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Dissemination of carbapenemase-producing Enterobacteriaceae in Poland

Dissemination of carbapenemase-producing Enterobacteriaceae in Poland. Marek Gniadkowski National Medicines Institute Warsaw, Poland. Sources of information. Observations by: The National Reference Centre for Susceptibility Testing (NRCST) at the NMI

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Dissemination of carbapenemase-producing Enterobacteriaceae in Poland

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  1. Dissemination of carbapenemase-producing Enterobacteriaceae in Poland Marek Gniadkowski National Medicines Institute Warsaw, Poland

  2. Sources of information • Observations by: • The National Reference Centre for Susceptibility Testing (NRCST) at the NMI • The National Consultant for Clinical Microbiology at the Ministry of Health • The Division of Clinical Microbiology and Infection Prophylaxis at the NMI • Permanent contact with medical practitioners: • clinical microbiologists, IC specialists, clinicians • Major activities: • education (courses, workshops, specialization programmes, guidelines for diagnostics, IC & rational chemotherapy) • reference diagnostics • surveillance

  3. Sources of information • Clinical microbiology laboratories: • are obliged to register alert pathogens by the parliamentary act • are not obliged to send these to the NRCST; however: • a large number of them do that routinely • many participate readily in pathogen-based survey studies • 50 laboratories at secondary reference hospitals participate in EARS-Net • At this moment no hard data on the actual frequency of carbapenemases in Enterobacteriaceae or Gram-negative non-fermenters • Mainly information based on isolates communicated to the NRCST: • certainly underestimated • but not necessarily only a „top of an iceberg”

  4. Carbapenem-resistant enterics in Poland EARS-Net: % carbapenem – non-susceptible invasive isolates www.ecdc.europa.eu

  5. Major problem: KPC The first case: May 2008, hospital in Warsaw (HW1): • K. pneumoniae with imipenem MIC = 2mg/L • patient with multiple risk factors: • no travel history • moved from another hospital (HW4) with pneumonia of unknown etiology, cured with ceftriaxone & ciprofloxacin • UTI caused by K. pneumoniae KPC+, cured with amikacin • moved to a cardiology centre HW2 • rectal swab positive at admission – full isolation, no treatment, systematic screening • after ~1 month free of K. pneumoniae KPC+ Molecular analysis (4 isolates from HW1 & HW2): - KPC-2, SHV-12, TEM-1 - ST258 - 3 plasmids, including: - blaKPC-2 + blaTEM-1, low conjugation potential - blaSHV-12, good conjugation potential Baraniak et al. 2009

  6. KPC in Poland, 2008-2009 • 2008 – 5 hospitals in Warsaw: • 3 outbreaks in HW3, HW4 & HW5 • repeated episodes in HW1 & HW2 • 32 patients confirmed at the NRCST • 33 unique isolates (3 K. oxytoca) • 2009 – regional outbreak: • 10 hospitals in Warsaw and 2 in the suburbs: • 3 endemic sites; exports to other centers • 3 outpatient clinics, dialysis units, 1 NH • 6 other cities: • 3 documented imports from Warsaw; 1 from New York; 1 totally unknown • 82 patients confirmed by the NRCST • 86 unique isolates (2 E. coli) Baraniak et al. 2011

  7. KPC in Poland, 2008-2009 Molecular analysis: clonality data K. pneumoniae (n=114): – 97.4% ST258; sporadic ST11 and ST23 – ST258 in 1 PFGE type but 28 subtypes – similarity from ~72% – variety of subtypes even in 1 hospital – some subtypes present in different sites – the same subtypes in transmission cases – New York isolate – one of the subtypes E. coli (n=2): – always with K. pneumoniae – ST93 & ST224 K. oxytoca (n=3): – indistinguishable by PFGE HW3, 2008: 9 ST258 subtypes

  8. ~200-250 ~160 ~110-130 ~70 ~50 ~48 Leavitt et al/. 2010 KPC in Poland, 2008-2009 blaKPC genes & plasmids • KPC-2 (n=117), KPC-3 (n=2): • – Tn4401a with blaKPC-2/-3 (n=118) • – Tn4401b with blaKPC-3 (n=1) ~30 plasmid profiles: – 1 - 4 plasmids of ~40 - ~350kb per profile blaKPC plasmids: – ~48kb; fingerprint A – ~50kb; fgprt B – ~70kb – ~110 - 130kb; fgprt C – ~160kb; fgprt D – ~200 - 250kb - IncR - pETKp50-like: nt (n=48; K. pn ST258, E. co) pKpQIL-like: IncFIIK+FIB; (n=68; blaKPC-2/-3; all K. pn, K. ox)

  9. KPC in Poland, 2008-2009 • Conclusions: • key role of K. pneumoniae ST258 confirmed • key role of pKpQIL-like plasmids on wide scale • possible misidentification of Inc FIIAS-like plasmids • high plasticity of pKpQIL-like plasmids • amazing microdiversity of ST258: • PFGE and blaKPC plasmid levels • problems with molecular typing data interpretation: • changes in chromosomal and/or plasmid DNA may quickly differentiate isolates during outbreak • very similar or indistinguishable isolates may arise from independent influx • superior role of clinical / epidemiological data • need of more precise typing in outbreak investigations Baraniak et al. 2011

  10. KPC in Poland, 2010-2011 • 2010: • - the highest number of cases • - spread in Warsaw & area • - new transmissions or entries to other cities in & out of the region • - new regional outbreak (St. Cross) • - endemic situations • hospital outbreaks • more outpatients 2011: - general decrease in cases - decrease in several „critical” sites in Warsaw - new cities - new regional outbreak (Podlasie)

  11. Wołomin Zielonka KPC in Poland, 2008-2011 Konstancin Gdańsk Płock Kielce New York Radom V ’08 - XI ’11 Warsaw: 19 hospitals 12 outp. clinics Olsztyn Sochaczew Dobre Pruszków Maków Maz. Przasnysz Lublin V 2008 Warszawa Otwock Grudziądz Katowice Siemianowice Chęciny Grodzisk Maz. Morawica Jędrzejów Skierniewice Wyszków Piaseczno Białystok Bielsk Podlaski Łódź Sokółka Łomża >340 cases Wysokie Maz. Pułtusk

  12. KPC in Poland, 2008-2011 UTI – urine, urinary catheter GTC – rectal swab, stool II – blood, peritoneal fluid, central line RTI – BAL, bronchial exudate, tracheal aspirate SSTI – wounds, postop. wounds, pus, etc. RTC – sputum, nasopharyngeal swab

  13. KPC in Poland, 2008-2011 • Excellent cases of successful control • the majority of hospitals have not been reporting KPC after 1-2 cases or small outbreaks • some of the highly affected hospitals observe decrease in numbers of cases • Several hospitals with no success: • endemic situations • exports to other institutions • A number of hospitals with repeated episodes: • repeated introductions? • leaks in infection control? • Increased awareness • Survey study of K. pneumoniae being done

  14. MBLs in enterics in Poland, 2006-2011 2006 – 1st case in Bydgoszcz Species: E. cloacae, n=41 S. marcescens, n=15 K. oxytoca, n=13 K. pneumoniae, n=9 E. coli, n=1 Enterobacter sp., n=1 C. freundii, n=1 Enzymes: VIM – 58 isolates IMP – 3 isolates (S. marcescens) yet unknown – 2 isolates no NDM identified yet

  15. Carbapenem-resistant enterics in Poland • Problem in progress • Majority of isolates – ESBL / AmpC + porin alterations • Major issue – KPC • Minor issue – VIM • No NDM- or OXA-48-like identified so far • Increased awareness – hope for successful control in future

  16. Anna Baraniak Katarzyna Bojarska Janusz Fiett Anna Grabowska Małgorzata Herda Radosław Izdebski Dorota Żabicka Waleria Hryniewicz All clinical microbiologists from all over the country Many thanks to:

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