β-Lactamase Inhibitors Enhance the Synergy between β-Lactam Antibiotics and Daptomycin against Methicillin-Resistant Staphylococcus aureus

Henson, Karl Evans; Yim, Juwon; Smith, Jordan R.; Sakoulas, George; Rybak, Michael J.

doi:10.1128/aac.01564-16

Cited by 13 publications

(8 citation statements)

References 15 publications

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“…DAP synergy with other agents against MRSA has been demonstrated repeatedly in both in vitro and clinical settings (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Combinations with ␤-lactams and trimethoprimsulfamethoxazole, specifically, have been successful.…”

Section: Discussionmentioning

confidence: 98%

Combination of Tedizolid and Daptomycin against Methicillin-Resistant Staphylococcus aureus in an In Vitro Model of Simulated Endocardial Vegetations

Smith

Yim

Rice

et al. 2018

Antimicrob Agents Chemother

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Methicillin-resistant (MRSA) is a major pathogen responsible for health care-associated infections, and treatment options are limited. Tedizolid (TZD) is a novel oxazolidinone antibiotic with activity against MRSA. Previously, daptomycin (DAP) has demonstrated synergy with other antibiotics against MRSA. We sought to determine the efficacy of the combination of TZD and DAP against MRSA in an model of simulated endocardial vegetations (SEVs). TZD simulations of 200 mg once daily and DAP simulations of 6 mg/kg of body weight and 10 mg/kg once daily were tested alone and in the combinations TZD plus DAP at 6 mg/kg or DAP at 10 mg/kg against two clinical strains of MRSA, 494 and 67. These regimens were tested in SEV models over 8 days to determine the antibacterial activity of the regimens and whether synergy or antagonism might be present between the agents. Against both strains 494 and 67 and at both DAP dose regimens, the combination of TZD and DAP was antagonistic at 192 h. In all cases, DAP alone was statistically superior to DAP plus TZD. When the combination was stopped after 96 h, transitioning to DAP at 6 mg/kg or DAP at 10 mg/kg alone resulted in better antibacterial activity than either of the TZD-plus-DAP combinations, further demonstrating antagonistic effects. Against MRSA, we demonstrated that TZD and DAP have antagonistic activity that hinders their overall antimicrobial efficacy. The exact nature of this antagonistic relationship is still undetermined, but its presence warrants further study of the potentially harmful grouping of the two antibiotics in clinical use.

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Section: Discussionmentioning

confidence: 98%

Combination of Tedizolid and Daptomycin against Methicillin-Resistant Staphylococcus aureus in an In Vitro Model of Simulated Endocardial Vegetations

Smith

Yim

Rice

et al. 2018

Antimicrob Agents Chemother

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“…In addition to their role as carriers for antibiotics, some cationic surfactants exhibiting antimicrobial impact can be intercalated in the surface of lipid-based nanoparticles; these include amino acid–based surfactants and quaternary ammonium salts ( Colomer et al, 2013 ; Hwang et al, 2013 ; Tavano et al, 2014 ). The combination therapy of more than one antibacterial agent can reveal the synergistic activity against MRSA; thus the dose can be reduced to minimize the adverse effects ( Henson et al, 2017 ). Some investigations involve combining nanoparticles and antibacterial agents for the synergistic inhibition of MRSA infection.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Anti-MRSA Activity of Cationic Nanostructured Lipid Carriers in Combination With Oxacillin for Cutaneous Application

Alalaiwe

Wang

et al. 2018

Front. Microbiol.

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Nanoparticles have become a focus of interest due to their ability as antibacterial agents. The aim of this study was to evaluate the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of cationic nanostructured lipid carriers (NLC) combined with oxacillin against ATCC 33591 and clinical isolate. The cationic resource on the NLC surface was soyaethyl morpholinium ethosulfate (SME). NLC loaded with oxacillin was produced to assess the antibacterial activity and the effectiveness of topical application for treating cutaneous infection. The hydrodynamic diameter and zeta potential of oxacillin-loaded NLC were 177 nm and 19 mV, respectively. When combined with NLC, oxacillin exhibited synergistic MRSA eradication. After NLC encapsulation, the minimum bactericidal concentration (MBC) of oxacillin decreased from 250 to 62.5 μg/ml. The combined NLC and oxacillin reduced the MRSA biofilm thickness from 31.2 to 13.0 μm, which was lower than the effect of NLC (18.2 μm) and antibiotic (25.2 μm) alone. The oxacillin-loaded NLC showed significant reduction in the burden of intracellular MRSA in differentiated THP-1 cells. This reduction was greater than that achieved with individual treatment. The mechanistic study demonstrated the ability of cationic NLC to disrupt the bacterial membrane, leading to protein leakage. The cell surface disintegration also increased oxacillin delivery into the cytoplasm, activating the bactericidal process. Topical NLC treatment of MRSA abscess in the skin decreased the bacterial load by log 4 and improved the skin’s architecture and barrier function. Our results demonstrated that a combination of nanocarriers and an antibiotic could synergistically inhibit MRSA growth.

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“…This study found that neither PIP nor TAZ alone synergized with VAN against MRSA. This is notable considering recent data suggest TAZ can synergize with daptomycin against MRSA [6,14]. Given the lack of synergy observed between TAZ and VAN, it is plausible that PIP synergizes with VAN against MRSA but that TAZ is required to preserve PIP in the face of PC1 class A β-lactamase exposure.…”

Section: Discussion/conclusionmentioning

confidence: 98%

“…VAN at onehalf the MIC of each organism, TZP (30/4 mg/L), PIP (30 mg/L), and TAZ (12 mg/L) were tested alone and in combinations. The concentrations of TZP used in previous in vitro experiments with MRSA are variable [3,4,6,12]. We opted to use TZP 30/4 mg/L, to approximate free plasma concentrations observed with TZP 13.5 g continuous infusion, after the previously studied 105/12 mg/L concentration demonstrated bactericidal activity against MRSA in preliminary studies [4,13].…”

Section: Methodsmentioning

confidence: 99%

“…TAZ is a β-lactam compound that may possess intrinsic antibacterial activity. Recent data suggest ampicillin and/or sulbactam and PIP and/or TAZ synergize with daptomycin against MRSA [6]. Notably, synergy was not observed in 5/8 isolates exposed to daptomycin combined with either PIP alone or ampicillin alone, suggesting an important role for β-lactamase inhibitors in synergy between peptides and β-lactams.…”

Section: Introductionmentioning

confidence: 99%

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Exploring the Role of Piperacillin and Tazobactam in Combination with Vancomycin against Methicillin-Resistant <b><i>Staphylococcus aureus</i></b>

et al. 2019

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Previous studies have demonstrated synergy between piperacillin (PIP)-tazobactam (TAZ) (TZP) and vancomycin (VAN) against methicillin-resistant Staphylococcus aureus (MRSA). However, it is unknown whether PIP and/or TAZ synergizes with VAN against MRSA. We sought to determine whether PIP and/or TAZ synergizes with VAN against MRSA in vitro. The activity of PIP and/or TAZ with and without VAN (1/2 the minimum inhibitory concentration) was tested against 5 clinical MRSA isolates using a 24-h time-kill methodology. Antibiotic susceptibilities, accessory gene regulator (agr) operon functionality, and US strain type were also determined for the isolates. The combination of VAN and TZP was bactericidal against 3/5 isolates and synergistic against 4/5 isolates tested. Neither PIP nor TAZ alone combined with VAN demonstrated a significant reduction in bacterial growth. The combination of TZP and VAN was less active against the lone isolate with agr dysfunction. In summation, the combination of VAN with both PIP and TAZ was required for synergy against MRSA. This antibiotic combination may not be effective against unique MRSA strain types.

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β-Lactamase Inhibitors Enhance the Synergy between β-Lactam Antibiotics and Daptomycin against Methicillin-Resistant Staphylococcus aureus

Cited by 13 publications

References 15 publications

Combination of Tedizolid and Daptomycin against Methicillin-Resistant Staphylococcus aureus in an In Vitro Model of Simulated Endocardial Vegetations

Combination of Tedizolid and Daptomycin against Methicillin-Resistant Staphylococcus aureus in an In Vitro Model of Simulated Endocardial Vegetations

Synergistic Anti-MRSA Activity of Cationic Nanostructured Lipid Carriers in Combination With Oxacillin for Cutaneous Application

Exploring the Role of Piperacillin and Tazobactam in Combination with Vancomycin against Methicillin-Resistant <b><i>Staphylococcus aureus</i></b>

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