FMM/RAS/298: Strengthening capacities, policies and national action plans on prudent and responsible use of antimicrobials in fisheries Good aquaculture and biosecurity practices to minimize AMR Larry A. Hanson hanson@cvm.msstate.edu Aquatic AMR Workshop 1: 10-11 April 2017, Mangalore, India
ANTIMICROBIAL RESISTANCE MANAGMENT o AVOID DEVELOPMENT- Biosecurity Disease prevention Alternative treatments Judicious use o REDUCE PERSISTANCE Crop rotation/complete harvest Monitoring and disinfection? Antibiotic use restriction or rotation o AMR experience in channel catfish production
Biosecurity-Avoiding obligate pathogens and AMR strains o Fish source- critical factor Indiscriminant use of antibiotics during early stages can result in build up in system Fry and eggs sometimes given prophylactic bath treatments during handling- these may be critical during establishment of microbial flora and allow establishment of AMR. Know how fish produced and antibiotic usage- hatchery GAP Due to economics of hatchery systems and susceptibility of young- improper use of antibiotics at this stage is more common (also opportunity to spread pathogens and antibiotic resistance through industry Disinfection of tanks and ponds between batches. Separation of eggs from brooders and disinfection of egg surface (iodine, formalin, potassium permanganate)
Biosecurity- avoid obligate pathogens and introduction of AMR o Surveillance, quarantine and monitoring o Used of certified free stocks o Use pathogen free water, and processed feeds or SPF live/fresh feeds o Between farm security- On farm equipment, nets Limited access Cleaning/disinfecting trucks, trailers, boats entering facility o Within farm security Avoid water movement between ponds Disinfect nets and equipment Predator and scavenger control- mammals, birds and reptiles can shed fish pathogens
Disease prevention- reduces need for antibiotics o If you don t correct underlying cause disease will reoccur after treatment Pathogen Host Disease Environment
Disease prevention o Manage the environment to minimize stress and physical injury Water quality Handling Environment Manage predators Prevent aggression and cannibalism- remove dead o Minimize viral, water mold and parasite diseases (Predispose fish to bacterial disease and suppress feeding- resulting in subtherapeutic treatments) o Vaccines-if effective for bacterial pathogens and viruses o Good quality feed, freshness and amount
Non-antibiotic alternatives o Management to reduce pathogen load or transmission dose Fecal oral transmission- Allow time for gut to clear before feeding- reduces defecation where feeding- ESC every-other day feeding during peak disease season (feed restriction may help with others by reducing close contact) o Chemical treatments that interrupt transmission or stimulate resistant state in host Copper sulfate makes catfish less susceptible to columnaris disease Salt 1-5 ppt reduces F. columnare s ability to adhere to fish (Used during hauling) Potassium permanganate oxidizer kills surface bacteria and free bacteria in the water
Judicious Use of Antibiotics-medicated feeds- minimizes selective pressure o Use when needed and effective Must be diseased- no prophylactic use, no use for growth promotion must be susceptible bacteria pathogen- susceptibility testing Fish must feed well enough to get a therapeutic dose o Give for full treatment duration- antibiotic must persist long enough to kill pathogen o Use fresh good quality medicated feed- reliable licensed feed producer o Careful feeding practices- avoid wastage- AMR can develop in bacteria that grow in wasted feed
Judicious Use- Antibiotics-medicated feeds- regulation o Prescription- Licensed or certified health professional-requires VCPR Must know disease treated (has done the primary diagnosis- should follow up with AMR testing) population activity (feeding well enough for treatment) Must assure that producer is understands proper safe application, rate, duration and withdrawal time before slaughter and agrees to use it in that way o approved antibiotics from licensed source, licensed feed manufacturer Approval for species, pathogen, rate of application and withdrawal time- drug company must show efficacy, safety to user and fish and human food safety o Record keeping- producer, veterinarian/ licensed fish health professional, feed manufacturer
Judicious Use- Enforcement o must be consequences for improper use Illegal drugs human food chain- serious repercussions- human health and product Government agency in US FDA Enforcement branch- actively seeks out any illegal drug usage and presence on facility- results in condemnation of fish, large fines and imprisonment Monitors and traces prescription use drugs- through feed manufacturer Fillet (human food) monitored for residue if any found condemn lot, recall any on market and trace back to farm source Licensing (drug company, feed mill, fish health professional) - assigns legal responsibility and can inappropriate activity can result in revocation Can be industry driven through contracts or cooperatives
REDUCE PERSISTANCE o Minimize use-amr is a natural process. There is cost to the bacteria to maintain this state, minimal antibiotic use will minimize selective pressure and result in lower numbers of AMR pathogens. o Complete harvest and disinfection of production system prevents build up in system. o o Crop rotation if practical- breaks pathogen cycle Voluntary antibiotic use restriction or rotation on a facility for 2-3 production cycles.
Experience in Channel catfish production o Major pathogens Flavobacterium columnare Edwardsiella ictaluri (Enteric septicemia of catfish) and E piscicida Aeromonas hydrophila o Approved antibiotics- All medicated feeds all by Veterinary prescription in 2017 (Terramycin and Romet OTC in 2016). Terramycin-Oxytetracycline 10 days- 21 day withdrawal (rarely used- has been in past) Romet- Sulfadimethoxine-Ormetoprim 5 days- 3 day withdrawal (occasionally used) Aquaflor- Florfenicol 10 days- 15 day withdrawal (commonly used) o Cost $800 per ton vs. $390 for non-medicated
Catfish production Vaccinate and stock fry 7-8 days post hatch Stock fingerlings growth Ja n Fe b Ma r Ap r Ma y Ju n Jun 29 Ju l Au g Se p Oc t No v De c Brood pond Hatchery Fingerling pond stocking Grow out Harvest H GO Continuous production allows pathogen and AMR build up
Routine stress management o Dissolved oxygen intensely managed over summer months o Chlorides maintained above 100ppm to reduce nitrite toxicity o Use fresh, well formulated feeds o Stock fish in cool months to reduce handling stress
Columnaris- Management o Avoid damaging mucus layer- Handle during cool weather Use smooth surfaces or water cushion when handling Treat hauling tanks with 1-3 ppt salt Avoid damage to gills- particulates, ammonia, parasites o Manage ESC, Winter mortality, CCV o Vaccinate (effectiveness in fry not great, likely better in older fish) o Treatment with copper sulfate has been shown to help o Antibiotic medicated feed- Aquaflor labelled, Terramycin not labelled effective but not used, Romet not labelled and may not be effective
Enteric Septicemia of catfish-management o Avoid stress (DO and Nitrite) o While in 22-27 C window feed on alternate days This reduces transmission- enteric pathogen. Gut clearance before feeding reduces bacterial shedding when fish concentrated for feeding. Wise, D.J., Johnson, M.R., 1998. Effect of feeding frequency and Romet-medicated feed on survival, antibody response and weight gain of fingerling channel catfish (Ictalurus punctatus) after natural exposure to Edwardsiella ictaluri. Journal of the World Aquaculture Society 29, 170-176. o Vaccination- helps in fingerlings but losses still occur o Antibiotic treatment- Aquaflor (labelled), Romet (labelled), Terramycin (not labelled)
New Disease: Virulent Aeromonas hydrophila (VAH) High losses over a short time in warm months. First seen in 2009 Most important cause of disease in larger catfish Distinct strain Courtesy of William Hemstreet
Biosecurity: limiting VAH Spread Human o Moving infected fish?-not common Natural o Contaminated equipment & Water (correlation with seining frequency- Bebak et al. 2015. Prev. Vet. Med. 118, 161-168) o Predators and Scavengers. Experimentally shown to survive through gut of Egrets, pelicans, wood storks and cormorants
Management o Hold off feed at first signs of disease o Antibiotic medicated feed- aquaflor (Working on label, extra label use), Romet (not labelled), Terramycin (labelled) o Often re-occurs after treatment period finished. Suspect environmental factor(s) involved.
Observed antimicrobial resistance 2016 MSU-CVM DL Number evaluated percent Florfenicol percent Romet percent Terramycin percent MDR Aeromonas hydrophila 97 1.03 0 1.03 0 Aeromonas sobria 71 12.6 1.41 49.3 2.82 Aeromonas caviae 4 0 0 0 0 Edwardsiella ictaluri 41 14.6 0 12.2 12.2 Edwardsiella piscicida 18 5.55 0 0 0 Plesiomonas shigelloides 7 71.4 14.3 85.7 71.4 Streptococcus 4 0 0 0 0 Total 242 9.09 0.826 19.4 4.96 67 of A. sobria were with F. columnare, 7 were with E. ictaluri, 3 parasites, I saprolegina
AMR in catfish pathogens- Observations o Highest resistance seen in Aeromonas sobria This is a secondary pathogen, not usually the target of antibiotic treatment but often present during columnaris disease Also highest resistance to terramycin which is rarely used now o Second highest level of resistance seen in E. ictaluri Most are resistant to both Aquaflor and Terramycin Early research by Cooper et al. 1993 demonstrated a Romet and Terramycin resistance mediated by an R plasmid that was very similar to a R plasmid isolates from an E. coli. o Industry has seen increasing levels of Aquaflor resistance. May seriously impact treatment options. o Romet resistance subsided rapidly when it was used less often
Summary o Disease management is the most important component for AMR management o Antibiotic resistance will develop and may occur in non-target pathogens o Industry needs to be proactive to minimize the impact