common myths in treating calf diarrhea - cloudfront.net

Common Myths in Treating Calf Diarrhea

Geof Smith, DVM, PhD, Dipl. ACVIMDept. Population Health & Pathobiology

North Carolina State University

Introduction

• Diarrhea remains the leading cause of mortality prior to weaning in beef and dairy calves

• Must carefully consider treatment options• There are many different ideas and approaches for how to “best” treat diarrhea

• Some of these are supported by evidence‐based medicine and some are not

CALF DIARRHEATreatment Goals

1) Correct acid base, electrolyte, and free water abnormalities2) Provide nutritional support3) Eliminate/prevent E coli bacteremia4) numbers of E coli bacteria in the small intestine

Myth 1

One oral electrolyte is just as good as another• Tremendous differences in oral electrolyte products for sale in North America

• Many modeled after WHO recommendations for electrolyte therapy in humans

• Need to make sure oral electrolyte can adequately rehydrate calf

• AND correct/prevent the acidemia that almost always accompanies diarrhea

Oral Electrolytes in Calves

Ideal Properties1) Supply sufficient sodium to correct extracellular

fluid deficits2) Provide agents that facilitate intestinal

absorption of sodium and water (ie. glycine, acetate, or glucose)

3) Provide an alkalinizing agent (acetate, propionate, bicarbonate) to correct metabolic acidosis

Oral Electrolytes in Calves

Ideal Properties4) Provide sufficient energy (glucose) to correct

hypoglycemia (electrolytes often given instead of milk)

5) Facilitate a healthy gastrointestinal environment (doesn’t encourage microbial growth and/or encourages healing of damaged intestinal epithelium)

•Provide an excess of strong cations relative to the concentration of strong anions

Myth 2Diarrhea will resolve faster if we withhold milk

• Since the 1940’s routine recommendations have been to withhold milk from calves with diarrhea

• However no research has demonstrated this speeds intestinal healing OR resolution of diarrhea

• Calves need energy to live – continued milk feeding is important for successful treatment

“Rest the Gut” Theory

• Milk fed during oral electrolyte therapy is considered by some to exacerbate diarrhea

• Milk will supply nutrients for bacteria to use as an energy source

• This leads to further maldigestion and increased excretion of fluids (more diarrhea)

• Faster intestinal healing without milk• Less opportunity for overgrowth with bacteria

None of this has been demonstrated

“Rest the Gut”

• 42 dairy calves with diarrhea were divided into 3 groups

• Group 1‐ OES only for 2 days with gradual return to milk

• Group 2‐ partial removal of milk + OES• Group 3‐ OES and a full (whole) milk diet• Body weights, mortality, and fecal scores were monitored for 10 days

Garthwaite et al., J Dairy Sci 1994; 77:835‐843

“Rest the Gut”

Results• Calves in groups 1 and 2 lost weight for the first 4 days of treatment while calves in group 3 gained weight

• No difference in severity or duration of diarrhea between groups

• Although there was no mortality, calves in groups 1 and 2 were more depressed than calves in group 3

Garthwaite et al., J Dairy Sci 1994; 77:835‐843

Another Study

• 360 calves with naturally occurring diarrhea • Those with concurrent disease or that needed IV fluids were not included

• 180 calves got Resorb per label directions • 2 feedings of Resorb only for 2 days (4 feedings) and then 1 liter of milk mixed with 1 liter of Resorb thru day 4 or until diarrhea resolved

• 180 calves got Diaque per label:• 1 packet mixed with ½ gallon of milk twice daily for 2 days (continue if diarrhea persisted)

Another Study

Resorb Diaque P Value

Weight at start of trial (kg) 36.2 + 5.8 36.3 + 4.8 0.91

Weight 5 days after diarrhea 37.6 + 6.0 39.3 + 4.9 0.0066

Weight gain during treatment 0.6 + 2.9 2.7 + 3.1 <0.001

Weaning weight 60.2 + 7.2 67.5 + 7.8 <0.001

Time to resolution of diarrhea 8.0 days 6.2 days 0.0085

Goodell et al., J Dairy Sci 2012; 95:6677‐6686

“Rest the Gut” Theory

• Conclusion‐ OES do not have enough energy to sustain calves – therefore they need milk

• It is OK to skip one feeding if a calf is depressed and refuses to nurse – however milk should be resumed within 12 hours

• There is no proven benefit to withholding milk –you only further exacerbate the negative energy balance

Myth 3Without feeding antibiotics to calves – I have no

possibility of avoiding diarrhea

• In 2007 80% of dairy farms fed medicated milk replacers to calves

• A 2012 survey indicated that 56% of calf ranches were using medicated milk replacers (J Dairy Sci 2012; 95:2204)

• Continual feeding of antibiotics is now prohibited in many countries

• Efficacy of antibiotics to prevent diarrhea has not been scientifically supported in recent studies

• A review article published in 1955 stated that “the addition of chlortetracycline and oxytetracycline to milk replacers in the first 8 weeks of life decreases the incidence and severity of calf diarrhea”

• This paper led to the routine inclusion of antibiotics in milk replacers throughout the United States

J Dairy Sci 1955; 38:1102‐1138

Prevention of Calf Diarrhea

• The primary benefits of antibiotics were found to be better weight gain, improved coat appearance and decreased duration of diarrhea

• Mortality rate or actual incidence of diarrhea with or without antibiotics was not examined

• From the 1950’s thru the 1970’s – several studies were done using various antibiotics on prevention of calf diarrhea

Group Antibiotic Outcome Reference

280 Aryshirecalves

OralStreptomycin

Slight reduction in days ofdiarrhea (NS) – no effect on mortality or weight gain

Vet Rec 1960; 72:1186‐1199

Aryshirecalves

OralNeomycin

No effect on weight gain, mortality or days with diarrhea

Vet Rec 1960; 72:1186‐1199

Aryshirecalves

OralChlortetracycline

Significant reduction in mortality due to diarrhea –also reduced days of diarrhea

Vet Rec 1960; 72:1186‐1199

• Only study to document prophylactic administration of oral antibiotics decreases mortality

Prevention of Calf DiarrheaGroup Antibiotic Outcome Reference

10 Aryshirecalves

OralFurazolidone

No effect on mortality Vet Red 1971; 89:579‐582

28 Holstein calves

Neomycin and tetracycline

Oral administration for 5 days actually increased the occurrence of diarrhea as compared to controls

Am J Vet Res 1986; 47:987‐991

407 Holstein calves (California)

Neomycin Oral administration tended (P = 0.06) to increase the percentage of calves that developed diarrhea

Vet Med Small AnimClin 1978; 73:924‐930

46 dairy calves

Tetracycline No difference in incidence of diarrhea between groups

J Dairy Sci 1952; 35:846‐856


• Many of these studies indicate an increase in growth rate for calves fed antibiotics

• However – very limited information to indicate oral antibiotics are effective in preventing diarrhea

• Almost no research evaluating severity of diarrhea• Cannot find any literature demonstrating efficacy of orally administered neomycin


• Holstein calves fed MR containing oxytetracyclineand neomycin OR a probiotic from birth to 5 weeks of age

• BW, FE and both incidence and severity of diarrhea were similar between groups

J Dairy Sci 2002; 85:947‐950


• 80 Holstein heifers divided into 2 groups (fed non‐medicated MR throughout study)

• Monensin in grain starter• Aureomycin and lasalocid in grain starter

• From birth to 12 weeks of age – no difference in ADG, feed efficiency, proportion of calves that developed diarrhea or pneumonia

Prof Anim Sci 2010; 26:520‐526


• 358 calves divided into 4 groups:• MMR (oxy + neo) for the first 14 days of life + conventional antibiotic treatment

• MMR (oxy + neo) for the first 14 days of life + targeted antibiotic treatment

• Non‐medicated MR plus conventional therapy• Non‐medicated MR plus targeted therapy

J Dairy Sci 2009; 92:4707‐4714


• Cows were housed in hutches and monitored for 28 days

• Calves fed medicated MR had 31% more days with diarrhea as compared to calved fed non‐medicated MR

• Conclusion – Recent studies do not support the feeding of oral antibiotics to calves as a prevention for diarrhea – data would indicate no efficacy

J Dairy Sci 2009; 92:4707‐4714


• Chlortetracycline, neomycin, oxytetracycline, tetracycline and neo‐oxy combination products are still approved for control of scours caused by E. coli

• No modern data to support these claims• A new federal regulation (2010) restricts the feeding of medicated MRs to a period of 7‐14 days (continuous feeding prohibited)

Prevention of Calf Diarrhea• Producers are encouraged to transition from prophylactic antibiotic use to therapeutic antibiotic use

• Medicated MRs have been banned in the EU since the 1990’s – with Australia/NZ also having strict laws

• The traditional practice of feeding medicated MRs to calves should be discouraged – primarily due to lack of any documented benefit

• Conclusion – The use of oral antibiotics to prevent diarrhea cannot be recommended

Myth 4There is no role for antimicrobial therapy in

calves with diarrhea

• Most cases of calf diarrhea are caused by rotavirus or Cryptosporidium

• Since antimicrobials won’t kill these pathogens –they should never be used

• Strong opinions exist that antibiotics have no place in treating calf diarrhea unless Salmonella has been diagnosed

Statements on Antibiotics in Calf Diarrhea

• “There is no role per se for antibiotics (oral or systemic) in the treatment of calf diarrhoea” (Grove‐White, Irish Vet J 2004;57:722‐728)

• “Antibiotics are not an appropriate treatment choice for calf diarrhea and should be reserved for pneumonia” (Acta Vet Scand 2003; 44:97‐101)

Antibiotics to Treat Calf Diarrhea – Rationale?

1) A significant percentage of diarrheic calves are septic

• An early study indicated 82% of colostrum‐deprived calves with diarrhea were bacteremic (primarily E. coli)

• A much smaller percentage of calves with adequate passive transfer were bacteremic

J Pathol Bacteriol 1962;84:147‐168

Prevalence of Bacteremia• California – calf rearing facility

• 169 calves with diarrhea and depression• 28% (47/169) were bacteremic (E. coli)• 76% (129/169) had FPT• median age bacteremic calves = 8 days

Fecteau et al., Can Vet J 1997

• Prince Edward Island – Referral Hospital• 252 calves with diarrhea (dairy & beef)• 31% (78/252) were bacteremic (E. coli)• 46% (47/103) of FPT were bacteremic as compared to 18% (21/116) of calves with adequate passive transfer

• mean age bacteremic calves = 9 daysLofstedt et al., J Vet Int Med 1999

Antibiotics to Treat Calf Diarrhea –Rationale?

• About 1/3 of calves with diarrhea are bacteremic – with % higher in calves with FPT

• Calves with bacteremia consistently have a poor prognosis

• Therefore calves with diarrhea and depression, fever or documented FPT should absolutely receive Abs

• To withhold an effective treatment for a life‐threatening disease is unethical

2) Calves with diarrhea have increased numbers of coliform bacteria in their intestine• We have known for 70 years that calves with diarrhea have altered GI flora

• This occurs regardless of etiology or age of calf• E. coli numbers are increased 5 to 10,000‐fold in the small intestine

• Coliform overgrowth of the SI can persist for days following the diarrhea episode

Cornell Vet 1924; 14:218‐225 J Exp Med 1925; 41:89‐106

Coliform Bacteria in the Intestines of Calves

Coliform Overgrowth of Intestine

What does this mean?1) Has been associated with impaired glucose,

xylose and fat absorption (Am J Vet Res 1987; 48:719)

2) Can worsen the morphologic damage present in the small intestine

3) Perhaps contributes to the increased bacteremia rates in calves with diarrhea

Antibiotics to Treat Calf Diarrhea – Rationale?

• Could make an argument that if antimicrobial use in calves with diarrhea were able to decrease numbers of coliform bacteria in the small intestine you could:

• Decrease morphologic damage• Reduce number of days with diarrhea• Reduce bacteremia• Decrease mortality• Increase growth rates

• Critical measures of efficacy• mortality rate• growth rate in survivors• severity of diarrhea in survivors• duration of diarrhea in survivors

• Reviewed all refereed articles since 1950• oral antibiotics in naturally acquired diarrhea• oral antibiotics in experimentally induced diarrhea• parenteral antibiotics in naturally acquired diarrhea• parenteral antibiotics in experimentally induced diarrhea

Constable, J Vet Int Med 2004; 18:8‐17

Conclusions

• Specific antibiotics are effective in mortality & growth rate when administered to calves with diarrhea

• Several studies with simple diarrhea show calves recovering faster with antibiotics

• 318 calves enrolled at 6 sites (UK, France, Germany)• Calves were divided into 3 groups

• Ampicillin IM q24h• Ampicillin‐sulbactam IM q24h• Untreated control

• Treatment started immediately on detection of diarrhea

Parenteral Antibiotics – Naturally Occurring Diarrhea

• Mortality rates decreased with antibiotics• Ampicillin – 14% (15/107)• Ampicillin‐sulbactam – 10% (10/105)• Controls – 26% (28/106)

• Did not look at duration or severity of diarrhea• Study provides support for routine administration of parenteral antibiotics in calves with undifferentiated diarrhea

Vet Rec 1987; 121:162‐166

Appropriate Antibiotic Use

• needs to target coliform bacteria• suitable MIC’s much be reached in small intestine• coliform bacteria must be susceptible to antibiotic (‐lactamase production)

• need to minimize risk of developing multiple antibiotic resistance

Currently Approved Antibiotics for Control and/or Treatment of Diarrhea

1) Chlortetracycline (Aureomycin, ChlorMax or CLTC 100)

2) Oxytetracycline (300 Pro LA, Agrimycin, Biomycin 200, Calf scours bolus, Terramycin bolus, Terramycin granular)

3) Tetracycline (Duramycin‐10, Tet‐Sol 324)

4) Neomycin (Neomed power or oral solution)

5) Neomycin‐oxytet combo (Neo‐Terramycin)

6) Sulfamethazine (Sustain III boluses, SMZ‐Med 454), Sulmet)

Approved Antibiotics ‐ Diarrhea

• No studies exist with any of these drugs to document efficacy in treating calf diarrhea

• Tetracycline, oxytet, chlortet, and neomycin were approved as “safe” in the 1950’s

• It could be argued that extralabel antimicrobial use is justified in treating calf diarrhea due to the lack of any studies documenting efficacy of approved antibiotics

Antibiotics in Calf DiarrheaEvidenced based recommendations

BACTEREMIA (systemically ill)• Ceftiofur 1.1‐2.2 mg/kg, IM/SC, q 12 h (higher doses illegal now)

• Ampicillin trihydrate 10 mg/kg, IM (neck), q 12 h • Potentiated sulfonamides 25 mg/kg, IV/IM, q 24 h• Fluoroquinolones (not in the United States)

SMALL INTESTINE• Amoxicillin trihydrate 10 mg/kg, q 12 h• Amoxicillin trihydrate‐clavulanate potassium (5:1, 12.5 mg/kg, q 12 h

Summary

• Antibiotics are indicated for any calf with diarrhea and signs of systemic illness

• anorexia,• dehydration• lethargy• pyrexia• blood or mucosal shreds in manure (indicated breakdown of blood‐gut barrier)

• failure of passive transfer

Summary

• Antibiotics should probably not be administered to calves that simple diarrhea

• Normal appetite• Normal activity level• Normal rectal temperature• Normal hydration• No concurrent infection (umbilical, etc)

Myth 5Prebiotics or Probiotics are effective in treating

calf diarrhea

• Lots of folks focused on additives to milk to treat diarrhea and/or altering small intestinal flora

• Although commonly used in other species – no evidence that these approaches work in calves

Prebiotics

• Naturally occurring non‐digestible carbohydrates that supposed to “feed” good bacteria in the GI tract

• Limited research here in calves but no positive benefit was found to using them in one study

• Main target is increasing Bifidobacteria& lactic acid producing organisms

Prebiotics

• 75 Holstein heifers allocated to 1 of 3 groups (control, antibiotics, prebiotics)

• No difference in scour days, days treated or antibiotic/oral electrolyte doses

• Fecal bacterial counts (Lactobacilli, Bifidobacteria and Clostridial) did not change across groups at weeks 2, 4, 6 or 8

Livestock Science 2009; 125:149‐154

Prebiotics

Prebiotic Control Antibiotic

Birth weight (kg) 40.71 41.99 41.29

Final weight (kg) 74.93 75.79 76.70

ADG (g/d) 608 605 645

Hip height birth (cm) 79.71 80.10 80.32

Final hip height (cm) 91.73 92.62 92.15

Livestock Science 2009; 125:149‐154

Probiotics

• Lyophilized or live bacterial cultures given in an attempt to improve performance or increase resistance to enteric pathogens (DFM)

• No evidence to support that probiotics are effective for treating diarrhea

• Daily administration of lyophilized lactic‐acid producing bacteria for 10 days had no effect on C. parvum diarrhea of dairy calves (Am J Vet Res 1996; 57:1586‐1588)

Probiotics

• In calves with naturally occurring diarrhea – a probiotic formula (Lactobacillus rhamnosus GG) –did not change severity of diarrhea or mortality rate (J Vet Intern Med 2003; 17:940‐942)

• Probiotic (Lactobacillus pentosusWE7) administration ↑ days of diarrhea and induced inappetance in foals (JAVMA 2005; 226:2031‐2034)

Yeast Cell Wall Extract

• Some evidence that Saccharomyces cerevisiaefermentation products help with Salmonella

• Recent study using 40 dairy calves – half got yeast and half did not (2 weeks before challenge)

• Combination of water soluble product in milk along with an oral bolus

• Orally infected with Salmonella typhimurium at day 14


• Calves that received the yeast extract had fewer episodes of diarrhea and reduced fever

• Rumens from calves that were fed yeast were more developed (length of papillae)

• Intestinal colonization of Salmonella was reduced in yeast fed calves

• Slightly shorter duration of shedding after infection

Brewer et al. Vet Microbiol 2014; 172:248‐255


103.5

102.7

102.0

101.3



• Calves with Cryptosporidiosis got either 1) SmartCare plus XPC (T1) 2) BioMos (T2) or 3) maltodextrin (T3)

• Euthanized at 28 days to look at intestinal villi• T1 and T2 groups had more villi than T3 calves• T1 villi were taller and wider than other groups• Damaged or atrophied villi were less in T1 vs T2 or T3 groups

WBC 2016 – Dublin – P04‐004‐144

Myth 6Subcutaneous fluids are just as good as IV fluids

and better than oral electrolytes for resuscitating calves with diarrhea

• I see lots of calf ranches and some veterinarians commonly using 1‐2 liters of LRS or Normosol to treat diarrhea (either IV or SC)

• Deficit of calves is much higher – little known about how well SC fluids are absorbed in calves

Materials & Methods32 Holstein bull calves (7-21 days of age)

Treatment groups – 8 calves per groupA. OES - Diaque®

i. 1 package mixed with 2 quarts of water according to label instruction

B. IV fluids – Lactate Ringer solutioni. Bolus of 2 liters of LRS through a jugular catheter

C. SC fluids – Lactate Ringer solutioni. 2 liters of LRS over the thorax and neck – four sites (500ml each)

D. Hypertonic saline + OES – 7.2% hypertonic saline + Diaque® i. HSS through a jugular catheter (4ml/kg of BW) over 5 minutesii. Feeding 1 package mixed with 2 quarts of water according to

label instruction

Materials & MethodsSAMPLING

1. Blood sample at day 0 prior to induction for plasma protein and albumin concentrations

2. Treatment day• Time 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24

3. VetScan i-Stat:• blood pH, pCO2, bicarbonate, base excess, hematocrit,

hemoglobin, glucose, sodium, potassium, and anion gap concentrations

4. Plasma protein was determined at each time point and used to calculate change in plasma volume.

Results1. No significant difference between groups at time 0

2. Blood pH increase faster with the OES versus IV and SC fluids

3. Faster and more sustain increase in plasma volume with OES, IV and HSS+OES versus SC fluids

4. Faster and more sustain increase in glucose with OES and HSS+OES versus IV and SC fluids

5. Fecal score did not appear to be affected by treatment.

Discussion

1. Higher pH in OES group over the study period = faster increase due to alkalinizing agent

2. First report of SC fluids for treatment of neonatal diarrhea

3. Slower increase in plasma volume and minimal improvement in base excess with SC fluids = not optimal for rapid resuscitation

4. Significant increase in [glucose] up to two hours following OES solution administration = provide energy

Conclusions1. OES with or without HSS appeared to be

better than 2 liters of IV or SC fluids for resuscitation of calves with diarrhea and mild to moderate acidosis

2. Delayed absorption does not make SC administration a good choice for rapid resuscitation in calves with diarrhea and acidosis

CALF DIARRHEATreatment Goals

1) Correct acid base, electrolyte, and free water abnormalities2) Provide nutritional support3) Eliminate/prevent E coli bacteremia4) numbers of E coli bacteria in the small intestine

common myths in treating calf diarrhea - cloudfront.net

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