Managing Gram-Negative Infections in Solid Organ Transplantation: A Comprehensive Overview
This overview addresses the challenges posed by gram-negative infections in solid organ transplantation. It delves into the epidemiology and clinical implications of specific pathogens such as ESBL-producing E. coli, K. pneumoniae, and P. aeruginosa, emphasizing their prevalence in kidney, liver, heart, and lung transplants. Highlighted are the mechanisms of resistance, the impact on patient outcomes, and the importance of effective antibiotic stewardship, screening, and prophylaxis to manage infections effectively in transplant recipients.
Managing Gram-Negative Infections in Solid Organ Transplantation: A Comprehensive Overview
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Presentation Transcript
Gram-Negative Infections in Solid Organ Transplantation Murat Akova, MD, FESCMID Hacettepe University School of Medicine Department of InfectiousDiseases Ankara, Turkey
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
CTX-M Encoding Plasmid Woodford N, et al. AAC 2009; 53:4472
Global Epidemiology of CTX-M Enzymes Bewan ER, et al. J Antimicrob Chemother 2017;72:2145
Carbapenemases in Enterobacteriaceae KPC NDM OXA-48 VIM Courtesy of DM Livermore
Epidemiology of KPC-Kp Lee C-R, et al. Frontiers Microbiol 2016;7:895
Epidemiology of OXA-48 Producers Bonomo RA, et al. Clin Infect Dis 2018;66:1290
Epidemiology of NDM Producers Bonomo RA, et al. Clin Infect Dis 2018;66:1290
Antibiotic Consumption and Resistance Collignan P, et al. PLoS One 2015;10:e116746
Control of Corruption and Resistance Collignan P, et al. PLoSOne 2015;10:e116746
Collignon P, et al. Lancet Planet Health 2018;2:e398
Resistance Corruption Infrastructure Collignon P, et al. Lancet Planet Health 2018;2:e398
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
Quinolone 3rd gen. cephalosporin Collignon P, et al. Lancet Planet Health 2018;2:e398
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
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
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
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%
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
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
Guideline Recommendations on MDR Gram (-)ves Bartoletti M, te al. Infect Dis Clin N Am 2018;32:551
Donor Acceptance with MDR-GN Bartoletti M, te al. Infect Dis Clin N Am 2018;32:551
Antibiotic Prophylaxis Bartoletti M, te al. Infect Dis Clin N Am 2018;32:551
Conclusions • MDR Gram-negatives have a significant impact on SOT recipients • Several issues remain uncertain • Selection of recipients • Screening • Prophylaxis • Infection control • Treatment
