Antibacterial policy and microflora in NICU

Mari-Liis Ilmoja

Tallinn Children`s Hospital

Birthweight

(g)

Incidence(Neonatal Research Network)

Incidence

Tallinn Children`s Hospital

2005

400 - 500 43%

54%

501 - 750 43%

751 - 1000 28%

1001 - 1250

15%

14%1251 - 1500

7%

Pediatrics 2002; 110:285-291

VLBW infants and LONS

LONS in VLBW premature newborns

CONS

Candida spp.

Enterococcus spp.

Staph. aureus

Str. agalactiae

Pseudomonas spp.

Klebsiella spp.

Enterobacter spp.

E.coli

muu

Karlowicz, M. G. et al. Pediatrics 2000Isaacs, D. Arch Dis Child Fetal Neonatal Ed 2003

80 %MR

LONS in the NICU of Tallinn Children`s Hospital in 2005

7%7%

11%

75%

CONS

Acinetobacter

Klebsiella spp.

Enterobacter spp.

M.-L. Ilmoja 2006

N=28

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

Baltimore, R. S. et al. Pediatrics 2001;108:1094-1098

Susceptibility of E.coli to Ampicillin

Antibiotics?! Intrapartum antibiotic prophylaxis?

Dinsmoor M et al; Obstetrics and Gynecology 2005

Effects of IP Penicillin Prophylaxis on Intestinal Bacterial Colonization in Infants

No (%) of colonized infantsOrganism Non-antibiotic exposed Antibiotic exposed Pvalue

Enterobacteria 16 (64) 13 (52) 0,58Amoxicillin-resistant 12 (75) 10 (77) 0,79EnterobacteriaEnterococci 17 (68) 15 (60) 0,73Staphylococci 22 (88) 21 (84) 1Bacteroides 7 (28) 13 (52) 0,15Clostridium 10 (40) 3 (12) 0,04Bifidobacterium 12 (48) 6 (24) 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

Clark, R. H. et al. Pediatrics 2006

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.

VLBW (n=1338); colonization with Candida in 20-60% infants

0% 20% 40% 60% 80% 100%

Pappu-Katikaneni 1991

Rowen 1992

Saiman 1995

Huang 1996

Kicklighter 1999

Kaufman 2000

Huang 2004

C. albicans C. parapsilosis C. tropicalis C. glabrata muu

(D Kaufman et al. Clin Microbiol Rev 2004; 17:638-680; YC Huang J Hosp Inf 2004; 58:200-203)

Colonization with Candida

0

10

20

30

40

50

%

<1000g 1000-1499g 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 parenteralantibiotics 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

10 (9,6%)17 (17%)Died

68 (65%)56 (56%)< 37 GW

33,4 ± 5,534,1 ± 5,5Gestational week

34 (32%) 17

22 (22%) 15

weight < 1500 g incl < 1000 g

2292 ± 11472338 ± 1218birthweight (g)

63/4161/39male/female

104100Newborn

Group IIGroup I

Demographic data

10 (9,6%)17 (17%)Died

68 (65%)56 (56%)< 37 GW

33,4 ± 5,534,1 ± 5,5Gestational week

34 (32%) 17

22 (22%) 15

weight < 1500 g incl < 1000 g

2292 ± 11472338 ± 1218birthweight (g)

63/4161/39male/female

104100Newborn

Group IIGroup I

9,4%

222

2005.a.

AB treatment for (suspected) congenital infection

P=0,00025,5 ± 3,48,1 ± 3,8Length of course (days)

79 (76%)

90 (90%)

Initial AB treatment

75 (72%)

53 (53%)

Inf. risk factors ( 1)

Group II (N = 104)

Group I (N = 100)

AB treatment for (suspected) congenital infection

P=0,00025,5 ± 3,48,1 ± 3,8Length of course

(days)

79 (76%)

90 (90%)

Initial AB treatment

75 (72%)

53 (53%)

Inf. risk factors ( 1)

Group II (N = 104)

Group I (N = 100)

67%

3,27

2005.a.

P = 0,0028,5 ± 4,213 ± 6,7Length of course

P = 0,02812,3 ± 108,2 ± 3,4

Age at the diagnosis of NI

34 (36%)

37 (37%)

Nosocomial infection (NI)

Group II(N = 104)

Group I(N = 100)

Nosocomial infection

Nosocomial infection

P = 0,0028,5 ± 4,213 ± 6,7Length of course

P = 0,02812,3 ± 108,2 ± 3,4

Age at the diagnosis of NI

34 (36%)

37 (37%)

Nosocomial infection (NI)

Group II(N = 104)

Group I(N = 100)

21%

8,7

2005.a.

Positive blood cultures

KONS (MR)

Enterobacteriaceae (ESBL-)

Enterobacteriaceae (ESBL+)

Enteroc.faec.

GBSPseudomonas

SerratiaStaph.aur.

Candida

Group I Group II

Positive blood cultures

KONS (MR)

Enterobacteriaceae (ESBL-)

Enterobacteriaceae (ESBL+)

Enteroc.faec.

GBSPseudomonas

SerratiaStaph.aur.

Candida

Group I Group II2005

Positive cultures from other sites (trachea, pharynx, CSF)

Enterobacteriaceae (ESBL-)

Enterobacteriaceae (ESBL+)

KONS (MR)

Acinetobacter

Pseudomonas

Staph. aur

KONSCandida

Group I Group II

Positive cultures from other sites (trachea, pharynx, CSF)

Enterobacteriaceae (ESBL-)

Enterobacteriaceae (ESBL+)

KONS (MR)

Acinetobacter

Pseudomonas

Staph. aur

KONSCandida

Group I Group II2005

Treatment of nosocomial infection

Vanco

Vanco+Mer

Mer

Cef III

Vanco+Cef III

Gen+Cef III

Gen

B-lakt.inh

Vanco+Gen

Cef II

Oxa

Group I(N = 37)

Group II(N = 34)

Treatment of nosocomial infection

Vanco+Gen

Meron

B-lact+Gen

Cef II

Cef III+Gen

Tallinn Children`s Hospital, 2005

Methicillin-resistant CONS

0

2

4

6

8

10

12

MIC of Vancomycin

microg/ml

2002 2003 2004 2005

Risk factors of nosocomial infection

Without NI(N = 36)

With NI (N = 34)

OR(95% CI)

Indwelling vascularcatheters

19(52%)

30(93%)

13,42(2,7 – 64,7)

Mean duration (d) 2,5 8,1

Birthweight < 1500 g 5(13%)

20(62%)

10,3(3,1 – 33,8)

Mechanical ventilation 23(63%)

27(84%)

3,05(0,9 – 9,85)

Mean duration (d) 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

0

2000

4000

6000

8000

10000

12000

2003 2099 10232 2969

2004 1105 4640 1157

2005 315 2152 672

Tienam Meronem Vancomycin

M.-L. Ilmoja 2006

ICU