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

Abstract

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.

Aptamer-Targeted Drug Delivery for Staphylococcus aureus Biofilm

“…To increase our chance of success, we encapsulated both vancomycin and rifampicin in the liposomes. This antibiotic combination has proven synergistic in several studies (Deresinski, 2009;Rose and Poppens, 2009;Niska et al, 2013;Vergidis et al, 2015;Jørgensen et al, 2016;Boudjemaa et al, 2017), and we found that with this combination we needed only one-tenth of drug-loaded liposomes for eradication of S. aureus biofilm (Table S2). We hypothesized that optimal antimicrobial effect would be obtained by releasing the content in a bolus fashion, and we therefore designed low-temperature sensitive formulation that would release the loaded antibiotics at mild hyperthermia treatment (Figure 4B).…”

Synergistic Potential of Antimicrobial Combinations Against Methicillin-Resistant Staphylococcus aureus

“…Given that rifampicin interferes with the DNA synthesis while vancomycin disrupts the bacterial cell wall synthesis, the drug combination may disturb cell reproduction in different stages. For example, when vancomycin combined with rifampicin, significantly higher cell damage and decrease in biofilms thicknesses were detected (Boudjemaa et al, 2017).…”

Phosphonic Acid Fluorescent Organic Nanoparticles for High-Contrast and Selective Staining of Gram-Positive Bacteria

“…1−3 Even though electrochemical biosensors, 4 as well as magnetic trapping and imaging of bacteria, 5−7 have revealed to be efficient, optical detection stirs particular attention because high-resolution and time-resolved mapping of bacteria surface can be achieved, giving access for instance to dynamic interactions with antibiotics. 8 It also enables higher levels of sensitivity, down to the zeptomolar concentration and single bacterium level. 9 This is particularly true when using bioconjugated gold nanoparticles, which yield neat red-to-blue colorimetric contrast due to bacteria recognition causing aggregation 10 or provide sensitive vibrational fingerprint by resorting to surfaceenhanced resonance spectroscopy.…”

“…Fast and selective detection of pathogens represents high technological and scientific challenges in the context of outbreaks or infections contracted after hospitalization to avoid dissemination and severe health complications. Stimuli-responsive nanostructured surfaces and nanoparticles have thus emerged to gain speed and portability. − Even though electrochemical biosensors, as well as magnetic trapping and imaging of bacteria, − have revealed to be efficient, optical detection stirs particular attention because high-resolution and time-resolved mapping of bacteria surface can be achieved, giving access for instance to dynamic interactions with antibiotics . It also enables higher levels of sensitivity, down to the zeptomolar concentration and single bacterium level .…”