Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics

Abstract

In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance.

Early-onset neonatal sepsis: rate and organism pattern between 2003 and 2008

“…3 Other recent data from single centers described an overall incidence of EONS of 2.07 cases per 1000 live Early-onset neonatal sepsis in Canada M Sgro et al births in Boston, 15 whereas in a French population the incidence was 1.19 per 1000 births. 16 However, this discrepancy is likely a result of the fact that ours is based solely on admissions to level 3 NICUs, rather than including a birth cohort.…”

“…16 However, this discrepancy is likely a result of the fact that ours is based solely on admissions to level 3 NICUs, rather than including a birth cohort.…”

Antimicrobial Resistance of <b><i>Escherichia coli</i></b> Strains Causing Neonatal Sepsis between 1998 and 2008

“…Joseph et al [21] observed an increase in the proportion of infections caused by ampicillin-resistant E. coli in the period between 1988 and 1993 (67%) compared to the earlier period between 1982 and 1987 (25%) which was concomitant with the fact that in the second period 61% of the mothers received intrapartum ampicillin in contrast with the first period when only 17% received this therapy. Terrone et al [22], Bizarro et al [17] and Kunh et al [23] found a possible association between antenatal antibiotic treatment, prolonged antepartum exposure to ampicillin and infection with ampicillin-resistant E. coli . However, there are also several studies that have demonstrated that this relationship does not exist [20].…”

Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis

“…We also gathered data on potential explanatory variables (ie, variables that might explain variance in incidence or risk of group B streptococcus; 21 Andersen et al 22 Ekelund et al 23 Kuhn et al 24 Fluegge et al 25 Berardi et al 26 Trijbels-Smeulders et al 27 van den Hoogen et al 28 Hasseltvedt et al 29 Hajdu et al 30 Neto et al 31 Janek et al 32 Carbonell-Estrany et al 33 Lopez Sastre et al 34 Andreu et al 35 Persson et al 36 Heath et al 37 Oddie et al 38 Weisner et al 39 Vergnano et al 40 Subtotal (I 2 =98·6%, p=0·000)…”