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Gram negative infections in hematologic stem cell transplantation

This article discusses the frequency, mortality rate, predictive factors, and effectiveness of antimicrobial treatments for MDR/XDR-GNB in HSCT patients. It also explores the relevance of timing in treatment outcomes. The article presents data on resistance patterns and the incidence of MDR/XDR-GNB in allo- and auto-HSCT. Additionally, it highlights the risk factors for pre-engraftment infections and the importance of tailored infection control measures and new antibacterial drugs.

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Gram negative infections in hematologic stem cell transplantation

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  1. Ematologia Gram negative infections in hematologicstemcelltransplantation Corrado Girmenia Ematologia, Azienda Policlinico Umberto I Sapienza Università di Roma

  2. P.aeruginosa MDR Acinetobacterspp MDR E.coli CR E.coli ESBL K.pneumonie CR K.pneumonie ESBL

  3. Inter-regionaldiffusion, endemicity OXA48 KPC 2005 KPC 2008 E OXA48 KPC 2007 OXA48 2001 E E OXA48 E OXA48 OXA48 2010 KPC OXA48 OXA48

  4. Geographic Distribution of NDM producersBiomedRes Int. 2014;2014:249856.4

  5. Management of MDR/XDR-GNB in HSCT patients: keyissues • Is MDR/XDR-GNB frequent in HSCT patients? • Ismortality rate high in patients with MDR/XDR-GNB? • Are therefactorshighlypredictive of MDR/XDR-GNB during neutropenia? • Are currentantimicrobialtreatmentseffectiveagainst MDR/XDR-GNB? • Is timing of treatment relevant for the outcome?

  6. Management of MDR/XDR-GNB in HSCT patients: keyissues • Is MDR/XDR-GNB frequent in HSCT patients? • Ismortality rate high in patients with MDR/XDR-GNB? • Are therefactorshighlypredictive of MDR/XDR-GNB duringneutropenia? • Are currentantimicrobialtreatmentseffectiveagainstMDR/XDR-GNB? • Is timing of treatment relevant for the outcome?

  7. Gram-negative isolates and resistancepatterns: 157 isolates from Allo-SCT E.coli 5/17 (29.4%) CRKpresistantalso to Colistin No. of isolates E.coli ESBL+ 39% K.pn K.pn KPC+ 55% Other P.aer P.aer MDR 43% K.pn ESBL+ KPC- 26% Other MDR 17%

  8. ClinInfectDis 2017 Gram-negative isolates and resistancepatterns: 162 isolates from Auto-SCT E.coli No CRKpresistantalso to Colistin No. of isolates E.coli ESBL+ 29% Other K.pn K.pn ESBL+ KPC- 38% K.pn KPC+ 27% P.aer P.aer MDR 14% Other MDR 3%

  9. Incidence of ESBL+CS-GNB in allo-HSCT: • 36/149 (24%) GNBs • 36/1118 (3.2%) allo-HSCTs • Incidence of CR-GNB in allo HSCT: • 29/149 (19%) GNBs • 29/1118 (2.6%) allo-HSCTs • Overall MDR/XDR • 43.6% of GNBs • 5.8% of allo-HSCTs • Incidence of ESBL+CS-GNB in auto-HSCT: • 39/151 (25.8%) GNBs • 39/1625 (2.4%) auto-HSCTs • Incidence of CR-GNB in auto-HSCT: • 9/151 (5.9%) GNBs • 9/1625 (0.5%) auto-HSCTs • Overall MDR/XDR • 31.8% of GNBs • 3.0% of auto-HSCTs

  10. Management of MDR/XDR-GNB in HSCT patients: keyissues • Is MDR/XDR-GNB frequent in HSCT patients? • Ismortality rate high in patients with MDR/XDR-GNB? • Are therefactorshighlypredictive of MDR/XDR-GNB duringneutropenia? • Are currentantimicrobialtreatmentseffectiveagainstMDR/XDR-GNB? • Is timing of treatment relevant for the outcome?

  11. ClinInfectDis 2017 Probability of mortalityat 4 months from transplant: Multivariate analysis

  12. Management of MDR/XDR-GNB in HSCT patients: keyissues • Is MDR/XDR-GNB frequent in HSCT patients? • Ismortality rate high in patients with MDR/XDR-GNB? • Are therefactorshighlypredictive of MDR/XDR-GNB duringneutropenia? • Are currentantimicrobialtreatmentseffectiveagainstMDR/XDR-GNB? • Is timing of treatment relevant for the outcome?

  13. Pre-transplant GN infection and risk of pre-engraftmentbacteremia

  14. MDR/XDR GNB colonization and risk of pre-engraftmentbacteremia

  15. MDR/XDR GNB colonization and risk of pre-engraftmentbacteremia

  16. ClinInfectDis 2017 Riskfactors for pre-engraftmentGram negative infections Multivariate analysis

  17. Management of MDR/XDR-GNB in HSCT patients: keyissues • Is MDR/XDR-GNB frequent in HSCT patients? • Ismortality rate high in patients with MDR/XDR-GNB? • Are therefactorshighlypredictive of MDR/XDR-GNB duringneutropenia? • Are currentantimicrobialtreatmentseffectiveagainstMDR/XDR-GNB? • Is timing of treatment relevant for the outcome?

  18. Haematologica 2013; 98 (12)

  19. ClinInfectDis 2017 Gram-negative isolates and resistancepatterns: 157 isolates from Allo-SCT E.coli 5/17 (29.4%) CRKpresistantalso to Colistin No. of isolates E.coli ESBL+ 39% K.pn K.pn KPC+ 55% Other P.aer P.aer MDR 43% K.pn ESBL+ KPC- 26% Other MDR 17%

  20. Meropenem-vaborbactam • Imipenem-relebactam • Aztreonam-avibactam • Cefiderocol • Plazomicin • Eravacycline

  21. Management of MDR/XDR-GNB in HSCT patients: keyissues • Is MDR/XDR-GNB frequent in HSCT patients? • Ismortality rate high in patients with MDR/XDR-GNB? • Are therefactorshighlypredictive of MDR/XDR-GNB duringneutropenia? • Are currentantimicrobialtreatmentseffectiveagainstMDR/XDR-GNB? • Is timing of treatment relevant for the outcome?

  22. P=0.04 CRKptargetedtherapy 45% 21% No CRKptargetedtherapy

  23. Susceptibility pattern of the colonizing isolate At leasttwoactive agents Standard empiricantibiotictherapydiscouraged in patients with colonization by MDR bacteria Consideractiveempirictherapyalso in noncolonizedpatientsduring an ongoingoutbreak

  24. News in the epidemiology and outcome of MDR/XDR Gramneginfections in HSCT populations • Good news: • Tailoredinfection-control measures • New antibacterialdrugs and new antimicrobialstrategies (early, risk-basedtreatments) • Bad news: • Infection-control measuresmay be difficult to apply and recrudescence of theseinfectionsfrequentlyoccurs • Emergingresistance to new molecules • Continuousepidemiologysurveyis the keystrategythatleadsourfightagainsttheseinfectionsparticularly (butnotonly)in high riskpopulations

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