Wall-July PV-Review - VetLearn.com

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Compendium August 2002 Infective Endocarditis 621 Criteria for the Antemortem Diagnosis of Infective Endocarditis Without Echocardiographic Examination A murmur of recent onset plus Positive blood culture results (it is preferable to find more than one of the same microbe) plus Clinical findings and laboratory data consistent with bacteremia and IE With Echocardiographic Examination Aortic valve • Echocardiographic appearance is pathognomonic Mitral valve • Echocardiographic appearance is suggestive of IE • Supportive clinical data Signalment Murmur of recent onset Positive blood culture results Fever one unvented for anaerobic culture, and one vented for aerobic culture. 9–11,14 If acute sepsis is suspected, take three cultures 1 hour apart, and then institute antibiotic therapy. 10,42 Many negative blood cultures in humans with IE are due to infection with Bartonella, a fastidious, gramnegative organism. 31 The incidence of Bartonella endocarditis is unknown but less than that of bacterial endocarditis and has been proven in a few dogs. Bartonella resides within or on the surface of RBCs, making it difficult to isolate from blood cultures; therefore, special techniques are recommended. 31–34 Special cultivation methods may be necessary to isolate fastidious pathogens. Tissue culture methods may be required for obligate, intracellular organisms, such as Coxiella, some Bartonella, and Chlamydia. Extraction of nucleic acid from blood and subsequent polymerase chain reaction amplification has been beneficial in the early diagnosis of bacteremia and confirmation of infection with fastidious or unculturable agents. 31,34 TREATMENT Prolonged parenteral administration of one or more bactericidal antibiotics is recommended. The goal of treatment is to kill the organism as well as minimize and manage the consequences of infection. Therapy is ideally based on blood culture antibiogram results, but treatment is usually initiated before results. 46–49 Within the vegetation, organisms are protected, become meta- www.VetLearn.com Principles of Antibiotic Treatment of Infective Endocarditis • Use bactericidal antibiotics. • Ensure high antibiotic serum concentrations by administering high doses intravenously. • Continue IV antibiotic administration for at least 1 to 2 weeks. • Replace IV administration of antibiotics by SC administration when the former is no longer practical. • Continue antibiotic therapy for at least 2 to 3 months. • Use oral antibiotics only after at least 1 month of IV and SC administration. bolically dormant, and are less vulnerable to the killing activities of antimicrobials. 8–11,14 Because antibiotics reach the central areas of avascular vegetations by passive diffusion, antimicrobial therapy should be bactericidal and antibiotic serum concentrations should be high. 46 High serum concentrations are mandatory, and antibiotic serum concentrations should be maintained at the high end of the therapeutic range for at least 1 month. 4,6,9–13 We recommend at least 1 to 2 weeks of IV antibiotic therapy followed by subcutaneous (SC) administration 50 for several weeks, if possible; then oral bactericidal antibiotics should be continued for 1 to 2 months. 47 For some drugs, SC administration produces higher serum concentrations than oral administration. For example, the sodium salt of ampicillin administered at 10 mg/kg SC achieves a peak serum concentration of up to 80 µg/ml, whereas administration at 20 to 30 mg/kg PO achieves a serum concentration of only 2 to 4 µg/ml. Likewise, the salt of amoxicillin administered at 20 mg/kg PO achieves a peak serum concentration of only 8 µg/ml. Among the cephalosporins, cephapirin administered at 20 to 30 mg/kg SC produces peak serum concentrations of 20 to 30 µg/kg, and the same dosage of cefazolin produces peak serum concentrations of 40 to 60 µg/ml. Cephalexin at 30 mg/kg PO produces a peak concentration of 25 µg/ml. Clindamycin administered at 10 mg/kg SC produces a peak serum concentration of 8 µg/ml compared with 5 µg/kg when administered orally at the same dose. 50 The most common infective bacteria are known, and their antimicrobial sensitivity patterns are somewhat predictable (Table 1). If blood cultures are negative or treatment is deemed necessary before culture results are obtained, ampicillin, a first-generation cephalosporin, or ticarcillin plus gentamicin or amikacin may be used. A fluoroquinolone may be substituted for an aminogly-
622 Small Animal/Exotics Compendium August 2002 Table 1. Antimicrobial Recommendations for Bacteria Commonly Isolated in Dogs with Infective Endocarditis 9–11,13,14,42,48–50 Antibiotic Staphylococci a Streptococci Gram-Negative Organisms Anaerobes Cephalosporins First generation S S V R Second generation S S V Gram negative Third generation Cefotaxime b V S S c S Ceftiofur d V V V V Penicillin G R S R S Ampicillin R S V V Amoxicillin–clavulanate V S V S Ticarcillin e S S V V Ticarcillin–clavulanate f S S S S Fluoroquinolones S V S R Aminoglycosides S V S R Clindamycin g V S R S a Coagulase-positive staphylococci. b Claforan ® , Hoechst Marion Roussel. c Pseudomonas resistant. d Naxcel ® , Pharmacia and Upjohn Co. e Ticar ® , GlaxoSmithKline. f Timentin ® , GlaxoSmithKline. g Cleocin ® , Pharmacia and Upjohn Co. R = usually resistant; S = usually sensitive; V = Variable sensitivity; use only if indicated by antibiogram. coside. 49 Clindamycin or metronidazole administration extends the anaerobic spectrum. A good combination is clindamycin plus enrofloxacin. Aminoglycoside therapy duration should be limited to 5 to 7 days because renal toxicity is possible and concurrent fluid support is necessary 8–11 (Table 2). The choice for SC antibiotic administration should ideally be based on an antibiogram, but if blood cultures are negative or not performed, ceftiofur (2.2 mg/kg SC q12h), azithromycin (5 mg/kg SC q12h), or ticarcillin (50 to 100 mg/kg SC q8h) may be used. 14 We recommend that blood cultures be performed 4 weeks after treatment to ensure eradication of the organism. Patients, including those with negative cultures, are monitored for improvement via constitutional signs, serial CBC and serum chemistry profiles, and echocardiography. The emergence of overt CHF is ominous. Although it may offer temporary amelioration of signs, glucocorticoid administration is associated with decreased survival. 6 Supportive therapy is always a component of treatment. Acid–base, fluid, and electrolyte balance must be addressed. Nutritional support may be an important component of therapy and may be maintained by either parenteral or tube alimentation. The consequences of valvular destruction must be addressed. www.VetLearn.com Although a positive influence on disease progression is unproven, 51 angiotensin-converting enzyme (ACE) inhibition is usually recommended if there is unequivocal left-atrial or left-ventricular enlargement. Enalapril (0.25 mg/kg PO q12h for 1 week followed by 0.5 mg/kg PO q12h) or benazepril (0.25 mg/kg PO q24h for 1 week followed by 0.5 mg/kg PO q24h) are common choices. Spironolactone (1 to 2 mg/kg PO q12h), an aldosterone antagonist, may be added to the regimen as cardiac enlargement progresses. A diuretic and digoxin (0.005 to 0.01 mg/kg PO q12h) should be used if CHF is overt. Again, the influence of digoxin on disease progression may be negligible. 52 Furosemide (1 to 4 mg/kg PO q12h) is the diuretic of choice. A serum digoxin concentration should be obtained after 7 days of treatment from a sample drawn at 6 hours after the morning dose. For most laboratories, a desirable serum digoxin concentration is 1 to 1.5 ng/ml. Renal function and serum electrolyte monitoring at 1 to 2 weeks and then monthly is recommended. Augmented afterload reduction may be a useful adjunct to ACE inhibition. Adjuvant afterload reduction (arteriolar dilation) may result in reduction of aortic or mitral regurgitant volume. When the total peripheral arteriolar resistance is decreased by increasing the total arteriolar cross-sectional area, the change
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