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?