Subinhibitory Dalbavancin Attenuates Exotoxin Production from Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus<i>In Vitro</i>

Hobdey, Sarah E.; Katahira, Eva J.; Dockstader, Pamela; Davidson, Stephen M.; Bond, Laura; Bolz, Devin D.; Bryant, Amy E.; Stevens, Dennis L.

doi:10.1128/aac.01090-17

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…In this sense, bacteria are frequently exposed to Sub-MIC of the antimicrobial agent and these conditions could result in mutagenesis and release of microbial virulence factors (Andersson and Hughes, 2014;Jo and Ahn, 2016;Larsen et al, 2016;Huijbers et al, 2019). Thus, it is important to evaluate the effects of the antimicrobial agents in pathways related to mutagenesis and virulence (Hobdey et al, 2017;Duan et al, 2018). We first showed that EbEO did not induce the expression of recA which is the first gene in the SOS response.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial and Antivirulence Action of Eugenia brejoensis Essential Oil in vitro and in vivo Invertebrate Models

Filho

Silva

et al. 2020

Front. Microbiol.

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Eugenia brejoensis L. (Myrtaceae) is an endemic plant from caatinga ecosystem (brazilian semi-arid) which have an E. brejoensis essential oil (EbEO) with reported antimicrobial activity. In this work, in vitro and in vivo models were used to characterize the inhibitory effects of EbEO in relation to Staphylococcus aureus. EbEO inhibited the growth of all tested S. aureus strains (including multidrug resistance isolates) with values ranging from 8 to 516 µg/mL. EbEO also synergistically increased the action of ampicillim, chloramphenicol, and kanamycin. The treatment with subinhibitory concentrations (Sub-MIC) of EbEO decreased S. aureus hemolytic activity and its ability to survive in human blood. EbEO strongly reduced the levels of staphyloxanthin (STX), an effect related to increased susceptibility of S. aureus to hydrogen peroxide. The efficacy of EbEO against S. aureus was further demonstrated using Caenorhabditis elegans and Galleria mellonella. EbEO increased the lifespan of both organisms infected by S. aureus, reducing the bacterial load. In addition, EbEO reduced the severity of S. aureus infection in G. mellonella, as shown by lower levels of melanin production in those larvae. In summary, our data suggest that EbEO is a potential source of lead molecules for development of new therapeutic alternatives against S. aureus.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial and Antivirulence Action of Eugenia brejoensis Essential Oil in vitro and in vivo Invertebrate Models

Filho

Silva

et al. 2020

Front. Microbiol.

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“…In the case of S. aureus optimal AUC24hr/MIC ratios for dalbavancin are predicted to be 100-300, much lower than the 400-600 target suggested for vancomycin [30,31]. Some in vitro data suggest that dalbavancin might possess other advantages over classical glycopeptides including greater potency against organisms in the bio lm state and the ability to suppress bacterial exotoxin production, though this has not been corroborated in clinical studies [32,33]. Dalbavancin is highly active against most clinically relevant Gram-positive organisms with the notable exception of vancomycin resistant enterococci, or more rarely vancomycin resistant Staphylococcus aureus (VRSA) carrying the vanA gene, as well as some species seldom encountered as pathogens such as Enterocloster clostridioformis [26,27,28].…”

Section: Introductionmentioning

confidence: 97%

Experience with Dalbavancin Use in Various Gram-positive Infections within Aberdeen Royal Infirmary OPAT Service

McSorley

Reyes

Tonna

et al. 2023

Preprint

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Purpose: dalbavancin, approved in 2014 for Gram-positive acute bacterial skin and skin structure infections (ABSSSI), has pharmacokinetics enabling treatment with one or two doses. Dalbavancin might be useful in outpatient parenteral antibiotic therapy (OPAT) of deep-seated infections otherwise requiring inpatient admission. We documented our experience with pragmatic dalbavancin use to assess its effectiveness for varied indications, on and off label, as primary or sequential consolidation therapy. Methods: patients prescribed dalbavancin between 1st December 2021 and 1st October 2022 were screened for demographics of age, sex, Charlson comorbidity index (CCI), allergies, pathogens, doses of dalbavancin, other antibiotics administered and surgery. Where available, infection markers were recorded. Primary outcome was cure at end of treatment. Secondary outcomes were adverse events and for treatment failures, response to salvage antibiotics. Results: Sixty seven percent of patients were cured. Cure rates by indication were 93 % for ABSSSI, 100 % for bacteraemia, 90 % for acute osteomyelitis, 0 % for chronic osteomyelitis, 75 % for native joint septic arthritis and 33 % for prosthetic joint infection. Most bone and joint infections not cured did not have source control and the goal of treatment was suppressive. Successful suppression rates were greater at 48 % for chronic osteomyelitis and 66 % for prosthetic joint infections. Adverse events occurred in 14 of 102 patients. Conclusion: This report adds to clinical experience with dalbavancin for off label indications whilst further validating its role in ABSSSI. Dalbavancin as primary therapy in deep seated infections merits investigation in formal clinical trials.

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“…In the case of Staphylococcus aureus, optimal AUC 24 h /MIC ratios for dalbavancin are predicted to be 100–300, much lower than the 400–600 target suggested for vancomycin [ 30 , 31 ]. Some in vitro data suggest that dalbavancin might possess other advantages over classical glycopeptides including greater potency against organisms in the biofilm state and the ability to suppress bacterial exotoxin production, though this has not been corroborated in clinical studies [ 32 , 33 ]. Dalbavancin is highly active against most clinically relevant Gram-positive organisms with the notable exception of vancomycin-resistant enterococci or more rarely vancomycin-resistant Staphylococcus aureus (VRSA) carrying the vanA gene, as well as some species seldom encountered as pathogens such as Enterocloster clostridioformis [ 26 – 28 ].…”

Section: Introductionmentioning

confidence: 99%

Experience with dalbavancin use in various gram-positive infections within Aberdeen Royal Infirmary OPAT service

McSorley,

Reyes,

Tonna

et al. 2024

Infection

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Purpose Dalbavancin, approved in 2014 for Gram-positive acute bacterial skin and skin structure infections (ABSSSI), has pharmacokinetics enabling treatment with one or two doses. Dalbavancin might be useful in outpatient parenteral antibiotic therapy (OPAT) of deep-seated infections, otherwise requiring inpatient admission. We documented our experience with pragmatic dalbavancin use to assess its effectiveness for varied indications, on- and off-label, as primary or sequential consolidation therapy. Methods Patients prescribed dalbavancin between 1 December 2021 and 1 October 2022 were screened for demographics of age, sex, Charlson comorbidity index (CCI), allergies, pathogens, doses of dalbavancin, other antibiotics administered and surgery. Where available, infection markers were recorded. The primary outcome was a cure at the end of treatment. Secondary outcomes included any adverse events and for those with treatment failures, response to salvage antibiotics. Results Sixty-seven per cent of patients were cured. Cure rates by indication were 93% for ABSSSI, 100% for bacteraemia, 90% for acute osteomyelitis, 0% for chronic osteomyelitis, 75% for native joint septic arthritis and 33% for prosthetic joint infection. Most bone and joint infections that were not cured did not have source control, and the goal of treatment was suppressive. Successful suppression rates were greater at 48% for chronic osteomyelitis and 66% for prosthetic joint infections. Adverse events occurred in 14 of 102 patients. Conclusion This report adds to clinical experience with dalbavancin for off-label indications whilst further validating its role in ABSSSI. Dalbavancin as primary therapy in deep-seated infections merits investigation in formal clinical trials.

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Subinhibitory Dalbavancin Attenuates Exotoxin Production from Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureusIn Vitro

Cited by 3 publications

References 30 publications

Antimicrobial and Antivirulence Action of Eugenia brejoensis Essential Oil in vitro and in vivo Invertebrate Models

Antimicrobial and Antivirulence Action of Eugenia brejoensis Essential Oil in vitro and in vivo Invertebrate Models

Experience with Dalbavancin Use in Various Gram-positive Infections within Aberdeen Royal Infirmary OPAT Service

Experience with dalbavancin use in various gram-positive infections within Aberdeen Royal Infirmary OPAT service

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