Activity of Aerosolized #Levofloxacin Against #Burkholderia cepacia in a Mouse Chronic #Lung #Infection Model (Antimicrob Agents Chemother., abstract)

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

Activity of Aerosolized Levofloxacin Against Burkholderia cepacia in a Mouse Chronic Lung Infection Model

Mojgan Sabet, David C. Griffith

DOI: 10.1128/AAC.01988-19

 

ABSTRACT

Burkholderia cepacia complex is an opportunistic pathogen capable of causing chronic pulmonary infections. These studies were conducted to demonstrate the activity of aerosolized levofloxacin in a chronic mouse lung infection model caused by B. cepacia isolates from cystic fibrosis patients. Treatment with aerosolized levofloxacin for four days produced at least one log CFU of bacterial killing against all strains tested and suggests possible utility in the treatment of lung infections caused by B. cepacia.

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

Keywords: Burkholderia cepacia; Levofloxacin; Animal models.

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Evaluating the role of #Burkholderia pseudomallei K96243 #toxins BPSS0390, BPSS0395, and BPSS1584 in persistent #Infection (Cell Microbiol., abstract)

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

Cell Microbiol. 2019 Aug 10:e13096. doi: 10.1111/cmi.13096. [Epub ahead of print]

Evaluating the role of Burkholderia pseudomallei K96243 toxins BPSS0390, BPSS0395, and BPSS1584 in persistent Infection.

Ross BN1, Micheva-Viteva S2, Hong-Geller E2, Torres AG1,3.

Author information: 1 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX. 2 Los Alamos National Laboratory, Los Alamos, NM. 3 Department of Pathology, University of Texas Medical Branch, Galveston, TX.

 

Abstract

Burkholderia pseudomallei is the causative agent of melioidosis, a disease with a mortality rate of up to 40% even with treatment. Despite the ability of certain antibiotics to control initial infection, relapse occurs in treated patients. The inability of antibiotics to clear this bacterial infection is in part due to persistence, an evasion mechanism against antibiotics and host defenses effects. Evaluation of antibiotic efficacy against B. pseudomallei revealed that up to 48% of in vitro grown populations can survive in a persister state. Toxin-antitoxin (TA) systems have been previously implicated in modulating bacterial persistence. We generated 3 isogenic TA mutants and found that loss of each toxin gene did not alter antibiotic persistence or macrophage survival. In response to macrophage-induced persistence, all three toxin mutants demonstrated increased intracellular susceptibility to levofloxacin which in part was due to the inability of the mutants to induce persistence after nitric oxide or nutrient starvation. In an inhalational model of murine melioidosis, both ΔBPSS0395 and ΔBPSS1584 strains were attenuated and treatment with levofloxacin led to significant reduction in lung colonization and reduced splenic colonization by ∆BPSS0395. Based on our findings, these toxins deserve additional evaluation as putative therapeutic targets.

This article is protected by copyright. All rights reserved.

KEYWORDS: Burkholderia; antibiotic resistance; chronic infection; persistence; toxin-antitoxin

PMID: 31400259 DOI: 10.1111/cmi.13096

Keywords: Melioidosis; Antibiotics; Levofloxacin; Burkholderia pseudomallei.

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#Antibiotic susceptibility of #Legionella pneumophila strains isolated in #England and #Wales 2007–17 (J Antimicrob Chemother., abstract)

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

Antibiotic susceptibility of Legionella pneumophilastrains isolated in England and Wales 2007–17

R E Wilson, R L R Hill, V J Chalker, M Mentasti, D Ready

Journal of Antimicrobial Chemotherapy, dky253, https://doi.org/10.1093/jac/dky253

Published: 24 July 2018

 

Abstract

Objectives

Antibiotic susceptibility of Legionella pneumophila is poorly understood, with treatment of Legionnaires’ disease often based on empirical choice. The aim of this study was to determine the antibiotic susceptibility of L. pneumophilastrains.

Methods

Antibiotic susceptibility of 92 L. pneumophila strains isolated in England and Wales between 2007 and 2017 was determined using a microbroth dilution methodology for each agent tested. MICs and MBCs were determined and compared with published intracellular concentrations of each agent tested.

Results

The MIC range of erythromycin was 0.06–1 mg/L, the MIC range of rifampicin was 0.0001 mg/L, the MIC range of ciprofloxacin was 0.004–0.25 mg/L and the MIC range of levofloxacin and moxifloxacin was 0.03–0.25 mg/L. The MBC range of erythromycin was 1–32 mg/L, but the MBC range of ciprofloxacin was the same as the MIC range. For levofloxacin and moxifloxacin the MBC range was elevated by one dilution and two dilutions, respectively. Typically, intracellular bronchial secretion concentrations of erythromycin might be expected to reach a suitable level to exceed the MIC range; however, 91 of 92 (98.9%) isolates had an MBC below the expected intracellular concentrations, which indicated erythromycin may have variable efficacy. MIC and MBC values of ciprofloxacin, levofloxacin and moxifloxacin were below achievable intracellular levels within bronchial secretions. Comparison of the MIC/MBC correlation showed very little clustering for erythromycin, but strong clustering for levofloxacin and to a lesser extent ciprofloxacin.

Conclusions

Use of the MIC/MBC linkage analysis seems an appropriate way forward for antimicrobial susceptibility testing and supports current guidance recommending levofloxacin for the treatment of Legionnaires’ disease.

Topic: antibiotics – rifampin – erythromycin – genetic linkage analysis – ciprofloxacin – bodily secretions – legionella pneumophila – legionnaires’ disease – country of wales – levofloxacin – moxifloxacin – antimicrobial susceptibility – antimicrobial susceptibility test – dilution technique – dilute (action) – malnutrition-inflammation-cachexia syndrome

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2018. 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/about_us/legal/notices)

Keywords: Antibiotics; Drugs Resistance; Legionalla pneumophila; England; Wales; rifampin; erythromycin; ciprofloxacin; levofloxacin; moxifloxacin.

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Increasing Prevalence of #Rifampicin-Resistant Mycobacterium #tuberculosis is Associated with the Transmission of Strains Harboring Compensatory Mutations in #China: A 10-year Comparative Analysis (AAC, abstract)

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

Increasing Prevalence of Rifampicin-Resistant Mycobacterium tuberculosis is Associated with the Transmission of Strains Harboring Compensatory Mutations in China: A 10-year Comparative Analysis

Fengmin Huo1,  Jingjing Luo1,  Jin Shi2,  Zhaojing Zong1,  Wei Jing1, Wenzhu Dong1,  Lingling Dong1,  Yifeng Ma1,  Qian Liang1,  Yuanyuan Shang1, Hairong Huang1* and Yu Pang1*

Author Affiliations: 1 National Clinical Laboratory on Tuberculosis, Beijing Key laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China; 2 Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China

 

ABSTRACT

In this report, we conducted bacterial population profile studies to assess trends of rifampicin (RIF) resistance from 2005 to 2015 of Mycobacterium tuberculosis (MTB) isolates collected across China. A total of randomly selected 273 and 269 MTB isolates from 2005 and 2015, respectively, were analyzed. The rates of RIF resistance (36.4%), isoniazid resistance (39.0%), and levofloxacin resistance (25.7%) in 2015 were significantly higher than in 2005 (28.2%, 30.0%, and 15.4%, respectively; P < 0.05). Genotypic data revealed 256 (95.2%) Beijing-type isolates in 2015, a rate significantly higher than that of 2005 (86.4%) (P < 0.01). A higher proportion of mutations were identified within the rifampin resistance determining region (RRDR) of rpoB in isolates from 2015 (99.0%) than in 2005 isolates (85.7%, P< 0.01). In addition, a significantly higher proportion of RIF-resistant isolates carrying compensatory mutations were observed in 2015 (31.6%) than in 2005 (7.8%). Notably, the great majority of these compensatory mutations (91.9%) were observed in isolates that harbored a mutation of codon 531 of the rpoB gene. In conclusion, our data demonstrate that resistance to RIF, isoniazid, and levofloxacin has become significantly more prevalent during the past decade. In addition, the prevalence of the Beijing genotype significantly increased from 2005 to 2015. Notably, a significantly increased frequency of strains with mutations in rpoC or rpoA is observed in those that have codon 531 mutations suggests that they may be compensatory, and may play a role in facilitating transmission.

 

FOOTNOTES

*Corresponding author. Mailing address for Yu Pang: Beijing Chest Hospital, Capital Medical University, No. 97, Machang, Tongzhou District, Beijing, 101149, China. Phone: 86 10 8950 9359. Fax: 86 10 8950 9359. E-mail: pangyupound@163.com.

*Mailing address for Hairong Huang: Beijing Chest Hospital, Capital Medical University, No. 97, Machang, Tongzhou District, Beijing, 101149, China. Phone: 86 10 8950 9359. Fax: 86 10 8950 9359. E-mail: huanghairong@tb123.org.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Tuberculosis; China; Rifampicin.

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#Surveillance of #Levofloxacin #Resistance in #Helicobacter pylori Isolates in #Bogotá – #Colombia (2009-2014) (PLoS One, abstract)

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

Open Access / Peer-reviewed / Research Article

Surveillance of Levofloxacin Resistance in Helicobacter pylori Isolates in Bogotá-Colombia (2009-2014)

Alba A. Trespalacios-Rangél , William Otero, Azucena Arévalo-Galvis, Raúl A. Poutou-Piñales, Emiko Rimbara, David Y. Graham

PLOS / Published: July 25, 2016 /  http://dx.doi.org/10.1371/journal.pone.0160007

 

Abstract

Increased resistance of Helicobacter pylori to clarithromycin and metronidazole has resulted in recommendation to substitute fluoroquinolones for eradication therapy. The aims of the study were to determine the prevalence and changes in primary levofloxacin resistance related to H. pylori gyrA sequences. The study utilized H. pylori strains isolated from patients undergoing gastroscopy in Bogotá, Colombia from 2009 to 2014. Levofloxacin susceptibility was assessed by agar dilution. Mutations in gyrA sequences affecting the quinolone resistance-determining region (QRDR) were evaluated by direct sequencing. Overall, the mean prevalence of primary levofloxacin resistance was 18.2% (80 of 439 samples). Resistance increased from 11.8% (12/102) in 2009 to 27.3% (21/77) in 2014 (p = 0.001). gyrA mutations in levofloxacin resistant strains were present in QRDR positions 87 and 91. The most common mutation was N87I (43.8%, 35/80) followed by D91N (28.8%, 23/80) and N87K (11.3%, 9/80). Levofloxacin resistance increased markedly in Colombia during the six-year study period. Primary levofloxacin resistance was most often mediated by point mutations in gyrA, with N87I being the most common QRDR mutation related to levofloxacin resistance.

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Citation: Trespalacios-Rangél AA, Otero W, Arévalo-Galvis A, Poutou-Piñales RA, Rimbara E, Graham DY (2016) Surveillance of Levofloxacin Resistance in Helicobacter pylori Isolates in Bogotá-Colombia (2009-2014). PLoS ONE 11(7): e0160007. doi:10.1371/journal.pone.0160007

Editor: Massimiliano Galdiero, Second University of Naples, ITALY

Received: February 15, 2016; Accepted: July 12, 2016; Published: July 25, 2016

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: Data are available from Figshare: https://figshare.com/s/c1928ecda291ed2c61fa doi: 10.6084/m9.figshare.3386065.

Funding: This work was supported by COLCIENCIAS (Colombia), Grant 120340820464, Pontificia Universidad Javeriana, Bogotá, D.C. (Colombia) Grant 00004554 and by Michael E. DeBakey Veterans Affairs Medical Center Internal Project and the Baylor College of Medicine, United States. Dr. Graham was supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service Grant DK56338, which funds the Texas Medical Center Digestive Diseases Center and DK067366.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Levofloxacin; Helicobacter Pylori.

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