results of the rescuing study - combacte
TRANSCRIPT
WP5 “RESCUING”
REtrospective observational Study to assess the
clinical management and outcomes of hospitalised
patients with Complicated Urinary tract Infection in
countries with a high prevalence of multidrug
resistant Gram-negative bacteria
Rationale • cUTI are among most frequent community as well
health-care related infections
• Increasing prevalence of MDR-GNB (multi-drug resistant Gram-negative bacteria) worldwide is a major concern
• To provide current data from European regions with a high prevalence of MDR GNB regarding:
– Antimicrobial resistance among patients with cUTI
– Clinical management and outcomes of hospitalised patients with cUTI
– Costs of cUTI
Complicated
Urinary Tract Infection (cUTI)
Complicated urinary tract infection occurs in individuals with
functional or structural abnormalities of the genitourinary
tract, including pyelonephritis
FDA 2015.cUTI: Developing Drugs for Treatment Guidance for Industry
Pyelonephritis Catheter-related UTI
Nephrolithiasis Urinary diversion
Selected Countries
Spain
Italy
Hungary
Romania
Bulgaria
Greece
Turkey
Israel
1,006 episodes 1,148 isolates
Country Hospital Principal Investigator
Bulgaria Emergency Hospital Pirogov Prof. Dora Tancheva
Bulgaria University Hospital Queen Joanna Prof. Rossitza Vatcheva-
Dobrevska
Greece Attikon University Hospital Prof. Sotirios Tsiodras
Greece Hippokration Hospital Prof. Emmanuel Roilides
Hungary Kenezy Gyula Hospital Prof. Istvan Várkonyi
Hungary Soproni Erzsébet Oktató Kórház és Rehabilitációs Intézet Dr. Judit Bodnár
Hungary Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi
Oktatókórház Dr. Aniko Farkas
Israel Beilinson Hospital, Rabin Medical Center Dr. Noa Eliakim
Israel Rambam Health Care Campus Prof. Mical Paul
Israel Tel Aviv Medical Center Prof. Yehuda Carmeli
Italy AORN dei Colli Monaldi Prof. Emanuele Durante
Italy Azienda ospedaliero-universitaria policlinico di modena Prof. Cristina Mussini
Italy National Institute for Infectious Diseases L. Spallanzani Dr. Nicola Petrosillo
Romania Infectious Diseases Hospital Sfanta Parascheva Iasi Dr. Andrei Vata
Romania National Institute for Infectious Diseases "Prof Dr Matei Bals" Prof. Adriana Hristea
Spain Bellvitge University Hospital Dr. Miquel Pujol
Spain Hospital Universitario 12 de Octubre Dr. Julia Origüen
Spain Hospital Universitario Virgen Macarena Prof. Jesus Rodriguez-Baño
Turkey Ankara Numune Egitim ve Araştırma Hastanesi Dr. Arzu Yetkin
Turkey Istanbul University Cerrahpasa Medical School Prof. Nese Saltoglu
RESCUING: Epidemiological characteristics
Nº of episodes: 1006 episodes
Gender (F/M) 545 (54%) / 461 (46%)
Age (mean, SD) 66y (+ 17.8)
Admission: (cUTI/Other reason)
651 (64.7%)/ 355 (35.3%)
Admitted from:
Home 828 (82.3%)
LTCF 48 (4.8%)
Nursing Home 45 (4.5%)
Other hospital 85 (8.5%)
Charlson Score (median IQR) 2 (1-4)
Discharge
Died before discharge 90 (8.9%)
Home 805 (80%)
Hospital/LTCF 111 (11,1%)
Nº of episodes
Functional capacity
Independent 535 (53%)
Needs assistance 219 (21.8%)
Does not leave home 89 (8.8%)
Bedridden 160 (15.9%)
UTI within year 263 (26.1%)
Antibiotic within 30 days 203 (20.2%)
FQ 54/203 (26,6%)
Amoxi-clav 32 (15.7%)
2nd G Cephaloporins 6 (2.9%)
3erd G Cephalosporins 19 (9.3%)
Carbapenems 17 (8.3%)
Fosfomycin 9 (4.4%)
Nº of episodes
cUTI acquisition site
Community 556 (55.3%)
Healthcare related 254 (25.2%)
Hospital 196 (19.5%)
Infection source
Indwelling urinary catheterisation 340 (33.8%)
Pyelonephritis normal anatomy 200 (19.9%
Obstructive uropathy 157 (15.6%)
Urinary tract diversion 92 (9.1%)
Other events 217 (21.6%)
Infection severity
Septic shock/severe sepsis 149/938 (15.9%)
Bloodstream infection 241 (24%)
Aetiology (1148 isolates) / Source of Infection (1006 episodes)
Source E coli n=565 (49%)
KP n=168 (15%)
P.aeruginosa
n=97 (8%)
P.mirabilis n=79 (7%)
Enteroc spp n=82
Indwelling urinary catheterisation
(n=340)
127/340 37%
63/340 18.5%
58/340 17%
40/340 11.7%
49/340 14.4%
Pyelonephritis normal anatomy
(n=200)
151/200 75%
25/200 12.5%
4/200 2%
13/200 6.5%
1/200 0.5%
Obstructive uropathy (n=157)
100/157 63%
26/157 16.5%
12/200
6%
11/157 7%
9/157 5.7%
Urinary tract diversion (n=92)
48/92 52%
19/92 20%
10/200 5%
2/92 2.1%
12/92 13%
Others (n=217) 139/217
64% 35/217
16% 13/200
6.5% 13/217 10.6%
11/217 5%
Patterns of antimicrobial resistance by the four
main identified bacteria
AMG-
R
FQ-
R
3rd Gen
Ceph-R
PIP/TAZ
-R
CARB-
R
Resistance to
>3antimicrobial
categories
(MDR)
Resistance
>5antimicrobial
categories
(XMDR)
E. coli
n=565 (49.2%) 18.5% 39.0% 24.1% 10.4% 1.8% 14.5% 0.4%
K. pneumoniae
n=168 (14.6%) 49.4% 61.4% 63.7% 40.5% 17.9% 53% 13.1%
P. aeruginosa
n=97 (8.4%) 31.9% 43.3% 50.5% 24.7% 37.1% 37.1% 14.4%
P. mirabilis
n=79 (6.9%) 36.7% 55.7% 25.4% 7.6% 5.0% 24.1% 1.3%
Magiorakos, Clin Microbiol Infect 2012; 18: 268–281
MDR and XMDR / Source of Infection
Source (episodes) MDR (>3)
XMDR
(>5)
Indwelling urinary catheterisation (n=340)
136/340 40%
27/340 7.9%
Pyelonephritis normal anatomy (n=200)
34/200 17%
5/200 2.5%
Obstructive uropathy (n=157)
41/157 26.1%
7/157 4.4%
Urinary tract diversion (n=92) 22/92 23.9
7/92 7.6%
Others (n=217) 50/217
23% 11/217
5%
AG, FQ, BL-I, 3GC, CP
Predictive factors of MDR. Univariate analysis
14
Susceptible
n (%)
MDR
n (%) p value (*)
Mean age +SD 65+18.7 66+16.8 0.526
Male gender 270 (39.1) 150 (67.1) <0.001
Admission: Elective 97 (14) 44 (17.1) 0.236
Admission reason: UTI 477 (69) 145 (56.4) <0.001
Admitted from Health Care System 98 (14.2) 67 (26.1) <0.001
Underlying disease
Congestive Heart failure 134 (19.4) 47 (18.3%) 0.701
Cerebral-vascular disease 122 (17.7) 60 (23.3) 0.048
Chronic pulmonary disease 91 (13.2) 44 (17.1) 0.122
Diabetes mellitus 186 (26.9) 64 (24.9) 0.531
Chronic kidney disease 191 (27.6) 72 (28) 0.909
Chronic Liver disease 35 (5.1) 15 (5.8) 0.637
Charlson > 3 299 (43.3) 119 (46.3) 0.403
Organ transplant 45 (6.5) 20 (7.8 0.492
Immunosuppression 64 (9.3) 30 (11.7) 0.270
Steroids 46 (6.7) 22 (8.6) 0.313
Functional capacity: Dependent 298 (43.3%) 138 (53.9) 0.003
15
Susceptible
n (%)
MDR
n (%)
p value
(*)
Source
Indwelling urinary
catheterisation
189 (27.4) 119 (46.3) <0.001
Pyelonephritis normal
tract anatomy
164 (23.7) 32 (12.5) <0.001
Obstructive uropathy 114 (16.5) 38 (14.8) 0.523
Anatomical tract
modification
64 (9.3) 20 (7.8) 0.476
Other 160 (23.2) 48 (18.7) 0.139
Shock - Severe sepsis 104 (16.2) 36 (14.9) 0.635
Aetiology
E. coli 478 (69.2) 81 (31.5%) <0.000
K.pneumoniae 81 (11.7) 87 (33.9) <0.001
P.aeruginosa 57 (8.2) 38 (14.8) <0.003
P. mirabilis 56 (8.1) 23 (8.9) 0.676
Predictive factors of MDR. Univariate analysis
% MDR infection by COUNTRY
20
40
60
Bulgaria Greece Turkey Italy Israel Romania Hungary Spain
%M
R in
fectio
n
Bulgaria
Greece
Turkey
Italy
Israel
Romania
Hungary
Spain
% MDR infection by CENTER
0
20
40
60
80
MR
infe
ctio
n
Emergency Hospital Pirogov
Hippokration Hospital
Ankara Numune Research and Training Hospital
Nat. Inst. for Infectious Diseases L.Spallanzani
Kenezy Gyula Hospital
Univ.Hosp. Queen Joanna
Rambam Health Care Campus
Nat. Inst. for Infectious Diseases M.Bals
AORN dei Colli - Monaldi
Policlinico di Modena
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
Cerrahpasa Medical School
Rabin Medical Center Campus Beilinson
Tel Aviv Medical Center
Infectious Diseases Hospital Sfanta Parascheva Iasi
Hosp.Univ.12 de Octubre
Hosp.Univ.Virgen Macarena
Attikon University Hospital
Hosp.Univ.Bellvitge
Soproni Erzsébet Oktató Kórház és Rehabilitációs Intézet
Predictive model
multiresistance
• Patients from 20 different hospitals (8 countries) to study factors that predict multiresistant infection.
• Hospitals/ countries presented higher or lower % of MR, so the baseline probability of MDR infection into each of the hospitals is different.
• Model estimation:
• Mixed effects logistic regression.
• Stepwise selection method based on Akaike Information Criteria (AIC) to identify the variables that explain the bulk of the MR infection.
• Bootstrapping resampling method.
Methods
• Potential predictors include patient’s age, sex, source, admitted
from, functional capacity score, myocardial infarction, congestive
heart failure, peripheral vascular disease, cerebrovascular
disease, dementia, chronic pulm disease,ulcer disease,diabetes
mellitus, chronic kidney disease, hemiplegia, solid tumour, liver
disease, metastatic, Charlson, acquisition site, indwelling urinary
catheter, urinary retention, organ transplant, organ transplant
kidney, immunosuppressive therapy, active chemotherapy,
corticosteroid therapy, uti within year, antibiotic within 30d, QUIN,
PEN, CEFA, CARBA, OTHER, infection severity, neurogenic
bladder, obstructive uropathy, renal impairment and urinary tract
modification.
Estimated predictive
model for MDR
Factors OR CI95% p-value
(Intercept) 0.10 0.06 0.15 <0.00001
Gender (Male) 1.80 1.29 2.51 0.00050
Admitted from medical facility 1.33 0.86 2.08 0.19762
Acquisition in a medical facility 2.47 1.66 3.67 <0.00001
Indwelling urinary catheter 1.36 0.92 2.01 0.11857
UTI within year 2.03 1.36 3.03 0.00051
Antibiotic within 30d 1.55 1.03 2.34 0.03753
OR: Odds Ratio; CI95%: confidence interval at 95%
Ranking of importance of predictors
Adquisition medical facility
Gender (Male)
UTI within year
Indwelling urinary catheter
Admited from medical facility
Antibiotic within 30d
0 5 10 15 20 25F value
ROC Curve
Model performance
Specificity
Sensitiv
ity
1.0 0.8 0.6 0.4 0.2 0.0
0.0
0.2
0.4
0.6
0.8
1.0
AUC= 0.78 CI95% 0.74 - 0.81
Observed vs predicted by center
10
20
30
Attikon University HospitalSoproni Erzsébet Oktató Kórház és Rehabilitációs IntézetHosp.Univ.BellvitgeHosp.Univ.Virgen MacarenaKenezy Gyula HospitalSzabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi OktatókórházCerrahpasa Medical SchoolHosp.Univ.12 de OctubrePoliclinico di ModenaAORN dei Colli - MonaldiRabin Medical Center Campus BeilinsonTel Aviv Medical CenterUniv.Hosp. Queen JoannaInfectious Diseases Hospital Sfanta Parascheva IasiNat. Inst. for Infectious Diseases L.SpallanzaniNat. Inst. for Infectious Diseases M.BalsRambam Health Care CampusHippokration HospitalAnkara Numune Research and Training HospitalEmergency Hospital Pirogov
centre_name
Ob
se
rved
Pre
dic
ted
Conclusions
• The epidemiology of cUTI is changing
• There's an increasing importance of cUTI-HCR infections and
among them of MDR K.pneumoniae isolates
• Rates of antibiotic resistance vary according to source of
infection and aetiology
• Our model performed among patients with cUTI selected:
gender, admission, acquisition, indwelling urinary catheter, uti
within year and antibiotics within 30d as significant predictive
factors for MDR pathogens
WP5 Team (Alphabetically)
• Addy, Ibironke AiCuris Anti-infective Cures, EFPIA, WP5 Lead
• Babich, Tanya Tel-Aviv University
• Carratala, Jordi Bellvitge University Hospital, Barcelona
• Corthals, Sophie University Medical Centre Utrecht
• Couperus, Janet University Medical Centre Utrecht
• Cuperus, Nienke University Medical Centre Utrecht
• Eliakim-Raz, Noa Tel-Aviv University
• Gibbs, Julie North Bristol NHS Trust
• Grier, Sally North Bristol NHS Trust
• McGowan, Alasdair North Bristol NHS Trust
• Morris, Steve University College London
• Leibovici, Leonard Tel-Aviv University, Academic WP5 Lead
• Pujol, Miquel Bellvitge University Hospital, Academic WP5 Lead
• Shaw, Evelyn Bellvitge University Hospital
• Vallejo-Torres, Laura University College London
• Vigo, Joan Miquel Area d'Informàtica FICF
• van den Heuvel, Leo University Medical Centre Utrecht
• Vank,Christiane AiCuris Anti-infective Cures, EFPIA
• Vuong, Cuong AiCuris Anti-infective Cures, EFPIA
Country Hospital Principal Investigator
Bulgaria Emergency Hospital Pirogov Prof. Dora Tancheva
Bulgaria University Hospital Queen Joanna Prof. Rossitza Vatcheva-Dobrevska
Greece Attikon University Hospital Prof. Sotirios Tsiodras
Greece Hippokration Hospital Prof. Emmanuel Roilides
Hungary Kenezy Gyula Hospital Prof. Istvan Várkonyi
Hungary Soproni Erzsébet Oktató Kórház és Rehabilitációs Intézet Dr. Judit Bodnár
Hungary Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi
Oktatókórház Dr. Aniko Farkas
Israel Beilinson Hospital, Rabin Medical Center Dr. Noa Eliakim
Israel Rambam Health Care Campus Prof. Mical Paul
Israel Tel Aviv Medical Center Prof. Yehuda Carmeli
Italy AORN dei Colli Monaldi Prof. Emanuele Durante
Italy Azienda ospedaliero-universitaria policlinico di modena Prof. Cristina Mussini
Italy National Institute for Infectious Diseases L. Spallanzani Dr. Nicola Petrosillo
Romania Infectious Diseases Hospital Sfanta Parascheva Iasi Dr. Andrei Vata
Romania National Institute for Infectious Diseases "Prof Dr Matei Bals" Prof. Adriana Hristea
Spain Bellvitge University Hospital Dr. Miquel Pujol
Spain Hospital Universitario 12 de Octubre Dr. Julia Origüen
Spain Hospital Universitario Virgen Macarena Prof. Jesus Rodriguez-Baño
Turkey Ankara Numune Egitim ve Araştırma Hastanesi Dr. Arzu Yetkin
Turkey Istanbul University Cerrahpasa Medical School Prof. Nese Saltoglu