Infective Endocarditis Diagnosis, Antimicrobial Therapy, and ...

e410 Circulation June 14, 2005TABLE 9. Therapy for Native Valve or Prosthetic Valve Enterococcal Endocarditis Caused by Strains Susceptible to Penicillin,Gentamicin, and VancomycinRegimenDosage* and RouteDuration,wkStrength ofRecommendationCommentsAmpicillin sodiumor12 g/24 h IV in 6 equally divided doses 4–6 IA Native valve: 4-wk therapy recommendedfor patients with symptoms of illness 3mo; 6-wk therapy recommended forpatients with symptoms 3 moAqueous crystallinepenicillin G sodiumplusGentamicin sulfate†Vancomycin hydrochloride§plusGentamicin sulfate18–30 million U/24 h IV either continuously orin 6 equally divided doses3 mg/kg per 24 h IV/IM in 3 equally divideddosesPediatric dose‡: ampicillin 300 mg/kg per 24 hIV in 4–6 equally divided doses; penicillin300 000 U/kg per 24 h IV in 4–6 equallydivided doses; gentamicin 3 mg/kg per 24 hIV/IM in 3 equally divided doses30 mg/kg per 24 h IV in 2 equally divideddoses3 mg/kg per 24 h IV/IM in 3 equally divideddosesPediatric dose: vancomycin 40 mg/kg per 24 hIV in 2 or 3 equally divided doses; gentamicin3 mg/kg per 24 h IV/IM in 3 equally divideddoses4–6 IA Prosthetic valve or other prosthetic cardiacmaterial: minimum of 6 wk of therapyrecommended4–66 IB Vancomycin therapy recommended only forpatients unable to tolerate penicillin orampicillin6 6 wk of vancomycin therapy recommendedbecause of decreased activity againstenterococci*Dosages recommended are for patients with normal renal function.†Dosage of gentamicin should be adjusted to achieve peak serum concentration of 3–4 g/mL and a trough concentration of 1 g/mL (see text). Patients witha creatinine clearance of 50 mL/min should be treated in consultation with an infectious diseases specialist.‡Pediatric dose should not exceed that of a normal adult.§See text and Table 4 for appropriate dosing of vancomycin.older than patients with other types of endocarditis, was afactor in their ability to tolerate prolonged aminoglycosidetherapy in combination with cell wall–active agents andprompted an abbreviated aminoglycoside course. Despitelimiting the duration of aminoglycosides (median treatmenttime was 15 days), the overall cure rate was comparable tothat of longer courses of combined therapy. The implicationsof this work are extremely practical and deserve further studybefore routine use of shortened aminoglycoside therapy incombination regimens for treatment of enterococcal endocarditiscan be recommended.Enterococci Susceptible to Penicillin,Streptomycin, and Vancomycin and Resistantto GentamicinAminoglycoside resistance in enterococci is most commonlythe result of the acquisition of plasmid-mediatedaminoglycoside-modifying enzymes. Strains that are resistantto high levels of gentamicin are resistant to other aminoglycosides,but some of these strains are susceptible to streptomycin.All E faecium are intrinsically resistant to amikacin,kanamycin, netilmicin, and tobramycin, and E faecalis areoften resistant to kanamycin and amikacin. Infecting strainsof enterococci recovered from patients with endocarditisshould be tested for susceptibility to both gentamicin andstreptomycin but not other aminoglycosides.The suggested regimens for antimicrobial therapy areshown in Table 10. The duration of therapy is the samewhether gentamicin or streptomycin is used and whether thepatient has native or prosthetic valve endocarditis.In patients with normal renal function, streptomycin shouldbe administered every 12 hours and the dosage adjusted toachieve a 1-hour serum concentration of 20 to 35 g/mL anda trough concentration of 10 g/mL. Patients with acreatinine clearance of 50 mL/min should be treated inconsultation with an infectious diseases specialist.Enterococci Resistant to Penicillin and Susceptibleto Aminoglycosides and VancomycinTable 11 presents the antimicrobial regimens suggested forthe treatment of endocarditis caused by enterococci susceptibleto vancomycin and aminoglycosides and resistant topenicillin. E faecium are more resistant to penicillin, withMICs usually 16 g/mL as compared with E faecalis, withMICs usually 2 to 4 g/mL of penicillin. Ampicillin MICsusually are 1 dilution lower than those of penicillin. Theactivity of piperacillin is similar to that of penicillin, butticarcillin, aztreonam, antistaphylococcal penicillins (nafcillinand methicillin), cephalosporins, cephamycins, and meropenemhave limited or no activity against enterococci. Imipenemhas some activity against enterococci.Downloaded from circ.ahajournals.org by on June 26, 2007