Download Nosocomial Infections - Middle East Critical Care Assembly

Nosocomial Infections
Emergence of Antimicrobial
Resistance
Mazen Kherallah, MD, FCCP
King Faisal Specialist Hospital & Research Center
Impact of Antibiotic Restriction on Resistance
Neurosurgical Intensive Care Unit in London
60
All antibiotics stopped
50
40
30
20
10
0
1968
Total infections
1969
1970
Infections due to Klebseilla aerogenes
Price. Lancet. 1970
Rate of Device-Related
Infections in ICU
No. infection per 1000
device days
100
80
60
40
20
0
Pneumonia
BS-CRI
KFSH-Jeddah
UTI
Decrease in Hospital-acquired ICU
Infection Rates, NNIS, 1990-1999
Type of ICU CR-BSI (%)
VAP (%)
CR-UTI (%)
Medical
44
56
46
Surgical
31
38
30
Pediatric
32
26
59
Possible Explanation for
Decrease in Infection Rate
• Efforts to prevent infections: new research
findings, prevention guidelines
• Shift of health care from hospital-based care
• True decrease secondary to adhesion to
infection control policies
Antimicrobial Resistance:
A Global Problem
• ICAAC 1998
• Antimicrobial Resistance Symposium: 200
attendees
• Infectious disease physicians (25%),
microbiologist (25%), other physicians,
pharmacists, etc. (50%)
• 80% agreed that antimicrobal resistance is
increasing70% believed resistant pathogens
cause greater mortality
Antimicrobial Resistance:
A Global Problem
In the past year North
have you seen
America
>5 patients with:
South
America
Europe
Africa
Asia
VRE
55%
7%
6%
25%
100%
ESBL
54%
91%
50%
71%
83%
Resistant
Acinetobacter
46%
100%
16%
71%
100%
Rates of Resistance Among Nosocomial Infections Reported
in Intensive Care Patients, Comparison of 1999 (JanuaryJuly) with Historical Data
VRE
Methicillin/CNS
MRSA
3rd Ceph/E.coli
3rd Ceph/K.Pneum.
Imipenem/seud
Quinolone/Pseud.
3rd Ceph/Pseud.
3rd Ceph/Enterobacter
0
10
20
30
40
50
% Resistance
January-July 1999
1993-1998
60
70
80
90
Percentage of Resistance
KFSH&RC Jeddah
100
90
80
44
70
65
70
35
30
ESBL
Ceft/Acinet.
60
95
50
40
30
56
20
10
5
0
MRSA
VRE
Emerging Pathogens
• Methicillin-resistant Staphylococcus aureus
(MRSA)
• Methicillin-resistant Staphylococcus
epidermitis (MRSE)
• Vancomycin-resistant enterococci (VRE)
• Vancomycin-intermediate Staphylococcus
aureus (VISA)
• Extended-spectrum beta-lactamase (ESBL)producing gram-negative organisms
• Multidrug-resistant Acinetobacter spp.
% MRSA
Percentage of Nosocomial Staphylococcus aureus
Reported as Resistant to Methicillin, by year
45
40
35
30
25
20
15
10
5
0
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998
Year
National Nosocomial Infections Surveillance (NNIS), 1989-1998: system Data
% resistant
Methicillin Resistant
Staphylococci by setting
90
80
70
60
50
40
30
20
10
0
ICU
S.aureus
Non-ICU
Outpatient
Coagulase-negative Staphylococci
Fridkin. Clin Infect Dis.1999
35
0.8
30
0.7
0.6
25
0.5
20
0.4
15
0.3
10
0.2
5
0.1
0
0
1990
1991
Centers (n)
1992
1993
1994
Infection rate (per 1000 days)
1995
1996
1997
Linear (Infection rate (per 1000 days))
International Network for Surveillance and Prevention of Emerging
Antimicrobial Resistance (INSPEAR)
Infections per 1000 days
Number of participating hospital
Secular Trend in MRSA Infections
INSPEAR, 1990-1997
Methicillin-Resistant
Staphylococcus aureus:
Current Status
• Endemic beginning 1980 in hospitals
• Increasing reports of community infections:
– Pediatric outpatients in Chicago
– Alaskan natives
– 4 Pediatric deaths: MMWR 1998
Epidemiology of VRE
• Present in all 50 states in the United States
• Number of isolated continues to grow
• Recognized in Europe, Japan, Central and
South America
• Resistance to alternate antibiotic therapy
continues to be a problem
Progression of Vancomycin Resistance
Enterococci
Resistant Isolates
30
25
20
15
10
5
0
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999
Non-ICU
ICU
Mortone. WJ. Infect Control Hosp Epidemiol. 1998
NNIS Antimicrobial Resistance Surveillance Report 1999
Risk Factors for VRE
• Prior broad spectrum antibiotics (especially
cephalosporins and vancomycin)
• Prolonged hospitalization
• Immunocompromised host
• Neutropenia
• Admission to an intensive care unit
• Renal failure requiring dialysis
Noskin. J Lab Clin Med. 1997
Antibiotics and Colonization
with VRE
Antimicrobial
Penicillins
Odds Ration
2.2
P
0.10
2nd and 3rd
Cephalosporins
Metronidazole
9.4
<0,001
3.6
0.02
Quinolons
2.2
0.40
Vancomycin
3.6
0.007
Ostrowsky. Arch Intern Med. 1999
Use of Vancomycin in US and
Rate of VRE
Usage of Vancomycin
Rate of VRE
20
18
100
16
14
80
12
60
10
8
40
% VRE
Kilogram of vanco (X100) purchased
120
6
4
20
2
0
0
84
85
86
87
88
89
90
91
92
93
94
95
96
97
Kirsl et al. Historical usage of vancomycin. Antimicrob Agent Chemo 1998
National Nosocomial Infection Surveillance System (CDC)
Independent Predictors of Vancomycin-Resistant
Enterococci in Adult Intensive Care Units
Change in Predictor
Estimated Change
in Rate of VRE
+++
P-value
Cephalosporin use (3rd)
++
0.0002
Vancomycin use
++
0.0001
Type of ICU
+
0.01
Non-ICU VRE rate
NNIS
0.0001
Enterococcal Resistance by
Species
90
80
70
60
50
Ampicillin resistant
Vancomycin resistant
40
30
20
10
0
E. faecium
E. fecalis
Jones. Diagn. Microbiol Infect Dis. 1998
Outcome of Enterococcus
faecium Bacteremia
Outcome Measure
VSE
(n=32)
13 (41)
VRE
(n=21)
16 (76)
0.009
Directly related
3 (9)
8 (38)
0.01
Indirectly related
6 (19)
5 (24)
0.24
Unrelated
4 (13)
3 (14)
0.31
Survival
19 (59)
5 (24)
0.009
Total hospital costs
$56,507
$83,897
0.04
Mortality
P
Stosor. Arch Intern Med. 1998
Impact of Formulary Change on VRE
Empiric therapy for febrile neutropenia
Factor
1998
1999
P
Cefepime
32
491
<0.0001
Piperacillin
755
71
<0.0001
Total cephalosporins
394
727
<0.0001
VRE colonization (per
1000 pt. Days)
VRE bacteremia
1.48
5.50
<0.0001
4
12
Antibiotic:
Lisgaris. IDSA (abstract). 2000
Prevention of GRE
Therapy for Febrile Neutropenia
• Purpose: reduce glycopeptide resistant
enterococci (GRE)
• Situation: 50% colonization rate in
oncology units
• Methods:
– Phase 1: no intervention (ceftazidime)
– Phase 2a and 2b: replace ceftazidime with
piperacillin/tazobactam
– Phase 3: return to ceftazidime
Bradley. JAC. 1999
Results
Phase
Colonization
Infection
1
57%
5
2a
29%
0
2b
8%
0
3
36%
3
Phase 1 vs 2b (P<0.001)
Bradley. JAC. 1999
Impact of CDC Guidelines on
Endemic VRE
Site
Barrier
Vancomycin
VRE
Precautions
Use
Colonization
Infection
NY
28% to 92%
-
MD
Initial 64%
59%
IN
22% to 88%
-
50%
35%
But not statistically
significant
0
80%
M. Montecalvo et al. Ann Int Med. 1999
J Morris et al. Ann Int Med. 1995
E Jochimsen et al. ICHE 1999
Emergence of Vancmycin-Intermediate
Staphylococcus aureus (VISA) in the World
• First episode reported in Japan, 1996
• Predicted risk factors:
– MRSA colonization/infection
– Frequent/sustained vancomycin exposure
• Predicted high risk population
–
–
–
–
ESRD on hemodialysis
Long-term CVCs
Rehab/skilled nursing facility patients
Prolonged ICU stay
Extended Spectrum -lactamases
ESBLs
• 1983: first reported in Europe
• 1988:: reported in the United States
• 1990’s: increased prevalence globally:
– ICU’s
– Acute care
– Extended care
• 2000: Problematic nosocomial pathogen
Extended Spectrum -lactamases
ESBLs
• ESBL inactivates oxyamino beta-lactams and
fourth-generation cephalosporins (to some extent)
and aztreonam
• Large plasmids encoding multiple antibiotic
resistance determinants including aminoglycoside
modifying enzymes
• Strains producing ESBL are typically sensitive to
cephamycins and carbapenems
• Common ESBL-producers: K. pneumoniae, and
less common other Enterobactericae
Klebsiella pneumoniae
Resistance to third-generation cephalosporins
CDC
14
12
Rate%
10
ICU
Non-ICU
8
6
4
2
0
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998
Fridkin and Gaynes. Clin Chest Med. 1999
K. pneumoniae Resistant to ExtendedSpectrum -lactam (ESBL) at NNIS
Evidence of Inter-hospital Transmission
70
60
%ESBL
50
Hospital A
0-20 miles from A
>20 miles from A
40
30
20
10
0
86
87
88
89
90
91
92
93
Mannel DL, et al. Infect Control Hosp Epidemiolo 1997
Emergence of Carbapenemresistant Acinetobacter spp.
• Frequent use of aminoglycosides,
fluroquinolones, ureidopenicillins and third
generation cephalosporins
• Reported from South America, Europe, Far
East, Middle East, and United States
• Numerous outbreaks (some strains
susceptible only to polymyxin B)
• High mortality rates
• Endemic in some hospitals
Endemic Carbapenem-Resistant
Acinetobacter spp. In Brooklyn, New York
• 15 hospitals
• November 1997, all aerobic bacteria collected
• Acinetobacter spp. (233) accounted for 10% of the
gram negative bacilli
• Carbapenem resistance ranged from 0-100%
• 10% of isolated were susceptible only to polymyxin
• Risk factors
– Use of third generation cephalosporins plus aztreonam
– Environment and healthcare worker hands
contamination documented
– PFGE documented inter- and intra-hospital spread
Antimicrobial Susceptibility of 233 Acinetobacter spp.,
15 Hospital, Brooklyn, New York
Polymixin B
Amikacin
Gentamicin
Ciprofloxacin
Imipenem
Ceftazidime
Ceftriaxone
Pip/tazobactam
Ampiillin/sulbactam
0
20
40
60
80
100
VM Manikal et al. CID. 2000
Control Measures
• Barrier precautions
• Oxyamino beta-lactam restriction
• Selective bowel decontamination
Antimicrobial Utilization and
Resistance
• Interdisciplinary team in Indianapolis to
control resistant organisms
• Interventions:
– Reduce third generation cephalosporin use
– Reduce imipenem use
– Encourage use of ampicillin/sulbactam and
piperacillin/tazobactam
– Enhance compliance with infection control
– Education regarding antimicrobial resistance
Antimicrobial Utilization and
Resistance
Rate of Resisatance (%)
Bacteria
1994
1998
VRE
16
6
E. cloacae
61
28
E. Aerogenes
63
11
Acinetobacter
17
9
MRSA
34
23
Piperacillin/tazobactam
resistant
Smith. Pharmacotherapy 1999
Impact of Formulary Changes on MRSA and
Ceftazidime Resistant K. Pneumoniae
No. of new cases per 1000
discharges
25
20
15
10
5
0
Baseline Intervention
MRSA
CRKP
• Reduce usage of
cephalosporins,
imipenem,
clindamycin and
vancomycin
• Increased use of lactam/-lactamase
inhibitors
Landman. Clin. Infect Dis. 1999
Ceftazidime Resistant K. pneumoniae
Cleveland VA Medical Center
35
800
30
700
Resistance (%)
500
20
400
15
300
10
200
5
100
0
0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
Months
%ceftaz. Res.
Ceftaz Use (Gm)
P/T Use (Gm/10)
45
48
Antibiotic use (g)
600
25
Cephalosporin Use and ESBL KP in ICUs
Indianapolis VA
Clone B
Cephalosporin use
6
300
5
250
4
200
3
150
2
100
1
50
0
0
1993
1994
1995
1996
1997
1999
2000
DDD/1000 patients days
No. of episodes/1000 patients days
Clone A
Impact of a Rotating Empiric Antibiotic
Schedule on Infectious Mortality in an
Intensive Care Unit
No rotation
Rotation
35
30
25
20
15
10
5
0
rGPC/1000 patient days
rGNR/1000 patient days
Raymond DP. Crit Care Med 01-Jun-2001, 29(6);1101-8
Impact of a Rotating Empiric Antibiotic
Schedule on Infectious Mortality in an
Intensive Care Unit
VAP Mortality%
35
30
25
20
15
10
5
0
No rotation
Rotation
Raymond DP. Crit Care Med 01-Jun-2001, 29(6);1101-8
Conclusion
• Epidemiology of resistance in gram-negative
and gram-positive organisms is complex, and is
influenced, in part, by selective antimicrobial
pressure
• Control measures for emerging resistance
include:
– Traditional infection control measures: contact
isolation
Conclusion
Judicious Use of Antimicrobial
• Decrease cephalosporin use
• Increase extended-spectrum penicillin/betalactamase inhibitor use
• Limit carbapenem and vancomycin use to
desired therapy
Handwashing compared to
Alcohol Hand
Time required
Efficacy
Acceptance by
personnel
Soap and Water
Handwashing
Alcohol Hand
Rub
30-120 seconds
10-30 seconds
Good to very
good
Excellent
Poor
Excellent