Bacteraemia due to extensively drug-resistant Pseudomonas aeruginosa sequence type 235 high-risk clone: Facing the perfect storm

ABSTRACTThe ability ofPseudomonas aeruginosato develop resistance to most antimicrobials represents an important clinical threat worldwide. We report the dissemination in several Colombian hospitals of two predominant lineages of extensively drug-resistant (XDR) carbapenemase-producingP. aeruginosastrains. These lineages belong to the high-risk clones sequence type 111 (ST111) and ST235 and harborblaVIM-2on a class 1 integron andblaKPC-2on a Tn4401transposon, respectively. Additionally,P. aeruginosaST1492, a novel single-locus variant of ST111, was identified. Clonal dissemination and the presence of mobile genetic elements likely explain the successful spread of XDRP. aeruginosastrains in Colombia.

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Long-term Persistence of an Extensively Drug-Resistant Subclade of Globally Distributed Pseudomonas aeruginosa Clonal Complex 446 in an Academic Medical Center

Clinical Infectious Diseases ◽

10.1093/cid/ciz973 ◽

2019 ◽

Vol 71 (6) ◽

pp. 1524-1531 ◽

Cited By ~ 3

Author(s):

Nathan B Pincus ◽

Kelly E R Bachta ◽

Egon A Ozer ◽

Jonathan P Allen ◽

Olivia N Pura ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

High Risk ◽

Clonal Complex ◽

Medical Center ◽

Academic Medical Center ◽

Small Subset ◽

Drug Resistant ◽

Extensively Drug Resistant ◽

Academic Medical ◽

Globally Distributed

Abstract Background Antimicrobial resistance (AMR) is a major challenge in the treatment of infections caused by Pseudomonas aeruginosa. Highly drug-resistant infections are disproportionally caused by a small subset of globally distributed P. aeruginosa sequence types (STs), termed “high-risk clones.” We noted that clonal complex (CC) 446 (which includes STs 298 and 446) isolates were repeatedly cultured at 1 medical center and asked whether this lineage might constitute an emerging high-risk clone. Methods We searched P. aeruginosa genomes from collections available from several institutions and from a public database for the presence of CC446 isolates. We determined antibacterial susceptibility using microbroth dilution and examined genome sequences to characterize the population structure of CC446 and investigate the genetic basis of AMR. Results CC446 was globally distributed over 5 continents. CC446 isolates demonstrated high rates of AMR, with 51.9% (28/54) being multidrug-resistant (MDR) and 53.6% of these (15/28) being extensively drug-resistant (XDR). Phylogenetic analysis revealed that most MDR/XDR isolates belonged to a subclade of ST298 (designated ST298*) of which 100% (21/21) were MDR and 61.9% (13/21) were XDR. XDR ST298* was identified repeatedly and consistently at a single academic medical center from 2001 through 2017. These isolates harbored a large plasmid that carries a novel antibiotic resistance integron. Conclusions CC446 isolates are globally distributed with multiple occurrences of high AMR. The subclade ST298* is responsible for a prolonged epidemic (≥16 years) of XDR infections at an academic medical center. These findings indicate that CC446 is an emerging high-risk clone deserving further surveillance.

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Genome sequencing and characterization of an extensively drug-resistant sequence type 111 serotype O12 hospital outbreak strain of Pseudomonas aeruginosa

Clinical Microbiology and Infection ◽

10.1111/1469-0691.12528 ◽

2014 ◽

Vol 20 (10) ◽

pp. O609-O618 ◽

Cited By ~ 35

Author(s):

A.A. Witney ◽

K.A. Gould ◽

C.F. Pope ◽

F. Bolt ◽

N.G. Stoker ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Genome Sequencing ◽

Sequence Type ◽

Drug Resistant ◽

Outbreak Strain ◽

Hospital Outbreak ◽

Extensively Drug Resistant

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Colistin plus meropenem combination is synergistic in vitro against extensively drug-resistant Pseudomonas aeruginosa, including high-risk clones

Journal of Global Antimicrobial Resistance ◽

10.1016/j.jgar.2019.04.012 ◽

2019 ◽

Vol 18 ◽

pp. 37-44 ◽

Cited By ~ 5

Author(s):

María M. Montero ◽

Sandra Domene Ochoa ◽

Carla López-Causapé ◽

Brian VanScoy ◽

Sonia Luque ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

High Risk ◽

Drug Resistant ◽

Extensively Drug Resistant

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Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in an In Vitro Pharmacodynamic Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02542-19 ◽

2020 ◽

Vol 64 (4) ◽

Author(s):

María Montero ◽

Sandra Domene Ochoa ◽

Carla López-Causapé ◽

Brian VanScoy ◽

Sonia Luque ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

High Risk ◽

Therapeutic Option ◽

Drug Resistant ◽

Chemostat Model ◽

Content Type ◽

Extensively Drug Resistant ◽

Spanish Study ◽

Time Kill

ABSTRACT Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of C/T and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and C/T alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa ST175 isolates with different susceptibility levels to C/T. Static time-kill assays demonstrated superior synergistic or additive effect for C/T plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. C/T plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high risk-clones resistant to C/T.

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1597. Ceftolozane-Tazobactam and Meropenem Synergy Testing Against Multi-Drug and Extensively-Drug Resistant Pseudomonas aeruginosa

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1777 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S794-S795

Author(s):

Mary Francine P Chua ◽

Syeda Sara Nida ◽

Jerry Lawhorn ◽

Janak Koirala

Keyword(s):

Pseudomonas Aeruginosa ◽

Synergistic Effect ◽

Inhibitory Concentration ◽

Multidrug Resistant ◽

Additive Effect ◽

Teaching Hospitals ◽

Drug Resistant ◽

Extensively Drug Resistant ◽

Synergy Testing ◽

Concentration Indices

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, >0.5 to <1, >1 to <4, and >4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 >32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures

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Genomic analysis of an extensively drug-resistant Pseudomonas aeruginosa ST312 harbouring IncU plasmid-mediated blaKPC-2 isolated from ascitic fluid

Journal of Global Antimicrobial Resistance ◽

10.1016/j.jgar.2021.03.012 ◽

2021 ◽

Vol 25 ◽

pp. 151-153

Author(s):

Daniela Cristina Tartari ◽

Caetana Paes Zamparette ◽

Graciele Martini ◽

Sandra Christakis ◽

Luiz Henrique Costa ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Ascitic Fluid ◽

Genomic Analysis ◽

Drug Resistant ◽

Extensively Drug Resistant

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Complete Genome Sequences of Four Extensively Drug-Resistant Acinetobacter baumannii Isolates from Thailand

Microbiology Resource Announcements ◽

10.1128/mra.00949-20 ◽

2020 ◽

Vol 9 (40) ◽

Author(s):

Peechanika Chopjitt ◽

Thidathip Wongsurawat ◽

Piroon Jenjaroenpun ◽

Parichart Boueroy ◽

Rujirat Hatrongjit ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Complete Genome ◽

Sequence Type ◽

Clinical Isolates ◽

Drug Resistant ◽

Genome Sequences ◽

Content Type ◽

Type Isolate ◽

Resistant Genes ◽

Extensively Drug Resistant

ABSTRACT Here, we report the complete genome sequences of four clinical isolates of extensively drug-resistant Acinetobacter baumannii (XDRAB), isolated in Thailand. These results revealed multiple antimicrobial-resistant genes, each involving two sequence type 16 (ST16) isolates, ST2, and a novel sequence type isolate, ST1479.

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Draft Genome Sequence of a Clinically Isolated Extensively Drug-Resistant Pseudomonas aeruginosa Strain

Genome Announcements ◽

10.1128/genomea.00162-16 ◽

2016 ◽

Vol 4 (2) ◽

Author(s):

Bhavani Manivannan ◽

Niranjana Mahalingam ◽

Sudhir Jadhao ◽

Amrita Mishra ◽

Pravin Nilawe ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Genome Assembly ◽

Biofilm Formation ◽

Draft Genome ◽

Drug Resistant ◽

Draft Genome Assembly ◽

Extensively Drug Resistant ◽

History Of ◽

Urinary Tuberculosis

We present the draft genome assembly of an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain isolated from a patient with a history of genito urinary tuberculosis. The draft genome is 7,022,546 bp with a G+C content of 65.48%. It carries 7 phage genomes, genes for quorum sensing, biofilm formation, virulence, and antibiotic resistance.

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