Optimization of Phage-Antibiotic Combinations against Staphylococcus aureus Biofilms

Kebriaei, Razieh; Lehman, Susan M.; Shah, Rahi M.; Stamper, Kyle; Coyne, Ashlan J Kunz; Holger, Dana; Ghali, Amer El; Rybak, Michael J.

doi:10.1128/spectrum.04918-22

Cited by 14 publications

(8 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The bacteriophage-mediated changes in envelope architecture, related to enzymatic activity, resensitizes A.baumannii to colistin. Additionally, Friunaviruses are characterized by coding exopolysaccharidases that could increase the penetration of antibiotics into biofilm [ 41 , 42 , 43 , 44 ]. Similar findings were also found for other bacteria like Pseudomonas aeruginosa and Citrobacter amalonaticus [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Response Surface Methodology Application for Bacteriophage–Antibiotic Antibiofilm Activity Optimization

Grygorcewicz,

Gliźniewicz,

Olszewska

et al. 2023

Microorganisms

View full text Add to dashboard Cite

Phage–antibiotic combination-based protocols are presently under heightened investigation. This paradigm extends to engagements with bacterial biofilms, necessitating novel computational approaches to comprehensively characterize and optimize the outcomes achievable via these combinations. This study aimed to explore the Response Surface Methodology (RSM) in optimizing the antibiofilm activity of bacteriophage–antibiotic combinations. We employ a combination of antibiotics (gentamicin, meropenem, amikacin, ceftazidime, fosfomycin, imipenem, and colistin) alongside the bacteriophage vB_AbaP_AGC01 to combat Acinetobacter baumannii biofilm. Based on the conducted biofilm challenge assays analyzed using the RSM, the optimal points of antibiofilm activity efficacy were effectively selected by applying this methodology, enabling the quantifiable mathematical representations. Subsequent optimization showed the synergistic potential of the anti-biofilm that arises when antibiotics are judiciously combined with the AGC01 bacteriophage, reducing biofilm biomass by up to 80% depending on the antibiotic used. The data suggest that the phage–imipenem combination demonstrates the highest efficacy, with an 88.74% reduction. Notably, the lower concentrations characterized by a high maximum reduction in biofilm biomass were observed in the phage–amikacin combination at cA = 0.00195 and cP = 0.38 as the option that required minimum resources. It is worth noting that only gentamicin antagonism between the phage and the antibiotic was detected.

show abstract

Section: Discussionmentioning

confidence: 99%

Response Surface Methodology Application for Bacteriophage–Antibiotic Antibiofilm Activity Optimization

Grygorcewicz,

Gliźniewicz,

Olszewska

et al. 2023

Microorganisms

View full text Add to dashboard Cite

show abstract

“…Biofilms of P. aeruginosa isolated from diabetic and non-diabetic wounds resist removal by phages compared to biofilms formed by environmental isolates. However, this partial eradication of biofilm by phages can aid in complementing antibiotics that are unable to penetrate biofilms in a clinical set-up [ 46 , 47 , 48 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Antibiofilm Activity of Pseudomonas aeruginosa Phages on Isolates from Wounds of Diabetic and Non-Diabetic Patients

Suresh,

Saldanha,

Bhaskar Shetty

et al. 2023

Microorganisms

View full text Add to dashboard Cite

The persistence of organisms as biofilms and the increase in antimicrobial resistance has raised the need for alternative strategies. The study objective was to compare the ability of isolated bacteriophages to remove in vitro biofilms formed by Pseudomonas aeruginosa isolated from the environment with those isolated from diabetic and non-diabetic wounds. P. aeruginosa were isolated from clinical and environmental sites, and antimicrobial susceptibility was tested. Bacteriophages were isolated and characterized based on plaque morphology and host range. A reduction in the viable count assayed the lytic ability of candidate phages. The crystal violet method was used to determine the residual biofilm after 24 h of phage treatment on 72-h-old biofilms. The statistical significance of phage treatment was tested by one-way ANOVA. Of 35 clinical isolates, 17 showed resistance to 1 antibiotic at least, and 7 were multidrug resistant. Nineteen environmental isolates and 11 clinical isolates were drug-sensitive. Nine phages showed 91.2% host coverage, including multidrug-resistant isolates. Phages eradicated 85% of biofilms formed by environmental isolates compared to 58% of biofilms of diabetic isolates and 56% of biofilms of non-diabetic isolates. Clinical isolates are susceptible to phage infection in planktonic form. Biofilms of P. aeruginosa isolated from diabetic wounds and non-diabetic wounds resist removal by phages compared to biofilms formed by environmental isolates. All phages were efficient in dispersing PAO1 biofilms. However, there was a significant difference in their ability to disperse PAO1 biofilms across the different surfaces tested. Partial eradication of biofilm by phages can aid in complementing antibiotics that are unable to penetrate biofilms in a clinical set-up.

show abstract

“…My suspicion, in fact, is that in explicit terms, this math may be less useful than can be the case for preclinical studies, if only because there is less opportunity to make the detailed measurements that many of these models require, e.g., such as of bacterial concentrations, phage titers in association with targeted bacteria, phage adsorption rate constants, phage burst sizes, etc. These are all as found in situ while treating infections caused by what are typically somewhat uncharacterized bacterial strains and, in many cases, also in combination with antibiotics [ 41 , 57 , 86 , 87 , 88 , 89 ], which can have antagonistic impacts on phage infection abilities [ 41 , 51 , 85 , 90 ]. In particular for the latter, note that of 18 clinical phage therapy studies that I was able to obtain—published in 2023 or, at the time of writing, which are published but still online ahead of print—at least 16 indicate treatments using phages in combination with antibiotics [ 57 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ].…”

Section: Discussionmentioning

confidence: 99%

Automating Predictive Phage Therapy Pharmacology

Abedon

2023

Antibiotics

View full text Add to dashboard Cite

Viruses that infect as well as often kill bacteria are called bacteriophages, or phages. Because of their ability to act bactericidally, phages increasingly are being employed clinically as antibacterial agents, an infection-fighting strategy that has been in practice now for over one hundred years. As with antibacterial agents generally, the development as well as practice of this phage therapy can be aided via the application of various quantitative frameworks. Therefore, reviewed here are considerations of phage multiplicity of infection, bacterial likelihood of becoming adsorbed as a function of phage titers, bacterial susceptibility to phages also as a function of phage titers, and the use of Poisson distributions to predict phage impacts on bacteria. Considered in addition is the use of simulations that can take into account both phage and bacterial replication. These various approaches can be automated, i.e., by employing a number of online-available apps provided by the author, the use of which this review emphasizes. In short, the practice of phage therapy can be aided by various mathematical approaches whose implementation can be eased via online automation.

show abstract

Optimization of Phage-Antibiotic Combinations against Staphylococcus aureus Biofilms

Cited by 14 publications

References 47 publications

Response Surface Methodology Application for Bacteriophage–Antibiotic Antibiofilm Activity Optimization

Response Surface Methodology Application for Bacteriophage–Antibiotic Antibiofilm Activity Optimization

Comparison of Antibiofilm Activity of Pseudomonas aeruginosa Phages on Isolates from Wounds of Diabetic and Non-Diabetic Patients

Automating Predictive Phage Therapy Pharmacology

Contact Info

Product

Resources

About