High #incidence of #MDR and #XDR #Pseudomonas aeruginosa isolates obtained from #patients with #ventilator-associated #pneumonia in #Greece, #Italy and #Spain as part of the MagicBullet clinical trial (J Antimicrob Chemother., abstract)

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

High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial

Astrid Pérez, Eva Gato, José Pérez-Llarena, Felipe Fernández-Cuenca, María José Gude, Marina Oviaño, María Eugenia Pachón, José Garnacho, Verónica González, Álvaro Pascual, José Miguel Cisneros, Germán Bou

Journal of Antimicrobial Chemotherapy, dkz030, https://doi.org/10.1093/jac/dkz030

Published: 08 February 2019

 

Abstract

Objectives

To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial.

Methods

Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST.

Results

Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235.

Conclusions

MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains.

Topic: antibiotics – phenotype – polymerase chain reaction – pseudomonas aeruginosa – antibiotic resistance, bacterial – colistin – ciprofloxacin – ceftazidime – clone cells – drug combinations – electrophoresis, gel, pulsed-field – epidemiology, molecular – greece – ichthyosis, x-linked – imipenem – italy – respiratory system – sequence tagged sites – spain – spectrometry, mass, matrix-assisted laser desorption-ionization – sodium thiosulfate – antimicrobial susceptibility – tazobactam – ventilator-associated pneumonia – ceftolozane – avibactam – carbapenem resistance

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; Pseudomonas aeruginosa; Pneumonia; Italy; Spain; Greece; Colistin; Ciprofloxacin; Ceftazidime; Iminpenem; Tazobactam; Ceftolozane; Avibactam.

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Current #trends in the #treatment of #pneumonia due to #MDR #Gramnegative #bacteria (F1000Res., abstract)

[Source: F1000 Research, full page: (LINK). Abstract, edited.]

Current trends in the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria [version 2; referees: 2 approved]

Richard R. Watkins1,2, David Van Duin3

Author details: 1 Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH, 44302, USA; 2 Department of Medicine, Northeast Ohio Medical University, Rootstown, OH, 44272, USA; 3 Department of Medicine, University of North Carolina, Chapel Hill, NC, 27514, USA

 

Abstract

Pneumonia is one of the most common infections worldwide. Morbidity, mortality, and healthcare costs increase substantially when pneumonia is caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). The ongoing spread of antimicrobial resistance has made treating MDR-GNB pneumonia increasingly difficult. Fortunately, there have been some recent additions to our antibiotic armamentarium in the US and Europe for MDR-GNB, along with several agents that are in advanced stages of development. In this article, we review the risk factors for and current management of MDR-GNB pneumonia as well as novel agents with activity against these important and challenging pathogens.

Keywords: Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, antibiotics

Corresponding author: Richard R. Watkins

Competing interests: RRW serves on an advisory board and speakers’ bureau and has received research support from Allergan. DvD serves on advisory boards for Allergan, Achaogen, Shionogi, Tetraphase, Sanofi Pasteur, MedImmune, and Astellas and has received research funding from Steris Inc. and Scynexis.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright:  © 2019 Watkins RR and Van Duin D. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Watkins RR and Van Duin D. Current trends in the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria [version 2; referees: 2 approved]. F1000Research 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.2)

First published: 30 Jan 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.1)

Latest published: 06 Feb 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.2)

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; Pneumonia.

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Current #trends in the #treatment of #pneumonia due to #MDR Gram-negative #bacteria (F1000Res., abstract)

[Source: F1000 Research, full page: (LINK). Abstract, edited.]

Current trends in the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria [version 1; referees: 2 approved]

Richard R. Watkins1,2, David Van Duin3

Author details: 1 Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH, 44302, USA; 2 Department of Medicine, Northeast Ohio Medical University, Rootstown, OH, 44272, USA; 3 Department of Medicine, University of North Carolina, Chapel Hill, NC, 27514, USA

 

Abstract

Pneumonia is one of the most common infections worldwide. Morbidity, mortality, and healthcare costs increase substantially when pneumonia is caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). The ongoing spread of antimicrobial resistance has made treating MDR-GNB pneumonia increasingly difficult. Fortunately, there have been some recent additions to our antibiotic armamentarium in the US and Europe for MDR-GNB, along with several agents that are in advanced stages of development. In this article, we review the risk factors for and current management of MDR-GNB pneumonia as well as novel agents with activity against these important and challenging pathogens.

Keywords: Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, antibiotics

Corresponding author: Richard R. Watkins

Competing interests: RRW serves on an advisory board and speakers’ bureau and has received research support from Allergan. DvD serves on advisory boards for Allergan, Achaogen, Shionogi, Tetraphase, Sanofi Pasteur, MedImmune, and Astellas and has received research funding from Steris Inc. and Scynexis.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright:  © 2019 Watkins RR and Van Duin D. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Watkins RR and Van Duin D. Current trends in the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria [version 1; referees: 2 approved]. F1000Research 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.1)First published: 30 Jan 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.1)

Latest published: 30 Jan 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.1)

Keywords: Antibiotics; Drugs Resistance; Pneumonia.

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What causes #pneumonia in #children who have had their #jabs? (Thorax, summary)

[Source: Thorax, full page: (LINK). Summary, edited.]

Editorial

What causes pneumonia in children who have had their jabs?

Gemma L Saint,  Dan B Hawcutt,  Paul S McNamara

DOI: http://dx.doi.org/10.1136/thoraxjnl-2018-212625

___

Emergency department physicians and paediatricians frequently have to decide how best to manage community-acquired pneumonia (CAP). For a febrile child who has increased respiratory effort, oxygen requirement and a chest X-ray (CXR) consistent with lobar pneumonia, the decision to commence antibiotic therapy is straightforward. However, other patients may present more of a dilemma. What about children with respiratory symptoms but only a low-grade (<38°C) fever? Or children whose respiratory symptoms are sufficient to require admission, but whose CXR is equivocal? Current British Thoracic Society (BTS) guidelines state all children with a clinical diagnosis of CAP should be given antibiotics.1 However, with increasing concern about antimicrobial resistance, consideration needs to be given to the likelihood of a bacterial cause.

(…)

Copyright information:  © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords: Pneumonia; Seasonal Influenza.

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Dose Selection and Validation for #Ceftazidime – #Avibactam in Adults with Complicated Intra- #Abdominal #Infections, Complicated #UTI and Nosocomial #Pneumonia (Antimicrob Agents Chemother., abstract)

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

Dose Selection and Validation for Ceftazidime-Avibactam in Adults with Complicated Intra-Abdominal Infections, Complicated Urinary Tract Infections and Nosocomial Pneumonia

Shampa Das, Jianguo Li, Todd Riccobene, Timothy J. Carrothers, Paul Newell, David Melnick, Ian A. Critchley, Gregory G. Stone, Wright W. Nichols

DOI: 10.1128/AAC.02187-18

 

ABSTRACT

Avibactam is a non-β-lactam β-lactamase inhibitor that has been approved in combination with ceftazidime for the treatment of complicated intra-abdominal infections, complicated urinary tract infections and nosocomial pneumonia, including ventilator-associated pneumonia. In Europe, ceftazidime-avibactam is also approved for the treatment of Gram-negative infections with limited treatment options. Selection and validation of the ceftazidime-avibactam dosage regimen was guided by an iterative process of population pharmacokinetic (PK) modelling, whereby population PK models for ceftazidime and avibactam were developed using PK data from clinical trials and updated periodically. These models were used in probability of target attainment (PTA) simulations using joint pharmacodynamic (PD) targets for ceftazidime and avibactam derived from preclinical data. Joint PTA was calculated based on the simultaneous achievement of the individual PK/PD targets (50% free time above the ceftazidime-avibactam minimum inhibitory concentration (MIC) for ceftazidime and free time above a critical avibactam threshold concentration of 1 mg/l for avibactam). The joint PTA analyses supported a ceftazidime-avibactam dosage regimen of 2,000 + 500 mg every 8 h by 2-h intravenous infusion for patients with creatinine clearance (CrCL) >50 ml/min across all approved indications and modified dosage regimens for patients with CrCL ≤50 ml/min. Subgroup simulations for individual Phase III patients showed that the dosage regimen was robust, with high target attainment (>95%) against MICs ≤8 mg/l achieved regardless of older age, obesity, augmented renal clearance or severity of infection. This review summarizes how the approved ceftazidime-avibactam dosage regimens were developed and validated using PK/PD targets, population PK modeling, and PTA analyses.

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

Keywords: Antibiotics; Drugs Resistance; Pneumonia; Ceftazidime; Avibactam.

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#Clinical and #Laboratory Findings of #MERS-CoV #infection (Jpn J Infect Dis., abstract)

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

Jpn J Infect Dis. 2018 Dec 25. doi: 10.7883/yoken.JJID.2018.187. [Epub ahead of print]

Clinical and Laboratory Findings of MERS-CoV infection.

Hwang SM1,2,3, Na BJ4, Jung YM5, Lim HS6, Seo JE6, Park SN6, Cho YS6, Song EH6, Seo JY6, Kim SR6, Lee GY6, Kim SJ6, Park YS6, Seo HS3,6.

Author information: 1 Korea Centers for Disease Control and Prevention. 2 Department of Health Policy, Health & Welfare Bureau. 3 Department of Preventive Medicine, Korea University College of Medicine. 4 Department of Preventive Medicine Seoul Metropolitan Government Civil health care bueau. 5 Korea Armed Forces Nursing Academy. 6 Department of Tuberculosis, Seobuk Hospital.

 

Abstract

There is a paucity of data regarding the differentiating characteristics of patients with laboratory confirmed and those negative for Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea. This is a hospital-based retrospective study comparing MERS-CoV-positive patients with MERS-CoV-negative patients. A total of 7 positive patients and 55 negative patients with a median age of 43 (P = 0.833) were included. No statistical differences were observed in relation to sex and the presence of comorbidities. At the time of admission, headache (28.6% vs 3.6%; OR, 10.60; 95% CI, 1.22-92.27), myalgia (57.1% vs. 9.1%; OR, 13.33; 95% CI, 2.30-77.24), and diarrhea (57.1% vs 14.5%; OR, 7.83; 95% CI, 1.47-41.79) were common among MERS-CoV-positive patients. MERS-CoV patients were more likely to have a low platelet count (164±76.57 vs 240±76.57) and eosinophil (0.27±0.43 vs. 2.13±2.01; p-value<0.001). Chest radiography with diffuse bronchopneumonia was more frequent in MERS-CoV-positive patients than in negative patients (100% vs 62.5%; p-value=0.491). Symptoms of headache, myalgia, and diarrhea, laboratory characteristics of low counts of platelet and eosinophil, Also, chest X-ray revealed that diffuse bronchopneumonia might have enhance the ability to detect which patients were infected with MERS-CoV in South Korea.

KEYWORDS: MERS; coronavirus; pneumonia; radiographic characteristics

PMID: 30584196 DOI: 10.7883/yoken.JJID.2018.187

Keywords: MERS-CoV; Pneumonia; South Korea.

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#Mortality, #morbidity, and hospitalisations due to #influenza #LRTI, 2017: an analysis for the Global Burden of Disease Study 2017 (Lancet Resp Med., abstract)

[Source: The Lancet Respiratory Medicine, full page: (LINK). Abstract, edited.]

Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017

GBD 2017 Influenza Collaborators †

Open Access / Published: December 12, 2018 / DOI: https://doi.org/10.1016/S2213-2600(18)30496-X

 

Summary

Background

Although the burden of influenza is often discussed in the context of historical pandemics and the threat of future pandemics, every year a substantial burden of lower respiratory tract infections (LRTIs) and other respiratory conditions (like chronic obstructive pulmonary disease) are attributable to seasonal influenza. The Global Burden of Disease Study (GBD) 2017 is a systematic scientific effort to quantify the health loss associated with a comprehensive set of diseases and disabilities. In this Article, we focus on LRTIs that can be attributed to influenza.

Methods

We modelled the LRTI incidence, hospitalisations, and mortality attributable to influenza for every country and selected subnational locations by age and year from 1990 to 2017 as part of GBD 2017. We used a counterfactual approach that first estimated the LRTI incidence, hospitalisations, and mortality and then attributed a fraction of those outcomes to influenza.

Findings

Influenza LRTI was responsible for an estimated 145 000 (95% uncertainty interval [UI] 99 000–200 000) deaths among all ages in 2017. The influenza LRTI mortality rate was highest among adults older than 70 years (16·4 deaths per 100 000 [95% UI 11·6–21·9]), and the highest rate among all ages was in eastern Europe (5·2 per 100 000 population [95% UI 3·5–7·2]). We estimated that influenza LRTIs accounted for 9 459 000 (95% UI 3 709 000–22 935 000) hospitalisations due to LRTIs and 81 536 000 hospital days (24 330 000–259 851 000). We estimated that 11·5% (95% UI 10·0–12·9) of LRTI episodes were attributable to influenza, corresponding to 54 481 000 (38 465 000–73 864 000) episodes and 8 172 000 severe episodes (5 000 000–13 296 000).

Interpretation

This comprehensive assessment of the burden of influenza LRTIs shows the substantial annual effect of influenza on global health. Although preparedness planning will be important for potential pandemics, health loss due to seasonal influenza LRTIs should not be overlooked, and vaccine use should be considered. Efforts to improve influenza prevention measures are needed.

Funding

Bill & Melinda Gates Foundation.

Keywords: Seasonal Influenza; Pneumonia; Worldwide.

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