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      First detection of autochthonous extensively drug-resistant NDM-1 Pseudomonas aeruginosa ST235 from a patient with bloodstream infection in Italy, October 2019

      case-report

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          Abstract

          Background

          Pseudomonas aeruginosa (PA) is one of the most common and serious causes of healthcare-associated bacteremia. The emergence and dissemination of multidrug-resistant (MDR) and extensively drug-resistant (XDR) PA strains pose a major clinical concern. ST235-PA is a high-risk clone which shows a high capacity to acquire antibiotic resistance. Here we describe the first autochthonous New Delhi metallo-β-lactamase (NDM)-producing Pseudomonas aeruginosa ST235 identified in Italy.

          Case presentation

          In October 2019, a patient residing in an elderly health care and rehabilitation facility, was hospitalized and died from sepsis caused by an XDR-PA. The strain belonged to the high-risk clone sequence type ST235. Whole genome sequencing (WGS) revealed the presence of genes encoding NDM-1 and multiple β-lactamases, many clinically significant multidrug efflux pump complexes and also the virulence gene ExoU, which is associated with a high cytotoxic phenotype.

          Conclusions

          Few strains of NDM-1-PA have been identified worldwide, all belonging to ST235. The combination of ST235 and ExoU is a predictor of highly unfavorable prognosis. The potential spread of these high-risk clones in healthcare settings is worrisome because treatment options are limited. Early identification of high-risk clones could help in outbreaks investigation and infections control.

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          Influence of virulence genotype and resistance profile in the mortality of Pseudomonas aeruginosa bloodstream infections.

          Carmen Peña, Gabriel Cabot, Silvia Gómez-Zorrilla … (2015)
          The type III secretion system (TTSS) is a major virulence determinant of Pseudomonas aeruginosa. The objective of this study was to determine whether the TTSS genotype is a useful prognostic marker of P. aeruginosa bacteremia mortality. We also studied the potential association between TTSS genotypes and multidrug-resistant (MDR) profiles, and how this interaction impacts the outcome of bloodstream infections.
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            Results from a 13-Year Prospective Cohort Study Show Increased Mortality Associated with Bloodstream Infections Caused by Pseudomonas aeruginosa Compared to Other Bacteria.

            Joshua Thaden, Lawrence Park, Stacey A Maskarinec … (2017)
            The impact of bacterial species on outcome in bloodstream infections (BSI) is incompletely understood. We evaluated the impact of bacterial species on BSI mortality, with adjustment for patient, bacterial, and treatment factors. From 2002 to 2015, all adult inpatients with monomicrobial BSI caused by Staphylococcus aureus or Gram-negative bacteria at Duke University Medical Center were prospectively enrolled. Kaplan-Meier curves and multivariable Cox regression with propensity score models were used to examine species-specific bacterial BSI mortality. Of the 2,659 enrolled patients, 999 (38%) were infected with S. aureus, and 1,660 (62%) were infected with Gram-negative bacteria. Among patients with Gram-negative BSI, Enterobacteriaceae (81% [1,343/1,660]) were most commonly isolated, followed by non-lactose-fermenting Gram-negative bacteria (16% [262/1,660]). Of the 999 S. aureus BSI isolates, 507 (51%) were methicillin resistant. Of the 1,660 Gram-negative BSI isolates, 500 (30%) were multidrug resistant. The unadjusted time-to-mortality among patients with Gram-negative BSI was shorter than that of patients with S. aureus BSI (P = 0.003), due to increased mortality in patients with non-lactose-fermenting Gram-negative BSI generally (P < 0.0001) and Pseudomonas aeruginosa BSI (n = 158) in particular (P < 0.0001). After adjustment for patient demographics, medical comorbidities, bacterial antibiotic resistance, timing of appropriate antibiotic therapy, and source control in patients with line-associated BSI, P. aeruginosa BSI remained significantly associated with increased mortality (hazard ratio = 1.435; 95% confidence interval = 1.043 to 1.933; P = 0.02). P. aeruginosa BSI was associated with increased mortality relative to S. aureus or other Gram-negative BSI. This effect persisted after adjustment for patient, bacterial, and treatment factors.
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              Multidrug-Resistant Pseudomonas Infections: Hard to Treat, But Hope on the Horizon?

              Lynn Nguyen, Joshua Garcia, Katherine Gruenberg … (2018)
              As the sixth most common nosocomial pathogen in the USA, Pseudomonas aeruginosa poses a significant threat to patients within the healthcare system. Its intrinsic and acquired resistance mechanisms also significantly limit the choices for antimicrobial therapy, prompting an increase in the research and development of antibacterial agents with enhanced activity against multidrug-resistant (MDR) P. aeruginosa. While many approved and pipeline antibiotics have activity against wild-type P. aeruginosa, only four new antibiotics have promising activity against MDR P. aeruginosa: ceftazidime-avibactam (Avycaz®), ceftolozane-tazobactam (Zerbaxa®), cefiderocol, and imipenem-cilastatin/relebactam. The goal of this paper is to review the epidemiology and mechanisms of resistance in P. aeruginosa as well as explore the newly approved and pipeline agents that overcome these mechanisms of resistance.
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                Author and article information

                Contributors
                Maria Chironna:
                ORCID: https://orcid.org/0000-0002-1043-1256
                maria.chironna@uniba.it
                Journal
                Journal ID (nlm-ta): Antimicrob Resist Infect Control
                Journal ID (iso-abbrev): Antimicrob Resist Infect Control
                Title: Antimicrobial Resistance and Infection Control
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2047-2994
                Publication date (Electronic): 25 May 2020
                Publication date PMC-release: 25 May 2020
                Publication date Collection: 2020
                Volume: 9
                Electronic Location Identifier: 73
                Affiliations
                [1 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, Department of Biomedical Sciences and Human Oncology, Hygiene Unit, , University of Bari “Aldo Moro”, ; P.zza G. Cesare 11, 70124 Bari, Italy
                [2 ]GRID grid.416651.1, ISNI 0000 0000 9120 6856, Department of Infectious Diseases, , Istituto Superiore di Sanità, ; Roma, Italy
                [3 ]Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Foggia, Italy
                [4 ]San Paolo Hospital, ASL, Bari, Italy
                Author information
                https://orcid.org/0000-0002-1043-1256
                Article
                Publisher ID: 734
                DOI: 10.1186/s13756-020-00734-5
                PMC ID: 7249406
                PubMed ID: 32450907
                SO-VID: 27c5aa22-8c14-4e25-937c-6ba17b40e59f
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 11 March 2020
                Date accepted : 9 May 2020
                Categories
                Subject: Case Report
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: pseudomonas aeruginosa,extensively-drug resistant,new delhi metallo beta-,lactamase,whole-genome sequencing, st235, sepsis
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: pseudomonas aeruginosa, extensively-drug resistant, new delhi metallo beta-, lactamase, whole-genome sequencing, st235, sepsis

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