Effect of gentamicin dosing interval on therapy of viridans streptococcal experimental endocarditis with gentamicin plus penicillin

Gavaldá, Joan; Pahissa, Albert; Almirante, Benito; Laguarda, M; Crespo, E; Pou, Leonor; Fernández, F.

doi:10.1128/aac.39.9.2098

Cited by 20 publications

(29 citation statements)

References 35 publications

(42 reference statements)

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“…The advantage of once-daily administration of aminoglycosides for the treatment of endocarditis is presently under discussion (3,5,11,16,17,35; Dorscher et al, 30th ICAAC). The combinations of aminoglycosides administered once-a-day with penicillin or ceftriaxone have been found to be effective in studies using pencillin-susceptible (3,13,16,35), -tolerant (16), -resistant (16), and nutritionally variant (16) viridans streptococcal or staphylococcal (Gavaldà et al, 35th ICAAC) endocarditis models.…”

Section: Discussionmentioning

confidence: 99%

“…The combinations of aminoglycosides administered once-a-day with penicillin or ceftriaxone have been found to be effective in studies using pencillin-susceptible (3,13,16,35), -tolerant (16), -resistant (16), and nutritionally variant (16) viridans streptococcal or staphylococcal (Gavaldà et al, 35th ICAAC) endocarditis models. Based on these results, a successful clinical trial was conducted using the combination of ceftriaxone plus netilmicin, both administered once-a-day during 2 weeks to treat patients with streptococcal endocarditis (14).…”

Section: Discussionmentioning

confidence: 99%

“…2 to 2.1 kg) by the method of Garrison and Freedman (15), modified as described by 31,32). The induction of non-bacterial thrombotic endocarditis was done as previously described (16,17). Briefly, a polyethylene catheter was inserted through the right carotid artery into the left ventricular cavity and was left in place throughout the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, pharmacodynamic data obtained from the animal model (22,23,39) have shown that the aminoglycoside exhibit concentration-dependent killing, supporting the idea that once-a-day administration might be more efficacious. Along this line, the efficacy of gentamicin given once a day has been shown to be effective for the treatment of experimental endocarditis due to viridans streptococci (3,16,34) and due to Staphylococcus aureus (J. Gavaldà, M. Laguarda, J. A. Capdevila, L. Pou, E. Crespo, and A. Pahissa, Abstr.…”

mentioning

confidence: 99%

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Efficacy of Teicoplanin-Gentamicin Given Once a Day on the Basis of Pharmacokinetics in Humans for Treatment of Enterococcal Experimental Endocarditis

López

Gavaldá

Martín

et al. 2001

Antimicrob Agents Chemother

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With the aim of investigating home therapy for enterococcal endocarditis, we compared the efficacy of teicoplanin combined with gentamicin given once a day or in three daily doses (t.i.d.) with the standard treatment, ampicillin plus gentamicin administered t.i.d., for treating experimental enterococcal endocarditis. The antibiotics were administered by using "human-like pharmacokinetics" (H-L), i.e, pharmacokinetics like those in humans, that simulated the profiles of these drugs in human serum. Animals with catheter-induced endocarditis were infected intravenously with 10 8 CFU of Enterococcus faecalis EF91 (MICs and MBCs of ampicillin, gentamicin, and teicoplanin, 0.5 and 32, 16 and 32, and 0.5 and 1 g/ml, respectively) and were treated for 3 days with ampicillin H-L at 2 g every 4 h plus gentamicin H-L at 1 mg/kg every 8 h, or teicoplanin H-L at 10 mg/kg every 24 h, alone or combined with gentamicin, administered at dose of H-L at 1 mg/kg every 8 h or H-L at 4.5 mg/kg every 24 h. The results of therapy for experimental endocarditis due to EF91 showed that teicoplanin alone was as effective as ampicillin alone in reducing the bacterial load (P > 0.05). The combination of ampicillin or teicoplanin with gentamicin was more effective than the administration of both drugs alone in reducing the log 10 CFU/gram of aortic vegetation (P < 0.01 and P < 0.05, respectively). Teicoplanin plus gentamicin H-L at 4.5 mg/kg, both administered every 24 h, showed an efficacy equal to the "gold standard," ampicillin plus gentamicin H-L at 1 mg/kg t.i.d. (P > 0.05). Increasing the interval of administration of gentamicin to a single daily dose combined with teicoplanin resulted in a reduction of bacteria in the vegetations equivalent to that achieved with the recommended regimen of ampicillin plus thrice-daily gentamicin in the treatment of experimental endocarditis due to E. faecalis. Teicoplanin plus gentamicin, both administered once a day, may be useful home therapy for selected cases of enterococcal endocarditis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Efficacy of Teicoplanin-Gentamicin Given Once a Day on the Basis of Pharmacokinetics in Humans for Treatment of Enterococcal Experimental Endocarditis

López

Gavaldá

Martín

et al. 2001

Antimicrob Agents Chemother

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“…Pharmacodynamic data obtained from animal models (17,18,37) have shown concentration-dependent killing by the aminoglycosides, which supports the idea that administration of these drugs once a day might be more effective. Along this line, gentamicin given once a day has been shown to be effective against experimental endocarditis due to viridans group streptococci (2,11,28) and experimental endocarditis due to Enterococcus faecalis (13,20) and in in vitro simulations of enterococcal endocarditis (14,32). To date, the efficacy of gentamicin administered once a day against MSSA has not been evaluated.…”

mentioning

confidence: 99%

Efficacy of Ceftriaxone and Gentamicin Given Once a Day by Using Human-Like Pharmacokinetics in Treatment of Experimental Staphylococcal Endocarditis

Gavaldá

López

Martin

et al. 2002

Antimicrob Agents Chemother

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We compared the efficacy of ceftriaxone combined with gentamicin, both given once a day, with that of cloxacillin given every 4 h plus gentamicin given once a day or in three daily doses (t.i.d.) for the treatment of experimental methicillin-susceptible staphylococcal endocarditis. The antibiotics were administered by using human-like (H-L) pharmacokinetics that simulated the profiles of these drugs in human serum. Animals with catheter-induced endocarditis were infected intravenously with 10 5 CFU of Staphylococcus aureus S5 (MICs and minimal bactericidal concentrations of cloxacillin, ceftriaxone, and gentamicin, 0.5 and 2 g/ml, 4 and 8 g/ml, and 0.5 and 1 g/ml, respectively).

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Drug–Drug Combinations

Turnidge

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Antimicrobial combination therapy has a long history. The potential for synergy between two antimicrobial agents has been sought using in vitro techniques such as disk approximation, checkerboard titration, in vitro killing experiments with fi xed drug concentrations, through the use of in vitro pharmacodynamic models, through animal models, and through retrospective and prospective clinical studies. The most widely examined combinations are those that include aminoglycosides, especially for the treatment of serious Pseudomonas aeruginosa infections, and for the management of enterococcal and staphylococcal endocarditis. The in vitro and animal studies of P. aeruginosa support the concept that combinations of aminoglycosides with β-lactams improve effi cacy and outcomes. Some models suggest that the mechanism of improved effi cacy relates less to synergy and more the prevention of the selection of aminoglycoside-resistant mutants. However, human clinical studies to date have failed to demonstrate convincingly that there are better outcomes with combination therapy in terms of effi cacy or the prevention of resistance emergence. For endocarditis, there has been strong evidence accumulated for combination therapy enterococcal endocarditis using in vitro and animal models, although there are no randomised clinical data to confi rm these. Data supporting the use of combination in staphylococcal therapy has been less robust, and Panton-valentine leukocidin producing S. aureusCell-wall active agent + clindamycin or linezolid the role of combination treatment for this indication is now in question. Ultimately, an in vitro or animal model of the pharmacodynamic interaction of drug classes that can be shown to predict clinical outcomes is still required. Such a model does not currently exist.

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Effect of gentamicin dosing interval on therapy of viridans streptococcal experimental endocarditis with gentamicin plus penicillin

Cited by 20 publications

References 35 publications

Efficacy of Teicoplanin-Gentamicin Given Once a Day on the Basis of Pharmacokinetics in Humans for Treatment of Enterococcal Experimental Endocarditis

Efficacy of Teicoplanin-Gentamicin Given Once a Day on the Basis of Pharmacokinetics in Humans for Treatment of Enterococcal Experimental Endocarditis

Efficacy of Ceftriaxone and Gentamicin Given Once a Day by Using Human-Like Pharmacokinetics in Treatment of Experimental Staphylococcal Endocarditis

Drug–Drug Combinations

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