Antibiotic Tolerance and Combination Therapy

Bean, David C.; Wigmore, Sarah M.

doi:10.1128/mbio.00120-15

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…The recent paper by Haaber and colleagues entitled “Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure” ( 1 ) revealed a possible alternative mechanism by which pathogens become less susceptible to standard therapy by screening for inducible antibiotic resistance in Staphylococcus aureus USA300 strain FP3757. We agree with the sentiments expressed by Bean and Wigmore ( 2 ) about the timeliness of this article and the need to examine antibiotic combinations, especially with increasing multidrug-resistant pathogens. Furthermore, this article highlighted some of the potential pitfalls of combination therapy and stressed the need for further research in this area.…”

Section: Lettersupporting

confidence: 83%

“Tolerance” of Misused Terminology? Enforcing Standardized Phenotypic Definitions

Dimitrijovski

Jensen

Espedido

et al. 2015

mBio

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Section: Lettersupporting

confidence: 83%

“Tolerance” of Misused Terminology? Enforcing Standardized Phenotypic Definitions

Dimitrijovski

Jensen

Espedido

et al. 2015

mBio

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“…The combination of an antibiotic with another potentially synergistic antibiotic, or with a compound that would potentiate the activity of the antibiotic, is attractive in the light of the dearth of clinical options. While such combinations can have extraordinary medical value (as exemplified by the combination of β-lactams with β-lactamase inhibitors), − every aspect to the selection and implementation of successful combination therapy is a scientific challenge. − With respect to this challenge, useful guidance may be provided by Nature.…”

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confidence: 99%

Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the β-Lactam Antibiotics

et al. 2018

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The bulgecins are iminosaccharide secondary metabolites of the Gram-negative bacterium Paraburkholderia acidophila and inhibitors of lytic transglycosylases of bacterial cell-wall biosynthesis and remodeling. The activities of the bulgecins are intimately intertwined with the mechanism of a cobiosynthesized β-lactam antibiotic. β-Lactams inhibit the penicillin-binding proteins, enzymes also critical to cell-wall biosynthesis. The simultaneous loss of the lytic transglycosylase (by bulgecin) and penicillin-binding protein (by β-lactams) activities results in deformation of the septal cell wall, observed microscopically as a bulge preceding bacterial cell lysis. We describe a practical synthesis of the three naturally occurring bulgecin iminosaccharides and their mechanistic evaluation in a series of microbiological studies. These studies identify potentiation by the bulgecin at subminimum inhibitory concentrations of the β-lactam against three pathogenic Gram-negative bacteria and establish for the first time that this potentiation results in a significant increase in the bactericidal efficacy of a clinical β-lactam.

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How do fluorescence spectroscopy and multimodal fluorescence imaging help to dissect the enhanced efficiency of the vancomycin–rifampin combination against Staphylococcus aureus infections?

Boudjemaa

Briandet

Fontaine‐Aupart

et al. 2017

Photochem Photobiol Sci

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Staphylococcus aureus is one of the most frequent pathogens responsible for biofilm-associated infections. Among current clinical antibiotics, very few enable long-term successful treatment. Thus, it becomes necessary to better understand antibiotic failures and successes in treating infections in order to master the use of proper antibiotic therapies. In this context, we took benefit from a set of fluorescence spectroscopy and imaging methods, with the support of conventional microbiological tools to better understand the vancomycin-rifampin combination (in)efficiency against S. aureus biofilms. It was shown that both antibiotics interacted by forming a complex. This latter allowed a faster penetration of the drugs before dissociating from each other to interact with their respective biological targets. However, sufficiently high concentrations of free vancomycin should be maintained, either by increasing the vancomycin concentration or by applying repetitive doses of the two drugs, in order to eradicate rifampin-resistant mutants.

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Antibiotic Tolerance and Combination Therapy

Cited by 3 publications

References 7 publications

“Tolerance” of Misused Terminology? Enforcing Standardized Phenotypic Definitions

“Tolerance” of Misused Terminology? Enforcing Standardized Phenotypic Definitions

Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the β-Lactam Antibiotics

How do fluorescence spectroscopy and multimodal fluorescence imaging help to dissect the enhanced efficiency of the vancomycin–rifampin combination against Staphylococcus aureus infections?

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