Issue 19, 2023

Antimicrobial efficacy of a nitric oxide-releasing ampicillin conjugate catheter lock solution on clinically-isolated antibiotic-resistant bacteria

Abstract

Antibiotic lock therapy (ALT) is standard clinical practice for treating bacteremia linked with catheter-related bloodstream infections (CRBSIs). However, this strategy frequently fails against multi-drug-resistant bacteria in clinical settings. In this study, a novel approach to utilize a nitric oxide (NO) donor S-nitroso-N-acetyl-penicillamine (SNAP)-conjugated to ampicillin antibiotic (namely SNAPicillin) as a catheter lock solution is presented. The conjugate of two antimicrobial agents is anticipated to overcome the challenges of bacterial infection caused by antibiotic-resistant bacteria in ALT applications. Nitric oxide release from the SNAPicillin lock solution at varying concentrations was measured at 0 and 24 h time points in a catheter model system, which revealed tunable NO release at physiological levels. The clinical strains of E. coli (CDC AR-0089) and S. marcescens (CDC AR-0099) were screened using a zone of inhibition assay against standard antibiotics which confirmed the antibiotic resistance in bacteria. The minimum inhibitory concentration (MIC) testing of SNAPicillin unveiled the lowest MIC value for SNAPicillin against both E. coli and S. marcescens (1 and 2 mM of SNAPicillin, respectively) with an 8.24- and 4.28-log reduction in bacterial load compared to controls, respectively. In addition, while the ampicillin-treated biofilm demonstrated resistance toward the antibiotic, SNAPicillin led to >99% reduction in exterminating biofilm buildup on polymeric catheter surfaces. Lastly, the SNAPicillin lock solution was determined to be biocompatible via hemolysis and cell compatibility studies. Together, these results emphasize the promising potential of SNAPicillin lock solution with the dual-action of NO and ampicillin in overcoming bacterial challenges on medical devices like central venous catheters and other medical device interfaces.

Graphical abstract: Antimicrobial efficacy of a nitric oxide-releasing ampicillin conjugate catheter lock solution on clinically-isolated antibiotic-resistant bacteria

Supplementary files

Article information

Article type
Paper
Submitted
05 may 2023
Accepted
09 iyl 2023
First published
11 iyl 2023

Biomater. Sci., 2023,11, 6561-6572

Antimicrobial efficacy of a nitric oxide-releasing ampicillin conjugate catheter lock solution on clinically-isolated antibiotic-resistant bacteria

M. K. Chug, L. Griffin, M. Garren, E. Tharp, G. H. Nguyen, H. Handa and E. J. Brisbois, Biomater. Sci., 2023, 11, 6561 DOI: 10.1039/D3BM00775H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements