Role of tolerance in cloxacillin treatment of experimental Staphylococcus aureus endocarditis. Journal of Infectious Diseases , —3. Goldman, P. Significance of methicillin tolerance in experimental staphylococcal endocarditis.
Antimicrobial Agents and Chemotherapy 15 , —6. Rajashekaraiah, K. Clinical significance of tolerant strains of Staphylococcus aureus in patients with endocarditis. Annals of Internal Medicine 93 , — Korzeniowski, O. Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts.
Annals of Internal Medicine 97 , — Freeman, R. Treatment of Staphylococcus aureus endocarditis: an analysis based on 25 proven cases.
European Heart Journal 7 , — Ribera, E. Effectiveness of cloxacillin with and without gentamicin in short-term therapy for right-sided Staphylococcus aureus endocarditis. Chambers, H. Right-sided Staphylococcus aureus endocarditis in intravenous drug abusers: two-week combination therapy. Torres-Tortosa, M. Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis.
Short-course therapy for right-side endocarditis due to Staphylococcus aureus in drug abusers: cloxacillin versus glycopeptides in combination with gentamicin. Clinical Infectious Diseases 33 , —5. Rubinstein, E. Staphylococcal endocarditis—recommendations for therapy. Clinical Microbiology and Infection 4 , 3S27 — Small, P. Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Levine, D. Slow response to vancomycin or vancomycin plus rifampicin in methicillin-resistant Staphylococcus aureus endocarditis.
McGrath, B. Bactericidal activities of teicoplanin, vancomycin, and gentamicin alone and in combination against Staphylococcus aureus in an in vitro pharmacodynamic model of endocarditis.
Antimicrobial Agents and Chemotherapy 38 , — Kaatz, G. Daptomycin compared with teicoplanin and vancomycin for therapy of experimental Staphylococcus aureus endocarditis. Antimicrobial Agents and Chemotherapy 34 , —5. Kobasa, W. Therapy for experimental endocarditis due to Staphylococcus epidermidis.
Review of Infectious Diseases 5 , S —7. John, M. Staphylococcus aureus prosthetic valve endocarditis: optimal management and risk factors for death. Clinical Infectious Diseases 26 , —9. Karchmer, A. Staphylococcus epidermidis causing prosthetic valve endocarditis: microbiological and clinical observations as guides to therapy. Annals of Internal Medicine 98 , — Bayer, A. Endocarditis and intravascular infections. Churchill Livingstone, Philadelphia, PA. Baddour, L. Clinical Infectious Diseases 26 , 66 — Tam, V.
Once-daily aminoglycoside in the treatment of Enterococcus faecalis endocarditis: case report and review.
Pharmacotherapy 20 , —9. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation.
Volume Article Contents Abstract. Viridans streptococci and Streptococcus bovis. Staphylococcus aureus. Prosthetic valve endocarditis. Yu et al. In a series of in vitro studies by Archer et al.
Thus, the antimicrobial activity of rifampin was maintained by the prevention of emergence of rifampin-resistant mutants in the presence of a second or third agent. Experimental animal models can be an invaluable tool to bridge the gap between the artificial environment of an in vitro system on the one hand and the complicated in vivo milieu within a human host on the other.
Experimental IE has been studied extensively in both rats and rabbits by establishing intracardiac vegetations via insertion of a polyethylene catheter across the aortic or tricuspid valves.
When the etiologic organism is injected intravenously into catheterized animals, IE is reproducibly established. This model has been used to study both disease pathogenicity and the response to antimicrobial therapy. As noted above, numerous investigations have confirmed the superior in vivo synergistic efficacy of CWAs in combination with aminoglycosides compared with single-drug regimens in experimental IE due to VGS, S.
These studies have been summarized in detail by Fantin et al. Synergy dosing strategies. As noted in the Enterococci section above, achievable aminoglycoside levels required for synergistic killing of enterococci and VGS appear to be considerably lower than those needed to reliably kill susceptible gram-negative pathogens e.
In addition, the impact of antibiotic dosing intervals on synergistic killing of pathogens responsible for IE remains of critical importance. This has been linked to the time-dependent killing features of such agents, as well as the lack of any substantial postantibiotic effect of penicillin G, with or without aminoglycosides, particularly for VGS and enterococci [ 24 ].
There has been extensive controversy about the optimal dose interval for the aminoglycoside component of the CWA-aminoglycoside synergistic regimens for IE due to common gram-positive pathogens. As noted by Fantin et al. This relationship is particularly important given the lack of significant postantibiotic effects, as noted above. In a rabbit aortic valve IE model, Join-Lambert et al. These in vivo observations were consistent with the in vitro findings of Mainardi et al.
Brandt et al. Of note, other double-CWA combinations, such as ampicillin plus vancomycin, were not synergistic in vivo. Table 1 summarizes the largest studies of combination therapy for humans with IE due to common pathogens [ 27—42 ].
Clinical outcomes reported in selected studies of combination treatment for infective endocarditis IE due to common pathogens. Although in vitro studies have demonstrated synergy with the combination of penicillin G plus streptomycin or gentamicin, such combination therapy has not been definitively established as being more effective than penicillin G or ceftriaxone alone in human trials [ 27 ].
It appears that the major advantage of combination therapy in VGS IE is the ability to shorten the course of treatment for uncomplicated infection from 4—6 weeks to 2 weeks short-course therapy. For example, studies by Wilson et al. Moreover, Francioli et al. A recent study by Sexton et al. The other major advantage of the short-course, once-daily ceftriaxone-aminoglycoside regimen is its applicability to outpatient treatment strategies [ 28 , 32 ].
For such strains, the AHA recommends that gentamicin be given for the first 2 weeks of a 4-week course of penicillin G or ampicillin. The benefit of combination therapy with a CWA and aminoglycosides has not been definitively established by human clinical trials of S. In nonaddicts with left-sided IE due to S. Current AHA recommendations advise provision of aminoglycosides in combination with CWAs only for the first 3—5 days of therapy in patients with left-sided native valve IE due to S.
This latter recommendation is based solely on the potential for more-rapid bacteremia clearance. Although this recommendation is supported by the AHA guidelines, there are no specific studies to confirm the enhanced efficacy of such an approach with regard to improved outcome, reduction in metastatic complications, or mitigation of valvular damage. Initial studies of combination therapy for right-side native valve IE due to S.
These investigations failed to show any microbiologic or clinical improvement in outcome associated with the addition of the aminoglycoside [ 33—35 ]. Subsequent studies from San Francisco General Hospital California confirmed the excellent efficacy of 2-week courses of nafcillin plus tobramycin, as well as 4-week courses of predominantly orally administered ciprofloxacin plus rifampin, for treatment of right-side IE due to S.
The high efficacy rates for short-course parenteral and oral combination therapy for right-side IE due to S. Of note, a recent study by Ribera et al. In addition, Fortun et al. In a retrospective study by Karchmer et al. Although these data have not been prospectively confirmed, most experts suggest that therapy for PVE due to methicillin-resistant strains of S. Although current AHA guidelines for treatment of enterococcal IE have recommended combined treatment with penicillin G or ampicillin plus an aminoglycoside for a total duration of 4—6 weeks [ 4 ], these investigators evaluated the clinical outcomes when the total duration of aminoglycoside therapy was reduced.
This approach was driven by the fact that aminoglycoside toxicity mostly affects the elderly population, the prime target group for enterococcal IE. Although no direct restriction on the duration of aminoglycoside therapy was specified, study patients had a median total duration of antibiotic therapy of 42 days, with a median of 15 days of combined therapy with a CWA plus the aminoglycoside.
It is of note that these outcome figures compared favorably with most historical control studies of enterococcal IE [ 2 , 5 ]. In an open, prospective, multicenter study, 18 cases of definite IE were evaluated. Of these 18 cases, 13 were caused by HLRAg isolates. The combination of ampicillin plus ceftriaxone showed in vitro bactericidal synergy against 7 HLRAg strains tested, with either an additive or indifferent effect observed in the remaining strains; it is of note that no evidence of clinical or microbiologic relapse was observed during the 3-month follow-up period.
Two patients died, but there was no evidence of active infection noted at autopsy. It should be emphasized that these data have been published in abstract form only, and we anxiously await full publication of these data. There are few proven synergistic approaches for the treatment of IE that have been globally demonstrated via in vitro models, experimental IE models, and human clinical trials, except treatment of IE caused by enterococci. It appears that short-course CWA-aminoglycoside combinations are highly effective against VGS IE, which makes affected patients amenable to outpatient therapeutic strategies in uncomplicated cases.
Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy.
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Effective treatment of multidrug-resistant enterococcal experimental endocarditis with combinations of cell wall-active agents. J Infect Dis. Gavalda J, Torres C, et al. Efficacy of ampicillin plus ceftriaxone in treatment of experimental endocarditis due to Enterococcus faecalis strains highly resistant to aminoglycosides. To comment on this article, contact editor uspharmacist. Featured Issue Featured Supplements.
Summary IE continues to be a life-threatening infection that often requires a prolonged duration of antibiotic therapy and sometimes surgery in order to be treated appropriately. Related CE. View More CE. Related Content. Take Quiz. Ovarian Cancer. All rights reserved. Reproduction in whole or in part without permission is prohibited. Organisms from the HACEK group may not be identified in blood cultures for a week or longer, necessitating empiric antibiotic therapy during this period.
Patients with bacterial endocarditis should be monitored carefully. Blood cultures should be obtained to ensure eradication of the organism. Gentamicin blood levels should be monitored with dosage adjustments as indicated and renal function should be assessed frequently when an aminoglycoside is administered. If a prolonged course of gentamicin is planned, a hearing assessment should be performed. Fever usually resolves within several days of initiation of effective antibiotic treatment, although fever may persist longer with S.
Persistent fever after the first week of treatment suggests a septic embolic complication or inadequate antibiotic therapy. The recurrence of fever after an initial defervescence suggests a septic or nonseptic embolic event, a drug hypersensitivity reaction or the emergence of a resistant strain. Surgical replacement of an infected valve is necessary if congestive heart failure secondary to valvular regurgitation persists or worsens during antibiotic treatment.
More extensive discussion of surgical management of bacterial endocarditis is available elsewhere. The diagnosis of bacterial endocarditis is based on clinical, laboratory and echocardiographic criteria. Empiric treatment is initiated in any patient who is suspected of having bacterial endocarditis.
Once the causative organism is established, the appropriate antibiotic regimen can be started. By following the recommendations, most patients with bacterial endocarditis can be cured. Already a member or subscriber? Log in. Interested in AAFP membership? Learn more. Address correspondence to Robert L. Blake, Jr. Reprints are not available from the authors. Prevention of bacterial endocarditis.
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