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 ina 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

Num

ber o

f iso

late

s

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

ESBL-Producing Escherichia coli

E. coli CTX-M-9

Proportion of 3rd Generation Cephalosporin ResistantEscherichia coli isolates

2001 2006

Proportion of 3rd Generation Cephalosporin ResistantEscherichia coli isolates (2011)

10 to <25%

2011

Bacterial Urinary Tract Infection After SOTin 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 GNBIsolates 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 DesrepressedAmpC β-lactamase GNB Infection in Kidney Recipients

Linares L. Am J Transpl 2008

Extended-Spectrum β-Lactamase-ProducingBacterial 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 RecipientsEpidemiology 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 pneumoniaein 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%.

IDSA Report

Boucher HW. Clin Infect Dis 2009

• 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-rESKAPE88 cases

rESKAPE39 cases (17.5%)

Epidemiology, antibiotic therapy, and outcomes ofbacteremia caused by rESKAPE in SOT Recipients

Bodro M. ICAAC 2012Hospital de Bellvitge (Jan 2007- Mar 2012)

ESKAPE pathogens isolated in 224 bacteremiasIn 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 bacteremiaIn 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 SOTRecipients 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

Proportion of Carbapenems Resistant Pseudomonas aeruginosa Isolates (2011)

10-<25%

2011

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

Heart RS. Curr Opin Infect Dis 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?

La Pedrera, Gaudí, Barcelona

Thank you for your attention!