Emergence of NDM-1-Producing Pseudomonas aeruginosa Nosocomial Isolates in Attica Region of Greece
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Collection
2.2. Antimicrobial Susceptibility Testing
2.3. Detection of Antimicrobial Resistance Genes and Known Chromosomal Point Mutations
2.4. Molecular Typing
2.5. Whole-Genome Sequencing (WGS)
2.6. Phylogenomic Relationship
2.7. Nucleotide Accession Numbers
3. Results
3.1. Bacterial Isolates and Details on Patients’ Hospitalization
3.2. Antimicrobial Susceptibility Testing
3.3. Molecular Typing
3.4. Detection of Antimicrobial Resistance Genes and Known Chromosomal Point Mutations
3.5. Genetic Environment of blaNDM-1
3.6. Detection of Virulence Genes
3.7. Phylogenetics
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
- Sendra, E.; Fernández-Muñoz, A.; Zamorano, L.; Oliver, A.; Horcajada, J.P.; Juan, C.; Gómez-Zorrillav, S. Impact of multidrug resistance on the virulence and fitness of Pseudomonas aeruginosa: A microbiological and clinical perspective. Infection 2024, 52, 1235–1268. [Google Scholar] [CrossRef] [PubMed]
- Jean, S.S.; Harnod, D.; Hsueh, P.R. Global Threat of Carbapenem-Resistant Gram-Negative Bacteria. Front. Cell. Infect. Microbiol. 2022, 12, 823684. [Google Scholar] [CrossRef] [PubMed]
- López-Causapé, C.; Cabot, G.; Del Barrio-Tofiño, E.; Oliver, A. The versatile mutational resistome of Pseudomonas aeruginosa. Front. Microbiol. 2018, 9, 685. [Google Scholar] [CrossRef] [PubMed]
- Pan, Y.P.; Xu, Y.H.; Wang, Z.X.; Fang, Y.P.; Shen, J.L. Overexpression of MexAB-OprM efflux pump in carbapenem-resistant Pseudomonas aeruginosa. Arch. Microbiol. 2016, 6, 565–571. [Google Scholar] [CrossRef]
- Cabot, G.; Bruchmann, S.; Mulet, X.; Zamorano, L.; Moyà, B.; Juan, C.; Haussler, S.; Oliver, A. Pseudomonas aeruginosa ceftolozane-tazobactam resistance development requires multiple mutations leading to overexpression and structural modification of AmpC. Antimicrob. Agents Chemother. 2014, 6, 3091–3099. [Google Scholar] [CrossRef]
- Angeletti, S.; Cella, E.; Prosperi, M.; Spoto, S.; Fogolari, M.; De Florio, L.; Antonelli, F.; Dedej, E.; De Flora, C.; Ferraro, E.; et al. Multi-drug resistant Pseudomonas aeruginosa nosocomial strains: Molecular epidemiology and evolution. Microb. Pathog. 2018, 123, 233–241. [Google Scholar] [CrossRef]
- Tenover, F.C.; Nicolau, D.P.; Gill, C.M. Carbapenemase-producing Pseudomonas aeruginosa—An emerging challenge. Emerg. Microbes Infect. 2022, 11, 811–814. [Google Scholar] [CrossRef]
- Gill, C.M.; Aktaþ, E.; Alfouzan, W.; Bourassa, L.; Brink, A.; Burnham, C.D.; Canton, R.; Carmeli, Y.; Falcone, M.; Kiffer, C.; et al. The ERACE-PA Global Surveillance Program: Ceftolozane/tazobactam and Ceftazidime/avibactam in vitro Activity against a Global Collection of Carbapenem-resistant Pseudomonas aeruginosa. Eur. J. Clin. Microbiol. Infect. Dis. 2021, 40, 2533–2541. [Google Scholar] [CrossRef]
- Tsakris, A.; Pournaras, S.; Woodford, N.; Palepou, M.F.; Babini, G.S.; Douboyas, J.; Livermore, D.M. Outbreak of infections caused by Pseudomonas aeruginosa producing VIM-1 carbapenemase in Greece. J. Clin. Microbiol. 2000, 38, 1290–1292. [Google Scholar] [CrossRef]
- Giakkoupi, P.; Vourli, S.; Polemis, M.; Kalapothaki, V.; Tzouvelekis, L.S.; Vatopoulos, A.C. Supplementation of growth media with Zn2+ facilitates detection of VIM-2-producing Pseudomonas aeruginosa. J. Clin. Microbiol. 2008, 46, 1568–1569. [Google Scholar] [CrossRef]
- Karampatakis, T.; Antachopoulos, C.; Tsakris, A.; Roilides, E. Molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa in an endemic area: Comparison with global data. Eur. J. Clin. Microbiol. Infect. Dis. 2018, 377, 1211–1220. [Google Scholar] [CrossRef] [PubMed]
- Pappa, O.; Kefala, A.M.; Tryfinopoulou, K.; Dimitriou, M.; Kostoulas, K.; Dioli, C.; Moraitou, E.; Panopoulou, M.; Vogiatzakis, E.; Mavridou, A.; et al. Molecular Epidemiology of Multi-Drug Resistant Pseudomonas aeruginosa Isolates from Hospitalized Patients in Greece. Microorganisms 2020, 8, 1652. [Google Scholar] [CrossRef] [PubMed]
- Papagiannitsis, C.C.; Verra, A.; Galani, V.; Xitsas, S.; Bitar, I.; Hrabak, J.; Petinaki, E. Unravelling the Features of Success of VIM-Producing ST111 and ST235 Pseudomonas aeruginosa in a Greek Hospital. Microorganisms 2020, 8, 1884. [Google Scholar] [CrossRef] [PubMed]
- Jovcic, B.; Lepsanovic, Z.; Suljagic, V.; Rackov, G.; Begovic, J.; Topisirovic, L.; Kojic, M. Emergence of NDM-1 metallo-β-lactamase in Pseudomonas aeruginosa clinical isolates from Serbia. Antimicrob. Agents Chemother. 2011, 55, 3929–3931. [Google Scholar] [CrossRef]
- Tafaj, S.; Gona, F.; Rodrigues, C.F.; Kapisyzi, P.; Caushi, F.; Rossen, J.W.; Cirillo, D.M. Whole-Genome Sequences of Two NDM-1-Producing Pseudomonas aeruginosa Strains Isolated in a Clinical Setting in Albania in 2018. Microbiol. Resour. Announc. 2020, 9, e01291-19. [Google Scholar] [CrossRef]
- Kabic, J.; Fortunato, G.; Vaz-Moreira, I.; Kekic, D.; Jovicevic, M.; Pesovic, J.; Ranin, L.; Opavski, N.; Manaia, C.M.; Gajic, I. Dissemination of Metallo-beta-Lactamase-Producing Pseudomonas aeruginosa in Serbian Hospital Settings: Expansion of ST235 and ST654 Clones. Int. J. Mol. Sci. 2023, 24, 1519. [Google Scholar] [CrossRef] [PubMed]
- Tsilipounidaki, K.; Gkountinoudis, C.G.; Florou, Z.; Fthenakis, G.C.; Miriagou, V.; Petinaki, E. First Detection and Molecular Characterization of Pseudomonas aeruginosa bla[NDM-1] ST308 in Greece. Microorganisms 2023, 11, 2159. [Google Scholar] [CrossRef] [PubMed]
- Strateva, T.; Keuleyan, E.; Peykov, S. Genomic insights into NDM-1-producing Pseudomonas aeruginosa: Current status in a Bulgarian tertiary hospital and on the Balkans. Acta Microbiol. Immunol. Hung. 2024, 71, 99–109. [Google Scholar] [CrossRef]
- Del Barrio-Tofiño, E.; López-Causapé, C.; Oliver, A. Pseudomonas aeruginosa epidemic high-risk clones and their association with horizontally-acquired beta-lactamases: 2020 update. Int. J. Antimicrob. Agents 2020, 56, 106196. [Google Scholar] [CrossRef]
- Kocsis, B.; Gulyás, D.; Szabó, D. Diversity and Distribution of Resistance Markers in Pseudomonas aeruginosa International High-Risk Clones. Microorganisms 2021, 9, 359. [Google Scholar] [CrossRef]
- Maltezou, H.C.; Kontopidou, F.; Dedoukou, X.; Katerelos, P.; Gourgoulis, G.M.; Tsonou, P.; Maragos, A.; Gargalianos, P.; Gikas, A.; Gogos, C.; et al. Action plan to combat infections due to carbapenem-resistant Gram-negative pathogens in acute-care hospitals in Greece. J. Glob. Antimicrob. Res. 2013, 2, 11–16. [Google Scholar] [CrossRef] [PubMed]
- Papagiannitsis, C.C.; Tryfinopoulou, K.; Giakkoupi, P.; Pappa, O.; Polemis, M.; Tzelepi, E.; Tzouvelekis, L.S.; Carbapenemase Study Group; Vatopoulos, A.C. Diversity of acquired β-lactamases amongst Klebsiella pneumoniae in Greek hospitals. Int. J. Antimicrob. Agents 2012, 39, 178–188. [Google Scholar] [CrossRef] [PubMed]
- Basset, P.; Blanc, D.S. Fast and simple epidemiological typing of Pseudomonas aeruginosa using the double-locus sequence typing [DLST] method. Eur. J. Clin. Microbiol. Infect. Dis. 2014, 33, 927–932. [Google Scholar] [CrossRef] [PubMed]
- Oliver, A.; Rojo-Molinero, E.; Arca-Suarez, J.; Beşli, Y.; Bogaerts, P.; Cantón, R.; Cimen, C.; Croughs, P.D.; Denis, O.; Giske, C.G.; et al. Pseudomonasaeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: Update from ESGARS-ESCMID/ISARPAE Group. Clin. Microbiol. Infect. 2024, 30, 469–480. [Google Scholar] [CrossRef] [PubMed]
- Oliver, A.; Mulet, X.; López-Causapé, C.; Juan, C. The increasing threat of Pseudomonas aeruginosa high-risk clones. Drug Resist. Updat. 2015, 21–22, 41–59. [Google Scholar] [CrossRef] [PubMed]
- Cholley, P.; Stojanov, M.; Hocquet, D.; Thouverez, M.; Bertrand, X.; Blanc, D.S. Comparison of double-locus sequence typing [DLST] and multilocus sequence typing [MLST] for the investigation of Pseudomonas aeruginosa populations. Diagn. Microbiol. Infect. Dis. 2015, 82, 274–277. [Google Scholar] [CrossRef]
- Magalhães, B.; Valot, B.; Abdelbary, M.M.H.; Prod’hom, G.; Greub, G.; Senn, L.; Blanc, D.S. Combining Standard Molecular Typing and Whole Genome Sequencing to Investigate Pseudomonas aeruginosa Epidemiology in Intensive Care Units. Front. Public Health 2020, 8, 3. [Google Scholar] [CrossRef]
- Recio, R.; Mancheño, M.; Viedma, E.; Villa, J.; Orellana, M.A.; Tamayo, J.L.; Chaves, F. Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence. Antimicrob. Agents Chemother. 2020, 64, e01759-19. [Google Scholar] [CrossRef]
- Kocsis, B.; Toth, A.; Gulyas, D.; Ligeti, B.; Katona, K.; Rokusz, L.; Szabo, D. Acquired qnrVC1 and blaNDM-1 resistance markers in an international high-risk Pseudomonas aeruginosa ST773 clone. J. Med. Microbiol. 2019, 68, 336–338. [Google Scholar] [CrossRef]
- Khan, A.; Shropshire, W.C.; Hanson, B.; Dinh, A.Q.; Wanger, A.; Ostrosky-Zeichner, L.; Arias, C.A.; Miller, W.R. Simultaneous Infection with Enterobacteriaceae and Pseudomonas aeruginosa Harboring Multiple Carbapenemases in a Returning Traveler Colonized with Candida auris. Antimicrob. Agents Chemother. 2020, 64, e01466-19. [Google Scholar] [CrossRef]
- Urbanowicz, P.; Izdebski, R.; Baraniak, A.; Żabicka, D.; Ziółkowski, G.; Hryniewicz, W.; Gniadkowski, M. Pseudomonas aeruginosa with NDM-1, DIM-1 and PME-1 b-lactamases, and RmtD3 16S rRNA methylase, encoded by new genomic islands. J. Antimicrob. Chemother. 2019, 74, 3117–3119. [Google Scholar] [CrossRef] [PubMed]
- Hong, J.S.; Song, W.; Park, M.J.; Jeong, S.; Lee, N.; Jeong, S.H. Molecular Characterization of the First Emerged NDM-1-Producing Pseudomonas aeruginosa Isolates in South Korea. Microb. Drug Resist. 2021, 27, 1063–1070. [Google Scholar] [CrossRef]
- Takahashi, T.; Tada, T.; Shrestha, S.; Hishinuma, T.; Sherchan, J.B.; Tohya, M.; Kirikae, T.; Sherchand, J.B. Molecular characterisation of carbapenem-resistant Pseudomonas aeruginosa clinical isolates in Nepal. J. Glob. Antimicrob. Resist. 2021, 26, 279–284. [Google Scholar] [CrossRef] [PubMed]
- Zwittink, R.D.; Wielders, C.C.; Notermans, D.W.; Verkaik, N.J.; Schoffelen, A.F.; Witteveen, S.; Ganesh, V.A.; de Haan, A.; Bos, J.; Bakker, J.; et al. Multidrug-resistant organisms in patients from Ukraine in the Netherlands, March to August 2022. Eurosurveillance 2022, 27, 2200896. [Google Scholar] [CrossRef] [PubMed]
- Mataseje, L.F.; Pitout, J.; Croxen, M.; Mulvey, M.R.; Dingle, T.C. Three separate acquisitions of bla[NDM-1] in three different bacterial species from a single patient. Eur. J. Clin. Microbiol. Infect. Dis. 2023, 42, 1275–1280. [Google Scholar] [CrossRef] [PubMed]
- Jung, H.; Pitout, J.D.D.; Matsumura, Y.; Strydom, K.A.; Kingsburgh, C.; Ehlers, M.M.; Kock, M.M. Genomic epidemiology and molecular characteristics of bla[NDM-1]-positive carbapenem-resistant Pseudomonas aeruginosa belonging to international high-risk clone ST773 in the Gauteng region, South Africa. Eur. J. Clin. Microbiol. Infect. Dis. 2024, 43, 627–640. [Google Scholar] [CrossRef]
- Daaboul, D.; Osman, M.; Kassem, I.I.; Yassine, I.; Girlich, D.; Proust, A.; Mounir, C.; Zerouali, K.; Raymond, J.; Naas, T.; et al. Neonatal sepsis due to NDM-1 and VIM-2 co-producing Pseudomonas aeruginosa in Morocco. J. Antimicrob. Chemother. 2024, 79, 1614–1618. [Google Scholar] [CrossRef]
- Hernández-García, M.; Cabello, M.; Ponce-Alonso, M.; Herrador-Gómez, P.M.; Gioia, F.; Cobo, J.; Cantón, R.; Ruiz-Garbajosa, P. First detection in Spain of NDM-1-producing Pseudomonas aeruginosa in two patients transferred from Ukraine to a university hospital. J. Glob. Antimicrob. Resist. 2024, 36, 105–111. [Google Scholar] [CrossRef]
- Abdouchakour, F.; Aujoulat, F.; Licznar-Fajardo, P.; Marchandin, H.; Toubiana, M.; Parer, S.; Lotthé, A.; Jumas-Bilak, E. Intraclonal variations of resistance and phenotype in Pseudomonas aeruginosa epidemic high-risk clone ST308: A key to success within a hospital? Int. J. Med. Microbiol. 2018, 308, 279–289. [Google Scholar] [CrossRef]
- Prakki, S.R.S.; Hon, P.Y.; Lim, Z.Q.; Thevasagayam, N.M.; Loy, S.Q.D.; De, P.P.; Marimuthu, K.; Vasoo, S.; Ng, O.T. Dissemination of Pseudomonas aeruginosa blaNDM-1-positive ST308 Clone in Singapore. Microbiol. Spectr. 2023, 11, e0403322. [Google Scholar] [CrossRef]
- Chew, K.L.; Octavia, S.; Ng, O.T.; Marimuthu, K.; Venkatachalam, I.; Cheng, B.; Lin, R.T.P.; Teo, J.W.P. Challenge of drug resistance in Pseudomonas aeruginosa: Clonal spread of NDM-1-positive ST-308 within a tertiary hospital. J. Antimicrob. Chemother. 2019, 74, 2220–2224. [Google Scholar] [CrossRef]
- Teo, J.Q.; Tang, C.Y.; Lim, J.C.; Lee, S.J.; Tan, S.H.; Koh, T.H.; Sim, J.H.; Tan, T.T.; Kwa, A.L.; Ong, R.T. Genomic characterization of carbapenem-non-susceptible Pseudomonas aeruginosa in Singapore. Emerg. Microbes Infect. 2021, 10, 1706–1716. [Google Scholar] [CrossRef] [PubMed]
- Liew, S.M.; Rajasekaram, G.; Puthucheary, S.D.; Chua, K.H. Detection of VIM-2-, IMP-1-, and NDM-1-producing multidrugresistant Pseudomonas aeruginosa in Malaysia. J. Glob. Antimicrob. Resist. 2018, 13, 271–273. [Google Scholar] [CrossRef] [PubMed]
- Polemis, M.; Mandilara, G.; Pappa, O.; Argyropoulou, A.; Perivolioti, E.; Koudoumnakis, N.; Pournaras, S.; Vasilakopoulou, A.; Vourli, S.; Katsifa, H.; et al. COVID-19 and Antimicrobial Resistance: Data from the Greek Electronic System for the Surveillance of Antimicrobial Resistance—WHONET-Greece (January 2018–March 2021). Life 2021, 11, 996. [Google Scholar] [CrossRef] [PubMed]
Patient No. | Age | Sex | Isolate No. | Hospital | Department of Hospitalization | Specimen | Date of Isolation | Days from Hospital Admission to Isolation |
---|---|---|---|---|---|---|---|---|
1 | 73 | M | 9953 | H1 | COVID-19 ICU | Blood | 17 January2022 | 30 |
2 | 63 | F | 9959 | H1 | COVID-19 ICU | BAL | 17 January 2022 | 11 |
3 | 59 | M | 9954 | H1 | COVID-19 ICU | Tissue | 3 February 2022 | 23 |
4 | 67 | F | 9955 | H1 | ICU | Blood | 2 March 2022 | 23 |
5 | 32 | M | 9956 | H1 | ICU | Wound | 8 March 2022 | 220 |
6 | 64 | F | 9957 | H1 | Neurology | Blood | 10 May 2022 | 43 |
7 | 70 | F | 9958 | H1 | Medical | Blood | 17 May 2022 | 14 |
8 | 77 | M | 9951 | H1 | COVID-19 | Urine | 22 May 2022 | 0 |
9 | 51 | F | 9960 | H1 | Neurology | Rectal swab | 7 June 2022 | 116 |
10 | 76 | F | 9962 | H1 | COVID-19 | Drainage | 8 July 2022 | 30 |
11 | 90 | M | 9963 | H1 | Medical | Urine | 22 July 2022 | 0 |
12 | 53 | M | 9964 | H1 | Neurosurgery | BAL | 23 July 2022 | 54 [Transferred from ICU to NS] |
13 | 58 | M | 9965 | H1 | Cardiology | BAL | 27 July 2022 | 0 [Transferred from ICU of another hospital] |
14 | 76 | M | 9966 | H1 | Medical | Urine | 18 August 2022 | 0 |
15 | 89 | F | 9952 | H1 | Medical | Urine | 16 September 2022 | 0 |
16 | 88 | F | 9912 | H2 | Medical | pus | 06 October 2022 | 10 |
17 | 67 | F | 10071 | H2 | Medical | pus | 12 December 2022 | 12 |
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Pappa, O.; Louka, C.; Karadimas, K.; Maikousi, E.; Tzoukmani, A.; Polemis, M.; Panopoulou, A.-D.; Daniil, I.; Chryssou, S.; Mellou, K.; et al. Emergence of NDM-1-Producing Pseudomonas aeruginosa Nosocomial Isolates in Attica Region of Greece. Microorganisms 2024, 12, 1753. https://doi.org/10.3390/microorganisms12091753
Pappa O, Louka C, Karadimas K, Maikousi E, Tzoukmani A, Polemis M, Panopoulou A-D, Daniil I, Chryssou S, Mellou K, et al. Emergence of NDM-1-Producing Pseudomonas aeruginosa Nosocomial Isolates in Attica Region of Greece. Microorganisms. 2024; 12(9):1753. https://doi.org/10.3390/microorganisms12091753
Chicago/Turabian StylePappa, Olga, Christina Louka, Kleon Karadimas, Evangelia Maikousi, Angeliki Tzoukmani, Michalis Polemis, Anna-Danai Panopoulou, Ioannis Daniil, Stella Chryssou, Kassiani Mellou, and et al. 2024. "Emergence of NDM-1-Producing Pseudomonas aeruginosa Nosocomial Isolates in Attica Region of Greece" Microorganisms 12, no. 9: 1753. https://doi.org/10.3390/microorganisms12091753
APA StylePappa, O., Louka, C., Karadimas, K., Maikousi, E., Tzoukmani, A., Polemis, M., Panopoulou, A.-D., Daniil, I., Chryssou, S., Mellou, K., Kjeldgaard, J. S., Zarkotou, O., Papagiannitsis, C., & Tryfinopoulou, K. (2024). Emergence of NDM-1-Producing Pseudomonas aeruginosa Nosocomial Isolates in Attica Region of Greece. Microorganisms, 12(9), 1753. https://doi.org/10.3390/microorganisms12091753