Unexpected synergistic and antagonistic antibiotic activity against Staphylococcus biofilms

Dall, G; Tsang, Jerry; Gwynne, Peter; Mackenzie, Samuel P.; Simpson, A. H. R. W.; Breusch, Steffen; Gallagher, Maurice P.

doi:10.1093/jac/dky087

Cited by 46 publications

(38 citation statements)

References 77 publications

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“…For instance, the MIC does not allow a differentiation between the bacteriostatic and bactericidal activities of an HDP. Furthermore, an HDP may be bactericidal and eradicate biofilms (Dall et al, 2018;Swedan et al, 2019). Bacteriostatic antibiotics act by fully or partially inhibiting bacterial growth (Wiegand et al, 2008); however, growth will resume after removal of the antibiotic.…”

Section: Biological Assays To Determine Moamentioning

confidence: 99%

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions

2019

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Section: Biological Assays To Determine Moamentioning

confidence: 99%

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions

2019

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“…To analyze the antibacterial performance of gentamicin containing ECM envelope, in vivo experiments were conducted using an established New Zealand White rabbit cardiac device pocket infection model 26,27 . In this study, five different species of bacteria, three Gram‐positive [MRSA (ATCC 33591) (Supporting Information Table S6), S. aureus (ATCC 29213) (Supporting Information Table S2), S. epidermidis (ATCC 35984) (Supporting Information Table S3)]and two Gram‐negative [ E. coli (ATCC 25922) (Supporting Information Table S4) and P. aeruginosa (ATCC 25922) (Supporting Information Table S5)], were tested in five separate experiments.…”

Section: Methodsmentioning

confidence: 99%

“…[22][23][24][25] When given as monotherapy, gentamicin has also demonstrated in vitro efficacy against established Staphyloccocal biofilms. 26 However, there are major limitations associated with systemic use of gentamicin therapy including the potential development of nephrotoxicity and otoxocity. 27 Local gentamicin delivery to the site that potentially harbors pathogens, may overcome some of these risks.…”

Section: F I G U R E 1 Extracellular Matrix Envelopementioning

confidence: 99%

“…To analyze the antibacterial performance of gentamicin containing ECM envelope, in vivo experiments were conducted using an estab-lished New Zealand White rabbit cardiac device pocket infection model. 26,27 In this study, five different species of bacteria, three For each bacterial strain, three groups of animals were included.…”

Section: Efficacy Of Gentamicin Containing Ecm Envelopementioning

confidence: 99%

“…and aerobic Gram‐negative organisms 22–25 . When given as monotherapy, gentamicin has also demonstrated in vitro efficacy against established Staphyloccocal biofilms 26 . However, there are major limitations associated with systemic use of gentamicin therapy including the potential development of nephrotoxicity and otoxocity 27 .…”

Section: Introductionmentioning

confidence: 99%

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Preclinical evaluation of efficacy and pharmacokinetics of gentamicin containing extracellular‐matrix envelope

Sohail

Garrigos

Elayi

et al. 2020

Pacing Clinical Electrophis

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Background Using synthetic antibiotic‐eluting envelope (ABE) is an effective intervention for prevention of cardiovascular implantable electronic device (CIED) infection. The biologic extracellular‐matrix envelope (ECME), may offer potential advantages over the synthetic ABE. To further minimize the risk of infection, the ECME can be hydrated in gentamicin prior to CIED implantation. We aimed to evaluate the efficacy and pharmacokinetics (PK) of gentamicin containing ECME in an animal model. Methods For all experiments, the ECME was hydrated in gentamicin (40 mg/Ml) (treatment) for 2 min. In vitro antimicrobial efficacy against six different bacterial species was assessed. In vivo experiments were conducted using a rabbit model of CIED pocket infection. Serum and ECM gentamicin concentrations were measured. Five different organisms were inoculated into the device pocket of control (ECME hydrated in 0.9% saline) and treatment groups. Macroscopic appearance and colony forming units from CIED, ECME, and tissue were determined. Results No bacteria were recovered from any culture after 12 h of exposure to the gentamicin containing ECME. Serum gentamicin levels dropped below the limit of quantification at 15 h after implant. Gentamicin concentration in the ECME remained relatively stable for up to 7 days. Signs of clinical infection were observed in the control but not in the treatment group. In the presence of gentamicin, statistically significant reduction was demonstrated across all tested bacterial species. Conclusions In this preclinical animal infection model, gentamicin containing ECME was highly effective in reducing bacterial burden in the implant pocket, while systemic exposure after implantation remained low.

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Strategies to Improve the Potency of Oxazolidinones towards Bacterial Biofilms

Ndukwe

Wiedbrauk

Boase

et al. 2022

Chemistry An Asian Journal

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Biofilms are part of the natural lifecycle of bacteria and are known to cause chronic infections that are difficult to treat. Most antibiotics are developed and tested against bacteria in the planktonic state and are ineffective against bacterial biofilms. The oxazolidinones, including the last resort drug linezolid, are one of the main classes of synthetic antibiotics progressed to clinical use in the last 50 years. They have a unique mechanism of action and only develop low levels of resistance in the clinical setting. With the aim of providing insight into strategies to design more potent antibiotic compounds with activity against bacterial biofilms, we review the biofilm activity of clinically approved oxazolidinones and report on structural modifications to oxazolidinones and their delivery systems which lead to enhanced anti‐biofilm activity.

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Unexpected synergistic and antagonistic antibiotic activity against Staphylococcus biofilms

Abstract: This study found that gentamicin and daptomycin were the only effective single-agent antibiotics against established Staphylococcus biofilms. Interestingly the addition of a bacteriostatic antibiotic was found to antagonize the ability of gentamicin to eradicate Staphylococcus biofilms.

Cited by 46 publications

References 77 publications

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions

Preclinical evaluation of efficacy and pharmacokinetics of gentamicin containing extracellular‐matrix envelope

Strategies to Improve the Potency of Oxazolidinones towards Bacterial Biofilms

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