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Gram-Negative Infections in Solid Organ Transplantation

Gram-Negative Infections in Solid Organ Transplantation. Murat Akova, MD, FESCMID Hacettepe University School of Medicine Department of Infectious Diseases Ankara, Turkey. WHO 2017. Classification ß-Lactamases. Class Active site Examples Substrates

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Gram-Negative Infections in Solid Organ Transplantation

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  1. Gram-Negative Infections in Solid Organ Transplantation Murat Akova, MD, FESCMID Hacettepe University School of Medicine Department of InfectiousDiseases Ankara, Turkey

  2. WHO 2017

  3. Classification ß-Lactamases Class Active site Examples Substrates ASerineTEM, SHV,CTX-M Penicillins, 3rd GCs KPC All beta-lactams B Zn++ IMP, VIM, NDM All beta-lactams, not monobactams C SerineAmp C Cephamycins, 3rd GCs D Serine OXA All beta-lactams Ambler, RP. Philos Trans R Soc Lond B Biol Sci1980;289:321

  4. CTX-M Encoding Plasmid Woodford N, et al. AAC 2009; 53:4472

  5. Global Epidemiology of CTX-M Enzymes Bewan ER, et al. J Antimicrob Chemother 2017;72:2145

  6. Carbapenemases in Enterobacteriaceae KPC NDM OXA-48 VIM Courtesy of DM Livermore

  7. Epidemiology of KPC-Kp Lee C-R, et al. Frontiers Microbiol 2016;7:895

  8. Epidemiology of OXA-48 Producers Bonomo RA, et al. Clin Infect Dis 2018;66:1290

  9. Epidemiology of NDM Producers Bonomo RA, et al. Clin Infect Dis 2018;66:1290

  10. Antibiotic Consumption and Resistance Collignan P, et al. PLoS One 2015;10:e116746

  11. Control of Corruption and Resistance Collignan P, et al. PLoSOne 2015;10:e116746

  12. Collignon P, et al. Lancet Planet Health 2018;2:e398

  13. Resistance Corruption Infrastructure Collignon P, et al. Lancet Planet Health 2018;2:e398

  14. Parameters Related with Antibiotic Resistance • Increased resistance • Poor infrastructure (Poor santiation) • Bad governance (Corruption) • Low health expenditure • Privatization in health sector • Higher GDP per capita • High education index • Decreased resistance • Urbanization, internet and electiricty access • Socialized health services • No relationship or undetermined • Antibiotic use • Climate Collignon P, et al. Lancet Planet Health 2018;2:e398

  15. Quinolone 3rd gen. cephalosporin Collignon P, et al. Lancet Planet Health 2018;2:e398

  16. Gram (-)ve InfectionsKidney Transplantation • Recurrent UTI • Structural abnormalities • Renal cyst infection • Surgical site infection • Perigraft infected hematoma • ESBL (+) E. coli • 12% of all infections • 70% UTI • CR-K. pneumoniae • P. aeruginosa • UTI, HAP • A. baumannii • 3% bacteremia • VAP Aguado JM, et al. Transplant Rev 2018;32:36

  17. Gram (-)ve InfectionsLiver Transplantation Silva TS, te al. Curr Opin Infect Dis 2018;31:499 Intraabdominal abscesses Intraabdominal infected hematomas Tertiary peritonitis Infected biliomas Cholangitis R Recurrent biliary infection

  18. MDR Gram (-)ve InfectionsLiver Transplantation • Usually early post-tx (12-24 days) • ESBL (+) Enterobacteriaceae • 5.5%-7.0%, mainly by E. coli and K. pneumoniae • Carbapenem-R Enterobacteriaceae (CRE) • 6.0%-12.9% • x 5 mortality as compared to CSE • Mostly intraabdominal infections, HAP, UTI Aguado JM, et al. Transplant Rev 2018;32:36

  19. MDR Phenotype in Bacteremia in Liver Tx Shi SH, et al. Transpl Infect Dis 2009;11:405 Rana MM, etal. Transpl Infect Dis2013;15:E157 In general >50% in certain series A. baumannii 62.5% Enterobacteriaceae 54.8% S. maltophilia 54.2% P. aeruginosa 51.5%

  20. Gram (-)ve InfectionsHeart Transplantation • Pneumonia during the 1st month post-tx • MDR P. aeruginosa • Carbapenem-R A. baumannii (CRAB) • MDR S. maltophilia • Associated bacteremia is frequent • Mediastinitis and sternal SSI • 2.5% • ESBL E. coli and non-fermenters Aguado JM, et al. Transplant Rev 2018;32:36

  21. Gram (-)ve InfectionsLungTransplantation • P. aeruginosa in cystic fibrosis • Pre-tx colonization >50% • Leading cause of HAP, 25% of cases • Bronchiolitis obliterans , bronchovascular fistula • CRAB • HAP, UTI, catheter associated BSI • Burkholderia cepacia • Chronic lung infections, mediastinitis/abscesses • <50% MDR Aguado JM, et al. Transplant Rev 2018;32:36

  22. Guideline Recommendations on MDR Gram (-)ves Bartoletti M, te al. Infect Dis Clin N Am 2018;32:551

  23. Donor Acceptance with MDR-GN Bartoletti M, te al. Infect Dis Clin N Am 2018;32:551

  24. Antibiotic Prophylaxis Bartoletti M, te al. Infect Dis Clin N Am 2018;32:551

  25. Conclusions • MDR Gram-negatives have a significant impact on SOT recipients • Several issues remain uncertain • Selection of recipients • Screening • Prophylaxis • Infection control • Treatment

  26. Thank you…

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