In vitro antimicrobial activity of imipenem in combination with vancomycin or teicoplanin againstStaphylococcus aureus andStaphylococcus epidermidis

Several studies have previously reported synergistic effects between vancomycin and a given ␤-lactam or a given aminoglycoside against methicillin-resistant Staphylococcus aureus (MRSA) strains. The aim of our study was to exhaustively compare the effects of different combinations of a ␤-lactam, vancomycin, and/or an aminoglycoside against 32 clinical MRSA strains with different aminoglycoside susceptibility patterns. The effects of 26 different ␤-lactam-vancomycin and 8 different aminoglycoside-vancomycin combinations were first studied using a disk diffusion screening method. The best interactions with vancomycin were observed with either imipenem, cefazolin, or netilmicin. By checkerboard studies, imipenem-vancomycin and cefazolinvancomycin each provided a synergistic bacteriostatic effect against 22 strains; the mean fractional inhibitory concentration (FIC) indexes were 0.35 and 0.46 for imipenem-vancomycin and cefazolin-vancomycin, respectively. The vancomycin-netilmicin combination provided an indifferent effect against all of the 32 strains tested; the mean of FIC index was 1.096. The mean concentrations of imipenem, cefazolin, netilmicin, and vancomycin at which FIC indexes were calculated were clinically achievable. Killing experiments were then performed using imipenem, cefazolin, netilmicin, and vancomycin at one-half of the MIC, alone and in different combinations, against 10 strains. The vancomycin-netilmicin regimen was rarely bactericidal, even against strains susceptible to netilmicin. The imipenem-vancomycin and cefazolin-vancomycin combinations were strongly bactericidal against six and five strains, respectively. The addition of netilmicin markedly enhanced the killing activity of the combination of cefazolin or imipenem plus vancomycin, but only for the MRSA strains against which the ␤-lactam-vancomycin combinations had no bactericidal effect. It is noteworthy that the latter strains were both susceptible to netilmicin and heterogeneously resistant to methicillin.

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

In Vitro Synergistic Effects of Double and Triple Combinations of β-Lactams, Vancomycin, and Netilmicin against Methicillin-Resistant Staphylococcus aureus Strains

Rochon-Edouard¹,

Pestel-Caron²,

Lemeland³

et al. 2000

“…There have been many contradictory observations with regard to the combination effect of vancomycin and ␤-lactam against S. aureus clinical isolates, including additive and/or synergistic effects (2,4,15,18,19,20,21) and antagonistic effects (7, 9, 14; H. Hanaki, S. Ohkawa, Y. Inaba, T. Hashimoto, and K. Hiramatsu, Abstr. 38th Intersci.…”

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confidence: 99%

Combination Effect of Vancomycin and β-Lactams against a Staphylococcus aureus Strain, Mu3, with Heterogeneous Resistance to Vancomycin

Aritaka

Hanaki

Cui

et al. 2001

We tested the combined activity of vancomycin and seven ␤-lactam antibiotics against Staphylococcus aureus clinical strain Mu3, which displays heterogeneous resistance to vancomycin. When combined with vancomycin, four of the seven tested ␤-lactams exhibited an additive effect at or near their MICs, while all showed an antagonistic effect at lower, sub-MIC levels. This study implicated the unpredictable nature of combination therapy of ␤-lactams and vancomycin against S. aureus with reduced susceptibility to vancomycin.

“…Synergistic interactions between glycopeptides and ␤-lactams against methicillin-resistant staphylococci have been documented in several studies (3,10,13,16,17). As most extensively demonstrated by Climo and coworkers (10), combinations of vancomycin and ␤-lactams appear to be synergistic, especially against staphylococcal strains with reduced susceptibility to vancomycin.…”

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confidence: 86%

Interactions between Glycopeptides and β-Lactams against Isogenic Pairs of Teicoplanin-Susceptible and -Resistant Strains of Staphylococcus haemolyticus

Vignaroli

Biavasco

Varaldo

2006

Four isogenic derivatives with stably increased glycopeptide MICs (all become resistant to teicoplanin) were obtained from four glycopeptide-susceptible clinical isolates of Staphylococcus haemolyticus. All strains were extensively analyzed and compared for a number of distinctive features. In particular, the results provided insights into the puzzling issue of antistaphylococcal interactions between glycopeptides and ␤-lactams, especially the paradox of double zones around ␤-lactam disks and the relationships between autolysis rate and type of interaction.