Successful #treatment with #daptomycin and #ceftaroline of #MDR #Staphylococcus aureus native #valve #endocarditis: a case report (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Successful treatment with daptomycin and ceftaroline of MDR Staphylococcus aureus native valve endocarditis: a case report

François-Régis Duss, Cristina Garcia de la Mària, Antony Croxatto, Stefano Giulieri, Frédéric Lamoth, Oriol Manuel, José M Miró

Journal of Antimicrobial Chemotherapy, dkz253, https://doi.org/10.1093/jac/dkz253

Published:  11 July 2019

 

Abstract

Objectives

The best therapeutic approach for treating MRSA endocarditis remains unknown, particularly in cases of high vancomycin MICs. We report here a case of daptomycin-non-susceptible, ceftaroline-resistant and fosfomycin-resistant MRSA native left valve endocarditis that was successfully treated with valve repair and a combination of high-dose daptomycin and ceftaroline.

Methods

Antimicrobial testing of the clinical strain was performed using Etest and microdilution broth methods. Time–kill and chequerboard methodologies were used to test the activity of antibiotic combinations.

Results

By Etest, the MIC of vancomycin was 2 mg/L, the MIC of daptomycin was 2 mg/L, the MIC of fosfomycin was 1024 mg/L and the MIC of ceftaroline was 1.5 mg/L. At the standard inoculum (105 cfu/mL), the three combinations of daptomycin plus ceftaroline, cloxacillin or fosfomycin were synergistic and bactericidal. However, when these combinations were tested using a higher inoculum (108 cfu/mL), all combinations were synergistic, but only daptomycin plus ceftaroline had bactericidal activity.

Conclusions

These results confirmed a synergistic effect between daptomycin plus ceftaroline and increased bactericidal activity against MRSA, suggesting that this combination may be effective for the treatment of invasive MRSA infection. Our experience highlights the potential clinical use of synergy testing to guide difficult treatment decisions in patients with MDR MRSA infection.

Topic: endocarditis – vancomycin – staphylococcus aureus – cloxacillin – endocarditis, infectious, native valve – daptomycin – fosfomycin – methicillin-resistant staphylococcus aureus – ceftaroline – malnutrition-inflammation-cachexia syndrome

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; Endocarditis; Ceftaroline; Daptomycin.

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#Intestinal #Bile Acids Induce a Morphotype Switch in #Vancomycin-Resistant #Enterococcus that Facilitates Intestinal Colonization (Cell Host Microbe, abstract)

[Source: Cell, Host & Microbe, full page: (LINK). Abstract, edited.]

Intestinal Bile Acids Induce a Morphotype Switch in Vancomycin-Resistant Enterococcus that Facilitates Intestinal Colonization

Peter T. McKenney, Jinyuan Yan, Julien Vaubourgeix 8, Simone Becattini, Nina Lampen, Andrew Motzer, Peter J. Larson, Daniel Dannaoui, Sho Fujisawa, Joao B. Xavier, Eric G. Pamer 9

Published: April 25, 2019 / DOI: https://doi.org/10.1016/j.chom.2019.03.008

 

Highlights

  • VRE forms long chains and biofilms in physiological concentrations of bile acids
  • This morphotype switch is reversed by cations
  • Selection against chaining is linked to sensitivity to the antibiotic daptomycin
  • Chaining-deficient VRE mutants exhibit reduced persistence in the gut

 

Summary

Vancomycin-resistant Enterococcus (VRE) are highly antibiotic-resistant and readily transmissible pathogens that cause severe infections in hospitalized patients. We discovered that lithocholic acid (LCA), a secondary bile acid prevalent in the cecum and colon of mice and humans, impairs separation of growing VRE diplococci, causing the formation of long chains and increased biofilm formation. Divalent cations reversed this LCA-induced switch to chaining and biofilm formation. Experimental evolution in the presence of LCA yielded mutations in the essential two-component kinase yycG/walK and three-component response regulator liaR that locked VRE in diplococcal mode, impaired biofilm formation, and increased susceptibility to the antibiotic daptomycin. These mutant VRE strains were deficient in host colonization because of their inability to compete with intestinal microbiota. This morphotype switch presents a potential non-bactericidal therapeutic target that may help clear VRE from the intestines of dominated patients, as occurs frequently during hematopoietic stem cell transplantation.

Keywords: Enterococcus – VRE – bile – microbiota – morphotype – faecium – faecalis – colonization resistance

Keywords: Antibiotics; Drugs Resistance; Vancomycin; Daptomycin; Enterococcus.

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Disrupting #Membrane #Adaptation Restores In Vivo Efficacy of #Antibiotics Against #MDR #Enterococci and Potentiates Killing by Human Neutrophils (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Disrupting Membrane Adaptation Restores In VivoEfficacy of Antibiotics Against Multidrug-Resistant Enterococci and Potentiates Killing by Human Neutrophils

Sandra Rincon, Diana Panesso, William R Miller, Kavindra V Singh, Melissa R Cruz, Ayesha Khan, An Q Dinh, Lorena Diaz, Rafael Rios, Yousif Shamoo, Jinnethe Reyes, Truc T Tran, Danielle A Garsin, Cesar A Arias

The Journal of Infectious Diseases, jiz131, https://doi.org/10.1093/infdis/jiz131

Published: 02 April 2019

 

Abstract

Daptomycin resistance in enterococci is often mediated by the LiaFSR system that orchestrates the cell membrane (CM) stress response. Activation of LiaFSR through the response regulator LiaR generates major changes in CM function and architecture (membrane adaptive response), permitting the organism to survive the antibiotic attack. Here, using a laboratory strain of Enterococcus faecalis, we developed a novel Caenorhabditis elegans model of daptomycin therapy and showed that disrupting LiaR-mediated CM adaptation restores the in vivo activity of daptomycin. The LiaR effect was also seen in a clinical strain of DAP-resistant E. faecium using a murine model of peritonitis. Furthermore, alteration of the CM response increased the ability of human-PMNs to readily clear both E. faecalis and MDR-E. faecium. Our results provide proof-of-concept that targeting the CM adaptive response restore the in vivo activity of antibiotics, prevent resistance and enhance the ability of the innate immune system to kill infecting bacteria.

LiaR, daptomycin, Caenorhabditis elegans, PMNs, phagocytosis

Issue Section: Major Article

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Daptomycin; Enterococcus spp.

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