Susceptibility to tulathromycin in Mannheimia haemolytica isolated from feedlot cattle over a 3-year period

Abstract

Mannheimia haemolytica isolated from feedlot cattle were tested for tulathromycin resistance. Cattle were sampled over a 3-year period, starting 12 months after approval of tulathromycin for prevention and treatment of bovine respiratory disease. Nasopharyngeal samples from approximately 5,814 cattle were collected when cattle entered feedlots (N = 4) and again from the same cattle after ≥60 days on feed. The antimicrobial use history for each animal was recorded. Mannheimia haemolytica was isolated from 796 (13.7%) entry samples and 1,038 (20.6%) ≥ 60 days samples. Of the cattle positive for M. haemolytica, 18.5, 2.9, and 2.4% were administered therapeutic concentrations of tulathromycin, tilmicosin, or tylosin tartrate, respectively. In addition, 13.2% were administered subtherapeutic concentrations of tylosin phosphate in feed. In years one and two, no tulathromycin-resistant M. haemolytica were detected, whereas five isolates (0.4%) were resistant in year three. These resistant isolates were collected from three cattle originating from a single pen, were all serotype 1, and were genetically related (≥89% similarity) according to pulsed-field gel electrophoreses patterns. The five tulathromycin-resistant isolates were multi-drug resistant also exhibiting resistance to oxytetracycline, tilmicosin, ampicillin, or penicillin. The macrolide resistance genes erm(42), erm(A), erm(B), erm(F), erm(X) and msr(E)-mph(E), were not detected in the tulathromycin-resistant M. haemolytica. This study showed that tulathromycin resistance in M. haemolytica from a general population of feedlot cattle in western Canada was low and did not change over a 3-year period after tulathromycin was approved for use in cattle.

Integrative and Conjugative Elements (ICEs) in Pasteurellaceae Species and Their Detection by Multiplex PCR

“…The genomes of two of these strains, Pmu12591 and Pmu12601, were sequenced without revealing any changes in their rRNAs or ribosomal proteins, or other relevant genes that could account for elevated MICs to TIL (Vester and Douthwaite, 2001 ; Peric et al, 2003 ). Similar observations for M. haemolytica strains with no obvious molecular explanation have been made elsewhere for TUL resistance (Alexander et al, 2013 ) and also for GAM resistance (DeDonder et al, 2016 ). Up-regulation of one or more endogenous efflux system could possibly account for these anomalous macrolide phenotypes.…”

“…Possibly the acquisition of these macrolide resistance genes is a recent event and the presence of int1 is indicative of ICE functionality, which has not yet been lost in the sequences that have been transferred more recently. Finally, although lack of detection is not a proof of absence, we note that the erm (42), msr (E), and mph (E) genes have yet to be reported in European (Table 3 ) (Rose et al, 2012 ), Australian (Dayao et al, 2016 ), and Canadian animals (Alexander et al, 2013 ).…”

“…In these cases, resistance was achieved via point mutations in the drug binding site on the ribosome, as we have seen previously in the P. multocida strains Pmu14421, Pmu14424, and Pmu14426 with A2059G substitutions in the 23S rRNA genes in all six of their rrn operons, and the M. haemolytica strain Mh14717 which had A2058G mutations in all six of its rrn operons (Olsen et al, 2015 ). This same mechanism could explain the macrolide resistance phenotypes of Canadian M. haemolytica isolates that lack all the erm (42) , msr (E), and mph (E) genes (Alexander et al, 2013 ). In the related Pasteurellaceae species Haemophilus parasuis , the A2059G mutation has been reported in an Australia isolate from swine respiratory infection (Dayao et al, 2016 ).…”

A large potentiation effect of serum on the in vitro potency of tulathromycin against Mannheimia haemolytica and Pasteurella multocida

“…Tulathromycin is a broad spectrum antimicrobial drug. Its spectrum of activity includes aerobic and anaerobic gram-positive bacteria, gram-negative cocci and Mannheima, Pasteurella, Actinobacillus, Haemophilus, Bordetella and Helicobacter, as well as mycoplasma, chlamydia and rickettsia species (Evans, 2005;Godinho et al, 2005a,b;Alexander et al, 2013;Villarino et al, 2013). As with other macrolides and triamilides, tulathromycin binds to the 50S ribosomal subunit, leading to blockade of transpeptidation and translocation reactions, to inhibit protein synthesis and hence prevent cell growth (Evans, 2005;Andersen et al, 2012).…”

A literature review of antimicrobial resistance in Pathogens associated with bovine respiratory disease

“…Similar publications specific for pathogens of BRD did not begin appearing in the literature until the early 1980s. Resistance genes have been found and described for the common bacterial pathogens associated with BRD for the tetracyclines (Singer et al, 1998;Kehrenberg et al, 2005;O'Connor et al, 2010;D'Amours et al, 2011;Klima et al, 2011;Michael et al, 2012b), fluoroquinolones (Michael et al, 2012b;Pardon et al, 2013), beta-lactams ( Klima et al, 2011;Michael et al, 2012b;Alexander et al, 2013a), macrolides (Desmolaize et al, 2011a, b;Kadlec et al, 2011;Klima et al, 2011;Michael et al, 2012b), sulfonamides (Michael et al, 2012b), lincosamides (Desmolaize et al, 2011b;Kadlec et al, 2011;Michael et al, 2012b), phenicols (Kehrenberg et al, 2008;Katsuda et al, 2012;Michael et al, 2012b), and aminoglycosides (Michael et al, 2012b;Alexander et al, 2013a). Lubbers and Hanzlicek described the available literature on antimicrobial resistance by categorizing the information into two categories: (1) authors reporting the percentage of isolates that are susceptible or resistant, or (2) the minimal inhibitory concentration (MIC) distribution, i.e.…”