Проблемные Грам+ микроорганизмы в стационаре. Выбор

+
.
.
«
»
(+)
S. aureus
- MRSA
- VISA
- VRSA
Enterococcus spp.
,
MRSA
MRSA (methicillin-resistant S.aureus) –
S.aureus,
,
;
-
(
).
- MRSA
o CA-MRSA (community-associated MRSA) –
MRSA,
,
o HA-MRSA (healthcare-associated MRSA) –
MRSA,
British Society for Antimicrobial Chemotherapy Working Party on Community-onset MRSA Infection. J
Antimicrob Chemother 2008; 61 (5): 976-94/
,
MRSA
,
~35%
- 30-50%
~45%
- 70%
Infectious
disease
No. of deaths
Year
MRSA
19,000
20051
AIDS
14,561
20072
TB
644
20063
Viral
hepatitis
5793
20021
DeLeo and Chambers JCI 2009
adapted from Klevens JAMA 2007
1.Boucher CID 2008; 46(Suppl 5):S344-9
2. http://www.cdc.gov/hiv/topics/surveillance/basic.htm#ddaids
3 http://www.cdc.gov/TB/publications/factsheets/statistics/TBTrends.htm
MRSA:
< 0,05
25
=NS
20
<
0,05
15
10
5
0
(-)
MRSA
MSSA
Shor, e.a. Crit Care 2006
Mortality in MRSA and MSSA bacteraemia
two meta-analyses
MRSA
MSSA
50
Mortality (%)
40
30
36
RR=1.42
P<0.001
23
20
29
RR=2.12
P<0.001
12
10
0
1980–2000
N=3963
1990–2000
N=2209
MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible S. aureus; RR, relative risk.
Cosgrove et al. Clin Infect Dis 2003;36:53–59
Whitby. Med J Aust. 2001;175:264–267
MRSA vs. MSSA:
34,2 %
35
p<0,01
30
25
19,6 %
20
15
10
5
0
MSSA
MRSA
(n=245)
(n=193)
Shurland S., e.a. Inf Contr Hosp Epidemiol 2007; 28:273-8.
MRSA vs. MSSA:
-
MRSA
MSSA
.
-
?
Shurland S., e.a. Inf Contr Hosp Epidemiol 2007; 28:273-8.
, 2006-2007 (n=2382)
S.aureus
20,0%
0,5%
Enterococcus
spp, 5,7
Stenotrophomonas
1,8%
Enterobacteriaceae
34,5%
(+)
Acinetobacter
spp.
11,1
P.aeruginosa
26,4%
– 24,5 %
, 2006-2007 (n=2382)
(+)
S. aureus (76,9 %)
(24,5 %)
Enterococcus spp. (23,1 %)
E. faecalis
(42,2 %)
E. faecium
(37,8 %)
(20 %)
(+)
~ 50%
~ 25%
– MRSA; ~ 50%
-R
~15 %
,
(+)
–
:
Results of EU-VAP/CAP Study*
Other
2%
S. pneumoniae
4%
H. influenzae /
M. catarrhalis
6%
P. aeruginosa
17%
Other
Enterobacteriaceae
13%
A. baumannii
15%
K. pneumoniae
9%
E. coli
10%
MRSA
11%
*Endorsed by European Society of Intensive Care Medicine (ESICM)
Koulenti D, et al. Crit Care Med 2009
MSSA
13%
Enterobacter spp
3.9%
Pseudomonas aeruginosa
4.3%
Klebsiella spp
4.8%
Escherichia coli
5.6%
Candida spp
9.0%
Serratia spp
1.7%
Acinetobacter baumannii
1.3%
CoNS
31.3%
Methicillin resistance
75% of CoNS isolates
41% of S. aureus isolates
Vancomycin resistance
60% of Enterococcus faecium
isolates
2% of Enterococcus faecalis
isolates
Enterococci
9.4%
Staphylococcus aureus
20.2%
CoNS: coagulase-negative Staphylococcus species.
Wisplinghoff et al. Clin Infect Dis. 2004;39:309–317.
(+) –
SENTRY (
)
)
S.aureus –
1. G.J. Moet et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 7–13
1998-2004.
(+)
26,4%
,
,
,
,
!
,
,
,
SENTRY (
)
)
1998-2004.
,
!
1. G.J. Moet et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 7–13
2.
.,
.
:
,
.
. 2004, .6,
2.
(+)
, 2006-2008 (n=2382)
5
%
57
5,1
63
37,2
43
10,3
9,2
23,2
38,4
13,7
22,9
1,3
9,4
10,9
1,7
5,6
0
Enterococcus spp.
S.aureus
(+)
10,8
12,5
19,3
20
40
60
80
Kozlov R.S., e.a. ICAAC 2008. K-4108
MRSA
7,7
10,9
/
42,1
54,8
77,5
0
10
20
30
40
50
60
70
80
%
L. Stratchounski, e.a.
ECCMID 2003
MRSA –
:(8,9)
,
–
Fluoroquinolones
–
Aminoglycosides
Cephalosporins
–
Macrolides
–
(8)
–
(
)(8)
.
(8)
(8)
(8)
–
(8)
–
–
(9)
(10)
–
–
–
(10)
–
(8)
I
(8)
–
–
(9)
–
(10)
(11)
*ICU: Intensive Care Unit
(8) Boyce JM. Clin Updates Infect Dis 2003;6:1-6.
(9) Graffunder EM et al. J Antimicrob Chemother 2002;49:999-1005.
(10) Haddadin AS et al. Postgrad Med J 2002;78:385-92.
(11) ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416.
(10)
,
:
1.
.
2.
.
:
.
1.
2.
.
3.
.
MRSA?
•
•
•
•
•
•
PRP
MRSE
VRE
MRSA
(R+I) S.aureus
54.4
33.4
0
0
0
0
2006-2007
2001-2002
2.4
0
0.9
0.3
0.17
0.8
24.8
6.9
52.8
9
54
13
43
27.1
53.2
30.6
41.9
37
50.8
39.5
57
42.9
0
10
20
30
40
50
60
Dekhnich A., e. a. ECCMID 2009
Enterococcus spp.
0
E. faecalis
E. faecium
0
39.1
11
66.1
4
69.5
45
69.5
52
55.8
56
45.8
72
88.1
70
0
10
20
30
40
50
60
70
80
90
%
5
(
/
15
/ ,
,
),
— 15-20
/ .
4
,
,
.
?
(
)
,
.
Vancomycin Susceptibility
Breakpoints in Staphylococci
MIC (µg/ml)
Interpretation
2
Susceptible
4-8
Intermediate
16
Resistant
CLSI
C
S.aureus
MRSA-
,
?
MRSA-
,%
:
60
52
50
40
29
30
20
8
10
0
0,5
1
2
,
Gould I. Int J Antimicrob Agent 2008; 31(Suppl.2):1-9.
(%)
65,0
31,1
12
8
25
6
51
2
32
64
16
8
4
2
0,9 0,0 0,0 0,0 0,0 0,0 0,0 0,0 0,0
1
0,
5
0,
01
5
0,
03
0,
06
0,
12
5
0,
25
0,0 0,0 0,0 0,0
3,0
,
.,
.
2008; 4.
MRSA,
100
87,5
90
80
70
60
%
50
40
30
20
10
6,9
5,6
0
0.5;
.,
.,
Staphylococcus aureus
:
.
. 2002; 4 (4): 325–36.
.
= 1;
2;
.
.
.
.
Staph. aureus «
vitro
52%
» in
23%
8%
Mohr JF, Murray BE. Point: vancomycin is not obsolete for the treatment of infection caused by methicillin- resistant
Staphylococcus aureus. Clin Infect Dis 2007; 44:1536–42.
-
Retrospective review
70
P = 0.002
Multivariate linear regression
Only trough > 20 g/ml for
all (RR, 2.82)
Only duration of
vancomycin > 14 days
if vasopressor use
excluded (RR, 3.33)
Renal Toxicity (%)
60
50
40
30
20
10
0
< 15
15-20
> 20
Vanco Serum Trough Levels
Jeffres MD, et al. Clin Ther. 2007;29:1107-15.
http://sia-r.ru/literature/
"
MRSA,
.
."
–
(+)
DRP
MRSA, MRSE, VRE,
(+)
-
/
Roberts. Clin Pharmacokinet 2006;45:755-773
vs.
,
MRSA
-
,
S. aureus
,
80% (60/75)
,%
60
53% 52%
63,5%
MRSA
(54/85) (p=0,03)
59%
52%
50
43%
36%
40
30
20
=N
S
=N
S
ITT
S.aureus
<0,0
1
10
0
MRSA
Wunderink RG et al. Chest
2003;124:1789-97.
,
MRSA
Retrospective analysis of 2 randomised, double-blind studies
Survival (% Patients)
100
90
80
70
60
Linezolid
Vancomycin
50
4
9
14
19
Time After Diagnosis (Days)
Adapted from Wunderink R, Rello J, et al. CHEST. 2003;124:1789-1797.
24
29
MRSA
Clinical Cure (% Patients)
Retrospective analysis of 2 randomised, double-blind studies
70
60
50
40
Vancomycin
Linezolid
53.7
48.9
45.4
36.7
62.2
37.7
35.2
30
21.2
20
10
P = 0.07
P = 0.02
P = 0.06
P = 0.01
VAP
Gram+ VAP
S. aureus
VAP
(n = 179)
MRSA VAP
0
(n = 434)
(n = 214)
Adapted from Kollef MH, Rello J, et al. Intensive Care Med. 2004;30:388-394.
(n = 70)
,
MRSA
21
i
2010
ZEPHyR
Linezolid in the treatment of subjects with nosocomial pneumonia proven to
be due to methicillin-resistant Staphylococcus aureus
,
,
1225
156
ZEPHyR presented at the 48th Annual Meeting of the Infectious
Diseases Society of America. October 21, 2010. Vancouver , Canada
MRSA.
MRSA
MRSA
78%
78%
ITT
mITT
PP
Kunkel M, Chastre JE, Kollef M, et al. Linezolid vs vancomycin in the treatment of nosocomial pneumonia proven due to methicillin-resistant
Staphylococcus aureus. Abstract presented at 48th Annual Meeting of the Infectious Diseases Society of America; Vancouver, Canada;
October 23, 2010.
23
2010 ., 48th annual meeting of the IDSA, Vancouver, Canada
,,
IDSA recommendations.
.
MRSA.
MRSA.
60
57.6
50
p=0,042
40
46.6
30
,
MRSA,%
20
10
0
600
12
ZEPHyR presented at the 48th Annual Meeting of the Infectious
Diseases Society of America. October 21, 2010. Vancouver , Canada
15
12
–
1
,
MRSA2
2
1
MRSA –
1
–
, /
3
S. aureus;
LaPlante, Rybak. Exp Opin Pharmacother 2004;5:2321–2331
Silverman et al. Antimicrob Agents Chemother 2003;47:2538–2544
2
3
1,
(+)
(+)
2
2,3
2,3
4
4
1
Canepari et al. Antimicrob Agents Chemother 1990;34:1220–1226;
Silverman et al. Antimicrob Agents Chemother 2003;47:2538–2544
3
Alborn et al., Antimicrob Agents Chemother 1991;35:2282–2287;
4
Steenbergen et al. J Antimicrob Chemother 2005;55:283–288
2
(
1
•
)
2
3
1–
,
2–
3–
1Steenbergen
et al. J Antimicrob Chemother 2005;55:283–288
K+
vs
:
1
1
:1–3
–
–
–
–
–
1. Finberg RW et al. Clin Infect Dis 2004;39:1314–1320
2. Pankey GA, Sabath LD. Clin Infect Dis 2004;38:864–870
3. Alder J, Eisenstein B. Curr Infect Dis Rep 2004;6:251–253
in vitro
(1–4
),
,
(+)
1
3
4
MRSA, VISA,
MRSE VRE2
1Wale
et al. J Med Microbiol 1989;30:45–49
Rybak et al. Antimicrob agents Chemother 2000;44(4):1062-6
3Raad I et al. Antimicrob Agents Chemother 2005;49:5046–5050
4Steenbergen et al. J Antimicrob Chemother 2005;55:283–288
:
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
:
Staphylococci
Streptococci
Enterococci*
Enterococci*
GramGram-positive strains that are resistant to multiple firstfirst-line antibiotics,
including:1,2
Staphylococcus aureus,
aureus,
Staphylococcus haemolyticus
CoagulaseCoagulase-negative staphylococci
Streptococcus pyogenes*
pyogenes*
Streptococcus agalactiae*
agalactiae*
Streptococcus dysgalactiae subsp.
subsp. equisimilis*
equisimilis*
Group G streptococci
Clostridium perfringens
Peptostreptococcus spp.
spp.
S. aureus (MRSA)
MRSA)
S. epidermidis (MRSE)
MRSE)
S. aureus (VRSA)
VRSA)
enterococci (VRE)
*
*
< 1mg/ml
:
,
S.aureus
,
S.aureus
:
-
:
-
:
,
,
-
,
,
<10
<1
>400
15-20
25-30
2
>400
,
<1
,
15-20
8-12 .
1,5
,
.
Clin Infect Dis 2009; 49:325-7
MSSA
MRSA
MRSA<1
15-20
-
. .
/ (8-12
15
,
>1
•
•
•
/ ,
Cmin
/ )
.
,
,
,
2010 .
?
?
antibiotic.ru
:
,
,
- e-mail:
kachanka.elena@mail.ru)
(
(
)
)
(USAID)
(USP)
,
.
.