Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin:

Dressel, Dana C.; Tornatore-Reuscher, Michelle A.; Boschman, Cynthia R.; Stosor, Valentina; Zembower, Teresa; Postelnick, Michael; Noskin, Gary A.; Peterson, Lance R.

doi:10.1016/s0732-8893(99)00088-7

Cited by 14 publications

(12 citation statements)

References 12 publications

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“…Currently, it is considered that, in ampicillin-susceptible enterococci, gentamicin MICs lower than 500 g/ml are predictive of (i) in vitro synergy between a cell wall-active agent and gentamicin at concentration such as 4 g/ml, which is low enough to be achievable in clinical practice, and (ii) of a ben-eficial effect of the combination in vivo (3,9). There are, however, some controversies about amoxicillin concentrations used to detect synergism with gentamicin in enterococci.…”

Section: Discussionmentioning

confidence: 99%

“…There are, however, some controversies about amoxicillin concentrations used to detect synergism with gentamicin in enterococci. Some authors recommend concentrations of at least the MIC of amoxicillin or more (17,18), while others use amoxicillin at half the MIC or less (4,9,22). We used an amoxicillin concentration of half the MIC because it was the first low concentration allowing us to point out a synergism defined according to the American Society for Microbiology recommendations.…”

Section: Discussionmentioning

confidence: 99%

“…We used an amoxicillin concentration of half the MIC because it was the first low concentration allowing us to point out a synergism defined according to the American Society for Microbiology recommendations. All experiments with intermediate-level resistance to gentamicin in enterococci are made with amoxicillin concentration of one-half and one-quarter the MIC (4,9).…”

Section: Discussionmentioning

confidence: 99%

“…However, Dressel at al (9). have already reported the lack of synergism between amoxicillin and gentamicin in three clinical isolates of enterococci, despite gentamicin MICs below 500 g/ml (8 and 16 g/ml).…”

mentioning

confidence: 95%

“…Some authors reported a single clinical isolate of E. faecalis among 18 strains with gentamicin MICs of 256 g/ml by aph(2Љ)-Ic expression, which expressed no synergism with amoxicillin in vitro (4). Dressel et al (9) found three clinical E. faecalis among 4,411 isolates of Enterococcus spp. expressing low-level resistance to gentamicin (MIC at 8 and 16 g/ml), which had lost synergism with amoxicillin in vitro.…”

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confidence: 99%

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Relationship between the Level of Acquired Resistance to Gentamicin and Synergism with Amoxicillin in Enterococcus faecalis

Aslangul¹,

Ruimy²,

Chau³

et al. 2005

Antimicrob Agents Chemother

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In enterococci, intrinsic low-level resistance to gentamicin does not abolish synergism with a cell wall-active antibiotic while high-level resistance due to acquired aminoglycoside-modifying enzymes does. To study the impact of intermediate levels of resistance to gentamicin (64 < MIC < 500 g/ml), we selected in vitro three consecutive generations of mutants of Enterococcus faecalis JH2-2 with MICs of gentamicin at 128 g/ml for G1-1477, 256 g/ml for G2-1573, and 512 g/ml for G3-1688. E. faecalis 102, which is highly resistant to gentamicin by enzymatic inactivation was used as control. In in vitro killing curves experiments, gentamicin concentrations allowing bactericidal activity and synergism in combination with amoxicillin increased from 4 g/ml (1/16th the MIC), 16 g/ml (one-eighth the MIC), 64 g/ml (one-quarter the MIC), and 256 g/ml (one-half the MIC) for strains JH2-2, G1-1477, G2-1573 and G3-1688, respectively. As expected, no bactericidal effect of the combination or synergism could be obtained with strain 102. In rabbits with aortic endocarditis caused by strain G1-1477 or G2-1573, combination therapy with amoxicillin and gentamicin was significantly more active than amoxicillin alone (P < 0.05) but not in those infected with the strains G3-1688 and 102. Thus, intermediate levels of resistance to gentamicin was not associated with a loss of a beneficial effect of the gentamicin-amoxicillin combination in vivo even though higher concentrations of gentamicin were necessary to achieve in vitro synergism. Therefore, the use of an MIC of 500 g/ml as a clinical cutoff limit to predict in vivo benefit of the combination remains a simple and effective tool.Optimal antimicrobial therapy for serious enterococcal infections requires the use of synergistic bactericidal combinations of a cell wall-active agent, such as penicillin or a glycopeptide, with an aminoglycoside. Enterococcus faecalis, the most frequently isolated enterococcal species, is intrinsically resistant to low levels of aminoglycosides due to inefficient active transport of aminoglycosides across the cytoplasmic membrane. However, a bactericidal effect is observed when amoxicillin is combined with gentamicin even on strains with MICs of gentamicin ranging from 4 to 64 g/ml (18). By contrast, no synergistic bactericidal effect is observed in combining a cell wall-active antibiotic with gentamicin on strains with high-level resistance to aminoglycosides (MIC Ͼ 500 g/ml) such as those which have acquired genes encoding aminoglycoside-modifying enzymes by horizontal transfer (19).However, Dressel at al (9). have already reported the lack of synergism between amoxicillin and gentamicin in three clinical isolates of enterococci, despite gentamicin MICs below 500 g/ml (8 and 16 g/ml). The aminoglycoside resistance mechanism was not described in the report. Chow et al. (4, 5) also described E. faecalis harboring a novel gentamicin resistance gene, aph(2Љ)-Ic, which compromised ampicillin-gentamicin synergism despite a gentamicin MIC of 256 g/ml.We previou...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

mentioning

confidence: 99%

See 3 more Smart Citations

Relationship between the Level of Acquired Resistance to Gentamicin and Synergism with Amoxicillin in Enterococcus faecalis

Aslangul¹,

Ruimy²,

Chau³

et al. 2005

Antimicrob Agents Chemother

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New aspect of the synergistic antibacterial action of ampicillin and gentamicin

Barnes

Herrero

Albesa

2005

International Journal of Antimicrobial Agents

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Medical treatment of prosthetic vascular graft infections: Review of the literature and proposals of a Working Group

Revest¹,

Camou²,

Senneville³

et al. 2015

International Journal of Antimicrobial Agents

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More than 400000 vascular grafts are inserted annually in the USA. Graft insertion is complicated by infection in 0.5-4% of cases. Vascular graft infections (VGIs) are becoming one of the most frequent prosthesis-related infections and are associated with considerable mortality, ranging from 10 to 25% within 30 days following the diagnosis. Treatment of VGI is based on urgent surgical removal of the infected graft followed by prolonged antibiotherapy. Data regarding the best antibiotherapy to use are lacking since no well designed trial to study antimicrobial treatment of VGI exists. Moreover, since VGIs demonstrate very specific pathophysiology, guidelines on other material-related infections or infective endocarditis treatment cannot be entirely applied to VGI. A French multidisciplinary group gathering infectious diseases specialists, anaesthesiologists, intensivists, microbiologists, radiologists and vascular surgeons was created to review the literature dealing with VGI and to make some proposals regarding empirical and documented antibiotic therapy for these infections. This article reveals these proposals.

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Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin:

Cited by 14 publications

References 12 publications

Relationship between the Level of Acquired Resistance to Gentamicin and Synergism with Amoxicillin in Enterococcus faecalis

Relationship between the Level of Acquired Resistance to Gentamicin and Synergism with Amoxicillin in Enterococcus faecalis

New aspect of the synergistic antibacterial action of ampicillin and gentamicin

Medical treatment of prosthetic vascular graft infections: Review of the literature and proposals of a Working Group

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