Monthly Update
Issue Contributors: Virginia Sinnott, DVM, DACVECC
Editor: William B. Henry DVM, DACVS  
June 2014

Antibitotic Therapy: The Brave New World

Virginia Sinnott, DVM, DACVECC 

 

Over the last decade, the emergence of antibiotic resistant pathogens along with a plateau in development of new antibiotic drugs has led to intense study of the circumstances under which bacteria develop resistance. This has led to the reversal of some of the antibiotic therapy truisms many veterinarians were taught in veterinary school. This article aims to briefly review the basic principles of antibiotic therapy and update the practioner on recent changes. 


While all veterinarians were taught in veterinary school to obtain samples for culture with every infection they treat, the cost to the client of these cultures and, occasionally, the difficulty or risk in obtaining said samples forces practioners to treat in the absence of culture information a lot of the time. Additionally, even when cultures are obtained, the results are not available at best for 48-72 hours and thus antibiotic therapy is almost always commenced in the absence of culture information. In order to avoid blind guessing (and the persuasive but often biased advice of drug representatives) a rational, step-wise approach can be used. 


The goal of antibiotic susceptibility testing is to expose a pathogen isolated from a patient to several different antibiotics. A minimum inhibitory concentration (MIC) is obtained by exposing the pathogen to decreasing concentrations of a particular antibiotic. The lowest concentration that inhibits growth of the organism is the MIC. This will be expressed in micrograms per milliliter and is a good guideline for the antibiotic blood levels required produce a treatment cure. Because this testing happens in vitro, the onus is on the clinician to interpret the results with relevant physiology of the infection site in mind. Protected spaces such as the prostate, brain and eye will likely see lower concentrations of the antibiotic and thus achieving blood levels in excess of the MIC should be the goal with infection in these locations. Thus, higher doses and more frequent intervals may be required. Additionally infections in relatively avascular areas (i.e. the airway mucosal secretions as in the case of Bordatella bronchiseptica infection) may be best treated with drugs which concentrate in neutrophils and other cells of the immune system since blood flow to this mucosal barrier is minimal while diapedesis of neutrophils to site of these infections is abundant. It is likely for this reason that azithromycin and enrofloxacin appear anecdotally to result in more treatment cures for Bordatella pneumonia than penicillins such as Clavamox despite similar in vitro sensitivities. 


Once an MIC is obtained, a dose is often recommended based on that MIC by the laboratory. Because these doses do not take into account the location of the infection and the severity of the infection in that patient, it is generally recommended to use those doses as a guideline. In order to know how best to dose an antibiotic regime, it is important to know whether the killing properties of a drug are based on the maximum concentration achieved in the patient (concentration dependent antibiotics) or based on the time that the concentration of the antibiotic remains above the MIC in the patient (time-dependent). Table 1 identifies this property for commonly used drugs. For non-life-threatening infections in otherwise healthy patients (i.e. UTI, pyoderma, incisional infections), a target of 4X the MIC is adequate for concentration dependent drugs and 50% time in the dosing interval above MIC is appropriate for time-dependent drugs. For severe infections or immune-compromised patients it is important to target more aggressive goals, with the goal to be 8-10X MIC for concentration dependent drugs and >75% of the dosing interval time above MIC for time-dependent drugs.   
 

While discussions of time above MIC and how many multipliers above MIC a drug concentration should be seem logical in an academic discussion, applying this to a clinical case can be a bit of a burdensome leap that leaves the clinician flipping between text books, formularies and package inserts. This is not realistic for modern practice and using a single reference such as the TARGET guide can help. It is available free as an iOS application for iPhone/iPad  (search "TARGET (vet)" to avoid department store aps) and free online at  http://target.naccvp.com. Hardcopies of the book are available from your Bayer representative and are often given away at the Bayer booth at conferences. Screen shots from the iPhone/iPad application will be used throughout the following example.  


A nine-month-old female Golden Retriever puppy presents for hematuria and pollakiuria. Her vitals and PE are normal. Urine is obtained via cystocentesis and sent to the lab for a culture. In house UA reveals numerous WBCs and bacteria. You also place a drop of urine sediment on a slide and allow it to air dry and stain it with dif-quick (this is a good practice with suspected UTIs to confirm whether you're dealing with rods or cocci!). Microscopy reveals rod bacteria. What antibiotic should be chosen? 


To answer this, we need only ask ourselves a few questions. The first is: What is our expectation of resistance? Has the patient been exposed to antibiotics themselves or potentially exposed to animal or human family members recently on antibiotics? If the patient has recently been on antibiotics, which drug was used? Resistance can be predicted from this information. Animals that have recently been on a penicillin or cephalosporin will carry strains of bacteria that express beta-lacatamase. Clavulanic acid is a beta-lactamase inhibitor so in a dog recently exposed to cephalexin for a skin infection, using Clavamox to treat a UTI would be reasonable. In this case the puppy had no previous antibiotic exposure so our expectation of resistance is LOW. We then ask ourselves which drug to choose by evaluating the urinary tract section of the TARGET book. Figure 1 suggests that there are several fair options. Since we know we are dealing with rods, we look only at the columns for E.coli and Proteus. To whittle down the choices, the clinican can ask themselves a few more questions. The first is, "Is this infection life threatening?" Since UTIs are uncomfortable but not life threatening, one can afford to pick a non ideal choice and thus take an escalation approach. (i.e. start with a 'first-line' drug and then reach for "bigger guns" if there is not a clinical response. 
 

 

For life-threatening infections such as pneumonia or septic peritonitis, the clinician must take the opposite approach: reach for a very "big gun" if there is an expectation of resistance, and then deescalate when cultures return. However, in this case, since there is no expectation of resistance and the infection is not life threatening, a first line choice is appropriate. First line choices include penicillins and cephalosporins. Looking again at figure 1, Both cephalexin and amoxicillin would be considered first line choices but cephalexin is considered a poor choice for E. coli while Amoxicillin is fair. This is because many E. coli isolates, even in antibiotic nave patients, are resistant to cephalexin while amoxicillin remains a good choice for E.coli in those that have very little antibiotic exposure. Notice that even for amoxicillin TARGET rates it only as "Fair". This is because the TARGET book compiles ALL cultures received by Antech, including those from animals treated with multiple antibiotics before cultures were obtained. Thus, again, the clinician needs to apply the information from this book with their patient in mind. This is a young, antibiotic nave dog with a non-life threatening infection. Amoxicillin is a fine choice. But how do we decide the dosing interval?


Another section in the application evaluates concentration curves to help determine dosing intervals. Figure 2 is the dose curve for amoxicillin in dogs. As discussed earlier, to achieve a treatment cure in a healthy patient, dosing such that 50% of the time is above the MIC is required. Since we don't yet know the exact MIC for these bacteria, we must use the maximum sensitivity MIC of 8 mcg/mL. Evaluating the curve reveals that at the 22mg/kg dose, the drug spends about 4 hours above the MIC of 8mcg/mL. To achieve 50% time above the MIC, therefore, the dosing interval must be every 8 hours. Thus prior to cultures returning the dog must be dosed TID. When the culture returns, the actual MIC can be overlaid on this curve and another dosing plan can be created. For example, if the MIC is actually 2mcg/mL, for the 22mg/kg dose about 8 hours is spent above the MIC so the interval can be reduced to twice a day.


In addition to antibiograms such as those provided by the TARGET book, additional considerations representing a change from what was taught in veterinary schools to graduates of 2008 or earlier is the "get in quickly, hit 'em hard, get out quickly" philosophy. The concept here is to use the highest dose of effective antibiotics to quickly kill a pathogen and then stop therapy before commensal flora have endured sufficient selection pressure to either acquire resistance or to skew the population towards those bacteria with innate resistance. The idea here is that a generation of bacteria can live, breed and die in 8 hours or less under ideal conditions. Therefore antibiotic courses that last even 5-7 days may be enough to kill for tens of generations of bacterial growth. Thus, uncomplicated UTIs may be treated with a week of antibiotics and severe infections such as pneumonia or pyelonephritis may only require 12-14 days of therapy whereas in the past weeks or months of therapy may have been recommended. It also means that drugs with long half-lives such as cefovecin (Convenia) may select FOR resistance to an extreme degree since they take 4-6 hours to get to tissue concentrations above the MIC (selecting for resistance while the concentration is below MIC for almost a generation of bacterial growth) and they stay in the tissues of animals below MIC for weeks after the infection is cleared while shorter half-life drugs such as Clavamox persist in the animal below MIC for only hours after the last dose. While this difference likely won't affect the current infection being treated, the NEXT infection encountered by the animal may be much more likely to be resistant in the Convenia-treated treated animal due to prolonged exposure to antibiotics by the animal's commensal flora.


When a known infection is causing morbidity in veterinary patient, antibiotics can be life saving. However, it is important to select antibiotics with care, taking into account the likelihood of resistance, the severity of the infection and co-morbidities that may impact the probability of a treatment cure. Selecting antibiotics rationally, based on what pathogens are likely to infect a particular region of infection along with obtaining cultures whenever possible will help to ensure ongoing access to and the success of antimicrobial therapy for all veterinarians.



Additional Reading and References


1) Boothe DM, Small Animal Clinical Pharmacology and Therapeutics, 2nd edition, Elsevir, St. Louis, MO, 2012. Chapter 6: Principles of Antimicrobial Therapy pp 128-188.
2) Bonagura JD, Twedt DC, Kirk's Current Veterinary Therapy XIV, Elsevir, St. Louis, MO, 2009, Chapter 266: Rational Empiric Antimicrobial Therapy, pp 1225-1229. 

 

Tech Tip

Editor's Note: This month's Tech Tip was provided by Dr. Barbara Korry, a Tufts Class of 1985, a former student of mine, and a faithful reader of our monthly newsletters. Cowesett Animal Hospital, Warwick, RI. 

 

Post- Op Confinement: Prepare Your  Pet for a Successful Recovery! 

 

A critical piece of surgical recovery is exercise restriction. The idea of cage or house confinement for long periods after surgery is daunting to most dog owners and gaining compliance is critical. Fortunately, every pet has to eat and there are numerous food dispensing toys to help make cage confinement humane and successful. We will help make you feel more comfortable in your ability to restrict your pet's activity to enable a successful recovery. We make this information available as soon as surgery is planned with this handout and sources for enrichment toys. Don't wait until the discharge appointment as preparation and coaching your pet before hand will lead to success.

 

Keeping Your Dog Happy and Content for Successful Post Op Recovery:

You have invested time and money, your dog has endured a somewhat stressful surgical experience, and your doctors and veterinary staff have made every effort to ensure a good outcome. What is needed now is a successful recovery at home. Along with medication, monitoring the surgical incision, bandage care, and keeping recheck appointments, your pet's activity restriction is critical to a successful recovery. Follow our instructions and call us if you have any questions or concerns. 

 

We understand it is difficult to confine your pet for a long period but this is essential to a successful recovery and we want to make this process as easy as possible on you and your pet. You will need to prepare a safe and appropriately sized confinement area at home. This may be a crate, a small baby gated half bathroom, pantry, or closet; child's playpen or pack-n-play; child's indoor fenced play area are some of the options, your discharge nurse will explain what is needed. Make sure there is non-slip floor covering. Inexpensive thin rubber throw rug carpet pads and similar thin rubber stair runners are available at discount stores and can be placed temporarily on hardwood or tile flooring and stairs. Make sure a soft bed is available, ideally with a washable cover. Water should be available, in a heavy tip proof bowl if your dog has an Elizabethan Collar or is wearing a bandage.


The most difficult part of exercise restriction is keeping your dog occupied while strictly confined and allowing your dog to expend energy safely when unsupervised. Fortunately, all dogs need to eat and this can provide your dog with hours of safe activity. We recommend that you feed your dog's entire daily ration from food toys. Your dog will be able to occupy themselves in a very natural and pleasant way by spending time and energy consuming their food. Figuring out access to their food via food toys also burns mental energy and will help keep your dog distracted and content with the challenge. If your dog is wearing an Elizabethan Collar to prevent licking or chewing wounds or bandages, you may remove the collar for meals if you are safely able to replace it. Some of the toys can be used even while wearing an Elizabethan Collar. Let your dog use the toys before surgery so they are familiar with them. Monitor your dog's use of the toys to ensure they use them safely and that your dog does not become frustrated with the toy prior to the surgery.

 

"Kongs" are the most useful as they will take the most time for your dog to empty. A 50 pound dog will go through 6 to 10 stuffed Kongs in a day. 

  • Start with a Kong stuffed with taste canned food to introduce this food toy to your dog.
  • Once your dog has the hang of this, you do not need to stuff the Kong with canned food, you may moisten dry kibble, stuff the Kong, then freeze it for a longer lasting treat.
  • Add a small cube of cheese, bacon or hot dog at the bottom before stuffing, place a thin layer of peanut butter inside before stuffing. It's fun for your dog to discover what's inside and work to get it out.
  • You can prestuff and freeze a day's worth of Kongs. They can be cleaned in hot soapy water, rinsed and air dried, ready to be stuffed and frozen. 

 

Kibble Dispensing Toys: There are many versions of these such as Squirrel Dude and Twist and Treat (both by Premier Pet Products) which can be adjusted to your dog's kibble size. Your dog can generally manipulate these even with an E-Collar on. Remember to familiarize your dog with these toys prior to surgery so your dog is confident and happy about eating this way.

 

Natural Bones are NOT recommended as they are hard enough to fracture teeth and damage the intestinal tract. If you think your dog may destroy and eat parts of the food dispensing toys, offer them only when supervision is possible. Even the black Ultra Kongs can be destroyed by very aggressive chewers. If you supervise your dog you can remove the toy once it is emptied.

 

Chewy.comAmazon.com and Kongcompany.com are good sources of  toys and information. We want your pet's post operative confinement to be stress free and successful; please ask if you have any concerns about how to care for your pet after surgery.  

 

 

 

  

 

In This Issue
Antibiotic Therapy: The Brave New World
Tech Tip
CT Scan Diagnostics
Business Tip
Continuing Education
Wellness Practice Educational Tips
Previous Tech Tips
Newsletter Archive
CT Scan Diagnostic 

CCVS CT Scan Hours: 

  

8:00 AM-6:00PM 7 days a week.  1-800-457-4900  

The breakdown of CT charges are as follows:

1. CT Scan, In patient $905.00 (case already hospitalized at CCVS or referred to CCVS for work up and treatment and has a CT scan)  
2. CT Scan, Additional image (if you add an additional scan site $300.00)  
3. CT Scan, Out patient $985.00 **(case sent to CCVS exclusively for a CT; this includes charges for doctor overseeing case, IV catheter, and fluids post CT).  
4. CT "Met Check" $590.00  
5. CT STAT fee, $50.00 (on top of whatever you are doing). 

These charges cover the CT, the contrast, radiologists read, rapid infuser, sevo anesthesia, and technician fee if we need to call someone in for the CT. It does not cover injectable drugs, if needed for IV anesthesia; estimated additional cost $50.00-$75.00. 

 _______________________


Cholecystitis is often difficult to diagnose via plain radiographs. Laboratory values are often very helpful. The early diagnosis of the presence or absence of peritonitis requires an astute ultrasonographer or a CT. The following two CT images demonstrate it's diagnostic value when making a pre-surgical decision.

 

See scans >>

 

Business Tip

Job Descriptions

 

An accurate job description, composed with clarity and brevity and based on the careful analysis of the tasks performed, is essential not only for the staffing process but for job evaluation and the full range of Human Resources functions. Without job description as a guideline, interviewing job candidates would be difficult, selecting the right person would be a gamble. Performance appraisals would be more guess work, evaluations for promotions would be subject to personal rather than professional considerations, selecting for training would be haphazard, and comparison structure might be invalid. Having a set of job descriptions

does not automatically solve all personnel problems. But considering how valuable and useful they are, it is surprising that many companies avoid them.

 

Job Description Manuals for Your Practice

 

The Practice Manager / Office Manager is responsible for providing every staff member with full written job description manual. These should each include: 
 

A. Mission statement of the practice.
 

B. Office policies, practice rules and levels of discipline.

 

C. General staff member duties and responsibilities. 

 

D. A specific duties list for the position and descriptions of how to perform these functions.

 

Each practice is unique, so the job descriptions in one practice can vary from those in another practice. It is vital and powerful to develop job descriptions that truly parallel the functions in your own practice. 


Developing job description manuals for every staff member is not an overnight process. But if it is addressed methodically, it can be done. Here are steps to follow as you, or your Practice Manager/Office Manager, work to develop full job descriptions for each position in your practice:

 

1. List out all of the positions within your office, including your own. 

2. Set up a binder for each position in the practice, and work out the duties of each position, ensuring that they are specific to the position. The binders each should include A-D above. 

3. As they occur to you, add other jobs or duties of jobs that should be include in your job description manuals. 

4. Present "rough" drafts of the job manual to each staff member for the respective position held. 

5. Have each staff member go through the descriptions you've created and add anything you might have missed.

 

Developing job description manuals is time consuming but worth the effort. It provides prospective employee or a new employee an understanding of what the job entails. Often check lists of tasks completed or accomplished are helpful.

It is in this context that the following guidelines are issued so that with little practice and training the companies would be able to develop and update an on going basis their job descriptions. 

 

There are many examples that can be found online. Some companies provide free samples to help get you started.   


 

 

Continuing Education Opportunities

All our lectures provide 2 hours of Continuing Education Credits. You can register online through our websites, Boston Veterinary Specialists and

Cape Cod Veterinary Specialists. A meal is provided during each lecture. Your technicians are welcome as well.

Our lecture series will begin again in the fall.

Wellness Practice Newsletters
Editors note:
Dr. Beverly Mason, Medical Director for our two general practices, writes a monthly newsletter that is emailed to our clients and printed for a handout to clients coming into the practices. They have been copied, pasted and passed around on the Internet. They are very concise, informative, and seasonally appropriate topics. Our general practice technicians find them helpful to educate their clients in the office and the email version gets very positive feedback on our Facebook and Yelp  accounts. We thought you might like to use them in your own practices and will provide them to you each month.      
     
This Quarter's Wellness Practice Newsletter: 
  
 
Previous Tech Tips 


Visit Our Newsletter Archive
Read our May newsletter article -Risk Management of Anesthesia - by visiting our newsletter archive!