ISCAID Antimicrobial Use Guidelines
World Small Animal Veterinary Association World Congress Proceedings, 2014
Jane E. Sykes, BVSc(Hons), PhD, DACVIM
School of Veterinary Medicine, University of California-Davis, Davis, CA, USA

The International Society for Companion Animal Infectious Diseases (ISCAID) Antimicrobial Guidelines Working Group was formed to develop guidelines for antimicrobial drug use in dogs and cats, because of concerns that antimicrobial drug resistance has dramatically increased in prevalence among isolates from dogs and cats in the last decade. The guidelines are to be published in open access format so that they are widely available. The members of the ISCAID Working Group are Scott Weese, Joseph Blondeau, Dawn Boothe, Edward Breitschwerdt, Luca Guardabassi, Andrew Hillier, Michael Lappin, David Lloyd, Mark Papich, Shelley Rankin, Jane Sykes, and John Turnidge. Input has also been obtained from panels of Diplomates of relevant specialty groups. It should be noted that members of the working group receive support from a variety of industry groups that provide funding for honoraria and research (listed at www.iscaid.org). The guidelines development process has been in part sponsored by an unconditional grant from Bayer Animal Health.

Guidelines for treatment of urinary tract disease in dogs and cats and superficial pyoderma have been published (www.iscaid.org). Guidelines for treatment of respiratory disease and bloodstream infections are in preparation. During the course of guideline development, it became clear that there is a significant lack of objective, published information. Accordingly, recommendations are based on available data, whenever present, along with expert opinion, considering principles of infectious diseases, antimicrobial treatment, antimicrobial resistance, pharmacology, and internal medicine. Funding for studies on antimicrobial resistance in companion animals is badly needed. Clinical trials that evaluate antimicrobial drug regimes for bacterial infections in dogs and cats are encouraged.

Because of the increased prevalence of antimicrobial drug resistance, the need to properly document the presence of an infection before initiating antimicrobial drug treatment is more important than ever. In veterinary medicine, this may be at odds with client financial resources. However, inappropriate use of antimicrobial drugs is wasteful of client resources when an infection is not present or a multidrug-resistant pathogen is present, and risks selection for antimicrobial-resistant bacteria that may be harmful to the pet, other animals, and also humans that are in contact with the animal. Clinicians should choose laboratories for culture and susceptibility (C&S) testing that follow protocols and use breakpoints published by the Clinical and Laboratory Standards Institute (CLSI), EUCAST or other internationally recognized institutions. The Working Group hopes that veterinarians will re-think the empiric use of antimicrobial drugs, especially when the underlying condition is not immediately life-threatening. An emphasis on rational antimicrobial treatment needs to be made to pet owners, as has been made in human medicine. The guidelines do not provide specific recommendations for hygiene and disinfection, but posters describing appropriate measures and guideline documents are available from veterinary associations in North America and in Europe and these should be followed.

Some of the basic recommendations within the urinary and superficial pyoderma guidelines are summarized below. Doses of specific antimicrobial drugs are listed in the guidelines themselves.

Guidelines for Urinary Tract Disease

Simple Uncomplicated Urinary Tract Infection (UTI)

Definition: Sporadic bacterial infection of the bladder in an otherwise healthy individual with normal urinary tract anatomy and function.

 A clinically significant infection implies the presence of dysuria, pollakiuria, and/or stranguria. Diagnosis of UTI cannot be made on the basis of clinical signs alone.

 Sediment analysis alone is not adequate for diagnosis because of the variable quality of interpretation. It is supporting evidence for the presence of UTI.

 Complete urinalysis and quantitative aerobic C&S testing should be performed for all cases. Free-catch samples should not be used.

 For cystocentesis specimens, counts ≥ 103 CFU/ mL indicate UTI. For catheterized specimens, counts ≥ 104 in males and ≥ 105 CFU/mL in females are significant.

 Bacterial isolation should only be attempted in clinics with appropriate laboratory facilities, proper biosafety containment and waste management, and adequately trained individuals. A recent study showed that in-house "urine paddles" may be useful to rule out the presence of infection but these do not reliably identify bacteria and can generate false-negative results (Ybarra et al. 2014).

 Treatment is indicated to relieve patient discomfort while awaiting C&S test results. Recommendations for initial treatment are amoxicillin (11–15 mg/kg PO q 8 h) or trimethoprim-sulfonamide (15 mg/kg PO q 12 h). Additional information obtained from the CLSI since publication of the guidelines suggests that amoxicillin could be used q 12 h.

 Veterinarians are encouraged to document and monitor resistance patterns among isolates from their hospital.

 If C&S testing reveals a resistant isolate and there is a lack of clinical response, treatment should be changed to an appropriate antimicrobial drug.

 Treatment is typically for 7 to 14 days, but shorter treatment times (≤ 7 days) may be effective. Since publication of the guidelines, two studies have provided evidence to support this. In one study, a 3-day course of once-daily, high-dose enrofloxacin was as effective for treatment of uncomplicated UTIs in dogs as 14 days of clavulanic acid-amoxicillin (Westropp et al. 2012). In another study, a 3-day course of trimethoprim-sulfamethoxazole was as effective for treatment of uncomplicated UTIs in dogs as 10 days of cephalexin (Clare et al. 2014), although long-term microbiologic cure rates in both groups of dogs were less than 50%.

 There is no evidence that intra- or post-treatment urinalysis or urine culture is indicated in the absence of ongoing clinical signs of UTI.

Complicated UTI

Definition: A UTI that occurs in the presence of an anatomic or functional abnormality or a comorbidity that predisposes the animal to persistent infection, recurrent infection, or treatment failure. Recurrent UTIs, as defined by the presence of 3 or more episodes of UTI during a 12-month period, also indicate complicated infection.

 The same general principles as for uncomplicated UTI apply.

 Efforts should be made to identify the underlying cause; consider referral.

 Treatment should be based on the results of C&S testing.

 Although 4 weeks is generally used for treatment, more studies are needed that evaluate the shortest duration of treatment for different comorbidities.

 Urine culture could be considered after 5–7 days of treatment to ensure treatment has been effective, and should be performed 7 days after treatment is discontinued. If there is a lack of clinical response, additional investigation and management of the underlying cause should be made.

 There is insufficient evidence to recommend "pulse" or chronic low-dose treatment, urinary antiseptics, and nutritional supplements such as cranberry juice extract for prevention of UTIs.

Subclinical Bacteriuria

Definition: Presence of bacteria in the urine as determined by positive bacterial culture, in the absence of clinical signs of UTI.

 Treatment may not be necessary, but could be considered if there is a high risk of ascending or systemic infection (e.g., patients with underlying renal disease).

 Diagnosis and management of the underlying cause is critical.

Urinary Catheters

 Clinical signs of UTI absent: no culture or treatment indicated.

 Removal of urinary catheters: urine culture is reasonable if the risk and implications of a UTI are high. There is no indication for routine use of prophylactic antimicrobials.

 Clinical signs of UTI present: perform a culture after replacement of the urinary catheter with a new catheter. Several mL of urine should be removed to clear the catheter before a specimen is obtained for culture. Alternatively, remove the catheter and perform a cystocentesis. Culture from the collection bag, and culture of the catheter tip after removal are not recommended. Treatment should follow the guidelines for complicated and uncomplicated UTIs, and is more likely to be successful after catheter removal.

Pyelonephritis

 C&S testing should always be performed.

 Treatment should be initiated while awaiting culture results, using antimicrobials effective against Gram-negative Enterobacteriaceae. A fluoroquinolone is a reasonable first choice, after which treatment should be based on C&S results. If combination treatment was used initially and C&S results indicate that both drugs are not required, the spectrum should be narrowed.

 Treatment for 4 to 6 weeks is recommended until further information becomes available.

 Culture is recommended 1 week after starting treatment and 1 week after treatment is discontinued.

Guidelines for Superficial Bacterial Folliculitis in Dogs (Superficial Pyoderma)

The cause of most superficial bacterial folliculitis (SBF) in dogs is Staphylococcus pseudintermedius. In the past, S. pseudintermedius infections could be routinely treated successfully with beta-lactam antimicrobials. However, methicillin-resistant S. pseudintermedius (MRSP), which is often highly multiresistant, has now spread rapidly throughout the world. This has focused attention on the need to ensure that diagnosis and treatment of SBF is managed in an optimal way so as to resist the spread of this organism, the proliferation of resistant clones, and the wasteful and ineffective use of antimicrobial drugs to which this organism is resistant.

 Staphylococci are not able to invade normal skin and thus SBF only occurs when there is an underlying problem such as allergic dermatoses, hyperadrenocorticism, hypothyroidism, or demodicosis. These need to be differentiated from SBF.

 Early signs of SBF are papules and pustules associated with the hair follicles. Subsequently, annular areas of alopecia, scaling, erythema and hyperpigmentation may appear, commonly surrounded by epidermal collarettes.

 Diagnosis of SBF should be supported by cytological examination and the demonstration of coccoid bacteria associated with inflammatory cells and within phagocytes. Inflammatory infiltrates and phagocytosis may be reduced or absent in patients with immunosuppression associated with underlying diseases or therapy. Cytology is also important for identification of coinfection with Malassezia pachydermatis.

 SBF must be distinguished from other causes of folliculitis and pustular disease. It should be differentiated from demodicosis by deep skin scrapings and from dermatophytosis by fungal culture. Such tests are required when history and clinical signs are suggestive but not typical of SBF, or when antibacterial treatment fails.

 Culture is essential if there is a poor response to 2 weeks of appropriate systemic antimicrobial therapy, emergence of new lesions 2 weeks or more after the initiation of such therapy, presence of residual lesions after 6 weeks of therapy combined with cytology demonstrating infection with cocci, when cytology reveals intracellular bacterial rods, and when there has been a history of a multidrug-resistant infection in the dog or a dog that shares the household. C&S testing is encouraged in cases of recurrent SBF infection or when there has been a history of treatment with antimicrobial drugs.

 Owners should be taught how to recognize when progress is not being made so that they may seek veterinary advice prior to the end of a course of treatment.

 Specimens for culture should be taken from pustules. If pustules are not found, specimens may be taken from pus beneath crusts and from papules or epidermal collarettes. No surface disinfection should be carried out.

 Contact with owners should be maintained to promote effective compliance and to determine if and when failure to respond to treatment, or recurrence, occurs.

 In recurrent infection, an effective diagnostic plan should be formulated to identify and resolve underlying disease.

 Topical antimicrobials (ointments, gels, and creams) should be considered, which can be applied to localised lesions 2 to 3 times daily. Such products may contain antibiotics (e.g., mupirocin), silver sulfadiazine, benzoyl peroxide, and hydroxyl acids (e.g., lactic acid). More extensive areas of infection can be treated with shampoos, lotions, sprays, and rinses. These contain antiseptics such as chlorhexidine, benzoyl peroxide, ethyl lactate, povidone iodine, triclosan, and hydroxyl acids; they are commonly used 2 to 3 times weekly and until 7 days after lesions resolve, with contact times of 10 minutes if possible before rinsing or conditioners. They can then be used for prophylaxis on a weekly or less frequent basis depending on response.

 Selection of appropriate drugs for systemic therapy depends on availability, safety, cost, local prevalence of resistant staphylococci and patient-specific factors. Empirical choices can be made in non-recurrent cases and when there has been no history of antimicrobial drug exposure. Otherwise, drug selection should be based on C&S tests. First-tier empirical drugs include clindamycin, first-generation cephalosporins, potentiated sulphonamides, and lincomycin. When first-tier drugs are not appropriate and topical therapy cannot be used, second-tier drugs may be chosen; these include fluoroquinolones, doxycycline, chloramphenicol, and rifampin. Most of the Working Group members felt that third-generation cephalosporins should be second-tier drugs, but the evidence to support their placement in this category was lacking, and so they were listed as first- or second-tier drugs.

 Systemic antimicrobial drugs given at subtherapeutic doses or as pulse therapy have been used to prevent or delay recurrence, but such protocols are likely to promote the development of antimicrobial resistance and are discouraged.

References

1.  Weese JS, Blondeau JM, Boothe D, Breitschwerdt EB, Guardabassi L, Hillier A, Lloyd DH, Papich MG, Rankin SC, Turnidge JD, Sykes JE. Antimicrobial Use Guidelines for treatment of urinary tract disease in dogs and cats: antimicrobial guidelines working group of the International Society for Companion Animal Infectious Diseases. Vet Med Int. 2011; Epub Jun 27.

2.  Hillier A, Lloyd DH, Weese JS, Blondeau JM, Boothe D, Breitschwerdt EB, Guardabassi L, Hillier A, Lloyd DH, Papich MG, Rankin SC, Turnidge JD, Sykes JE. 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). Vet Dermatol. 2014;25(3):163-e43.

3.  Ybarra WL, Sykes JE, Wang Y, Byrne BA, Westropp JL. Performance of a veterinary urine dipstick paddle system for diagnosis and identification of urinary tract infections in dogs and cats. J Am Vet Med Assoc. 2014;244(7):814–819.

4.  Westropp JL, Sykes JE, Irom S, Daniels JB, Smith A, Keil D, Settje T, Wang Y, Chew DL. Evaluation of the efficacy and safety of high dose short duration enrofloxacin treatment regimen for uncomplicated urinary tract infections in dogs. J Vet Intern Med. 2012;26(3):506–512.

5.  Clare S, Hartmann FA, Jooss M, Bachar E, Wong YY, Trepanier LA, Viviano KR. Short- and long-term cure rates of short-duration trimethoprim- sulfamethoxazole treatment in female dogs with uncomplicated bacterial cystitis. J Vet Intern Med. 2014;28(3):818–826.

  

Speaker Information
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Jane E. Sykes, BVSc(Hons), PhD, DACVIM
School of Veterinary Medicine
University of California-Davis
Davis, CA, USA


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