1. Antibacterial policy and microflora in NICU Mari-Liis Ilmoja Tallinn Children`s Hospital

2. Birthweight (g) Incidence (Neonatal Research Network) Incidence Tallinn Children`s Hospital 2005 400 - 50043% 54% 501 - 75043% 751 - 100028% 1001 - 1250 15% 14% 1251 - 1500 7% Pediatrics 2002; 110:285-291 VLBW infants and LONS

3. LONS in VLBW premature newborns Karlowicz, M. G. et al. Pediatrics 2000 Isaacs, D. Arch Dis Child Fetal Neonatal Ed 2003 80 % MR

4. LONS in the NICU of Tallinn Children`s Hospital in 2005 M.-L. Ilmoja 2006 N=28

5. 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

6. 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

7. 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

8. Baltimore, R. S. et al. Pediatrics 2001;108:1094-1098 Susceptibility of E.coli to Ampicillin

9. Antibiotics?! Intrapartum antibiotic prophylaxis? Dinsmoor M et al; Obstetrics and Gynecology 2005

10. Effects of IP Penicillin Prophylaxis on Intestinal Bacterial Colonization in Infants No (%) of colonized infants OrganismNon-antibiotic exposedAntibiotic exposed Pvalue Enterobacteria16 (64)13 (52) 0,58 Amoxicillin-resistant12 (75)10 (77) 0,79 Enterobacteria Enterococci17 (68)15 (60) 0,73 Staphylococci22 (88)21 (84) 1 Bacteroides7 (28)13 (52) 0,15 Clostridium10 (40)3 (12) 0,04 Bifidobacterium 12 (48)6 (24) 0,18 Jaureguy F et al.; JCM 2004

11. 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

12. 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.

13. VLBW (n=1338); colonization with Candida in 20-60% infants (D Kaufman et al. Clin Microbiol Rev 2004; 17:638-680; YC Huang J Hosp Inf 2004; 58:200-203)

14. Colonization with Candida (L Saiman et al. Pediatr Infect Dis J 2001; 20:1119-1124; D Kaufman et al. Clin Microbiol Rev 2004; 17:638-680 )

15. 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

16. 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

17. Somebody to blame for? Colonization with resistant Gram-positive organisms did not increase with length of training Baker K, Clin Pediatrics, 2006

18. Tallinn Children`s Hospital: September 2003 - strict antibiotic policy accurate diagnosis choice of antibiotic length of course

19. 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)

20. 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

21. 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.

22. AB treatment for (suspected) congenital infection P=0,0002 5,5 ± 3,48,1 ± 3,8 Length 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)

23. AB treatment for (suspected) congenital infection P=0,000 2 5,5 ± 3,48,1 ± 3,8 Length 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.

24. P = 0,002 8,5 ± 4,2 13 ± 6,7 Length of course P = 0,028 12,3 ± 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

25. P = 0,002 8,5 ± 4,2 13 ± 6,7 Length of course P = 0,028 12,3 ± 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.

26. Positive blood cultures

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

30. Treatment of nosocomial infection Group I (N = 37) Group II (N = 34)

31. Treatment of nosocomial infection Tallinn Children`s Hospital, 2005

32. Methicillin-resistant CONS 2002 200320042005

33. Risk factors of nosocomial infection

34. Conclusions  Strict antibiotic policy can reduce the antibiotic burden and the antimicrobial resistance pattern in NICU without increase of septic complications.

35. Cost of antibiotics (EURO) Tallinn Children`s Hospital M.-L. Ilmoja 2006 ICU