFSA Panel for Additives and Products or Substances used in Animal Feed (FEEDAP), in charge of the assessment and endorsement of ToR2, and providing advice and data needed for ToR1 assessments; European Medicines Agency (EMA), who was represented by an external expert and EMA secretariat as members of the Working Group (WG); Valeria Bortolaia, who was member of the WG until 17 April 2020; EFSA staff members: Angelica Amaduzzi, Gina Cioacata, Pilar Garc ıa-Vello, Michaela Hempen, Rita Navarrete, Daniel Plaza and Anita Radovnikovic; EMA staff members: Barbara Freischem, Zoltan Kunsagi, Nicholas Jarrett, Jordi Torren, and Julia Fabrega (currently EFSA staff). The BIOHAZ Panel wishes also to acknowledge the EMA Committee for Medicinal Products for Veterinary Use (CVMP) and their experts

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 11: Sulfonamides

[EN] The specific concentrations of sulfonamides in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data are available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were identified for three sulfonamides: sulfamethazine, sulfathiazole and sulfamerazine. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these antimicrobials.SIThe BIOHAZ Panel, leading Panel in charge of the adoption of the scientificopinion and assessment of Term of Reference 1 (ToR1, antimicrobial resistance) wishes to thank thefollowing for the support provided to this scientific output: EFSA Panel on Animal Health and Welfare(AHAW Panel), who supported ToR1 assessments development and endorsement of those sectionsunder their remit (animal production, main use of antimicrobials); EFSA Panel for Additives andProducts or Substances used in Animal Feed (FEEDAP), in charge of the assessment and endorsementof ToR2, and providing advice and data needed for ToR1 assessments; European Medicines Agency(EMA), who was represented by an external expert and EMA secretariat as members of the WorkingGroup (WG); Valeria Bortolaia, who was member of the WG until 17 April 2020; EFSA staff members:Angelica Amaduzzi, Gina Cioacata, Pilar Garc ıa-Vello, Michaela Hempen, Rita Navarrete, Daniel Plazaand Anita Radovnikovic; EMA staff members: Barbara Freischem, Zoltan Kunsagi, Nicholas Jarrett, JordiTorren, and Julia F abrega (currently EFSA staff). The BIOHAZ Panel wishes also to acknowledge theEMA Committee for Medicinal Products for Veterinary Use (CVMP) and their experts

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 2: Aminoglycosides/aminocyclitols: apramycin, paromomycin, neomycin and spectinomycin

[EN] The specific concentrations of apramycin, paromomycin, neomycin and spectinomycin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield, were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC for these antimicrobials, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for apramycin and neomycin, whilst for paromomycin and spectinomycin, no suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these four antimicrobialsSIThe BIOHAZ Panel, leading Panel in charge of the adoption of the scientific opinion and assessment of Term of Reference 1 (ToR1, antimicrobial resistance) wishes to thank the following for the support provided to this scientific output: EFSA Panel on Animal Health and Welfare (AHAW Panel), who supported ToR1 assessments development and endorsement of those sections under their remit (animal production, main use of antimicrobials); EFSA Panel for Additives and Products or Substances used in Animal Feed (FEEDAP), in charge of the assessment and endorsement of ToR2, and providing advice and data needed for ToR1 assessments; European Medicines Agency (EMA), who was represented by an external expert and EMA secretariat as members of the Working Group (WG); Valeria Bortolaia, who was member of the WG until 17 April 2020; EFSA staff members: Angelica Amaduzzi, Gina Cioacata, Pilar Garc ıa-Vello, Michaela Hempen, Rita Navarrete, Daniel Plaza and Anita Radovnikovic; EMA staff members: Barbara Freischem, Zoltan Kunsagi, Nicholas Jarrett, Jordi Torren, and Julia F abrega (currently EFSA staff). The BIOHAZ Panel wishes also to acknowledge the EMA Committee for Medicinal Products for Veterinary Use (CVMP) expert

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 10: Quinolones: flumequine and oxolinic acid

[EN] The specific concentrations of flumequine and oxolinic acid in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data are available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. No suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these antimicrobialsSIThe BIOHAZ Panel, leading Panel in charge of the adoption of the scientific opinion and assessment of Term of Reference 1 (ToR1, antimicrobial resistance) wishes to thank the following for the support provided to this scientific output: EFSA Panel on Animal Health and Welfare (AHAW Panel), who supported ToR1 assessments development and endorsement of those sections under their remit (animal production, main use of antimicrobials); EFSA Panel for Additives and Products or Substances used in Animal Feed (FEEDAP), in charge of the assessment and endorsement of ToR2, and providing advice and data needed for ToR1 assessments; European Medicines Agency (EMA), who was represented by an external expert and EMA secretariat as members of the Working Group (WG); Valeria Bortolaia, who was member of the WG until 17 April 2020; EFSA staff members: Angelica Amaduzzi, Gina Cioacata, Pilar Garc ıa-Vello, Michaela Hempen, Rita Navarrete, Daniel Plaza and Anita Radovnikovic; EMA staff members: Barbara Freischem, Zoltan Kunsagi, Nicholas Jarrett, Jordi Torren, and Julia F abrega (currently EFSA staff). The BIOHAZ Panel wishes also to acknowledge the EMA Committee for Medicinal Products for Veterinary Use (CVMP) and their expert

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 1: Methodology, general data gaps and uncertainties

[EN] The European Commission requested EFSA to assess, in collaboration with EMA, the specific concentrations of antimicrobials resulting from cross-contamination in non-target feed for food-producing animals below which there would not be an effect on the emergence of, and/or selection for, resistance in microbial agents relevant for human and animal health, as well as the levels of the antimicrobials which could have a growth promotion/increase yield effect. The assessment was performed for 24 antimicrobial active substances, as specified in the mandate. This scientific opinion describes the methodology used, and the main associated data gaps and uncertainties. To estimate the antimicrobial levels in the non-target feed that would not result in emergence of, and/or selection for, resistance, a model was developed. This ‘Feed Antimicrobial Resistance Selection Concentration’ (FARSC) model is based on the minimal selective concentration (MSC), or the predicted MSC (PMSC) if MSC for the most susceptible bacterial species is unavailable, the fraction of antimicrobial dose available for exposure to microorganisms in the large intestine or rumen (considering pharmacokinetic parameters), the daily faecal output or rumen volume and the daily feed intake. Currently, lack of data prevents the establishment of PMSC and/or FARSC for several antimicrobials and animal species. To address growth promotion, data from an extensive literature search were used. Specific assessments of the different substances grouped by antimicrobial classes are addressed in separate scientific opinions. General conclusions and recommendations were made.SIThe BIOHAZ Panel, leading Panel in charge of the adoption of the scientific opinion and assessment of Term of Reference 1 (ToR1, antimicrobial resistance) wishes to thank the following for the support provided to this scientific output: EFSA Panel on Animal Health and Welfare (AHAW Panel), who supported ToR1 assessments development and endorsement of those sections under their remit (animal production, main use of antimicrobials); EFSA Panel for Additives and Products or Substances used in Animal Feed (FEEDAP), in charge of the assessment and endorsement of ToR2, and providing advice and data needed for ToR1 assessments; European Medicines Agency (EMA), who was represented by an external expert and EMA secretariat as members of the Working Group (WG); Valeria Bortolaia, who was member of the WG until 17 April 2020; EFSA staff members: Angelica Amaduzzi, Gina Cioacata, Pilar Garc ıa-Vello, Michaela Hempen, Rita Navarrete, Daniel Plaza, Anita Radovnikovic and Cristiana Ventura; EMA staff members: Barbara Freischem, Zoltan Kunsagi, Nicholas Jarrett, Jordi Torren and Julia Fabrega (currently EFSA staff). The BIOHAZ Panel wishes also to acknowledge the EMA Committee for Medicinal Products for Veterinary Use (CVMP) and their experts, as well as the members of the EARS-Vet and the EURL-AR that provided data and/or information for this scientific output

Tuberculosis in seals caused by a novel member of the Mycobacterium tuberculosis complex: Mycobacterium pinnipedii sp. nov.

A comparison of Mycobacterium tuberculosis complex isolates from seals (pinnipeds) in Australia, Argentina, Uruguay, Great Britain and New Zealand was undertaken to determine their relationships to each other and their taxonomic position within the complex. Isolates from 30 cases of tuberculosis in six species of pinniped and seven related isolates were compared to representative and standard strains of the M. tuberculosis complex. The seal isolates could be distinguished from other members of the M. tuberculosis complex, including the recently defined ‘Mycobacterium canettii’ and ‘Mycobacterium caprae’, on the basis of host preference and phenotypic and genetic tests. Pinnipeds appear to be the natural host for this ‘seal bacillus’, although the organism is also pathogenic in guinea pigs, rabbits, humans, Brazilian tapir (Tapirus terrestris) and, possibly, cattle. Infection caused by the seal bacillus is predominantly associated with granulomatous lesions in the peripheral lymph nodes, lungs, pleura, spleen and peritoneum. Cases of disseminated disease have been found. As with other members of the M. tuberculosis complex, aerosols are the most likely route of transmission. The name Mycobacterium pinnipedii sp. nov. is proposed for this novel member of the M. tuberculosis ..

Por don Zoilo de Melgareio Presbitero Canonigo de la Colegial Iglesia desta ciudad, en el pleito de possession, a que salio doña Leonor de Lieuana, muger de don Pedro Baçan de Gallegos

A 110/094(37

Evaluation of Four DNA Typing Techniques in Epidemiological Investigations of Bovine Tuberculosis

ABSTRACT DNA fingerprinting techniques were used to type 273 isolates of Mycobacterium bovis from Australia, Canada, the Republic of Ireland, and Iran. The results of restriction fragment length polymorphism (RFLP) analysis with DNA probes from IS 6110 , the direct repeat (DR), and the polymorphic GC-rich sequence (PGRS) were compared with those of a new PCR-based method called spacer oligonucleotide typing (spoligotyping) developed for the rapid typing of Mycobacterium tuberculosis (J. Kamerbeek et al., J. Clin. Microbiol. 35:907–914, 1997). Eighty-five percent of the isolates harbored a single copy of IS 6110 , and 81.5% of these carried IS 6110 on the characteristic 1.9-kb restriction fragment. RFLP analysis with IS 6110 identified 23 different types, RFLP analysis with the DR probe identified 35 types, RFLP analysis with the PGRS probe identified 77 types, and the spoligotyping method identified 35 types. By combining all results, 99 different strains could be identified. Isolate clusters were frequently associated within herds or were found between herds when epidemiological evidence confirmed animal movements. RFLP analysis with IS 6110 was sufficiently sensitive for the typing of isolates with more than three copies of IS 6110 , but RFLP analysis with the PGRS probe was the most sensitive typing technique for strains with only a single copy of IS 6110 . Spoligotyping may have advantages for the rapid typing of M. bovis , but it needs to be made more sensitive. </jats:p