#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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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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Mechanisms of high-level #ceftolozane/tazobactam #resistance in #Pseudomonas aeruginosa from a severely #neutropenic patient and treatment success from synergy with #tobramycin (J Antimicrob Chemother., abstract)

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

Mechanisms of high-level ceftolozane/tazobactam resistance in Pseudomonas aeruginosa from a severely neutropenic patient and treatment success from synergy with tobramycin

Wonhee So, James Shurko, Ralph Galega, Rod Quilitz, John N Greene, Grace C Lee

Journal of Antimicrobial Chemotherapy, dky393, https://doi.org/10.1093/jac/dky393

Published: 08 October 2018

___

Sir,

We read the article by Fraile-Ribot et al.1 with great interest and herein report another case of ceftolozane/tazobactam-resistant Pseudomonas aeruginosabacteraemia that developed after 5 weeks of exposure to ceftolozane/tazobactam. A retrospective review of the medical records of a single patient case does not mandate review by the University of South Florida College of Medicine Institutional Review Board (IRB), thus informed consent was not required.

… The patient had AML and was induced with cladribine, cytarabine, filgrastim plus mitoxantrone on days 1–6 then reinduced with 5 days of cladribine plus cytarabine on days 15–19. The patient had a long history of hidradenitis…

___

Topic: pseudomonas aeruginosa – neutropenia – tobramycin – tazobactam – ceftolozane

Issue Section: Research letter

© 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/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Pseudomonas aeruginosa; Ceftolozane; Tazobactam; Tobramycin.

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#Antibacterial activity of #ceftolozane / #tazobactam alone and in combination with other antimicrobial agents against #MDR #Pseudomonas aeruginosa (J Antimicrob Chemother., abstract)

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

Antibacterial activity of ceftolozane/tazobactam alone and in combination with other antimicrobial agents against MDR Pseudomonas aeruginosa

Marguerite L Monogue, David P Nicolau

Journal of Antimicrobial Chemotherapy, dkx483, https://doi.org/10.1093/jac/dkx483

Published:  18 December 2017

 

Abstract

Objectives

Broad-spectrum antimicrobial resistance in Pseudomonas aeruginosa (PSA) isolates is a growing concern as our therapeutic options have become significantly limited. Although ceftolozane/tazobactam (C/T) has been shown to be highly active against MDR PSA pathogens, combination regimens are often employed in real-world settings. To assist the clinical decision-making process regarding the selection of combination antibiotics and dosages for this pathogen, we performed time–kill studies assessing clinical free peak and trough C/T concentrations alone and in combination with eight anti-pseudomonal agents against four clinical MDR PSA isolates.

Methods

Time–kill analyses were performed over 24 h in duplicate using C/T concentrations reflective of the free peak concentrations of a 3 g dose every 8 h (q8h; 120/25.2 mg/L) and the peak and trough of a 1.5 g q8h dose (60/12.6 and 7.5/1.6 mg/L) in humans. The activity of C/T 120, 60 and 7.5 mg/L alone and C/T 7.5 mg/L in combination with free peak and trough concentrations of clinical doses for cefepime, ciprofloxacin, colistin, aztreonam, meropenem, piperacillin/tazobactam, fosfomycin and amikacin was tested for all isolates.

Results

C/T 3 and 1.5 g q8h peak concentrations demonstrated killing against the MDR PSA. Colistin and fosfomycin were synergistic with C/T as dual therapy and triple therapy regimens.

Conclusions

As a result of escalating resistance, PSA is an increasingly challenging pathogen in the clinical setting. Our findings aid in the identification of novel treatment options using achievable drug exposures for the treatment of MDR PSA.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Pseudomonas aeruginosa; Colistin; Ceftolozane; Tazobactam.

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