Le infezioni da patogeni MDR nel Paziente ematologico · Le infezioni da patogeni MDR nel Paziente ematologico. Corrado Girmenia. Ematologia, Azienda Policlinico Umberto I. Sapienza

Le infezioni da patogeni MDR nel Paziente ematologico

Corrado GirmeniaEmatologia, Azienda Policlinico Umberto I

Sapienza Università di Roma

IT-NON-00443-WT-06-2021

E.coliESBL

E.coliCR

K.pneumonieESBL

K.pneumonieCR

P.aeruginosaMDR Acinetobacter spp

MDR

Country Year Total N %RAustria 2009 463 0.0 %

2010 509 0.6 %2011 610 0.2 %2012 738 0.8 %2013 910 1.2 %2014 971 0.6 %2015 1022 0.8 %2016 1198 0.7 %2017 1109 1.0 %

France 2009 1268 0.2 %2010 1432 0.1 %2011 1640 0.0 %2012 1627 0.5 %2013 1842 0.7 %2014 2013 0.5 %2015 2244 0.5 %2016 2528 0.4 %2017 2807 0.7 %

Spain 2009 575 0.2 %2010 1161 0.0 %2011 1144 0.3 %2012 1152 0.8 %2013 1241 1.6 %2014 1266 2.3 %2015 1483 2.2 %2016 1677 2.1 %2017 1442 2,7 %

Resistance trend to carbapenems of Klebsiella pneumoniae Isolates in Italy, France, Greece, Spain and Austria, 2009 - 2017

Country Year Total N %RGreece 2009 1627 43.5 %

2010 1687 49.1 %2011 1636 68.2 %2012 1460 60.5 %2013 1209 59.4 %2014 1088 62.3 %2015 1185 61.9 %2016 1180 66.9 %2017 1363 64,7 %

Italy 2009 304 1.3 %2010 731 15.2 %2011 615 26.7 %2012 845 29.1 %2013 1453 34.3 %2014 1315 32.9 %2015 1999 33.5 %2016 2307 33.9 %2017 2634 29,7 %

Inter-regional diffusion, endemicity

KPC2008

KPC2007

OXA48

OXA48

OXA48

OXA48

OXA482010

OXA48

OXA48

OXA482001

KPC

E

EE

E

KPC2005

Geographic Distribution of NDM producersBiomed Res Int. 2014;2014:249856.4

Management of MDR/XDR-GNB in hematologic patients: key issues

• Is MDR/XDR-GNB frequent in hematologic patients?• Is mortality rate high in patients with MDR/XDR-

GNB?• Are there factors highly predictive of MDR/XDR-

GNB during neutropenia?• Are current antimicrobial treatments effective

against MDR/XDR-GNB?






Gram-negative isolates and resistance patterns: 157 isolates from Allo-SCT

0

10

20

30

40

50

60

70

80

90

E.coli, overall E.coli ESBLK.pneumoniae, overall K.pneumoniae ESBL no KPCK.pneumoniae KPC P.aeruginosa, overall

No.

of

isolat

es

E.coliESBL+39%

K.pn ESBL

+ KPC-26%

K.pn KPC+55%

P.aerMDR43%

OtherMDR17%

5/17 (29.4%) CRKp

resistant alsoto Colistin

E.coli

K.pnP.aer Other

Gram-negative isolates and resistance patterns: 162 isolates from Auto-SCT

0

20

40

60

80

100

120

E.coli, overall E.coli ESBLK.pneumoniae, overall K.pneumoniae ESBL no KPCK.pneumoniae KPC P.aeruginosa, overall

No.

of

isolat

es

E.coliESBL+29% K.pn

ESBL+

KPC-38%

K.pn KPC+27%

P.aerMDR14%

OtherMDR3%

No CRKpresistant also

to Colistin

E.coli

K.pnP.aer

Other

Clin Infect Dis 2017

Incidence of ESBL+CS-GNB in allo HSCT:• 36/149 (24%) GNBs• 36/1118 (3.2%) allo-HSCTsIncidence of CR-GNB in allo HSCT:• 28/149 (19%) GNBs• 28/1118 (2.5%) allo-HSCTs

Overall MDR/XDR• 43% of GNBs• 5.7% of allo-HSCTs

CMI 2015;21:337-43

E.coli CAZ-R:30%K.pneumoniae CAZ-R: 58%E.cloacae CAZ-R: 54%P.aeruginosa CAZ-R: 55%

K.pneumoniae carba-R: 35%P.aeruginosa carba-R: 71%






Probability of mortality at 4 months from transplant: Multivariate analysis

Allo-HSCT Auto-HSCT

Variable HR (95% CI), p

Variable HR (95% CI), p

Age (+10y) 1.10 (1.01-1.20) 0.03 Lymphoma vs other diseases 6.17 (2.78-1.6)<0.001

Other diseases vs acute leukemia

0.42 (0.29-0.63) <0.001 Phase of the und disease attransplant: noCR vs CR

4.8 (2.19-10.34), <0.001

Phase of the und disease attransplant: noCR vs CR

2.16 (1.47-3.15)<0.001

Pre transplant neutropenia 3.82 (1.80-8.12)0.001

Pre auto-HSCT 1.76 (1.19-2.63) 0.006 Days of pre engraftmentneutropenia (PMN<100/cmm)

1.07 (1.04-1.18)<0.001

Days of pre engraftmentneutropenia (PMN<100/cmm)

1.03(1.01-1.04) <0.001 Gram neg bacterial infection 2.43 (1.22-4.84)0.01

Acute II-IV GVHD 2.15 (1.21-3.82)0.009

Gram neg bacterial infection 2.13 (1.45-3.13)<0.001

Clin Infect Dis 2017






MDR/XDR GNB colonization and risk of pre-engraftment bacteremia






Challenging issues in the choice of antibiotic therapyin the light of MDR epidemiology in hematology

• Therapy of Carbapenem Resistant Enterobacteria infections

• Therapy of ESBL+ Enterobacteria infections

• Therapy of MDR P.aeruginosa infections

• When to start targeted antibiotic therapy: after microbiological documentationvs empirically

Haematologica 2013; 98 (12)

Isolates Ceftazidime/avibactam Ceftolozane/tazobactam

% susceptible

E.coli ESBL 100 93 - 96

K.pneumoniae ESBL 100 42 - 79

KPC + enterobacteriaceae 97 – 100 1 - 4

Merop NS P.aeruginosa 87 78 - 96

XDR P.aeruginosa 67 - 74 46

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

A risk-based algorithm in the choice of empiricantibiotic therapy (EAT) of febrile neutropenia

Febrile neutropenia

Standard risk Escalation: Conventional EAT

High-Risk of XDR-MDR GNB

ESBL colonizationor previousinfection

Escalation: Conventional EAT

+-tigecyclin

De-escalation: NEMS or CEFT-

TZB

Carba-R colonization or

previous infectionDe-escalation

COL-S: COL + other, CAZ-AVI

COL-R: CAZ-AVI + other

COL: colimicin; CAZ-AVI: ceftazidime-avibactam; CEFT-TZB: ceftolozane-tazobactam; NEMS: carbapenems; other: meropenem high dose, tigecycline, aminoglycosides, fosfomycin,

ESBL colonizationRisk of bacteremia :8%

Mortality if bacteremia: 16%:

Carba-R colonizationRisk of bacteremia :28%

Mortality if bacteremia: 60%:

IT-NON-00443-WT-06-2021

Le infezioni da patogeni MDR nel Paziente ematologico · Le infezioni da patogeni MDR nel Paziente ematologico. Corrado Girmenia. Ematologia, Azienda Policlinico Umberto I. Sapienza

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