Epidemiology of Neonatal Early-Onset Sepsis in Israel, 2010-2015: Is it Time for Re-evaluation of the Empiric Treatment?

Dan Glikman 3,4 Nitzan Curiel 4 Aharona Glatman-Freedman 28 Orly Megged 1,2 Natan Keller 5,6 Or Kriger 7 Eli Somekh 8,9 Dana Tasher 8 Giora Gottesman 9,10 Alex Guri 2,11 Liat Ashkenazi-Hoffnung 9,12 Ilan Youngster 9,13 Jacky Herzlich 14 Schindler Yehudit 15 Dan Miron 16,17,18 Ranaa Damouni-Shalabi 18,19 Imad Kassis 18,20 Nili Nimri-Atrash 20 Karen Lavie 18,21 Tatiana Smolkin 22 Rimma Melamed 23,26 Mara Troitzky 24,26 Avi Sayag 24,25,26 מיכל שטיין 18,27
1Pediatrics, Shaare Zedek Medical Center
2The School of Medicine, The Hebrew University and Hadassah Medical Center
3Pediatric infectious disease unit, Galilee Medical Center
4The Faculty of Medicine in the Galilee, Bar-Ilan University
5Clinical Microbiology, Safra Pediatric hospital at the Sheba Medical center
6Ariel University, Ariel University
7Pediatric infectious disease unit, Safra Pediatric hospital at the Sheba Medical center
8Pediatric infectious disease unit, Wolfson Medical Center
9The Sackler School of Medicine, Tel Aviv University
10Pediatric infectious disease service, Meir Medical Center
11Pediatrics, Kaplan Medical Center
12Pediatrics B, Schneider Children's Medical Center of Israel
13Pediatric Division and Center for Microbiome Research, Assaf Harofeh Medical Center
14Neonatal intensive care unit, Maynei Hayeshuah Medical Center
15Microbiology, Maynei Hayeshuah Medical Center
16Pediatric Infectious Dosease Service, Emek Medical Center
17Pediatric infectious disease service, Ziv Medical Center
18The Rappaport Faculty of Medicine, Technion – Israel Institute of Technology
19Pediatrics, Bnai Zion Medical Center
20Pediatric infectious disease unit, Ruth Rappaport Children's Medical Center , Rambam
21Neonatal intensive care unit, Carmel Medical Center
22Neonatal intensive care unit, Baruch Padeh Medical Center
23Pediatric infectious disease unit, Soroka University Medical Center
24Neonatal intensive care unit, Barzilai Medical Center
25Pediatrics, Barzilai Medical Center
26The School of Medicine, Ben-Gurion University of the Negev
27Infectious Disease and Infection Control Unit, Hillel Yaffe Medical Center
28Israel Center for Disease Control, Ministry of Health

Background: Data regarding current antimicrobial resistance in neonatal early-onset sepsis (EOS) and possible resistance risk factors are essential for determining the optimal empiric regimen.

Methods: EOS data retrospectively collected nationwide in Israel in 18 hospitals for 2010-2015. EOS defined as bacteremia or meningitis during the first 7 days of life for full-terms and 3 days for pre-terms.

Results: Participating hospitals represented 75% of the total birth cohort in Israel (~180,000 live births (LB)/year). Of 488 EOS cases (0.63/1,000LB), 271 (56%) were full-term and 217 (44%) were pre-term (0.35 and 0.28/1,000LB, respectively). Gram-negative pathogens predominated over Gram-positive (0.35 vs. 0.28/1000LB, respectively) (OR 1.28 [95%CI 1.07-1.52], p<0.01). E.coli, Group B Streptococcus, and K.pneumoniae were most prevalent (0.23, 0.21, and 0.06/1000LB, respectively). mong the 277 Gram-negatives, 16% were gentamicin-resistant, 14% were extended-spectrum beta-lactamase (ESBL)-positive, 10% were gentamicin-resistant and ESBL-positive (50% of gentamicin-resistant isolates), and 3.5% were amikacin-resistant. Higher resistance rates were found among pre-terms vs. full-terms:18% vs. 14% gentamicin-resistant (OR=1.38 [95%CI 0.6-3.1],p=0.44), 16% vs. 5% ESBL, 8% vs. 5% ESBL and gentamicin-resistant, and 4.5% vs. 3% amikacin-resistant, respectively.

Gentamicin resistance or ESBL’s in Gram-negatives were not associated with previous maternal hospitalizations or antimicrobials during pregnancy.

Mortality was documented in 22% of neonates with Gram-negatives and 8% with Gram-positives (p<0.01); Gentamicin resistance was associated with increased mortality (OR=2.82; [95%CI 1.14-6.95], p<0.05).

Conclusions: In this nationwide survey, EOS caused predominantly by Gram-negatives with high gentamicin-resistance rates, without identifiable resistance risk factors. As EOS is life threatening we suggest considering modification of the current empiric therapy for amikacin-based regimens.

מיכל שטיין
Dr מיכל שטיין
מרכז רפואי הילל יפה








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