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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). • • • • 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 • Carbapenem-resistant A. baumannii • 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 • • • • • • • 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 • An uncomplicated De-escalation strategy • presentation • Without specific risk presentations • for resistant pathogens • In centres where infections due to resistant pathogens are rare Pts with complicated Individual risk factors for resistant pathogens • Centres where resistant pathogens are frequent Where are we going to? • • 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. Thank you for your attention! La Pedrera, Gaudí, Barcelona