updating antibiotic resistant trends in hap and vap in ap countries

Po-Ren Hsueh
National Taiwan University Hospital
Lancet Infect Dis 2008
Updating Antibiotic Resistant Trends
in HAP/VAP in AP Countries
HAP
(Ward)
VAP
(ICU)
HCAP
(Nursing Home)
Hospital-acquired Pneumonia
Hospital Mortality and
Inappropriate initial Antimicrobial Therapy
Based on Classification of Infection Source
Micek S T et al. Antimicrob Agents Chemother 2010;54:1742-8.
Masterton RG et al. J Antimicrob Chemother 2008;62:5-34.
Asian HAP Working Group. Am J Infect Control 2008;36:S83-92.
Am J Respir Crit Care Med 2005;171:388–416.
HCAP , HAP
Guidelines
Key Elements Driving Development of Bacterial
Resistance and Risk of Treatment Failure
Wiest R, et al. Gut 2012;61:297e310.
Local
epidemiology
and resistance
profiles
Severity
of
patients

KPC
NDM
CR-, MDR-, XDR-,
PDR-PA
CR-, MDR-, XDR-,
PDR-AB
Main MDRO in
Hospitals
Sputum from a ICU Patient
Predictors of Mortality for MDR GNB Infection
The study, The Patient, the Bug or the Drug?
Meta-analysis
 Acinetobacter spp, P. aeruginosa, and Enterobacteriaceae
 Independent predictors
Vardakas KZ et al. J Infect 2013;66:401-14.
Risk ratio 95% CI
Cancer 1.65 1.13-2.39
Prior or current ICU stay 1.27 1.02-1.56
Septic shock 3.36 2.47-4.57
ICU stay 2.15 1.45-3.20
Pneumonia 1.6 1.09-2.52
Isolation of MDRGN bacteria 1.49 1.21-1.83
Inappropriate definitive treatment 2.05 1.12-3.76
Inappropriate empirical treatment 1.37 1.25-1.51
Male gender 1.13 1.05-1.21
Beyond comorbidity and severity scores, inappropriate
treatment and MDR were also identified as predictors of
mortality
Risk Factors for
Multidrug-Resistant Pathogens (MDRP)

HAP, VAP, HCAP
 Antimicrobial therapy in preceding 90 days
 Current hospitalization of 5 days or more
 High frequency of antibiotic resistance in the community
or in the specific hospital unit
 Presence of risk factor for HCAP
 Hospitalization for 2 days or more in preceding 90 days
 Residence in a nursing home or extended care fascility
 Home infusion therapy (including antibiotics)
 Chronic dialysis within 30 days
 Home wound care
 Family member with MDRP
 Immunosuppressive disease and/or therapy
Bonten MJ et al. Am J Respir Crit Care Med 2005;171:388-416.
De-escalation Therapy
Administer the broadest-spectrum antibiotic
therapy
(>80% S or combination therapy)
To improve outcomes: decrease mortality, prevent
organ dysfunction, and decrease length of hospital
stay
To minimize resistance and improve cost-
effectiveness
De-escalation:
Culture result, fever, short duration
P. aeruginosa, non-fermenters
Rello J. Crit Care Med 2004;32:2183-90.
Initial Empiric Antibiotic Therapy for HAP, VAP, HCAP
Risk Factors for MDRP, Late Onset,
Any Disease Severity

Potential pathogen Combination antibiotic therapy
Pathogens (early-onset) + Cefepime, ceftazidime
MDRP or
P. aeruginosa Imipenem or meropenem
K. pneumoniae (ESBL) or
Acinetobacter spp. Piperacillin-tazobactam
PLUS
Ciprofloxacin or levofloxacin
or
Amikacin, gentamicin, or tobramicin
PLUS
MRSA Linezolid or vancomycin
Bonten MJ et al. Am J Respir Crit Care Med 2005;171:388-416.
L. pneumophila
+ a macrolide (azithromycin) or
a fluoroquinolone
(CIP, LVX)
Piperacilline/Tazobactam trong điều trị MDR
P.seudomonas
Một vấn đề quan trọng khi sử dụng
Piperacilline/tazobactam cho điều trị MDR Pseudo là phải
xem xét đến là điểm gãy nhạy cảm của nó (≤64mcg/ml)
theo như khuyến cáo bởi CLSI cao gấp 2 lần điểm gãy của
Enterobactereacea (≤16mcg/ml).
Một NC cho thấy là BN nhiễm Pseudomonas aeruginosa
dùng Pip/Taz có tỷ lệ tử vong cao hơn khi MIC của
piperacillin 32-63 mcg/ml so với nhóm có MIC≤16mcg/ml .
Do đó khi MIC của piperacillin từ 32-64 mcg/ml thì nên
cân nhắc dùng KS khác hơn là piperacillin/tazobactam.
Expert Rev Anti Infect. Ther 8(1). 71-93 (2010)

Initial Empirical Antibiotic Treatment
for Late onset VAP- HAP in Asia
Potential pathogen
Recommended antibiotic regimen
MDR pathogens
P. aeruginosa
Acinetobacter
ESBL (+) K. pneumoniae
MRSA
Antipseudomonal carbepenem (imipenem or meropenem)
or beta-lactam/beta-lactamase inhibitor (piperacillin-
tazobactam)
± Fluoroquinolone (ciprofloxacin or levofloxacin)
or aminoglycoside (amikacin, gentamicin, or tobramycin)
± linezolid or vancomycin
cefoperazone/sulbactam + fluoroquinolones
or aminoglycosides
+ ampicillin/sulbactam (if sulbactam is not available)
± linezolid or vancomycin
or
fluoroquinolone (ciprofloxacin)
plus aminoglycoside
± linezolid or vancomycin
Asian HAP Working Group. Am J Infect Control 2008;36:S83-92.
14
11
9
18
21
17.8

16
9
23
20
28.2
16
23
18
7.6
5.8
7.7
26.3
42.1
23
17.6
13.1
11.8
0
10
20
30
40
50
China Korea Malaysia Philippines Taiwan Thailand
Etiology of HAP in Asia
K. pneumoniae P. aeruginosa A. baumannii MRSA
Chawla R. Am J Infect Control 2008;36:S93-100.
Comparison of major Microorganisms Isolated
from HAP and VAP in Asian Countries (N=2454)
Chung DR, Hsueh PR, Song JH et al. Am J Respir Crit Care Med 2011 (accepted)

30.1
42.8
4.9
0.7
67.3
82
51.1
0.2
0
10
20
30
40
50
60
70
80
90
100
CR MDR XDR PDR
P. aeruginosa Acinetorbactr spp.
Incidence of CR-, MDR-, XDR-, PDR-
P. aeruginosa and Acinetobacter spp.
%
HAP, VAP in Asia-Pacific
Chung DR, Hsueh PR, Song JH et al. Am J Respir Crit Care Med 2011 15;184:1409-17.
Carbapenems Non-susceptibility for
Major GNB Pathogens
COMPACT II study, Asia-Pacific, 2010
Kiratisin P et al. Int J Antimicrob Agents 2012;39:311-6.

(90)
(71)
(19)
(625)
(500
(135)
Healthcare-associated
Respiratory Tract Infections
147 Pathogens, NTUH, 2012
16.3
3.4
19
12.5
11.6
18.4
2.7
17
0 5 10 15 20
Others
S. marcescens
Enterobacter spp.
S. maltophilia
S. aureus
P. aeruginosa
Acinetobacter spp.
Klebsiella spp.
%
Resistance in Major HAP Pathogens
NTUH, 2011
27.2

39.6
20.6
39.6
27.5
40.4
21.8
36.3
30.2
9.8
32.9
0
10
20
30
40
50
60
70
Ceftazidime Cefepime Pip/Taz Ciprofloxacin Imipenem Amikacin
%
K. pneumoniae P. aeruginosa
A. baumannii
(ertapenem)
ESBL: 15.4%
Antimicrobial Resistance of Major
Pathogens causing HAI NTUH, 2012
Carbapenem Nonsusceptibility among GNB
Causing Healthcare-associated Infection
NTUH, 2000-2011
9.9

15.6
38.2
30.2
10.5
10.3
13
9.4
9.2
14.5
21
16.7
13
13.2
48.4
35.1
24.7
24.1
37.5
35.7
24.2
24.5
23.6
21.5
0
10
20
30
40
50
60

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
P. aeruginosa A. baumannii
% of isolates
Lai CC, Hsueh PR et al. J Antimicrob Chemother 2011;66:1374-82.
MRSA
K. pneumoniae
A. baumannii
P. aeruginosa
CTX
CAZ
CTX+CA CAZ+CA
CMZ
a
b
a-b ≥5 mm
c
d
c-d ≥5 mm
OR
ESBL
E. coli
K. pneumoniae
K. oxytoca
P. mirabilis
Susceptibility of Enterobacteriaceae
Cephalosporins
MIC (μg/ml)
CLSI-2009 CLSI-2012
EUCAST

Cefazolin ≤ 8 -
Cefotaxime ≤ 8 ≤ 1 ≤ 1
Ceftriaxone ≤ 8 ≤ 1 ≤ 1
Ceftazidime ≤ 8 ≤ 4 ≤ 1
Cefepime ≤ 8 ≤ 8 ≤ 1
Pip/Taz ≤ 16 ≤ 16 ≤ 8
≤ 2