Empirical Antibiotic Therapy
World Small Animal Veterinary Association World Congress Proceedings, 2013
Lauren A. Trepanier, DVM, PhD, DACVIM, DACVCP
University of Wisconsin-Madison, Madison, WI, USA

Is There Good Evidence of Bacterial Infection?

The first step in empirical antimicrobial therapy is to first critically ask whether there is good evidence of a bacterial infection. Too often, antimicrobials are prescribed on a "just in case" basis or because an owner resists additional diagnostics. There are several very real drawbacks of "just in case" antimicrobials: they add to the cost of the visit or hospitalization, without contributing to a diagnosis; they may lead to diarrhea, inappetance, or vomiting that obscure the underlying problem; they can cause adverse reactions or drug interactions; and importantly, they encourage the selection of resistant bacteria, both globally and in your hospital, and in that patient.

Fever alone is an inadequate criterion for prescribing an antimicrobial. If the probable source of fever cannot be localized during a physical exam, it is not possible to choose an appropriate spectrum of bacterial coverage or decide how long to treat. Physical exam findings that support the use of antibiotics without additional diagnostics are usually straightforward, such as skin pustules or epidermal collarettes, a traumatic wound with purulent exudate, or a carnassial tooth root abscess. Cytology should be performed on all exudates, particularly in areas endemic for systemic fungal infections, prior to considering antibacterials.

Leukocytosis alone is not a good justification for antimicrobials, since leukocytosis can result from stress, inflammation, or glucocorticoids. If a left shift and toxic change are present with leukocytosis, then a source of infection or significant inflammation should be pursued. Neutropenia with fever, however, is an established indication for empirical antimicrobials, at least in humans. Meta-analyses of studies in humans suggest that the benefit of antibacterials in neutropenic patients, even prior to fever, outweighs the negative effects of selecting for bacterial resistance.1 A beta lactam and fluoroquinolone combination is recommended in humans, which provides coverage against gut flora to include anaerobes and Enterococcus (beta lactam) and Gram negatives (fluoroquinolone).

Antimicrobials are inappropriate in most cats with lower urinary tract signs. There is a < 5% incidence of positive urine cultures in cats with lower urinary tract disease overall.2 Clients' money is better spent on a urinalysis and bladder imaging for stones. Cats at higher risk for bacterial urinary tract infections are those with diabetes mellitus (13% prevalence),3 perineal urethrostomies, chronic renal failure, or in older cats with dilute urine.2 For these cats, urine culture may be a good investment.

For cats with upper respiratory infections, there are no good studies comparing antimicrobials to placebo. Although Mycoplasma is commonly isolated from pharyngeal swabs in cats, underlying viral infection is typical, and cats have similar recovery rates whether antimicrobials with and without activity against Mycoplasma are used.4 When active Mycoplasma or Chlamydia infection are documented or suspected, doxycycline remains the drug of choice. Suspension is preferable to capsules, to decrease the risk of esophagitis.5-7

Diarrheas in dogs and cats are usually not caused by pathogenic bacteria. For example, in dogs with acute diarrhea, the prevalence of Salmonellosis (2%), Campylobacter (5%), and Clostridium difficile toxin (10%) is low.8 Empirical antimicrobials, such as amoxicillin or fluoroquinolones, are not indicated for most acute diarrheas. Fiber, probiotics, or bismuth/subsalicylate (in dogs), along with a short-term diet change, may be a better approach.

Finally, pancreatitis is usually sterile in dogs and cats. Antimicrobials are not indicated unless peritonitis, pancreatic abscess, or loss of intestinal mucosal integrity (bloody diarrhea with mucosal sloughing) develops. In humans, antimicrobials in necrotizing pancreatitis do not affect clinical outcomes, including mortality.9

Helpful Diagnostics in Lieu of Culture

Pyuria with bacteria in a urine sediment provides a strong indication for antimicrobials, although bacteriuria can be overdiagnosed. If cocci are frequently diagnosed in your in-house urine sediments, be cautious; stain precipitates can mimic cocci. The majority of urinary pathogens in dogs are Gram-negative rods.10 In cats, Gram-positive and Gram-negative pathogens occur at approximately the same rate; however, urinary tract infections are much less common in cats overall. The finding of intracellular bacteria on cytology is a strong rationale for antimicrobials. A Gram stain, which is immediate and cheap, narrows the spectrum to Gram positive, Gram negative, or mixed. Gram stains are underutilized in companion animal practice. For a review of technique, see www.life.umd.edu/classroom/bsci424/LabMaterialsMethods/GramStain.htm.

Deciding About Cultures

Cultures are not necessary for first-time empirical treatment of many routine bacterial infections, to include acute contaminated wounds, carnassial tooth abscesses, infectious tracheobronchitis, superficial pyodermas, cat bite abscesses, or first-time bacterial cystitis in adult dogs. Cultures are important for any second-line antimicrobial treatment, to include lack of response to empirical treatment, relapse after treatment discontinuation, or waxing and waning signs. Avoid antibiotic roulette in these cases! With recurrent urinary tract infections, serial cultures can be helpful, as repeated culture of the same organism suggests inadequate clearance (immunosuppression, poor compliance, uroliths, or prostatitis with inadequate drug penetration), while different organisms suggest ascending infections (due to ectopic ureters, urethral incompetence, vulvar fold pyoderma), or poor perineal hygiene.

Cultures are important for serious or life-threatening infections, to include pyothorax, endocarditis, osteomyelitis, joint sepsis, pyelonephritis, or sepsis. Cultures are also recommended for suspected hospital-acquired infections (those developing > 72 hours after admission), since nosocomial bacteria may have multidrug resistance patterns.11

Practical Culture Techniques

Urine is ideally set up for culture within 15 to 30 minutes of collection, but this is often impractical. Alternatively, a sterile syringe containing urine can be capped and refrigerated immediately, for up to 12 hours prior to culture. While some fastidious bacteria may not survive storage > 1 hour, this approach is adequate in most situations and allows quantitative cultures. For aerobic cultures of small fluid volumes, our microbiologist recommends BBL CultureSwab Plus (Amies gel formulation without charcoal; Fisher Scientific). Fluids for culture should not be placed in heparin or EDTA. For both anaerobic and aerobic cultures - recommended for bile, body fluid, and pus - transport media should be used. A.C.T.II agar tubes (Remel) contain a nonnutritive semisolid medium to which you can add fluid or swabs, although fluid is preferable; organisms are stable for 24 hours for culture setup. Mycoplasma cultures from tracheal wash samples13 can be run from either CultureSwab Plus (no charcoal) or A.C.T.II tubes.

If your laboratory does not provide cultures at an affordable price with a useful turnaround time, talk to the laboratory manager about your concerns. In-house cultures are also an option and may not require an incubator. One author recommends inoculation of blood agar and MacConkey plates with a sterile calibrated loop or pipette, followed by incubation 11 cm under a 60-watt bulb for 24 hours.14 Positive plates are submitted for identification and susceptibility.

Empirical First-Line Regimens

First, use the narrowest spectrum drug for the suspected organism. For example, choose amoxicillin instead of amoxicillin-clavulanate for a cat abscess, and doxycycline rather than a fluoroquinolone for suspected Bordetella infectious tracheobronchitis.15

Second, consider tissue penetration. It should be assumed that urinary tract infections in male dogs involve the prostate, and antimicrobials with good prostatic penetration, such as fluoroquinolones,17 doxycycline, chloramphenicol, or potentiated sulfonamides should be chosen. For bronchitis without pneumonia, drugs that achieve high concentrations in bronchial secretions should be prescribed, to include fluoroquinolones, doxycycline, azithromycin, or potentiated sulfonamides. Beta lactams and aminoglycosides, which are relatively polar, have poor penetration into the prostate, eye, testes, or bronchial secretions.

Finally, treat for the shortest effective period possible. There is a trend toward the use of shorter courses of antimicrobials in human patients, with equivalent efficacy compared to longer regimens.18 Acute sinusitis,19 pneumonia,20 and uncomplicated urinary tract infections21 are treated effectively with 3- to 7-day courses of antibiotics in humans. Pediatric bacterial otitis can be treated with a single dose of azithromycin, which is as effective as 7 doses. Community-acquired pneumonia treatment is continued for only 2–3 days beyond resolution of fever.18 In veterinary medicine, there is little evidence to support the longer antibiotic courses that are recommended in textbooks. Consider using these shorter antibiotic regimens, with a follow-up culture one week after discontinuation. Shorter treatment regimens are less expensive for clients (allowing more resources for diagnostics and followup), are associated with better compliance, and, importantly, lead to less bacterial resistance.18

Common isolates from bacterial infections in dogs

Indication

Most common organisms

Empirical antimicrobial

Bacterial cystitis

E. coli (51%)10

Amoxicillin/clavulanate (female)
Fluoroquinolone (male)

Endocarditis*

Gram positives (51%; esp. Strep canis);22
Gram negatives (22%);
Bartonella (20%)

Cephalexin plus fluoroquinolone, awaiting cultures and Bartonella testing

Hepatobiliary

72% negative cultures (bile)
E. coli, Gram positives, anaerobes23

Amoxicillin/clavulanate plus fluoroquinolone

Joint sepsis*

Staph. sp.24,25

Cephalexin

Osteomyelitis*

Staph. and Strep26

Cephalexin

Pneumonia

Young dogs: Bordetella, other Gram negatives27

Doxycycline (apparently low risk of enamel discoloration)

Prostatitis

E. coli

Fluoroquinolone

Pyometra

E. coli28

Fluoroquinolone

Superficial pyoderma

Staph pseudintermedius

Cephalexin

* Cultures strongly recommended

Common isolates from bacterial infections in cats

Abscess

Pasteurella, anaerobes29

Amoxicillin (95% efficacy)29

Hepatobiliary

64% negative cultures (bile)23
Mixed Gram positives, negatives, and anaerobes

Amoxicillin/clavulanate plus fluoroquinolone

Pyelonephritis

E. coli, Enterococcus30

Base on urine sediment

Pyothorax*

Anaerobes, Pasteurella31

Penicillin (awaiting culture)

* Cultures strongly recommended

Typically effective antimicrobials for different bacterial types

Gram-positive aerobes

Commonly
effective
Penicillin
Amoxicillin, ampicillin
Clindamycin (except Enterococcus)
Cephalexin (except Enterococcus)
Chloramphenicol

Typically ineffective
Metronidazole

Beta-lactamase-producing Gram-positive aerobes

Commonly effective
Amoxicillin/clavulanate
Cephalexin
Clindamycin
Fluoroquinolones (Staph > Strep)
Potentiated sulfonamides

Typically ineffective
Penicillin, amoxicillin, ampicillin
Metronidazole

Gram-negative aerobes

Commonly
effective
Fluoroquinolones
Aminoglycosides
Amoxicillin/clavulanate (urine)
Cephalexin (urine)
Chloramphenicol
Potentiated sulfonamides

Typically ineffective
Clindamycin, azithromycin
Metronidazole

Anaerobes

Commonly effective
Metronidazole
Amoxicillin/clavulanate
Clindamycin, azithromycin
Chloramphenicol

Typically ineffective
Fluoroquinolones
Aminoglycosides
Cephalexin

References

References are available upon request.

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Lauren A. Trepanier, DVM, PhD, DACVIM, DACVCP
University of Wisconsin-Madison
Madison, WI, USA


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