PEDIATRICS Vol. 121 No. 4 April 2008, pp. 689-696 (doi:10.1542/10.1542/peds.2007-2171)
ARTICLE |
Changing Patterns in Neonatal Escherichia coli Sepsis and Ampicillin Resistance in the Era of Intrapartum Antibiotic Prophylaxis
Divisions of a Perinatal Medicine
e Infectious Diseases, Department of Pediatrics
b Department of Internal Medicine
c Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut
d Department of Quality Improvement Support Services, Yale-New Haven Hospital, New Haven, Connecticut
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
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OBJECTIVE. The goal was to determine current trends in Escherichia coli-related early- and late-onset sepsis and patterns of ampicillin resistance in relation to institutional changes in the use of intrapartum antibiotic prophylaxis.
METHODS. A retrospective review of data for all infants with E coli sepsis at Yale-New Haven Hospital from 1979 to 2006 was performed. Study periods were based on predominant intrapartum antibiotic prophylaxis practices at Yale-New Haven Hospital, that is, (1) 1979 to 1992 (no formal intrapartum antibiotic prophylaxis), (2) 1993 to 1996 (risk factor-based), and (3) 1997 to 2006 (screening-based). Sepsis rates and patterns of ampicillin resistance were compared.
RESULTS. Fifty-three cases of E coli early-onset sepsis and 129 cases of E coli late-onset sepsis were identified over 3 eras. In very low birth weight (<1500 g) infants, increases in E coli early-onset sepsis (period 1: 2.83 cases per 1000 very low birth weight admissions; period 2: 7.12 cases per 1000 very low birth weight admissions; period 3: 10.22 cases per 1000 very low birth weight admissions), intrapartum ampicillin exposure, and ampicillin-resistant E coli were observed. Intrapartum ampicillin exposure was determined to be an independent risk factor for ampicillin-resistant E coli early-onset sepsis. For the first time, a significant increase in E coli late-onset sepsis was observed in preterm infants (period 1: 10.39 cases per 1000 very low birth weight admissions; period 2: 16.01 cases per 1000 very low birth weight admissions; period 3: 21.66 cases per 1000 very low birth weight admissions) and term infants (period 1: 4.07 cases per 1000 admissions; period 2: 4.22 cases per 1000 admissions; period 3: 8.23 cases per 1000 admissions).
CONCLUSIONS. Studies to provide a better understanding of potential consequences of intrapartum antibiotic exposure and its contribution to evolving trends in neonatal sepsis are urgently needed.
Key Words: very low birth weight • bacteremia • group B streptococcus
Abbreviations: EOS—early-onset sepsis • GBS—group B streptococcus • IAP—intrapartum antibiotic prophylaxis • GA—gestational age • VLBW—very low birth weight • LOS—late-onset sepsis • Y-NHH—Yale-New Haven Hospital • NBSCU—newborn special care unit • PROM—prolonged rupture of membranes • BW—birth weight • LR—logistic regression
Bloodstream infections are a significant cause of neonatal morbidity and death. Early-onset sepsis (EOS) (bloodstream infection at 
72 hours of life) is a major contributor to these sequelae. In developed countries, group B streptococcus (GBS) emerged as the leading etiologic agent of EOS in the 1970s, with case fatality rates as high as 55%.1 Beginning in 1992, national guidelines for the use of intrapartum antibiotic prophylaxis (IAP) to prevent neonatal GBS infection were published.2–5 The current guidelines recommend universal screening for GBS colonization in pregnant women at 35 to 37 weeks of gestation, with penicillin as the first-line agent for IAP.5 Widespread adoption of these guidelines has resulted in a significant decrease in GBS-related EOS.6
Most premature infants are delivered before the gestational age (GA) at which routine GBS screening and IAP are recommended, but an estimated 65% of very low birth weight (VLBW) (<1500-g) neonates are exposed to antibiotics before delivery.7 Although current guidelines advocate GBS screening and IAP even in the setting of threatened preterm delivery,5 compliance with these guidelines is not always achieved.8 Furthermore, premature neonates often receive intrapartum antimicrobial exposure for reasons other than maternal GBS colonization. The substantial risks and consequences of infection in the vulnerable preterm population are likely responsible for this practice, although consensus opinion regarding the use of intrapartum antimicrobial therapy, other than to prevent GBS disease, is limited.9,10
The increase in the intrapartum antibiotic exposure of term and preterm neonates has raised significant concerns. Concerns regarding the widespread use of antimicrobial agents in the parturient population, a group not previously exposed to significant antimicrobial treatment, are based on existing data that suggest that frequent prolonged exposure to broad-spectrum antibiotics may alter the normal maternal microbiologic flora. This may result in passage of and subsequent colonization of the neonatal skin and gastrointestinal tract with resistant and potentially pathogenic bacteria.11 Potential unintended consequences of intrapartum antibiotic exposure at any GA could include increased rates of neonatal sepsis attributable to virulent and resistant pathogens, development of antibiotic-resistant infections beyond the perinatal period in the mother or her infant, and changes in community patterns of antibiotic resistance.12–14
Some of these fears were realized when several centers reported the emergence of Escherichia coli over GBS as the predominant organism responsible for EOS, as well as increased rates of E coli ampicillin resistance, after initiation of IAP.14–17 Additional investigation determined that these concerning trends were primarily limited to the preterm population,15–19 a group particularly susceptible to E coli infection15,20–22 and, once infected, at increased risk of sepsis-related morbidity and death.15,23,24 Almost no attention has focused on the potential impact of IAP on the organisms responsible for late-onset sepsis (LOS) (bloodstream infection at >72 hours of life), a more-prevalent problem with significant morbidity and mortality rates.22,25
As the rate of intrapartum antibiotic exposure continues to increase,20 its potential effects, both positive and negative, on the organisms responsible for neonatal sepsis warrant additional investigation. We sought to evaluate potential trends in the incidence and antibiotic susceptibility patterns of E coli-related EOS and LOS in conjunction with changes in intrapartum antibiotic use over nearly 3 decades. Intrapartum antibiotic exposure was evaluated as a potential risk factor for E coli antibiotic resistance over the same time period.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Study Design
The Yale-New Haven Hospital (Y-NHH) newborn special care unit (NBSCU) is a 46-bed, tertiary care, referral center for infants with complex medical and surgical conditions. E coli has been the most common Gram-negative pathogen responsible for both EOS and LOS at our NBSCU for >75 years and therefore was chosen for review.25 Data on all E coli-positive blood cultures from newborns and infants collected between January 1, 1979, and December 31, 2006, were obtained from the microbiology laboratory. These included cultures collected at any day of life from inpatients in the Y-NHH NBSCU, as well as those from neonates
30 days of age in the emergency department, wards, ICU, or ambulatory clinic. Subjects included both inborn and outborn infants and, with respect to NBSCU inpatients, included only those with long-term admissions (>24 hours). Most referring institutions were local or regional Connecticut hospitals that are part of the Yale-New Haven Health System. The records of all infants were reviewed, and maternal charts linked to the infants were examined. Data on intrapartum risk factors for neonatal infection, data on maternal antibiotic exposure, and neonatal data including demographic characteristics, antibiotic exposure, E coli antibiotic susceptibility patterns, risk factors for infection, and outcomes were collected. The majority of newborns identified (125 of 178 infants) were inborn; therefore, the 28-year study period was divided on the basis of the predominant IAP practices at Y-NHH, that is, (1) 1979 to 1992 (no formal IAP guidelines), (2) 1993 to 1996 (risk factor-based IAP), and (3) 1997 to 2006 (screening-based IAP). Predominant screening practices at referring institutions over most of the study period, before the recommendations for universal screening and IAP, were not known. Sepsis rates, patterns of ampicillin resistance, and demographic data for the affected population were compared among eras.
Definitions
Sepsis
Sepsis was defined as a positive blood culture for E coli and was classified, according to the infant's age, as EOS (72 hours of life) or LOS (>72 hours of life). Multiple positive blood cultures from a single patient with identical antibiotic susceptibility patterns were considered a single episode.
Risk Factors, Symptoms, and Outcomes
Intrapartum antibiotic therapy was defined as the use of 
1 antimicrobial agent from the onset of labor until the time of delivery. Because the duration of labor can vary, no time constraints were placed on this definition. Preterm labor, maternal fever, prolonged rupture of membranes (PROM), chorioamnionitis, and sepsis-related death were defined as described.26 Prolonged intubation was defined as the need for mechanical ventilation for greater than 14 days. The presence of a central vascular catheter was included if the catheter was placed before the onset of infection. Surgery was included as a potential risk factor if it occurred 7 days before the onset of sepsis.
Laboratory Analyses
Blood cultures were assessed by using a carbon dioxide detection system (Bactec II or 9240; Becton Dickinson, Franklin Lakes, NJ). Antibiotic susceptibility patterns were tested by using standard disk diffusion methods.27
Statistical Analyses
The SPSS 13.0 statistical software package (SPSS, Chicago, IL) was used for data analyses. The VLBW population, given its substantial risk for infection, was analyzed both separately and as part of the entire cohort. We documented and analyzed linear trends in EOS, LOS, ampicillin resistance, and intrapartum antibiotic use over the study periods by using 
2 analysis of trends. Data pertaining to EOS and LOS were presented as number of cases per 1000 NBSCU admissions for the entire population and number of cases per 1000 VLBW NBSCU admissions for the VLBW population. This denominator was chosen to incorporate both inborn and outborn cases of sepsis.
Intrapartum, demographic, hospital course, and outcome data were compared among periods. For neonates who experienced >1 episode of sepsis (n = 4), demographic data (eg, GA, birth weight [BW], and gender) pertaining to each were evaluated once, and only the first episode of sepsis was evaluated in logistic regression (LR) modeling. Continuous data were compared by using analysis of variance, and dichotomous data were analyzed by using Fisher's exact test if 1 cell contained <5 or the 2 test if cells contained 5.
Factors associated with ampicillin-resistant E coli EOS and LOS were analyzed separately. Maternal, intrapartum, and neonatal data were analyzed individually by using ampicillin resistance as a binary variable and the primary outcome of interest. Analyses included the effects of intrapartum antibiotic exposure and its duration, postnatal antibiotic exposure and its duration, demographic data, and the presence and duration of use of support apparatus (eg, central vascular catheter). Unadjusted comparisons were made by using the 2 test or Fisher's exact test for dichotomous data and Student's t test or the Wilcoxon rank-sum test for continuous data. Covariates with P values of <.10 were then included in the multivariate LR analysis using ampicillin resistance as the dependent variable. Adjusted odds ratios were calculated for each covariate when possible. P values of <.05 were considered significant.
Ampicillin-resistant cases of sepsis were also analyzed as an independent variable in analyses assessing the potential effects of ampicillin-resistant E coli sepsis on certain outcomes of interest (eg, death). Unadjusted comparisons were made by using the 2 test or Fisher's exact test. Covariates with P values of <.10 were then included in the multivariate LR analysis. Adjusted odds ratios were calculated. P values of <.05 were considered significant. This study was approved by the human investigation committee of Yale University.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Demographic Data From the Y-NHH NBSCU for 1979 to 2006
Between January 1, 1979, and December 31, 2006, there were 140442 live births and 22755 admissions to the Y-NHH NBSCU, including 4316 VLBW infants. The total number of admissions per year (P = .164), the number of VLBW admissions per year (P = .180), and the mean length of hospital stay for the VLBW population (P = .107) did not change significantly over 28 years, but survival rates of VLBW neonates increased significantly (P < .0001).
Intrapartum Antibiotic Use/Exposure
The proportions of neonates with E coli sepsis with intrapartum antibiotic exposure increased significantly over the 3 study periods, both in the entire cohort (period 1: 16%; period 2: 22%; period 3: 66%; P < .0001) and in the VLBW population (period 1: 22%; period 2: 36%; period 3: 85%; P < .0001), with the majority of exposure (61 of 92 neonates) occurring in conjunction with the institutional adoption of IAP guidelines for GBS and PROM (1997–2006).
Sepsis
There were a total of 1385 cases of neonatal sepsis at Y-NHH during the study period, including 232 cases of EOS (17%) and 1153 cases of LOS (83%). E coli was the responsible organism in 182 (13%) of these cases, which occurred in 178 infants (125 inborn and 53 outborn). Cases were further classified and analyzed as EOS and LOS.
E coli EOS
Trends
There were 53 cases of E coli EOS in 53 newborns, including 27 cases in 27 VLBW neonates. There was a significant decrease in the overall incidence of EOS, attributed to any organism, over the study periods (period 1: 12.03 cases per 1000 NBSCU admissions; period 2: 12.02 cases per 1000 NBSCU admissions; period 3: 7.19 cases per 1000 NBSCU admissions; P = .007). No significant change was observed in the incidence of E coli EOS (period 1: 1.72 cases per 1000 NBSCU admissions; period 2: 2.60 cases per 1000 NBSCU admissions; period 3: 3.13 cases per 1000 NBSCU admissions; P = .125). The incidence of GBS EOS decreased significantly, particularly after the adoption of screening-based IAP (period 1: 5.79 cases per 1000 NBSCU admissions; period 2: 8.45 cases per 1000 NBSCU admissions; period 3: 2.67 cases per 1000 NBSCU admissions; P < .001).
For VLBW newborns, no consistent trends (P = .585) in the overall incidence of EOS were observed (Fig 1A). However, a significant increase (P < .001) in the incidence of E coli EOS was observed (Fig 1B). No significant change in the incidence of GBS-related EOS in VLBW neonates was detected (period 1: 6.14 cases per 1000 VLBW NBSCU admissions; period 2: 1.78 cases per 1000 VLBW NBSCU admissions; period 3: 4.21 cases per 1000 VLBW NBSCU admissions; P = .417).
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Characteristics of neonates with E coli EOS were compared across study periods (Table 1). The mean GA and BW of E coli-infected infants decreased significantly, whereas the proportions delivered after preterm labor and chorioamnionitis and intrapartum exposure to antibiotics, including ampicillin, increased significantly. No significant differences in outcomes were detected.
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E coli EOS in the VLBW Population
Mean GA (period 1: 28.7 weeks; period 2: 27.3 weeks; period 3: 25.2 weeks; P = .004) and BW (period 1: 1175 g; period 2: 934 g; period 3: 806 g; P = .006) decreased among VLBW neonates with E coli EOS. The proportions delivered after preterm labor (period 1: 50%; period 2: 75%; period 3: 82%; P = .318), PROM (period 1: 50%; period 2: 50%; period 3: 44%; P = .961), and chorioamnionitis (period 1: 0%; period 2: 50%; period 3: 50%; P = .080) did not change significantly but intrapartum ampicillin exposure did (period 1: 0%; period 2: 50%; period 3: 88%; P < .001).
Ampicillin-Resistant E coli EOS
Hospital-wide data, which included data from the NBSCU and obstetric wards, revealed no statistically significant change in the proportions of isolates of ampicillin-resistant E coli over the study periods (period 1: 30%; period 2: 37%; period 3: 41%; Y-NHH clinical microbiology data; P = .117). In the entire NBSCU population with E coli EOS, 20% of cases of E coli EOS (4 of 20 cases) were ampicillin-resistant before recommendations for GBS IAP (1979–1992), compared with 44% (4 of 9 cases) in the risk factor-based era (1993–1996) and 54% (13 of 24 cases) in the screening-based era (1997–2006; P = .061).
A significant increase in the proportion of ampicillin-resistant E coli EOS was identified in the VLBW population over the study period (P = .005). No cases of ampicillin-resistant E coli were observed from 1979 to 1992 (0 of 6 cases), compared with 25% from 1993 to 1996 (1 of 4 cases) and 64% from 1997 to 2006 (12 of 17 cases).
VLBW neonates with ampicillin-resistant E coli EOS were compared with those with ampicillin-sensitive E coli EOS and were determined to have a lower GA (25.2 weeks and 27.2 weeks, respectively; P = .036) and BW (804 g and 1003 g, respectively; P = .043), and a greater proportion had intrapartum ampicillin exposure (92% and 31%, respectively; P = .004). The effect of intrapartum ampicillin exposure on ampicillin resistance was evaluated in a LR analysis that controlled for the effects of GA and BW. Intrapartum ampicillin exposure was determined to be a significant independent risk factor for antibiotic resistance (adjusted odds ratio: 17.91; 95% confidence interval: 1.59–202.37; P = .020).
Aminoglycoside- and Third-Generation Cephalosporin-Resistant E coli EOS
No cases of gentamicin-resistant E coli EOS occurred in any of the 3 study periods. The only case of third-generation cephalosporin-resistant E coli EOS in the 28-year study period occurred in 2006 in a VLBW neonate.
E coli LOS
Trends
There were 129 cases of E coli LOS in 125 infants, including 67 cases in 64 VLBW neonates. Significant increases in the overall incidence of LOS (period 1: 28.48 cases per 1000 NBSCU admissions; period 2: 55.90 cases per 1000 NBSCU admissions; period 3: 75.97 cases per 1000 NBSCU admissions; P < .001) and the incidence of E coli LOS (period 1: 4.07 cases per 1000 NBSCU admissions; period 2: 4.22 cases per 1000 NBSCU admissions; period 3: 8.23 cases per 1000 NBSCU admissions; P < .001) over 28 years were observed. In the VLBW population, significant increases in the numbers of all cases of LOS (P < .001) (Fig 1A) and cases of E coli LOS (P = .006) (Fig 1B) were observed.
There were no statistically significant differences in GA and BW in neonates with E coli LOS over the study period. Statistically significant differences in intrapartum antibiotic exposure, intrapartum ampicillin exposure, and duration of central vascular catheter use were observed. No significant differences in use and/or duration of postnatal antibiotic treatment or outcomes were observed (Table 2).
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E coli LOS in the VLBW Population
Mean GA (period 1: 27.7 weeks; period 2: 27.7 weeks; period 3: 26.3 weeks; P = .103) and BW (period 1: 972 g; period 2: 959 g; period 3: 943 g; P = .917) did not change significantly among VLBW neonates with E coli LOS. Significant increases in intrapartum antibiotic exposure (period 1: 20%; period 2: 30%; period 3: 82%; P < .0001) and intrapartum ampicillin exposure (period 1: 10%; period 2: 20%; period 3: 42%; P = .028) were observed. No significant differences in use or duration of postnatal antibiotic treatment or outcomes were observed.
Ampicillin-Resistant E coli LOS
No statistically significant changes in the proportions of ampicillin-resistant E coli LOS in the entire cohort (P = .188) were observed over the study periods. Similarly, no differences in the VLBW population (P = .435) were observed.
Cases of ampicillin-resistant (n = 29) and ampicillin-sensitive (n = 38) E coli LOS in VLBW infants were compared. More infants with ampicillin-resistant strains of E coli had been exposed to intrapartum antibiotic treatment (ampicillin-resistant: 66%; ampicillin-sensitive: 47%), but this difference was not statistically significant (P = .215). Infants with ampicillin-resistant E coli had higher incidence rates of necrotizing enterocolitis (ampicillin-resistant: 62%; ampicillin-sensitive: 21%; P = .001) and sepsis-related death (ampicillin-resistant: 34%; ampicillin-sensitive: 11%; P = .031). Associations between E coli bacteremia and necrotizing enterocolitis and between intrapartum antibiotic use and necrotizing enterocolitis in the preterm population have been described.28,29 To address these associations, a multivariate LR analysis controlling for effects of prematurity, use and duration of use of support apparatuses and antibiotics, and the presence of patent ductus arteriosus was performed. A significantly higher incidence of necrotizing enterocolitis was maintained in the cohort with ampicillin-resistant E coli (adjusted odds ratio: 4.51; 95% confidence interval: 1.23–14.28; P = .026). No other significant differences were observed.
Aminoglycoside- and Third-Generation Cephalosporin-Resistant E coli LOS
No cases of gentamicin-resistant E coli LOS occurred in any of the 3 study periods. The only case of third-generation cephalosporin-resistant E coli LOS in the 28-year study period occurred in 2006 in a VLBW neonate.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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At Y-NHH, the total number of cases of EOS per 1000 live births has decreased and LOS has increased over 28 years. The decrease in EOS is likely related to the significant reduction in GBS EOS observed after the adoption of widespread IAP. No changes in the overall incidence or antibiotic resistance patterns of E coli EOS were observed in the entire population with adoption of this practice. In contrast, in our VLBW neonatal population, we observed significant increases in both EOS and LOS attributed to E coli, in addition to a significant increase in the proportion of ampicillin-resistant cases of E coli EOS. The EOS findings support similar trends described previously and extend them over nearly 3 decades at a single center.15–19 The documented increases in E coli LOS in the overall and VLBW neonates over such a long period of time are, to our knowledge, reported for the first time.
The increase in E coli EOS observed at Y-NHH in VLBW neonates is likely related to several factors. Although the overall number of VLBW admissions to our NBSCU did not change over the study period, the mean GA and BW of the VLBW cohort decreased significantly. Previous investigations documented a significant inverse relationship between prematurity and the risk of neonatal sepsis.30 This association is likely related to a more-immature immune system, ineffective skin barrier, and need for support apparatus, in addition to other factors. It is possible that this change in the demographic features of our VLBW population has created a more-vulnerable cohort with a larger proportion of extremely preterm neonates.
Intrapartum events and maternal factors are also thought to contribute to the risk of EOS. Given the threat and consequences of infections in premature newborns and their mothers, intrapartum antibiotic use has become common. In our cohort of VLBW neonates, intrapartum antibiotic exposure increased significantly over a 28-year period. Given the increased use of antibiotics in term pregnancies observed after the publication of the GBS IAP guidelines,20 one might speculate that the increase observed in our VLBW population was the result of the adoption of similar guidelines for the use of IAP for threatened preterm delivery and for PROM.5,9 However, no concurrent increase in the proportion of neonates delivered after the onset of preterm labor or PROM was observed in this cohort. Intrapartum antibiotic therapy in the preterm population may also be used to treat, among other conditions, chorioamnionitis and maternal infections.9,31,32 Under these circumstances, the duration of treatment and the antimicrobial drugs of choice are often at the discretion of the treating physician.10 Despite the increase in IAP, we did not observe a similar increase in maternal fever and/or chorioamnionitis. Although we cannot determine the exact causes of the trends in EOS observed at our institution, the increase in antibiotic exposure in the VLBW population and its association with ampicillin-resistant E coli EOS is one concerning finding that warrants additional investigation.
The incidence of LOS attributed to any organism and to E coli in the overall and VLBW populations has increased at Y-NHH. Although the cause of these trends is again likely to be multifactorial, the increase in LOS did not coincide with an increase in VLBW admissions or duration of hospitalization. It is possible that the increased survival rates in this population created a larger cohort of susceptible neonates requiring prolonged support, increasing their risk of exposure and subsequent infection. Unlike the association observed between intrapartum antibiotic exposure and ampicillin-resistant E coli EOS in the VLBW population, no such association was observed between postnatal antibiotic exposure and ampicillin-resistant cases of E coli LOS. The consistent use of fewer combinations of drugs for postnatal antimicrobial treatment, for shorter periods, may be partly responsible for this discrepancy.
Our findings exemplify the advantages and disadvantages of single-center, observational studies. The longitudinal collection of data over nearly 3 decades allowed us to compare changes in EOS, LOS, and E coli ampicillin resistance with changes in obstetric and neonatal practice. This lengthy period of observation helped to control for apparent fluctuations in infection rates observed over shorter periods. Conversely, limitations including sample size and exclusion of unknown factors, such as the number of sepsis episodes prevented through intrapartum antibiotic use, limit data interpretation. Trends in the overall use of intrapartum antibiotic therapy would have been useful to this investigation but could not be obtained from Y-NHH or from the multiple regional hospitals that refer neonates to our institution. Although we were able to identify trends, the causality of these findings could not be distinguished. We were unable to identify all potential confounding variables, and limited sample size made the integrity and precision of LR analyses with the addition of multiple independent variables increasingly unreliable. We recognize these restrictions and the pitfalls related to conclusions derived from association-based analyses of data lacking a control population.20
Neonatal sepsis continues to be a significant cause of morbidity and death. Intrapartum antibiotic exposure may contribute to this risk and to the growing problem of antibiotic-resistant organisms. Implementation of regimented guidelines for IAP to prevent GBS infection in term and near-term infants has led to a decrease in EOS.6 Strict compliance with these guidelines and ongoing surveillance of potential consequences of IAP are essential components of this continued success.8 Widespread, unrestricted, intrapartum antibiotic use, particularly in the preterm population, may have untoward effects. Additional studies to provide a better understanding of the potential risks and benefits of intrapartum antibiotic exposure for neonates are therefore needed.
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FOOTNOTES |
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Accepted Aug 30, 2007.
Address correspondence to Patrick G. Gallagher, MD, Department of Pediatrics, Yale University School of Medicine, 333 Cedar St, PO Box 208064, New Haven, CT 06520-8064. E-mail: patrick.gallagher{at}yale.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
| What's Known on This Subject Early-onset neonatal sepsis due to E coli, including ampicillin-resistant E coli bacteremia, is increasing in preterm infants, paralleling an increase in intrapartum antibiotic use.
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| What This Study Adds In preterm infants, this study identifies intrapartum ampicillin exposure as an independent risk factor for ampicillin-resistant E coli early-onset sepsis and describes a significant increase in E coli late-onset sepsis.
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