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This study examines the effects of antibiotic policy on the microflora of VLBW infants in a NICU setting. It evaluates the susceptibility of VLBW infants to infections and the role of various factors such as epidermal barriers, microflora, and immune response in infection development. The study also discusses the use of intrapartum antibiotic prophylaxis and antibiotic cycling/mixing and their impact on colonization with antibiotic-resistant organisms.
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Antibacterial policy and microflora in NICU Mari-Liis Ilmoja Tallinn Children`s Hospital
VLBW infants and LONS Pediatrics 2002; 110:285-291
LONS in VLBW premature newborns 80 % MR 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 N=28 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
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 infants Organism Non-antibiotic exposed Antibiotic exposed Pvalue Enterobacteria 16 (64) 13 (52) 0,58 Amoxicillin-resistant 12 (75) 10 (77) 0,79 Enterobacteria Enterococci 17 (68) 15 (60) 0,73 Staphylococci 22 (88) 21 (84) 1 Bacteroides 7 (28) 13 (52) 0,15 Clostridium 10 (40) 3 (12) 0,04 Bifidobacterium 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
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 (D Kaufman et al. Clin Microbiol Rev 2004; 17:638-680; YC Huang J Hosp Inf 2004; 58:200-203)
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)
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)
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
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. 222 9,4%
Group I (N = 100) Group II (N = 104) Inf. risk factors ( 1) 53 (53%) 75 (72%) Initial AB treatment 90 (90%) 79 (76%) Length of course (days) 8,1 ± 3,8 5,5 ± 3,4 P=0,0002 AB treatment for (suspected) congenital infection
Group I (N = 100) Group II (N = 104) Inf. risk factors ( 1) 53 (53%) 75 (72%) Initial AB treatment 90 (90%) 79 (76%) Length of course (days) 8,1 ± 3,8 5,5 ± 3,4 P=0,0002 AB treatment for (suspected) congenital infection 2005.a. 67% 3,27
Group I (N = 100) Group II (N = 104) 37 (37%) 34 (36%) Nosocomial infection (NI) 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
Group I (N = 100) Group II (N = 104) 37 (37%) 34 (36%) Nosocomial infection (NI) 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. 21% 8,7
Treatment of nosocomial infection Group I (N = 37) Group II (N = 34)
Treatment of nosocomial infection Tallinn Children`s Hospital, 2005
Methicillin-resistant CONS 2002 2003 2004 2005
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 M.-L. Ilmoja 2006