A combination therapy of Phages and Antibiotics: Two is better than one

Li, Xianghui; He, Yuhua; Wang, Zhili; Wei, Jiacun; Hu, Tongxin; Si, Jiangzhe; Tao, Guangzhao; Zhang, Lei; Xie, Longxiang; Abdalla, Abualgasim Elgaili; Wang, Guoying; Li, Yanzhang; Teng, Tieshan

doi:10.7150/ijbs.60551

Cited by 66 publications

(53 citation statements)

References 124 publications

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“…The first of these relies on the principle that if an infecting bacterium has become resistant to one antibiotic, it will still be susceptible to a second. As well as antibiotic combinations, phage therapy in parallel with antibiotic treatment is undergoing extensive testing in clinical trials and results are encouraging [305][306][307][308][309]. Powdered phage cocktails are being specifically designed for the treatment of respiratory infections [310].…”

Section: Conclusion and Prospects For The Futurementioning

confidence: 99%

β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects

Glen

Lamont

2021

Pathogens

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Pseudomonas aeruginosa is a major opportunistic pathogen, causing a wide range of acute and chronic infections. β-lactam antibiotics including penicillins, carbapenems, monobactams, and cephalosporins play a key role in the treatment of P. aeruginosa infections. However, a significant number of isolates of these bacteria are resistant to β-lactams, complicating treatment of infections and leading to worse outcomes for patients. In this review, we summarize studies demonstrating the health and economic impacts associated with β-lactam-resistant P. aeruginosa. We then describe how β-lactams bind to and inhibit P. aeruginosa penicillin-binding proteins that are required for synthesis and remodelling of peptidoglycan. Resistance to β-lactams is multifactorial and can involve changes to a key target protein, penicillin-binding protein 3, that is essential for cell division; reduced uptake or increased efflux of β-lactams; degradation of β-lactam antibiotics by increased expression or altered substrate specificity of an AmpC β-lactamase, or by the acquisition of β-lactamases through horizontal gene transfer; and changes to biofilm formation and metabolism. The current understanding of these mechanisms is discussed. Lastly, important knowledge gaps are identified, and possible strategies for enhancing the effectiveness of β-lactam antibiotics in treating P. aeruginosa infections are considered.

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Section: Conclusion and Prospects For The Futurementioning

confidence: 99%

β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects

Glen

Lamont

2021

Pathogens

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“…One intended application of phage is a therapy to kill pathogenic bacteria, as an alternative to traditional antibiotic treatments, or as a phage-antibiotic synergy (PAS) aiming to reduce the dose of antibiotics and the development of antimicrobial resistance (AMR). 75 The maintenance of efficacy and the lytic ability of our phage after cryopreservation was checked by measuring changes in optical density (OD 600 ) in a growth curve over a 24 h period. In this assay, the phage was cryopreserved with 10 mg·mL –1 PEG, thawed, and then added to a culture of E. coli , and the change in turbidity was measured by absorbance at 600 nm.…”

Section: Results and Discussionmentioning

confidence: 99%

Polymer-Mediated Cryopreservation of Bacteriophages

et al. 2021

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Bacteriophages (phages, bacteria-specific viruses) have biotechnological and therapeutic potential. To apply phages as pure or heterogeneous mixtures, it is essential to have a robust mechanism for transport and storage, with different phages having very different stability profiles across storage conditions. For many biologics, cryopreservation is employed for long-term storage and cryoprotectants are essential to mitigate cold-induced damage. Here, we report that poly(ethylene glycol) can be used to protect phages from cold damage, functioning at just 10 mg·mL –1 (∼1 wt %) and outperforms glycerol in many cases, which is a currently used cryoprotectant. Protection is afforded at both −20 and −80 °C, the two most common temperatures for frozen storage in laboratory settings. Crucially, the concentration of the polymer required leads to frozen solutions at −20 °C, unlike 50% glycerol (which results in liquid solutions). Post-thaw recoveries close to 100% plaque-forming units were achieved even after 2 weeks of storage with this method and kill assays against their bacterial host confirmed the lytic function of the phages. Initial experiments with other hydrophilic polymers also showed cryoprotection, but at this stage, the exact mechanism of this protection cannot be concluded but does show that water-soluble polymers offer an alternative tool for phage storage. Ice recrystallization inhibiting polymers (poly(vinyl alcohol)) were found to provide no additional protection, in contrast to their ability to protect proteins and microorganisms which are damaged by recrystallization. PEG’s low cost, solubility, well-established low toxicity/immunogenicity, and that it is fit for human consumption at the concentrations used make it ideal to help translate new approaches for phage therapy.

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“…Although phage treatment failed to save the infected animals, the significantly delayed mortality encouraged us to evaluate the potential of phage as adjunctive therapy to second-line antibiotics as an alternative countermeasure against MDR Y. pestis . It has been shown in various case reports and animal model studies that combining antibiotics with phages may enhance bacterial clearance, increase antibiotic penetration into biofilms and decrease the emergence of phage resistance (see reviews [33,34]).…”

Section: Discussionmentioning

confidence: 99%

Phage therapy potentiates second-line antibiotic treatment against pneumonic plague

Vagima

Gur

Aftalion

et al. 2022

Preprint

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Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by Yersinia pestis bacteria, can currently be treated efficiently with antibiotics. However, in the case of multidrug-resistant (MDR) bacteria, alternative treatments are required. Bacteriophage (phage) therapy has shown efficient antibacterial activity in various experimental animal models and in human patients infected with different MDR pathogens. Herein, we evaluated the efficiency of фA1122 and PST phage therapy, alone or in combination with second-line antibiotics, using a well-established mouse model of pneumonic plague. Phage treatment significantly delayed mortality and limited bacterial proliferation in the lungs. However, the treatment did not prevent bacteremia, suggesting that phage efficiency may decrease in circulation. Indeed, in vitro phage proliferation assays indicated that blood has inhibitory effects on lytic activity, which may be the major cause of treatment inefficiency. Combining phage therapy and second-line ceftriaxone treatment, which are individually insufficient, provided protection that led to survival of all infected animals, presenting a synergistic protective effect that represents a proof of concept for efficient combinatorial therapy in an emergency event of a plague outbreak involving MDR Y. pestis strains.

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A combination therapy of Phages and Antibiotics: Two is better than one

Cited by 66 publications

References 124 publications

β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects

β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects

Polymer-Mediated Cryopreservation of Bacteriophages

Phage therapy potentiates second-line antibiotic treatment against pneumonic plague

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