Rational Antibiotic Use in Small Animal Practice – Specific Clinical

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Rational Antibiotic Use in Small Animal Practice – Specific Clinical Scenarios
Peter Foley,
MSc, DVM, DACVIM
Perioperative Antibiotic Use
The goal in surgery is always to prevent a surgical site infection rather than to treat it
after it has occurred. Care must be taken to emphasize sterile surgical technique and to
not cut corners. Gentle tissue handling, meticulous hemostasis, judicious use of suture
materials and electrocautery, and accurate apposition of tissue without obstruction of
blood supply will also minimize the risk of surgical site infections. Even in situations of
excellent sterile technique, the risk of surgical site infection is never 0%. The longer a
surgery takes, the greater is the risk of wound infection. In fact, the risk of surgical site
infection doubles for every hour of surgery time. This is likely due to suppression of the
local immune system with increased tissue handling and cautery, more suture material
used, and prolonged exposure of tissue to the microbial environment. Even anesthesia
time alone, independent of surgical time, increases the risk of surgical site infection by up
to 30% for every hour of anesthesia. This prolonged anesthesia time can be due to
perioperative diagnostic procedures such as radiographs; preparation and disinfection of
the surgical site; delays in starting the surgery, etc. Anesthetic drugs may suppress or
compromise the local immune system due to direct effects, poor oxygenation, and poor
perfusion. Excessive traffic of people in the operating room may increase the risk of
infection by up to 30%
Antibiotics may be used prophylactically in cases where the risk of contamination is
relatively high (such as in clean-contaminated or contaminated surgeries), or when
infection would be disastrous should it occur (eg: orthopedic implant infection). It is still
open to debate how efficacious prophylactic antibiotics are in clean surgeries. There
have been conflicting results in studies on clean surgeries comparing patients who receive
antibiotics prophylactically versus placebo. The fear is that prophylactic antibiotics may
select for resistant infections.
It is generally recommended to use prophylactic antibiotics when the surgery is
contaminated [eg: the gastrointestinal tract (GI) is being entered], when the surgery is
longer than 90 minutes, or when orthopedic implants are being used. While a variety of
different antibiotics can be used prophylactically, cefazolin 22 mg/kg IV every 90
minutes is commonly used for orthopedic surgeries and those on the upper GI tract. The
first dose of prophylactic antibiotic is usually given intravenously 30 minutes prior to
starting the surgery. If the lower GI tract is involved, antibiotics with better anaerobic
spectrum are usually advised. Cefoxitin 22 mg/kg IV every 90 minutes could be used
instead of cefazolin, or metronidazole could be used in combination with cefazolin.
Antibiotics should not be continued in the hours or days after the surgery unless gross
contamination was documented or strongly suspected. Studies have shown that animals
that were given prophylactic antibiotics for days after surgery actually had a higher risk
of developing infections than those who received no antibiotics.
In the days postoperatively, the healing incision may look inflamed and the patient may
run a slight fever (especially cats receiving hydromorphone). Such clinical signs may
merely be due to normal inflammation and healing, and may not indicate bacterial
infection. Any discharge from a surgical incision, however, is unusual, and is more likely
to be due to an infection than normal healing. If a discharge is present, antibiotics may
be considered to treat or prevent infection.
Treating Urinary Tract Infections:
First time bacterial cystitis:
Urinary tract infections are relatively common in female dogs. If the patient is young or
middle-aged, with clinical signs that are confined to the lower urinary tract (polakiuria
and stranguria), some practitioners will simply prescribe a safe antibiotic that is excreted
in high quantities in the urine without resorting to further diagnostic testing if it is a first
time occurrence (eg amoxicillin 20-30 mg/kg PO q12hr). This is often the strategy
pursued in human medicine. While this approach can work well in a lot of cases, it is
ideal to perform a urinalysis and urine culture and sensitivity to determine if the bacteria
isolated is susceptible to the antibiotic selected.
Older dogs and cats and recurrent urinary tract infections:
In older patients with lower urinary tract signs, and in cases where the urinary tract signs
are recurrent, it is best to perform more extensive diagnostic testing to identify factors
that may be predisposing the patient to urinary tract infections. In these patients, in
addition to a urinalysis and urine culture and sensitivity, I recommend performing a
complete blood count (CBC) and serum biochemistry profile to rule out endocrine or
systemic diseases such as diabetes mellitus, hyperadrenocorticism, or chronic renal
failure; and radiographs or ultrasound of the urinary tract to rule out bladder neoplasia or
cystic calculi that may be harboring infection. In these patients I usually start therapy
with amoxicillin 20-30 mg/kg PO q12hr while I am awaiting urine culture and sensitivity
results.
Interpreting Minimum Inhibitory Concentration (MIC) data:
Disk diffusion (Kirby-Bauer technique) antibiotic susceptibility testing is usually
sufficient for selecting an antibiotic that will be effective in a particular urinary tract
infection, but it is important to remember that the concentration of the antibiotic in the
test disk approximates the concentration that will be present in the patient’s serum. Some
antibiotics, especially beta lactam antibiotics, are excreted in very high quantities in the
urine. In fact many renally excreted antimicrobial drugs will reach urine concentrations
10 to 100 times greater than the concentration in serum. As a result, antibiotics that
appear to have intermediate sensitivity on a disk diffusion susceptibility test may well be
completely effective in treating a urinary tract infection. One way to more accurately
determine the efficacy of an antibiotic in treating a particular urinary tract infection is to
measure the MIC of a series of antibiotics against a particular urine sample. The MIC
measures the concentration of the antibiotic that will inhibit growth of the bacterium in
question. The concentration of the antibiotic that is likely to be bactericidal is four times
the MIC. In order to use MIC data, you need to know the concentration of antibiotic that
is likely to be present in urine. There are tables listing these concentrations of common
antibiotics in most textbooks with chapters on treating urinary tract infections (eg:
Greene’s Infectious Diseases of the Dog and Cat, 4th ed, page 1029; and Ettinger and
Feldman’s Textbook of Veterinary Internal Medicine, 7th ed, page 2042).
Recurrent UTI
When a urinary tract infection keeps recurring, a careful diagnostic investigation should
be conducted to try to identify what host factors may be predisposing the patient to the
infections. A urine culture and sensitivity (ideally including MIC) should be performed
to determine which antibiotics should be successful. A urinalysis should be performed to
rule out the presence of glucosuria. A CBC and serum biochemistry profile should be
performed to identify systemic diseases that may reduce host immunity in the urinary
tract, for example: neutropenia, hyperadrenocorticism, diabetes mellitus, and chronic
renal failure. Abdominal radiographs and ultrasound can help identify uroliths, bladder
masses, and any other anatomic abnormalities that could be predisposing the patient to
infections. Contrast radiographs or CT, or cystoscopy may also be required to fully rule
out anatomic abnormalities like ectopic ureters.
Long-term suppressive antibiotic therapy (periodic antimicrobial dosing)
Some patients can have frustrating, recurrent episodes of urinary tract infections despite
appropriate antibiotic selection and no evidence of underlying predisposing factors. One
controversial therapy in these situations is to give chronic once daily antibiotics to try to
keep infections from recurring. The antibiotic is usually given just before bedtime so that
it accumulates and remains in the bladder overnight. Examples of antibiotics that have
been used in this way include amoxicillin, cephalexin, trimethroprim sulpha (TMS), and
enrofloxacin. This therapy is controversial because studies proving its efficacy are
lacking, it may encourage the development of antimicrobial resistance, and it may be
used as a substitute for appropriate diagnostic investigation into predisposing factors. If
suppressive therapy is to be used at all, it should be as a last resort after any urinary tract
infection has been at least temporarily eliminated, and a full diagnostic workup has been
performed.
Antibiotics with urinary catheters
Urinary catheters may introduce bacteria into the urinary bladder. Even if the catheter is
placed completely aseptically, the presence of foreign material impairs the local immune
system function and serves as a conduit of bacteria into the urinary tract. Urinary tract
infections are common a few days after placement of a urinary catheter, even if a closed
urine collection system is used. This is because the bacteria can travel up the outside of
the catheter even more easily than up the lumen of the catheter. Given this likelihood of
a UTI, some veterinarians may be tempted to place the patient on prophylactic antibiotics
at the time of catheter placement to try to prevent an infection from becoming
established. This would be a mistake, however, as there is little evidence that
prophylactic antibiotics prevent infection – instead they merely tend to promote the
development of an infection that is resistant to the antibiotic selected. Antibiotics should,
therefore, be avoided in patients with an indwelling urinary catheter. It is prudent to
culture the urine at the time the catheter is removed to document any bacterial infections
that may have been introduced by the catheter. In some cases, it may be necessary to
have a patient on antibiotics while a urinary catheter is in place, despite this propensity
for selecting for a resistant infection. Such cases include patients with a life-threatening
bacterial infection (eg: sepsis) who must have a urinary catheter in place (eg: urethral
obstruction, paralysis, profound debilitation, etc). In these cases where the patient must
be on antibiotics at the same time as a catheter is in place, it is especially important to
culture the urine at the time the urinary catheter is removed, to document what bacteria
might be present and what antibiotics they are susceptible to.
Antibiotics and feline lower urinary tract disease (FLUTD)
Bacterial cystitis is rare in cases of FLUTD. Antibiotic use in FLUTD is not warranted,
and is potentially dangerous, unless a bacterial infection can be detected on urine culture.
Occult urinary tract infections
Occult urinary tract infections are those in which a bacterial infection is documented on
urine culture, and yet the patient is experiencing no clinical signs of infection (ie: no
evidence of stranguria, polakiuria, dysuria, and hematuria). These infections are
relatively common in patients with diabetes mellitus and hyperadrenocorticism. The
conventional wisdom in the past was to always treat these infections with appropriate
antibiotics, based on sensitivity data, in an attempt to decrease the risk of more serious
ascending infections (ie pyelonephritis). Some have advised against treating occult UTIs
as there is little evidence that it is beneficial, and some evidence from human medicine
that it might actually increase the likelihood of recurrent UTI. The treatment of occult
UTI in human medicine is currently discouraged, and the issue of treating occult UTI in
animals is currently being debated in the American College of Veterinary Internal
Medicine.
Lyme Disease
The question often arises whether to treat with antibiotics every animal that tests positive
for Lyme disease on a 4Dx snap test. The usual policy is to treat positive animals only if
they have clinical signs that could be attributed to Lyme disease (lameness, proteinuria,
anorexia, etc). A dog that tests positive, but has no clinical signs may be one of the many
dogs that have had a subclinical infection, and were able to clear the infection. In human
medicine, taking a single dose of doxycycline within 72 hours of being bitten by a tick
has been shown to be effective in preventing Lyme disease. No such study has yet been
performed in dogs. At present, most internists do not recommend automatically treating
every dog that has been bitten by a tick. While doxycycline (10 mg/kg PO q12-24hr for 4
weeks) is most commonly prescribed for Lyme disease, amoxicillin (20 mg/kg PO q8hr
for 4 weeks) also seems to be effective.
Leptospirosis
The drug of choice for Leptospira infections in dogs is doxycycline 5 mg/kg PO or IV
q12hr for 2 weeks. In patients that are vomiting, ampicillin (20 mg/kg IV q6hr) can be
used instead, until the patient is able to begin a 2 week course of doxycycline. Other
dogs living in the house with a dog with clinical leptospirosis may become infected from
the sick dog, or may have been exposed to the same source of infection as the sick dog.
Because of this, and the risk of zoonotic transmission of leptospirosis to humans in the
household, it is currently recommended to treat all other dogs in the household with
doxycycline 5 mg/kg PO q12hr for 2 weeks, and ideally check their acute and
convalescent titres against Leptospira.
Anaplasma phagocytophilum
Anaplasmosis is rare in the Atlantic region, but at least one case has been documented. It
causes a variety of non-specific clinical signs including lethargy, anorexia, lameness,
stiffness, and oculo-nasal discharge. Mild to marked thrombocytopenia is typically, but
not always present. The 4Dx snap test is the most common way to diagnose infection.
The most common treatment is with doxycycline 5-10 mg/kg PO q12hr for 14-21 days.
Upper respiratory infections in cats
Upper respiratory infections (URI) in cats are very common. Usually viruses such as
herpes and calici are involved, but occasionally Chlamydia and Bordetella can be
involved. Opportunistic bacterial infections are common after the initial viral infections
have disrupted the host defense mechanisms. Because antibiotics are ineffective in
treating the most common causes of URI in cats (herpes and caliciviruses), antibiotic
therapy is usually reserved for cases where a significant suspicion of Chlamydia or
Bordetella is present, or where the cat has a thick, green nasal discharge and anorexia,
suggesting the presence of a secondary bacterial infection. Antibiotics commonly used in
these situations include doxycycline 5 mg/kg PO q12hr for 14-21 days, TMS 15 mg/kg
PO q12hr for 7-14 days, enrofloxacin 5 mg/kg PO q24hr for 7-14 days, and azithromycin
5-10 mg/kg PO q24hr for 3-5 days. At AVC we are currently conducting a study of
shelter cats with URI, attempting to identify the prevalence of herpes virus, calicivirus,
Chlamydia, and Bordetella. In the case of any Bordetella isolates cultured, we are also
performing sensitivity to determine what antibiotics are effective against these strains.
Bordetella bronchiseptica infections in dogs
Many cases of bordetellosis are mild and resolve without the need of antibiotics. In these
cases, the patient remains bright with an adequate appetite. In cases where the patient is
more severely affected, antibiotics may be required. Ideally an oropharyngeal swab,
transtracheal wash, or bronchoalveolar lavage should be cultured as this organism
displays a high level of antimicrobial resistance. While culture results are pending,
empirical treatment with doxycycline 5 mg/kg PO q12hr, amoxicillin-clavulanate 12.5-25
mg/kg PO q12hr, or TMS 15-30 mg/kg PO q12hr are usually selected.
Parvoviral enteritis
While parvoviral enteritis is obviously caused by a virus that is obviously immune to
antibiotics, the profound immunosuppression the virus causes by its destruction of rapidly
dividing bone marrow stem cells leaves the host open to potentially fatal opportunistic
infections from normal gastrointestinal (GI) bacteria. This mixed bag of bacteria requires
a broad spectrum of antibiotic coverage. Since the patients most commonly affected by
parvoviral infection are growing puppies, enrofloxacin should ideally not be used, as it
has been know to cause joint damage in growing animals. If the patient is not yet
profoundly neutropenic, ampicillin 22 mg/kg IV q6hr is usually prescribed. If the patient
becomes profoundly neutropenic, gentamycin 6.6 mg/kg IV q24hr is usually administered
along with the ampicillin if the patient is well hydrated (to avoid renal toxicity). If the
patient is not well hydrated, cefoxitin 22 mg/kg IV q6-8hr can be given as a single agent.
Aspiration pneumonia
Aspiration pneumonia can occur with severe vomiting or regurgitation, particularly in
severely debilitated animals, animals under general anesthesia, and animals with
esophageal disease. While the worse damage to the lungs in aspiration pneumonia is
thought to be caused by the introduction of gastric acid into the lungs, GI bacteria are
also introduced into the lungs and can grow in the damaged lung tissue. Ideally a sample
of lung or tracheal fluid (transtracheal wash or bronchoalveolar lavage) should be
cultured to determine which antibiotics should be selected. In many pneumonia patients,
however, their degree of respiratory compromise places them at significant risk for these
diagnostic procedures. Often a broad spectrum combination of antibiotics, such as
ampicillin 22 mg/kg IV q6-8hr and enrofloxacin 5 mg/kg IV q24hr, is selected to combat
the various types of GI bacteria that might be present. After a few days, if the animal is
eating adequately, they can be switched to oral amoxicillin and enrofloxacin and
discharged from the hospital. It can take several weeks to clear the infection. It is
recommended to recheck thoracic radiographs every two weeks to chart recovery. The
antibiotics should be continued for 2 weeks beyond resolutions of radiographic signs of
pneumonia (a minimum of 4 weeks).
Bite and scratch wounds and abscesses
If abscesses are present, lancing and lavaging them is more important than antibiotic
therapy in clearing the infection. In many cases antibiotics are probably not even
required. The problem comes when it is unclear if there is a concurrent bacterial cellulitis
or fasciitis that would benefit from antimicrobial therapy. Culture of the abscess or
wound is useful in determining what antimicrobial therapy would be most appropriate.
While culture results are pending, a variety of antibiotics could be selected. I usually
choose amoxicillin-clavulanate 12.5-25 mg/kg PO q12hr.
Necrotizing fasciitis
This fulminant infection of the skin, subcutis, and fascia is most commonly caused by βhemolytic group G Streptococcus organisms. Aggressive surgical debridement of the
affected tissue and intensive supportive care are essential in the treatment of these cases.
Culture and sensitivity will help determine the most appropriate antibiotic, but
clindamycin 5-10 mg/kg IV q12hr seems to be the best choice while awaiting culture
results.
Bacterial prostatitis
This is a disease of intact male dogs. Castration usually results in clearing of the
infection and prevention of recurrence. Urine culture or prostatic wash can help
determine the most appropriate antibiotic to use. Penetration of antibiotics into the
prostate gland is difficult. Enrofloxacin 5 mg/kg PO q24hr or TMS 15-30 mg/kg PO
q12hr are usually selected for their ability to penetrate the prostate gland.
Sepsis
Sepsis caused by GI bacteria (eg: severe enteritis, peritonitis, and pyometra) requires a
broad spectrum coverage (eg: ampicillin 22 mg/kg IV q6hr and enrofloxacin 5 mg/kg IV
q24hr) while culture and sensitivity results are pending. Often surgery is urgently
required to address the source of the sepsis (eg: intestinal rupture).
Pyoderma
In patients with pruritic skin lesions, skin scraping cytology and/or impression smears are
useful in ruling in bacterial pyoderma, and ruling out yeast and mites. If it is a simple,
isolated case of bacterial pyoderma, cephalexin 30 mg/kg PO q12hr or cefpodoxime 5-10
mg/kg PO q24hr for 14-28 days are often sufficient in clearing most infections. If the
pyoderma is relapsing/recurrent, there is often an underlying predisposing cause that
should be identified (eg: atopy, hypothyroidism, hyperadrenocorticism). If the infection
is non-responsive to the initially selected antibiotic, the skin should be cultured to
determine which bacterium is present [especially to rule out methicillin-resistant
Staphylococcus pseudointermedius (MRSP)]. While awaiting culture and sensitivity
results, topical therapy with chlorhexidine or other antibacterial shampoo can be initiated.
Bacterial otitis externa
Bacterial otitis externa is usually secondary to some underlying predisposing factor (eg
atopy or seborrhea). Once the infection becomes established, inflammation inadvertently
creates an excellent environment in the ear canal for the growth of bacteria: a warm,
moist, narrowed ear canal with poor circulation of air. Most topical combination
antimicrobial and anti-inflammatory ear medications are effective in decreasing the
inflammation in the canal and eliminating the bacteria. I have had considerable success
with topical 2% Burrow’s solution and 1% hydrocortisone in propylene glycol (q12hr for
7-14 days). The Burrow’s solution is an astringent that dries up the ear, and the
hydrocortisone decreases the edema and heat caused by inflammation in the ear canal. It
is now my first choice in dealing with bacterial otitis externa.
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