2015 Merck Advanced Medicine Symposium - Audience Q&A from NAVC

2015 Merck Advanced Medicine Symposium - Audience Q&A from NAVC

Monday, January 19, 2015

The opinions expressed in these answers are those of the speakers and do not necessarily reflect the official label recommendations and point of view of the company or companies that manufacture and/or market and of the pharmaceutical agents, products, or services mentioned.

Leptospirosis — Insights Into Emergency Management


How long does Leptospira take to be inactivated by UV light and freezing temps?
Unsure – not sure specific data is available on this.

Do you routinely test for leptospirosis when renal failure appears to be more chronic?
No, not at this time. We typically only test for leptospirosis with acute presentation of illness, which is the most common type of disease presentation that we see. While chronic renal failure (CRF) may exist (due to chronic inflammation) as a secondary consequence to leptospirosis, it’s unlikely that testing would be rewarding months to years later, as the MAT (microscopic agglutination test) levels would be low (as it’s not active infection).

We see a lot of leptospirosis in Detroit but most cases present hypothermic and anuric.  Is this common?
Ultimately, it depends on how late in the stage of the disease that the patient presents. If your pet owners have financial limitations, they may not bring their pets in until end-stage disease, when the patient is already severely azotemic and oliguric or anuric. Ideally, immediate and prompt recognition of clinical signs warrants veterinary attention immediately, as the prognosis is better while the patient is polyuric (versus anuric).

Can a carrier bitch spread disease to pups?
Evidence does show that leptospires can be transmitted via placental transfer, so while rare, yes, it is possible. 

How often is hypokalemia the only lab abnormality in early leptospirosis cases due to Na/K ATPase inhibition?
Clinically, I don’t see this. Most diseases don’t typically present with only one lab abnormality. While we can see hypokalemia with leptospirosis, I certainly wouldn’t use this as the “only” lab abnormality observed. 

What about additional carriers? Rabbits? Deer? Elk? Campground exposure?
According to the World Health Organization, “virtually all mammalian species can harbor leptospires in their kidneys and act as source of infection to human beings and other animals. However, cattle, buffaloes, horses, sheep, goat, pigs, dogs and rodents are common reservoirs of leptospires. Rodents were the first recognized carriers of leptospirosis. They are the only major animal species that can shed leptospires throughout their lifespan without clinical manifestations, i.e., prolonged carrier state. They are incriminated as a primary source of infection to human beings. Although serovars Ichterohaemorrhagiae, Copenhageni, Grippotyphosa and Ballum have been often associated with rodents, other serovars have also been isolated. Pigs and cattle can excrete very large amounts of leptospires in the carrier state (i.e., chronic leptospiral colonization of the renal tubules) and can be an important source of human infection. http://www.searo.who.int/about/administration_structure/cds/CDS_leptospirosis-Fact_Sheet.pdf 

During the winter or cold spells, is the leptospirosis inactivation temporary or permanent?
Unsure – not sure specific data is available on this.

How long must the cold last to be permanent?
Unsure – not sure specific data is available on this.

In the Michigan study that showed 10% to 20% carriers, I assume that was based on seropositive results.  Is that really enough to say that the animal is a carrier without a urine culture as a confirmatory test?
The paper we are discussing is Stokes JE, Kaneene JB, Schall WD, et al. Prevalence of serum antibodies against six Leptospira serovars in healthy dogs. J Am Vet Med Assoc. 2007;230(11):1657-1664. In this study, they assessed vaccinated and unvaccinated dogs (prior to the release of the 4-serovar vaccine) and used microscopic agglutination tests (MAT) to determine antibody titers. What they found was that among healthy dogs from the lower peninsula of Michigan, >20% had antibodies against leptospiral serovars that were “incriminated as causing clinical canine leptospirosis.” Lastly, urine cultures aren’t typically done to confirm leptospirosis. Leptospirosis cultures themselves can be done, but are very costly and take weeks to months to confirm.

What diagnostic confirmatory test do you recommend?
Personally, I have only used the MAT thus far. I haven’t had the opportunity to use the IDEXX ELISA or PCR, so don’t have any experience with it personally, but I do like how you can potentially get faster in-house results. That said, these tests likely have the same limitations as the MAT. Early onset of disease (where there hasn’t been an opportunity for the body to mound an antibody response) and the use of antibiotics can result in a false-negative test. 

So what are the actual odds that a patient with elevated liver enzymes with no azotemia has leptospirosis?
Based on literature assessed by the ACVIM Consensus Statement, the likelihood of just seeing a patient with hepatic injury without acute kidney injury (AKI) is rarer but possible. Eighty to 90% of leptospirosis cases just show azotemia as the primary organ undergoing dysfunction; of those that have elevated liver enzymes, the majority are concurrently azotemic.

What is the accuracy of the IDEXX in-house test?
As mentioned before, I have only personally used the MAT test at this time. I’ve never used the IDEXX ELISA or PCR so I don’t have any experience with it personally, but I do like how you can potentially get faster in-house results. That said, these tests likely have the same limitations as the MAT. Early onset of disease (where there hasn’t been an opportunity for the body to mound an antibody response) and the use of antibiotics can result in a false-negative test. When in doubt, I would consult directly with IEXX to evaluate their sensitivity and specificity.

Why do you like MAT testing over PCR?
I prefer PCR, as it is more accurate and faster. However, as a veterinary specialist, I see a different patient population that are referrals. Most veterinarians have already started antibiotics prior to transferring the case to me, and therefore I know the results will be skewed (e.g., I can’t test for PCR as the patient has already been started on antibiotics for several days)! For this reason, before you start a patient on antibiotics (when you suspect it has leptospirosis), please, please, please make sure to save pre-treatment blood work! 

What is the treatment if anuric?
I’d have to refer you to a detailed acute kidney injury resource as this answer can take pages and pages! The best option: hemodialysis or continuous renal replacement therapy (CRRT) at a local veterinary school or specialty center. If this is not available, I typically recommend intravenous (IV) fluid therapy with careful management of ins and outs, monitoring urine output, weighing the patient four to six times/day, and use of drugs to increase urine output or renal blood flow—e.g., low dose dopamine, furosemide, and mannitol constant rate infusions (CRIs) as needed.

What about penicillin and doxycycline together to prevent shedding?
Based on the ACVIM consensus statement, only one is warranted. Traditionally, I prefer a parenteral (e.g., intravenous) antibiotic first while the patient is hospitalized (e.g., amoxicillin/clavulanic acid) and discharge the patients on doxycycline (or start it once they are no longer anorexic or vomiting).

How do you suggest that hospitalized patients be walked to urinate or defecate to avoid contamination?
One consideration is to place an indwelling urinary catheter and to mix the urine with an appropriate disinfectant when disposing of the urine or urinary collection system (e.g., accelerated hydrogen peroxide, iodine-based, etc.). Do NOT put this in the urinary collection system while it is connected to the patient. I don’t worry too much about “contamination” as once we have started appropriate antibiotic therapy, the risk of shedding of leptospires after 48 to 72 hours is generally considered to be minimal.

Can you discuss antibiotic therapy for exposed dogs with no clinical signs?
Personally, I look at the risk of the household and exposure to other animals, children, etc. I would discuss the importance of hygiene and preventative care (e.g., such as vaccines) with the pet owners. Remember, even healthy animals can carry and shed leptospires (as seen with the Michigan State study from 2007 by Stokes et al.). I would encourage appropriate hygiene and vaccination as I am awaiting test results in asymptomatic patients; I would not just routinely put all “at risk” patients that are asymptomatic on doxycycline. Vaccination is safer than routine, random antibiotic administration to all. If, however, the pet owners are at risk (e.g., immunosuppressed, young children, poor hygiene), I would discuss their risk and consider antibiotics based on appropriate client communication and risk factors.

What are your thoughts on IV doxycycline while in the hospital? 
This is fine to do, but is cost prohibitive at our hospital. If it’s not expensive, you can certainly use it. If you can manage the patient’s nausea and vomiting (e.g., maropitant, ondansetron), then you can start enteral antibiotics relatively quickly. It is really clinician’s preference. I prefer to use a less expensive injectable penicillin initially. 

Please review the cleaning instructions again.
In general, appropriate protective gear should be used when handling patients suspected of leptospirosis (e.g., any AKI patient). This includes gloves, eye shields (if handling urine), and appropriate hygiene (e.g., washing hands thoroughly after handling the patient or any bodily fluids). The use of appropriate disinfectants should be used (e.g., accelerated hydrogen peroxide, iodine-based disinfectants).

Thoughts about 2-way versus 4-way vaccination?            
It’s a no brainer for me to use the 4-way instead of the 2-way. The serovars within the 2-way vaccine are less commonly seen nowadays (hence, why we don’t commonly see that young, icteric, acutely ill dog anymore). Broad coverage is important to help maximize protection. More importantly, use a vaccine that helps decrease shedding of leptospires in urine to help prevent zoonotic risk and exposure and that protects against disease and mortality.

If patient is showing signs of disseminated intravascular coagulation (DIC) do you treat with transfusions and heparin or is treating the underlying disease usually sufficient?
We don't use heparin to treat DIC anymore, because most of the time we are catching it in the hypocoagulable (versus the hypercoagulable) stage. In general, removal of the underlying nidus is more important. If the patient is clinically coagulopathic or the prothrombin time/partial thromboplastin time (PT/PTT) are significantly prolonged in the face of thrombocytopenia, I would discuss the use of fresh frozen plasma (FFP) with the owner (at 10‒20 mL/kg, IV, or until the coagulation panel is normalized).

How do you decontaminate the environment?
The appropriate disinfectants should be used (e.g., accelerated hydrogen peroxide, iodine-based disinfectants). There isn’t really an effective way of decontaminating the environment (e.g., soil); I would discuss better preventative care with the owner instead. As shedding of organisms can persist (e.g., leptospuria) for weeks to months, prevention is imperative. Despite the good prognosis for leptospirosis, aggressive preventative care is warranted in dogs. This will help minimize zoonotic risk to pet owners and veterinary professionals; help minimize the chronic carrier state in dogs (which can result in further spread); prevent costly hospitalization; and minimize the risk of chronic injury (chronic renal failure). A leptospirosis prevention package should be initiated with the following:

  • Environmental changes: This should be initiated to include rodent control; appropriate fencing; and landscaping changes to remove stagnant/standing water.
  • Annual vaccination: The decision to vaccinate should be based on an endemic area, exposure of the dog, and risk factors (e.g., access to streams/stagnant water or urbanized wildlife). Ideally, vaccination with a 4-way leptospirosis strain should be utilized. Vaccination is important to help prevent/aid in the prevention of shedding to reduce infection of other animals and possible human exposure.

What should the target packed cell volume (PCV) and total solids (TS) be for sighthounds on fluids? For others?
While I commonly recommend using a goal of achieving PCV/TS of 35% and 5 g/dL, this may not be possible with certain breeds or in certain environments. As sighthounds are traditionally polycythemic (e.g., greyhounds, 55%), I would use TS as a better indicator. Likewise, at elevation (e.g., Colorado), patients are typically polycythemic due to hypoxemia. When in doubt, assess the patient appropriately for assessment of hydration with multiple factors (e.g., weight gain, hemodilution, isosthenuria, urine volume, urine color, physical examination findings).

Non-healing Corneal Ulcers in Dogs — Battling the Boxer and Beyond

Shelby Reinstein, DVM, MS, DACVO 

(Q&A still to come)

Canine Otitis Externa —  My Favorite Topical and Systemic Treatments

Wayne Rosenkrantz, DVM, DACVD

Do certain dog foods show up more commonly as the cause of ear problems?
There are no specific dog foods that create ear problems more than others. Any protein, meat, or cereal grain can create a food-induced reaction that could manifest as an otitis. To approach a food-induced otitis, do a complete dietary history and avoid previously fed proteins in the form of a novel protein diet or use a hydrolyzed diet (e.g., Hills’ Prescription Diet z/d® Ultra, Royal Canin Hydrolyzed Protein (HP), or Purina Veterinary Diets® HA Hydrolyzed™). Feed the diet exclusively for at least 8 weeks and if the pet is improved than re-challenge and see if symptoms reoccur.

Clients frequently say dogs are allergic to grains. Do grains ever play a role in food allergy or is that just a marketing ploy by certain food companies?
Yes, grains can create food allergies but so do meat proteins. Although there is currently a “Grain Fee Diet Craze” in the human and veterinary dietary world, grain-free diets are not necessarily the solution to performing a good dietary trial in dogs. For example, if a pet is on a lamb and rice diet and the pet is allergic to lamb and the owner switches to a lamb but grain-free diet the problem will still exist. Always base your elimination diet on avoiding both previously fed meat and cereal grain proteins.

How many days after discontinuing topical medications and flushing do you perform a culture?
Previously it was thought to wait 48 to 72 hours after discontinuing topical medication or flushing before a culture is performed but now if cytology supports active infection (i.e., bacteria present with inflammatory cells) I will commonly take the culture regardless of the timing of recent medications.

How do you explain to clients why you want to pursue atopy or food allergy when only one ear is affected?
Although allergies can create bilateral otitis it is not uncommon for one ear to be more severely affected than the other and you can just see one ear affected as well. This may reflect the development of infection due to more severe self-trauma to one particular ear and some dogs do prefer to scratch at one ear over the other. As infections reoccur they create damage to the ear canal lining making subsequent infections in the same ear more common.

When performing sample collection and ear cleaning, do you perform the procedure or have a technician do it?
Personally I prefer to take deeper ear samples or saline flush obtained samples myself. A technician can take routine swabs. A technician can perform ear cleaning, particularly when just bulb flushing is performed. Some technicians are also very good with infant feeding tube flushing through a hand-held surgical head otoscope. I would recommend, however, that a veterinarian perform deeper cleaning and flushing especially when the tympanum is ruptured or when the video-otoscope is utilized. 

How do you feel about long-acting treatments?
Long-acting treatments can have value in patients where clients cannot medicate ears daily. There are both lanolin anhydrous and aqueous based products, with aqueous based products now available in thermally active gels. The latter is my preference as they are more easily removed or flushed from the ear during the treatment process.

How often should owners clean their dog’s ears at home?
The frequency of ear cleaning at home is case dependent. Some cases may benefit from the daily or every other day (EOD) application of mild cleansers and disinfectants. In other situations, weekly use of cleansers/disinfectants or cerumenolytics may be adequate. Owners should always be instructed on how to use products prior to dispensing.

Do you use EnteDerm™ ointment for ears?
I don’t use this product as it contains older active ingredients (nystatin, neomycin, thiostrepton, and triamcinolone) that are not as commonly effective as the newer generation of ear products.

What do you use for cat ears with Malassezia?
I have had success using many of the canine products, such as Posatex® and Mometamax® (Merck Animal Health). I will also make compound a mixture of miconazole/dexamethasone in a saline base in some cases. Special care needs to be taken in cats with ruptured tympanums, as they are more sensitive to ototoxic reactions then dogs. If a ruptured tympanum is detected I will sometime avoid topical products and treat with systemic fluconazole, itraconazole, or terbinafine.

Do you sedate or use a general anesthetic in a painful ear or treat first for 3 days and then recheck to flush?
In painful ears I will commonly sedate or use general anesthesia. General anesthesia is needed in cases where tympanums are ruptured and middle ear flushing is needed. Often you will not know what or how to treat an otitis case until a complete exam is performed. Many cases need follow-up sedation or anesthesia for proper evaluation of therapy and further cleaning and flushing.

Do you ever use NSAIDs or systemic steroids with topical steroids (especially potent topical)?
Yes I commonly use topical and oral steroids together in ears with moderate to severe proliferative changes. I am less concerned about the combined effects when used short-term. Some of the newer steroids, e.g., mometasone and hydrocortisone aceponate, maintain high local tissue concentrations but have less concerns about systemic absorption. I don’t find NSAIDs have a lot of value in reducing proliferative otitis changes but they can be used to help with pain and can be used with the safer topical steroids that do not have systemic absorption.

What about Vetericyn®?
Vetericyn (Innovasyn) can be used to disinfect and clean ears. Its active ingredient is hypochlorous acid. I suspect it could be of value to use in mild otitis cases but I have not personally used it in ears. Through a study performed at one of my practices it was not found to be overly impressive in the control of canine pyoderma but was found to be safe and non-irritating.

Have you seen dogs with severe otitis media or otitis interna become septic?
I cannot say I have seen a widespread septicemia from a case of otitis media or interna, but I have seen dogs develop severe vestibular disease and generalized debilitation. I have also seen the reverse scenario where a septic dog could develop otitis interna and media. Any case of otitis media or interna should be treated with systemic therapy based on cytology and culture and sensitivity.

Respiratory Disease in Dogs and Cats — If They Can't Breathe Nothing Else Matters

Carol Reinero, DVM, PhD, DACVIM (SAIM)

What do you recommend to safely sedate cats/dogs in respiratory distress?
There are many, many options for sedation which depend on co-morbid conditions (e.g., heart disease), patient age, prior response to sedatives (if known), etc.  I personally will generally start off with one of the opioids, such as butorphanol or buprenorphine; in dogs, I might also give a low dose of acepromazine. 

Both fluoroquinolones and doxycycline are contraindicated in young animals.  What are you using in puppies and kittens?
Fluoroquinolones and doxycycline are relatively, not absolutely, contraindicated in young animals. If I were treating a life-threatening pneumonia and I thought a fluoroquinolone was appropriate and didn’t have other reasonable options, I wouldn’t hesitate to use it.  Animals have to live to be able to develop long-term side effects, after all. Having said that, tetracyclines would not be an optimal choice for a life-threatening pneumonia because they are static antibiotics. Important principles to follow are:

  • Select an antibiotic based on culture and sensitivity whenever possible
  • Use a broad spectrum antibiotic until culture results are available
  • Use a cidal, not static antibiotic
  • Use a parenteral (not oral) antibiotic, at least initially for severe pneumonia

Empiric choices for a severe life-threatening pneumonia would include a beta-lactam with a fluoroquinolone (or if well hydrated without existing renal disease, aminoglycoside) or monotherapy with meropenem/imipenem. For less severe pneumonias, combination therapy with a beta-lactam (potentiated ampicillin, second- or third-generation cephalosporin) with a fluoroquinolone or monotherapy with trimethoprim sulfonamide or with amoxicillin/clavulanate would be reasonable.

Where did you get leaches quickly?
Interestingly, these are available online. Because I don’t want to recommend one company over another, I’d just recommend doing a search for “buy medical leeches.” 

What are the breathing patterns for diaphragmatic hernias?
The breathing patterns for diaphragmatic hernias will vary a bit depending on a number of factors. If the diaphragmatic hernia was caused by trauma, then pain and co-morbid conditions (flail chest, pulmonary contusions, pneumothorax or hemothorax) can make the breathing look rapid and shallow, or a focal paradoxical breathing pattern or mixed inspiratory/expiratory effort, or predominantly inspiratory. A chronic diaphragmatic hernia may resemble the breathing pattern of pleural cavity disorders—e.g., rapid and shallow, predominantly inspiratory or a more diffuse paradoxical breathing pattern. 

What is the difference between stridor and stertor?
Stertor is caused by airway obstruction in the nasal passages and nasopharynx and the inspiratory noise created sounds like a snore. Dogs and cats are not obligate nasal breathers, so as long as they open their mouth (and don’t have other lower airway obstruction), the noise and the airflow obstruction will resolve.  Stridor is a high-pitched inspiratory noise caused by airflow obstruction from the level of the larynx to the extrathoracic trachea. Severe stridor can indicate a life-threatening obstruction.


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