Antimicrobial stewardship: What it is and why it matters

Antimicrobials have tremendous therapeutic benefits in human and veterinary patients. After vaccination, antibiotics are probably the most important medical intervention of the 20th century in terms of reducing suffering and death. Of course, antimicrobials can also have significant adverse effects. And any use of antimicrobials, including appropriate therapeutic use, creates a selection pressure that can result in emergence of antimicrobial resistance (AMR) or an increase in the abundance of resistant bacteria. Adverse effects and the development of resistance reduce the potential benefits of antibiotics. Antimicrobial stewardship is the concept of using antibiotics in a manner that maximizes their benefits, minimizes risks, and conserves the effectiveness of these important drugs.1 Changing when and how we use antibiotics is the key to achieving these goals. Antimicrobial stewardship involves three general strategies: 1) Preventing infectious disease occurrence 2) Reducing overall antimicrobial use 3) Using antimicrobials in ways that maximize the benefits, minimize the adverse effects, and reduce the development of antibiotic resistance Preventing infections Preventing bacterial infections automatically reduces the need for, and hence the use of, antimicrobials. This involves encouraging clients to provide appropriate husbandry and preventive care, including vaccination, proper nutrition, isolation of sick animals, and other prophylactic measures. Prevention of infection also involves proper biosecurity practices in the hospital, including assiduous hand hygiene, use of personal protective equipment (PPE) when handling patients with infections, appropriate isolation procedures for animals with contagious disease, and proper sanitation of rooms and equipment to prevent nosocomial infection. Following evidence-based protocols for medical interventions that can lead to infection (e.g. the placement of urinary catheters; surgery and other invasive procedures; and the use of immunosuppressive therapies) also helps to reduce iatrogenic infections and the need for antimicrobials. Reducing antimicrobial use Any use of antibiotics creates the conditions for development of antimicrobial resistance, even in the case of necessary, targeted use. Reducing the overall use of these drugs reduces the risk of AMR. We can use fewer antibiotics by adhering to several general principles: Obtaining a probable or definitive diagnosis through history, physical examination, and clinical laboratory testing, so we do not use antibiotics in patients who do not have bacterial infections. Delaying the use of antibiotics in cases where the patient’s condition might not be due to bacterial infection may also be appropriate. Using alternatives to antibiotics where appropriate, such as topical treatment of superficial pyoderma, nonantibiotic treatments for acute diarrhea, etc. Prescribing shorter courses of antibiotic treatment where there is evidence this course of action is effective and discontinuing antimicrobials when clinical cure is achieved, rather than relying on a fixed, arbitrary length of treatment. Not using antibiotics in moribund patients not expected to recover. Not testing for the presence of bacteria or prescribing antimicrobials in the absence of relevant clinical signs attributable to these organisms. For example, it is not recommended to culture urine in the absence of clinical signs of urinary tract infection (UTI). Further, it is not recommended to culture sites that are normally colonized by commensal bacterial, such as the nose or vagina. Prudent use of antibiotics There is clear evidence antibiotics are often used inappropriately and excessively in human medicine.2 Though there is less data, it appears very likely the problem is as serious or even more extensive in veterinary medicine.3,4 Fortunately, there is also some evidence the development and implementation of antibiotic stewardship guidelines can reduce the inappropriate use of antimicrobials in veterinary hospitals.5 Being aware of when antibiotic use is warranted and when it is not, as well as following evidence-based guidelines for antimicrobial therapy, can reduce misuse and prevent AMR. Maximizing the benefits of antibiotic treatment and minimizing adverse effects and AMR require judicious selection and use of antimicrobial drugs. This involves selecting drugs and dosages based on culture and sensitivity results whenever possible. If culture results are not available, empirical drug selection should be guided by the type of bacterial infections typically reported for the same species, site of infection, and clinical symptoms seen in a given patient. It is also recommended to develop and use antibiograms (summaries of culture results and resistance patterns) specific to a given hospital. The duration of treatment with antimicrobials should be as short as possible, and should be based on published guidelines or research evidence and the individual patient’s clinical signs. Veterinarians routinely use much longer antibiotic courses than physicians employ for similar infections. For example, evidence-based guidelines recommend a three- to five-day course of antibiotic treatment for bacterial urinary tract infections (UTI) in small animals,6 which is similar to the common practice in human medicine. However, clinicians routinely prescribe antibiotics for seven to 10 days (or even longer) for uncomplicated UTIs. This is likely due to reliance on expert opinion or personal experience, rather than evidence-based guidelines in making treatment decisions. One popular myth is that longer antibiotic courses or treatment extending past the resolution of clinical signs reduces the risk of AMR. This idea has not held up well over time, and the evidence no longer supports it.7 Fixed minimum courses of antibiotic treatment do not reduce AMR—they only increase the risk of adverse effects and may contribute to resistance. As such, antimicrobials should be discontinued once there is clinical or microbiological evidence the infection has been eliminated or once an alternative diagnosis has been made for patients initially thought to have bacterial infections. A de-escalation approach to antibiotic therapy is recommended in most cases to reduce adverse effects and the development of resistance. This means that when there is uncertainty about the spectrum of coverage needed to control a bacterial infection in a specific patient, multiple antimicrobials may be initiated empirically. However, as soon as culture results or other evidence is available indicating the identity and sensitivity profile of the pathogens, unnecessary drugs should be discontinued. If antibiotics are added based on culture results or failure to respond to initial antimicrobial therapy, unnecessary or ineffective antibiotics should be discontinued. The most appropriate antimicrobial to use in a given patient is ideally determined by culture and sensitivity testing. This may not always be possible, however, and general guidelines for which pathogens are most often found in specific infections, as well as which antibiotics are commonly effective for these pathogens, can be helpful. A better alternative to these guidelines when individual patient testing is not possible is to have data illustrating the pathogens and their antimicrobial sensitivity patterns within the patient population seen at a particular hospital or clinic. An antibiogram is a summary of culture and sensitivity results for a particular facility that can be a useful guide for empirical antimicrobial selection. In my practice, for example, I collect and summarize the results of all urine cultures run on our patients every six months. This information is broken down by species and by sensitivity results. The most recent antibiogram indicated the most common pathogen in our canine and feline UTIs was Escherichia coli, and that these infections were sensitive to amoxicillin 84 percent of the time, to potentiated amoxicillin 84 percent of the time, and to trimethoprim sulfa 94 percent of the time. This information, along with knowledge of the potential adverse effects and costs of the various antimicrobials available, helps our clinicians to select the most appropriate drug for each case. Creating these antibiograms also helps us to keep track of the development of antimicrobial resistance in our patient population and the emergence of new pathogens. There are many situations in which antibiotics are commonly used in companion animal medicine when they are not indicated, and this misuse contributes to unnecessary adverse effects and the development of AMR. The most common is probably the use of antimicrobials “just in case,” when bacterial infection has not been confirmed, when infections are likely to be self-limiting, or in an attempt to prevent infections. Evidence from human medicine makes it clear that most anxiety-driven use of antimicrobials does more harm than good in terms of causing adverse drug reactions and contributing to AMR, rather than preventing illness.8 Common misuses of antimicrobials in small animal medicine include: Acute upper respiratory disease in dogs and cats Acute diarrhea or acute hemorrhagic diarrhea syndrome (a.k.a hemorrhagic gastroenteritis) Hematuria in cats without culture-confirmed UTI, especially cats younger than 10 years of age Asymptomatic bacteriuria Dental procedures Perioperative use in patients classified by the American Society of Anesthesiologists’ (ASA’s) staging system as Stage 1 or 2 who are undergoing clean procedures Extended postoperative use in patients without established infection or sepsis Guidelines for antibiotic use in specific conditions A number of evidence-based clinical practice guidelines (CPG) are now available to help small animal veterinarians practice good antimicrobial stewardship. These CPGs provide criteria for determining when antibiotic use is or is not warranted, selecting appropriate antimicrobials, and choosing suitable dosages and treatment duration. Below is a summary of the key points from several of these guidelines. That said, I encourage all small animal clinicians to read them in full and keep copies handy for regular reference. Respiratory tract infections9 Feline upper respiratory tract disease: The majority of cases of upper respiratory tract disease (URTD) in cats are caused by viral agents, particularly feline herpesvirus (FHV-1) and feline calicivirus (FCV). However, primary and secondary bacterial infections can occur. Bacteria are inevitably present in the upper respiratory tract of cats, so determining the causal role of such organisms in individual cases is difficult. Expert consensus guidelines include the following principles: Acute URTD Cytology of nasal discharge is not a reliable guide to diagnosis or antimicrobial therapy in cats with acute URTD. Culture of nasal discharge is not a reliable guide to diagnosis or antimicrobial therapy in cats with acute URTD. Antimicrobials should not be used in most cats with serous nasal discharge lacking a purulent component. Even in cats with purulent discharge, it is recommended not to begin antimicrobial treatment for 10 days unless the patient also has a fever, inappetence, lethargy, or other systemic signs. Many cats with primary viral and secondary bacterial rhinitis undergo spontaneous resolution within 10 days. Recommended first-line treatment for acute bacterial URTD in cats is a seven- to 10-day course of doxycycline at 5 mg/kg PO BID or 10 mg/kg PO SID. Amoxicillin at 22 mg/kg PO BID is an acceptable alternative. Potentiated amoxicillin should only be used if there is a high rate of beta-lactam-resistant organisms in the local population based on antibiogram data. There is limited evidence cefovecin may be inferior to doxycycline and amoxicillin for acute URTD in cats, so this is not recommended as a first-line treatment. Cats not responding to initial empirical therapy within 10 days should be evaluated more thoroughly before additional antimicrobials are prescribed. Chronic URTD Cats with signs of bacterial URTD persisting for longer than 10 days and not responsive to initial antimicrobial therapy should be evaluated for underlying pathology. This workup may include: Advanced imaging of the nasal cavity Rhinoscopy, with collection of lavage and biopsy samples for bacterial and fungal culture, and histopathology and collection of samples for URD polymerase chain reaction (PCR) Antimicrobial treatment of chronic URTD should only be employed for cats with severe clinical symptoms. Such cats often have ongoing predisposing factors that make a clinical cure unlikely; the symptomatic benefits of antimicrobials diminish with overuse and the development of AMR, so cats with mild symptoms should generally not be treated with antibiotics. Antimicrobial treatment in cats with chronic URTD should be guided by culture and sensitivity results based on nasal lavage or tissue biopsy samples. First-line drugs (e.g. doxycycline, amoxicillin) should be used before fluoroquinolones or third-generation cephalosporins, unless there is evidence of resistance to these first-line drugs. Azithromycin should be reserved for cases in which chlamydial infection is unlikely and first-line drugs (doxycycline and amoxicillin) are ineffective. There is little evidence to guide duration of therapy in chronic URTD. Expert opinion recommends a minimum treatment of seven days and continued treatment as long as there is progressive improvement and for one week beyond plateau or resolution of clinical signs. Repeated culture for monitoring is generally not recommended, and treatment after the initial workup is typically guided by clinical response. In cats with recurrent signs, the use of the previously effective antibiotic for seven to 10 days is recommended. Repeated prophylactic antimicrobial treatment is not recommended, though there may be some individuals in whom this is necessary to control clinical symptoms when a cure is not achievable. Canine infectious respiratory disease complex (CIRD) Previously known as infectious tracheobronchitis or kennel cough, CIRD is characterized by acute onset coughing with or without sneezing; fever is uncommon. Coinfection with multiple respiratory pathogens is common in dogs with CIRD, and all can be present without clinical symptoms, making identification of a specific causal agent difficult. Culture is rarely indicated in acute cases, and PCR testing is more useful for establishing the prevalence of various agents in a population than for identifying the cause of clinical illness in an individual patient. The majority of cases of CIRD have a viral etiology—both viral and bacterial cases typically resolve spontaneously within 10 days. Expert consensus guidelines include the following principles: Antibiotics should be considered in cases of CIRD within the first 10 days of symptoms only in cases presenting with fever, lethargy, or inappetence and purulent or mucopurulent nasal discharge. In cases of bacterial CIRD with appropriate clinical signs and no indication of pneumonia, first-line therapy should be doxycycline at 5mg/kg PO BID or 10mg/kg PO SID for seven to 10 days. Potentiated amoxicillin may be considered if doxycycline is ineffective or not tolerated. However, the most common primary bacterial agents in CIRD, Bordetella bronchiseptica and Mycoplasma spp., are usually resistant to this drug, so it may only be helpful for treating infection with secondary, opportunistic pathogens. CIRD does not predispose to chronic respiratory disease. Therefore, if clinical signs do not resolve spontaneously or with antimicrobial treatment within 10 days, a more thorough evaluation for other disease is recommended. Simply adding or changing antibiotic drugs is not appropriate in such cases. Primary bacterial bronchitis Primary bronchitis may be suspected in dogs or cats with chronic cough when other relevant differential diagnoses have been excluded (e.g. pneumonia, cardiac disease, parasitosis, neoplasia, etc.). Definitive diagnosis requires airway wash samples for cytology and culture. Expert opinion guidelines suggest: Antibiotic therapy should be based on culture results from airway wash sample. Doxycycline is recommended as the first-line, empirical treatment while awaiting culture results. Treatment should be given for seven to 10 days and, if improvement is seen, continued for one week past resolution of clinical signs. Chronic or recurring disease is possible; additional treatment or monitoring through thoracic radiography and repeated airway sampling may be indicated in some patients. Pneumonia Pneumonia can be primary, especially in puppies, but it is most often secondary to viral infections, aspiration, and other causes. It is diagnosed based on physical exam, clinicopathologic, and radiographic findings. Expert opinion guidelines for antimicrobial treatment recommend that: In most cases, antimicrobial therapy should be based on culture of airway lavage samples if possible. However, rapid initiation of antibiotic therapy is recommended, and treatment should not be delayed for more than a few hours for collection of culture samples. In cases of presumed aspiration pneumonia, culture samples may not be a reliable guide to antimicrobial therapy. Empirical antimicrobial treatment should be initiated while waiting for culture results in most cases. In hospitalized patients, a parenteral fluoroquinolone (e.g. enrofloxacin) and an antimicrobial effective against anaerobic and Gram-positive organisms (e.g. ampicillin or clindamycin) are appropriate first-line drugs. Ideally, a de-escalation strategy based on culture results should be pursued as soon as possible. The choice of oral antibiotics for patients who are discharged from the hospital should be based on culture results and clinical response. There is little data to guide duration of antibiotic treatment for pneumonia in dogs and cats. In humans, treatment is typically seven to 10 days. One prospective study found no difference in resolution or relapse in dogs treated for 14 days. Recommendations to treat for four to six weeks are arbitrary and not evidence-based, so shorter treatment periods based on clinical signs and radiography are more appropriate. Urinary tract infections10 Subclinical bacteriuria A common misconception is that the presence of bacteria in the urine is always abnormal and must be treated. It is now widely recognized in human medicine, and beginning to be recognized in veterinary medicine, that asymptomatic or subclinical bacteriuria is not unusual, and antimicrobial treatment is neither indicated nor beneficial in these cases. Current guidelines define subclinical bacteriuria as the presence of bacteria confirmed by culture from a properly collected urine sample in the absence of clinical symptoms of lower urinary tract disease (e.g. hematuria, stranguria, pollakiuria, etc.). Cytological findings (e.g. hematuria, pyuria, proteinuria, bacteria in urine sediment) are not consistently predictive of positive culture and so are useful, but insufficient to diagnose neither UTI nor subclinical bacteriuria. Subclinical bacteriuria is common, reported at rates of two to 12 percent in healthy dogs and 15 to 75 percent in dogs with conditions such as obesity, diabetes mellitus, intervertebral disk disease (IVDD) or chronic paralysis, and immunosuppressive drug use. There is less data for cats, but rates of one to 13 percent have been reported in healthy individuals. Subclinical bacteriuria has not been associated with increased risk of developing lower or upper bacterial urinary tract infections in dogs or humans. Even in immunocompromised populations such as the elderly, pregnant women, patients with chronic disease or endocrinopathies, and those on immunosuppressive medications, treatment of subclinical bacteriuria is not recommended in humans, as it has been shown to have no benefits and increases the risk of adverse drug effects and antibiotic resistance. Treatment cost may also be a factor for some. Urine culture should not be performed in the absence of clinical symptoms of lower urinary tract disease, since treatment of subclinical bacteriuria is not indicated. Pyuria and abnormal urine odor are not sufficient predictors of bacterial cystitis to justify urine culture or antibiotic treatment in the absence of clinical symptoms. Further, bacterial count on urine culture cannot be used to distinguish subclinical bacteriuria from bacterial cystitis. There is currently no evidence the use of adjunctive treatments (e.g. cranberry or probiotics) is beneficial for treatment or prevention or subclinical bacteriuria. Sporadic bacterial cystitis Diagnosis: Sometimes called “uncomplicated UTI,” sporadic cystitis involves acute lower urinary tract symptoms known or suspected to be due to bacterial infection. Urinalysis results supportive of bacterial cystitis in patients with appropriate clinical symptoms include pyuria, hematuria, and bacteria present in the urine sediment. This may be used to make a presumptive diagnosis. Presence of bacteria should be confirmed by culture in all patients if possible. This is especially critical in cats younger than 10 years of age, in whom bacterial cystitis is uncommon compared to sterile cystitis. Culture samples obtained by cystocentesis are preferred. Voided samples or those collected during placement of urinary catheter should be critically assessed to distinguish contamination from bacterial cystitis, which is supported by higher bacterial load (>100,000 CFU/mL), species of bacteria commonly associated with UTI, and isolation of only a single species as opposed to growth of multiple species of bacteria. Treatment: Isolated incidents or fewer than three incidents in a 12-month period should be treated as sporadic cystitis, regardless of the presence of comorbidities, such as kidney disease or endocrinopathies. Patients with more than three incidents of bacterial cystitis in a 12-month period should be managed as for recurrent bacterial cystitis. Patients with bacteriuria and no clinical symptoms of cystitis should be managed as recommended for subclinical bacteriuria. Clinical symptoms are caused primarily by inflammation, so the use of nonsteroidal anti-inflammatory drugs (NSAID) should be considered. In humans, analgesics may be as effective as antimicrobials in relieving clinical symptoms. It is reasonable to use NSAIDs in patients with cystitis while waiting for the results of urine culture. Empirical antibiotic treatment in patients with suspected sporadic cystitis is reasonable. Antibiotic choice should ideally be guided by antibiogram data from the patient’s source population. In the absence of population-specific antibiogram data, amoxicillin is an appropriate first-line antibiotic in most regions. It is unclear if potentiated amoxicillin is necessary or preferable, as even beta-lactamase-producing bacteria may be sensitive to amoxicillin due to high urine concentrations. Trimethoprim-sulfonamides are also an appropriate first choice, and serious adverse effects are unlikely with the standard short recommended treatment course. Nitrofurantoin, fluoroquinolones, and third-generation cephalosporins should be reserved for cases shown not to be susceptible to first-line drugs by appropriate culture and sensitivity testing. The usual recommended treatment course for sporadic bacterial cystitis is three to five days. There is currently no evidence the use of adjunctive treatments (e.g. cranberry products or probiotics) is beneficial for treatment or prevention or sporadic bacterial cystitis. Lack of clinical response within 48 hours should prompt further diagnostic investigation. Empirical change in antibiotics in response to treatment failure without relevant culture and sensitivity results or additional diagnostic investigation is unlikely to be successful and is not recommended. Cultures results and clinical response should be used to guide changes in empirical antibiotic choice if indicated. Posttreatment culture or urinalysis is not recommended when symptoms have resolved. Recurrent bacterial cystitis Diagnosis: Three or more episodes of bacterial cystitis within a 12-month period or two or more episodes within a six-month period constitute recurrent bacterial cystitis. Cases of recurrent cystitis should be investigated to identify underlying causes and to distinguish between persistent, relapsing, and recurring infection. Appropriate diagnostic techniques would include repeat urine culture, urinary tract imaging, and systemic diagnostic testing to investigate potentially predisposing comorbidities. Cystoscopy and biopsy of the bladder mucosa may be indicated in some cases (e.g. clinical signs with repeated negative urine cultures), but this is rarely performed in humans, and there is a lack of evidence regarding its utility in dogs and cats. Treatment: Long antibiotic treatment courses (e.g. four weeks) have previously been recommended for recurrent cystitis. However, the specific causes of persistent, relapsing, and recurring infections may require different treatment regimes, and there is growing evidence supporting shorter treatment courses in humans. Broad recommendations for treatment duration in dogs and cats are not possible currently due to the lack of relevant evidence. Short courses (three to five days) should be considered for recurrent infections, while longer courses (seven to 14 days) may be appropriate for persistent or relapsing infections. Use of NSAIDs for symptomatic relief while awaiting urine culture should be considered. Culture results and clinical response should be used to guide changes in antimicrobial treatment. It is appropriate to continue a specific antibiotic when sensitivity testing shows likely efficacy and clinical symptoms have improved. It is appropriate to change antibiotics when sensitivity testing suggests lack of efficacy and clinical symptoms persist. If clinical symptoms are resolved, some experts recommend continuing antibiotic therapy even if sensitivity testing suggests resistance, as in vitro sensitivity testing does not always reflect the true efficacy of treatment in patients. Culture during treatment is not recommended for short treatment courses (three to five days). It is unclear if culture during longer treatment courses (seven to 14 days) is beneficial. If a culture is done during treatment, positive results should trigger further diagnostic evaluation, not simply a change in antibiotic. Negative results may help guide the duration of treatment, though they do not always predict microbiological cure. Repeating culture five to seven days after cessation of treatment when clinical signs have resolved may be considered, but it should be viewed as a tool for distinguishing between persistent, relapsing, and recurring infection, not as an indication for further antibiotic treatment. Patients with bacteria and no clinical symptoms should be managed as recommended for subclinical bacteriuria. Prevention: Daily antibiotic administration has been shown to reduce recurrence of bacterial cystitis and to increase the prevalence of antibiotic resistance in humans. There is little relevant evidence in dogs and cats, so the potential risks and benefits of ongoing antibiotic use should be considered in the context of each individual case. There is limited and mixed evidence regarding the effects of prophylactic adjunctive therapies such as cranberry products, probiotics, and methenamine in humans and dogs. As such, the use of such products is neither recommended nor discouraged. Upper urinary tract infection (pyelonephritis) Diagnosis: Definitive diagnosis of pyelonephritis is challenging, and there is no single pathognomonic finding. Diagnosis is supported by culture-confirmed UTI accompanied by systemic signs (e.g. fever, neutrophilia), renal or abdominal pain, azotemia, urinary casts, and renal pelvic dilation or blunting of papillae on ultrasound. Animals with immunosuppressive conditions or medications or fever should also have blood cultures taken at the same time as a urine culture sample is collected. Antibiotic sensitivity testing must be based on serum levels of antibiotics, rather than urine concentrations. Inform the lab running urine cultures that pyelonephritis is expected so that urine breakpoints are not applied. Evaluation for leptospirosis should be considered in dogs with negative urine culture and a clinical presentation consistent with pyelonephritis. Treatment: Empirical treatment should be initiated immediately while awaiting culture results. Initial treatment should include drugs appropriate for treating Enterobacteriaceae, which are commonly found in pyelonephritis. A fluoroquinolone or cefpodoxime are appropriate first-choice oral antimicrobials, while cefotaxime or ceftazidime are appropriate IV drugs. Oral treatment is as effective as parenteral treatment and should be used in patients with normal appetite and minimal systemic clinical symptoms. A de-escalation approach to antibiotic therapy is recommended. In cases for which broad-spectrum coverage with multiple antimicrobials is initiated empirically, unnecessary drugs should be discontinued as soon as culture results are available indicating the sensitivity profile of pathogens. If multiple antibiotics are used initially and resistance to one of them is apparent on culture, it may be replaced with another drug to which the organism is susceptible. However, substitution is not necessary if there has been a sufficient clinical response to the other antibiotic being used. If resistance is reported to both drugs and clinical symptoms have not improved, treatment should be changed to a drug to which the pathogen appears sensitive in vitro. If resistance is reported to both drugs, but there has been significant improvement in clinical symptoms, continuation of current treatment may be appropriate despite in vitro test results. Alternative diagnoses should be reconsidered if there is no clinical response within 72 hours despite antimicrobial treatment that should be expected to be effective based on culture and sensitivity results. Antimicrobial treatment duration of four to six weeks has previously been recommended. However, treatment in humans is typically seven to 14 days, and there is little evidence to suggest longer treatment should be necessary in dogs. In the absence of specific evidence, treatment duration of 10 to 14 days is recommended. A recheck of all abnormal parameters present on diagnosis and of urine culture should be performed one to two weeks after cessation of therapy. A positive urine culture result in the absence of clinical symptoms or relevant abnormalities on other diagnostic tests should be managed as recommended for asymptomatic bacteriuria. Urinary catheters The prevalence of bacteriuria following urinary catheterization in dogs and cats is high (10 to 55 percent). The majority of these are likely cases of subclinical bacteriuria, which should be distinguished from bacterial cystitis on the basis of clinical signs. Cytological analysis of urine is not a reliable indicator of cystitis in catheterized patients. Urine culture is not indicated in the absence of clinical signs of cystitis or other suspicion of bacterial infection in catheterized patients. Prophylactic use of antimicrobials in patients with indwelling urinary catheters is not recommended. Treatment of bacteriuria or removal of urinary catheter when bacteriuria is detected is not indicated in the absence of clinical signs of cystitis. Culture of catheter tip is not recommended. Routine urine culture after removal of urinary catheters is not indicated, though such testing may be appropriate for some cases. Antibiotic treatment following removal of urinary catheters in the absence of signs of cystitis is not recommended. When patients develop signs of cystitis or system signs of infection while a urinary catheter is in place, ideally the catheter should be removed and a urine sample obtained by cystocentesis for culture. A new catheter should then be placed. If it is necessary to maintain a urinary catheter in a patient with confirmed bacterial cystitis, antimicrobials should be selected and used as recommended for sporadic bacterial cystitis, though the presence of the catheter may reduce the chances of successful treatment. Urinary tract surgery When possible, urine culture should be performed on a sample obtained by cystocentesis prior to any surgical or endoscopic urinary tract procedure. If significant bacteriuria is identified, antimicrobial treatment for three to five days should be considered prior to the procedure. Perioperative antibiotics should be considered prior to surgical procedures involving the urinary tract if preexisting bacteriuria has been identified by culture. A first- or second-generation cephalosporin should be given no more than 60 minutes prior to the procedure and repeated every two half-lives for that drug until surgical closure. Perioperative antibiotic treatment should not continue for more than 24 hours after the procedure unless preoperative bacteriuria or infection was identified and additional treatment for this is indicated. Urolithiasis Urine culture should be performed in all patients with urolithiasis, regardless of the suspected stone type. Culture of surgically removed uroliths is indicated in dogs for known or suspected struvite uroliths if the preoperative urine culture was negative. If bacteriuria is identified in patients with known or suspected infection-associated uroliths and signs of cystitis, antimicrobials should be selected based on sensitivity testing. The optimal duration of antibiotic treatment during medical dissolution therapy for uroliths is not known. It is thought short courses (e.g. seven days) should be sufficient to control signs of cystitis and support dissolution therapy when urease-producing bacteria (e.g. Staphylococcus pseudintermedius, Proteus spp.) are present. If non-urease producing bacteria are identified (e.g. E. coli) and there are no signs of cystitis, antimicrobial therapy during urolith dissolution may not be indicated. Superficial bacterial folliculitis11 Diagnosis is usually based on clinical lesions and cytology showing presence of cocci. Bacterial culture is indicated in the following circumstances: Less than 50 percent reduction in the extent of lesions after two weeks of appropriate antimicrobial therapy. Emergence of new lesions two weeks or more after the initiation of antimicrobial therapy. Residual lesions and presence of cocci on cytology after six weeks of antimicrobial therapy. Presence of intracellular rod-shaped bacteria on cytology. History or multidrug-resistant infection in the patient or a close companion. Topical therapy without use of systemic antimicrobials is preferred when possible. Shampoos, lotions, rinses, and other products can be selected based on the extent of the lesions and other details of the specific case. Expert consensus suggests duration of antimicrobial treatment of at least three weeks and a minimum of seven days beyond clinical resolution. Expert consensus guidelines discourage concurrent use of glucocorticoids during treatment of bacterial folliculitis. Miscellaneous antimicrobial uses Perioperative antibiotics: Inappropriate use of antibiotics in surgical cases can harm patients and foster antibiotic resistance. The risk of infection and sepsis associated with surgical procedures is related to technique and patient characteristics, and it is significantly influenced by the nature of the surgical procedure and the condition of the patient (often categorized by the American Society of Anesthesiologists’ [ASA’s] staging system). The following classification of surgical procedures and associated surgical site infection (SSI) risk are useful for informing decisions about antibiotic use. The higher the risk of infection based on surgery type, the more likely antibiotic use is to be beneficial.12 ASA staging has been adapted to veterinary patients and can help in assessing the risk of SSI. General principles of antibiotic use in reducing SSIs include Low-risk patients (ASA Class 1 to 2 with clean procedures) do not require antibiotic prophylaxis. High-risk patients (ASA Class 3 to 5, patients with systemic infections, infected wounds, or undergoing clean-contaminated, contaminated, or dirty procedures) should receive antibiotics perioperatively. If pathogens associated with skin are likely contaminates (e.g. Staphylococci and Pasteurella), consider cefazolin (20 mg/kg IV) preoperatively and repeat at 90-minute intervals until closure of the incision. If pathogens associated with the gastrointestinal tract or other viscera are likely, consider ampicillin (20 mg/kg IV) preoperatively and repeat at 90-minute intervals until closure of the incision. In critical patients (ASA Class 4 to 5) or if peritoneal spillage of intestinal contents or pus occurs, ampicillin or cefazolin can be supplemented by enrofloxacin (5 mg/kg IV) to provide better coverage of Gram-negative bacteria. Administer antibiotics 30 to 60 minutes prior to the incision, typically at induction. If the procedure is prolonged, IV doses should be repeated every 90 minutes. One or two additional doses can be considered after surgery to cover late bacterial growth, but antibiotic administration should not continue more than 24 hours after the procedure unless established infection is present. Extended postoperative antibiotic use is often not indicated in the absence of established infection or sepsis present prior to surgery, and it can cause patient harm. Perioperative antibiotics are not routinely indicated for dentistry. The concern about bacteremia and endocarditis associated with dental procedures has proven unfounded. Antibiotics may be indicated for dentistry patients with established oral infection, especially osteomyelitis. The bottom line Like our counterparts in human medicine, veterinarians frequently use antibiotics excessively and inappropriately. Our intention is to protect and benefit our patients, but the results are often unnecessary harm from these medicines for those who do not need antimicrobial therapy and reduced efficacy for antimicrobial drugs, which is detrimental to those patients who truly do need them. Much of the inappropriate use of antibiotics is driven by outdated habits and practices, as well as a lack of familiarity with the evidence regarding when and how to best use antimicrobials. These factors can be mitigated by better evidence and education. However, common flaws in human reasoning are also frequently to blame. Research in cognitive biases and the impact of how we make medical decisions has shown veterinarians and our clients share patterns of thought that encourage inappropriate use of medications.13-18 The following are just a few of the cognitive biases that lead us to misuse antimicrobial therapies: Commission bias: The tendency to favor action over inaction when faced with a potential health problem. We and our clients have a powerful need to “do something” even when doing nothing is likely better for the patient. Attribution bias: The tendency to give credit for clinical improvement to particular actions we have taken. When patients are better after antimicrobial treatment, veterinarians and pet owners often assume the treatment is the reason for the improvement. For example, despite strong evidence feline interstitial cystitis is self-limiting and antibiotics do nothing to shorten the clinical course, it is still difficult to convince clients and some veterinarians that antibiotics are not indicated when their use has been associated with resolution in the past. Impact bias: We overestimate the benefits and underestimate the harms of our medical treatments. Availability bias: We remember the rare cases in which we may not have prescribed a treatment we should have and we forget the more numerous cases that either got better without treatment or were harmed by it. This leads us to favor treatment over inaction, even when the evidence suggests treatment is not indicated. Unlike the lack of evidence, which can be corrected through research and education, such mental habits that lead to inappropriate antimicrobial use can only be overcome by awareness and an individual commitment to continually combat them. We must retrain ourselves as clinicians to follow evidence-based guidelines when they are available, even if they contradict our instincts or personal experience. We must continually ask ourselves, “Why am I prescribing this drug? Is it truly necessary? Is there something else I could do that has less risk or will not contribute to AMR? How can I educate the client that it may be better for their pet not to have an antibiotic?” In addition to recognizing the seriousness of AMR and the need for better antimicrobial stewardship, committing ourselves to developing new habits in practice is needed if we are to maintain the usefulness of these tremendously powerful therapies and best serve the health of our patients. Brennen McKenzie, MA, MSc, VMD, cVMA, discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists’ opinions do not necessarily reflect those of Veterinary Practice News. REFERENCES Guardabassi L, Prescott J. Antimicrobial Stewardship in Small Animal Veterinary Practice: From Theory to Practice. Vet Clin North Am Small Anim Pract. 2015;45(2). doi:10.1016/J.CVSM.2014.11.005 Chua K-P, Fischer MA, Linder JA. Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study. BMJ. 2019;364. doi:10.1136/BMJ.K5092 Rantala M, Hölsö K, Lillas A, Huovinen P, Kaartinen L. Survey of Condition-Based Prescribing of Antimicrobial Drugs for Dogs at a Veterinary Teaching Hospital. Vet Rec. 2004;155(9). doi:10.1136/VR.155.9.259 Shea A, McCarthy R, Lindenmayer J. Therapeutic Antibiotic Use Patterns in Dogs: Observations from a Veterinary Teaching Hospital. J Small Anim Pract. 2011;52(6):310. doi:10.1111/J.1748-5827.2011.01072.X JS W. Investigation of Antimicrobial Use and the Impact of Antimicrobial Use Guidelines in a Small Animal Veterinary Teaching Hospital: 1995-2004. J Am Vet Med Assoc. 2006;228(4). doi:10.2460/JAVMA.228.4.553 Weese JS, Blondeau JM, Boothe D, et al. 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;2011:263768. doi:10.4061/2011/263768 Llewelyn MJ, Fitzpatrick JM, Darwin E, et al. The antibiotic course has had its day. BMJ. 2017;358:j3418. doi:10.1136/bmj.j3418 Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf. 2014;5(6):229. doi:10.1177/2042098614554919 Lappin MR, Blondeau J, Boothe D, et al. 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. J Vet Intern Med. 2017;31(2):279-294. doi:10.1111/jvim.14627 Weese JS, Blondeau J, Boothe D, et al. International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Vet J. 2019;247:8-25. doi:10.1016/j.tvjl.2019.02.008 Hillier A, Lloyd DH, Weese JS, et al. 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. doi:10.1111/vde.12118 Nelson LL. Surgical site infections in small animal surgery. Vet Clin North Am Small Anim Pract. 2011;41(5):1041-1056, viii. doi:10.1016/j.cvsm.2011.05.010 Canfield P, Whitehead M, Johnson R, O’Brien C, Malik R. Case-based Clinical Reasoning in Feline Medicine: 2: Managing Cognitive Error. J Feline Med Surg. 2016;18(3). doi:10.1177/1098612X16631233 Canfield PJ, Whitehead ML, Johnson R, O’Brien CR, Malik R. Case-based clinical reasoning in feline medicine. J Feline Med Surg. 2016;18(1):35-45. doi:10.1177/1098612X15623116 Vandeweerd J-M, Vandeweerd S, Gustin C, et al. Understanding Veterinary Practitioners’ Decision-Making Process: Implications for Veterinary Medical Education. J Vet Med Educ. 2012;39(2):142-151. doi:10.3138/jvme.0911.098R1 Whitehead M, Canfield P, Johnson R, O’Brien C, Malik R. Case-based Clinical Reasoning in Feline Medicine: 3: Use of Heuristics and Illness Scripts. J Feline Med Surg. 2016;18(5). doi:10.1177/1098612X16643251 McKenzie BA. Veterinary clinical decision-making: Cognitive biases, external constraints, and strategies for improvement. J Am Vet Med Assoc. 2014;244(3). doi:10.2460/javma.244.3.271 Scott I, Soon J, Elshaug A, Lindner R. Countering Cognitive Biases in Minimising Low Value Care. Med J Aust. 2017;206(9). doi:10.5694/MJA16.00999

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