Is Draxxin a good substitute for Erythromycin?
Katherine Haman, Mary Peters, Sonia Mumford
Draxxin – a Team Effort
Betsy Hall, Craig Olsen, Bruce Stewart, Marcia House
Sonia Mumford, Mary Peters, Sharon Lutz, Chris Patterson, Joy Evered, Susan Gutenberger, Guppy Blair, Kim True, Laura Sprague, Andy Goodwin, Brad Thompson, Jim Bowker, Dave Erdahl
Doug Munson (IDFG), Craig Banner (ODFW), Linda Rhodes (NOAA), Diane Elliott (USGS), Jed Varney (Pacific Seafoods), Hugh Mitchell (AquaTactics), Pat Gaunt (Mississippi State) Cowlitz Salmon Hatchery, Little White Salmon Hatchery Carson, Klickitat, Warm Springs, Leavenworth, Nez Perce hatcheries
Vertical transmission of R. salmoninarum
20 years of managing R. salmoninarum
Notes from three spring Chinook hatcheries:
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Percentage of spawned females, OD => 0.2
Warm Springs Little White Carson
Bacterial Kidney Disease (Renibacterium salmoninarum)
Image credit: M. Peters, USFWS
Erythromycin (injectable) is no longer available (new update, possibly available with new manufacturer this summer under INAD)
Draxxin (tulathromycin) in vitro MIC is 0.5 ug/mL (NWIFC, NOAA; 2014)
No pre-spawn mortality in adult SCS at 5 mg/kg, IP or Dorsal sinus (USFWS, 2014) Rough bioassay indicated tulathromycin uptake in kidneys (NOAA,
2014) Was this at a level and duration to be effective?
A Brief History:
Pilot Pharmacokinetic Study, 2015
Controls vertical transmission and reduces pre-spawn mortality
Draxxin pK study design – replicated at LWS & CSH
5mg/kg IP injections in adult, female SCS at LWS and CSH Study duplicated due to differing ave. water temp at
LWS (46-48F) and CSH (54-58) LWS also injected a small group with 10 mg/kg
Sacrifice 3 fish at various time points over a 56 day period 6 fish at each time point, 102 fish total
Measure drug concentration in ovary, kidney, and muscle NY Dept. of Ag, FDA-approved method HPLC-MS/MS
Objective: Does tulathromycin concentration exceed the in vitro MIC, and if so, for how long?
Time Injected Fish Sampled
Uninjected Control
Tissues Collected For LC-MassSpec
Tissues Collected for Histo
0 (Monday) 3 1 Muscle, Kidney, Ovary Heart, Liver, Kidney, Intestine
4 (Monday) 3 Muscle, Kidney, Ovary 8 (Monday) 3 Muscle, Kidney, Ovary Day1 (Tues) 3 1 Muscle, Kidney, Ovary Heart, Liver Kidney,
Intestine Day 2 (Weds) 3 Muscle, Kidney, Ovary Day 3 (Thursday) 3 Day 4 (Friday) 3 1 Day 7 (Monday) 3 1 Muscle, Kidney, Ovary Heart, Liver Kidney,
Intestine Day 9 (Weds) 3 Muscle, Kidney, Ovary Day 11 (Friday) 3 Muscle, Kidney, Ovary Day 14 (Monday) 3 1 Muscle, Kidney, Ovary Day 21 (Monday) 3 1 Muscle, Kidney, Ovary Day 28 (Monday) 3 1 Muscle, Kidney, Ovary Heart, Liver Kidney,
Intestine Day 35 (Monday) 3 1 Muscle, Kidney, Ovary
Draxxin pK study design – replicated at LWS & CSH
Preliminary results, residues through 48 hours
0
10
20
30
40
50
0 10 20 30 40 50
ppm
Dra
xxin
Hours post-injection
Draxxin tissue residues (ppm) LWS and Cowlitz SCS
Kidney-LKidney-C
Preliminary results, residues through 48 hours
0
2
4
6
8
10
0 10 20 30 40 50
ppm
Dra
xxin
Hours post-injection
Draxxin tissue residues (ppm) LWS and Cowlitz SCS
Muscle-LMuscle-C
Preliminary results, residues through 48 hours
0
2
4
6
8
10
0 10 20 30 40 50
ppm
Dra
xxin
Hours post-injection
Draxxin tissue residues (ppm) LWS and Cowlitz SCS
Egg-LEgg-C
Preliminary results: above the MIC in eggs & kidney
How long does Draxxin remain above the MIC?
Preliminary results, residues through 35 days
0
5
10
15
20
25
0 200 400 600 800
ppm
Dra
xxin
Hours post-injection
Draxxin tissue residues (ppm) Cowlitz SCS
Kidney-CEgg-CMuscle-C
Preliminary results, residues through 35 days
0
2
4
6
8
10
0 200 400 600 800
ppm
Dra
xxin
Hours post-injection
Draxxin tissue residues (ppm) Cowlitz SCS
Kidney-CEgg-CMuscle-C
Preliminary results, 10 mg/kg dose
0
10
20
30
40
50
60
70
80
90
0 10 20 30 40 50 60
ppm
Dra
xxin
Hours post-injection
Draxxin tissue residues (ppm) averaged, 10 mg/kg dose, LWS SCS
Kidney
Muscle
Egg
Preliminary results, 10 mg/kg dose
0
2
4
6
8
10
12
14
0 10 20 30 40 50 60
ppm
Dra
xxin
Hours post-injection
Draxxin tissue residues (ppm) averaged, 10 mg/kg dose, LWS SCS
Kidney
Muscle
Egg
Conclusions and uncertainties Draxxin is detectable in the kidney, muscle and eggs above the MIC
Kidney concentrations are higher than muscle and egg Metabolism
Muscle residues implications for carcass outplanting
Egg residue dropped below MIC at day 4 above MIC days 7 through 35
Will Draxxin help us control BKD?
If we discontinue antibiotic injections of adult SCS, will BKD once again be major cause of mortality?
Questions?