Activity of # imipenem / #relebactam against #MDR #Pseudomonas aeruginosa in #Europe: SMART 2015–17 (J Antimicrob Chemother., abstract)

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

Activity of imipenem/relebactam against MDR Pseudomonas aeruginosa in Europe: SMART 2015–17

Sibylle H Lob, James A Karlowsky, Katherine Young, Mary R Motyl, Stephen Hawser, Nimmi D Kothari, Melinda E Gueny, Daniel F Sahm

Journal of Antimicrobial Chemotherapy, dkz191, https://doi.org/10.1093/jac/dkz191

Published: 13 May 2019

 

Abstract

Objectives

Relebactam is a diazabicyclooctane non-β-lactam inhibitor of Ambler class A and C β-lactamases that is in clinical development in combination with imipenem/cilastatin. The current study evaluated the in vitro activity of imipenem/relebactam against 5447 isolates of Pseudomonas aeruginosasubmitted to the SMART global surveillance programme in 2015–17 by 67 clinical laboratories in 22 European countries.

Methods

MICs were determined using the CLSI broth microdilution reference method (Eleventh Edition: M07, 2018). Relebactam was tested at a fixed concentration of 4 mg/L in combination with doubling dilutions of imipenem. MICs were interpreted using EUCAST clinical breakpoints (version 8.1); imipenem breakpoints were applied to imipenem/relebactam.

Results

Rates of susceptibility to imipenem and imipenem/relebactam (MIC ≤4 mg/L) were 69.4% and 92.4%, respectively, for all isolates of P. aeruginosa. Over one-third of all isolates (34.9%, 1902/5447) were MDR; lower respiratory tract isolates (38.3%, 1327/3461) were more frequently MDR than were intraabdominal (28.5%, 355/1245) or urinary tract (29.7%, 212/714) isolates. Of all MDR isolates, 78.2% were susceptible to imipenem/relebactam, a rate that was 50–77 percentage points higher than the rate of susceptibility to imipenem or any other β-lactam tested; rates of susceptibility to imipenem/relebactam were similar for MDR isolates from lower respiratory tract (77.8% susceptible), intraabdominal (80.3%) and urinary tract (76.4%) infections. Overall, relebactam restored imipenem susceptibility to 75.2% (1254/1668) of imipenem-non-susceptible isolates of P. aeruginosa and to 69.6% (947/1361) of imipenem-non-susceptible isolates with an MDR phenotype.

Conclusions

Relebactam restored in vitro susceptibility to imipenem for most imipenem-non-susceptible and MDR clinical isolates of P. aeruginosa from European patients.

Topic: phenotype – pseudomonas aeruginosa – imipenem – lactams – respiratory system – urinary tract – infection

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Pseudomonas aeruginosa; Relebactam; Imipenem; European Region.

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Challenge of drug #resistance in #Pseudomonas aeruginosa: clonal spread of #NDM1-positive ST-308 within a tertiary #hospital (J Antimicrob Chemother., abstract)

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

Challenge of drug resistance in Pseudomonas aeruginosa: clonal spread of NDM-1-positive ST-308 within a tertiary hospital

Ka Lip Chew, Sophie Octavia, Oon Tek Ng, Kalisvar Marimuthu, Indumathi Venkatachalam, Bernadette Cheng, Raymond T P Lin, Jeanette W P Teo

Journal of Antimicrobial Chemotherapy, dkz169, https://doi.org/10.1093/jac/dkz169

Published: 12 May 2019

 

Abstract

Objectives

MDR Pseudomonas aeruginosa is a serious global threat to healthcare institutions. The mechanism by which drug resistance can be acquired is variable, but acquired carbapenemase production has been reported in P. aeruginosa. An investigation was performed to determine the rate and genomic epidemiology of New Delhi MBL (NDM) in β-lactam-non-susceptible isolates.

Methods

P. aeruginosa isolates from a tertiary hospital in Singapore between January 2015 and February 2018 were investigated for the presence of NDM genes.

Results

Out of 298 pan-β-lactam-non-susceptible isolates, 31 were found to be NDM positive (10.4%). WGS demonstrated that all 31 NDM-positive isolates were clonal, belonging to ST-308. blaNDM was chromosomally inserted within an integrative and conjugative element (ICE), ICETn43716385. The NDM-P. aeruginosa isolates possessed an extensive repertoire of both cell-associated [flagella, pili, alginate/biofilm, LPS, type III secretion system (T3SS) and type VI secretion system (T6SS)] and secreted virulence factors. Antibiograms revealed higher rates of drug resistance in NDM-positive isolates compared with their non-NDM counterparts. The NDM isolates remained 100% susceptible only to colistin.

Conclusions

The combination of chromosomal mutations, acquired resistance genes and virulence factors likely facilitated the persistent and ongoing spread of the ST-308 clade of P. aeruginosa within the hospital. Our study illustrates the particular threat of NDM-positive P. aeruginosa in a tertiary hospital setting in the era of antimicrobial resistance.

Topic: pseudomonas aeruginosa – mutation – colistin – epidemiology – drug resistance – alginates – biofilms – bodily secretions – chromosomes – drug resistance, microbial – bacterial fimbria – flagella – genes – genome – lactams – singapore – persistence – virulence factors – antibiogram – resistance genes – type iii protein secretion system complex – whole genome sequencing

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; Beta-lactams; NDM1; Pseudomonas aeruginosa; Nosocomial outbreaks.

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#Plasmid carrying #blaCTX-M-2 and blaGES-1 in #XDR #Pseudomonas aeruginosa from #CSF (Antimicrob Agents Chemother., abstract)

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

Plasmid carrying blaCTX-M-2 and blaGES-1 in extensively drug-resistant Pseudomonas aeruginosa from cerebrospinal fluid

Anelise Stella Ballaben, Renata Galetti, Leonardo Neves Andrade, Joseane Cristina Ferreira, Doroti de Oliveira Garcia, Paulo da Silva, Yohei Doi, Ana Lucia Costa Darini

DOI: 10.1128/AAC.00186-19

 

ABSTRACT

Extended-spectrum β-lactamases (ESBL) are spread worldwide in Order Enterobacterales (1, 2) but are less common in Pseudomonas aeruginosa, consequently little is known regarding genetic environment and plasmid carrying blaESBL genes in this species (3).…

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

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; Pseudomonas aeruginosa; Plasmids.

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Potentiation of #imipenem by #relebactam for #Pseudomonas aeruginosa from #bacteraemia and respiratory infections (J Antimicrob Chemother., abstract)

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

Potentiation of imipenem by relebactam for Pseudomonas aeruginosa from bacteraemia and respiratory infections

Carolyne Horner, Shazad Mushtaq, David M Livermore, BSAC Resistance Surveillance Standing Committee

Journal of Antimicrobial Chemotherapy, dkz133, https://doi.org/10.1093/jac/dkz133

Published: 29 April 2019

 

Abstract

Background

Imipenem resistance in Pseudomonas aeruginosa most often entails loss of the ‘carbapenem-specific’ porin OprD; more rarely it reflects acquired carbapenemases. Loss of OprD only confers resistance to imipenem if AmpC β-lactamase is expressed, and we investigated whether this mechanism was overcome by relebactam, a developmental diazabicyclooctane β-lactamase inhibitor.

Methods

Consecutive P. aeruginosa isolates causing bacteraemia or hospital-onset lower respiratory tract infections were collected between 2014 and 2016 under the aegis of the BSAC Resistance Surveillance Programme. Imipenem MICs were determined centrally by BSAC agar dilution, with relebactam at a fixed concentration (4 mg/L).

Results

For most imipenem-susceptible P. aeruginosa (726/759, 95.7%), the MICs of imipenem alone were 0.5–2 mg/L and were decreased 3- to 4-fold by addition of relebactam, as based on geometric means or modes. For most imipenem-resistant P. aeruginosa (82/92, 89%), imipenem MICs were 8–16 mg/L, and were reduced to 1–2 mg/L by relebactam. These patterns applied regardless of whether the isolates were susceptible to penicillins and cephalosporins or had phenotypes suggesting derepressed AmpC or up-regulated efflux. Imipenem MICs for five P. aeruginosa with MBLs remained high (≥16 mg/L) regardless of relebactam.

Conclusions

Potentiation of imipenem by relebactam was almost universal, in accordance with the view that endogenous pseudomonal AmpC ordinarily protects against this carbapenem to a small degree. Imipenem MICs were reduced to the current breakpoint, or lower, except for MBL producers. Potentiation was not compromised by derepression of AmpC or up-regulation of efflux.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Pseudomonas aeruginosa; Imipenem; Relebactam.

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#ESBLs and #resistance to #ceftazidime / #avibactam and #ceftolozane / #tazobactam combinations in #Escherichia coli and #Pseudomonas aeruginosa (J Antimicrob Chemother., abstract)

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

ESBLs and resistance to ceftazidime/avibactam and ceftolozane/tazobactam combinations in Escherichia coli and Pseudomonas aeruginosa

José-Manuel Ortiz de la Rosa, Patrice Nordmann, Laurent Poirel

Journal of Antimicrobial Chemotherapy, dkz149, https://doi.org/10.1093/jac/dkz149

Published: 23 April 2019

 

Abstract

Objectives

To evaluate the efficacy of the recently launched β-lactam/β-lactamase inhibitor combinations ceftazidime/avibactam and ceftolozane/tazobactam against ESBL-producing Escherichia coli and Pseudomonas aeruginosa strains.

Methods

A series of ESBL-encoding genes (blaTEM, blaSHV, blaCTX-M, blaVEB, blaPER, blaGES and blaBEL) was cloned and expressed in E. coli or P. aeruginosa recipient strains. Cultures of E. coli TOP10 harbouring recombinant plasmids and therefore producing the different ESBLs tested were grown in order to perform measurements of catalytic activities, using benzylpenicillin, ceftazidime and ceftolozane as substrates. IC50s were additionally determined for clavulanic acid, tazobactam and avibactam.

Results

We showed here an overall better activity of ceftazidime/avibactam compared with ceftolozane/tazobactam toward ESBL-producing E. coli and P. aeruginosa. Several ESBLs of the GES, PER and BEL types conferred resistance to ceftolozane/tazobactam in E. coli and P. aeruginosa. For GES-6 and PER-1 producers, resistance to ceftolozane/tazobactam could be explained by a high hydrolysis of ceftolozane and a low activity of tazobactam as an inhibitor. On the other hand, PER-producing P. aeruginosa also exhibited resistance to ceftazidime/avibactam.

Conclusions

Altogether, the results show that the ESBL PER-1, which is widespread worldwide, may be a source of resistance to both ceftolozane/tazobactam and ceftazidime/avibactam. Excellent activity of ceftazidime/avibactam was highlighted for both ESBL-producing E. coli and ESBL-producing P. aeruginosa.

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; E. Coli; Pseudomonas aeruginosa; Ceftazidime; Avibactam; Ceftolozane; Tazobactam.

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Filamentous #bacteriophages are associated with chronic #Pseudomonas #lung #infections and #antibiotic resistance in #cysticfibrosis (Sci Transl Med., abstract)

[Source: Science Translational Medicine, full page: (LINK). Abstract, edited.]

Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis

Elizabeth B. Burgener1,*, Johanna M. Sweere2,3, Michelle S. Bach2, Patrick R. Secor4, Naomi Haddock3, Laura K. Jennings4, Rasmus L. Marvig5, Helle Krogh Johansen6,7, Elio Rossi6, Xiou Cao2, Lu Tian8, Laurence Nedelec9, Søren Molin10, Paul L. Bollyky2,3,† and Carlos E. Milla1,†

1 Center for Excellence in Pulmonary Biology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA. 2 Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA. 3 Stanford Immunology, Stanford University, Stanford, CA 94305, USA. 4 Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA. 5 Center for Genomic Medicine, Rigshospitalet–Copenhagen University Hospital, Copenhagen, Denmark. 6 Department of Clinical Microbiology, Rigshospitalet, Copenhagen Ø, Denmark. 7 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark. 8 Biomedical Data Science Administration and Statistics, Stanford University, Stanford, CA 94305, USA. 9 Primary Care and Population Health, Stanford University, Stanford, CA 94305, USA. 10 The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.

*Corresponding author. Email: eburgener@stanford.edu

† Co-senior authors.

Science Translational Medicine  17 Apr 2019: Vol. 11, Issue 488, eaau9748 / DOI: 10.1126/scitranslmed.aau9748

 

Infection-boosting phage

Chronic Pseudomonas aeruginosa infection is common in patients with cystic fibrosis (CF). Filamentous bacteriophage (Pf phage) can infect P. aeruginosa and has been shown to contribute to the virulence of infection in animal models. However, whether Pf phage plays a role in the pathogenicity of P. aeruginosa in CF is unknown. Now, Burgener et al. showed that Pf phage was abundantly expressed in sputum samples from two large cohorts of patients with CF. The presence of Pf phage was associated with increased antibiotic resistance and reduced lung function. The results suggest that Pf phage might play a role in the pathogenicity of P. aeruginosa infection in CF.

 

Abstract

Filamentous bacteriophage (Pf phage) contribute to the virulence of Pseudomonas aeruginosa infections in animal models, but their relevance to human disease is unclear. We sought to interrogate the prevalence and clinical relevance of Pf phage in patients with cystic fibrosis (CF) using sputum samples from two well-characterized patient cohorts. Bacterial genomic analysis in a Danish longitudinal cohort of 34 patients with CF revealed that 26.5% (n = 9) were consistently Pf phage positive. In the second cohort, a prospective cross-sectional cohort of 58 patients with CF at Stanford, sputum qPCR analysis showed that 36.2% (n = 21) of patients were Pf phage positive. In both cohorts, patients positive for Pf phage were older, and in the Stanford CF cohort, patients positive for Pf phage were more likely to have chronic P. aeruginosa infection and had greater declines in pulmonary function during exacerbations than patients negative for Pf phage presence in the sputum. Last, P. aeruginosa strains carrying Pf phage exhibited increased resistance to antipseudomonal antibiotics. Mechanistically, in vitro analysis showed that Pf phage sequesters these same antibiotics, suggesting that this mechanism may thereby contribute to the selection of antibiotic resistance over time. These data provide evidence that Pf phage may contribute to clinical outcomes in P. aeruginosa infection in CF.

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
http://www.sciencemag.org/about/science-licenses-journal-article-reuse

This is an article distributed under the terms of the Science Journals Default License.

Keywords: Antibiotics; Drugs Resistance; Pseudomonas aeruginosa; Cystic fibrosis; Bacteriophages.

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#Spanish nationwide #survey on #Pseudomonas aeruginosa #antimicrobial #resistance mechanisms and #epidemiology (J Antimicrob Chemother., abstract)

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

Spanish nationwide survey on Pseudomonas aeruginosa antimicrobial resistance mechanisms and epidemiology

Ester del Barrio-Tofiño, Laura Zamorano, Sara Cortes-Lara, Carla López-Causapé, Irina Sánchez-Diener, Gabriel Cabot, Germán Bou, Luis Martínez-Martínez, Antonio Oliver

Journal of Antimicrobial Chemotherapy, dkz147, https://doi.org/10.1093/jac/dkz147

Published: 15 April 2019

 

Abstract

Objectives

To undertake a Spanish nationwide survey on Pseudomonas aeruginosamolecular epidemiology and antimicrobial resistance.

Methods

Up to 30 consecutive healthcare-associated P. aeruginosa isolates collected in 2017 from each of 51 hospitals were studied. MICs of 13 antipseudomonal agents were determined by broth microdilution. Horizontally acquired β-lactamases were detected by phenotypic methods and PCR. Clonal epidemiology was evaluated through PFGE and MLST; at least one XDR isolate from each clone and hospital (n = 185) was sequenced.

Results

The most active antipseudomonals against the 1445 isolates studied were colistin and ceftolozane/tazobactam (both 94.6% susceptible, MIC50/90 = 1/2 mg/L) followed by ceftazidime/avibactam (94.2% susceptible, MIC50/90 = 2/8 mg/L). Up to 252 (17.3%) of the isolates were XDR. Carbapenemases/ESBLs were detected in 3.1% of the isolates, including VIM, IMP, GES, PER and OXA enzymes. The most frequent clone among the XDR isolates was ST175 (40.9%), followed by CC235 (10.7%), ST308 (5.2%) and CC111 (4.0%). Carbapenemase production varied geographically and involved diverse clones, including 16.5% of ST175 XDR isolates. Additionally, 56% of the sequenced XDR isolates showed horizontally acquired aminoglycoside-modifying enzymes, which correlated with tobramycin resistance. Two XDR isolates produced QnrVC1, but fluoroquinolone resistance was mostly caused by QRDR mutations. Beyond frequent mutations (>60%) in OprD and AmpC regulators, four isolates showed AmpC mutations associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam.

Conclusions

ST175 is the most frequent XDR high-risk clone in Spanish hospitals, but this nationwide survey also indicates a complex scenario in which major differences in local epidemiology, including carbapenemase production, need to be acknowledged in order to guide antimicrobial therapy.

Topic: phenotype – polymerase chain reaction – pseudomonas aeruginosa – mutation – colistin – epidemiology – ceftazidime – clone cells – drug resistance, microbial – electrophoresis, gel, pulsed-field – epidemiology, molecular – fluoroquinolones – spain – enzymes – tobramycin – aminoglycosides – antimicrobials – tazobactam – extended-spectrum beta lactamases – malnutrition-inflammation-cachexia syndrome – ceftolozane – avibactam

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; Spain; Colistin; Ceftazidime; Fluoroquinolones; Tobramycin; Aminoglycosides; Tazobactam; Avibactam.

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