Dual β-lactam combination therapy for multi-drug resistant Pseudomonas aeruginosa infection: enhanced efficacy in vivo and comparison with monotherapies of penicillin-binding protein inhibition

Siriyong, Thanyaluck; Murray, Rachael M.; Bidgood, Lucy E.; Young, Simon A.; Parcell, Benjamin J.; Voravuthikunchai, Supayang Piyawan; Coote, Peter J.

doi:10.1038/s41598-019-45550-z

Cited by 22 publications

(25 citation statements)

References 51 publications

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“…The combination of a carbapenem antibiotic with colistin increased the eradication of P. aeruginosa infections [42]. Dual β-lactam therapy also has been shown to have enhanced efficacy in killing P. aeruginosa [119], with an example being ceftazidime-avibactam paired with meropenem [120].…”

Section: β-Lactam Antibiotics: Inhibitors Of Pbpsmentioning

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: β-Lactam Antibiotics: Inhibitors Of Pbpsmentioning

confidence: 99%

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

Glen

Lamont

2021

Pathogens

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“… 10 , 90 Against non-MBL P. aeruginosa , in vitro studies have shown synergistic activity for combinations of piperacillin and a third-generation cephalosporin, piperacillin and cefepime, ceftazidime and meropenem, and ceftazidime/avibactam and meropenem, whereas synergistic activity against MBL P. aeruginosa has been shown for the combination of aztreonam and ceftazidime/avibactam. 10 , 87 , 91 – 94 Further, the combination of aztreonam and piperacillin/tazobactam has been shown to result in antagonism against P. aeruginosa . 10 , 95 Additionally, combinations of meropenem and ampicillin/sulbactam and of imipenem plus ampicillin/sulbactam have been shown to have synergistic activity against CRAB.…”

Section: Reviewmentioning

confidence: 99%

Infectious disease: how to manage Gram-positive and Gram-negative pathogen conundrums with dual beta-lactam therapy

FakhriRavari¹,

Simiyu²,

Morrisette³

et al. 2022

DIC

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In the interest of transparency, we ask you to disclose all relationships/activities/interests listed below that are related to the content of your manuscript. "Related" means any relation with for-profit or not-for-profit third parties whose interests may be affected by the content of the manuscript. Disclosure represents a commitment to transparency and does not necessarily indicate a bias. If you are in doubt about whether to list a relationship/activity/interest, it is preferable that you do so.The following questions apply to the author's relationships/activities/interests as they relate to the current manuscript only.

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“…Nano-penicillin ( Yariv et al, 2015 ) or nano-ampicillin can be introduced to fight drug-resistant Streptococcus pneumoniae . Combinatorial beta-lactams ( Siriyong et al, 2019 ) synthesized in pure-nano form as explained in ( Yariv et al, 2015 ) may be applied to address multi-drug resistant Pseudomonas aeruginosa .…”

Section: Future Research Perspectivesmentioning

confidence: 99%

Nanoantibiotics: Functions and Properties at the Nanoscale to Combat Antibiotic Resistance

et al. 2021

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One primary mechanism for bacteria developing resistance is frequent exposure to antibiotics. Nanoantibiotics (nAbts) is one of the strategies being explored to counteract the surge of antibiotic resistant bacteria. nAbts are antibiotic molecules encapsulated with engineered nanoparticles (NPs) or artificially synthesized pure antibiotics with a size range of ≤100 nm in at least one dimension. NPs may restore drug efficacy because of their nanoscale functionalities. As carriers and delivery agents, nAbts can reach target sites inside a bacterium by crossing the cell membrane, interfering with cellular components, and damaging metabolic machinery. Nanoscale systems deliver antibiotics at enormous particle number concentrations. The unique size-, shape-, and composition-related properties of nAbts pose multiple simultaneous assaults on bacteria. Resistance of bacteria toward diverse nanoscale conjugates is considerably slower because NPs generate non-biological adverse effects. NPs physically break down bacteria and interfere with critical molecules used in bacterial processes. Genetic mutations from abiotic assault exerted by nAbts are less probable. This paper discusses how to exploit the fundamental physical and chemical properties of NPs to restore the efficacy of conventional antibiotics. We first described the concept of nAbts and explained their importance. We then summarized the critical physicochemical properties of nAbts that can be utilized in manufacturing and designing various nAbts types. nAbts epitomize a potential Trojan horse strategy to circumvent antibiotic resistance mechanisms. The availability of diverse types and multiple targets of nAbts is increasing due to advances in nanotechnology. Studying nanoscale functions and properties may provide an understanding in preventing future outbreaks caused by antibiotic resistance and in developing successful nAbts.

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Dual β-lactam combination therapy for multi-drug resistant Pseudomonas aeruginosa infection: enhanced efficacy in vivo and comparison with monotherapies of penicillin-binding protein inhibition

Cited by 22 publications

References 51 publications

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

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

Infectious disease: how to manage Gram-positive and Gram-negative pathogen conundrums with dual beta-lactam therapy

Nanoantibiotics: Functions and Properties at the Nanoscale to Combat Antibiotic Resistance

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