Transcript Diapositiva 1

Multidrug-Resistant Bacteria
in Solid Organ Transplantation
Jordi Carratalà
Department of Infectious Diseases
IDIBELL-Hospital Universitari de Bellvitge
A 10-Year Study of Infection-Related Mortality in
a Cohort Of 1218 Renal Transplant Recipients
Linares L. Transpl Proc 2007
Bloodstream Infections Among Transplant Recipients
Results of a Nationwide Surveillance in Spain
Kidney
Liver
Heart
Lung
Pancreas
1400
1012
291
167
65
Episodes (n)
121
134
32
17
17
Patients (n)
102
105
24
14
13
Incidence (%)
8.6
13.2
11
10.2
26.1
Transplants (n)
Moreno A. Am J Transpl 2007
Etiology of 321 Episodes of Bacteremia in SOT Recipients
E. coli
127
CNS
284
17%
8%
A. baumanii
60
37%
6%
Pseudomonas spp
47
6%
4% 5%
RESITRA
Klebsiella spp
29
Enterococcus spp
46
S. aureus
37
Moreno A. Am J Transpl 2007
Bloodstream Infections Among SOT Recipients
Proportion of Resistant Organisms (2003-2005)
14.5%
Resistant
Number of isolates
Susceptible
9.7%
16.2%
Enteric bacilli
No-fermentative
S. aureus
Overall, 12% of isolates were MDR
MRSA Bacteremia in Liver Transplant Recipients
Rochester, USA: 6.5%
Lee SO. Liver Transpl 2011
Kyoto, Japan:
7.7%
Lida T. Liver Transpl 2010
Clichy, France:
14%
Donskey CJ. NEJM 2009
Bert F. Liver Transpl 2010
MRSA infection in SOT recipients has been associated
with increased mortality (OR 9.0)
Yamada K. Tohoku J Exp Med 2011
ESBL-Producing Escherichia coli
E. coli CTX-M-9
Proportion of 3rd Generation Cephalosporin Resistant
Escherichia coli isolates
2001
2006
Proportion of 3rd Generation Cephalosporin Resistant
Escherichia coli isolates (2011)
10 to <25%
2011
Bacterial Urinary Tract Infection After SOT
in the RESITRA Cohort
•
Bacterial urinary tract infection, kidney transplant vs. others
in the RESITRA cohort (4388 pts).
•
192 pts (4.4%) with 249 episodes of urinary infection
(0.23 episodes/1000 transplant days).
•
156 pts were kidney or kidney/pancreas recipients.
•
Escherichia coli (58%), 26% were ESBL-producing strains.
•
Risk factors: age, female sex, and posttransplant dialysis.
Vidal E. Transplant Infect Dis 2012
Risk Factors for Infection with Extended-Spectrum
and AMpC ß-Lactamase-Producing Gram Negative
Rods in Renal Transplantation
•
A cohort observational study (2003-2006).
• 417 kidney transplant recipients (61 kidney/pancreas).
• Incidence of ESBL-producing and desrepressed AMpC
ß-Lactamases was 11.8% (49 patients).
• The most frequent bacteria was E. coli (35/60) followed
by Klebsiella spp (12/60).
Linares L. Am J Transpl 2008
Β-lactamase Mediated Resistance in GNB
Isolates and Source of Infection
Bacteremia: 10 episodes (17%)
Risk Factors for ESBL-Producing and Desrepressed
AmpC β-lactamase GNB Infection in Kidney Recipients
Variable
Adjusted OR
95% CI
Kidney-Pancreas Tx
3.5
1.6 – 7.8
Prior antibiotic use
2.1
1.1 – 4.1
Posttransplant dialysis
3.1
1.5 – 6.4
Posttransplant urinary
5.8
2.2 – 14.9
obstruction
Linares L. Am J Transpl 2008
Extended-Spectrum β-Lactamase-Producing
Bacterial Infections in Adult SOT Recipients
•
Retrospective case series of 20 cases of ESBL-producing
bacterial infections (2003-2006).
•
•
Median time to infection from Tx was 3.5 yrs (1-23 yrs)
Overall, 85% of pts received inadequate empiric antibiotic
therapy.
•
•
•
19 pts had clinical resolution; 1 patient died.
12 pts required readmission due to recurrence.
Among 12 pts with recurrent infections, 75% received
inadequate empiric antibiotic therapy
Winters HA. Ann Pharmacother 2011
Klebsiella pneumoniae Infection in SOT Recipients
Epidemiology and Antibiotic Resistance
•
•
Prospective study of 1,057 SOT recipients (2003-2007).
Of 116 episodes of KP infection, 62 (53%) were ESBL-
producing strains (47 episodes <1month after TX).
•
•
•
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34 pts (39%) had bacteremia; 15 due to resistant strains.
None strain was KPC.
The most frequent site of infection was urinary tract (72%).
ESBL-producing strains were > frequent in KT recipients
and in those requiring dialysis.
•
There were 4 deaths and 3 were due to resistant strains.
Linares L. Transplant Proc 2010
Proportion of Klebsiella Pneumoniae Resistant Isolates (2011)
10-<25%
<1%
≥50%
3rd generation cephalosporins R
Carbapenem R
Infection with KPC-producing Klebsiella pneumoniae
in Solid Organ Transplantation
•
Outbreak of 12 cases of KPC-2
producing KP in Sao Paulo.
•
Incidence: 26% KT (6); 17% HT (2);
13% LT (4). Median time to infection: 20 days.
•
Site of infection: urinary tract (4), bacteremia (4), pneumonia (2), SSI (2).
•
All but 1 patient had received prior antibiotic therapy (30 days).
•
Treatment: Tige + PB (3); PB + carbapenem (3); PB (3); Tige + Imip (1)
• Overall 30-day mortality: 42%.
Bergamasco MD. Transplant Infect Dis 2012
IDSA Report
Boucher HW. Clin Infect Dis 2009
Drug-resistant ESKAPE (rESKAPE)
•
Vancomycin-resistant E. faecium
•
Methicillin-resistant S. aureus (MRSA)
•
ESBL-producing K. pneumoniae
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Carbapenem-resistant A. baumannii
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Carbapenem and quinolone-resistant P. aeruginosa
•
Derepression chromosomic β-lactam and ESBL
producing Enterobacter spp.
Epidemiology, antibiotic therapy, and outcomes of
bacteremia caused by rESKAPE in SOT Recipients
224 cases of bacteremia
127 (57%) ESKAPE bacteremia
Non-rESKAPE
88 cases
Hospital de Bellvitge (Jan 2007- Mar 2012)
rESKAPE
39 cases (17.5%)
Bodro M. ICAAC 2012
ESKAPE pathogens isolated in 224 bacteremias
In SOT Recipients: Bellvitge Hospital (2007-2012)
Organism
ESKAPE total
(n= 127)
R-ESKAPE
(n= 39)
Enterococcus faecium
7
0
Staphylococcus aureus
14
4
Klebsiella pneumoniae
29
7
Acinetobacter baumannii
5
5
Pseudomonas aeruginosa
25
20
Enterobacter spp.
8
3
Risk factors for rESKAPE bacteremia
In SOT Recipients by Multivariate Analysis
Variable
OR
95% CI
Prior transplantation
4.8
1.1 – 22.7
Nosocomial acquisition
4.0
1.3 – 12.2
Prior antibiotic therapy
3.0
1.1 – 9.7
Septic shock
3.5
1.5 – 8.3
Bodro M. ICAAC 2012
Antibiotic therapy and outcomes of SOT
Recipients with rESKAPE Bacteremia
Variable
rESKAPE
n=54
Other
n=185
P
Inadequate ATB therapy
43%
18%
0.003
ICU admission
48%
21%
0.001
Mechanical ventilation
33%
15%
0.001
Overall case-fatality rate (30d)
42%
15%
0.001
Bodro M. ICAAC 2012
Proportion of Carbapenems Resistant
Pseudomonas aeruginosa Isolates (2011)
10-<25%
2011
Infections Caused by Pseudomonas aeruginosa
in SOT Recipients
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•
•
•
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904 SOT recipients (Kidney, Liver, Pancreas)
MDR Pseudomonas aeruginosa (≥ 3 ATBs)
110 episodes of infection (76 patients)
Urinary tract infection: 42%
Bacteremia: 30 episodes (27%)
Incidence:
- P. aeruginosa
8.4%
- MDR P. aeruginosa 35%
Mortality:
- P. aeruginosa 4%
- MDR P. aeruginosa 2.6%
Linares L. SEIMC 2008
Severe Infection in a Lung Transplant Recipient Caused by
Donor-Transmitted Carbapenem-R Acinetobacter baumanii
A 50-year-old female lung recipient with a proven donor transmission
of carbapenem-R ABAU (BlaOXA-23) belonging to a new multilocus
sequence type (ST231)
Martins N. Transplant Infect Dis 2011
Multidrug-Resistant Acinetobacter baumanii causing
Necrotizing Fasciitis in a Pancreas-Kidney
Transplant Recipient
Clemente WT. Transplantation 2012
Heart RS. Curr Opin Infect Dis 2012
Empirical Treatment of Suspected Bacteremia in
SOT Recipients
Escalation strategy
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An uncomplicated
De-escalation strategy
•
presentation
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Without specific risk
presentations
•
for resistant pathogens
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In centres where infections
due to resistant pathogens
are rare
Pts with complicated
Individual risk factors
for resistant pathogens
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Centres where resistant
pathogens are frequent
Where are we going to?
•
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Increasing prevalence of MDR bacteria in SOT recipients.
Updated knowledge of local epidemiology and resistance
patterns.
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No new drugs to treat infections due MDR organisms
will be available.
•
Selective effect of the increasing use of last resort ATBs
of great concern.
•
Need to improve preventive strategies and to optimize
ATB therapy.
Thank you for your attention!
La Pedrera, Gaudí, Barcelona