What's new in foal medicine (Proceedings)

Rhodococcus equi

     What 's new in treatment ?

Standard treatment is erythromycin + rifampin

More recently replaced with:

     • -Azithromycin + rifampin

     • -Clarithromycin + rifampin

Resistance to macrolides or rifampin is now being encountered

A study compared MIC data between 2000 and 2006:

     • Over the 6 year period, the MIC of rifampin increased from 0.081 to 0.187 µg/ml

     • MIC of erythromycin increased from 0.258 to 0.583 µg/ml

Another study from 2008 (Giguere et al, ACVIM 2008)

           • 2 isolates were resistant to rifampin

           • 17 isolates were resistant to all 3 macrolides and rifampin

Overall prevalence of resistance was 3.7 % of isolates

Survival rate of foals infected with resistant isolates was lower than of those with susceptible isolates

     • 25 % vs. 70 %, P < 0.004

Resistant Isolates

We have found resistance in isolates from foals

Very concerning

Ask your micro lab to perform susceptibility testing of R. equi isolates

Not done routinely

Other Options

Other options for treatment?

Other macrolides ?

     • Tilmicosin (Micotil) ?

In vitro studies show concentrations achieved in serum, pulmonary fluids and cells is below the MIC

Clinical experience also suggest that it is not effective

Tulathromycin (Draxxin)

Unknown efficacy at this point

In one study comparing tulathromycin with azithromycin in the treatment of undiagnosed pulmonary abscesses:

It took significantly longer for pulmonary abscesses to resolve

Seems fairly safe, but high rate of self-limiting diarrhea in 30 % and IM swelling in 32 %.

Requires further study; cannot be recommended at this time

Doxycycline

Effective: 10 mg/kg q 12 h PO achieves serum and tissue concentrations > MIC of R. equi

It shows synergism with rifampin

Clinical experience suggests it is effective in treating foals with R. equi

Clinically the response appears slower as compared to response to macrolide + rifampin

Good option for macrolide-resistant strains and for foals that have adverse reactions to macrolides

Controversies

Is R. equi plasma protective?

7 published studies

     • 5 show improvement

          o 2 were natural infections on farms

          o 3 were experimental infections

     • 2 showed no difference in incidence of pneumonia

          o Both on farm setting

          o One showed reduced incidence of disease 19.1 vs. 30 %, but it was not statistically difference

Controversies

     • Prophylaxis with antibiotics?

     • One study showed benefit of azithromycin for 2 weeks

     • Concern over resistance to macrolides with indiscriminate use

     • Not recommended

Differentiating R. equi foals

In evaluating a foal with established pneumonia, how can you differentiate between R. equi pneumonia from those caused by other bacteria, while waiting culture results?

  We recently performed a study comparing these:

  Vet J 2009

     • Highly suggestive of R. equi:

          o White cell counts >20,000cells/µL (86% specificity)

          o Fibrinogen concentrations >700mg/dL (92% specificity),

          o Radiological evidence of thoracic abscessation (85% specificity)

          o Gram-positive coccobacilli in tracheal aspirates (91% specificity)

Extrapulmonary Disorders with R. equi

Reuss et al JAVMA: 2009

74 % of foals with R. equi had extrapulmonary involvement

     • Most common forms:

          o Diarrhea 33 %

          o Immune-mediated polysynovitis 25 %

          o Ulcerative enterocolitis 21 %

          o Intra-abdominal abscess 17 %

          o Uveitis 11 %

          o Pyogranulomatous hepatitis 11 %

          o Septic synovitis 9 %

          o Bacteremia 7%

Extrapulmonary Disorders

Survival was higher among foals without these disorders

     • 82 % vs. 43 % survival

     • These foals with extrapulmonary forms were also sicker foals

          o Sick for longer time prior to admission

          o Higher white count and neutrophil count

          o More had been previously examined and referred

Update on Lawsonia intracellularis

Agent of Equine Proliferative Enteropathy

Syndrome of hypoproteinemia, weight loss, lethargy, diarrhea

Pot belly appearance, poor doer

2 mo – yearling (most 3-7 mo of age)

Transmission is thought to occur by the fecal-oral route

Unknown definitive host; wildlife and domestic animals have been proposed

Found in feces of striped skunks, followed by Virginian opossums, jackrabbits, and coyote Pusterla, 2008

Disease occurs as sporadic cases and outbreaks

Lawsonia intracellularis infections

     Clinical signs:

lethargy, weight loss, diarrhea, poor hair coat, pot belly, and edema, fever

Mild cases may be difficult to diagnose

Poor doer, daily weight gain reduced, low serum protein

Crypt cell proliferation and abscesses

Diagnosis

Fecal PCR

Serology > 1:30 – U of Minnesota

Both should be run simultaneously

Neither is highly sensitive

Abdominal US - very thick small intestine

Look for concurrent diseases

Parasites, Pneumonia

Treatment Options:

     • Macrolide

          o Azithromycin: 10 mg/kg PO, q 24 h x 5 days, then q 48 h

          o Clarithromycin: 7.5 mg/kg PO, q 12 h

          o +/- rifampin 5 mg/kg PO, q 12 h

Tetracycline group:

     • Oxytetracycline: 6 mg/kg IV, q 12-24 h

     • Doxycycline: 10 mg/kg PO, q 12 h

     • Chloramphenicol:

          o 40-50 mg/kg PO, q 6-8 h

Treatment

If the horse is very sick (not eating, lethargic, fevers):

1. Start with IV oxytetracycline for 1-3 d, then switch to doxycycline orally

2. Then continue with doxycycline for 2 weeks

Monitor creatinine closely while on tetracycline

     • Can develop renal failure

     • If not that sick (still eating, stable vitals)

     • Use doxycycline from the start

     • 10 mg/kg PO q 12 h

     • Supportive and nursing care

Lawsonia intracellularis

     • Survival is high with treatment: 82-93 %

     • Long term follow up – yearlings in KY have sold for less money, however they suffer no apparent long term effects

     • Race earnings are no different

Diarrhea in Foals

New Findings

                     Retrospective Analysis of Diarrhea in Foals

University of Florida, 2009: Frederick, 2009 JVIM

233 cases

An agent was identified in 55 % of foals

     • Rotavirus 20 %

     • Clostridium perfringens 18 %

     • Salmonella 12 %

     • Parasites 7 %

     • Clostridium difficile 5 %

     • Coronavirus 1 %

     • Cryptosporidium spp 1 %

     • Parasites (n=16):

          o Roundworms (P. equorum); n=10

          o Strongyles (n=6)

          o Giardia (n=3)

          o Trichostrongylus (n=1)

          o S. westeri (n=1)

     • 87 % survived

Survival did not vary with infectious agent

Nonsurvivors: Higher heart rate, PCV, BUN, creatinine

Blood cultures were positive in 49 % of foals

75 % of isolates were Gram negative; 25 % Gram positive

Most common

      E coli (36 %)

      Enterococcus spp (11 %)

      Salmonella cultured in 6 %

      Clostridium cultured in 3 %

      This demonstrates the importance of covering enteritic foals with systemic antibiotics

Fibrinogen: An Indicator of Osteomyelitis

     Fibrinogen and Osteomyelitis

Newquist 2009, JAVMA

Basis for study: Foals with OM of the physis or epiphysis are difficult to detect if they do not have concurrent joint involvement

These foals do not have swollen joints

Owners often believe the lameness is due to trauma

     • Compared 4 groups: Foals were 1-119 days old

          o Foals with OM (n=17)

          o Foals with septic arthritis that did not have OM (n=17)

          o Foals with pneumonia (n=20)

          o Foals with no infection (angular limb deformities) (n=22)

Fibrinogen

     • Results

          o OM was significantly associated with a fibrinogen ≥ 900 mg/dl

          o The Positive Predictive Value of fibrinogen ≥ 900 mg/dl in detecting OM was 84.2 %

          o Fibrinogen ≥ 900 was associated with not having OM

          o The Negative Predictive Value was 98.3 %

          o Fibrinogen 500-800 was significantly associated with having pneumonia or septic arthritis without OM

          o Fibrinogen 200-400 was significantly associated with lack of infection

     • Mortality:

          o 11/17 (65 %)* of foals with OM were euthanized

          o 7/17 (41 %)* of foals with septic arthritis

          o 2/20 (10 %) of foals with pneumonia

          o 0 of foals with angular limb deformities

          o No significant difference between OM and septic arthritis

Conclusions

1. Suspect OM in a lame foal with fibrinogen = 900 mg/dl

2. Fibrinogen concentration of 500-800 were associated with arthritis or pneumonia, but should not be used as a definitive diagnostic test as PPV is low

3. These rules don't apply to foals with R. equi, as fibrinogen is quite high in those foals even without OM

New Studies on Altrenogest (Regumate)

     Study 1

Effects of altrenogest treatment of mares in late pregnancy on parturition and on neonatal viability of their foals.

Exp Clin Endocrinol Diabetes. 2008 Jul;116(7):423-8. Neuhauser S, et al.

Study 1: Altrenogest

0.088 mg/kg daily altrenogest administered during late gestation (d 280) until parturition to 6 mares, with 7 control mares

Cross over design, over 2 years

Administered altrenogest until foaled

Altrenogest

     Results

          o Gestational length tended to be shorter

          o 2nd stage labor was prolonged (P < 0.05)

          o Foals in the altrenogest group had a lower RR during the first 30 min

          o Higher pH and BE

          o Significantly more neonatal problems (3/6)

Study 1: Neonatal problems

     • 2/6 altrenogest foals died :

          o 1 due to dystocia

          o 1 died 30 min post-birth, due to respiratory depression

     • 1/6 required oxygen insufflation at 30 min post-birth

     • None of control foals had these problems

Study 2: Altrenogest

Effect of altrenogest-treatment of mares in late gestation on adrenocortical function, blood count and plasma electrolytes in their foals.

Equine Vet J. 2009 Jul;41(6):572-7., Neuhauser S, et al.

Study 2: Altrenogest

Same mares as previous study

Treatment group: Double dose altrenogest from d 280 on ; Control group

Evaluated CBC, electrolytes and ACTH stimulation response

Study 2: Results

Altrenogest group foals had a lower NEUTROPHIL:LYMPHOCYTE ratio, consistent with immaturity

Plasma cortisol was higher

No differences in ACTH stim except at 15 min

Plasma potassium and calcium were lower

Conclusions

Altrenogest treatment of pregnant mares prolonged labor, did not lengthen gestation

Reduced NEUTROPHIL:LYMPHOCYTE ratio consistent with tendency for shorter gestation, and suggests immaturity or immunomodulatory effect of altrenogest

2/6 foals died and 1/6 required oxygen in the altrenogest group, associated with prolonged labor

Questions routine use of altrenogest!

Parasite Resistance

     Roundworms

Last few years have documented resistance to:

     • Ivermectin or Pyrantel pamoate

Pinworms (Oxyuris equi)

Recent paper documented resistance to ivermectin also