#Carbapenem-Resistant Gram-Negative #Infections in #Children (Antimicrob Agents Chemother., abstract)

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

Carbapenem-Resistant Gram-Negative Infections in Children.

David Aguilera-Alonso, Luis Escosa-García, Jesús Saavedra-Lozano, Emilia Cercenado, Fernando Baquero-Artigao

DOI: 10.1128/AAC.02183-19

 

ABSTRACT

Carbapenem-resistant organisms (CRO) are a major global public health threat. Enterobacterales through carbapenemase production hydrolyze almost all β-lactams. Infections caused by CRO are challenging to treat due to the limited number of antimicrobial options. This leads to significant morbidity and mortality. Over the last few years, several new antibiotics effective against CRO have been approved. Some of them (e.g., plazomicin or imipenem-cilastatin-relebactam) are currently only approved for adults; others (e.g., ceftazidime-avibactam) have recently been approved for children. Recommendations for antibiotic therapy of CRO infections in pediatric patients are based on evidence mainly from adult studies. The availability of pediatric pharmacokinetics and safety data is the cornerstone to broaden the use of proposed agents in adults to the pediatric population. This article provides a comprehensive review of the current knowledge regarding infections caused by CRO with a focus on children which includes epidemiology, risk factors, outcomes and antimicrobial therapy management, with particular attention to new antibiotics.

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

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Gram-negative bacteria; Pediatrics.

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A new #antibiotic selectively kills Gram-negative #pathogens (Nature, abstract)

[Source: Nature, full page: (LINK). Abstract, edited.]

A new antibiotic selectively kills Gram-negative pathogens

Yu Imai, Kirsten J. Meyer, […] Kim Lewis

Nature (2019)

 

Abstract

The current need for novel antibiotics is especially acute for drug-resistant Gram-negative pathogens1,2. These microorganisms have a highly restrictive permeability barrier, which limits the penetration of most compounds3,4. As a result, the last class of antibiotics acting against Gram-negative bacteria was developed in the 1960s2. We reason that useful compounds can be found in bacteria that share similar requirements for antibiotics with humans, and focus on Photorhabdus symbionts of entomopathogenic nematode microbiomes. Here we report a new antibiotic that we name darobactin, from a screen of Photorhabdus isolates. Darobactin is coded by a silent operon with little production under laboratory conditions, and is ribosomally synthesized. Darobactin has an unusual structure with two fused rings that form post-translationally. The compound is active against important Gram-negative pathogens both in vitro and in animal models of infection. Mutants resistant to darobactin map to BamA, an essential chaperone and translocator that folds outer membrane proteins. Our study suggests that bacterial symbionts of animals contain antibiotics that are particularly suitable for development into therapeutics.

Author notes: These authors contributed equally: Yu Imai, Kirsten J. Meyer

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Keywords: Antibotics; Gram-Negative Bacteria; Darobactin.

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#Difficult-to-Treat #Antibiotic-Resistant #GramNegative #Pathogens in the #ICU: #Epidemiology, #Outcomes, and #Treatment (Semin Respir Crit Care Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Semin Respir Crit Care Med. 2019 Aug;40(4):419-434. doi: 10.1055/s-0039-1696662. Epub 2019 Oct 4.

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment.

Strich JR1,2, Kadri SS1.

Author information: 1 Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland. 2 United States Public Health Service, Commissioned Corps, Rockville, Maryland.

 

Abstract

Antibiotic resistance among gram-negative pathogens is a world-wide problem that poses a constant threat to patients in the intensive care unit and a therapeutic challenge for the intensivist. Furthermore, the substantial economic burden and increased mortality associated with infections due to highly resistant gram-negative pathogens exacerbate these challenges. Understanding the mechanisms, epidemiology, and risk factors for these infections is paramount to the successful control of outbreaks and for guiding therapy which often entails use of antibiotics with suboptimal efficacy and/or toxicity profiles. In this review we will discuss the global epidemiology, burden, risk factors, and treatment of highly resistant gram-negative infections as they apply to the intensive care population.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

PMID: 31585469 DOI: 10.1055/s-0039-1696662

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Keywords: Antibiotics; Drugs Resistance; Intensive Care; Gram Negative Bacteria.

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#Pandrug #resistant #Gramnegative #bacteria: a systematic review of current #epidemiology, #prognosis and #treatment options (J Antimicrob Chemother., abstract)

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

Pandrug-resistant Gram-negative bacteria: a systematic review of current epidemiology, prognosis and treatment options

Stamatis Karakonstantis, Evangelos I Kritsotakis, Achilleas Gikas

Journal of Antimicrobial Chemotherapy, dkz401, https://doi.org/10.1093/jac/dkz401

Published: 05 October 2019

 

Abstract

Background

The literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial.

Objectives

To consolidate the relevant literature and identify treatment options for PDR GNB infections.

Methods

A systematic search in MEDLINE, Scopus and clinical trial registries was conducted. Studies reporting PDR clinical isolates were eligible for review if susceptibility testing for all major antimicrobials had been performed. Characteristics and findings of retrieved studies were qualitatively synthesized.

Results

Of 81 studies reviewed, 47 (58%) were published in the last 5 years. The reports reflected a worldwide dissemination of PDR GNB in 25 countries in 5 continents. Of 526 PDR isolates reported, Pseudomonas aeruginosa (n=175), Acinetobacter baumannii (n=172) and Klebsiella pneumoniae (n=125) were most common. PDR GNB were typically isolated in ICUs, but several studies demonstrated wider outbreak potential, including dissemination to long-term care facilities and international spread. All-cause mortality was high (range 20%–71%), but appeared to be substantially reduced in studies reporting treatment regimens active in vitro. No controlled trial has been performed to date, but several case reports and series noted successful use of various regimens, predominantly synergistic combinations, and in selected patients increased exposure regimens and newer antibiotics.

Conclusions

PDR GNB are increasingly being reported worldwide and are associated with high mortality. Several treatment regimens have been successfully used, of which synergistic combinations appear to be most promising and often the only available option. More pharmacokinetic/pharmacodynamic and outcome studies are needed to guide the use of synergistic combinations.

Issue Section: Systematic review

© 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)

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Keywords: Antibiotics; Drugs Resistance; Gram-negative bacteria.

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Adjunctive #transferrin to reduce the emergence of #antibiotic #resistance in Gram-negative #bacteria (J Antimicrob Chemother., abstract)

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

Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria

Brian M Luna, Ksenia Ershova, Jun Yan, Amber Ulhaq, Travis B Nielsen, Sarah Hsieh, Paul Pantapalangkoor, Brian Vanscoy, Paul Ambrose, Sue Rudin, Kristine Hujer, Robert A Bonomo, Luis Actis, Eric P Skaar, Brad Spellberg

Journal of Antimicrobial Chemotherapy, dkz225, https://doi.org/10.1093/jac/dkz225

Published: 06 June 2019

 

Abstract

Background

New strategies are needed to slow the emergence of antibiotic resistance among bacterial pathogens. In particular, society is experiencing a crisis of antibiotic-resistant infections caused by Gram-negative bacterial pathogens and novel therapeutics are desperately needed to combat such diseases. Acquisition of iron from the host is a nearly universal requirement for microbial pathogens—including Gram-negative bacteria—to cause infection. We have previously reported that apo-transferrin (lacking iron) can inhibit the growth of Staphylococcus aureus in culture and diminish emergence of resistance to rifampicin.

Objectives

To define the potential of apo-transferrin to inhibit in vitro growth of Klebsiella pneumoniae and Acinetobacter baumannii, key Gram-negative pathogens, and to reduce emergence of resistance to antibiotics.

Methods

The efficacy of apo-transferrin alone or in combination with meropenem or ciprofloxacin against K. pneumoniae and A. baumannii clinical isolates was tested by MIC assay, time–kill assay and assays for the selection of resistant mutants.

Results

We confirmed that apo-transferrin had detectable MICs for all strains tested of both pathogens. Apo-transferrin mediated an additive antimicrobial effect for both antibiotics against multiple strains in time–kill assays. Finally, adding apo-transferrin to ciprofloxacin or meropenem reduced the emergence of resistant mutants during 20 day serial passaging of both species.

Conclusions

These results suggest that apo-transferrin may have promise to suppress the emergence of antibiotic-resistant mutants when treating infections caused by Gram-negative bacteria.

Topic: antibiotics – iron – antibiotic resistance, bacterial – ciprofloxacin – gram-negative bacteria – transferrin – meropenem – malnutrition-inflammation-cachexia syndrome

Issue Section: ORIGINAL RESEARCH

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Keywords: Antibiotics; Drugs Resistance; Meropenem; Ciprofloxacin; Transferrin.

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