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
Transplants (n) 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
Moreno A. Am J Transpl 2007
Etiology of 321 Episodes of Bacteremia in SOT Recipients
CNS284
E. coli127
A. baumanii 60
Pseudomonas spp47
Enterococcus spp46
Klebsiella spp29
S. aureus37
37%
17%
8%
6%
6%
5%4%
Moreno A. Am J Transpl 2007RESITRA
Bloodstream Infections Among SOT Recipients
Proportion of Resistant Organisms (2003-2005)
14.5%
9.7%
16.2%
Resistant
Susceptible
Enteric bacilli No-fermentative S. aureus
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f is
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tes
Overall, 12% of isolates were MDR
MRSA Bacteremia in Liver Transplant Recipients
Donskey CJ. NEJM 2009
Rochester, USA: 6.5%
Lee SO. Liver Transpl 2011
Kyoto, Japan: 7.7%
Lida T. Liver Transpl 2010
Clichy, France: 14%
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
Proportion of 3rd Generation Cephalosporin Resistant
Escherichia coli isolates (2011)
10 to <25%
2011
Bacterial Urinary Tract Infection After SOT
in the RESITRA Cohort
Vidal E. Transplant Infect Dis 2012
• 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.
• 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).
Risk Factors for Infection with Extended-Spectrum
and AMpC ß-Lactamase-Producing Gram Negative
Rods in Renal Transplantation
Linares L. Am J Transpl 2008
Β-lactamase Mediated Resistance in GNB
Isolates and Source of Infection
Bacteremia: 10 episodes (17%)
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
Risk Factors for ESBL-Producing and Desrepressed
AmpC β-lactamase GNB Infection in Kidney Recipients
Linares L. Am J Transpl 2008
Extended-Spectrum β-Lactamase-Producing
Bacterial Infections in Adult SOT Recipients
Winters HA. Ann Pharmacother 2011
• 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
Klebsiella pneumoniae Infection in SOT Recipients
Epidemiology and Antibiotic Resistance
Linares L. Transplant Proc 2010
• 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).
• 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.
Proportion of Klebsiella Pneumoniae Resistant Isolates (2011)
3rd generation cephalosporins R Carbapenem R
10-<25% <1%
≥50%
Infection with KPC-producing Klebsiella pneumoniae
in Solid Organ Transplantation
Bergamasco MD. Transplant Infect Dis 2012
• 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%.
• Vancomycin-resistant E. faecium
• Methicillin-resistant S. aureus (MRSA)
• ESBL-producing K. pneumoniae
• Carbapenem-resistant A. baumannii
• Carbapenem and quinolone-resistant P. aeruginosa
• Derepression chromosomic β-lactam and ESBL
producing Enterobacter spp.
Drug-resistant ESKAPE (rESKAPE)
224 cases of bacteremia
127 (57%) ESKAPE bacteremia
Non-rESKAPE
88 cases
rESKAPE
39 cases (17.5%)
Epidemiology, antibiotic therapy, and outcomes of
bacteremia caused by rESKAPE in SOT Recipients
Bodro M. ICAAC 2012Hospital de Bellvitge (Jan 2007- Mar 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 Other P
n=54 n=185
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% 0.001Bodro M. ICAAC 2012
Infections Caused by Pseudomonas aeruginosa
in SOT Recipients
• 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
Martins N. Transplant Infect Dis 2011
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)
Multidrug-Resistant Acinetobacter baumanii causing
Necrotizing Fasciitis in a Pancreas-Kidney
Transplant Recipient
Clemente WT. Transplantation 2012
Empirical Treatment of Suspected Bacteremia in SOT Recipients
Escalation strategy
• An uncomplicated
presentation
• Without specific risk
for resistant pathogens
• In centres where infections
due to resistant pathogens
are rare
De-escalation strategy
• Pts with complicated
presentations
• Individual risk factors
for resistant pathogens
• Centres where resistant
pathogens are frequent
• Increasing prevalence of MDR bacteria in SOT recipients.
• Updated knowledge of local epidemiology and resistance
patterns.
• 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.
Where are we going to?