The Effects of Vancomycin and β-Lactam Antibiotics on Vancomycin-Resistant<i>Staphylococcus aureus</i>

Haraga, Isao; Nomura, Sadahiro; Nagayama, Ariaki

doi:10.1056/nejm199911183412117

Cited by 23 publications

(18 citation statements)

References 3 publications

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“…Our definition of synergy included a consideration of these natural variations. A low concentration of ␤-lactam antibiotic has been associated with an antagonistic effect when combined with vancomycin (6,10). Antagonism was observed with the MDD method only in the presence of a low to intermediate concentration of vancomycin.…”

Section: Discussionmentioning

confidence: 99%

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Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods

Huang

Chen

et al. 2016

J Clin Microbiol

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Modified disk diffusion (MDD) and checkerboard tests were employed to assess the synergy of combinations of vancomycin and ␤-lactam antibiotics for 59 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Mu50 (ATCC 700699).Bacterial inocula equivalent to 0.5 and 2.0 McFarland standard were inoculated on agar plates containing 0, 0.5, 1, and 2 g/ml of vancomycin. Oxacillin-, cefazolin-, and cefoxitin-impregnated disks were applied to the surface, and the zones of inhibition were measured at 24 h. The CLSI-recommended checkerboard method was used as a reference to detect synergy. The MICs for vancomycin were determined using the Etest method, broth microdilution, and the Vitek 2 automated system. Synergy was observed with the checkerboard method in 51% to 60% of the isolates when vancomycin was combined with any ␤-lactam. The fractional inhibitory concentration indices were significantly lower in MRSA isolates with higher vancomycin MIC combinations (P < 0.05). The overall agreement between the MDD and checkerboard methods to detect synergy in MRSA isolates with bacterial inocula equivalent to McFarland standard 0.5 were 33.0% and 62.5% for oxacillin, 45.1% and 52.4% for cefazolin, and 43.1% and 52.4% for cefoxitin when combined with 0.5 and 2 g/ml of vancomycin, respectively. Based on our study, the simple MDD method is not recommended as a replacement for the checkerboard method to detect synergy. However, it may serve as an initial screening method for the detection of potential synergy when it is not feasible to perform other labor-intensive synergy tests.V ancomycin and other glycopeptide antibiotics are currently the standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) (1). The emergence of MRSA with reduced vancomycin susceptibility (SA-RVS) raises concerns about the reliability of vancomycin for the treatment of MRSA (2). Resistance during treatment with daptomycin has raised similar concerns about its effectiveness for life-threatening MRSA infections (3). Low serum levels and the bacteriostatic activity of tigecycline against MRSA limit its use for the treatment of MRSA bacteremia (4).The combination of vancomycin and ␤-lactam antibiotics offers a potential option for management of MRSA infections (5). This concept is based on several in vitro and animal studies that demonstrated a synergistic effect of vancomycin-␤-lactam combinations against MRSA (6-11).The current study was designed to determine the utility of a modified disk diffusion (MDD) test to assess synergy and antagonism for combinations of vancomycin and ␤-lactam antibiotics among clinical isolates of MRSA (8, 12). The CLSI checkerboard method was used as the reference for the determination of synergy. We determined the vancomycin MIC breakpoint where synergy is most commonly observed in MRSA isolates. MATERIALS AND METHODSBacterial isolates. Fifty-nine unique clinical isolates of MRSA with vancomycin MICs of Ն0.5 g/ml were obtained from patients at the Kaohsiung Veterans General Hospital in Taiwan ...

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Section: Discussionmentioning

confidence: 99%

“…This concept is based on several in vitro and animal studies that demonstrated a synergistic effect of vancomycin-␤-lactam combinations against MRSA (6)(7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods

Huang

Chen

et al. 2016

J Clin Microbiol

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“…However, the true clinical significance of the heteroresistant phenotype remains to be elucidated. Against staphylococci with heteroresistance to vancomycin, the effect of therapy with a combination of vancomycin and ␤-lactam antibiotics can be either antagonistic or synergistic (1,16,19,37). Routine laboratory techniques, such as the disk diffusion method and the E-test, fail to detect heteroresistance to vancomycin in staphylococci (3).…”

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confidence: 99%

Nosocomial Spread of a Staphylococcus capitis Strain with Heteroresistance to Vancomycin in a Neonatal Intensive Care Unit

Zwet¹,

Debets-Ossenkopp²,

Reinders³

et al. 2002

J Clin Microbiol

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A premature infant in a neonatal intensive care unit (NICU) developed a bloodstream infection caused by coagulase-negative staphylococci (CoNS) sensitive to vancomycin. The infection persisted for 3 weeks, despite therapy with vancomycin and replacement of all intravenous catheters. The neonate died due to necrotizing enterocolitis which developed during the ongoing sepsis. We screened this strain and 216 other strains of CoNS from cultures of blood obtained from neonates between 1997 and 2000 for heteroresistance to vancomycin. Forty-eight isolates, including the strain that caused ongoing sepsis, proved heteroresistant. All isolates were identified as Staphylococcus capitis and were identical, just as their resistant stable subcolonies were, when they were genetically fingerprinted by amplified-fragment length polymorphism analysis. The heteroresistant phenotype of this endemic strain was confirmed by population analysis. We conclude that heteroresistance to vancomycin occurs in S. capitis and might be the cause of therapeutic failures in NICUs. Moreover, heteroresistant strains can become endemic in such units.

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“…Hanaki et al documented antagonistic interactions between vancomycin and ceftizoxime against Mu 3, and he developed Mu 3 agar on the basis of these findings for the detection of hetero-VRSA (6). Besides these, many other results have been reported regarding the efficacy of vancomycin--lactam combinations against S. aureus strains with reduced susceptibilities to vancomycin-synergistic (or additive) and antagonistic effects (7,8,(22)(23)(24)(25)(26).…”

Section: Resultsmentioning

confidence: 99%

“…Haraga et al also performed population analyses with several hetero-VRSA strains to evaluate combination effects (22). Their data demonstrated similar results to ours, that is antagonistic effects at <1 g/mL but synergistic effects at >8 g/mL of -lactam antibiotics (in their data, they did Vancomycin ( g/mL) Mu 3 Number of CFU (log10) Instead of population analyses used by our and Haraga s study, Hiramatsu et al adopted the broth dilution methods and Howe used the E-test to evaluate the combination effects (4,22,23). There are also other reports regarding the combination effects of vancomycin--lactams (7,8,(24)(25)(26).…”

Section: Resultsmentioning

confidence: 99%

Efficacy of Vancomycin-beta-lactam Combinations Against Heterogeneously Vancomycin-Resistant Staphylococcus aureus (hetero-VRSA)

et al. 2003

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There have been conflicting data about the interactions between vancomycin and -lactam agents against Staphylococcus aureus strains with heterogeneous resistance to vancomycin. We evaluated the efficacy of these combinations against Mu 3 and heterogeneously vancomycin-resistant S. aureus (hetero-VRSA) strains which were isolated from Korean patients using a population analysis method. Antagonistic effects were observed when less than 1 g/mL of -lactam antibiotics was combined with vancomycin, whereas synergistic effects were noticed with more than 4 g/mL of -lactam antibiotics. The antagonistic effects at low concentrations of -lactams were most prominent at 2 g/mL of vancomycin, which were the vancomycin MICs of tested hetero-VRSA strains. This study showed the variable effects of vancomycin--lactam combinations depending on the concentrations of -lactam antibiotics and this property could be used to develop screening methods for hetero-VRSA strains.

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The Effects of Vancomycin and β-Lactam Antibiotics on Vancomycin-ResistantStaphylococcus aureus

Cited by 23 publications

References 3 publications

Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods

Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods

Nosocomial Spread of a Staphylococcus capitis Strain with Heteroresistance to Vancomycin in a Neonatal Intensive Care Unit

Efficacy of Vancomycin-beta-lactam Combinations Against Heterogeneously Vancomycin-Resistant Staphylococcus aureus (hetero-VRSA)

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