COMPANION ANIMAL MEDICINE

Antimicrobial Use and Antimicrobial Resistance in Companion Animal Medicine

Veterinarians, as well as other medical practitioners, have long relied on antimicrobial drugs in the treatment of infectious diseases. As antibiotic resistance becomes an issue of increasing concern, it is important for health professionals to be more selective in their use of these drugs. This module gives an overview of current antibiotic use in small animal practice, of factors leading to the development of antimicrobial drug resistance, and of clinical approaches to enhance the prudent use of antibiotics in veterinary practice.

LEARNING OUTCOMES

This submodule aims to describe the use of antimicrobial drugs in small animal practice, as well as how they may be used more judiciously. By the end of the module, you will be able to:

• Identify the frequency of antimicrobial use in small animal practice.
• Summarize the classes and types of antimicrobials commonly used in small animal practice.
• Discuss the clinical applications where antimicrobial use may be reduced.
• Describe the association between antimicrobial use and the occurrence of antimicrobial resistance.
• Demonstrate understanding of the use of bacterial culture with antimicrobial susceptibility testing as an important diagnostic tool to support antimicrobial therapy.

SECTIONS

• Case Study Scenario
• Antimicrobial Use in Small Animal Practice
• Antimicrobial Use and Antimicrobial Resistance in Companion Animal Medicine
• Improving Antimicrobial Use
• Case Study Wrap-Up
• Summary
• References

Veterinarian Dr. Colleen Murphy with Spaniel

Two dogs sleeping together on comfy chair

Sue Harrington, DVM, is a small-animal clinician at the Kelva School of Veterinary Medicine. Don Bosch is a journalist with a local newspaper who has heard that antimicrobial use by veterinarians may contribute to the occurrence of antimicrobial resistance in humans, and this has led certain individuals and organizations to recommend a ban on antimicrobial use in animals. Don also has a dog that was recently treated with antimicrobials for a bladder infection and has an appreciation for the importance of these medications in treating his own pet. Don wants to interview Sue to write an article for his paper investigating antimicrobial use in small animals and the potential impact of antimicrobial use in small animals on the occurrence of antimicrobial resistance.

Classes and Types of Antimicrobials Used in Small Animal Practice

Table 1: The most frequently prescribed antimicrobials or antimicrobial classes to dogs and cats.

Source: Murphy, 2010
*All other antimicrobials or antimicrobial classes were prescribed at frequency of 5 percent or less.

Table 2: The most frequently prescribed antimicrobials or antimicrobial classes to dogs and cats for diseases associated with the skin and urinary system.

Source: Murphy, 2010
*All other antimicrobials or antimicrobial classes were prescribed at a frequency of less than 3 percent unless otherwise noted.

Table 3: The most frequently prescribed antimicrobials to dogs and cats for diseases associated with the gastrointestinal system.

Source: Murphy, 2010
*All other antimicrobials or antimicrobial classes were prescribed at a frequency of less than 10 percent unless otherwise noted.

Table 4: The most frequently prescribed antimicrobials to dogs and cats for diseases associated with the respiratory system.

Source: Murphy, 2010
*All other antimicrobials or antimicrobial classes were prescribed at a frequency of less than 10 percent unless otherwise noted.

KNOWLEDGE CHECK

Recently, associations were observed between cephalexin use (a first-generation cephalosporin) in dogs and antimicrobial resistance to a ß-lactam inhibitor combination (amoxicillin-clavulanic acid), third-generation cephalosporins (ceftriaxone, cefoxitin) and cephamycins (ceftiofur). Dogs that were treated with cephalexin had a higher risk of resistance to these antimicrobials, three to eight times higher, when compared to dogs not treated with antimicrobials. The development of antimicrobial resistance was faster in dogs treated with cephalexin than in dogs not treated with antimicrobials. These are extremely important findings since cephalexin is the most commonly prescribed antimicrobial in dogs and these antimicrobials are critically important in the treatment of human infections. It suggests that the use of cephalexin may provide significant selection pressure for the occurrence of antimicrobial resistance.

Legend: Cephalexin-Treated Dogs vs. Dogs Untreated with Antimicrobials Interpretation At any given time, the percentage of fecal E. coli isolates that were susceptible to the above antimicrobials was significantly lower in dogs treated with cephalexin (red line) than in dogs that were not treated with antimicrobials (black line). In other words, antimicrobial-resistant fecal E. coli isolates from dogs treated with cephalexin were isolated more frequently and at a faster rate than in dogs that were not treated with antimicrobials.

A comparison of the times to loss of susceptibility in fecal E. coli isolates in dogs treated with cephalexin compared to dogs untreated with antimicrobials. In all three step graphs, the cephalexin line remained the exact same while the untreated line differed from graph to graph. Cephalexin took a step drop to 0.85 at 7 days, 0.75 at 14 days, 0.70 at 28 days, and 0.60 at 90 days, remaining constant throughout till the end at day 180. In the Susceptibility to Ceftiofur graph, the untreated group remained at 1% of isolates susceptibility to TIO, until day 90 when it lowered to 0.80, where it remained till day 180. In the Susceptibility to Amoxicillin-clavulanic Acid graph, the untreated group immediately took a step down to 0.95% of isolates susceptible to AMC at day 7, 0.90 at day 14, and 0.80 at day 90 where it remained until day 180. In the Susceptibility to Ceftriaxone graph, the untreated group remained constant at 1% of isolated susceptibility to CRO throughout the entire 180 day period.

Note:

1. Cephalexin treatment was started 0−12 hours after the Day 0 sample was collected and duration of cephalexin treatment ranged from 5 to 14 days.
2. The study population were dogs (n=33 cephalexin treated, n=8 untreated) from primary care (nonreferral) small animal veterinary hospitals (n=21) in southern Ontario and were treated with cephalexin for a disease condition that was diagnosed and managed by the attending veterinarian.

Recently, a study looked at antimicrobial use by veterinarians and observed some areas where it could be improved. These include eliminating the common use of antimicrobials in elective, uncomplicated sterilization surgeries (e.g., spaying, castration) and reducing antimicrobial use in other clean surgical procedures. Antimicrobial use could likely be reduced for diseases such as feline lower urinary tract disease, feline upper respiratory tract disease, and canine infectious tracheobronchitis (2). In one population of cats, antimicrobial use could possibly be reduced by up to 25 percent if the common use of antimicrobials to treat feline upper respiratory tract disease and feline lower urinary tract disease was discontinued (2).

Using antimicrobials only when appropriate is important, as are antimicrobial selection and application. There is some evidence to suggest that fluoroquinolones and cefovecin may be overused, particularly in cats (2) (Table 1)—and veterinarians need to ensure that the dosing of antimicrobials is appropriate. Dosing antimicrobials below the recommended dose could lead to treatment failure, thereby possibly requiring the use of additional antimicrobials. This may provide additional selection pressure for the occurrence of antimicrobial resistance. As well, dosing antimicrobials above the recommended dose ranges could lead to adverse events like toxicity.

Appropriate use of antimicrobials requires knowledge of many factors. Veterinarians synthesize this information with other clinical and diagnostic data to make the best choice for a positive clinical outcome.

KNOWLEDGE CHECK

Table 5: The frequency of antimicrobial use in specific conditions diagnosed and managed by the attending veterinarian (3).

Source: Murphy, 2010

Table 6: The dosing of antimicrobials by small animal veterinarians when compared to a readily available pocket-type formulary designed as a practical aid to veterinarians (20).

KNOWLEDGE CHECK

KNOWLEDGE CHECK

• A small number of antimicrobial drugs compose the most frequently prescribed antibiotics in veterinary medicine, and many of these are also prescribed in people.
• Antimicrobial drug use can lead to resistance to the drug prescribed, and even other antibiotics.
• Prudent, judicious use of antibiotics includes consideration of when to use them, length of therapy, and specific drug selection.
• There are many situations in small animal practice in which antibiotic use is unnecessary and can be eliminated.
• Bacterial culture and sensitivity are very useful guides for judicious antimicrobial drug use.

1. DANMAP. 2007. Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark. Accessed May 2010.
2. Murphy, CP. 2010. Antimicrobial resistance, antimicrobial use and infection control in community small animal veterinary hospitals in southern Ontario. (A thesis presented to the Faculty of Graduate Studies of the University of Guelph in partial fulfillment of requirements for the degree of Doctor of Philosophy.) University of Guelph, Guelph Ontario Canada. 
3. Weese, JS. 2006. Investigation of antimicrobial use and the impact of antimicrobial use guidelines in a small animal veterinary teaching hospital: 1995−2004.  Journal of the American Veterinary Medical Association. 228:553−8.
4. Watson, AD, and JE Maddison. 2001. Systemic antibacterial drug use in dogs in Australia. Australian Veterinary Journal. 79:740−6.
5. Odensvik, K, K Grave, and C Greko. 2001. Antibacterial drugs prescribed for dogs and cats in Sweden and Norway 1990-1998. Acta Veterinaria Scandinavica. 42:189−98.
6. Prescott, JF, WJ Hanna, R Reid-Smith, et al. 2002. Antimicrobial drug use and resistance in dogs. Canadian Veterinary Journal. 43:107−16.
7. Rantala, M, K Holso, A Lillas, et al. 2004. Survey of condition-based prescribing of antimicrobial drugs for dogs at a veterinary teaching hospital. Veterinary Record. 155:259−62.
8. Holso, K, M Rantala, A Lillas, et al. 2005. Prescribing antimicrobial agents for dogs and cats via university pharmacies in Finland—patterns and quality of information. Acta Veterinaria Scandinavica. 46:87−93.
9. Murphy, CP, RJ Reid-Smith, JF Prescott, et al. 2009. Occurrence of antimicrobial resistance in selected bacteria in healthy dogs and cats presented to private veterinary clinics in Southern Ontario. Canadian Veterinary Journal. 50:1047−53.
10. Ogeer-Gyles, J, KA Mathews, W Sears, et al. 2006. Development of antimicrobial drug resistance in rectal Escherichia coli isolates from dogs hospitalized in an intensive care unit. Journal of the American Veterinary Medical Association. 229:694−9.
11. Medleau, L, RE Long, J Brown, et al. 1986. Frequency and antimicrobial susceptibility of Staphylococcus species isolated from canine pyodermas. American Journal of Veterinary Research. 47:229−31.
12. Rantala, M, E Lahti, J Kuhalampil, et al. 2004. Antimicrobial resistance in Staphylococcus spp., Escherichia coli and Enterococcus spp. in dogs given antibiotics for chronic dermatological disorders, compared with non-treated control dogs. Acta Veterinaria Scandinavica. 45:37−45.
13. Faires, MC. 2008. Evaluation of methicillin-resistant Staphylococcus aureus and characterization of S. pseudintermedius in dogs and cats. (A thesis presented to the Faculty of Graduate Studies of the University of Guelph in partial fulfillment of requirements for the degree of Master of Science) University of Guelph, Guelph Ontario Canada. 
14. Trott, DJ, Filippich LJ, Bensink JC, et al. 2004. Canine model for investigating the impact of oral enrofloxacin on commensal coliforms and colonization with multidrug-resistant Escherichia coli. Journal of Medical Microbiology. 53: 439−43.
15. Canadian Veterinary Medical Association. 2000. Guidelines on the prudent use of antimicrobial drugs in animals. Accessed May 2010.
16. American Association of Feline Practitioners. 2001. Basic guidelines of judicious therapeutic use of antimicrobials in cats. Accessed May 2010. 
17. American Veterinary Medical Association. 2006. American association of feline practitioners/American animal hospital association basic guidelines of judicious therapeutic use of antimicrobials. Accessed May 2010.
18. American Association of Feline Practitioners/American Animal Hospital Association. 2006. Basic guidelines of judicious therapeutic use of antimicrobials. Accessed May 2010.
19. Morley, PS, Apley MD, Besser TE, et al. 2005. Antimicrobial drug use in veterinary medicine. Journal of Veterinary Internal Medicine, 19:617−29.
20. Allen, DG, JK Pringle, DA Smith, K Pasloske, and K Dayger. 2005. Handbook of Veterinary Drugs. Baltimore, Maryland. Lippincott Williams and Wilkins.

Salmonella Typhimurium Associated with Rodents

Outbreak of Multidrug-Resistant Salmonella Typhimurium Associated with Rodents Purchased at Retail Pet Stores

This submodule provides a case study involving antibiotic use in pocket pets. The module will present an outbreak scenario and highlight the prevalence of antimicrobial use in the pocket pet industry, as well as provide insight into proper antimicrobial use and stewardship in veterinary medicine.

LEARNING OUTCOMES

This submodule aims discuss the outbreak of multidrug-resistant items purchased at retail pet stores. By the end of the module, you will be able to:

• Identify how antibiotics are frequently used in the pocket pet industry and how the use of antibiotics in pocket pets may select for antimicrobial resistance.
• Discuss how animal and human health may both be impacted by antimicrobial resistance. 
• Describe how veterinarians in agriculture departments work with veterinarians and other health professionals in local, state, and federal health departments to investigate and control zoonotic disease.
• Summarize how the use of antibiotics may select for the dissemination of gene cassettes conveying resistance to multiple antibiotics.

SECTIONS

• Index Case
• Necropsy
• PFGE
• Pocket Pet Industry
• Summary
• References

Based on actual events as reported in the Morbidity and Mortality Weekly Report (MMWR), May 6, 2005 Volume 54 Number (17); pages 429−433.

KNOWLEDGE CHECK

You have recently been hired as the public health veterinarian at the Minnesota Department of Health. It’s only your second week on the job, and you are assigned the following case:

A five-year-old boy named Sam was ill for 14 days with severe diarrhea, stomach cramps, fever, and intermittent vomiting. Occasionally the diarrhea was bloody. When Sam’s mother, Lucy, took him to the doctor, the doctor treated Sam with oral fluids and gave Lucy instructions to give Sam plenty of fluids. The doctor also told her to call back if there was any change in Sam’s condition. Upon returning home from the clinic, Lucy found that Sam’s pet mouse (Melvin) had died. The mouse had been suffering from diarrhea and lethargy since they bought it at a pet store a few days before. Lucy wondered if Sam’s illness and Melvin’s illness were related. She contacted Sam’s pediatrician and the pet store where she bought Melvin. Staff at both locations told her that it sounded like Sam’s illness and Melvin’s illness were a coincidence.

With Lucy’s encouragement, the pediatrician agreed to submit Sam’s stool specimen to a clinical laboratory. A couple days later, the clinical laboratory reported that the stool specimen yielded Salmonella. The clinical laboratory forwarded the Salmonella isolate to the Minnesota State Public Health Laboratory and reported the case to the Minnesota Department of Health. The Minnesota Department of Health attempts to interview all people with a laboratory-confirmed Salmonella infection. As part of this routine surveillance, you contact Sam’s mom to inquire about possible sources of infection. During the course of your conversation, Lucy wonders if Sam’s illness could be related to the recent death of Sam’s pet mouse. You share your knowledge of Salmonella epidemiology with Sam’s mother:

Nontyphoidal Salmonella includes common serotypes such as: S. Typhimurium, S. Enteritidis, and S. Newport. Most mammals, birds, and reptiles are the reservoirs for nontyphoidal Salmonella. This means that most infections can ultimately be traced back to animals. The immediate source for human infections is usually food, but people can also become infected by direct ingestion of animal or human feces, usually by contaminating their hands and then putting their fingers in their mouths. Human salmonellosis usually causes self-limiting gastroenteritis, but can sometimes cause severe infections and even death, especially if the infection becomes systemic.

Initial Question

Interview

You learn that the Minnesota State Public Health Laboratory has indeed received the isolate from the clinical laboratory, serotyped the isolate as S. Typhimurium, and found the isolate to be resistant to ampicillin, chloramphenicol, streptomycin, sulfizoxazole, and tetracycline. The Minnesota State Public Health Laboratory will also do PFGE analysis. The PFGE results will be available at the end of the week. What other questions would you like to ask Lucy?

Necropsy of a pet mouse showing fecal staining and an enlarged spleen.

Hamster lungs with gross lesions of hemorrhagic, suppurative pneumonitis.
Photo: Arno Wünschmann, DVM, University of Minnesota

These lungs show clear evidence of a raging septicemia

The next day, you learn that the Salmonella isolate from Melvin (the mouse) is serotype Typhimurium—the same as the Salmonella isolate from Sam. However, you know that Typhimurium is a very common serotype and therefore this is not strong evidence linking the boy’s infection with that of his mouse. The antibiotic resistance pattern can also be used to determine if strains may be related. You note that the antibiotic susceptibility results are the same for both S. Typhimurium isolates. The laboratory results on Melvin isolate show resistance to ampicillin, chloramphenicol, streptomycin, sulfizoxazole, and tetracycline (R-type ACSSuT). This was the same resistance pattern in the boy’s isolate, and therefore provides some evidence that links the infections in the boy and his pet mouse.

You are also awaiting a call from the laboratory regarding the PFGE results from Sam’s isolate so that you can compare the PFGE pattern to the isolate from Melvin. The PFGE “fingerprint” is used to determine if the isolates’ DNA are related. Question: What would you do while you are waiting for the PFGE pattern from Melvin’s isolate?

The PFGE information on Sam’s isolate is now available. The PFGE pattern matches an isolate from an ill person in Kentucky and another from South Carolina; both of the patients report recent exposure to rodents. This PFGE pattern was uncommon, representing 23 of 17,737 isolates in the S. Typhimurium database. These three human cases might represent a common source outbreak.

Pulsed-Field Gel Electrophoresis Patterns of Salmonella Typhimurium Isolates with 3 sources (MN distributor hamster, MN human, a

You still do not know if the isolate from Melvin (the mouse) is related to the isolate from Sam (the child). The antibiotic resistance pattern is the same, but you do not know yet if there is a PFGE match between Sam and Melvin’s Salmonella isolates.

Even more interestingly, the CDC PulseNet search finds a matching PFGE pattern from a Salmonella outbreak that occurred this last month in another state. You call the state health department in this state and are surprised to learn that the outbreak was among workers at a pet store. Furthermore, some of the pet rodents at the pet store had been sick, and specimens from sick rodents had yielded Salmonella Typhimurium with the same antibiotic resistance pattern and PFGE pattern as the workers and as the isolate from Sam. Now you’re getting somewhere!

You call the public health veterinarian who investigated the outbreak at the pet store and who submitted the specimens from the rodents. The veterinarian tells you that the pet store obtained the rodents from a large distributor who had experienced a major die-off of rodents after receiving a shipment of 780 mice from Iowa. Diarrhea was present in the majority of ill mice. Distribution of the animals to pet stores was halted, but not before 243 of the original 780 mice had been sent to various pet stores where they were sold to the public. Of the remaining mice, 60 percent had died by the end of the month and the rest were humanely euthanized.

Source Identification

The PFGE results are in! You find that the PFGE pattern from Melvin’s Salmonella is indistinguishable from the pattern from Sam’s isolate. Furthermore, this PFGE pattern turns out to be rare in the PulseNet database, and so it is therefore likely that Melvin and Sam’s cases are related.

Control Measures

It is now time to move backward on the timeline. Where would a mouse get a Salmonella infection that is resistant to multiple antibiotics? What is your next step? Should you search to see if the other human cases with this particular PFGE pattern had rodent exposure prior to getting sick? This type of a study would be a good idea. Maybe there are more than three human cases involved. However, at this point you have gone beyond the bounds of your state and need to be working with other state health departments and with the CDC. The PulseNet search tells your investigative team that there have been 23 human cases of S. Typhimurium with this PFGE pattern since December of the previous year. CDC facilitates a conference call among state health officials from states that have cases with the key PFGE pattern. It is agreed that all cases would be interviewed. Of those interviewed, 13 of the 22 interviewed had pocket pet (small exotic animal) exposure, all within eight days of onset of symptoms. An additional two cases of the 22 interviewed contracted salmonellosis as a result of secondary exposure—infection from exposure to other people who originally got the infection from a pet rodent.

Additional Cases

The remaining seven (32 percent) had no recorded rodent exposure. This means that 68% of the matching human cases of S. Typhimurium in the database could be epidemiologically linked to the outbreak in the pocket pet industry.

The chart above shows that there were 28 cases of human S. Typhimurium isolates with outbreak PFGE patterns, of which 22 were interviewed. Of the 22 interviewed cases, 13 had pet rodent exposure (59%), 2 were secondary cases (9%), and 7 had no reported rodent exposure (32%).

You find that the type of pocket pet exposure was varied. Seven cases were linked to mice or rats used for feeding snakes, four cases were linked to pet mice or rats, and two more cases were linked to pet hamsters. The human cases are mapped out in order to see if there is a geographic cluster.

Number of rodent-associated human cases by state, reporting from 15 cases. There was one case each in Minnesota, Michigan, New Jersey, North Carolina, and Georgia. There were two cases each in Illinois, Missouri, Kentucky, Pennsylvania, and South Carolina. Once you map it, you see that this is a multifocal event, and you look for ways to explain how this same organism caused illness in many different places across the Eastern United States. You are also quite impressed that this outbreak now involves many people across the country, not just one child in Minnesota.

In collaboration with CDC, you work with your state department of agriculture to determine the origin of the rodents, to learn more about the pocket pet industry and to learn how animals are raised and distributed. You also want to know how this particular Salmonella came to be resistant to so many antibiotics.

Let’s see what you know about the pocket pet industry.

Rodent Antibiotics

Information on use of antimicrobials was obtained from five rodent breeders/distributors. Routine use of antimicrobials was documented in four facilities in which they were used for prevention of nonspecific rodent enteritis. Delivery of antimicrobial agents in drinking water occurred at weaning, before transport, and/or on arrival at the pet distributor. One pet distributor exclusively used rodent feed containing tetracycline.

An Arkansas small rodent breeder was routinely using both spectinomycin and another unknown antibiotic for animals that appeared stressed or had “wet tail” (nonspecific enteritis). The Iowa distributor linked to the original human outbreak administered spectinomycin for three days to all rodents upon arrival at the facilities; it was also given for three days prior to shipment. The Minnesota distributor did not use antimicrobials prophylactically, and unlike all the other surveyed breeders and distributors, worked closely with a veterinarian. The Georgia distributor fed modified pig feed containing tetracycline to all of their animals.

Salmonella & Antibiotics

Antimicrobial agents are often ineffective at alleviating clinical symptoms of salmonellosis. Antibiotics also can prolong shedding. The dissemination of multidrug-resistant Salmonella in pet rodents might have been facilitated by the use of prophylactic antimicrobials within the pocket-pet (e.g., hamsters, mice, and rats) animal industry. This use might have contributed to disease transmission in colonized animals and increased shedding of Salmonella. As such, the use of antibiotics in raising these animals may have increased transmission among animals, from animals to their human caretakers, and from animals to the people who purchased these animals as pets. Appropriate animal husbandry and hygiene practices, such as those used for the production of antibiotic-free laboratory rodents, could eliminate the need for nontherapeutic antimicrobials to prevent disease in rodents.

Public Awareness

Phage typing (another way to characterize Salmonella) of the S. Typhimurium isolates identified the isolates as Definitive Type 120 (DT120). S. Typhimurium DT120 is often multidrug-resistant and may possess antibiotic-resistance gene cassettes also found in S. Typhimurium DT104. Selective pressure for any one of these five antibiotics in the cassette selects for the entire cassette of resistance genes.

KNOWLEDGE CHECK

Antibiotic Recap

You take stock of the current information on antibiotic use in the rodents:

1. It is not known whether the infectious agent(s) involved in “nonspecific rodent enteritis” are bacterial, viral, or environmental. Diet and stress could be contributing factors with this syndrome.
2. The administration of antimicrobials for a Salmonella infection may lead to prolonged shedding of organisms, which would tend to increase transmission to both other rodents and to people.
3. Every time an antimicrobial agent is administered, there is a selective pressure for the survival of resistant strains. It would be helpful if outbreaks of nonspecific rodent enteritis were cultured and antimicrobial susceptibility tests run on targeted pathogens before administration of an antimicrobial agent.
4. Salmonella infections may be controlled but not always eliminated when antibiotics are administered to infected rodents. Customers who purchase animals do not continue to administer these antibiotics; therefore, the animal may become clinically ill soon after being purchased. A general rule with Salmonella is that clinically ill animals tend to shed in greater numbers than do animals with subclinical infections.

Traceback Diagram

The investigative team of agriculture and health department veterinarians provide the following information regarding the breeders, the distributors, and the particular animals that were owned by the human cases.

The tracebacks of all infected human cases led to the original outbreak occurring from three distributors: GA, AR, and IA. Multiple small rodent breeders supplied the GA and AR distributors, whereas an AR breeder specifically supplied the AR and IA distributors. That IA distributor shipped rodents to an IL distributor that supplied a MI distributor, which distributed to MI pet stores and led to one MI human case. It also shipped to a MN distributor that supplied MN pet stores and led to one MN human case. The AR distributor shipped to a pet store in IL-1 that led to human cases IL-1 and IL-2, a pet store in NJ that led to one NJ human case, a pet store in SC-2 that led to one human case called SC-2, and a pet store in MO that led to one human case and a second human case due to infection from the first human case. The GA distributor shipped to a pet store in KY-1 that led to one human case called KY-1, a pet store in KY-2 that led to one human case called KY-2, a pet store in GA-1 that led to one human case, a pet store in SC-1 that led to one human case called SC-1, and a pet store in GA-2 that led to one human case and a second human case due to infection from the first human case. There was also a NC distributor that had no contact with breeders related to the other distributor, but that distributed to a pet store in NC and led to one human case.

Veterinarians from the Minnesota Department of Agriculture were able to visit two of the implicated distributors. The Minnesota distributor had thoroughly cleaned and disinfected the facilities since the outbreak. The environmental samples were negative for Salmonella. At the Georgia facilities, environmental swabs yielded isolates that were indistinguishable from each other and closely related to the PFGE results from Sam, Melvin, and the Minnesota distributor. All of the isolates showed the same antibiotic-resistant cassette (susceptibility profile).

The facilities had no standard cleaning or sanitation procedures. The managers claimed that it is hard to convince employees to thoroughly clean so many cages, primarily due to time constraints. However, you recall that laboratory animals destined for research laboratories can be maintained free of Salmonella without the need for antibiotic treatments.

You also find that at least one retail pet store has a corporate policy stating that their pocket pet providers cannot use antimicrobials in their animals. Despite this policy, they still purchased animals from several producers that routinely used antimicrobials. This particular chain reportedly told customers that the rodents they purchased were likely to have diarrhea when taken home, and that the customers should use spectinomycin to treat the animals at home.

KNOWLEDGE CHECK

• There is clear evidence that pocket pets can serve as vehicles for transmission of Salmonella.
• Antimicrobial use in the pocket-pet industry is common. Antibiotic usage contributes to the selective pressure for the development and spread of multidrug-resistant organisms. Close contact between pocket pets and people—especially children that are generally more susceptible to enteric diseases and less likely to wash their hands—increases the risk that pocket pets will transmit their infections to people. Subsequent to this outbreak investigation, pocket pets must be considered a potential source for multidrug-resistant Salmonella infections.
• Producers/breeders of pocket pets should use diagnostic testing for nonspecific enteritis rather than using antibiotics just in case bacterial agents may be involved.
• Good husbandry and sanitation practices could help prevent transmission and eliminate the need for prophylactic antimicrobial treatment within the pet rodent industry.
• The prophylactic use of antimicrobials most likely contributed to multidrug-resistant Salmonella spread among the pet rodent breeding populations. Antimicrobials may prolong and mask the clinical signs of Salmonella infections and cause extended shedding of a higher number of organisms. This could result in an increased dissemination of the infection through a facility.
• Salmonella is a common enteric pathogen that is easily spread among most animals species, including humans, rodents, primates, birds, reptiles, and ruminants. It can readily develop resistance, and therefore inappropriate and unnecessary use of antimicrobials in raising animals is discouraged.

CDC: Outbreak of Multidrug-Resistant Salmonella Typhimurium Associated with Rodents Purchased at Retail Pet Stores

New England Journal of Medicine: Multidrug-Resistant Salmonella enterica Serotype Typhimurium Associated with Pet Rodents

CANINE PYODERMA

Antibiotic Use for Canine Pyoderma

Many diseases have the potential to predispose dogs to the development of superficial pyoderma. In order to appropriately and successfully use antibiotics in the treatment of canine superficial pyoderma, it is important for veterinarians to be familiar with these potentially underlying diseases. This module describes these diseases, as well as sound approaches for judiciously prescribing antimicrobial drugs to treat canine superficial pyoderma, in order to minimize the development of antibiotic resistance.

LEARNING OUTCOMES

This submodule aims to introduce appropriate treatment for canine superficial pyoderma, including the judicious use of antibiotics. By the end of the module, you will be able to:

• Discuss how antibiotics are frequently used in treatment of canine pyoderma.
• List the factors to be considered when choosing antibiotic therapy.
• Identify the underlying causes of canine pyoderma and possible diagnostic and treatment options.
• Describe the importance of bacterial culture and susceptibility testing, and effective communication with the client.
• Demonstrate understanding of how animal and human health each may be affected by antibiotic resistance.

SECTIONS

• Introduction
• Diagnostic Tests
• Choosing an Antibiotic
• Clinical Response to Treatment
• Lessons Learned
• Summary
• References

You are a recent graduate from veterinary school and have just started as a new associate in a rural veterinary hospital. You are the only doctor at the clinic today for this mixed animal practice—everyone else is out on farm calls. A long-time client of the practice (for both small and large animals) brings in her family’s resident farm dog, Junior, who is also her kids’ best friend and sleeps with the kids every night. You try to find Junior’s chart but are unsuccessful, as many charts have been misplaced during the clinic’s transition to electronic-based records.

Initial Case Presentation:
Junior is a four-year-old, neutered male Golden Retriever.

History:
Junior presents to your animal hospital with a history of “itching” that has been present for at least the past year-and-a-half, according to his owner Joyce. Recently, the kids have been complaining that Junior’s scratching has been making it difficult for them to fall asleep. On a scale from 1−10 (with 1 being mild pruritus and 10 being severe) Joyce grades Junior’s pruritus as a 7. The pruritus is year-round (nonseasonal), and since the kids started complaining Joyce has noticed that Junior has scabs and bumps on his skin. This was Joyce’s main concern today.

Differential Diagnoses

Based upon the history provided by Junior’s owner, you believe that the bumps and scabs are signs of a secondary superficial pyoderma, and you begin to formulate a list of differential diagnoses in your mind that could predispose a dog to develop superficial pyoderma.

KNOWLEDGE CHECK

Why do certain diseases/disorders predispose to infection?
1. Pruritic disorders
When a dog has itchy skin disorders such as allergic or parasitic diseases, the scratching, chewing, or biting will mechanically remove the stratum corneum, which is a very important skin barrier. Moreover, the process of chewing will result in skin overgrowth of Staphylococcus intermedius (which lives normally in the mouth, nares, and anal ring of dogs).

2. Hormonal disorders
Hypothyroidism and hyperadrenocorticism (Cushing’s disease) are not pruritic diseases but are often complicated by secondary skin infections that can become pruritic. The lack of thyroid hormone, which is very important to maintain the normal metabolism of almost all cells in the body, will result in abnormal function of the skin immune defense. In Cushing’s disease the state of chronic excess cortisol secretion will lead to skin atrophy (the “brick wall” becomes very thin), and to suppression of the normal immune defense.

3. Keratinization disorders
One of the main functions of the skin is to produce keratin and special lipids to form the stratum corneum, which is composed of completely keratinized epithelial cells (also known as corneocytes) and an intercellular lipid lamellae. A brick wall is a perfect analogy for the stratum corneum, where the brick is the corneocyte and the mortar is the lipid lamellae. Moreover, a brick wall is a barrier against the entrance of invaders, just as the stratum corneum is a barrier against microbial, chemical, and physical insults. Keratinization disorders can be primary or secondary and are associated with abnormalities of the stratum corneum. Therefore, animals with keratinization disorders are very prone to develop secondary skin infections. Keratinization disorders are nonpruritic disorders, but pruritus often follows from the secondary infections. Examples of keratinization disorders include acne, canine primary seborrhea, zinc responsive dermatosis, and sebaceous adenitis. 

What can predispose a dog to develop superficial pyoderma?
Several diseases/disorders can predispose animals to developing superficial pyoderma. This predisposition is often due to conditions that impair defense mechanisms of the skin. The skin has innate defense mechanisms which help defend against chemical, physical, and microbial insults. Some examples of these defense mechanisms include the stratum corneum, cells that resemble a brick wall; fatty acids that have a bacteriostatic effect; defensins, which are small antimicrobial peptides; and resident bacterial flora, which will compete with the pathogenic flora for space and nutrients. The skin normally defends itself well; therefore, it is smart to always consider a bacterial skin infection secondary until it is proven otherwise.

Physical Examination

You perform a thorough physical examination on Junior and find the following:

• Body Condition Score (BCS) = 7/9
• Erythema in inguinal region
• Excoriation on one pinna, but ear canals are clean with mild erythema and intact tympanic membranes
• Pustules, papules, and yellowish crusts on the ventral abdomen 
• Epidermal collarettes on the ventral abdomen/flanks with mild alopecia 
• Mild interdigital erythema localized to all four feet
• All other body systems are within normal limits

Your physical examination findings suggest that Junior has a superficial pyoderma, as you suspected, which is characterized by the presence of pustules, papules, yellowish crusts, and epidermal collarettes. Combining Junior’s clinical presentation (signs of superficial pyoderma and erythema localized to ventral abdomen, flanks, and paws) and the history provided by his owner, you begin to narrow your mental list of differential diagnoses. You would like to ask Joyce a few more questions in order to narrow in on a possible underlying cause for Junior’s skin condition.

What other questions would you like to ask Joyce?

To help narrow your list of differentials even further, you would like to run some tests.

Laboratory Findings

Your in-house tests reveal no mites on skin scraping and a large number of degenerative neutrophils with intracellular cocci on the impression smear (see picture below).

KNOWLEDGE CHECK

Other possible findings on skin scraping/impression smear:

	Adult Demodex canis mite
	Sarcoptic scabie var. canis mite
	Adult Sarcoptic scabie var. canis mite and egg
	Malassezia spp. fungi
	Cheyletiella spp. mite with characteristic hook-arrow
	Mixed bacteria of rods and cocci

Initial Treatment

Because of Junior’s pyoderma and significant pruritus, you tell Joyce that you would like to start him on some antimicrobial therapy (both topical and oral) because secondary pyoderma typically aggravates the pruritus associated with an allergic condition. You may also consider starting with topical antimicrobial alone for the first two weeks, prior to starting oral antibiotic, as some cases of more localized or less severe pyoderma will respond to topical therapy alone. Topical antimicrobial options include chlorhexidine-based shampoos for weekly baths and chlorhexidine spray or mousses for daily use on affected skin areas.

KNOWLEDGE CHECK

In order for an antibiotic to be effective at killing the bacteria present, it needs to reach adequate concentrations in the body organ of interest after oral dosing. Moreover, the antibiotic has to be efficacious against the organisms causing the infection and safe for the patient. The table below provides examples of some antibiotics that are good empiric choices for treating staphylococcal skin infections in dogs. You should remember two important things:

• The most common bacterium that causes skin infection in dogs is Staphylococcus intermedius, and most strains of this bacterium produce β-lactamase, which will inhibit the efficacy of many β-lactam antibiotics.
• The antibiotics that cannot be used empirically to treat a staphylococcus infection include: penicillins, ampicillin, and amoxicillin, which are all β-lactam antibiotics. Some synthetic potentiated penicillins (e.g., amoxicillin-clavulanic acid) and cephalosporins are β-lactamase resistant and may be used to treat infections empirically. In addition, you should not use tetracycline or streptomycin to treat staphylococcus infections empirically because most strains will be resistant to them.

The length of treatment of any episode of infection is also important to consider. Not treating an infection for an adequate period of time will result in nonresolution (despite possible clinical improvement) or frequent recurrence (or what may appear to be true recurrence but is actually nonresolution of initial infection). The rule of thumb regarding the treatment duration of superficial pyoderma is to treat each infection episode for seven days beyond the resolution of clinical signs. Total treatment duration may take up to six weeks. If Junior has been treated for this condition previously with antibiotics and the skin lesions never completely resolved, it is possible that the duration of treatment was inadequate or the bacteria may have developed resistance. The length of treatment may also affect owner compliance—you must emphasize the importance to your client of administering the antibiotic strictly as directed and completing antibiotic therapy as prescribed until the recheck appointment.

Although rare, adverse effects of antibiotic therapy can occur. Most oral antibiotics will cause nausea and sometimes vomiting and diarrhea. Owners should be aware of these potential side effects and should notify you if one or more occur. Clearly explain to the owner any possible side effects that may occur due to the medication you prescribe and possible ways to lessen these effects (e.g., for some antibiotics giving them with food or probiotics may help).

As mentioned above, with pyoderma it is very important that you recheck the patient to ensure that the skin lesions have completely resolved. This will help you decide whether or not at this subsequent visit you are going to perform a culture and susceptibility test. For example, if Junior had received antibiotic therapy multiple times in the past and the correct dose was used, you should perform culture and susceptibility testing.

You explain to the owner that you will need to recheck Junior in two to three weeks. Let the owner know that if there is less than a 50% reduction in lesions or new lesions are still appearing at the time of the recheck, you will perform culture and susceptibility testing before choosing another antibiotic empirically. If you elected to start topical therapy alone first, at the recheck visit you may elect to continue topical therapy if the infection is improving or start oral antibiotic if not improving.

Table 7: International Society for Companion Animal Infectious Diseases guidelines for systemic antimicrobial therapy* for canine superficial bacterial folliculitis (1)

*Therapy must be administered for at least three weeks or until seven days beyond resolution of lesions. Use of the agents listed should take account of restrictions on their use, drug interactions, and safety for the patient.

Table 8: Systemic antibiotics NOT recommended as empiric choice for Staphylococcal pyodermas

Keeping all of these considerations in mind, you choose to begin antibiotic therapy for Junior with oral cephalexin at 22−30 mg/kg twice daily and topical Chlorhexiderm shampoo (4% chlorhexidine). You send home enough antibiotic to cover Junior to his recheck appointment (scheduled for three weeks from now) plus one week. You advise Joyce not to delay the recheck appointment, in order to avoid an unnecessarily long course of antibiotics.

Junior’s owner (Joyce) had to cancel his recheck appointment and could not come back until four weeks after the original appointment. At this recheck you notice minimal improvement in Junior’s skin lesions even though he is still getting the antibiotic twice a day, every day, as recommended. Joyce reports the pruritus is still present and she now remembers that Junior had taken cephalexin before (a couple different times) for similar skin bumps, but only for two weeks at a time. The skin lesions always improved but Joyce’s kids reminded her that the bumps never completely resolved. Had you known this history at the initial appointment, you would have recommended culture and susceptibility testing at that time, to ensure appropriate antibiotic treatment this time around.

KNOWLEDGE CHECK

Culture and Susceptibility Testing

When you explain to Joyce that you are concerned about resistant bacteria she becomes very concerned. She explains that her aunt recently had a horrible skin infection that wouldn’t respond to antibiotic therapy, and she thinks it was a staph infection. She asks if Junior could have the same infection and if he could give it to her kids.

You try to calm Joyce down by explaining what you know about staphylococcal skin infections. Just as Staphylococcus intermedius is a common inhabitant of healthy dog skin and mucosa but can cause canine pyoderma, Staphylococcus aureus is a common inhabitant of healthy human skin and mucosa but can also cause infections. However, you explain to Joyce that while you cannot say for sure, her aunt most likely had an S. aureus infection whereas Junior most likely has an S. intermedius infection. You also explain that it has been reported that S. intermedius can occasionally be transmitted from dogs to humans, and although S. aureus is primarily found in people, animals can also become colonized or infected by this bacterium. You tell Joyce that the culture and susceptibility test will tell you what type of Staphylococcus species is causing Junior’s pyoderma and what antibiotic will best treat it. You stress that in the meantime, the family can avoid transfer of bacteria/bacterial infection by practicing good hygiene with frequent hand washing (especially those in close contact with Junior) and by giving and applying prescribed medications as directed.

Joyce agrees to the culture and susceptibility test, so you repeat cytology, which confirms a bacterial infection and inflammation. You rupture a pustule on Junior’s belly with a 25-gauge needle, collect the small amount of pus with a swab (see previous sidebar – 05a), and submit it for culture and susceptibility. Before Joyce and Junior leave your clinic, you provide Joyce with an informational handout about the common antibiotic resistant staph infection seen in people (Methicillin-resistant Staphylococcus aureus or MRSA) and how to help protect people who have pets with MRSA—Links Below.

More Information:

• General Information about MRSA in the Community
• For more information about pet owners visit University of Minnesota Center for Animal Health and Food Safety

Sensitivity Results and Summary

Four days later you receive Junior’s culture and susceptibility results.

Test Results: Numerous mixed flora indigenous to this site; Scant staphylococcus aureus-methicillin resistant

Susceptibility Results:

When you receive Junior’s culture and susceptibility results (left), you are a little surprised but not shocked. MRSA seems to be recognized more and more in animals (as well as humans). You are glad that you sent home the MRSA information sheet with Junior’s owner at his last appointment and hope that they have been following the guidelines it contains. You realize that you will have to spend more time discussing this situation with Joyce in order to dispel possible fears she may have due to her aunt’s recent infection.

You plan to discuss MRSA with Joyce when you next speak to her, and you do a little research to refresh your knowledge about MRSA. You find that Staphylococcus aureus infections, including MRSA, include superficial skin and ear infections as well as more serious infections such as surgical wound infections, bloodstream infections, pneumonia, osteomyelitis and endocarditis. Established risk factors for MRSA infections in humans include current or recent hospitalization or surgery, residence in a long-term care facility, dialysis, and indwelling percutaneous medical devices and catheters. Symptomatic and asymptomatic MRSA in pet animals has also been documented, so you realize that you need to educate your client about potential risks, precautions, and hand hygiene. You plan to reiterate the prevention points in the MRSA handout to Joyce when you call her and emphasize the importance of continued follow up appointments. Before you call Joyce, however, you must decide what antibiotic therapy you want to use to treat Junior’s resistant pyoderma.

Based upon the C&S results, what antibiotic do you want to start Junior on? Select an appropriate answer for each antibiotic listed below:

KNOWLEDGE CHECK

• Bacteria may be resistant—you should consider performing culture and susceptibility testing sooner rather than later.
• You need to choose the appropriate antibiotic and use the correct dose regimen.
• You should treat for the appropriate period of time and recheck (sooner rather than later!).
• Client communication and education is crucial to obtain compliance and treatment success.
• The symptoms may be ongoing if the underlying causes are not identified and pursued.

• Several diseases or disorders predispose dogs to the development of superficial pyoderma, via different mechanisms.
• Appropriate diagnostic tests should be conducted to rule out these underlying conditions.
• While empirical selection of antibiotics is appropriate and effective in some cases, some antibiotics should not be used empirically, and culture and sensitivity testing is indicated in other cases.
• Clear and comprehensive client education is very important in the successful treatment of canine superficial pyoderma.

Written by: Jamie Umber DVM, Sheila Torres DVM, PhD, and Jeff Bender DVM, MS

Reviewed by: Sandra Koch, DVM, MS, DACVD

1. Hillier, A, DH Lloyd, JS Weese, et al. 2014. Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases). Veterinary Dermatology. 25(3):163.

FELINE URINARY TRACT DISEASE

Antibiotic Use in Feline Urinary Tract Disease

Judicious use of antimicrobials encompasses the dual goals of eradicating of infection while avoiding development of antimicrobial resistance.

Judicious use of antimicrobials encompasses:

• Using an antibiotic only when indicated.
• Choosing a cost-effective agent which provides appropriate antibiotic coverage for the diagnosis that is suspected.
• Prescribing the optimal dose and duration of the antibiotic

You have recently graduated from veterinary school and are an associate in a small animal practice. Your boss, having a new employee, has decided to take a vacation, leaving you in charge of the clinic while she is away. Jan, a new client who has recently moved to the area, has made an appointment to see you today.

Initial case presentation:

Nemo is a four-year-old, neutered male, domestic long-haired cat.

History: Nemo comes to your animal hospital with a two-day history of inappropriate urination outside of his litter box, and pollakiuria (frequent urination). The owner is very concerned because although she loves Nemo, she simply cannot tolerate a cat that urinates in inappropriate locations and not in the litter box.

SECTIONS

• Questions to Ask
• Physical Examination
• Sample Collection and Sample Problem
• Culture
• Feline Idiopathic Cystitis
• Summary
• References

Every student of journalism knows the basics for getting the facts. These principles were memorialized by Rudyard Kipling in his tale of "The Elephant's Child" which opens with:

I keep six honest serving-men:
(They taught me all I knew)
Their names are What and Why and When
and How and Where and Who.

In reference to cats with lower urinary tract signs, the three most important questions veterinarians need to ask to differentiate medical from behavioral inappropriate urination are urine volume, urine frequency and urine locations (what, how and where; table).

Because you know how important a good history is, you decide to ask Jan some more questions. Which question would you ask?

KNOWLEDGE CHECK

Physical examination reveals the following:

• Body Condition Score—7/9 (overweight).
• Weight 13.0 lbs (5.9 kgs).
• Rectal temperature is 102.5° F.
• The urinary bladder is small and when palpated Nemo postures and urinates approximately 3mls of urine on the examination table.
• All other body systems are within normal limits.

Narrowing Your Differentials

Your physical examination has provided clues to Nemo’s problems. Based on your history and clinical exam findings, how would you localize the disease?

Now that we have localized the disease to the lower urinary tract, which diagnostic tests should you perform?

Diagnostic Tests

Selection of diagnostic tests is not an exact science, but knowing the prevalence of diseases associated with clinical signs and patient signalment can help to select tests likely to have the highest diagnostic utility. For example, the CBC is a good screening test for overall health, but it provides minimal diagnostic utility as to the cause of the lower urinary tract signs. Even for cats with bacterial infection of the bladder, CBC results are often unremarkable; however, acute kidney infection is usually associated with leukocytosis. A serum chemistry profile will evaluate internal organ function, but even if abnormal results are detected, they are rarely helpful in explaining lower urinary tract signs. Although both are very good screening tests, Nemo’s problem appears to be localized to the lower urinary tract. To rule out the most common diseases, Jan’s money would be best directed toward a urinalysis and X-rays.

You explain to Jan that a urinalysis and radiographs will be the most important tests to help identify what is the underlying source of Nemo’s problem. The urinalysis will identify the presence of blood, crystals, abnormal cells, or infection. The abdominal radiographs will look for urinary calculi.

Jan agrees and consents to the urinalysis and abdominal radiographs.

KNOWLEDGE CHECK

An important tool for any patient showing signs of a urinary tract disease is the urinalysis. This requires the collection of a urine sample. There are several methods for collecting urine, and each has advantages and disadvantages. For patients you suspect have a urinary tract infection, you should place a high priority on a technique that will obtain a sample with the least amount of contamination that can be used for bacterial culture.

Cystocentesis

Removal of urine from the bladder via cystocentesis guided by a firm hold on the bladder.

Cystocentesis following palpation

Cystocentesis (cat ultrasound) following palpation and ultrasound-guided cystcentesis stabilization of bladder.

Ultrasound-guided cystocentesis stabilization of bladder

KNOWLEDGE CHECK

Sample Problems

Nemo decides that he does not want to cooperate with your collection of a urine sample. After several attempts to isolate his urinary bladder, you come to the conclusion that his bladder is too small and Nemo appears too uncomfortable. When you explain to Jan that you can not get a sample, she responds, “Just give me some antibiotics, then, so I can start giving them to Nemo in the meantime.”

Getting a Sample

You explain to Jan that although Nemo could have an infection, there are many other diseases that cause similar signs. Without knowing what the problems is, prescribing a medication such as an antibiotic could lead to antibiotic resistance and would also just be wasting her money. You tell Jan that you will be able to give Nemo some pain medication to keep him comfortable until a urine sample can be obtained.

Jan agrees to leave Nemo with you so you can get the needed samples. You give Nemo buprenorphine (Buprenex , 0.01mg/kg, SC) to help keep him comfortable. Later that day you successfully obtain a urine sample via an ultrasound-guided cystocentesis. During the urine collection, you note that although the urinary bladder appeared thickened, you did not notice any unusual masses or growths.

Results

Feline Lateral radiograph

Urinalysis

KNOWLEDGE CHECK

Mineral composition of 11,174 feline uroliths evaluated at the MUC, 2007.

*Analyzed by polarizing light microscopy or infrared spectroscopy.

**Uroliths did not contain at least 70% of mineral type listed; no nucleus or shell detected.

***Uroliths contained an identifiable nucleus and one or more surrounding layers of a different mineral type.

What To Do Next?

Based on your physical examination, patient history, and laboratory findings, you are unsure whether Nemo may have a bladder infection or some other underlying inflammatory process such as idiopathic Feline Lower Urinary Tract Disease (iFLUTD).

You tell Jan that the lab findings indicate either a urinary tract infection or inflammation. You think that the best way to proceed is to culture the urine and then prescribe an antibiotic if warranted based on culture results.

She responds by saying, “If you’re going to give me an antibiotic anyway, why waste my money and culture the urine? Besides, I'll be lucky if I can even get Nemo to take pills.”

KNOWLEDGE CHECK

Diagnostic vs. Therapeutic Urine Cultures

What are diagnostic urine cultures?

• Quantitative urine cultures before initiating antibiotic therapy is considered to be the gold standard for diagnosis of bacterial urinary tract infections (UTI).
• Diagnostic urine cultures provide accurate identification of specific bacterial species and aid in the selection of antibiotics. It also facilitates differentiation of recurrent UTIs caused by relapses from recurrent UTIs caused by reinfections.
• If a patient is currently being treated with an antibiotic, it should be discontinued for three to five days before diagnostic urine culture to minimize inhibition of bacterial growth.

What are therapeutic urine cultures?

• Culture of urine at strategic times during antibiotic therapy (“therapeutic urine cultures”) is an effective method of assessing therapy. Therapeutic cultures are essential for determining why a patient may not be responding to treatment.
• For patients with a high risk of morbidity and mortality (e.g., prostatitis, pyelonephritis, immunosuppression, urinary tract obstruction), evaluation of urine culture and urinalysis three to five days after initiating therapy allows for verification of antibiotic effectiveness before the development of irreversible organ damage or systemic spread of disease. The same strategy should be considered when prescribing antibiotics with a high risk of toxicity.

Benefits of therapeutic urine cultures:

1. Timely test of antibiotic efficacy
2. Verification of proper antibiotic administration
3. Early detection of bacterial resistance to antibiotics
4. Timely detection of persistent infections
5. Provision of justification for early discontinuation of potentially toxic antibiotics

Suggested times to culture urine to diagnose and monitor persistent urinary tract infections:

I. Diagnostic

• Before administration of therapy

II. Therapeutic

• 3 to 5 days after initiating therapy
• Any time clinical signs of laboratory abnormalities recur during therapy
• Before discontinuing therapy

III. Surveillance

• 7 to 14 days after stopping therapy
• 1 to 2 months after stopping therapy
• 3 to 6 months after stopping therapy
• Any time clinical signs recur

Initial Treatment

Jan reluctantly agrees to the urine culture saying, “Well, I guess if that’s what we need to do. No offense doc, but I really don’t want to be in here for the same problem in another month!”

Initial Treatment:

While waiting for urine culture results, you prescribe an analgesic (Buprenorphine, 0.01mg/kg q 8 to 12 hours between the cheek and gums) to keep Nemo comfortable. You tell Jan that the urine culture and sensitivity should be available in two days. If Nemo stops producing urine or continues to be uncomfortable, she needs to bring him back in immediately! You explain that a blockage in the urinary tract is a life-threatening situation.

Empiric antibiotic therapy is the use of an appropriate antibiotic when the exact etiologic agent is unknown.

When is it okay to use empiric antibiotic therapy?

Empiric antibiotic therapy should only be started when depriving a patient of therapy (while waiting for urine culture and sensitivity results) may result in harm or worsening of the condition.

• When the agent is not known, selection of the antibiotic should be based on the most likely agent to be found in that location. 
• Antibiotic selection needs to be selected not only on the suspected agent, but also on the ability to obtain a therapeutic concentration at the site of infection. For most tissues, plasma concentration can be used to predict tissue concentration. However, areas with poor blood supply can be problematic (abscesses). Lipid membranes can also affect drug profusion (CNS, eye, prostate).

Guidelines for Empiric Antibiotic Therapy

Empiric Antibiotic Therapy, World Small Animal Veterinary Association World Congress Proceedings, 2009. Helio Autran de Morais, DVM, PhD, AVCIM; Oregon State University

Culture Results

Culture results: Two days after sending Nemo home with analgesic therapy, you receive the results of the urine culture.

Culture, Urine

Test results: No growth after 48 hours.

Diagnoses of LUTD in Cats (No. [%])

in reports of three studies (1980−1997; 1982-1985; 1993−1995)

NA = Not applicable.

*More than one cause of LUTD was identified in some cats.

Feline idiopathic cystitis (FIC)—also called interstitial cystitis—is the most common diagnosis in cats with lower urinary tract signs. FIC is a diagnosis of exclusion, meaning that the term FIC is used if all diagnostics fail to confirm the presence of another disease such as urinary stones. Cats suffering from FIC make frequent attempts to urinate, probably as a result of bladder discomfort, and often are found to have blood in their urine. Signs of lower urinary tract disease in cats with nonobstructive FIC often resolve spontaneously within a couple of weeks regardless of treatment. Most treatments attempt to prevent subsequent recurrence of signs.

Stress seems to be an important factor in the development of FIC in cats. Possible sources of stress in a cat's life may include environmental changes, changes in food schedule, and changes in the number of animals in the household. Environmental enrichment and modification can reduce stress and decrease the severity and frequency of FIC episodes.

Cornell Feline Health Center: Feline Lower Urinary Tract Disease

Feline Idiopathic Cystitis
By Wendy C. Brooks, DVM, DABVP

Veterinary Partner: Idiopathic Cystitis in Cats

KNOWLEDGE CHECK

Treatment Plan

You explain to Jan your treatment plan for Nemo which includes Buprenorphine for pain relief, a diet change to canned food to increase Nemo’s water consumption, and using a product like Feliway while he adjusts to the move and the new house. You also recommend that she place an additional litter box in a different area of the house so Nemo can choose which location he is more comfortable with. Then you remind her cats like clean litter boxes so she should clean all the boxes out at least once if not twice per day.

Jan says, “I don’t understand. Why am I not getting any antibiotics? Doesn’t Nemo have an infection?”

You tell her, “No, Nemo does not have an infection. Improper use of antibiotics has caused a huge problem recently with the development of antibiotic-resistant ‘super bugs.’ Using an antibiotic when it is not indicated can create resistant bacteria strains that are not easily treated and have the potential to be transmitted to other animals or even people.”

Jan says, “Is that like this MRSA superbug I’ve been hearing about? That sounds awful! I don’t want Nemo to get that and I certainly don’t want to get that myself!”

What is antimicrobial resistance?

• Antimicrobial resistance occurs when a microorganism develops the ability to resist the action of an antimicrobial. Basically, the microorganism develops the ability to survive and reproduce in the presence (and dose) of an antimicrobial that used to prevent these actions.
• Antimicrobial resistance could occur through:

1. “Selection pressure”—even if an effective antimicrobial is used, rarely, if ever, will 100% of the organisms be killed during the course of treatment. The few surviving and potentially resistant organisms could then transfer their genetic material to offspring or other unrelated organisms.
2. Mutations—bacteria that were at one time susceptible to an antibiotic can acquire resistance through mutation of their genetic material or by acquiring pieces of DNA that code for the resistance properties from other bacteria. The DNA that codes for resistance can be grouped in a single easily transferable package. This means that bacteria can become resistant to many antimicrobial agents because of the transfer of one piece of DNA.

Examples of resistant strains of bacteria that have developed:

• Methicillin Resistant Staphylococcus aureus (MRSA)
• Multidrug Resistant Tuberculosis (MDR TB)—TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampicin
• Extremely Drug Resistant Tuberculosis (EDR TB)—TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (amikacin, kanamycin, or capreomycin)
• Staphylococcus pseudintermedius
• Fluoroquinolone-resistant Campylobacter
• Multi Drug Resistant Salmonella
• Vancomycin Resistant Enterococci (VRE)

Update

A few days after Nemo’s appointment, you call for an update. Jan reports that Nemo is doing wonderfully and has gone back to using his litter box. She can tell that he feels a whole lot better and is adjusting well to the diet change.

Jan thanks you for the wonderful care you gave Nemo. You remind Jan that she can discontinue the buprenorphine once it is finished, but everything else prescribed is something she should continue doing with Nemo to prevent recurrence of the idiopathic cystitis.

• In a feline patient with lower urinary tract signs, it is important to differentiate medical versus behavioral inappropriate urination.
• Signs indicating medical inappropriate urination include urination on various locations and horizontal surfaces, hematuria being more likely, and more likely in a household with fewer cats.
• Diagnostic testing including urinalysis and urine culture via cystocentesis, abdominal radiographs, and abdominal ultrasound are also very important to differentiate the causes for lower urinary tract signs such as infection, stones, and neoplasia.
• Feline Idiopathic Cystitis (FIC) is diagnosed with all the above testing is negative for an alternative cause.
• Treatment for FIC includes pain medication, reducing stress, diet change and increasing water consumption, increasing availability to litter boxes, and to clean litter boxes at least once daily.

1. Osborne, C, J Lulich, J Kruger, et al. 2009. Analysis of 451,891 Canine Uroliths, Feline Uroliths, and Feline Urethral Plugs from 1981 to 2007: Perspectives from the Minnesota Urolith Center. The Veterinary clinics of North America. Small Animal Practice. 39(1):183.
2. Lulich, J, and C Osborne. 2004 Urine culture as a test for cure: why, when, and how? The Veterinary clinics of North America. Small Animal Practice. 34(4):1027.
3. Lekcharoensuk, C, C Osborne, J Lulich. 2001. Epidemiologic study of risk factors for lower urinary tract diseases in cats. Journal of the American Veterinary Medical Association. 218(9):1429-1435.

FELINE UPPER RESPIRATORY INFECTIONS

Feline Upper Respiratory

In most cases of feline upper respiratory infections, the use of antimicrobials is not indicated. Most upper respiratory tract infections are due to viral infections, often uncomplicated by secondary bacterial infections. The International Society of Companion Animal Infectious Diseases (ISCAID) guidelines suggests a ten-day monitoring period prior to considering antibiotic treatment; antibiotics may be warranted earlier if the patient’s clinical condition is getting worse.

In some cases, feline upper respiratory tract infections are caused by a primary bacterial infection. In these cases antibiotic therapy is needed. ISCAID guidelines are useful in determining when to provide antibiotics and which to choose.

LEARNING OUTCOMES

• Be aware of the guidelines for feline upper respiratory infections set by the ISCAID.
• Name the underlying causes of feline upper respiratory infections.
• Determine the appropriate diagnostic tests and interpretations for cases of feline upper respiratory infection.
• Explain when the use of antibiotics is appropriate for cases of feline upper respiratory infections and which two antibiotics would be appropriate to use empirically.
• Identify three alternative treatment options for antibiotics in cases of feline upper respiratory infection and describe when these treatment options are appropriate.

SECTIONS

• Common Causes
• Supplemental Information to Video
• Questions
• References

Feline herpesvirus

Feline viral rhinotracheitis, caused by feline herpesvirus (FHV), is an upper respiratory tract infection that can be associated with secondary bacterial infections. After FHV infection, most cats become lifelong carriers of the virus. Stress or corticosteroid treatment may cause virus reactivation and shedding in oronasal and conjunctival secretions. Infection with FHV requires direct contact with other infected cats and cats who are shedding the FHV virus. Shedding may last for three weeks from oral, nasal, and conjunctival secretions.

Clinical signs of FHV include acute rhinitis and conjunctivitis, and usually pyrexia, depression, and anorexia. Some affected cats may also develop ulcerative, dendritic keratitis.

To establish a diagnosis of FHV, samples of conjunctival, corneal, or oropharyngeal swabs are needed for PCR (polymerase chain reaction) tests. Corneal scrapings or biopsies can also be used. It is not recommended that cats who have been recently vaccinated with a modified-live virus vaccine be sampled because of the likelihood of isolating the vaccine strain.

For treatment of FHV, nursing and supportive care are necessary. Anorexic cats should be fed a diet that is highly palatable, soft, and warm. Mucolytic drugs, such as bromhexine, or nebulization with saline may offer additional relief. Systemic antiviral drugs may be used for the treatment of severe infections, and topical antivirals may be needed in cases of acute FHV ocular disease. Broad-spectrum antibiotics should only be administered with FHV cases that develop secondary bacterial infections which last more than ten days or get worse after five to seven days or if fever and anorexia are present concurrently with mucopurulent nasal discharge.

For prevention, regular vaccination is recommended. For shelters or catteries, annual revaccination is recommended.

Feline calicivirus

Feline calicivirus (FCV) is a highly variable virus, meaning there are many strains that can either be benign or highly virulent. Infection with FCV occurs mainly through direct contact of sick, acutely infected, or virus carrying cats who shed FCV in their oronasal and conjunctival secretions.

Common clinical signs of FCV include oral ulcers, upper respiratory signs, and fever. Cats with "virulent systemic FCV disease" may show clinical signs of pyrexia, cutaneous edema, ulcerative lesions on the head and limbs, or jaundice. FCV may be isolated from nearly all cats with chronic stomatitis or gingivitis. The mortality rate is high in virulent systemic FCV disease-infected cats, especially in adult cats.

Virus isolation and reverse-transcriptase PCR are used to diagnose FCV from conjunctival and oral swabs, blood, skin scrapings, and lung tissue samples. The diagnosis of virulent systemic FCV disease requires virus isolation in the presence of corresponding clinical signs.

Treatment for FCV involves supportive care therapy, including fluid therapy. Anorexic cats should be fed a diet that is highly palatable, soft, and warm. Mucolytic drugs, such as bromhexine, or nebulization with saline may offer additional relief. Broad-spectrum antibiotics should only be administered with FCV cases that develop secondary bacterial infections as per FHV above.

For prevention, vaccination is recommended. Annual vaccine boosters are recommended for cats in higher-risk situations, such as shelters or catteries.

Bordetella bronchiseptica

Bordetella bronchiseptica is a Gram-negative bacterium that colonizes the respiratory tract of felines and is considered to be a primary pathogen of domestic cats. The bacterium is shed in oral and nasal secretions of infected cats. It can establish chronic infections once it colonizes the ciliated epithelium of the respiratory tract.

B. bronchiseptica is associated with a wide range of respiratory signs from fever, coughing, sneezing, ocular discharge, and lymphadenopathy to severe pneumonia with dyspnea, cyanosis, and death.

Bacterial culture and PCR lack sensitivity in confirming B. bronchiseptica infections. Samples for isolation can be obtained from swabs of the oropharynx or via transtracheal wash and bronchoalveolar lavage.

Because B. bronchiseptica may progress to the lower respiratory tract, antimicrobial therapy is necessary even when clinical signs are mild. The use of antimicrobial sensitivity testing is recommended to provide guidance for appropriate antibiotic therapy. When antimicrobial sensitivity data is unavailable, the use of tetracyclines are recommended. Doxycycline is the preferred antimicrobial. Cats with severe B. bronchiseptica infection require additional supportive care and nursing care. 

A vaccine against B. bronchiseptica is available for cats, but is considered a noncore vaccine. In other words, routine vaccination is not recommended for all cats because B. bronchiseptica generally causes mild disease. Rather, only cats specifically at risk of infection should receive the vaccine, such as those in shelters, catteries, other high-density populations, or populations that have a history of confirmed disease.

Chlamydophila felis

Chlamydophila felis is a Gram-negative bacterium that primarily colonizes the conjunctiva. Disease transmission requires close contact between cats, especially through ocular secretions, as the bacterium does not survive well outside the host. Most cases are frequently associated with conjunctivitis and occur in cats under one year of age.

Clinical signs of C. felis can include intense conjunctivitis with pain, blepharospasm, and extreme hyperemia of the nictitating membrane. Transient fever, inappetence, and weight loss may occur shortly after infection, although most infected cats remain well overall and continue to eat.

The preferred method for diagnosing C. felis is through PCR of ocular swab samples. In unvaccinated cats, antibody detection can be used to indicate infection.

For treatment of C. felis, tetracyclines are generally the antimicrobial of choice with doxycycline being the preferred option. Vaccination is an option for prevention and should be considered especially in shelter environments or multicat households with a history of confirmed chlamydial disease. When vaccination is not feasible, single housing and routine hygiene measures are needed to avoid cross-infection. Cats living together for longer terms should be regularly vaccinated. In breeding catteries where C. felis infection is endemic, eradication involves treatment of all cats with doxycycline for at least four weeks (Gruffydd-Jones et al., 2009). Once clinical signs have been controlled, the cats should be vaccinated.

Physical Exam Findings

* Temperature: 101.2° F

* Pulse: 184 beats per minute

* Respirations: 28 breaths per minute

* Mucous membrane color and capillary refill time (CRT): Pink and <2 seconds

* Body Condition Score (BCS): 5/9

* General appearance: bright, alert, and responsive (BAR)

* Eyes: Mild serous ocular discharge with mild crusting at the medial canthus of both eyes (OU)

* Ears: within normal limits with minimal debris noted

* Lymph Nodes: no peripheral lymphadenopathy noted

* Integumentary: no lesions noted

* Abdominal palpation: nonpainful, no masses or organomegaly noted

* Digestive: smooth intestines palpated normally

* Genitourinary: small bladder, external genitalia within normal limits

* Respiratory: clear lungs in all fields, patient sneezing, bilateral mucopurulent nasal discharge

* Circulatory: no murmur or arrhythmia noted, pulses strong and synchronous

* Nervous: WNL

* Musculoskeletal: Ambulatory and weight-bearing all four limbs

* Pain Score: 0/5

After History

1. Because you know how important a good history is, you decide to ask Jonathan some more questions. Which questions would you ask?

Answer: Answers here may vary, but should include basic historical questions about the onset and duration of disease, and whether the disease has worsened since it started. Additional questions could include: Is Sienna indoor only or is she an indoor/outdoor cat? Have new animals been introduced into the household, including newly fostered animals, newly adopted animals, or even animals that are being temporarily watched for friends (catsitting)? Are there any other pets at home? If so, what kind and how many? Has Sienna boarded at a clinic or cattery, or visited a groomer recently? Are there any new environmental changes in the house (this may include respiratory irritants or other stressors)? Is there any recent history of travel with Sienna? If so, when and where, and were there other animals present? Have you given Sienna any medications or treatments since the signs first started? Has she had a history of a similar condition before? When did she last receive vaccines? Which ones?

After Physical Exam

1. Your physical examination has provided clues to Sienna’s problems. Based on your history and clinical exam findings, where would you localize the disease?

Answer: Upper respiratory tract

2. What should be included on your differential diagnosis list based on where you localized the disease?

Answer: Feline herpesvirus, Feline calicivirus, bacterial infections are less likely

3. Based on your differential diagnosis, which diagnostic tests should you perform?

Answer: Fluorescein stain to rule out corneal ulcer. Consider FHV or FCV conjunctival or nasal swab for PCR, but clinical significance might be questionable in an isolated case compared to an outbreak in a cattery.

Before Treatment

5. What treatment options are available for the different types of upper respiratory infections in cats (remember to consider ISCAID guidelines)?

Answer: It is important to remember that the disease is self-limiting in many cats and supportive care should be considered above prescribing antibiotics. If clinical signs persist for longer than ten days or worsen to systemic signs in five to seven days, antibiotics should be considered. Systemic signs include fever, anorexia, profound lethargy, and brown/green/hemorrhagic nasal discharge. White or yellow nasal discharge is consistent with inflammation and is not synonymous with infection.

6. How would you like to proceed with treatment?

Answer: Steam therapy, highly palatable or aromatic food, maintenance of hydration, appetite stimulants if needed.

1. Egberink, H., Addie, D., Belák, S., Boucraut-Baralon, C., Frymus, T., Gruffydd-Jones, T., . . . Horzinek, M. C. (2009). Bordetella Bronchiseptica Infection in Cats: ABCD Guidelines on Prevention and Management. Journal of Feline Medicine and Surgery,11(7), 610-614. doi:10.1016/j.jfms.2009.05.010
2. Gaskell, R. M., Dawson, S., & Radford, A. (2006). Feline Respiratory Disease. In C. E. Greene (Author), Infectious Diseases of the Dog and Cat(Third ed., pp. 145-158). MO: Saunders.
3. Gruffydd-Jones, T., Addie, D., Belák, S., Boucraut-Baralon, C., Egberink, H., Frymus, T., . . . Horzinek, M. C. (2009). Chlamydophila Felis Infection: ABCD Guidelines on Prevention and Management. Journal of Feline Medicine and Surgery,11(7), 605-609. doi:10.1016/j.jfms.2009.05.009
4. ISCAID. (n.d.). Retrieved from https://iscaid.org/
5. Lappin, M., Blondeau, J., Boothe, D., Breitschwerdt, E., Guardabassi, L., Lloyd, D., . . . Weese, J. (2017). Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. Journal of Veterinary Internal Medicine,31(2), 279-294. doi:10.1111/jvim.14627
6. Richards, J. R., Elston, T. H., Ford, R. B., Gaskell, R. M., Hartmann, K., Hurley, K. F., . . . Sparkes, A. H. (2006). The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel Report. Journal of the American Veterinary Medical Association,229(9), 1405-1441. doi:10.2460/javma.229.9.1405