Transcript Antibiotic policy and microbial colonization

Antibacterial policy and
microflora in NICU
Mari-Liis Ilmoja
Tallinn Children`s Hospital
VLBW infants and LONS
Birthweight
(g)
Incidence
(Neonatal Research Network)
Pediatrics 2002; 110:285-291
400 - 500
501 - 750
751 - 1000
1001 1250
1251 1500
Incidence
43%
43%
28%
15%
Tallinn Children`s
Hospital
2005
54%
14%
7%
LONS in VLBW premature newborns
80 %
MR
CONS
Candida spp.
Enterococcus spp.
Staph. aureus
Str. agalactiae
Pseudomonas spp.
Klebsiella spp.
Enterobacter spp.
E.coli
muu
Karlowicz, M. G. et al. Pediatrics 2000
Isaacs, D. Arch Dis Child Fetal Neonatal Ed 2003
LONS in the NICU of Tallinn Children`s
Hospital in 2005
7%
N=28
7%
11%
75%
CONS
Acinetobacter
Klebsiella spp.
Enterobacter spp.
M.-L. Ilmoja 2006
Susceptibility of VLBW Infants to
infections
•
•
•
•
•
•
•
Epidermal and epithelial barriers
Intact endothelial tissues
Gastrointestinal mucosa
Microflora
Complement, Cytokines
Neutrophils, Monocytes
T-cells,B-cells, antibodies
• Immature skin
• Humidification  moist skin
that favors the growth
of microorganizms
• Enhanced adherence of
bacteria to epithelial cells
• Colonization of ET and NG tubes
• Trauma from endotracheal and
nasopharyngeal suctioning
• Immature peristalsis and reduced absorption,
favoring micoorganism overgrowth
• Competitive bacterial microflora diminished
by broad-spectrum antibiotics
Antibiotics?!
Intrapartum antibiotic prophylaxis?
• GBS sepsis : 5,9 1,7 per 1,000
• E.coli sepsis : 3,2  6,8 per 1,000
Neonatal Research Network, 1991-1993 and 1998-2000
Susceptibility of E.coli to Ampicillin
Baltimore, R. S. et al. Pediatrics 2001;108:1094-1098
Intrapartum antibiotic prophylaxis?
Dinsmoor M et al; Obstetrics and Gynecology 2005
Effects of IP Penicillin Prophylaxis on
Intestinal Bacterial Colonization in Infants
Organism
No (%) of colonized infants
Non-antibiotic exposed Antibiotic exposed Pvalue
Enterobacteria
Amoxicillin-resistant
Enterobacteria
Enterococci
Staphylococci
Bacteroides
Clostridium
Bifidobacterium
16 (64)
12 (75)
13 (52)
10 (77)
0,58
0,79
17 (68)
22 (88)
7 (28)
10 (40)
12 (48)
15 (60)
21 (84)
13 (52)
3 (12)
6 (24)
0,73
1
0,15
0,04
0,18
Jaureguy F et al.; JCM 2004
Antibiotic combination?!
• Treatment of suspected maternofetal infection
with a combination of Amoxicillin + Cefotaxime +
Netilmycin resulted in rapid growth of
staphyococci and Candida spp.
• Babies , treated with Amoxicillin and Netilmicin ,
were colonized with Klebsiella oxytoca and E.
coli.
Bonnemaison E; Biol of Neon 2003
De Man P et al, The Lancet 2000
For patients receiving ampicillin, the concurrent use of
Cefotaxime during the3 first days after birth might be
associated with an increased risk of death, compared with
the concurrent use of gentamicin.
Clark, R. H. et al. Pediatrics 2006
VLBW (n=1338); colonization with
Candida in 20-60% infants
Huang 2004
Kaufman 2000
Kicklighter 1999
Huang 1996
Saiman 1995
Rowen 1992
Pappu-Katikaneni 1991
0%
C. albicans
20%
C. parapsilosis
40%
60%
C. tropicalis
80%
C. glabrata
100%
muu
(D Kaufman et al. Clin Microbiol Rev 2004; 17:638-680;
YC Huang J Hosp Inf 2004; 58:200-203)
Colonization with Candida
50
40
%
30
20
10
0
1000-1499g
<1000g
term
birthweight
GI tract
skin
trachea
UTI
(L Saiman et al. Pediatr Infect Dis J 2001; 20:1119-1124;
D Kaufman et al. Clin Microbiol Rev 2004; 17:638-680)
Antibiotic cycling or mixing?!
• A monthly rotation
of Gentamicin,
Piperacillin-tazobactam
and Ceftazidime.
• Rotation of parenteral
antibiotics has no detectable
effect in decreasing
the resistant Gram neg
bacilli in a tertiary NICU
Toltzis P et al; Pediatrics 2002
Antibiotic cycling or mixing?!
• Antibiotic prescription patterns balancing
the use of different antimicrobials should
be promoted to reduce the selection
pressure that aids the development of
resistance.
Sandiumenge A et al; J of Antimicrobial Chemotherapy 2006
Somebody to blame for?
Colonization with
resistant Gram-positive
organisms
did not increase
with length of training
Baker K, Clin Pediatrics, 2006
Tallinn Children`s Hospital:
September 2003 - strict antibiotic
policy
• accurate diagnosis
• choice of antibiotic
• length of course
• Aim of the study :
to evaluate the results of antibiotic
policy
• Methods:
retrospective chart review of two
periods, Jan - June, 2003 ( I group)
and Oct, 2003 - Febr,2004 (II group)
Demographic data
Group I
Group II
Newborn
100
104
male/female
61/39
63/41
birthweight (g)
2338 ± 1218
2292 ± 1147
weight < 1500 g
incl < 1000 g
22 (22%)
15
34 (32%)
17
Gestational week
34,1 ± 5,5
33,4 ± 5,5
< 37 GW
56 (56%)
68 (65%)
Died
17 (17%)
10 (9,6%)
Demographic data
2005.a.
Group I
Group II
Newborn
100
104
male/female
61/39
63/41
birthweight (g)
2338 ± 1218
2292 ± 1147
weight < 1500 g
incl < 1000 g
22 (22%)
15
34 (32%)
17
Gestational week
34,1 ± 5,5
33,4 ± 5,5
< 37 GW
56 (56%)
68 (65%)
Died
17 (17%)
10 (9,6%)
222
9,4%
AB treatment for (suspected)
congenital infection
Group I
Group II
(N = 100)
(N = 104)
Inf. risk factors ( 1)
53
(53%)
75
(72%)
Initial AB treatment
90
(90%)
79
(76%)
Length of course
8,1 ± 3,8
5,5 ± 3,4
(days)
P=0,0002
AB treatment for (suspected)
congenital infection
2005.a.
Group I
Group II
(N = 100)
(N = 104)
Inf. risk factors ( 1)
53
(53%)
75
(72%)
Initial AB treatment
90
(90%)
79
(76%)
Length of course
8,1 ± 3,8
5,5 ± 3,4
(days)
67%
P=0,000
2
3,27
Nosocomial infection
Group I
Group II
(N = 100)
(N = 104)
Nosocomial
infection (NI)
37
(37%)
34
(36%)
Age at the
diagnosis of NI
8,2 ± 3,4
12,3 ± 10
P=
0,028
Length of course
13 ± 6,7
8,5 ± 4,2
P=
0,002
Nosocomial infection
2005.a.
Group I
Group II
(N = 100)
(N = 104)
Nosocomial
infection (NI)
37
(37%)
34
(36%)
Age at the
diagnosis of NI
8,2 ± 3,4
12,3 ± 10
P=
0,028
Length of course
13 ± 6,7
8,5 ± 4,2
P=
0,002
21%
8,7
Positive blood cultures

Group I
Group II






KO
En
GB
En
En
ter
ter
ter
S
NS
oc.
oba
oba
(MR
fae
cte
cte
)
c.
r ia
r ia
cea
cea
e (E
e (E
SB
SB
L-)
L+)
Pse
Ser
rat
udo
ia
mo
nas
Sta
ph.
aur
.
Ca
ndi
da
Positive blood cultures

Group I
2005

Group II





KO
En
GB
En
En
ter
ter
ter
S
NS
oc.
oba
oba
(MR
fae
cte
cte
)
c.
r ia
r ia
cea
cea
e (E
e (E
SB
SB
L-)
L+)
Pse
Ser
rat
udo
ia
mo
nas
Sta
ph.
aur
.
Ca
ndi
da
Positive cultures from other sites
(trachea, pharynx, CSF)
Group I
Group II









En
te
En
KO
Ac
Pse
St a
KO
ter
ine
NS
NS
ph.
udo
rob
o
t
oba
b ac
( MR
a
m
act
u
r
ona
cte
ter
)
eria
i
r
s
a
cea
cea
e (E
e (E
SB
SB
L-)
L+)
Ca
nd
ida
Positive cultures from other sites
(trachea, pharynx, CSF)
Group I
2005

Group II








En
te
En
KO
Ac
Pse
St a
KO
ter
ine
NS
NS
ph.
udo
rob
o
t
oba
b ac
( MR
a
m
act
u
r
ona
cte
ter
)
eria
i
r
s
a
cea
cea
e (E
e (E
SB
SB
L-)
L+)
Ca
nd
ida
Treatment of nosocomial infection
Group I
(N = 37)
Group II
(N = 34)
Vanco
Vanco+Mer
Mer
Cef III
Vanco+Cef III
Gen+Cef III
Gen
B-lakt.inh
Vanco+Gen
Cef II
Oxa
Treatment of nosocomial
infection
Vanco+Gen
Meron
B-lact+Gen
Cef II
Cef III+Gen
Tallinn Children`s Hospital, 2005
Methicillin-resistant CONS
12
10
MIC of
Vancomycin
microg/ml
8
6
4
2
0
2002
2003
2004
2005
Risk factors of nosocomial infection
Indwelling vascular
catheters
With NI
(N = 34)
(95% CI)
19
30
13,42
(52%)
(93%)
(2,7 – 64,7)
Mean duration (d)
Birthweight < 1500 g
Mechanical ventilation
Mean duration (d)
OR
Without NI
(N = 36)
2,5
5
8,1
20
10,3
(13%)
(62%)
(3,1 – 33,8)
23
27
3,05
(63%)
(0,9 – 9,85)
(84%)
1,8
5,7
Conclusions
 Strict antibiotic policy can reduce the antibiotic burden
and the antimicrobial resistance pattern in NICU without
increase of septic complications.
Cost of antibiotics (EURO)
Tallinn Children`s Hospital
ICU
12000
10000
8000
6000
4000
2000
0
2003
2004
2005
Tienam
Meronem
Vancomycin
2099
1105
315
10232
4640
2152
2969
1157
672
M.-L. Ilmoja 2006