Infective Endocarditis Diagnosis, Antimicrobial Therapy, and ...

Baddour et al Infective Endocarditis: Diagnosis and Management e409TABLE 8.Therapy for Prosthetic Valve Endocarditis Caused by StaphylococciRegimenDosage* and RouteDuration,wkStrength ofRecommendationCommentsOxacillin-susceptible strainsNafcillin or oxacillin 12 g/24 h IV in 6 equally divided doses 6 IB Penicillin G 24 million U/24 h IV in 4 to 6plusRifampin6plusGentamicin†900 mg per 24 h IV/PO in 3 equally divideddoses3 mg/kg per 24 h IV/IM in 2 or 3 equallydivided dosesPediatric dose‡: nafcillin or oxacillin 200 mg/kgper 24 h IV in 4–6 equally divided doses;rifampin 20 mg/kg per 24 h IV/PO in 3 equallydivided doses; gentamicin 3 mg/kg per 24 hIV/IM in 3 equally divided doses2equally divided doses may be used in place ofnafcillin or oxacillin if strain is penicillinsusceptible (minimum inhibitory concentration0.1 g/mL) and does not produce-lactamase; vancomycin should be used inpatients with immediate-type hypersensitivityreactions to -lactam antibiotics (see Table 3for dosing guidelines); cefazolin may besubstituted for nafcillin or oxacillin in patientswith non–immediate-type hypersensitivityreactions to penicillinsOxacillin-resistant strainsVancomycin 30 mg/kg 24 h in 2 equally divided doses 6 IB Adjust vancomycin to achieve 1-h serumplusRifampin 900 mg/24 h IV/PO in 3 equally divided doses 6concentration of 30–45 g/mL and troughconcentration of 10–15 g/mL (see text forgentamicin alternatives)plusGentamicin3 mg/kg per 24 h IV/IM in 2 or 3 equally2divided dosesPediatric dose: vancomycin 40 mg/kg per 24 hIV in 2 or 3 equally divided doses; rifampin 20mg/kg per 24 h IV/PO in 3 equally divideddoses (up to adult dose); gentamicin 3 mg/kgper 24 h IV or IM in 3 equally divided doses*Dosages recommended are for patients with normal renal function.†Gentamicin should be administered in close proximity to vancomycin, nafcillin, or oxacillin dosing.‡Pediatric dose should not exceed that of a normal adult.serum gentamicin concentrations may be performed in mostlaboratories, whereas streptomycin serum concentrations requirespecial laboratory testing. Studies of single daily dosingof aminoglycosides compared with dosing every 8 hours inanimal models of enterococcal endocarditis have yieldedconflicting results. These results may reflect different pharmacokineticsof aminoglycosides in animals as comparedwith humans. Until more data demonstrate that once-dailydosing of an aminoglycoside is as effective as multipledosing, gentamicin or streptomycin should be administered indaily multiple divided doses rather than a daily single dose topatients with enterococcal endocarditis.In patients with normal renal function, gentamicin shouldbe administered every 8 hours and the dosage adjusted toachieve a 1-hour serum concentration of 3 g/mL and atrough concentration of 1 g/mL. Increasing the dosage ofgentamicin in these patients did not result in enhancedefficacy but did increase the risk of nephrotoxicity. 127 Inpatients with mildly abnormal renal function (creatinineclearance 50 mL/min), the dosage of gentamicin should beadjusted and the serum concentrations closely monitored toachieve the target concentrations above. In patients with moreseverely reduced renal function (creatinine clearance 50mL/min), treatment should be in consultation with an infectiousdiseases specialist.The duration of antimicrobial therapy in native valveendocarditis depends on the duration of infection beforediagnosis and onset of effective therapy. Patients with 3months’ duration of symptoms may be treated successfullywith 4 weeks of antimicrobial therapy, whereas patients with3 months’ duration of symptoms require 6 weeks oftherapy. 128,129 Patients with prosthetic valve endocarditisshould receive at least 6 weeks of antimicrobial therapy.Vancomycin therapy should be administered only if apatient is unable to tolerate penicillin or ampicillin. Combinationsof penicillin or ampicillin with gentamicin are preferableto combined vancomycin-gentamicin because of thepotential increased risk of ototoxicity and nephrotoxicity withthe vancomycin-gentamicin combination. Moreover, combinationsof penicillin or ampicillin and gentamicin are moreactive than combinations of vancomycin and gentamicin invitro and in animal models of experimental endocarditis.Patients with native valve endocarditis should receive 6weeks of vancomycin-gentamicin therapy; patients with prostheticvalve infection also should receive at least 6 weeks oftherapy.Findings from a 5-year, nationwide, prospective study of93 episodes of definite enterococcal endocarditis are noteworthybecause they suggest that the duration of aminoglycosidetherapy could be shortened to 2 to 3 weeks. 130 Thesepatients, who were managed in Sweden between 1995 and1999, represent the largest series of enterococcal endocarditiscases published to date. The age of these patients, who wereDownloaded from circ.ahajournals.org by on June 26, 2007