First Emergence of Resistance to Macrolides and Tetracycline Identified in Mannheimia haemolytica and Pasteurella multocida Isolates from Beef Feedlots in Australia

Bovine respiratory disease (BRD) causes high morbidity and mortality in beef cattle worldwide. Antimicrobial resistance (AMR) monitoring of BRD pathogens is critical to promote appropriate antimicrobial stewardship in veterinary medicine for optimal treatment and control. Here, the susceptibility of Mannheimia haemolytica and Pasteurella multicoda isolates obtained from BRD clinical cases (deep lung swabs at post-mortem) among feedlots in four Australian states (2014–2019) was determined for 19 antimicrobial agents. The M. haemolytica isolates were pan-susceptible to all tested agents apart from a single macrolide-resistant isolate (1/88; 1.1%) from New South Wales (NSW). Much higher frequencies of P. multocida isolates were resistant to tetracycline (18/140; 12.9%), tilmicosin (19/140; 13.6%), tulathromycin/gamithromycin (17/140; 12.1%), and ampicillin/penicillin (6/140; 4.6%). Five P. multocida isolates (3.6%), all obtained from NSW in 2019, exhibited dual resistance to macrolides and tetracycline, and a further two Queensland isolates from 2019 (1.4%) exhibited a multidrug-resistant phenotype to ampicillin/penicillin, tetracycline, and tilmicosin. Random-amplified polymorphic DNA (RAPD) typing identified a high degree of genetic homogeneity among the M. haemolytica isolates, whereas P. multocida isolates were more heterogeneous. Illumina whole genome sequencing identified the genes msr(E) and mph(E)encoding macrolide resistance, tet(R)-tet(H) or tet(Y) encoding tetracycline resistance, and blaROB-1 encoding ampicillin/penicillin resistance in all isolates exhibiting a corresponding resistant phenotype. The exception was the tilmicosin-resistant, tulathromycin/gamithromycin-susceptible phenotype identified in two Queensland isolates, the genetic basis of which could not be determined. These results confirm the first emergence of AMR in M. haemolytica and P. multocida from BRD cases in Australia, which should be closely monitored.

[1]  J. Glanville,et al.  A systematic review and network meta-analysis of injectable antibiotic options for the control of bovine respiratory disease in the first 45 days post arrival at the feedlot , 2019, Animal Health Research Reviews.

[2]  D. Jordan,et al.  Antimicrobial use and stewardship practices on Australian beef feedlots. , 2019, Australian veterinary journal.

[3]  E. Reddi,et al.  Keratin nanoparticles co-delivering Docetaxel and Chlorin e6 promote synergic interaction between chemo- and photo-dynamic therapies. , 2019, Journal of photochemistry and photobiology. B, Biology.

[4]  T. Parkinson,et al.  Diseases of Cattle in Australasia: A Comprehensive Textbook , 2019 .

[5]  M. Goberna,et al.  Native soil microorganisms hinder the soil enrichment with antibiotic resistance genes following manure applications , 2019, Scientific Reports.

[6]  B. Lubbers,et al.  Applying definitions for multidrug resistance, extensive drug resistance and pandrug resistance to clinically significant livestock and companion animal bacterial pathogens-authors' response. , 2018, The Journal of antimicrobial chemotherapy.

[7]  S. Douthwaite,et al.  Integrative and Conjugative Elements (ICEs) in Pasteurellaceae Species and Their Detection by Multiplex PCR , 2018, Front. Microbiol..

[8]  S. Ahmed,et al.  Molecular Characterization of Isolated Mannheimia haemolytica and Pasteurella multocida from Infected Sheep and Goats Using RAPD and ERIC Markers , 2018, Asian Journal of Animal and Veterinary Advances.

[9]  S. Schwarz,et al.  Antimicrobial Resistance in Pasteurellaceae of Veterinary Origin , 2018, Microbiology spectrum.

[10]  R. M. Anholt,et al.  Antimicrobial Susceptibility of Bacteria That Cause Bovine Respiratory Disease Complex in Alberta, Canada , 2017, Front. Vet. Sci..

[11]  M. Workentine,et al.  Effects of nasal instillation of a nitric oxide-releasing solution or parenteral administration of tilmicosin on the nasopharyngeal microbiota of beef feedlot cattle at high-risk of developing respiratory tract disease. , 2017, Research in veterinary science.

[12]  E. Timsit,et al.  Prevalence and antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from the lower respiratory tract of healthy feedlot cattle and those diagnosed with bovine respiratory disease. , 2017, Veterinary microbiology.

[13]  T. McAllister,et al.  Antimicrobial usage and resistance in beef production , 2016, Journal of Animal Science and Biotechnology.

[14]  F. El Garch,et al.  Monitoring of antimicrobial susceptibility of respiratory tract pathogens isolated from diseased cattle and pigs across Europe, 2009-2012: VetPath results. , 2016, Veterinary microbiology.

[15]  M. Tabatabaei,et al.  Molecular characterization of Pasteurella multocida isolates obtained from poultry, ruminant, cats and dogs using RAPD and REP-PCR analysis , 2016, Molecular biology research communications.

[16]  G. Harhay,et al.  Observations on macrolide resistance and susceptibility testing performance in field isolates collected from clinical bovine respiratory disease cases. , 2016, Veterinary microbiology.

[17]  N. Noyes,et al.  Mannheimia haemolytica in Feedlot Cattle: Prevalence of Recovery and Associations with Antimicrobial Use, Resistance, and Health Outcomes , 2015, Journal of veterinary internal medicine.

[18]  B. Nanduri,et al.  Application of Functional Genomics for Bovine Respiratory Disease Diagnostics , 2015, Bioinformatics and biology insights.

[19]  T. Barnes,et al.  Antimicrobial susceptibility of Histophilus somni isolated from clinically affected cattle in Australia , 2014, The Veterinary Journal.

[20]  I. Morrissey,et al.  Antimicrobial susceptibility monitoring of respiratory tract pathogens isolated from diseased cattle and pigs across Europe: the VetPath study. , 2014, Veterinary microbiology.

[21]  R. Zaheer,et al.  Pathogens of Bovine Respiratory Disease in North American Feedlots Conferring Multidrug Resistance via Integrative Conjugative Elements , 2013, Journal of Clinical Microbiology.

[22]  J. Turnidge,et al.  Control of Fluoroquinolone Resistance through Successful Regulation, Australia , 2012, Emerging infectious diseases.

[23]  C. Lindeman,et al.  A ten-year (2000–2009) study of antimicrobial susceptibility of bacteria that cause bovine respiratory disease complex—Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni—in the United States and Canada , 2012, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[24]  D. Call,et al.  Proximity-Dependent Inhibition of Growth of Mannheimia haemolytica by Pasteurella multocida , 2012, Applied and Environmental Microbiology.

[25]  R. Murray,et al.  Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. , 2012, The Journal of antimicrobial chemotherapy.

[26]  R. Zadoks,et al.  Molecular epidemiology of Pasteurella multocida in dairy and beef calves. , 2011, Veterinary microbiology.

[27]  S. Douthwaite,et al.  Combinations of Macrolide Resistance Determinants in Field Isolates of Mannheimia haemolytica and Pasteurella multocida , 2011, Antimicrobial Agents and Chemotherapy.

[28]  E. Brzuszkiewicz,et al.  Molecular Basis of Macrolide, Triamilide, and Lincosamide Resistance in Pasteurella multocida from Bovine Respiratory Disease , 2011, Antimicrobial Agents and Chemotherapy.

[29]  A. Confer,et al.  The epidemiology of bovine respiratory disease: What is the evidence for predisposing factors? , 2010, The Canadian veterinary journal = La revue veterinaire canadienne.

[30]  A. Confer,et al.  Comparison of Genotypic and Phenotypic Characterization Methods for Pasteurella Multocida Isolates from Fatal Cases of Bovine Respiratory Disease , 2010, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[31]  J. Campos,et al.  Haemophilus influenzae Clinical Isolates with Plasmid pB1000 Bearing blaROB-1: Fitness Cost and Interspecies Dissemination , 2010, Antimicrobial Agents and Chemotherapy.

[32]  M. Llagostera,et al.  Multiresistance in Pasteurella multocida Is Mediated by Coexistence of Small Plasmids , 2009, Antimicrobial Agents and Chemotherapy.

[33]  S. Abutarbush,et al.  Microbiological and histopathological findings in cases of fatal bovine respiratory disease of feedlot cattle in Western Canada. , 2008, The Canadian veterinary journal = La revue veterinaire canadienne.

[34]  L. Domínguez,et al.  β-Lactam Resistance in Haemophilus parasuis Is Mediated by Plasmid pB1000 Bearing blaROB-1 , 2007, Antimicrobial Agents and Chemotherapy.

[35]  M. Payton,et al.  Isolation and Antimicrobial Susceptibilities of Bacterial Pathogens from Bovine Pneumonia: 1994–2002 , 2004, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[36]  S. Srivastava,et al.  Molecular Variability among Strains of Pasteurella multocida Isolated from an Outbreak of Haemorrhagic Septicaemia in India , 2004, Veterinary Research Communications.

[37]  P. Cusack.  Effect of mass medication with antibiotics at feedlot entry on the health and growth rate of cattle destined for the Australian domestic market. , 2004, Australian veterinary journal.

[38]  T. Hasegawa,et al.  Similarity of Tetracycline Resistance Genes Isolated from Fish Farm Bacteria to Those from Clinical Isolates , 2003, Applied and Environmental Microbiology.

[39]  P M V Cusack,et al.  The medicine and epidemiology of bovine respiratory disease in feedlots. , 2003, Australian veterinary journal.

[40]  S. Djordjevic,et al.  Demonstration that Australian Pasteurella multocida isolates from sporadic outbreaks of porcine pneumonia are non-toxigenic (toxA-) and display heterogeneous DNA restriction endonuclease profiles compared with toxigenic isolates from herds with progressive atrophic rhinitis. , 1998, Journal of medical microbiology.

[41]  É. Chaslus-Dancla,et al.  Validation of random amplified polymorphic DNA assays by ribotyping as tools for epidemiological surveys of Pasteurella from animals. , 1996, Veterinary microbiology.

[42]  P. Blackall,et al.  In-vitro antibacterial properties of tilmicosin against Australian isolates of Pasteurella multocida and Pasteurella haemolytica from cattle. , 1993, Australian veterinary journal.

[43]  I. Nachamkin,et al.  Flagellin gene typing of Campylobacter jejuni by restriction fragment length polymorphism analysis , 1993, Journal of clinical microbiology.

[44]  A. Jones,et al.  Nucleotide sequence analysis of a transposon (Tn5393) carrying streptomycin resistance genes in Erwinia amylovora and other gram-negative bacteria , 1993, Journal of bacteriology.

[45]  V. Livrelli,et al.  Genetic determinant of the ROB-1 beta-lactamase in bovine and porcine Pasteurella strains , 1988, Antimicrobial Agents and Chemotherapy.

[46]  E. B. Wilson.  Probable Inference, the Law of Succession, and Statistical Inference , 1927 .

[47]  J. Coetzee,et al.  Treatment history and antimicrobial susceptibility results for Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolates from bovine respiratory disease cases submitted to the Iowa State University Veterinary Diagnostic Laboratory from 2013 to 2015 , 2018, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[48]  T. Mahony.  Evaluation of practices used to reduce the incidence of bovine respiratory disease in Australian feedlots , 2022 .

[49]  Europa.  The 2013 joint ECDC/EFSA report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks published. , 2015, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[50]  E. Brzuszkiewicz,et al.  ICEPmu1, an integrative conjugative element (ICE) of Pasteurella multocida: analysis of the regions that comprise 12 antimicrobial resistance genes. , 2012, The Journal of antimicrobial chemotherapy.

[51]  I. Chinen,et al.  [Evaluation of two techniques of molecular subtyping to study Pasteurella multocida]. , 2006, Revista Argentina de microbiologia.