Diagnóstico  

Clínico  y  Microbiológico  de  Bacteriemias

Hospital de  Pediatría  Garrahan

Bacteriemias  en  Pacientes  con  

Cáncer  y  Trasplante  de  Células  
Progenitoras  Hematopoyéticas
Dr.  Fabián  Herrera
Sección  Infectología  
CEMIC
Comisión  de  Infecciones  en  Pacientes  
Inmunocomprometidos
SADI
 Agenda
•Epidemiología  actual

•Impacto  clínico

•Factores  de  riesgo

•Tratamiento  empírico

•Conclusiones
Epidemiología  
 Etiología  de  Bacteriemias  en  pacientes  con  
cáncer.  ECIL-­
itutions caring 4:  38  centros  en  18  países  de  
both for adults and children as compared to paediatric-only centres.
Europa
aematology or
respectively).
adults, though
7 exclusively
sented haema-
T (32), alloge-
8). Six centres
y, and among
cal treatment
Data from pre-
the literature

rted from 33
eriod recorded
1 to 13 years;
d. The median Figure 1 Aetiology of bacteraemias (median prevalence with
m the respond- range) reported in the ECIL-4 questionnaire survey. Notes: CNS,
5%:15%). These coagulase negative staphylococci.
Mikulska  M.  J  Infect  2014;;68  (4):  321-­31  
¿Cuál  es  el  patógeno  resistente  que  representa  
el  mayor  problema  en  su  Unidad?

ECIL-­ 4:  38  centros  de  18  países  de  Europa

Enterobacterias  productoras  de  BLEE:     76  %

BGN  resistentes  a  Quinolonas: 46  %
P.  aeruginosa  resistente  a  Carbapenemes: 41  %
SCN  OXA  R: 38  %
EVR: 19  %
SAMR:   11  %

Mikulska  M.  J  Infect  2014;;68  (4):  321-­31  

 Antimicrobial resistance in Gram-negative rods causing bacteremia in hematopoietic stem

cell transplant patients: intercontinental prospective study of Infectious Diseases Working

Party of the European Bone Marrow Transplantation group

Avervuch  D.  Clin  Infect  Dis.  2017  Nov  13;;65(11):1819-­1828

Diana Averbuch1, Gloria Tridello2, Jennifer Hoek3, Malgorzata Mikulska4, Hamdi Akan5,
6 7 8 9
Lucrecia Yaňez San Segundo , Thomas Pabst , Tülay Özçelik , Galina Klyasova , Irene
65  centros  de  TCPH
25  países
Donnini10, Depei Wu11, Zafer Gülbas12, Tsila Zuckerman13, Aida Botelho de Sousa14, Yves
Europa,  Asia,  Australia  
Beguin15, Aliénor Xhaard16, Emmanuel Bachy17, Per Ljungman18, Rafael de la Camara19, Jelena

Rascon20, Isabel Ruiz Camps21, Antonin Vitek22, Francesca Patriarca23, Laura Cudillo24,

Radovan Vrhovac25, Peter J. Shaw26, Tom Wolfs27, Tracey O’Brien28, Batia Avni1, Gerda

Silling29, Firas Al Sabty30, Stelios Graphakos31, Marja Sankelo32, Henrik Sengeloev33, Srinivas

Pillai34, Susanne Matthes35, Frederiki Melanthiou36, Simona Iacobelli24, Jan Styczynski37, Dan

Engelhard1*, Simone Cesaro2*.

655  Episodios  de  Bacteriemia
704  aislamientos
*Equal contribution
 Perfil  de  Resistencia  en  
Enterobacterias

MDR
31,9%

AMG 32,5  %

Carba 8,4  %

BL 51,4  %

CIPRO 57,2  %

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
 Perfil  de  Resistencia  en  
Pseudomonas  aeruginosa

MDR 29,2%

AMG 26,8%

Carba 37,9%

BL
35,9%

CIPRO
30,2%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
 f
penem Susan K. tobramycin
(7%), and Seo (7%).
Results Twenty-three isolates www.elsevierhealth.com/journals/jin
were available for additi

Bacteriemias  en  Oncohematológicos:  USA

Prevalence and characteristics of CRE
testing, including 15 K. pneumoniae and four E. clo
a
strains.Transplantation-Oncology
All tested susceptible
Medicine, New York, NY,
Infectious
USA
Diseases Program,
to ceftazidime-avibac
Bacteremia due to carbapenem-resistant (MIC !4/4 mg/mL). BlaKPC was identified in 21 (91%) of t
New  York  Presbyterian  Hospital/  Weill  Cornell  Medical  
b
isolatesDivision
(16: of Pulmonary
KPC-3; and Critical
5: KPC-2). Care Medicine,
No other carbapenemWei
c
We identified 1992 BSI episodes in neutropenic patients Division of Biostatistics and Epidemiology, Weill Corne
Enterobacteriaceae in neutropenic patients
with hematologic malignancies during the study period, of
genesd were detected. Two imipenem- and meropen
Department of Pediatrics, Weill Cornell Medicine, New

Center  y  Memorial  Sloan  Kettering  Cancer  Center  

resistant
e K. pneumoniae
Department isolates& lacked
of Microbiology a carbapenem
Immunology, Weill Corn
with hematologic malignancies
which 43 (2.2%; 95% confidence interval [CI]: 1.6e2.9%)
were caused by CRE (Fig. 1). The proportion of BSIs due to
but possessed
f
Infectiousbla
outerg membrane
Diseases
Public Healthporin
and mutations
Service,
CTX-M-15
gene.
Research
in a K.Kettering
Memorial Sloan pneumoC
Institute, Rutgers New Jersey M
CRE at each hospital was 2.4% and 1.9%, respectively, and
varied from 0.8% to 3.0% by study year,
Michael J. Satlin a,*Journal,with
over time. CRE caused 4.7% of bacteremias
Ninano clear trendf
that
of Infection
Cohen
included a
, Kevin(2016)
C. Ma4xx,
Accepted
b
1e10
, 2016
July
f a c--
Available online -
€ lce Askin ,
Zivile Gedrimaite , Rosemary Soave , Gu
Liang Chen , Barry N. Kreiswirth , Thomas J. Walsh a,d,e,
g g

Susan K. Seo f
KEYWORDS Summary Objectives:
Carbapenem-resistant of bloodstream infectio
a Enterobacteriaceae; adult neutropenic patie
Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Weill Cornell
Neutropenic patients; Methods: We reviewed a
Medicine, New York, NY, USA
b Hematologic oncology centers. A cas
Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, USA
c malignancies; three controls of non-C
Division of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, NY, USA
BGN  R  Carbapenemes:  4,7%
d Bacteremia;
Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA
Results: CRE caused 43
e Prevalence;
Department of Microbiology & Immunology, Weill Cornell Medicine, New York, NY, USA Independent risk facto
Risk factors; odds ratio [aOR] 3.2
Enterobacterias R  a  Carbapenemes:  6,5%  
f
Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
g Outcomes
Public Health Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA trimethoprim-sulfameth
use, and having a prior
a median of 52 h from
Accepted 4 July 2016
Available online - - -

* Corresponding author. 1300 York Avenue, A-421, New York,

E-mail addresses: mjs9012@med.cornell.edu (M.J. Satlin), coh
org (Z. Gedrimaite), rsoave@med.cornell.edu (R. Soave), gua
KEYWORDS Summary Objectives: To determine the prevalence, risk factors, treatments, and outcome
kreiswba@njms.rutgers.edu (B.N. Kreiswirth), thw2003@med.co
Carbapenem-resistant of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) i
Enterobacteriaceae;
Neutropenic patients;
Hematologic
Bacteremia due to ca
adult neutropenic patients with hematologic malignancies.
http://dx.doi.org/10.1016/j.jinf.2016.07.002
Methods: We reviewed all BSIs between 2008 and 2012 in this population at two New York Cit
0163-4453/ª 2016 The British Infection Association. Published
oncology centers. A case-control study was conducted to identify CRE BSI risk factors, usin
malignancies; three controls of non-CRE BSIs per case.
Bacteremia;
Prevalence;
Risk factors;
Outcomes
Enterobacteriaceae in
Results: CRE caused 43 (2.2%) of Please
Independent risk factors for CREwith
cite this
1992 BSIs
BSI hematologic
article
overall andin4.7%
pressof
as:Gram-negative
Satlin MJ, et al.,bacteremia
malignancies, J Infect (2016),
were prior b-lactam/b-lactamase
odds ratio [aOR] 3.2; P Z 0.03) or carbapenem (aOR 3.0; P Z 0.05) use, curren
Bacteremia
http://dx.doi
inhibitor

trimethoprim-sulfamethoxazole (aOR 24; P Z 0.001) or glucocorticoid (aOR 5.4, P Z 0.004

(adjuste

Figure 1
with hematologic mal
use, and having a prior CRE culture (aOR 12; P Z 0.03). Patients with CRE bacteremia ha
a median of 52 h from culture collection until receipt of active therapy. They had a 51

Microbial characteristics of 1992 bloodstream infections in adult neutropenic patients from 2008 to 2012.
 1 Current epidemiology and antimicrobial resistance data for bacterial bloodstream

2 infections in patients with haematological

1. Clin Microbiol Infect.malignancies: an Italian
2015 Apr;21(4):337-43. doi: multicentre prospective
10.1016/j.cmi.2014.11.022. Epub 2014 Dec 3. Current epidemiology and
antimicrobial resistance data for bacterial bloodstream infections in
patients with hematologic malignancies: an Italian multicentre
3 survey prospective survey. Trecarichi EM(1),
1. ClinPagano L(2),Infect.
Microbiol Candoni2015A(3),Apr;21(4):337-43. doi:
Pastore D(4), Cattaneo C(5), Fanci R(6), Nosari A(7), Caira Epub
10.1016/j.cmi.2014.11.022. M(2),2014 Dec 3. Current ep
Spadea A(8), Busca A(9), Vianelliantimicrobial
N(10), Tumbarello M(11);data
resistance HeMABIS
for bacterial bloodstream
4 9  centros,  575  episodios  de  Bacteriemia.  Enero  2009  a  Diciembre  de  2012
Registry—SEIFEM Group, Italy. Author information:
patients
Clinica delle Malattie Infettive,prospective
Università survey.
(1)Istituto
with hematologic di
malignancies:
CattolicaTrecarichi
an Italian mult
del Sacro EM(1), Pagano L(2), Can

Perfil  de  resistencia:                                              

Pastore D(4), Cattaneo C(5), Fanci R(6), Nosari A(7), C
Cuore, Rome, Italy. Electronic address:
2 Spadea(2)Istituto
enricomaria.trecarichi@rm.unicatt.it.
1 A(8), Buscadi 3A(9), Vianelli N(10), Tumbarello
Ematologia, 4 M(1
5 Enrico Maria Trecarichi , Livio Pagano , Anna Candoni , Domenico Pastore , Chiara
Registry—SEIFEM
Università Cattolica del Sacro Cuore, Rome, Italy. Group, Italy. diAuthor information: (1)
(3)Clinica
Ematologia, Università di Udine, Clinica Klebsiella  pneumoniae  
delle Malattie
Udine, Italy.
Cuore, Rome,
Infettive,
(4)Ematologia
Italy. Electronic
con (n=43)
Università
address:
Cattolica
Trapianto Azienda Ospedaliero Universitaria Policlinico, Bari, Italy.
741,9%Civili,
6 Cattaneo5, Rosa Fanci , Annamaria Nosari, Morena Caira , Antonio Spadea , Alessandro Busca ,
6(5)U. O. Ematologia, Spedali 2
Brescia,
Operativa di Ematologia, Azienda Università
Italy. (6)Unità 8
enricomaria.trecarichi@rm.unicatt.it.
OspedalieraCattolica del Sacro
Universitaria
(2)Istituto di Em
Cuore, Rome, Italy. (3)C
Careggi,
9
Ematologia,e Università
Firenze, Italy. (7)Divisione di Ematologia di Udine,
Centro Trapianti Udine, Italy. (4)Emato
Midollo,
Ospedale Niguarda Ca' Trapianto Azienda Ospedaliero Universitaria Policlinico
1 Granda, Milano, Italy. (8)Ematologia, Istituto
7 Nicola Vianelli10, and Mario Tumbarello , for the HEMABIS registry – SEIFEM group, Italy.
(5)U. O. Ematologia, Spedali
Regina Elena, Roma, Italy. (9)Divisione di Ematologia, Ospedale le
34,9% Operativa di Ematologia,
Civili, Brescia, Italy. (6
Azienda Ospedaliera Universita
Molinette, Torino, Italy. (10)Istituto di Ematologia ed Oncologia
Firenze,
Clinica "Lorenzo e Ariosto Serágnoli," Italy. (7)Divisione
Ospedale, di Ematologia e Centro Tra
S. Orsola-Malpighi,
Università di Bologna, Bologna, Italy. (11)Istituto di Clinica Milano,
Ospedale Niguarda Ca' Granda, delle Italy. (8)Ematolo
8 Regina Elena, Roma, Italy. (9)Divisione
Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy. di Ematologia,
Molinette,
A prospective cohort study was conducted in Torino, Italy. (10)Istituto
nine hematology wards at di Ematologia ed
Clinica "Lorenzo e Ariosto Serágnoli," Ospedale, S. Ors
1 tertiary care centres or at university hospitals located throughout
Università di Bologna, Bologna, Italy. (11)Istituto di
9 Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy;
Italy from January 2009 to December 2012.55,8% All of the cases of
Malattie Infettive, Università Cattolica del Sacro Cuor
bacterial bloodstream infection (BBSI) occurring in adult patients
A prospective cohort study was conducted in nine hemato
with hematologic malignancies were included. A total of 668 bacterial
tertiary care centres or at university hospitals locate
2 isolates were recovered in 575 BBSI episodes. Overall, 3
10 Italy from January 2009the
Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy; Clinica di Ematologia,
to December 2012. All of the ca
susceptibility rates of Gram-negative bacteria were 59.1% to
bacterial bloodstream infection (BBSI) occurring in adu
ceftazidime, 20.1% to ciprofloxacin,
with 79.1% to meropenem,
hematologic 85.2% were
malignancies to included. A total o
amikacin, 469.2% to gentamicin andisolates
69.8% to 59,1%
piperacillin/tazobactam.
were recovered in 575 BBSI episodes. Overall,
11 Università di Udine, Italy; Ematologia con Trapianto Azienda Ospedaliero Universitaria
Resistance to third-generation cephalosporins
susceptibilitywas found
rates of in 98/265
Gram-negative bacteria were 59.
(36.9%) of Enterobacteriaceae isolates. Among Klebsiella pneumoniae
ceftazidime, 20.1% to ciprofloxacin, 79.1% to meropenem
strains, 15/43 (34.9%) were resistant to carbapenems.
amikacin, Of 66
69.2% to gentamicin and 69.8% to piperacilli
5
Pseudomonas aeruginosa isolates, Resistance
46 (69.7%) to were multidrug resistant. 6
12 Policlinico, Bari, Italy; U. O. Ematologia, Spedali Civili, Brescia, Italy; Unità Operativa di
Overall, the susceptibility rates(36.9%)
of Gram-positive
third-generation
69,8% were
bacteria
of Enterobacteriaceae
cephalosporins
97.4%
isolates.
was found
Among Klebsiell
to vancomycin and 94.2% to teicoplanin.
strains,Among
15/43the monomicrobial
(34.9%) cases to carbapenems. O
were resistant
of BBSI, the 21-day mortality rate was significantly
Pseudomonas aeruginosahigher for those
isolates, 46 (69.7%) were multid
7
13 Ematologia, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy; Divisione di Ematologia e
caused by Gram-negative bacteria Overall,
compared theto those caused by rates
susceptibility Gram- of Gram-positive bact
positive bacteria (47/278, 16.9% tovs.vancomycin
12/212, 5.6%; p < 0.001).
and 94.2% Among
to teicoplanin. Among the monom
Gram-negative bacteria, the mortality ratethe
of BBSI, was21-day
significantly
mortalityhigher
rate was significantly hi
for BBSI caused by K. pneumoniae,caused
P. aeruginosa, and Acinetobacter
by Gram-negative bacteria 8 compared to those caus
14 Centro Trapianti Midollo, Ospedale Niguarda Ca’ Granda, Milano, Italy; Ematologia, Istituto
 1 Current epidemiology and antimicrobial resistance data for bacterial bloodstream

2 infections in patients with haematological

1. Clin Microbiol Infect.malignancies: an Italian
2015 Apr;21(4):337-43. doi: multicentre prospective
10.1016/j.cmi.2014.11.022. Epub 2014 Dec 3. Current epidemiology and
antimicrobial resistance data for bacterial bloodstream infections in
patients with hematologic malignancies: an Italian multicentre
3 survey prospective survey. Trecarichi EM(1),
1. ClinPagano L(2),Infect.
Microbiol Candoni2015 A(3),Apr;21(4):337-43. doi:
Pastore D(4), Cattaneo C(5), Fanci R(6), Nosari A(7), Caira Epub
10.1016/j.cmi.2014.11.022. M(2),2014 Dec 3. Current ep
Spadea A(8), Busca A(9), Vianelliantimicrobial
N(10), Tumbarello M(11);data
resistance HeMABIS
for bacterial bloodstream
4 9  centros,  575  episodios  de  Bacteriemia.  Enero  2009  a  Diciembre  de  2012
Registry—SEIFEM Group, Italy. Author information:
patients
Clinica delle Malattie Infettive,prospective
Università survey.
(1)Istituto
with hematologic di
malignancies:
CattolicaTrecarichi
an Italian mult
del Sacro EM(1), Pagano L(2), Can

Perfil  de  resistencia:                                              

Pastore D(4), Cattaneo C(5), Fanci R(6), Nosari A(7), C
Cuore, Rome, Italy. Electronic address:
2 Spadea(2)Istituto
enricomaria.trecarichi@rm.unicatt.it.
1 A(8), Buscadi 3A(9), Vianelli N(10), Tumbarello
Ematologia, 4 M(1
5 Enrico Maria Trecarichi , Livio Pagano , Anna Candoni , Domenico Pastore , Chiara
Registry—SEIFEM
Università Cattolica del Sacro Cuore, Rome, Italy. Group, Italy. diAuthor information: (1)
(3)Clinica

AMIKA
Ematologia, Università di Udine, ClinicaPseudomonas  aeruginosa
Cuore,
delle Malattie
Udine, Italy.
Rome,
Infettive,
(4)Ematologia
Italy. Electronic
con
address:
(n=66)
Università Cattolica
Trapianto Azienda Ospedaliero Universitaria Policlinico, Bari, Italy.
734,9%Civili,
6 Cattaneo5, Rosa Fanci , Annamaria Nosari, Morena Caira , Antonio Spadea , Alessandro Busca ,
6(5)U. O. Ematologia, Spedali 2
Brescia,
Operativa di Ematologia, Azienda Università
Italy. (6)Unità 8
enricomaria.trecarichi@rm.unicatt.it.
OspedalieraCattolica del Sacro
Universitaria
(2)Istituto di Em
Cuore, Rome, Italy. (3)C
Careggi,
9
Ematologia,e Università
Firenze, Italy. (7)Divisione di Ematologia di Udine,
Centro Trapianti Udine, Italy. (4)Emato
Midollo,
Ospedale Niguarda Ca' Trapianto Azienda Ospedaliero Universitaria Policlinico
1 Granda, Milano, Italy. (8)Ematologia, Istituto
7 Nicola Vianelli10, and Mario Tumbarello , for the HEMABIS registry – SEIFEM group, Italy.
(5)U. O. Ematologia, Spedali
Regina Elena, Roma, Italy. (9)Divisione di Ematologia, Ospedale le
71,2%
Civili, Brescia, Italy. (6
MERO Operativa
Molinette, Torino, Italy. (10)Istituto di Ematologia,
di Ematologia ed Azienda Ospedaliera Universita
Oncologia
Firenze,
Clinica "Lorenzo e Ariosto Serágnoli," Italy. (7)Divisione
Ospedale, di Ematologia e Centro Tra
S. Orsola-Malpighi,
Università di Bologna, Bologna, Italy. (11)Istituto di Clinica Milano,
Ospedale Niguarda Ca' Granda, delle Italy. (8)Ematolo
8 Regina Elena, Roma, Italy.
Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.(9)Divisione di Ematologia,
Molinette,
A prospective cohort study was conducted in Torino, Italy. (10)Istituto
nine hematology wards at di Ematologia ed
Clinica "Lorenzo e Ariosto Serágnoli," Ospedale, S. Ors
tertiary care centres or at university hospitals located throughout
9 PTZ 1Istituto Università di Bologna, Bologna, Italy. (11)Istituto di
di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy;
Italy from January 2009 to December 2012.42,4% All of the cases of
Malattie Infettive, Università Cattolica del Sacro Cuor
bacterial bloodstream infection (BBSI) occurring in adult patients
A prospective cohort study was conducted in nine hemato
with hematologic malignancies were included. A total of 668 bacterial
tertiary care centres or at university hospitals locate
2 isolates were recovered in 575 BBSI episodes. Overall, 3
10 Italy from January 2009the
Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy; Clinica di Ematologia,
to December 2012. All of the ca
susceptibility rates of Gram-negative bacteria were 59.1% to
bacterial bloodstream infection (BBSI) occurring in adu
ceftazidime, 20.1% to ciprofloxacin,with 79.1% to meropenem, 85.2% were
to
CAZ hematologic malignancies included. A total o
amikacin, 469.2% to gentamicin andisolates
69.8% to54,6%
piperacillin/tazobactam.
were recovered in 575 BBSI episodes. Overall,
11 Università di Udine, Italy; Ematologia con Trapianto Azienda Ospedaliero Universitaria
Resistance to third-generation cephalosporins
susceptibilitywas found
rates of in 98/265
Gram-negative bacteria were 59.
(36.9%) of Enterobacteriaceae isolates. Among Klebsiella pneumoniae
ceftazidime, 20.1% to ciprofloxacin, 79.1% to meropenem
strains, 15/43 (34.9%) were resistant to carbapenems.
amikacin, Of 66
69.2% to gentamicin and 69.8% to piperacilli
5
Pseudomonas aeruginosa isolates, Resistance
46 (69.7%) to were multidrug resistant. 6
12 Policlinico,
CIPRO
Bari, Italy; U. O. Ematologia, Spedali Civili, Brescia, Italy; Unità Operativa di
Overall, the susceptibility rates(36.9%)
of Gram-positive
third-generation
bacteria were
of Enterobacteriaceae
cephalosporins
81,3%
97.4%
isolates.
was found
Among Klebsiell
to vancomycin and 94.2% to teicoplanin.
strains,Among
15/43the monomicrobial
(34.9%) cases to carbapenems. O
were resistant
of BBSI, the 21-day mortality rate was significantly
Pseudomonas higher
aeruginosa for those
isolates, 46 (69.7%) were multid
7
13 Ematologia, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy; Divisione di Ematologia e
caused by Gram-negative bacteria Overall,
compared theto those caused by rates
susceptibility Gram- of Gram-positive bact
0% 10% positive
20% bacteria
30% (47/278,
40% 16.9% vs.vancomycin
50% to 12/212,
60% 5.6%; p < 0.001).
70% 94.2%
and 80% Among90%
to teicoplanin. 100% the monom
Among
Gram-negative bacteria, the mortality ratethe
of BBSI, was21-day
significantly
mortalityhigherrate was significantly hi
for BBSI caused by K. pneumoniae,caused
P. aeruginosa, and Acinetobacter
by Gram-negative bacteria 8 compared to those caus
14 Centro Trapianti Midollo, Ospedale Niguarda Ca’ Granda, Milano, Italy; Ematologia, Istituto
 NTPF:  1997-­‐2017
CEMIC,  Neutropenia  Febril:  1997-­2017
Primer  evento  febril,  n:  1169 Rearte  N,  Herrera  F.  18th  ICID  2018.  Abst#  0816

Perfil  microbiológico
-­‐ Bacteriemia  (n=323):
Mayor  en  el  período  4: 27,7%  vs  27%  vs  22,4%  vs  36.7%,  p=0.002

1-­‐ SCN 1-­‐ SCN 1-­‐ SCN

2-­‐ S.  aureus 1-­‐ SCN
2-­‐ S.  aureus 2-­‐ S.  aureus
2-­‐ S.  aureus

1-­‐ E.  coli
1-­‐ E.  coli 2-­‐ Klebsiella
1-­‐ E.  coli 1-­‐ E.  coli 2-­‐ Klebsiella
2-­‐ Klebsiella 2-­‐ Klebsiella
45.1%
45.1%
42.2% 43.5%

1-­‐ PAE 1-­‐ PAE 1-­‐ PAE 1-­‐ PAE

1997-­‐2002 2003-­‐2008 2009-­‐2014 Dic  2014-­‐Oct  2017

 RESULTADOS
OMR  y  Fenotipos    en  323  Hemocultivos  
Rearte  N,  Herrera  F.  18th  ICID  2018.  Abst#  0816

p=0,001

p=0,001
p=0,001

p=0,001

p=0,13
 RESULTADOS
Perfil  de  Resistencia  ATB  en  BGN  
Rearte  N,  Herrera  F.  18th  ICID  2018.  Abst#  0816
p=0,0001

p=0,001

p=0,005
 Estudio  Multicéntrico  sobre  la  Etiología,  los  
Factores  de  Riesgo  y  la  Evolución  de  las  
Bacteriemias  por  Organismos  Multiresistentes  
en  Pacientes  con  Cáncer  o  Trasplante  de  
Células  Progenitoras  Hematopoyéticas
Herrera  F.1,  Laborde  A.2,  Jordán  R.3 ,Roccia  Rossi  I.4,  Guerrini  G.5,  Valledor  A.6,  Costantini  
P.7,  Dictar  M.8,  Nenna  A.9,  Caeiro  J.10,  Torres  D1,  González  Ibañez  M.2,  Pinoni  V.5,  
Inwinkelried E.3,  Palacios  C.4 Luck  M.7,  Racioppi  A.8,  Pasterán  F.11,  Corso  A.11,  Rapoport  
M11,  Nicola  F1,  Garcia  Damiano  M.2,  Giovanakis  M.3,Padlog  R.4,  Greco  G.6,  Bronzi  M.7,  
Valle  S.8,  Chaves  M.9,  Vilaró  M.10  ,  Carena  A. 1
Grupo  Argentino  de  Estudio  de  Bacteriemias  en  Pacientes  con  Cáncer  y  TCPH
1 CEMIC 6 Htal  Italiano  de  Buenos  Aires
2 FUNDALEU 7 Htal  Oncología  Angel  Roffo
3  Htal  Británico  de  Buenos  Aires 8 Inst.  Alexander  Fleming
4 HIGA  San  Martín  La  Plata 9  Htal  Oncología  Marie  Curie
5 HIGA  Rossi  La  Plata 10Centro  Médico  Privado  Córdoba
11ANLIS,  Malbrán
18th  ICID,  2018.  Buenos  Aires,  Argentina
Población:  Mayo  2014-­Enero  2018
• Se  incluyeron  1044 episodios  de  bacteriemias.
• Sexo  masculino:  589  (56,4%).  Edad:  53  años  (37-­64)
• Neutropenia:  681  (65,2%)  àAlto  riesgo  616  (90,5%)
• Criterios  de  Inclusión:
– Neoplasia  Hematológica:  633  (60,6%)
– TCPH:   223  (21,4%)
– Tumor  de  órgano  sólido:    187  (17,9%)
• Enfermedades  de  base:
• Leucemia  aguda:  411  (48%)
• Linfoma:   254  (29,7%)
• MM:   103  (12%)
Herrera  F.  18th  ICID,  2018.  Buenos  Aires,  Argentina
 Antecedentes  /  Factores  
Epidemiológicos
Variable n  (%)  
Quimioterapia  reciente  (1  mes  previo  al  ingreso) 727  (69,6%)
Hospitalización  mayor  a  30  días  previos  al  ingreso 523  (50,1%)
Colonización  previa  por  OMR 147  (14,1%)
Infección  previa  por  OMR 117  (11,2%)
Tratamiento  antibiótico  previo 491  (47%)
Piperacilina-­‐tazobactam 226  (21,6%)
Carbapenemes 192  (18,4%)
Profilaxis  con  fluorquinolonas   183  (17,5%)
 Características  Clínicas
Variable n  (%)   Mediana  (P25-­‐75)

Bacteriemia  con  foco  clínico 764  (73,2%)

Catéter 230  (22,2%)
Abdominal 223  (21,4%)
Respiratorio 93  (8,9%)
PPB 70  (6,7%)
Urinario 69  (6,6%)
Score  Apache  II 13  (10-­‐17)
Score  PITT  bacteriemia 0  (0-­‐2)
Fiebre 971  (93,4%)
Hipotensión 272  (26,1%)
 Características  microbiológicas
Bacilos gram  negativos:  706  (67,6%) Cocos  gram  positivos:  365  (35%)

Herrera  F.  18th  ICID  2018.  Buenos  Aires

 Perfil  de  Organismos  Multiresistentes
OMR:  441  (42,2%)
OMR

Herrera  F.  18th  ICID  2018.  Buenos  Aires,  Argentina

 Perfil  de  Resistencia:  Enterobacterias
Escherichia  coli  (n:  240) Klebsiella  spp  (n:  228)

Enterobacter spp (n:  51)

Herrera  F.18th  ICID  2018.  Buenos  Aires,  Argentina

Perfil  de  Resistencia:  BGN  No  
Fermentadores
Pseudomonas  aeruginosa  (n:  95)

Acinetobacter spp (n:  33)

Herrera  F.  18th  ICID  2018.  Buenos  Aires,  Argentina

Perfil  de  Resistencia:  Cocos  Gram  
Positivos

Herrera  F.  18th  ICID  2018.  Buenos  Aires,  Argentina

 Características  Diferenciales:                          
Neutropénicos  vs  No  Neutropénicos
Neutropénicos  (n:  289)
Mayor  Bacilos  Gram-­negativos 70,6  %  vs  54,4  % p:  0.0001
Mayor  OMR 54,3  %  vs  31,6  % p:  0.0001
Mayor  E-­BLEE 17,6  %   vs  5,3  % p:  0.0001
Mayor BGN-­MR 39,8  %  vs  14  % p:  0.0001
Mayor  R  Ciprofloxacina 43,9  %  vs  18,7% p:  0.0001
Mayor  R  Pip-­tazo 36,3 % vs  11,1 % p:  0.0001
Mayor  R  Imipenem 18,3  %  vs  7,6  % p:  0.002

No  Neutropénicos  (n:  171)

Mayor  Cocos Gram-­positivos 48,5  %  vs  31,8  % p:  0.0001
Mayor  S.  aureus 16,4  %  vs  7,3  % p:  0.002
Mayor  SAMR 7  %  vs  2,4  % p:  0.017
Mayor  S.  pneumoniae 7  % vs  0,7 % p:  0.0001
Herrera  F.  XVII  Congreso  SADI  2017.  Abst  #  OR  048
 Características  Diferenciales:
Neoplasias  Hematológicas  vs  Tumores  Sólidos  
Se  incluyeron  370 episodios  de  Bacteriemia
Neoplasia  hematológica:  291 (78,6%)  (>  Leucemia  Aguda)
Tumor  sólido:   79  (21,4%)

Tumor  sólido:
•Mayor  bacteriemias  por  Cocos  Gram-­positivos:  46.8  vs  34.4%,  p=0.04

Neoplasia  hematológica:
•Mayor  bacteriemias  por  OMR:   51.2  %  vs  21.5%,    p=0.001
•Mayor  bacteriemias  por  BGN-­MR:   35,7  %  vs  11,4  %,  p=  0.0001
•Mayor  bacteriemias  por  E-­BLEE:   15.5  %  vs  6.3%,        p=0.035  
•Mayor  Acinetobacter spp:   6,2  %  vs  0%,                  p=0.023
•Mayor  R  Ciprofloxacina:   37,8  %  vs  19  %,        p=0.002
•Mayor  R  Pip-­tazo:   31,3  %  vs  8,9  %,      p=  0.0001
•Mayor  R  Imipenem:   16,8  %  vs  3,8  %,      p=  0.003

Carena  A.  IDWeek  2016;;  New  Orleans,  USA. Abst  #  55860  

 Diferencias  según  Sitio  de  Inicio  y  
Adquisición  de  la  Infección
585  episodios  de  Bacteriemia  

Bacteriemia   Bacteriemia  Asociada   Bacteriemia  

Comunitaria al  Cuidado  de  la  Salud Nosocomial
BC BACS BN
59  (10.1  %) 130  (22.2  %) 396  (67,7%)

Carena  A.  ECCMID  2017.  Viena,  Austria.  Abst  #  630

 Perfil  Etiológico

p=  0,02
48,7  %

32,4  %
p=  0,037
25  %
p=  0,01
16,9  %
15,3  % p=  0,006
13,1  %

6,3  %
3,4  % 3,1  %
1  % 0  % 0,8  %
 Perfil  de  BGN-­MR  en  585  Bacteriemias  
según  Sitio  de  Adquisición
Feno%po y Mecanismo de Resistencia de OMR
p=  0,0001
45,00%
39,6  %
40,00%
35,00%
30,00%
p=  0,001
25,00% BC
20,00% 17,7  % BACS
12,3  % p=  0,004 p=  0,07 p=  0,031
15,00% BN
6,9  % 7,8  %
10,00%
5,1  % 5,1  % 4,8  % 4,8  %
5,00% 1,5  % 1,5  % 0,8  %
0  % 0% 0  %
0,00%
BGN-MR E-BLEE C-KPC PAE-MR Acineto-MR
Perfil  de  Resistencia  Antibiótica  
p=  0,0001

43,4  % p=  0,0001
p=  0,0001
37,1  % 35,9  %

p=  0,0001
22,9  %
19,7  %

12,3  %
11,9  % 8,5  %

5,1  % 3,4  %
3,8  %
0  %
Impacto  clínico
 Neutropenia  Febril:  Mortalidad
CEMIC:  1997-­2017
20%
17,8  % Episodios:   1169
18%
Bacteriemias:        323
16%
14%
12% Mortalidad por
9,6  % 9,85  %
10% Bacteriemia
7,05  % 10,5  %
8% Mortalidad global
7,2  %
6%
5,4  %
4%
5  %
2%
0%
1997-2002 2003-2008 2009-2014 2015-2017

81,3  % 88,9  % 90,7  % 92,6  % Alto  Riesgo

Rearte  N,  Herrera  F.  18th  ICID  2018.  Abst#  0816
 Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological
American Journal of Hematology Page 28 of 28

patients: clinical impact of carbapenem resistance in a multicentre prospective

ematol. 2016 Jul 18. doi: 10.1002/ajh.24489. [Epub ahead of
Bloodstream infections caused by Klebsiella pneumoniae in
survey
ematological patients: clinical impact of carbapenem resistance
ulticentre prospective survey. Trecarichi EM(1),AmPagano L(2),2016 Jul 18. doi: 10.1002/ajh.24489. [Epub ahead
J Hematol.
o B(3), Candoni A(4), Di Blasi R(2), Nadali G(5), print]
FianchiBloodstream
L(2), infections caused by Klebsiella pneumoniae
M(6), Sica S(2), Perriello V(7), Busca A(8), Aversa onco-hematological
F(9), Fanci patients: clinical impact of carbapenem res
Melillo L(11), Lessi F(12), Del Principe MI(13),inCattaneo a multicentre prospective survey. Trecarichi EM(1), Pagano
Martino B(3), Candoni A(4), Di Blasi R(2), Nadali G(5), Fianc
EnricoM(1);
Tumbarello Maria Trecarichi , Livio Pagano
HaematologicMalignancies , Bruno Martino , Anna Candoni , Roberta Di Blasi
Associated
Delia M(6), Sica S(2), Perriello V(7), Busca A(8), Aversa F(9)
tream Infections Surveillance (HEMABIS) registry R(10), - Sorveglianza
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85.5  %Emopatie
Surveillance (HEMABIS) , Alessandro
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atology, Policlinico Universitario Agostino Gemelli, Italy. Author information: (1)Institute of Infectious Diseas
Rome,
8
(3)Haematology, Bianchi
Busca , Franco 9
Melacrino
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Fanci Hospital,
, Lorella Reggio 11
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ia, Italy. (4)Division of Hematology and Stem Cell of Hematology, Policlinico Universitario Agostino Gemelli, Rom
Italy. (3)Haematology, Bianchi Melacrino Morelli Hospital, Reg
lantation, University Hospital of Udine, Udine, Italy.
Calabria, Italy. (4)Division of Hematology and Stem Cell
14
tion of Hematology, Department of Clinical and1 Experimental
Chiara Cattaneo , Mario Tumbarello for the Haematologic
Transplantation, Malignancies
University HospitalAssociated
of Udine, Udine, Bloodstream
Italy.
ne, University of Verona, Italy. (6)Hematology Section, (5)Section of Hematology, Department47.8  % of Clinical and Experime
ment of Emergency and Organ Transplant, University of Bari,
Medicine, University of Verona, Italy. (6)Hematology Section,
Italy. (7)Institute of Hematology, S. Maria della Misericordia
Department of Emergency and Organ Transplant, University of Ba
Infections
al, University of Surveillance
Perugia, Perugia, (HEMABIS) registry
Bari,
Italy. (8)Department – Sorveglianza
Italy.
of (7)Institute Epidemiologica
of Hematology, Infezioni
S. Maria Fungine in
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AOU Citta' dellaHospital,
SaluteUniversity
e of Perugia, Perugia, Italy. (8)Department
Scienza, Torino, Italy. (9)Hematology and BMT Unit, Azienda Hematology and Stem Cell Transplant Unit, AOU Citta' della Sa
Emopatie Maligne (SEIFEM) group, Italy.
liero-Universitaria di Parma, Parma, Italy; Department of della Scienza, Torino, Italy. (9)Hematology and BMT Unit, Azie
Ospedaliero-Universitaria di Parma, Parma, Italy; Department o
al and Experimental Medicine, Hematology and BMT Clinical Unit, and Experimental Medicine, Hematology and BMT Unit,
sity of Parma, Parma, Italy. (10)Haematology Unit, Careggi of Parma, Parma, Italy. (10)Haematology Unit, Careg
University
al and University of Florence, Florence, Italy. (11)Department
Hospital and University of Florence, Florence, Italy. (11)Depa
atology and Stem Cell Transplant Unit, IRCCS "Casa of Sollievo
Hematology and Stem Cell Transplant Unit, IRCCS "Casa Solli
Sofferenza" Hospital, San Giovanni Rotondo, Italy. della Sofferenza" Hospital, San Giovanni Rotondo, Italy.
1
partmentInstitute of Infectious
of Medicine, HaematologyDiseases,
Unit, Policlinico
University Universitario
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(12)Department Medicine,Gemelli,
HaematologyRome,Unit, Italy;University of Pa
(13)Cattedra di Ematologia, Dipartimento di Biomedicina e Italy. (13)Cattedra di Ematologia, Dipartimento di Biomedicina
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zione, Università Tor Vergata, Roma, Italy. (14)Hematology, 117
Prevenzione, 161
Università Tor Vergata, Roma, Italy. (14)Hematolo
2 Spedali Civili, Brescia, Italy. The aim of this study was to
Institute
i Civili, of Hematology,
Brescia, Italy. The aim Policlinico Universitario
of this study was to
risk Agostino
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suffering from hematolo
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from hematological
 py was defined as antimicrobial agents administered on the day after final antimicrobial susceptibility testing re
www.elsevierhealth.com/journals/jin

Bacteremia due to carbapenem-resistant

y represented as # of patients who died within 30 days/total # of patients. Medicine, New York, NY, USA
a
Transplantation-Oncology Infectious Diseases Program,

Bacteremia due to carbapenem-resistant b

Division of Pulmonary and Critical Care Medicine, Wei

Enterobacteriaceae
occus aureus: n Z 11; coagulase-negative
in neutropenic
Enterobacteriaceae in neutropenic
ceftriaxone-susceptible
patients
patients 7% for
Enterobacteriaceae,
c
d
e
Division of Biostatistics and Epidemiology, Weill Corne
Department of Pediatrics, Weill Cornell Medicine, New
Department of Microbiology & Immunology, Weill Corn

with hematologic with

Z 10; viridans group streptococci:
lity rates by pathogen were 17% for
malignancies
n Z hematologic
8). malignancies
AmpC-producing Enterobacteriaceae, 33% for P. ae
nosa, and 14% for Gram-positive bacteria. Survival an
f
g
Infectious Diseases Service, Memorial Sloan Kettering C
Public Health Research Institute, Rutgers New Jersey M

Michael J. Satlin a,*Journal of Infection

, Nina Cohen f
, Kevin(2016)
C. Ma4xx,
Accepted , 1e10
bJuly 2016
f a Available online -c--
a, Zivile Gedrimaite , Rosemary
f Soave , Gu € lce
b Askin ,
Michael J. Satlin *Liang
n:  1992   , NinaChenCohen
g
, Barry N., Kreiswirth
Kevin C. g Ma ,J. Walsh a,d,e,
, Thomas
Zivile Gedrimaite f, Susan K. Seo f Soave a, Gu
Rosemary € lce AskinKEYWORDS ,
c
p:  Summary
0.004Objectives:
g g a,d,e
Carbapenem-resistant of bloodstream infectio
p:  adult
<  0neutropenic
.001 patie
Liang Chen , Barry Transplantation-Oncology
N. Kreiswirth a , Thomas J. Walsh
Enterobacteriaceae;
Infectious Diseases Program, Division of Infectious Diseases,
Neutropenic
,
patients; Weill Cornell
Methods: We reviewed a
Susan K. Seo f Medicine, New York, NY, USA
b
Hematologic p:  oncology
<  0.001
centers. A cas
Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, USA
malignancies; three controls of non-C
c
Division of Biostatistics and Epidemiology, Weill Cornell Medicine,
Bacteremia; NY, USA
New York, Results: CRE caused 43
d
Department of Pediatrics, Weill Cornell Medicine, New York, NY,Prevalence;
USA Independent risk facto
e
Department of Microbiology & Immunology, Weill Cornell Medicine, RiskNew York, NY, USA
factors; odds ratio [aOR] 3.2
f
a Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New
Outcomes York, NY, USA trimethoprim-sulfameth
Transplantation-Oncology Infectious
g Diseases
Public Health Research Program, Division
Institute, Rutgers ofMedical
New Jersey Infectious Diseases,
School, Newark, NJ, USAWeill Cornell use, and having a prior
Medicine, New York, NY, USA a median of 52 h from
b
CRE:    AHR  
Accepted 4 July 2016
Division of Pulmonary and Critical Care Medicine,
Available online - - -
Weill 2,9  Cornell
;95  %  CMedicine,
I  1,3-­‐6,4  New
p=  0York,
.01 NY, USA
c
Division of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, NY, USA
* Corresponding author. 1300 York Avenue, A-421, New York,
d
Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA E-mail addresses: mjs9012@med.cornell.edu (M.J. Satlin), coh
e org (Z. Gedrimaite), rsoave@med.cornell.edu (R. Soave), gua
Department of Microbiology & Immunology,
KEYWORDS Weill Cornell
Summary Medicine, New
Objectives: To determine York, NY, USA
the prevalence, risk (B.N.
kreiswba@njms.rutgers.edu factors, treatments,
Kreiswirth), and outcome
thw2003@med.co

Bacteremia due to ca
f Carbapenem-resistant of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) i
Infectious Diseases Service, Memorial Sloan Kettering
Enterobacteriaceae; adult Cancer
neutropenic Center,
patients withNew York,malignancies.
hematologic NY, USA
http://dx.doi.org/10.1016/j.jinf.2016.07.002
g
Public Health Research Institute, Rutgers New Jersey Medical School, Newark, NJ,2012
Neutropenic patients; Methods: We reviewed all BSIs between 2008
0163-4453/ª and
2016 USA
The in this Infection
British population at two New
Association. York Cit
Published
Hematologic oncology centers. A case-control study was conducted to identify CRE BSI risk factors, usin
malignancies; three controls of non-CRE BSIs per case.

Accepted 4 July 2016

Available online - - -
Bacteremia;
Prevalence;
Risk factors;
Enterobacteriaceae in Please cite this article in press as: Satlin MJ, et al., Bacteremia
Results: CRE caused 43 (2.2%) of 1992 BSIs overall and 4.7% of Gram-negative bacteremia
with hematologic malignancies, J Infect (2016), http://dx.doi
Independent risk factors for CRE BSI were prior b-lactam/b-lactamase inhibitor (adjuste
odds ratio [aOR] 3.2; P Z 0.03) or carbapenem (aOR 3.0; P Z 0.05) use, curren
Outcomes trimethoprim-sulfamethoxazole (aOR 24; P Z 0.001) or glucocorticoid (aOR 5.4, P Z 0.004

with hematologic mal

use, and having a prior CRE culture (aOR 12; P Z 0.03). Patients with CRE bacteremia ha
a median of 52 h from culture collection until receipt of active therapy. They had a 51

* Corresponding author. 1300 York Avenue, A-421, New York, NY 10021, USA. Fax: þ1 212 746 8675.
Evolución  en  460  Bacteriemias  NTP  vs  No  NTP:  
Mortalidad  a  30  días

No-­‐Neutropénicos  
Sobrevida  acumulada  (%)

Neutropénicos  

p=0,225
(log  rank  test)

Score  de  APACHE  II  elevado  (>24)   3.57  (1.9-­‐6.6) 0.0001

Score  de  PITT    elevado  (>4) 3.88  (2.25-­‐6.7) 0.0001
Bacteriemia  por  OMR 2.29  (1.46-­‐3.6) 0.0001

Tiempo  (días) Carena  A.19˚  Simposio  de  la  ICHS    2016  -­ Santiago  de  Chile
Evolución  de  370  episodios  de  Bacteriemia  en  
Neoplasias  Hematológicas  vs  Tumores  Sólidos

NH
Sobrevida  acumulada  (%)

TS
p=0,017  
(log  rank  test)

Score  de  Charlson  >4 2,06  (1,04-­‐4,1) 0,03

Score  Apache  II  >24 2,69  (1,37-­‐5,27) 0,004
Score  PITT  >4 4,25  (2,3-­‐7,9) 0,001
Bacteriemia  por  OMR 2,15  (1,2-­‐3,7) 0,006

Tiempo  (días) Carena  A.  IDWeek  2016;;  New  Orleans,  USA. Abst  #  55860  
 Evolución  de  394  episodios  de  
Bacteriemia  por  Bacilos  Gram-­negativos
BGN-­‐NoMR BGN-­‐MR
Variable n:  226 n:  168 p
n  (%) n  (%)
Tratamiento  empírico  apropiado   205  (90,7%) 92  (54,8%) 0,0001
Retraso  de  TEA  (en  horas)    (mediana,  P25-­‐P75)   0 0  (0-­‐55) 0,0001
Bacteriemia  de  brecha 9  (4%) 24  (14,3%) 0,0001
Requerimiento  de  Terapia  Intensiva   43  (19%) 54  (32,1%) 0,003
Shock   43  (19%) 55  (32,7%) 0,002
Fallo  Multiorgánico   34  (15%) 45  (26,8%) 0,004
Respuesta  al  séptimo  día  de  tratamiento   170  (75,2%) 91  (54,2%) 0,0001
Mortalidad  temprana  (al  día  7)   27  (11,9%) 40  (23,8%) 0,002
Mortalidad  global  (al  día  30)   36  (15,9%) 58  (34,5%) 0,0001
Duración  de  internación  (días)    (mediana,  P25-­‐P75)   17  (8-­‐31) 31  (18-­‐43) 0,0001

Carena  A.  IDweek    2017.  San  Diego,  USA.  Abst  #  64391

 Análisis  de  supervivencia  (curva  de  Kaplan-­‐Meier)  y  mortalidad  
al  día  30  entre  BGN-­‐No  MR  (  n:  226  )  y  BGN-­‐MR (  n:  168)

BGN-­‐No  MR
Sobrevida  acumulada  (%)

BGN-­‐MR

p=0,0001
(log  rank  test)

Tiempo  (días) Carena  A.IDweek    2017.  San  Diego,  USA.  Abst  #  64391
 Bacteriemias  por  Bacilos  Gram-­negativos  
en  Neutropénicos:  476  episodios
Mortalidad  a  7  días:  19,53  %
Variable Odds  Ratio 95%  IC p

Foco  Respiratorio 3.67   1.21-­11.10 0,021

Foco  Piel  y  Partes  blandas 3.89 1.01-­14.94 0,048
Score  Charlson  >  4 2.76 1.06-­7.19 0,037
Shock 7.13 2.50-­20.33 <  0,0001
BGN  resistente  a  Meropenem 8.60 3.06-­24.14 <  0,0001

Herrera  F.  Enviado  IDWeek    2018,  San  Francisco,  USA

 Bacteriemias  por  Bacilos  Gram-­negativos  
en  Neutropénicos:  476  episodios
Mortalidad  a  30  días:26,47  %  
Variable Odds  Ratio 95%  IC p

Foco  Respiratorio 4.41 1.53-­12.73 0,006

Foco  Piel  y  Partes  blandas 3.66 1.00-­13.42 0,049
Score  Charlson  >  4 3.81 1.62-­8.91 0,002
Requerimiento  de  UTI 2.46 1.00-­6.04 0,049
Neoplasia  Refractaria 4.30 1.57-­11.78 0,005  
BGN  resistente  a  Meropenem 7.06 2.83-­17.14 <  0,0001
Shock 10.90 4.12-­29.85 <  0,0001
Herrera  F.  Enviado  IDWeek    2018,  San  Francisco,  USA
Factores  de  Riesgo
BGN-­MR:  Enterobacterias  productoras  de  BLEE,  
Enterobacterias  productoras  de  
Carbapenemasas,  P.  aeruginosa  Multiresistente
ATB  previo 1,2
Cefalosporinas  3ra  G  3,4,5,6,7
Profilaxis  con  Quinolonas  8,9
Uso  previo  de  carbapenemes13
Colonización  previa  10,12
Adquisición  nosocomial  3,11
Hospitalización  previa  6,7
Estadía  prolongada  7,8
Estadía  en  UTI  11
1  Gudiol  C.  JAC  2010
8 Lid  Ir  J  Med  Sci  2013
2 Gudiol  C.  JAC  2011 9 Rangaraj  G.  Cancer  2010
3 Huh  K.  Diag  Microbiol  Inf  Dis  2014
10 Vehreschild  T.  JAC  2014
4 Garnica  M.  Braz  J  Med  Biol  Res  2009
11 Kang  C.  Ann  Hematol  2012
5 Oliveira  A.  Bone  Marr  Transp  2007
12Alevizakos  M.  Int  J  Antimicrob  Agents  2016
6 Cornejo-­Juárez  P.  Plos  One  2012
13  Righi  E.  JAC  2017
7 Kim  S.  Ann  Hematol  2013  
 Colonización  e  Infección  por  BGN-­MR  
en  TCPH  en  Período  Temprano
n:  125
Frecuencia  de  infecciones  en  pacientes  colonizados  por  mismo  fenotipo  de  OMR

OMR Colonizados No colonizados p Tratamiento  

Empírico  
Global 40% 10% 0,005 basado  en  
BLEE 12,5% 0% 0,05 CHR:  59%  
KPC 29% 2% 0,02
PA-MR 75% 8% 0,005
Mayor  
OMR S E VPP VPN Prev frecuencia  de  
TE  apropiado
Global 82,3% 57,1% 40% 90% 25,8% (100%  vs  43%,  
BLEE 100% 54,8% 12,5% 100% 6,1% p  0,01)

KPC 66,7% 92,1% 28,6% 98,3% 4,5%

PA-MR 37,5% 98,3% 75% 91,9% 12,1%
Torres  D,  Herrera  F. XVII  Congreso  SADI  2017.  Abst  PD  040    
 Factores  de  Riesgo  para  BGN-­MR:  Multivariado
n:  394  bacteriemias  por  BGN    (  OMR:  42,6  %)
Variable OR  (95%  CI) OR  (95%  CI) p
No  ajustado Ajustado
Neoplasia  hematológica 1,6  (1,05-­‐2,4)
Enfermedad  de  reciente  diagnóstico 1,8  (1,2-­‐2,8)
Hospitalización  en  los  últimos  30  días 1,75  (1,2-­‐2,6)
Tratamiento  antibiótico  previo  (últimos  30  días) 3,6  (2,4-­‐5,4) 2,65  (1,5-­‐4,6) 0.001
Profilaxis  con  fluorquinolonas 2  (1,3-­‐3,3)
Internación  previa  en  terapia  intensiva 4,1  (1,8-­‐9,4) 2,79  (0,96-­‐8,1) 0.061
Catéter  venoso  central  previo  (últimas  2  semanas) 2,18  (1,4-­‐3,3)
Foco  mucositis  severa   4,4  (1,7-­‐11,6) 4,75  (1,6-­‐13,9) 0.005
Neutropenia 3  (1,9-­‐4,9) 2,37  (1,3-­‐4,5) 0.008
7  o  más  días  de  hospitalización  hasta  bacteriemia 5,17  (3,3-­‐8) 2,95  (1,7-­‐5,2) 0,0001
Colonización  o  aislamiento  previo  de  BGN-­‐MR 2,8  (1,6-­‐5) 2,39  (1,1-­‐5,3) 0.033
Colonización  actual  por  BGN-­‐MR 2,8  (1,4-­‐5,8)
Carena  A.  IDweek  2017  2017.  San  Diego,  USA  Abst  #  64391
Sensibilidad,  Especificidad,  VPP  y  VPN:
Punto  de  Corte  de  3  puntos.
Rendimiento  Predictivo  del  Score
Sensibilidad Especificidad VPP VPN
(IC  95  %) (IC    95  %) (IC  95  %) (IC  95  %)
58,3  % 83,2  % 72,4  % 72,6  %
(49-­67,3%) (76,7-­88,6%) (64,4-­79,2%) (67,9-­76,8% )

Rendimiento  Predictivo  del  Score:  Satisfactorio

(mediana  de  AUROC  0,78;;  IC  95%  0,73-­0,83)  
Episodios  de  Bacteriemia  con  ningún  FR  (0  puntos):  
Probabilidad  pos-­test  negativo:  6,87  %    
Episodios  de  Bacteriemia  con  ≥  3  puntos  vs  ≤  2:
OR  para  bacteriemia  por  BGN-­MR  de  6,96  (IC95%,  4-­12)
Carena  A.  IDweek  2017.  San  Diego,  USA  Abst  #  64391
 Tratamiento  Empírico  en  
Neutropénicos  de  Alto  Riesgo
¿Monoterapia  o  Tratamiento  
Combinado?
 Tratamiento  Empírico  en  Neutropenia  
Febril  de  Alto  Riesgo:  Guías
IDSA  2010 ECIL  4   SADI  2014 NCCN   AGIHO  
2013 2015 2017
Monoterapia  Elección:
Presentaciones  no  complicadas X X X X X
No  sospecha  o  confirmación  MR
ATB:  CFP/PTAZ/IMI/  MERO X X  y   X X   X  y  CAZ
CAZ
BLEE  monoterapia  IMI/  MERO X X X X

Combinado  Elección:
Sospecha  o  confirmación  MR X X X X X
Presentaciones  complicadas X X X
Neumonía Focos  de  
Hipotensión gravedad
Hipotensión
Colonización X X X X

Perfil  de  Resistencia  Local X X X X X

 Beta-lactam versus beta-lactam-aminoglyco
Beta-lactam versus beta-lactam-aminoglycoside combination
therapy in cancer patients with neutrop
therapy in cancer patients with neutropenia (Review)
This is a reprint of a Cochrane review, p
Paul M,
ed and maintained by The Cochrane Collaboration and published The Cochrane
inDickstein Library 2013,
Y, Schlesinger A, Grozinsky-Glasberg
Issue 6 S, Soar

Monoterapia
Paul M, Dickstein Y, Schlesinger A, Grozinsky-Glasberg S, Soares-Weiser K, Leibovici L
http://www.thecochranelibrary.com
71  Estudios
Tendencia  a  Menor  Mortalidad  global   1983-­2012
RR  0.87,  (95%  CI  0.75  -­ 1.02)
Sin  diferencias:  Igual  vs  diferente  β  Lactámico
Menor  Mortalidad  relacionada  Infección
RR  0.80,  (95%  CI  0.64  -­ 0.99)
Beta-lactam versus beta-lactam-aminogly
Copyright © 2013 The Cochrane Collabo

Limitaciones:
e combination therapy in cancer patients with neutropenia (Review)
. Published by John Wiley & Sons, Ltd.

•Mortalidad:  44  estudios  (62  %).  Falta  criterio  de  seguimiento  en  
algunos  estudios.
•Shock:  sólo  5  estudios,  1%  a  6%  de  la  muestra
•No  estratificaficación  por  foco  de  gravedad
•No  se  analizó  variable  OMR
 pies and haematopoietic stem cell transplants, as well as
Factors influencing mortality in neutropenic
radiotherapy ablativepatients with
doses delivered haematologic
with modern conforma-
tional techniques, have improved the long-term survival of
malignancies or solid tumours with bloodstream infection
cancer patients in recent years. Nevertheless, cytotoxic
chemotherapy remains one of the key therapeutic options, and
M. Marín1, C. Gudiol2,5, C. Ardanuy3, C. Garcia-Vidal2,5, L. Jimenez1, E. Domingo-Domenech4, F. J. Pérez6 and J. Carratalà2,5
1) Oncology Department, Institut Català d’Oncologia-ICO, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), 2) Infectious Disease Service, 3) Microbiology
Clin Microbiol Infect 2015; -: 1–8
Department, IDIBELL, Hospital Universitari
Clinical Microbiology and Infectionde© Bellvitge, 4) Hematology
2015 European Department,
Society of Clinical Institut
Microbiology Català d’Oncologia-ICO,
and Infectious Diseases. PublishedIDIBELL,
by ElsevierUniversity of Barcelona,
Ltd. All rights reserved
Barcelona, 5) Spanish Network for Research in Infectious Disease (REIPI), Instituto de Salud Carlos IIII, Madrid http://dx.doi.org/10.1016/j.cmi.2015.01.029
and 6) Clinical Research Unit, Institut Català
n:  510  episodios  
d’Oncologia-ICO, de  ofBBarcelona,
IDIBELL, University acteriemia  
Barcelona,eSpain
n  Pacientes  con  Neoplasias  Hematológicas
Factor  de  Riesgo OR  (95%  CI) OR  (95%  CI) p
No  ajustado Ajustado
Neoplasia  avanzada
Abstract 4,46  (2,2-­9,3) 8,7  (2,9-­25,7) <  0,001
Score  de  MASCC  <  21 6,7  (3,5-­12,7) 3,1  (1,3-­7,4) 0,01
The purpose of this study was to identify factors influencing mortality in neutropenic patients with haematologic malignancies or solid
Tratamiento  con  corticoides 4,0  (2,3-­6,9) 7,0  (3-­16,4) <  0.001
tumours with bloodstream infection (BSI). All episodes of BSI occurring in adult neutropenic patients with haematologic malignancies or
Bacilo  Gram-­negativo  Multiresistente 3,9  (1,9-­8,2)
solid tumours were prospectively recorded from January 2006 to 3,8  (1,2-­11,8)
December 2013. We analysed 0,019
the factors influencing mortality in both
groups of patients. We documented 602 consecutive episodes of BSI; 510 occurred in patients with haematologic malignancies and 92 in
Admisión  a  UTI 16  (8,3-­30,4) 15,2  (5,4-­42,7) <  0,001
patients with solid tumours. The overall case-fatality rates were 12% and 36%, respectively. Independent risk factors associated with a
Factor  Protector
higher case-fatality rate in patients with haematologic malignancies were: intensive care unit admission (odds ratio (OR), 15.2; 95%
confidence interval (CI), 5.4–42.7), advanced neoplasm (OR, 8.7; 95% CI, 2.9–25.7), corticosteroid therapy (OR, 7.0; 95% CI, 3–16.4),
ATB  empírico  combinado 0,3  (0,2-­0,6)
multidrug-resistant Gram-negative BSI (OR, 3.8; 95% CI, 1.2–11.8) for Supportive Care <  0,001
0,1(0,05-­0,3)
and a Multinational Association in Cancer risk
score of <21 (OR, 3.1; 95% CI, 1.3–7.4). By contrast, coagulase-negative staphylococci BSI (OR, 0.04; 95% CI, 0.004–0.5) and empirical
antibiotic combination therapy (OR, 0.1; 95% CI, 0.05–0.3) were found to be protective. Independent risk factors for overall case-fatality
rate in patients with solid tumours were: shock at presentation (OR, 14.3; 95% CI, 3.2–63.8), corticosteroid therapy (OR, 10; 95% CI,
2.3–44) and advanced neoplasm (OR, 7.8; 95% CI, 1.4–41.4). Prognostic factors identified in this study may help to detect those patients
 Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological

patients: clinical impact of carbapenem resistance in a multicentre prospective

Am J Hematol. 2016 Jul 18. doi: 10.1002/ajh.24489. [Epub ahead of
survey
print] Bloodstream infections caused by Klebsiella pneumoniae in
onco-hematological patients: clinical impact of carbapenem resistance
Am JPagano
in a multicentre prospective survey. Trecarichi EM(1), Hematol.L(2),2016 Jul 18. doi: 10.1002/ajh.24489. [Epub ahead of
print]
Martino B(3), Candoni A(4), Di Blasi R(2), Nadali G(5), Bloodstream
Fianchi L(2), infections caused by Klebsiella pneumoniae in
onco-hematological
Delia M(6), Sica S(2), Perriello V(7), Busca A(8), Aversa F(9), Fanci patients: clinical impact of carbapenem resista
n:  278 Factores  de  Riesgo  para  Mortalidad
in aCattaneo
R(10), Melillo L(11), Lessi F(12), Del Principe MI(13), multicentre prospective survey. Trecarichi EM(1), Pagano L(2
Enrico Maria Trecarichi , Livio Pagano , Bruno Martino , Anna Candoni , Roberta Di Blasi
Martino B(3), Candoni A(4), Di Blasi R(2), Nadali G(5), Fianchi L
C(14), Tumbarello M(1); HaematologicMalignancies Associated
Delia
Bloodstream Infections Surveillance (HEMABIS) registry M(6), Sica S(2), Perriello V(7), Busca A(8), Aversa F(9), Fa
- Sorveglianza
Variable
Epidemiologica Infezioni Funginein HR
R(10),
1* Emopatie Maligne(SEIFEM)
2
C(14),
95%  IC
Melillo
Tumbarello
p
group, L(11), 3Lessi F(12), Del Principe
4
M(1); HaematologicMalignancies
MI(13), Cattaneo 2
Associated
5
Italy. Author information: (1)Institute of 2Infectious 6
Diseases, 2 7
Gianpaolo Nadali , Luana Fianchi , Mario Delia , Simona Sica , Vincenzo Perriello , Alessandro
Bloodstream Infections Surveillance (HEMABIS) registry - Sorveglia
Shock  séptico 3.86
Policlinico Universitario Agostino Gemelli, Rome, Italy.
of Hematology, Policlinico Universitario Agostino Gemelli, 2.47-­6.02
(2)Institute
Epidemiologica
Rome, <  0.001
Infezioni Funginein Emopatie Maligne(SEIFEM) group,
Italy. Author
Italy. (3)Haematology, Bianchi Melacrino Morelli Hospital, Reggio information: (1)Institute of Infectious Diseases,
Insuficiencia  Respiratoria
Busca , Franco Aversa , Rosa Fanci , Lorella Melillo ,2.32
8 9 10 Policlinico
Calabria, Italy. (4)Division of Hematology and Stem Cell
of 1.45-­3.70
11
Federica Lessi
Hematology,
Transplantation, University Hospital of Udine, Udine, Italy.
, Maria Ilaria <  0.001
Universitario
Policlinico
12 Gemelli, Rome, Italy. (2)Insti
Agostino
Del Principe
Universitario Agostino Gemelli, Rome,
13

(5)Section of Hematology, Department of Clinical andItaly. (3)Haematology, Bianchi Melacrino Morelli Hospital, Reggio
Experimental
ATB  inadecuado
Medicine, University of14
Verona, Italy. (6)Hematology
1 1.87
Calabria,
Section, 1.06-­2.22 0.02
Italy. (4)Division of Hematology and Stem Cell
Chiara Cattaneo , Mario Tumbarello for the Haematologic Malignancies Associated Bloodstream
Transplantation,
Department of Emergency and Organ Transplant, University of Bari,
(5)Section of
University Hospital of Udine, Udine, Italy.
Hematology, Department of Clinical and Experimental
Klebsiella  pneumoniae  R  a  Carbapenemes 1.85
Medicine,
Hospital, University of Perugia, Perugia, Italy. (8)Department of
1.01-­3.42
Bari, Italy. (7)Institute of Hematology, S. Maria della Misericordia
University of 0.04
Verona, Italy. (6)Hematology Section,
Department of Emergency and Organ Transplant, University of Bari,
Hematology and Stem Cell Transplant Unit, AOU Citta' della Salute e
Infections Surveillance (HEMABIS) registry – Sorveglianza Epidemiologica Infezioni Fungine in
Bari, Italy. (7)Institute of Hematology, S. Maria della Misericor
della Scienza, Torino, Italy. (9)Hematology and BMT Unit, Azienda
Hospital, University of Perugia, Perugia, Italy. (8)Department of
Ospedaliero-Universitaria di Parma, Parma, Italy; Department of
Hematology and Stem Cell Transplant Unit, AOU Citta' della Salute
Factor  Protector  en  KP  R  a  Carbapenemes
Emopatie Maligne (SEIFEM) group, Italy. (  n:  161)
Clinical and Experimental Medicine, Hematology and BMT Unit,
della Scienza, Torino, Italy. (9)Hematology and BMT Unit, Azienda
University of Parma, Parma, Italy. (10)Haematology Unit, Careggi
Ospedaliero-Universitaria di Parma, Parma, Italy; Department of
Hospital and University of Florence, Florence, Italy.Clinical
(11)Department
and Experimental Medicine, Hematology and BMT Unit,
of Hematology and Stem Cell Transplant Unit, IRCCS "Casa Sollievo
ATB  combinado 0.32 University
della Sofferenza" Hospital, San Giovanni Rotondo, Italy. 0.19-­0.54 <  0.001
of Parma, Parma, Italy. (10)Haematology Unit, Careggi
Hospital and University of Florence, Florence, Italy. (11)Departme
(12)Department of Medicine, Haematology Unit, University of Padova,and Stem Cell Transplant Unit, IRCCS "Casa Sollievo
of Hematology
Italy. (13)Cattedra di Ematologia, Dipartimento di Biomedicina e
della Sofferenza" Hospital, San Giovanni Rotondo, Italy.
Prevenzione, Università Tor Vergata, Roma, Italy. (14)Hematology,
(12)Department of Medicine, Haematology Unit, University of Padova
1 Civili, Brescia, Italy. The aim of this study
Spedali was to
Italy. identify
(13)Cattedra di Ematologia, Dipartimento di Biomedicina e
Institute of Infectious Diseases, Policlinico Universitario Agostino Gemelli, Rome, Italy;
risk factors for mortality in patients suffering fromPrevenzione,
hematological Università Tor Vergata, Roma, Italy. (14)Hematology,
malignancies (HMs) with bloodstream infections (BSIs)Spedali
caused Civili,
by Brescia, Italy. The aim of this study was to iden
Klebsiella pneumoniae (KP). We conducted a prospective
riskcohort study
factors foronmortality in patients suffering from hematologica
2 in 13 Italian hematological units participating
Institute of Hematology, Policlinico Universitario Agostino Gemelli, Rome, Italy;
KP BSI in the HEMABIS
malignancies
registry-SEIFEM group. The outcome measured was deathKlebsiella
(HMs) with bloodstream infections (BSIs) caused by
within 21 pneumoniae
days (KP). We conducted a prospective cohort stud
Neutropenia:  Primer  Evento  Febril
CEMIC:  1997-­2017
Episodios:   1169
98,4% Bacteriemias:        323
93,8% 91,9%
83,8% 81,3%

67,9% p=  0,0001
60,3%

44,6%

36,2%
17,4% p=  0,0001
6,2% 3,2% 19,7%
1,6%
1,3% 8,1%

85,7  % 80,6  % 76,4  % 81,6  % p=  0,44 TEA

Rearte  N,  Herrera  F.  18th  ICID  2018.  Abst#  0816
 Tratamiento
Variable n  (%)  
TRATAMIENTO  EMPÍRICO                      MONOTERAPIA 711(68,1%)
Cefepime 52  (5%)
Piperacilina  -­‐ tazobactam 440  (42,1%)
Carbapenem 425  (40,7%)
Colistin 184  (17,6%)
Aminoglucósidos 70  (6,7%)
Vancomicina 360  (34,5%)
TRATAMIENTO  COMBINADO 333  (31,9%)
Carbapenem  +  colistin 126  (37,8%)
Carbapenem  +  amikacina 30  (9%)
Piperacilina-­‐tazobactam  +  amikacina 27  (8,1%)
Carbapenem  +  tigeciclina  +  colistin 22  (6,6%)
TRATAMIENTO  EMPÍRICO  APROPIADO 816  (78,2%)
 RESULTS
itge, Barcelona. 2Hacettepe University School of Medicine, Ankara, Turkey. 3Hospital Clínic i Provincial, Barcelona. 4Infectious Dise
nt, Ramon y Cajal Hospital, Madrid. 6Statistics Advisory Service, Institute of Biomedical Research of Bellvitge, Rovira i Virgili Uni
Impact of the inclusion of an aminoglycoside in the initial empirical antibiotic therapy on haematologic neutropenic patients
with Gram-negative bacteraemia
Aetiology in an era of widespread antimicrobial resistance (AMINOLACTAMTreatment study).and O
1,8 1,8 2 3 4 5
Royo-Cebrecos C , Gudiol C , Ayaz MC , Puerta-Alcalde P , Torres D , Martín-Dávila P , Escrihuela-Vidal F , 1
RES
Akova M 2, Cardozo C3, Herrera F4, Fortún J5, Bergas A1, Banegas A1, García-Vidal C3, Tebe C6, Pomares H7, Carratalà J1,8
enia A total of 576 microorganisms were isolated, 289 in Carbapenems were significa
.Department,the Baseline
Hospital Universitari de Bellvitge, Barcelona. 2Hacettepe University School
5Infectious monotherapy
characteristics
3
of Medicine, Ankara, Turkey. 4
Hospital Clínic i Provincial, Barcelona. Infectious Diseases Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas
group,
Diseases Department, Ramon y Cajal Hospital, andAdvisory287
Madrid. 6Statistics in the
Service, Institute of Biomedicalcombination
Research of Bellvitge, Rovira i Virgili University, 7monotherapy
ECCMID  2018;;  P0670 (65.8%
Haematology Department, Institut Català vs. 30.9%,
d’Oncologia, Barcelona. 8IDIBELL. p
an therapy group
ACKGROUND
enic
A total of 537 episodes were analysed
RESULTS A total of 576
p<0.001
the monotherap
of Combination
otic therapy for febrile neutropenia
Baseline characteristicsMonotherapy Aetiology P
therapy group
Treatment and Out
Characteristic
least one antipseudomonal ß-lactam.
therapy
ts on whether the addition of an N=272 (%) value
erse A total of 537 episodes were analysed A total N=
of 576265 (%) were isolated, 289 in
microorganisms Carbapenems were significan
may improve outcomes of neutropenic
gam-negative
a bacteraemia the monotherapy group, and 287 in the combination monotherapy (65.8% vs. 30.9%, p<0
Agein (years,
an era of median) 52 (17.2)
Combination 55.2 (15.3)
therapy group 0.025
microbial resistance. Characteristic Monotherapy P p<0.001
Male sex therapy(58.5)
159 158 (59.6) 0.852 p<0.001
N=272 (%) value
which is the most important adverse N= 265 (%)
lycosides,
Underlying
ß- may be avoided by using a
disease P= 0.22
Age (years, median) 52 (17.2) 55.2 (15.3) 0.025
n. + Acute myeloid Male sexleukaemia 159 (58.5) 94(59.6)
158 (34.6)0.852 104 (39.2) 0.26
gh-is to compare the efficacy
study
Acute
of ß- Underlying disease
lymphoblastic leukaemia 36 (13.2) 29 (10.9) 0.416
erapy with that of ß-lactam +
with Acute myeloid leukaemia 94 (34.6) 104 (39.2) 0.26 p<0.001
Non-Hodgkin
ombination therapy in the specific high- lymphoma
Acute lymphoblastic leukaemia 36 (13.2)
78 (28.7)
29 (10.9) 0.416
59 (22.3) 0.088 P= 0.22
era
aematologic neutropenic patients with myeloma
Multiple Non-Hodgkin lymphoma 78 (28.7) 19 (7) 0.088
59 (22.3) 19 (7.2) 0.934
m-negative (GN) bacteraemia in an era
Multiple myeloma 19 (7) 19 (7.2) 0.934
timicrobial resistance Other malignancies 45 (16.5) 54 (20.4) 0.252
Other malignancies 45 (16.5) 54 (20.4) 0.252
Infection/ Persistent 30-day
ComorbiditiesComorbidities 109 (40,2) 109
71 (26,8)(40,2)
0.001 71 (26,8) 0.001
METHODS Haematopoietic colonisation bacteraemia Infection/
case-30-day N
Persistent
Haematopoietic
stem cell stem celltransplant
transplant 83 (30.5) 71 (26.8)
83 (30.5)0.391 71 (26.8) by MDR0.391 fatality
colonisation bacteraemia case-
Allogeneic 5 (45.5) 18 (48.6) 0.852 by MDR
ation study: Observational,Allogeneic
retrospective 5 (45.5) 18 (48.6) organism 0.852 organism
rate fatality
rate
pective
odes of GN bacteraemia in haematologic Graft versus host disease 10 (10.9) 10 (5.6) 0.118
eutropenia. Patients Graft
tologic adequatelyversus
treated host disease
Neutropenia (<500/mm3) 181 (66.5) 10 (10.9)
245(84.5) <0.001 10 (5.6)
After 0.118adjustingandforAfter adjusting for patients’ bas
patients’ b
ß-lactam monotherapyNeutropenia MASCC index score < 21
for at least 48 hours (<500/mm3) 170 (62.5) 138 (52.1)
181 0.019
(66.5) centre, combination therapy
35 (6.1%)245(84.5) <0.001
episodes were polymocrobial, 15 (5.5%)
 Treatment and Outcomes

289 in Carbapenems were significantly more used as

bination monotherapy (65.8% vs. 30.9%, p<0.001).

p<0.001

p<0.001 P=0.92 Monotherapy

Combination
P= 0.22 therapy

Infection/ Persistent 30-day Nephrotoxicity

colonisation bacteraemia case-
by MDR fatality
organism rate

After adjusting for patients’ baseline characteristics

and centre, combination therapy was found to be
5 (5.5%)
associated with lower mortality, but it did not reach
in the
statistical significance (OR 0.64; CI 0.36-1.13,
ECCMID  2018;;  P0670
p=0.125).
 Impacto  de  la  Resistencia  Antibiótica  en  los  
Pacientes  Neutropénicos  con  Cáncer  y  Bacteriemia  
por  Pseudomonas  aeruginosa  (estudio  IRONIC)
Gudiol C,  Royo-­Cebrecos C, Ruiz-­Camps  I,  Puerta-­Alcalde  P,  Ayaz  MC,  Montejo  M,  
Herrera  F,  Martín-­Dávila  P,  del  Pozo  JL,  Manzur  A,  Marquez  I,  Escrihuela-­Vidal F,  
Aguilar-­Company  J,  Garcia-­Vidal  C,  Akova  M,  López-­Soria  L,  Torres  D,  Fortún  J,  
Sangro  P,  Carratalà  J.  

• Estudio  multicéntrico,  internacional  y  retrospectivo  

• Periodo  de  estudio:  Enero  2006-­ Agosto  2017
• Episodios  de  bacteriemia  por  P.  aeruginosa  en  pacientes  
neutropénicos  con  cáncer

XXII  Congreso  SEIMC  2018.  Bilbao,  España.  Abst  #  088

 357  
Tratamiento antibiótico y evolución episodios Tto combinado vs monoterapia
No.  (%)
Tratamiento antibiótico inicial Adecuado:  98.9%  vs  78.3%,  p=0.0001  
46  (12,9)
inadecuado Mortalidad  D  30  :  28.8%  vs  41.7%,  p=0.006
Tratamiento  antibiótico  inicial   184  (43,4)
combinado
Ingreso  en  UCI 114  (26,6)

Bacteriemia  persistente 21  (5,2) PAE MR vs no MR

Recaída  de  la  bacteriemia   14  (3,3)
Mortalidad  global  (30  días) 156  (36,4)
Mortalidad  precoz  (7  días) 98  (22,8)
Bacteriemia persistente: 10.4% vs 3.5%
Recaída: 8% vs 1.9%
Mortalidad global 52% vs 31.6%
Tratamiento  Empírico  y  Definitivo  para  
Bacteriemias    por  Escherichia  coli  y  
Klebsiella spp.  Productoras  de  BLEE:

¿Podemos  Utilizar  Piperacilina/  

tazobactam  en  Lugar  de    
Carbapenemes?
 50

Global prevalence of carbapenem resistance in neutropenic patients

Resistance (%)
40

and association
30 with mortality and carbapenem use: systematic
20 review and meta-analysis
10
Elda Righi1,2*, Anna Maria Peri2,3, Patrick N. A. Harris2, Alexander M. Wailan2, Mariana Liborio4,
0 Steven W. Lane5-7 and David L. Paterson2
Carbapenems Piperacillin/ Amikacin Fluoroquinolones Ceftazidime
tazobactam
J   A ntimicrob  
Hospital, C hemother.   2017   Mar   1of
;72(3):668-­‐677
1
Infectious Diseases Division, Santa Maria della Misericordia University Udine, Italy; 2The University Queensland, UQ Centre
Figure 3.
for Clinical Research (UQCCR), Brisbane, Australia; Department of Clinical and Biomedical Sciences Luigi Sacco,among
Percentages of resistance to carbapenems, piperacillin/tazobactam,
3 amikacin, fluoroquinolones and ceftazidime GNB and
III Division of
Pseudomonas spp. (expressed as percentage of all Pseudomonas
4 isolates) from BSIs in neutropenic patients. 5
Infectious Diseases, University of Milan, Milan, Italy; School of Medicine, Universidade de Fortaleza (UNIFOR), Fortaleza, Brazil; QIMR
Berghofer Medical Research Institute, Brisbane, Australia; 6Department of Haematology, Royal Brisbane and Women’s Hospital,
Brisbane, Australia; 7School of Medicine, University of Queensland, Australia
Study OR (95% CI) % Weight
Andria 2015
*Corresponding 4.69 (2.91,
author. Tel: þ61-(0)-733466072; Fax þ61-(0)-733465595; E-mail: 7.57) 72.3
elda.righi@libero.it
Moghnieh 2015 7.73 (1.50, 39.89) 6.2
Received 3 August
Kim 20082016; returned 8 September 2016; revised 21 September 2016;
2.88accepted 26 September
(1.02, 8.13) 15.4 2016
Mudau 2013 7.78 (1.52, 39.75) 6.2
Background: Carbapenem-resistant Gram-negative bacteria are recognized as a cause of difficult-to-treat infec-
tions associated with high mortality.
Overall 4.63 (3.08, 6.96) 100.0
Objectives: To perform2 a systematic review of currently available data on distribution, characteristics and out-
Q=1.57, P =0.67, I =0% NOTE: Weights are from
come associated with carbapenem-resistant bloodstream infections in adult neutropenic patients.
random-effects analysis
– 40 – 20 0 20 40
Methods: Included studies were identified through Medline, Embase and Cochrane databases between January
Figure 4.1995
Forestand
plotApril
of the2016. Random
association effect meta-analysis
of carbapenem resistance with was usedcarbapenem
previous to quantifyexposure.
the association betweenstudy-specific
Squares represent carbapenem estimates
resistance and mortality and between carbapenem exposure and resistance.
(size of the square reflects the study-specific statistical weight, i.e. the inverse of the variance), horizontal lines represent 95% CI and diamonds repre-
sent summary estimates with corresponding 95% CI.
Results: A total of 30 studies from 21 countries were included. Overall carbapenem resistance varied from 2% to
53% (median 9%) among studies. Infections due to carbapenem-resistant Pseudomonas spp. were reported in
18 (60%) studies Study OR (95% CI)
showing high median resistance rates (44% of all carbapenem-resistant % Weight
Gram-negatives and
19% of Pseudomonas isolates). Resistance of Enterobacteriaceae was less commonly reported and bloodstream
Andria 2015 4.76 (2.90, 7.80) 63.7
infections due to carbapenem-resistant
Trecarichi 2015 Klebsiella spp. were mainly documented from endemic
4.86 (0.94, 25.08) areas (Greece,
5.8
Italy, Israel). Carbapenem
Gedik 2014 resistance in Acinetobacter spp. was reported in 95.67
(30%) studies
(0.98, 32.62) (median
5.1 resistance
βL-­IβL  en  Tratamiento  de  Bacteriemias  
por  E-­BLEE:  Mortalidad
Análisis  post-­hoc  6  estudios  prospectivos  (βL-­IβL  vs  carbapenem)1
Empírico  (103): HR  1.14;;  95%  CI,  0.29-­4.40 p:  0.84
Definitivo  (  174): HR  0.76;;  95%  CI,  0.28-­2.07 p:  0.5
>  Focos  urinario  y  biliar
Correlato  con  CIM:    ≤  a  4  μ/ml

Pip-­tazo  (39):  focos  no  urinarios  <  Mortalidad  con  CIM  ≤  2  μ/ml  2

Pip-­taz  vs  Carbapenemes  (151):    OR  1.00,  95%  CI;;  0.45–2.17  3

<  OMR  e  inf  fúngicas:  7.4  vs  24.5%  (p:  <  0.01)

1Rodriguez-­Baño  J.  Clin  Infect  Dis  2012;;  54:  167-­74

2Retamar  P.  Antimicrob  Agents  Chemother  2013;;  57:  3402-­04
3Ming  Ng  T.  Plos  One  2016;;  11  (4):  e  0153696
1 β-Lactam/β-lactamase inhibitor combinations for the treatment of bloodstream

2 infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae: a

3 multinational, pre-registered cohort study.

Gutiérrez-­‐Gutiérrez  B.   Antimicrob  Agents  Chemother.  2016  Jun  20;60(7):4159-­‐69

Cohorte  internacional  retrospectiva.  Bacteriemias  por  E-­‐BLEE  y  EPC.  2004-­‐103

4

1 1 1
5 Authors: Belén
n:  365Gutiérrez-Gutiérrez, Salvador Pérez-Galera,
n:  601Elena Salamanca,
1 2
6 Pacientes  
Marina de Cueto, con  Calbo
Esther cáncer:   34  % Almirante,3 Pierluigi Viale,4 Antonio Oliver,5
, Benito

7 Vicente Pintado,6 Oriol Gasch,7 Luis Martínez-Martínez,8 Johann Pitout,9 Murat

8 Akova,10 Carmen Peña,11 José Molina,1 Alicia Hernández,Pacientes  

12
Mario Venditti, 13
Nuria
con  cáncer:   41  %

9 Prim,14 Julia Origüen,15

German Bou, 16
p=  0.6  log-­‐rank  test Evelina Tacconelli,17
Mario 18
p=  0.28  log-­‐rank  tAxel
Tumbarello, est
10 Hamprecht,19 Helen Giamarellou,20 Manel Almela,21 Federico Pérez,22 Mitchell J.

11 Schwaber,23 Joaquín Bermejo,24 Warren Lowman,25 Po-Ren Hsueh,26 Marta Mora-

12 Rillo,27 Clara Natera,28 Maria Souli,29 Robert A. Bonomo,22,30 Yehuda Carmeli,23 David
Mortalidad  comparable  según:  foco,  shock,  agente  etiológico  o  región
31 1,32 1,33
Empiric Therapy With Carbapenem-Sparing Regimens
for Bloodstream Infections due to Extended-Spectrum
Received 30 March 2017; editorial decision 16 June 2017; accepted
online August 19, 2017.
β-Lactamase–Producing Enterobacteriaceae: Results From
Members of the REIPI/ESGBIS/INCREMENT Group are listed in the
Correspondence: J. Rodríguez-Baño, Unidad de Gestión Clínica de En
a

the INCREMENT Cohort y Microbiología, Hospital Universitario Virgen Macarena, Avda Dr. Fed
Spain (jesusrb@us.es).
Zaira Raquel Palacios-Baena,1 Belén Gutiérrez-Gutiérrez,1 Esther Calbo,2 Benito Almirante,3 Pierluigi
Clinical Viale, 4
Antonio
Infectious Oliver,5 Vicente
Diseases ® Pintado,6 Oriol
2017;65(10):1615–23
Gasch,7 Luis Martínez-Martínez,8 Johann Pitout,9 Murat Akova,10 Carmen Peña,11 José Molina Gil-Bermejo,1 Alicia Hernández,12 Mario Venditti,13 Nuria
© The Author 2017. Published by Oxford University Press for the Infec
Prim,14 German Bou,15 Evelina Tacconelli,16 Mario Tumbarello,17 Axel Hamprecht,18 Helen Giamarellou,19 Manel Almela,20 Federico Pérez,21
of America. All rights reserved. For permissions, e-mail: journals.
Mitchell J. Schwaber,22 Joaquín Bermejo,23 Warren Lowman,24 Po-Ren Hsueh,25 José Ramón Paño-Pardo,26 Julián Torre-Cisneros,27 Maria Souli,28
29 22 30 1
Robert A. Bonomo, Yehuda Carmeli, David L. Paterson, Álvaro Pascual, and Jesús Rodríguez-BañoDOI: 10.1093/cid/cix606
1
; for the Spanish Network for Research in
of treatment
Infectious Diseases (REIPI)/European Study Group of Bloodstream Infections and Sepsis (ESGBIS)/INCREMENT Groupa
with aminoglycosides was 4  day
1 Mortality among patients treated with aminogl
Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología/Instituto de Biomedicina de Sevilla/Hospital Universitario Virgen Macarena/Universidad de Sevilla, and 2Hospital
Universitari Mútua de Terrassa, Universitat Internacional de Catalunya and 3Hospital Vall d’Hebrón, Barcelona, Spain; 4Teaching Hospital Policlinico S. Orsola Malpighi, Bologna, Italy; 5Hospital
only active drug was 21.9% (9/41); the differenc
Universitario Son Espases, Mallorca, 6Hospital Ramón y Cajal, Madrid, 7Hospital Parc Taulí, Barcelona, and 8Hospital Universitario M. de Valdecilla-IDIVAL, Santander, Spain; 9University of
enems was 1.5% (95% CI, –9.8 to 16.9), and the a
Calgary, Alberta, Canada; 10Hacettepe University School of Medicine, Ankara, Turkey; 11Hospital Bellvitge, Barcelona, and 12Hospital Virgen de la Arrixaca, Murcia, Spain; 13Policlinico Umberto
I, Rome, Italy; 14Hospital de la Santa Creu i Sant Pau, Barcelona, and 15Complejo Hospitalario Universitario A Coruña, Spain; 16Tübingen University Hospital and DZIF Partner Center, Germany;
17
Catholic University of the Sacred Heart, Rome, Italy; 18Institut für Mikrobiologie, Immunologie und mortality was 1.05 (95% CI, .51–2.16; P = .88).
Hygiene, Universitätsklinikum
Downloaded Köln, Cologne, Germany; 19Hygeia General Hospital, Athens,
from https://academic.oup.com/cid/article-abstract/6
Greece; 20Hospital Clinic, Barcelona, Spain; 21Louis Stokes Cleveland Veteran Affairs Medical Center,
by Case Duke Medical
Western CenterOhio;
Reserve University, 22
Library user Medical Center, National Center
Tel Aviv Sourasky
on Hospital
for Infection Control, Israel Ministry of Health, and Sackler Faculty of Medicine, Tel Aviv University; 23 26 February 2018
Español, Rosario, 24
Argentina; Wits Donald Gordon Medical Centre, Johannesburg,
South Africa; 25National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei; 26Hospital La Paz, Madrid, and 27Maimonides Biomedical Research Institute of Córdoba,
Unidades de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Reina Sofia University Hospital and University DISCUSSION
of Córdoba, Spain; 28National and Kapodistrian University of Athens,
29
Cohorte  con  Score  
School of Medicine, University General Hospital Attikon, Greece; Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center and Departments of Medicine, Pharmacology,

Australia
Cohorte  total
Biochemistry, and Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Ohio; and 30University of Queensland Centre for Clinical Research, Herston, Brisbane,
In this study,mortalidad  BLEE  ≥  11
we were unable to demonstrate tha
apy with OAD among patients with BSIs due
Background. There is little information about the efficacy of active alternative drugs to carbapenems except β-lactam/β-lactamase
associated
inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum with worse outcomes
β-lactamase–producing in terms of mo
Enterobacteriaceae
(ESBL-E). The objective of this study was to assess the outcomes of patients withfailure,
BSI dueortolength
ESBL-E of
whostay thanempiric
received carbapenems
therapy after
with such drugs (other active drugs [OADs]) or carbapenems.
confounders. Although these results cannot be
Methods. A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with
OADs or carbapenems was performed. Cox regression including a propensity that score carbapenems andwasOADs
for receiving OADs are equally
performed to analyzeeffective
30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed.
limited statistical power of the study, this is, to o
Results. Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were
AMV:  A
aminoglycosides the biggest
with OADsstudy
TB  activo  no  Carbapenem:  HR  0.75  (95%  CI  0.38-­1.48)  p=  0,42
(43 patients) and fluoroquinolones (20 patients). Empiric therapy was notproviding comparative
associated with mortality info
OADs, and
(hazard ratio [HR], 0.75; 95% confidence interval [CI], .38–1.48) in the Cox regression we Propensity
analysis. would have expectedpairs,
score–matched at least a
Comparison Between Carbapenems and β-Lactam/β-
Lactamase Inhibitors in the Treatment for Bloodstream
Infections Caused by Extended-Spectrum β-Lactamase-
Producing Enterobacteriaceae: A Systematic Review and
Meta-Analysis
Maged Muhammed, Myrto Eleni Flokas, Marios Detsis, Michail Alevizakos, and Eleftherios Mylonakis

Open  Forum  Infect  Dis.  2017  May  16;4(2):ofx099.

Infectious Diseases Division, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence

Background. Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum
β-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapen-
Study Enterobacteriaceae development.
em-resistant Events, Events, %

Methods.
ID RR  de  Mortalidad  con  Tratamiento  Empírico
We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking
RR (95% CI) for studies that
Treatment reported
Control Weight
mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or β-lactam/β-lactamase inhibitors (BL/BLIs).
Results. Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/
Gutiérrez-Gutiérrez et al (2009) 1.13 (0.74, 1.74) 39/195 30/170 30.83
BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of
patientsChaubey
with ESBL-PE
et al (2004) BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared
0.12 (0.01, 1.91) with those that
0/10 6/16received
4.91
2
empiric Cheng
BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83–1.37;
et al (2006) 2.63 (0.18, I38.30)
= 20.7%;
10/39P = .241).
0/4 In addi-
0.85
tion, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%)
Gudiol et al (2007) 0.80 (0.21, 3.05) 2/5 3/6 2.62
received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25–1.52; I2 =
84.6%; PKang
< .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI 1.21
et al (2009)
due(0.59,
to ESBL-Escherichia
2.47) 21/78
coli was10.53
8/36
not
2
associated
Lee with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491–2.095;
et al (2005) I =17.43)
2.17 (0.27, P = .046),1/13
62.5%; 4/24 compared
1.25
with theMetan
use of empiric carbapenems.
et al (2005) 0.45 (0.21, 0.96) 7/22 5/7 7.30
Conclusions. These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents
Ng et al (2012) 0.97 (0.59, 1.59) 17/57 29/94 21.06
for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.
Keywords.
Qureshi et alβ-lactam/β-lactamase
(2007) inhibitor (BL/BLIs); bloodstream infection (BSI); carbapenems; extended-spectrum
0.19 (0.01, 3.75) 0/8 1/4 β-lacta-
1.85

mase (ESBL).
Rodriguez-Bano et al (2004) 1.99 (0.73, 5.44) 6/31 7/72 4.05

To et al (2008) 1.47 (0.78, 2.76) 14/47 15/74 11.21

Tumbarello et al (2002) 0.29 (0.03, 2.49) 1/28 4/33 3.53

The incidence of infections

Overall (I-squared = 20.7%, p =caused
0.241) by extended-spectrum are associated with high mortality, prolonged
1.05 (0.83, 1.33) hospital
121/544 stay,100.00
109/529 and
β-lactamase-producing Enterobacteriaceae (ESBL-PE) is increased hospital costs [5, 6], and for these infections, carbap-
increasing [1–3], and, according to a 2013 report from the US enems are currently considered the first-line % 20,5  
22,1  therapy [5, 7,%8].
Centers of Disease Control and Prevention, 19% of healthcare-re-1
.00741 However, the use of carbapenems
135 has been linked to the devel-
lated Enterobacteriaceae infections are caused by ESBL-PE [4]. opment of carbapenem-resistant Enterobacteriaceae [8]. The
 2 bloodstream infection due to extended-spectrum β-lactamase-producing
1 Efficacy of β-lactam/β-lactamase inhibitor combinations for the treatment of
3 Enterobacteriaceae in hematological patients with neutropenia

2 bloodstream infection due to extended-spectrum β-lactamase-producing

4
3 Enterobacteriaceae in hematological patients with neutropenia
5 Authors: Carlota Gudiol1,2,25
Antimicrob  Agents  
*, Cristina Chemother  21,25
Royo-Cebrecos 017   Abdala3p, ii:  
Aug  25;61(8).  
, Edson e00164-­‐
Murat Akova17 4

6 Rocío Álvarez5, Guillermo Maestro-de la Calle6, Angela Cano7,25, Carlos Cervera8

4
Estudio  retrospectivo  multicéntrico
7 Wanessa T. Clemente9, Pilar Martín-Dávila10, Alison Freifeld11, Lucía Gómez12, Thomas
22  centros  de  9  países
1,2,25 1,25 3 4
5 Authors: Carlota Gudiol *, Cristina Royo-Cebrecos , Edson Abdala , Murat Akova ,
8 Gottlieb13, Mercè Gurguí14, Fabián Herrera15, Adriana Manzur16, Georg Maschmeyer17
6 • Pacientes  con  Neoplasias  Hematológicas  y  TCPH
Rocío Álvarez5, Guillermo
9 YolandaMaestro-de la Calle
Meije18,25, Miguel
6
, Angela
Montejo 19,25 Cano7,25, Carlos
, Maddalena Peghin20Cervera
8
,
, Jesús Rodríguez
• Neutropénicos
9 10 11 12
7 • Bacteriemia  por  E-­
Wanessa T. Clemente 21,25
, Pilar
10 Baño BLEE  (  E.  coli  y  Klebsiella
Martín-Dávila
, Isabel Ruiz-Camps 22,25
, Alison Freifeld
, Teresa spp:  99  %)
23
, Lucía Gómez
C. Sukiennik Tebe24, and Jord
, Cristian, Thomas
• Tratamiento  con  Carbapenem  o  BL-­IBL  por  al  menos  24  hs
13 11 Carratalà
14 1,25
*, for the BICAR
15 study group. 16 17
8 Gottlieb , Mercè Gurguí , Fabián Herrera
Punto  final  primario:  mortalidad  a  30  días , Adriana Manzur , Georg Maschmeyer ,
Punto  final  secundario:  mortalidad  a  7  y  14  días,  bacteriemia  persistente  
12 Affiliations: 1Infectious
18,25 Diseases Department, Bellvitge University Hospital, IDIBELL
9 Yolanda Meije , Miguel Montejo19,25, Maddalena Peghin20, Jesús Rodríguez-
o  recurrente,  colonización  por  bacteria  R  al   2
ATB,  superinfección.
3
13 University of Barcelona, Spain. Duran i Reynals Hospital, ICO. Instituto do Câncer do
21,25
0 Baño , Isabel Ruiz-Camps22,25, Teresa C. Sukiennik23, Cristian Tebe24, and Jordi
14 Estado de São Paulo, Faculty of Medicine, University of São Paulo, Brazil. 4Hacettepe
1 Carratalà1,25*, for the BICAR study group.
15 University School of Medicine, Ankara, Turkey. 5Clinical Unit of Infectious Diseases
 Supervivencia  al  día  30:              
Cohorte  Empírica  (n:  174)

p:  0.33

Sin  diferencias  en  enf  base,  edad,  NTP  alto  riesgo,  duración  NTP,  focos  de  gravedad,  
shock  y    microorganismo
 Supervivencia  al  día  30:              
Cohorte  Definitivo  (n:  251)

p:  0.99

Sin  diferencias  en  enf  base,  edad,  NTP  alto  riesgo,  duración  NTP,  focos  de  gravedad,  
shock  y    microorganismo
the IPW cohort, approximately 8% and 7% of patients in the carbapenems, adjusting for age, Pitt bacteremia score
Improved
Carbapenem Therapy Survival
Is Associated Compared Wit
With
PTZ and carbapenem groups, respectively, had inadequate
source control during the treatment course.
level of care (95% confidence interval [CI], 1.07–3.45
Figure 2 shows an IPW-adjusted Kaplan–Meier curve

Mortality
Tazobactam
Improved Survival for Patients
Compared With With Ex
Piperacillin- Receivedvital
January 2015.
23 June
status 2014;
at 14 accepted
days for 13patients
October 2014;
receiving electronically
empiric

Tazobactam for Patients

Spectrum With Extended- Bacteremia
β-Lactamase
There were 17 deaths (17%) in the PTZ group and 9 deaths
pared with empiric carbapenem therapy. The distr
Correspondence: Pranita D. Tamma, MD, MHS, Department of Ped
PTZ MICs were as follows: 2μg/ml (1%), 4μg/ml (3
(8%) in the carbapenem group within 14 days of the firstsion
Spectrum β-Lactamase Bacteremia pos-of Infectiousml (46%),
Diseases, Johns Hopkins University School of Med
and 16μg/ml (14%).
Wolfe St, Ste 3155, Baltimore, MD 21287 (ptamma1@jhmi.edu).
itive blood culture. Covariates independently associated with a
1
higher risk of death by day 14 included Pranita
higher D. Tamma, Jennifer
Pitt bacteremiaClinical H. Han,2 Clare
Infectious Rock,®
Diseases
3
Anthony D. Harris,3 Ebbing Lauten
2015;60(9):1319–25
1
Pranita D. Tamma, Jennifer H. Han, ClareSara 2 3
Rock,E. Anthony
Cosgrove D. 5Harris,
; for©
3
theEbbing
The DISCUSSION
Lautenbach,
Antibacterial
Author 2015.
2
Alice J. Hsu,
Resistance
Published by
4
Edina Avdic,
Leadership
Oxford University
4
Groupand
Press on behalf of t
scores
Sara E. and ICU-level
Cosgrove 5 care
; for the needed onResistance
Antibacterial day 1 of bacteremia.
Leadership ThereGroup
1
Department offor
Pediatrics, Diseases
Division ofSociety
Infectious of America.
Diseases, All rights
Johns Hopkinsreserved.
UniversityForSchool
Permissions, pl
of Medicine
was213  pacientes  con  E-­BLEE  con  CIM  a  Pip/tazo  ≤  16  μg/ml
a 1.92oftimes increased
Division ofrisk of death by Johns
day 14 patients re- of
1 2
Department Pediatrics, Infectious Diseases, Hopkins University School Medicine, Baltimore, Maryland; Department of Medicine,
Division
Division of Infectious Diseases, University of Pennsylvania of Infectious
School Diseases,
of Medicine, UniversityOur results
of Pennsylvania
journals.permissions@oup.com.
Philadelphia; 3
Department
suggest
of EpidemiologySchoolthat carbapenems
of Medicine,
and Public
should
Philadelphia;
Health, University of
3 be us
Departmen
ceiving empiric PTZ compared with patients receiving empiric 45 5
Empírico:  Carbapenem  vs  Pip/taz. Maryland
JohnsSchool
HopkinsofHospital,
Medicine,and Department ferred therapy
ofofMedicine,
Pharmacy, for patients
Johnsof Hopkins suspected
Hospital,
Diseases, andto have ESBLofb
Department
4
Maryland School of Medicine, Department of Pharmacy, Department Division Infectious Johns
Hopkins University School of Medicine, Baltimore, Maryland
DOI: 10.1093/cid/civ003
HIC: 55%
Hopkins University School of Medicine, Baltimore, liberal
However, Marylanduse of carbapenems is not witho
Definitivo:  Carbapenem
byPMN  <  100:  14.5  %
(See the Editorial Commentary by Perez and Bonomo on pages 1326–9.)
(See the Editorial Commentaryquence Perez andand canBonomo
result inonthe emergence
pages 1326–9.)of resistan
Background. The effectiveness of piperacillin-tazobactam (PTZ)agent for the [14, 15], severely
treatment limiting future treatment optio
of extended-spectrum
β-lactamase (ESBL) bacteremia is controversial. Background.
We compared The effectiveness
14-day mortality ofPTZ
fore, theofdecision piperacillin-tazobactam
vs to
carbapenems empiric(PTZ)
use empiricascarbapenem for th
therapy
therapy in a cohort of patients with ESBL bacteremia(ESBL)who all bacteremia
received definitive therapy withWe
is controversial. a carbapenem. 14-day mortalit
Methods. Patients hospitalized between January
β-lactamase
LRT:   0
2007.03 carefully considered aftercompared
and April 2014 with monomicrobial ESBL bacteremia were
factoring in relevant data
therapy in a cohort of patients with ESBL bacteremia who all received definit
included. A decrease of >3 doubling dilutions in the minimum inhibitory previous concentration history of ESBL colonization
for third-generation cephalo-or infection,
sporins tested in combination with 4 µg/mLMethods. of clavulanicPatients
acidCwas used hospitalized
Piperacilina/tazobactam
to hospital
confirm between
ESBL January
status.
or long-term-care
2007 and
The primary April 2014 with m
exposure
stay prior to infection ons
was empiric therapy, defined as antibioticincluded. A decreasetoof
therapy administered >3 doubling
a patient before ESBL dilutions in the
status was minimum
known. Patientsinhibitory
were conce
excluded if they did not receive a carbapenem sporins after ESBLin
tested production
combination
AHR:  1.92;;  95%  CI,  1.07-­3.45    p:  0.03    
cent
was identified.
PTZ
with 4 µg/mL
or cephalosporin
The primary outcomeacid
of clavulanic
exposure
was time
was to
[22–24].
used to confir
Ou
death from the first day of bacteremia. Propensity scores using inverse probability highlightofthe need for rapid diagnostics
exposure that can detec
was empiric therapy, defined as antibiotic therapyweighting
administered (IPW) were
to a patient before
used to estimate the probability that a patient would receivePT PTZ vs carbapenems empirically.
ence of resistance We calculated
mechanisms overall
earlier than tradition
hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. was identifi
excluded if they did not receive a carbapenem after ESBL production
death typic methods to identify antibiotic inverse
resistance.
Results. A total of 331 unique patients withfrom
ESBL the first day
bacteremia were ofidentified.
bacteremia. One Propensity
hundred three scores
(48%)usingpatients re- probabil
ceived PTZ empirically and 110 (52%) received used carbapenems
to estimate empirically.
the probability Although
that a risk
The adjusted the
patient addition
of deathwould of tazobactam
receive
was 1.92 timesPTZ
higher appears
vs carbapene to r
for patients receiving empiric PTZ compared hazard with empiric
ratios forcarbapenem
mortality censored therapy (95%
hydrolyzing at 14confidence
effect
days usingofinterval,
Cox1.07–3.45).
β-lactamase enzymeshazards
proportional on the
Conclusions. PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of
Results. A totalbeofconsidered.
331 unique ring patients
of piperacillin,
with the activity
ESBL of tazobactam is d
invasive ESBL infections, early carbapenem therapy should Our findings should notbacteremia
be extendedwere to identified.
β-lactam/β-lactamase inhibitor combinations ceivedinPTZ empirically
development, as limited when
and 110clinical (52%) adata
high concentration
received
are carbapenems
available of bacteria
for these agents.is present
empirically. The (“ino
adju
for patients receiving empiric fect”)
Keywords. ESBL; piperacillin-tazobactam; carbapenem; gram-negative;
PTZresistance.
compared
[25, 26]. The with empiric carbapenem
contribution of this proposed therapyphe
Conclusions. PTZ appearstoward inferiortreatment
to carbapenemsfailures, for the treatment
however, has not been of ESBL
the
O1121 The MERINO Trial: piperacillin-tazobactam versus meropenem for the definitive
treatment of bloodstream infections caused by third-generation cephalosporin non-
susceptible Escherichia coli or Klebsiella spp.: an international multi-centre open-
label non-inferiority randomised controlled trial

Patrick Harris*1 2 16, Paul Tambyah3 4, David Lye3 5, Yin Mo4, Tau Hong Lee5, Mesut Yilmaz6,
Febrero  2014  a  Julio  de  2017
Mero  1  gr  c/  8hs  vs  Pip/Tazo  4.5  gr  c/6  hs
Thamer Alenazi 7, Yaseen Arabi7, Marco Falcone8, Matteo Bassetti9, Elda Righi9, Benjamin
-­ Objetivo  primario:  Mortalidad  a  30  días
Rogers 10, Souha S. Kanj11, Hasan Bhally12, Jonathan Iredell13 14, Marc Mendelson15, Tom
-­ Objetivos  secundarios:
Boyles15, Resolución  clínica  y  microbiológica,  Recaída,  Superinfección
David Looke16 17, Spiros Miyakis18 19, Genevieve Walls20, Mohammed Al Khmais21,
Ahmed Mohamed
Resultados: Wadie Hassan Zikri 21, Amy Crowe22, Paul Ingram23 24, Nick Daneman25,

Paul BSI:  56.4%  

Griffin17 26 27, Eugene Athan28, Penelope Lorenc29, Peter Baker30, Anton Peleg31 32, Tiffany
ACS,  Foco  urinario:  60.9%  y  causado  por  E.  coli:  86.5%.
Mortalidad  a  30  días:  
Harris-Brown 33, David Paterson33 34
Pip/  tazo  23/187  (12.3%)  vs  Meropenem  7/191  (3.7%)
Diferencia  de  Riesgo  8.6%,  95%  CI  3.4%  to  14.5%;;  RR  3.4,  95%  CI  
1University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia, 2Royal Brisbane and
1.5  to  7.6;;  p=0.002
Women's Hospital, Department of microbiology, Pathology Queensland, Brisbane, Australia, 3National
University of Singapore, Yong Loo Lin School of Medicine, Singapore, Singapore, 4National University
ECCMID  2018;;  Abst  #  O1121    
Hospital Singapore, Department of Infectious Diseases, Singapore, Singapore, 5Tan Tock Seng
 Conclusiones
Infecciones  por  OMR,  particularmente  BGN,  en  pacientes  
con  cáncer  y  TCPH  representan  un  problema  frecuente  y  
creciente  en  Argentina.  

Perfil  epidemiológico  difiere  según  presencia  de  

neutropenia,  enfermedad  oncológica  y  sitio  de  adquisición.

Factor  de  Riesgo  independiente  de  mortalidad.

Podemos  estratificar  el  riesgo  de  OMR  en  cada  paciente  

según  presencia  de  diferentes  variables.
 Conclusiones  II
Tratamiento  empírico  en  Neutropenia  Febril  de  Alto  Riesgo:

Individualizado  para  cada  paciente  según:  

•Epidemiología  local  y  temporal  del  centro  
•Sitio  de  adquisición  
•Estado  hemodinámico  
•Focos  de  gravedad    
•Factores  de  riesgo  para  OMR

-­Combinado  en  pacientes  con  FR  para  OMR  y    curso

complicado.
-­Monoterapia  sigue  siendo  segura  en  ausencia  de
factores  anteriores.
 Conclusiones  III
•Bacteriemias  por  Escherichia  coli  y  Klebsiella spp.  
productoras  de  BLEE:

-­Tratamiento  con  Piperacilina-­tazobactam  solo  o

combinado  con  AMG  es  un  tema  controversial.

-­Podría  ser  una  alternativa  apropiada  en  bacteriemias

por  cepas  sensibles  y  con  CIM  baja,  pero  faltan  más  
datos  para  emitir  una  recomendación  firme.  
Muchas  Gracias