1. Le infezioni batteriche nel paziente oncoematologico Corrado Girmenia Ematologia, Azienda Policlinico Umberto I Sapienza University of Rome, Italy Ematologia

2. P. aeruginosa resistance (Europe, 2013) PTZ FQs AMGNEM CAZMDR EARS-NET

3. Resistance to third-generation cephalosporins (ESBL) Europe, 2013 EARS-NET Maps. Available at: www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/map_reports.aspx. Accessed November2014. EARS-NET Tables. Available at: www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/table_reports.aspx. Accessed November 2014. K. pneumoniae E. coli Overall EU trend EARS-NET 2013

4. Carbapenem-resistant Klebsiella pneumoniae – Europe 20132009 EARS-NET Percentage resistance <1% 1 to <5% 5 to <10% 10 to <25% 25 to <50% ≥50% No data reported or <10 isolates Not included

5. CPE are endemic in Italy and Greece!!!

6. www.ebmt.org/events MDR and XDR Gram negative bacteria in hematologic population

9. Pagano et al. Emerg Infect Dis 2014 57.6% mortality rate

10. Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: an Italian multicentre prospective survey Trecarichi et al CMI 2015 Prospective cohort study, nine Italian hematology wards, January 2009 to December 2012 A total of 668 bacterial isolates were recovered in 575 BBSI. Gram neg/Gram pos: 57%/43% susceptibility rates of Gram-negative bacteria were 59.1% to ceftazidime, 20.1% to ciprofloxacin, 79.1% to meropenem, 85.2% to amikacin, 69.2% to gentamicin and 69.8% to piperacillin/tazobactam. Resistance to 3rd gener. Cephalosporins: 36.9% of Enterobacteriaceae Among Klebsiella pneumoniae strains, 34.9% were carba resistant Of 66 Pseudomonas aeruginosa isolates, 69.7% were MDR 21 day mortality rate: Gram neg 16.9%, Gram pos 5.6% the mortality rate was significantly higher for BBSI caused by K. pneumoniae, P. aeruginosa, and Acinetobacter baumannii

11. 49.8% vs 74.7%; p<0.001

12. 6058 auto-SCTs (54% of all transpl.) 4389 allo_SCTs (72% of all transpl.)

15. A prospective, multicenter survey of Severe Infections by Gram Negative Bacteria in patients submitted to autologous and allogeneic stem cell transplant. (ClinicalTrials.gov, ID NCT02088840) Protocol code: SIGNB (Severe Infections by Gram Negative Bacteria) GITMO-AMCLI Survey 1 Jan 2014-31 Dec 2014 55 transplant centers Engraftment phase Follow-up at 4 months from transplant Cases enrolled: 1626 auto-SCT and 1121 allo-SCT

16. Auto-SCTAllo-SCT Total transplants16181096 No fever or infection676 (42%)281 (26%) FUO only468 (29%)374 (34%) Clin. documented infections only * 88 (5.4%) 61 (5.6%) Microb. documented infections*386 (24%)370 (34%) Gram-positive infections* 203 (12.4%)223 (20%) Gram-negative infections* 184 (11.4%) 163 (14.9%) Fungal infections* 10 (0.6%) 23 (2.1%) Viral infections* 4 (0.2%) 39 (3.6%) Preliminary data: 2714 evaluable cases *cases with one or more infections A prospective, multicenter survey of Severe Infections by Gram-Negative Bacteria in patients submitted to autologous and allogeneic SCT (ClinicalTrials.gov,ID NCT02088840)

17. Gram-negative isolates and resistance patterns: 190 isolates from Auto-SCT, 176 isolates from Allo-SCT ESC-R 54% XDR 54% A prospective, multicenter survey of Severe Infections by Gram-Negative Bacteria in patients submitted to autologous and allogeneic SCT (ClinicalTrials.gov,ID NCT02088840) No. of isolates XDR 50% ESC-R 33% Carba-R 12% ESC-R 19% Carba-R 54% ESC-R 26%

18. Correlation between colonization and infection by MDR/XDR pathogens during engrafment Auto-SCTAllo-SCT N. infections/total colonizations (%) E. coli ESC-R15/110 (14)7/78 (9) K. pneumoniae ESC-R6/34 (18)5/37 (13) K. pneumoniae Carba-R1/6 (17)16/30 (53) P. aeruginosa XDR2/13 (15)8/28 (29) A prospective, multicenter survey of Severe Infections by Gram-Negative Bacteria in patients submitted to autologous and allogeneic SCT (ClinicalTrials.gov,ID NCT02088840)

19. Age Type of donor Colonization by MDR Gram negative Pre-transplant Gram negative infection Risk factors for pre-engraftment Gram negative infections in allogeneic SCT patients

20. Mortality at 4 months from transplant % of all transplants A prospective, multicenter survey of Severe Infections by Gram-Negative Bacteria in patients submitted to autologous and allogeneic SCT (ClinicalTrials.gov,ID NCT02088840) Out of 51 allo-SCT patients who died before the engraftment in 23 cases (45%) the cause of death was a Gram negative septicemia

21. Previous allogeneic SCT N. of pre transplant chemotherapy lines Disease status at transplant Gram negative infection Variabili indipendenti correlate alla probabilità di sopravvivenza a 4 mesi dal trapianto

24. CountryYearSIRTotal N%S%I%R Austria200946300 100.0 %0.0 % Austria20105060350999.4 %0.0 %0.6 % Austria20116081161099.7 %0.2 % Austria20127275673898.5 %0.7 %0.8 % Austria201389721191098.6 %0.2 %1.2 % France2009126242126899.5 %0.3 %0.2 % France2010142831143299.7 %0.2 %0.1 % France2011163820164099.9 %0.1 %0.0 % France2012161098162799.0 %0.6 %0.5 % France20131821912184298.9 %0.5 %0.7 % Greece2009788131708162748.4 %8.1 %43.5 % Greece2010683176828168740.5 %10.4 %49.1 % Greece2011478431115163629.2 %2.6 %68.2 % Greece201254928883146037.6 %1.9 %60.5 % Greece201347912718120939.6 %1.0 %59.4 % Italy20093000430498.7 %0.0 %1.3 % Italy2010615511173184.1 %0.7 %15.2 % Italy20114331816461570.4 %2.9 %26.7 % Italy20125801924684568.6 %2.2 %29.1 % Italy201393024499145364.0 %1.7 %34.3 % Spain20095740157599.8 %0.0 %0.2 % Spain2010116100 100.0 %0.0 % Spain2011113824114499.5 %0.2 %0.3 % Spain2012113679115298.6 %0.6 %0.8 % Spain20131212920124197.7 %0.7 %1.6 % Susceptibility of Klebsiella pneumoniae Isolates to Carbapenems in Italy, France, Greece, Spain and Austria, 2009 - 2013 -

25. Crucial issues in the infection-control of CR-KP and other XDR infections: 1.Detection of carriers 2.Patients and staff coorting 3.Intrahospital strategy 4.Territorial intervention 5.Supervision by infection-control committee and health policy agencies

26. ECCMID 2013; eP698 Prospective, cross-sectional observational study of hospitalised patients colonised with carbapenemase resistant Klebsiella pneumoniae (CR-KP) M. Bartoletti et al (Bologna, IT) To compare the incidence and outcome of CR-KP infections among patient cohorts Incidence N/1000 colonization days – medicine :4.3 – Hematology: 26.3 – ICU: 13.1 – Surgical: 8.6 – SOT: 7.4 – Long Term Care: 4.7 KPC-attributable mortality – Hematology:75% – ICU:11% – SOT:7% – LTC: 5% – Medicine: 2% – Surgery:2% Medicine departments: Lowest risk of infection in CRKp colonized Lowest risk of death in CRKp infections In low risk departments CR-KP may be perceived as a clinically not relevant phenomenon. Low risk departments may represent the occult reservoir of CR-KP!!!!

27. CPE Control program starting from 2004 Local Infection Control Team was asked to report any new CPE case documented in any department of the hospital to the Central Infection Control Team For each event the LICT was asked to apply the following measures – Day 1 Nursing staff cohorting and barrier precautions Alert to the hospital administrator Stop of the transfers of the case and of contact patients to other units or to other hospitals Screening of contact patients for CPE by culturing rectal swabs – Day 2 and following days Extend CPE screening to contact patients already transferred from the involved unit at the time of index case Contact patients transferred to other units only after 3 CPE negative screening Cohorting as above for secondary cases The CICT visited all the hospitals where an outbreack occurred to help the local team to apply the programme Eurosurveillance 2014

29. 2006: several Israeli hospitals faced a clonal outbreak of CRKp that was not controlled by local measures. March 2007: the Israeli Ministry of Health launched a nationwide intervention and issued guidelines mandating – patient and staff cohorting – professional task force site visits at acute-care hospitals, evaluated infection-control policies and laboratory methods supervised adherence to the guidelines provided daily feedback on performance to hospital directors made additional interventions when and where necessary.

30. 79% relative reduction of the incidence compared with the previous year

31. Territorial Health government Interhospital Hospital Department Monitoring of MDR/XDR colonization (rectal swab). Contact-precautions Trained nursing staff Patients and staff cohorting Tailored therapeuitc strategies Multidisciplinary, interdepartment strategy Active supervision of the infect-control committee Shared interhospital infection-control strategy. Control of the patients flows Infection control strategies in SCT populations in an era of antibiotic resistance Territorial surveillance, dissemination of data Supervision of health policy agencies