# Anti-biofilm activity of bacteriophage-antibiotic combinations against MRSA

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2021 · $192,500

## Abstract

Summary/Abstract
 Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are problematic
because of the high associated treatment failures and elevated mortality rates. Staphylococci
including MRSA are the major cause of medical device infections (MDIs) due to their strong
capability to form biofilms. These bacterial biofilms resist host immune system and lead to
antibiotic failure due to limited antibiotic penetration, bacterial tolerance and development of
antibiotic resistance. Vancomycin is the recommended therapy for MRSA MDIs and daptomycin
is the primary antibiotic alternative to vancomycin for these infections; however, the development
of daptomycin resistance especially post vancomycin therapy has been reported with increasing
frequency. Although combination therapy of vancomycin or daptomycin with beta-lactam
antibiotics such as ceftaroline have demonstrated improved activity in vitro, these combinations
have not shown significant enhancements in MDIs caused by Staphylococci. Therefore, due to
the lack of effective MDI treatments, novel antibacterial options are critically needed. Obligately
lytic bacteriophages (phages) infect bacteria, replicate within the cell, lyse the cell to release their
progeny and reinitiate the infection cycle. These phages eradicate both antibiotic susceptible and
resistant bacteria in planktonic and biofilm forms. The combination of phage and antibiotics have
shown to re-sensitize previously multi-drug resistant bacteria to antibiotics. Synergistic and
antagonistic interactions in phage-antibiotic combinations are highly dependent on the
mechanism of bacterial inhibition of the antibiotic paired to the phage, bacterial host state (biofilm
versus planktonic) and bacterial growth age. Here we are offering a systematic investigation of
phage antibiotic combination using various standard of care antibiotics (SOC) to examine the
aforementioned parameters. The proposed research is significant especially due to lack of
information regarding the use of phage with SOC antibiotics against biofilm embedded MRSA
strains. Our central hypothesis is that the combination of phage-antibiotic will reduce the
vancomycin and daptomycin exposures required for efficacy against biofilm embedded MRSA
and further prevent the emergence of antibiotic resistance. We will test our central hypothesis by
first evaluating susceptibility of biofilm embedded MRSA to various phage-antibiotic
combinations and then performing in vitro two-compartment PK/PD biofilm models with
humanized pharmacokinetics to optimize novel phage-antibiotic combination therapies. We
expect that through optimizing therapy of MRSA-biofilm infections, we will improve patient care
and prolong the useful life of vancomycin and daptomycin for the management of MRSA MDIs.

## Key facts

- **NIH application ID:** 10285430
- **Project number:** 1R21AI163726-01
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Michael Joseph Rybak
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $192,500
- **Award type:** 1
- **Project period:** 2021-06-10 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285430

## Citation

> US National Institutes of Health, RePORTER application 10285430, Anti-biofilm activity of bacteriophage-antibiotic combinations against MRSA (1R21AI163726-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10285430. Licensed CC0.

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