Mechanism of Penicillin-Streptomycin Synergy for Clinical Isolates of Viridans Streptococci

Yee, Y. Cheung; Farber, Bruce F.; Mates, S M

doi:10.1093/infdis/154.3.531

Cited by 13 publications

(6 citation statements)

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“…Such an effect was not observed in vivo in the treatment of experimental enterococcal endocarditis (22). The absence of an in vivo PAE of the combination of a ␤-lactam plus an aminoglycoside against enterococci does not preclude the presence of a PAE against viridans streptococci because of differences in the mechanisms of action of this combination on the two microorganisms (28,29,44). The mechanism of synergism between penicillin and aminoglycosides against viridans streptococci is still controversial.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of synergism between penicillin and aminoglycosides against viridans streptococci is still controversial. Yee et al (44) showed a mechanism similar to that which occurs with E. faecalis (29), but Miller et al (28), using another strain of viridans streptococci, were unable to prove an increase in the rate of entry of aminoglycoside into bacteria in the presence of penicillin. Other mechanisms of synergy, not yet established, could explain the efficacy of gentamicin given once a day.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Gavaldá

Pahissa

Almirante

et al. 1995

Antimicrob Agents Chemother

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This study compares the effects of a total daily dose of gentamicin given once a day (q.d.) or three times a day (t.i.d.) in the therapy of experimental endocarditis in rabbits caused by penicillin-susceptible, penicillintolerant, or penicillin-resistant viridans streptococci. Four isolates were used in vivo: one penicillin susceptible (MIC < 0.03 g/ml), one penicillin tolerant (MBC/MIC, <0.03/>32 g/ml), and two penicillin resistant (MICs ‫؍‬ 0.5 and 2 g/ml). Animals were infected with one of the four isolates and assigned to one of the following treatment regimens: no treatment, procaine penicillin at 1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Gavaldá

Pahissa

Almirante

et al. 1995

Antimicrob Agents Chemother

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“…Interaction between penicillin and aminoglycosides using in vitro methods yields various results that vary from species to species and strain to strain Duperval et al 1975 ;Potgieter et al 1992 ;Vigliarolo et al 2007 ).There are confl icting data about whether the mechanism of synergy in viridans streptococci is related to enhanced uptake of aminoglycoside (Yee et al 1986 ;Miller et al 1986 ). As is frequently observed with enterococci, high-level "resistance" to aminoglycosides appears to abolish synergy (Farber et al 1983 ;Farber and Yee 1987 ).…”

Section: Viridans Streptococcimentioning

confidence: 99%

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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“…Nevertheless, mechanisms of penicillin-aminoglycoside interactions against these organisms, and the clinical significance of such combinations, continue to be areas of active investigation. Yee et al (189) recently demonstrated in Streptococcus mitis enhanced intracellular uptake of streptomycin and tobramycin in the presence of penicillin, with corresponding penicillin-aminoglycoside bactericidal synergism at 24 h of incubation. Against a strain which possessed high-level resistance to streptomycin (MIC, >2,000 pig/ml), penicillin augmented streptomycin uptake without associated synergistic killing.…”

Section: Mechanisms Of Bactericidal Synergismmentioning

confidence: 99%