Aquisição de bactéria gram-negativa multidroga resistente antes do transplante de fígado

147 Pages·2017·8.62 MB·English

MARISTELA PINHEIRO FREIRE

Aquisição de bactéria gram-negativa
multidroga resistente antes do transplante
de fígado : o impacto no desfecho

Tese apresentada à Faculdade de Medicina da
Universidade de São Paulo para obtenção do título
de Doutora em Ciências
Programa de Doenças Infecciosas e Parasitárias
Orientador: Prof. Dr. Edson Abdala

São Paulo
2017
Dados Internacionais de Catalogação na Publicação (CIP)
Preparada pela Biblioteca da
Faculdade de Medicina da Universidade de São Paulo

reprodução autorizada pelo autor

Freire, Maristela Pinheiro

Aquisição de bactéria gram-negativa multidroga resistente antes do transplante
de fígado: o impacto no desfecho / Maristela Pinheiro Freire -- São Paulo, 2017.
Tese (doutorado)--Faculdade de Medicina da Universidade de São Paulo.
Programa de Doenças Infecciosas e Parasitárias.
Orientador: Edson Abdala.

Descritores: 1.Transplante de fígado 2.Bactéria multi-droga resistente

3.Fator de risco 4.Mortalidade 5.Bacilo Gram-negative 6.Resistência a
carbapênico

USP/FM/DBD-244/17
MARISTELA PINHEIRO FREIRE

Multidrug-resistant gram-negative bacteria
acquired before liver transplantation : the
impact on the outcome

Thesis presented at the Faculdade de Medicina da
Universidade de São Paulo for acquisition of the
title of Philosophiae Doctor (PhD)
Infectious Diseases Program
Advisor: Prof. Dr. Edson Abdala

São Paulo
2017
This thesis is in accordance with the following rules, validity at the moment of
the publication.
References: adapted from International Committee of Medical Journals Editors
(Vancouver).
Universidade de São Paulo. Faculdade de Medicina. Divisão de Biblioteca e
Documentação. Guia de apresentação de dissertações, teses e monografias.
Authors: Anneliese Carneiro da Cunha, Maria Julia de A. L. Freddi, Maria F.
Crestana, Marinalva de Souza Aragão, Suely Campos Cardoso, Valéria
Vilhena. 3a edition. São Paulo: Divisão de Biblioteca e Documentação: 2011.
Abbreviations of periodic titles are in accordance with List of Journals Indexed
in Index Medicus.
TABLES OF CONTENTS

Abbreviations and Acronyms List
Figures List
Tables List
Resumo
Abstract
1 INTRODUCTION ................................................................................................................ 1
2 OBJECTIVES..................................................................................................................... 11
2.1 Primary objective ................................................................................. 11
2.2 Secondary objectives ......................................................................... 11
3 METHOD ............................................................................................................................. 12
3.1 Study Design ....................................................................................... 12
3.2 Participants .......................................................................................... 12
3.3 Prophylaxis .......................................................................................... 13
3.4 Immunosuppression ............................................................................ 14
3.5 Microbiology ........................................................................................ 14
3.5.1 Surveillance Culture .................................................................. 14
3.5.2 Processing of surveillance culture samples .............................. 15
3.5.3 Culture for diagnosis of infection ............................................ 17
3.5.4 Molecular typing – Pulsed Field Electrophoresis ................... 18
3.6 Definitions ............................................................................................ 21
3.6.1 Multidrug-resistant bacteria definition ........................................ 21
3.6.2 Diagnostic Criteria for bacterial colonization .......................... 22
3.6.3 Criteria for diagnosis of healthcare-associated infection ....... 22
3.6.4 Definition of acquisition of Multidrug-resistant bacteria ......... 23
3.6.5 Criteria for diagnosis of acute cellular rejection ..................... 24
3.6.6 Criteria for severity of liver failure: .......................................... 24
3.7 Statistical treatment ............................................................................ 25
3.7.1 Performance of surveillance culture: ......................................... 25
3.7.2 Outcome variables ................................................................... 25
3.7.3 Variables analyzed .................................................................. 26
3.7.4 Statistical analysis ................................................................... 28
4 RESULTS............................................................................................................................ 30
4.1 Characterization of the population ....................................................... 30
4.2 Surveillance cultures ............................................................................ 34
4.3 Identification of KPC-producing Enterobacteriaceae ........................... 36
4.4 Analysis of risk factors for Multidrug-resistant Gram-negative
bacteria acquisition after liver transplantation ...................................... 37
4.4.1 Analysis of risk factors for carbapenem-resistant K.
pneumoniae acquisition after liver transplantation .................... 39
4.4.2 Analysis of risk factors analysis of carbapenem-resistant A.
baumannii acquisition after liver transplantation ........................ 41
4.4.3 Analysis of risk factors analysis of carbapenem-resistant P.
aeruginosa acquisition after liver transplantation ...................... 44
4.5 Healthcare-associated infections (HAI) after liver transplantation ....... 46
4.5.1 Surgical site infections .............................................................. 48
4.5.2 Bloodstream Infections after Liver Transplantation ................... 50
4.5.3 Lower respiratory tract infection after liver transplantation ........ 51
4.5.4 Other types of infection after liver transplantation ..................... 52
4.6 Analysis of risk factors for healthcare-associated infection by MDR
GNB after liver transplantation ............................................................. 53
4.6.1 Analysis of risk factors analysis of healthcare-associated
infection by carbapenem-resistant K. pneumoniae after liver
transplantation ........................................................................... 56
4.6.2 Analysis of risk factors for healthcare-associated infection by
carbapenem-resistant A. baumannii after liver transplantation . 58
4.6.3 Analysis of risk factors for healthcare-associated infection by
carbapenem-resistant P. aeruginosa after liver
transplantation ........................................................................... 60
4.7 Evaluation of strains clonality through PFGE ...................................... 62
4.8 Survival analysis .................................................................................. 66
5 DISCUSSION..................................................................................................................... 69
6 BIBLIOGRAPHY ............................................................................................................... 84
7 APPENDIX
Abbreviations and Acronyms List

SOT – Solid organ transplantation
CMV – Cytomegalovirus
EBV – Epstein-Barr virus
HAI – Healthcare-associated infection
MDR – Multidrug-resistant bacteria
LT – Liver Transplantation
MRSA – Methicillin-resistant Staphylococcus aureus
MELD – Model for End-Stage Liver Disease
VRE – Vancomycin-resistant enterococci
GNB – Gram-negative bacilli
ESBL – Extended spectrum beta-lactamase
CRE – Carbapenem-resistant Enterobacteriaceae
CRPA – Carbapenem-resistant Pseudomonas aeruginosa
CRKP – Carbapenem-resistant Klebsiella pneumoniae
CVC – Central venous catheter
BHI – Brain Heart Infusion
CLSI – Clinical Laboratory Standards Institute
PFGE – Pulsed-field Gel Electrophoresis
SSI-OE – Organ-space Surgical Site Infection
SSI-I – Incisional surgical site infection
BSI – Bloodstream infection
UTI – Urinary tract infection
RR – Relative risk
CI – Confidence interval
OR – Odds Ratio
Figures List

Figure 1 – Distribution of PFGE pulsotype of carbapenem-resistant A.
baumannii strains from November 2009 to November 2011 ......... 62
Figure 2 – Dendogram of carbapenem-resistant A. baumannii strains from
eight patients who acquired CRAB before LT and developed
infection by CRAB after LT ............................................................ 63
Figure 3 – Distribution of PFGE cluster of carbapenem-resistant bla
KPC-
positive K. pneumoniae strains from January 2010 to November
2011 .............................................................................................. 64
Figure 4 – Dendogram of carbapenem-resistant K. pneumoniae isolated
from Liver transplant patients from November 2009 to
November 2011 ............................................................................. 65
Figure 5 – 60-day survival curve adjusted according to LT surgery duration
and post-LT dialysis, categorized by type of microorganism
isolated from HAI after LT.............................................................. 68
Tables List

Table 1 – Baseline diseases of 195 patients submitted to liver
transplantation ............................................................................. 31
Table 2 – Demographic and clinical characteristics of 195 patients
submitted to liver transplantation ................................................. 32
Table 3 – Sites, microorganisms and sensitivity profile of 50 infections
identified in up to ten days before liver transplantation ................. 33
Table 4 – Positivity rate of surveillance culture by site of harvest from the
different Multidrug-resistant Gram-negative bacteria in 180
patients submitted to liver transplantation ................................... 35
Table 5 – Performance of surveillance culture of different MDR GNB in
180 patients submitted to liver transplantation ............................ 35
Table 6 – Distribution of bla gene positivity rate among strains of
KPC
carbapenem-resistant Enterobacteriaceae isolated from
surveillance culture...................................................................... 36
Table 7 – Univariate analysis of risk factors for acquisition of MDR GNB
after LT in 105 patients – categorical variables ........................... 37
Table 8 – Univariate analysis for risk factors for acquisition of MDR GNB
after LT in 105 patients – continuous variables ........................... 38
Table 9 – Multivariate analysis of risk factors for acquisition of MDR
GNB after LT in 105 patients ....................................................... 38
Table 10 – Univariate analysis of risk factors for acquisition of
carbapenem-resistant K. pneumoniae after LT in 172 patients –
categorical variables.................................................................... 39
Table 11 – Univariate analysis of risk factors for acquisition of
carbapenem-resistant K. pneumoniae after LT in 172 patients
– continuous variables ................................................................. 40
Table 12 – Multivariate analysis of risk factors for acquisition of
carbapenem-resistant K. pneumoniae after LT in 172 patients....... 40
Table 13 – Univariate analysis of risk factors for acquisition of
carbapenem-resistant A. baumannii after LT in 171 patients –
categorical variables.................................................................... 42
Table 14 – Univariate analysis of risk factors for acquisition of
carbapenem-resistant A. baumannii after LT in 171 patients –
continuous variables.................................................................... 43