In vitro #bactericidal activity of #amoxicillin combined with different #cephalosporins against #endocarditis-associated #Enterococcus faecalis clinical isolates (J Antimicrob Chemother., abstract)

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

In vitro bactericidal activity of amoxicillin combined with different cephalosporins against endocarditis-associated Enterococcus faecalis clinical isolates

Nathan Peiffer-Smadja, Elena Guillotel, David Luque-Paz, Naouale Maataoui, F-Xavier Lescure, Vincent Cattoir

Journal of Antimicrobial Chemotherapy, dkz388, https://doi.org/10.1093/jac/dkz388

Published: 08 September 2019

 

Abstract

Background

The combination of amoxicillin with cefazolin could be an interesting regimen for the empirical therapy of severe infective endocarditis, but its activity against enterococci is unknown.

Objectives

To evaluate in vitro the bactericidal activity of the combination of amoxicillin with different cephalosporins including cefazolin.

Methods

Combinations of amoxicillin (at MIC × ¼) with cefazolin, cefotaxime, ceftriaxone, cefepime, ceftaroline or ceftobiprole (at the mean free plasma concentration) were studied using time–kill experiments for 10 endocarditis-associated Enterococcus faecalis strains and 2 reference strains.

Results

The combinations amoxicillin/cefazolin, amoxicillin/cefotaxime, amoxicillin/ceftriaxone and amoxicillin/cefepime were synergistic at 12 and 24 h against 12/12 strains and amoxicillin/ceftobiprole and amoxicillin/ceftaroline against 10/12 strains. The combination amoxicillin/cefepime was bactericidal at 24 h against 9/12 strains, the combination amoxicillin/cefazolin against 8/12 strains, the combinations amoxicillin/ceftaroline, amoxicillin/cefotaxime and amoxicillin/ceftobiprole against 7/12 strains and the combination amoxicillin/ceftriaxone against 6/12 strains.

Conclusions

The combination amoxicillin/cefazolin is as synergistic and bactericidal in vitro as amoxicillin/cefotaxime or amoxicillin/ceftriaxone against E. faecalis.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Amoxicillin; Cephalosporins; Endocarditis; Enterococcus faecalis.

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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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#Nontoxigenic Corynebacterium #diphtheriae #Infections, #Europe (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Summary, edited.]

Volume 25, Number 7—July 2019 / Letter

Nontoxigenic Corynebacterium diphtheriae Infections, Europe

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To the Editor: We read with interest the article by Dangel et al. analyzing nontoxigenic Corynebacterium diphtheriae infections in northern Germany during 2016–2017 (1). Among the cases, 2 patients originated from Poland; each experienced an invasive disease, 1 endocarditis and 1 sepsis. Poland and Germany are neighboring countries. In Poland, we also observed an accumulation of nontoxigenic C. diphtheriaeinfections during 2016–2017. In both countries, most infections were caused by isolates belonging to sequence type (ST) 8 biotype gravis, which we previously suspected of having increased pathogenic properties (2).

(…)

Keywords: Corynebacterium dipththeriae; European Region.

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#Bicarbonate Resensitization of #MRSA to #betaLactam #Antibiotics (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Bicarbonate Resensitization of Methicillin-Resistant Staphylococcus aureusto β-Lactam Antibiotics

Selvi C. Ersoy, Wessam Abdelhady, Liang Li, Henry F. Chambers, Yan Q. Xiong, Arnold S. Bayer

DOI: 10.1128/AAC.00496-19

 

ABSTRACT

Endovascular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major healthcare concern, especially infective endocarditis (IE). Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as ‘resistant’ to β-lactams, often leading to use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strains, representing the range of genotypes in current clinical circulation, were studied. We identified two distinct MRSA phenotypes upon AST using standard media, with or without sodium bicarbonate (NaHCO3) supplementation: one highly susceptible to the anti-staphylococcal β-lactams, oxacillin and cefazolin (‘NaHCO3-responsive’) and one resistant to such agents (‘NaHCO3-nonresponsive’). These phenotypes accurately predicted clearance profiles of MRSA from target tissues in experimental MRSA IE treated with each β-lactam. Mechanistically, NaHCO3 reduced expression of two key genes involved in the MRSA phenotype, mecA and sarA, leading to decreased production of penicillin-binding protein (PBP) 2a (that mediates methicillin resistance), in NaHCO3-responsive (but not in NaHCO3-nonresponsive) strains. Moreover, both cefazolin and oxacillin synergistically killed NaHCO3-responsive strains in the presence of the host defense antimicrobial peptide (LL-37) in NaHCO3-supplemented media. These findings suggest that AST of MRSA strains in NaHCO3-containing media may potentially identify infections caused by NaHCO3-responsive strains that are appropriate for β-lactam therapy.

Copyright © 2019 Ersoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Antibiotics; Drugs Resistance; MRSA; Staphylococcus aureus; Endocarditis; Bicarbonate; Oxacillin; Cefazolin; Beta-lactams.

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Successful #treatment of #Pseudomonas aeruginosa infective #endocarditis via #haemodialysis outpatient parenteral antimicrobial therapy: case report (J Antimicrob Chemother., abstract)

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

Successful treatment of Pseudomonas aeruginosainfective endocarditis via haemodialysis outpatient parenteral antimicrobial therapy: case report

Hector Maxwell-Scott, Rajeni Thangarajah, Amber Arnold, Paul Wade, John L Klein

Journal of Antimicrobial Chemotherapy, dkz096, https://doi.org/10.1093/jac/dkz096

Published: 04 March 2019

___

Sir,

Pseudomonas aeruginosa infective endocarditis (IE) is rare and difficult to treat, often requiring long hospital admissions for intravenous antibiotics. Outpatient parenteral antimicrobial therapy (OPAT) is one option for the management of infection allowing for shorter inpatient stays. Certain antibiotics can be dosed for administration on haemodialysis, allowing for haemodialysis OPAT (HD-OPAT), but less is known about their pharmacokinetics and pharmacodynamics in this setting. Here we present a case of P. aeruginosa IE successfully treated with HD-OPAT using ceftazidime and oral ciprofloxacin.

(…)

Keywords: Antibiotics; Pseudomonas aeruginosa; Endocarditis; Ceftazidime; Azithromycin.

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The Anti-Staphylococcal #Lysin, CF-301, Activates Key Host Factors in #Human #Blood to Potentiate #MRSA #Bacteriolysis (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

The Anti-Staphylococcal Lysin, CF-301, Activates Key Host Factors in Human Blood to Potentiate MRSA Bacteriolysis

Chiara Indiani, Karen Sauve, Assaf Raz, Wessam Abdelhady, Yan Q. Xiong, Cara Cassino, Arnold S. Bayer, Raymond Schuch

DOI: 10.1128/AAC.02291-18

 

ABSTRACT

Bacteriophage-derived lysins are cell wall hydrolytic enzymes which represent a potential new class of antibacterial therapeutics in development to address burgeoning antimicrobial resistance. CF-301, the lead compound in this class, is in clinical development as an adjunctive treatment to potentially improve clinical cure rates of Staphylococcus aureus bacteremia and infective endocarditis (IE) when used in addition to antibiotics. In order to profile CF-301’s activity in a clinically relevant milieu, we assessed its in vitro activity in human blood vs. in a conventional testing medium (cation-adjusted Mueller Hinton Broth [caMHB]). CF-301 exhibited substantially greater potency (32-≥100-fold) in human blood vs. caMHB in three standard microbiologic testing formats (e.g. broth dilution MICs, checkerboard synergy and time-kill assays). We demonstrated that CF-301 acted synergistically with two key human blood factors, human serum lysozyme (HuLYZ) and albumin (HSA), which normally have no nascent antistaphylococcal activity, against a prototypic MRSA strain (MW2). Similar in vitroenhancement of CF-301 activity was also observed in rabbit, horse and dog (but not rat or mouse) blood. Two well-established MRSA IE models in rabbit and rat were used to validate these findings in vivo by demonstrating comparable synergistic efficacy with standard-of-care anti-MRSA antibiotics, at > 100-fold lower lysin doses in the rabbit vs the rat model. The unique properties of CF-301 which enable bactericidal potentiation of antimicrobial activity via activation of ‘latent’ host factors in human blood may have important therapeutic implications for the durable improvements in clinical outcomes of serious, antibiotic-resistant staphylococcal infections.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Bacteriophages; Bacteremia; Endocarditis; MRSA; Staphylococcus aureus.

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#Dietary #Manganese Promotes #Staphylococcal #Infection of the #Heart (Cell Host Microbe, abstract)

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

Dietary Manganese Promotes Staphylococcal Infection of the Heart

Lillian J. Juttukonda, Evelien T.M. Berends, Joseph P. Zackular, Jessica L. Moore, Matthew T. Stier, Yaofang Zhang, Jonathan E. Schmitz, William N. Beavers, Christiaan D. Wijers, Benjamin A. Gilston, Thomas E. Kehl-Fie, James Atkinson, Mary K. Washington, R. Stokes Peebles, Walter J. Chazin, Victor J. Torres, Richard M. Caprioli, Eric P. Skaar9

9Lead Contact

Publication stage: In Press Corrected Proof /  DOI: http://dx.doi.org/10.1016/j.chom.2017.08.009

Article Info: 

Publication History: Published: September 21, 2017 – Accepted: August 17, 2017 – Received in revised form: June 29, 2017 – Received:March 15, 2017

 

Highlights

  • High levels of dietary manganese increase lethality and heart colonization by S. aureus
  • Calprotectin does not alter manganese availability in the heart
  • Mice fed a high-manganese diet have increased bioavailable manganese in the heart
  • S. aureus utilizes dietary manganese to protect against ROS and neutrophil killing

 

Summary

Diet, and specifically dietary metals, can modify the risk of infection. However, the mechanisms by which manganese (Mn), a common dietary supplement, alters infection remain unexplored. We report that dietary Mn levels dictate the outcome of systemic infections caused by Staphylococcus aureus, a leading cause of bacterial endocarditis. Mice fed a high Mn diet display alterations in Mn levels and localization within infected tissues, and S. aureus virulence and infection of the heart are enhanced. Although the canonical mammalian Mn-sequestering protein calprotectin surrounds staphylococcal heart abscesses, calprotectin is not released into the abscess nidus and does not limit Mn in this organ. Consequently, excess Mn is bioavailable to S. aureus in the heart. Bioavailable Mn is utilized by S. aureus to detoxify reactive oxygen species and protect against neutrophil killing, enhancing fitness within the heart. Therefore, a single dietary modification overwhelms vital host antimicrobial strategies, leading to fatal staphylococcal infection.

Keywords: nutritional immunity, diet, manganese, calprotectin, bacterial pathogenesis, Staphylococcus aureus, endocarditis, oxidative stress, neutrophils

Keywords: Staphylococcus Aureus; Endocarditis; Animal Models.

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