sepsis of newborn

7/23/2019 sepsis of newborn

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Epidemiologyof NeonatalEarly-onset SepsisKaren M. Puopolo, MD,

PhD*

Author Disclosure

Dr Puopolo has

disclosed no financial

relationships relevant

to this article. This

commentary does not

contain a discussion

of an unapproved/

investigative use of a

commercial product/

device.

Objectives After completing this article, readers should be able to:1. Describe the incidence and microbiology of neonatal early-onset sepsis (EOS).

2. Identify clinical risk factors for neonatal EOS.

3. Review the impact of group B streptococcal prophylaxis policies on the epidemiology

of neonatal EOS.

4. Delineate the differences in incidence, risk, and microbiology of neonatal EOS between

term and very low-birthweight infants.

AbstractNeonatal early-onset sepsis (EOS) continues to be a significant source of morbidity

and mortality among newborns, especially among very-low birthweight infants.Epidemiologic risk factors for EOS have been defined, and considerable resources are

devoted to the identification and evaluation of infants at risk for EOS. The widespread

implementation of intrapartum antibiotic prophylaxis for the prevention of early-

onset neonatal group BStreptococcus(GBS) disease has reduced the overall incidence

of neonatal EOS and influenced the microbiology of persistent early-onset infection.

Most early-onset neonatal GBS disease now occurs in preterm infants or in term

infants born to mothers who have negative GBS screening cultures. Ongoing clinical

challenges include reassessment of clinical risk factors for EOS in the era of GBS

prophylaxis; more accurate identification of GBS-colonized women; and continued

surveillance of the impact of GBS prophylaxis practices on the microbiology of EOS,

particularly among very low-birthweight infants.

IntroductionBacterial sepsis and meningitis continue to be major causes of morbidity and mortality in

newborns, particularly in very-low birthweight (VLBW) infants (birthweight 1,500 g).

Neonatal early-onset sepsis (EOS) is defined by the Centers for Disease Control and

Prevention (CDC) as blood or cerebrospinal fluid culture-

proven infection occurring in the newborn who is younger

than 7 days of age. (1) For the continuously hospitalized

VLBW infant, EOS is defined as culture-proven infection

occurring at fewer than 72 hours of age. (2) The alternative

definition in VLBW infants is justified by two findings:

1) the risks for infection in VLBW infants after 72 hours ofage primarily derive from the specifics of ongoing neonatal

intensive care rather than from perinatal risk factors, and

2) the organisms causing infection after 72 hours of age

among VLBW infants reflect the nosocomial flora of the

neonatal intensive care unit (NICU) more than perinatally

acquired maternal flora. (2)

The overall incidence of EOS in the United States in the

past 10 years is 1 to 2 cases per 1,000 live births; the

incidence is 10-fold higher in VLBW infants. (3)(4) Since

*Assistant Professor of Pediatrics, Harvard Medical School; Attending Physician, Channing Laboratory and Department of

Newborn Medicine, Brigham and Womens Hospital and Division of Newborn Medicine, Childrens Hospital, Boston.

Abbreviations

BWH: Brigham and Womens Hospital

CDC: Centers for Disease Control and Prevention

EOS: early-onset sepsisGBS: group BStreptococcus

IAP: intrapartum antibiotic prophylaxis

MRSA: methicillin-resistantStaphylococcus aureus

NICHD: National Institute of Child Health and

Development

NICU: neonatal intensive care unit

PCR: polymerase chain reaction

VLBW: very low birthweight

Article infectious disease

NeoReviews Vol.9 No.12 December 2008 e571

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the 1970s, the primary pathogen causing EOS in the

United States has been group B Streptococcus(GBS). Theincidence of EOS has fallen with the widespread imple-

mentation of intrapartum antibiotic prophylaxis (IAP)

for the prevention of early-onset GBS disease. The na-

tional incidence of GBS EOS has declined 80% from 1.7

cases per 1,000 live births in 1993 to 0.34 cases per

1,000 live births in 2003 to 2005. (1) Multiple studies

assessing the impact of GBS IAP policies demonstrate

that the incidence of non-GBS EOS is unchanged or

decreasing among term births. (4) Concern remains

about the impact of these policies on the incidence and

microbiology of EOS among VLBW infants.

Bacterial sepsis was the eighth leading cause of deathamong newborns in the United States in 2000 to 2001.

(5) Mortality from EOS decreased significantly in term

infants with improvements in NICU care over the past

20 years, primarily due to advances in respiratory support

(including surfactant replacement, high-frequency venti-

lation, inhaled nitric oxide, and extracorporeal mem-

brane oxygenation). Mortality rates from EOS are higher

in preterm infants. The most recent CDC active surveil-

lance data on infants who have early-onset GBS disease

revealed that 2.6% of term infants died of the infection

compared with 19.9% of infants born before 37 weeks

gestation, an eightfold increase in the risk of infection-

attributable mortality. (1) Among

VLBW infants, mortality is greater:

35% of VLBW infants who had EOS

died in a 2002 to 2003 National In-

stitute of Child Health and Develop-

ment (NICHD) Neonatal Network

cohort study compared with an over-

all 11% mortality among uninfected

VLBW infants. (3) Finally, neonatal

survivors of EOS may have severe

neurologic sequelae, attributable to

concomitant meningitis or from

hypoxemia resulting from septic

shock, persistent pulmonary hyper-

tension, and hypoxic respiratoryfailure. Hypotension and increased

concentrations of inflammatory cy-

tokines during sepsis also may in-

jure the developing neonatal cen-

tral nervous system.

Microbiology of EOSSince the 1980s, GBS has been the

leading cause of neonatal EOS in

the United States. Despite the

widespread implementation of IAP, early-onset GBS dis-

ease remains the leading cause of EOS in term infants(Table 1). However, coincident with the increased use of

IAP for GBS, gram-negative enteric bacteria have be-

come the leading cause of EOS in preterm infants (Table

2). (3)(4)(6) In Table 1, data from the CDC Active

Bacterial Core Surveillance program are compared with

data from our single center (the Brigham and Womens

Hospital [BWH]in Boston). The CDC data were ob-

tained from the Atlanta and San Francisco metropolitan

areas in 1998 to 2000. The BWH is a large maternity

hospital that has an average 9,000 deliveries per year. The

BWH data encompass all cases of EOS occurring in

infants cared for in the 50-bed Level III BWH NICU forthe period 1990 to 2007. Both data sets reveal a similar

spectrum of organisms, with a predominance of gram-

positive organisms, primarily GBS and other streptococ-

cal species. Table 2 compares data from the NICHD

Neonatal Network and our single center. The NICHD

data are from 16 centers over the period 2002 to 2003.

Our single-center data include cases of EOS occurring in

infants cared for in the BWH NICU from 1990 to 2007

whose birthweights were less than 1,500 g. Again, the

data sets are strikingly similar, with a predominance of

enteric bacilli, primarily Escherichia colibut including a

spectrum of other Enterobacteriaceae (Klebsiella,

Table 1.Organisms Causing Neonatal Early-onset

Sepsis

Organism

Centers forDisease Controland Prevention(n408) %

Brigham andWomens Hospital(n307) %

GBS 166 40.7 130 42.3Escherichia coli 70 17.2 64 20.8Other streptococci* 93 22.7 37 12.1Enterococcus 16 3.9 13 4.2Staphylococcus aureus 15 3.7 12 3.9CONS - - 14 4.6Listeria 6 1.5 2 0.7Bacteroides 5 1.2 14 4.6Klebsiella 9 2.2 4 1.3Haemophilus influenzae 9 2.2 6 2.0Other gram-negative 16 3.9 5 1.6Other 3 0.7 6 2.0Total gram-positive 299 73.3 211 68.7Total gram-negative 109 26.7 96 31.3

CONScoagulase-negativeStaphylococcus, GBSgroup BStreptococcus.*Other streptococci includeS pneumoniae, S bovis, S mitis,Peptostreptococcus,and viridans streptococci.Other gram-negative organisms include Pseudomonas, Proteus, Morganella, andYersinia.Other organisms includeBacillusand Clostridium.

Adapted from Hyde et al.Pediatrics.2002;110:690695.

infectious disease sepsis

e572 NeoReviews Vol.9 No.12 December 2008



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Pseudomonas, Haemophilus, and Enterobactersp) and theanaerobic speciesBacteroides.

EOS Caused by GBSGBS frequently colonizes the human genital and gastro-

intestinal tracts and the upper respiratory tract in young

infants. GBS are facultative diplococci that are primarily

identified by the Lancefield group B carbohydrate anti-

gen. They are subtyped further into nine distinct capsular

polysaccharide serotypes (types Ia, Ib, II, III, IV, V, VI,

VII, VIII). A potential tenth polysaccharide type recently

has been identified. (7) Most GBS EOS in the United

States currently is caused by types Ia, Ib, II, III, and VGBS. (1) Type III GBS more commonly are associated

with late-onset sepsis and meningitis.

Early-onset GBS infection is acquired in utero or

during passage through the birth canal. Approximately

20% to 30% of American women are colonized with GBS

at any given time. A longitudinal study of GBS coloniza-

tion in a cohort of primarily young, sexually active

women demonstrated that nearly 60% were colonized

with GBS at some time over a 12-month period. (8) In

the absence of IAP, approximately 50% of infants born to

mothers colonized with GBS are colonized at birth, and

1% to 2% of colonized infants develop invasive GBS

disease. Lack of maternally derived

protective capsular polysaccharide-

specific antibody is associated with

the development of invasive GBS

disease. Other factors predisposing

the newborn to GBS disease are less

well understood, but relative defi-

ciencies in complement, neutrophil

function, and innate immunity may

be important.

A number of studies helped de-

fine maternal and neonatal risk fac-

tors for GBS EOS. Benitz and asso-

ciates (9) performed a literature

review and data reanalysis of studiesof risk factors for GBS EOS from

the 1970s to the 1990s to generate

odds ratio estimates for several clin-

ical factors (Table 3). Maternal

GBS colonization alone was far

more predictive than any other ma-

ternal or neonatal clinical character-

istic, a finding that is the evidence

base for the current recommenda-

tion for use of IAP according to

maternal GBS colonization status.

Additional maternal clinical factors predictive of early-onset GBS disease include maternal intrapartum fever

(temperature 99.5F [37.5C]), the clinical diagnosis

of chorioamnionitis, and prolonged rupture of mem-

branes (18 h). Neonatal risk factors include prematu-

rity (37 weeks gestation) and low birthweight

(2,500 g), especially birthweight less than 1,000 g.

Although once considered a risk factor for GBS disease,

Table 2.Organisms Causing Early-onset Sepsis in

Very Low-birthweight Infants

Organism

National Instituteof Child Healthand Development(n102) %

Brigham andWomens Hospital(n95) %

GBS 12 11.8 20 21.1Escherichia coli 42 41.2 31 32.6Other streptococci* 9 8.8 12 12.6CONS 15 14.7 5 5.3Listeria 2 2.0 1 1.1Other gram-positive 8 7.8 5 5.3Bacteroides N/A - 9 9.5Haemophilus influenzae 2 2.0 3 3.2Enterobacter 4 3.9 1 1.1Citrobacter 3 2.9 2 2.1Other gram-negative 3 2.9 4 4.2Fungal 2 2.0 2 2.1Total gram-positive 46 45.1 43 45.3Total gram-negative 54 52.9 50 52.6

CONScoagulase-negativeStaphylococcus,GBSgroup BStreptococcus.*Other streptococci includeS pneumoniae, S mitis, viridans streptococci, and group AStreptococcus.Other gram-positive organisms includeBacillus,Corynebacterium,Staphylococcus aureus.Other gram-negative organisms include Klebsiella, Pseudomonas, Acinetobacter, Proteus, Morganella,andFusobacterium.

Adapted from Stoll et al.Pediatr Infect Dis J.2005;24:635639.

Table 3.Risk Factors for Early-onsetGBS Sepsis in the Absence of IAP

Risk FactorOdds Ratio (95%Confidence Interval)

Maternal GBS colonization 204 (100 to 419)Birthweight99.5F (37.5C)

4.05 (2.17 to 7.56)

GBSgroup BStreptococcus, IAPintrapartum antibiotic prophylaxis.Adapted from Benitz et al.Pediatrics.1999;103:e77.





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multiple gestation now is not considered an independent

risk factor for EOS. (10) GBS bacteriuria during preg-

nancy is associated with heavy colonization of the recto-

vaginal tract and is considered a significant risk factor for

EOS. Black race is associated with higher rates of GBS

EOS, although it is not entirely clear whether this simply

reflects the higher rate of GBS colonization in this pop-

ulation. The most recent CDC surveillance data demon-

strate a fourfold increased incidence of neonatal GBS

EOS among black infants compared with white infants.

(1)

IAP for the Prevention of Early-onsetGBS infection

After recognizing that maternal colonization with GBSwas the greatest risk factor for neonatal GBS disease,

multiple trials demonstrated that the use of intrapartum

penicillin or ampicillin significantly reduced the rate of

neonatal colonization with GBS and the incidence of

early-onset GBS disease. The ability to prevent neonatal

GBS colonization and neonatal EOS was demonstrated

most dramatically in a trial of only 160 women in 1986.

(11) IAP for the prevention of GBS EOS can be admin-

istered to pregnant women during labor based on specific

clinical risk factors for early-onset GBS infection or the

results of antepartum screening of pregnant women for

GBS colonization. In 1996, the CDC published consen-sus guidelines for the prevention of neonatal GBS disease

that endorsed the use of either a risk factor-based or

screening-based approach. (10) The CDC later con-

ducted a large retrospective cohort study of more than

600,000 births that demonstrated the superiority of the

screening-based approach for the prevention of neonatal

GBS disease. (12) Based on these results, the CDC issued

revised guidelines for the prevention of early-onset GBS

disease in 2002, recommending universal screening of

pregnant women for GBS by rectovaginal culture at

35 to 37 weeks gestation and management of IAP based

on screening results. (13) The revised guidelines can beaccessed at http://www.cdc.gov/mmwr/preview/

mmwrhtml/rr5111a1.htm or in PDF form at http://

www.cdc.gov/mmwr/PDF/rr/rr5111.pdf.

The CDC guideline includes specific recommenda-

tions for pregnant women who have documented GBS

bacteriuria or who previously delivered infants who had

GBS disease and for the use of IAP in women experienc-

ing threatened preterm labor. The revised guidelines also

address concerns over the documented emergence of

GBS resistance to erythromycin and clindamycin, antibi-

otics frequently used for IAP in women allergic to peni-

cillin. The CDC continues to recommend penicillin or

ampicillin for IAP. In those who have penicillin allergy,

testing of GBS screening isolates for antibiotic suscepti-

bility is recommended to guide the choice of antibiotic

(erythromycin, clindamycin, cefazolin, or vancomycin)

for IAP. Adequate IAP is defined as the administration

of one of the endorsed antibiotics 4 or more hours prior

to delivery. The revised CDC guideline also includes a

recommended algorithm for the evaluation of infants

born to mothers exposed to IAP.

Current Status of GBS EOSCDC active surveillance data for the United States from

1999 to 2005 demonstrate that the incidence of GBS

EOS has fallen to 0.34 cases per 1,000 live births in

2003 to 2005 (compared with 1.7 cases per 1,000 livebirths in 1993). (1) We recently evaluated the reasons for

persistent GBS EOS despite the use of a screening-based

approach to IAP at the BWH. (14)(15) We found that

most GBS EOS in term infants now occurs in infants

born to women who have negative antepartum screening

results for GBS colonization. Many of the mothers in this

study had other intrapartum risk factors for sepsis, un-

derscoring the importance of continued evaluation of

infants at risk for EOS in the era of GBS prophylaxis.

There is a low incidence (approximately 4%) of noncon-

cordance between results of maternal GBS screening

performed at 35 to 37 weeks gestation and repeatscreening on presentation for delivery at term, (16)

which may account for many cases of persistent GBS

EOS.

Bacterial culture remains the CDC-recommended

standard for detection of maternal GBS colonization. In

2002, the United States Food and Drug Administration

approved the first polymerase chain reaction (PCR)-

based rapid diagnostic test for use in detection of mater-

nal GBS colonization. The test can be completed in

1 hour and potentially allows for screening of pregnant

women on presentation for delivery. (17) Although this

type of testing could address the risk of antenatal false-negative GBS screens, the costs and technicalities of

providing continuous support for a real-time PCR-based

diagnostic are considerable, and most obstetric services

continue to rely on antenatal screening culture alone.

EOS Caused by E coliE coliis the second most common organism isolated in

EOS in all neonates and the single most common EOS

organism in VLBW infants. (3)(6) E coli are facultative

anaerobic gram-negative rods found universally in the

human intestinal tract and commonly in the human

vagina and urinary tract. There are hundreds of different





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antigenic types of E coli, but EOS E coli infections,

particularly those complicated by meningitis, are primar-

ily due to strains that have the K1-type polysaccharide

capsule. With the implementation of IAP against GBS,

an increasing proportion of EOS cases are caused by

gram-negative organisms. (4) Whether GBS IAP policies

are contributing to an absolute increase in the incidence

of EOS caused by gram-negative organisms, particularly

ampicillin-resistant gram-negative organisms, is contro-

versial.

In 2003, the CDC published a review of 23 reports of

EOS in the era of GBS prophylaxis, (4) which concluded

that there is no evidence of an increase in non-GBS EOS

among term infants. A case-control study of 132 cases of

neonatal EOS caused byE colioccurring from 1997 to2001 recently published by the CDC concluded that

exposure to intrapartum antibiotic therapy did not in-

crease the odds of invasive early-onset E coli infection.

(18) In fact, this study demonstrated a protective effect

of intrapartum antibiotic exposure on the risk ofE coli

EOS among term infants. However, worrisome increases

in non-GBS EOS and ampicillin-resistant EOS in VLBW

infants have been reported by single centers (19) and by

the NICHD Neonatal Research Network. (20) The mul-

ticenter NICHD Network documented an increase inE

coliEOS in VLBW infants from 3.2 cases per 1,000 live

births in 1991 to 1993 to 7.0 cases per 1,000 live birthsin 2002 to 2003.

Trends in the microbiology of EOS likely vary to some

extent by institution and may be influenced by local

obstetric practices as well as by local variation in indige-

nous bacterial flora. To address this important issue, the

CDC Active Bacterial Core Surveillance Program and the

NICHD Neonatal Research Network are conducting

active surveillance for early-onset neonatal sepsis from

2007 to 2009 that will include data on intrapartum

antibiotic exposure and collection of specific infecting

bacterial isolates for microbiologic study. (21) Informa-

tion from studies of this type may help guide clinicaldecisions regarding empiric antibiotic choice for EOS,

particularly in VLBW infants. Currently, when there is

strong clinical suspicion for sepsis in a critically ill infant,

the possibility of ampicillin-resistant gram-negative in-

fection suggests the consideration of empiric use of a

third-generation cephalosporin such as cefotaxime or

ceftazidime.

Other Organisms Responsible for EOSIn addition to GBS andE coli, a number of other patho-

gens that cause EOS in the United States deserve special

note. Listeria monocytogenes are gram-positive, beta-

hemolytic, motile bacteria that most commonly infect

humans via the ingestion of contaminated food. An

association with prepared foods held at moderate tem-

perature (particularly cheeses and deli meats) has been

documented, occasionally in epidemic outbreaks. These

bacteria do not cause significant disease in immunocom-

petent adults but can cause severe illness in the immuno-

compromised (ie, renal transplant patients), in pregnant

women and their fetuses, and in newborns. The true

incidence of listeriosis in pregnancy is difficult to deter-

mine because many cases are undiagnosed when they

result in spontaneous abortion of the previable fetus.

Obligate anaerobic bacteria (primarily the encapsulated

enteric organismBacteroides fragilis) can cause neonatal

EOS and justify the use of both aerobic and anaerobicblood culture bottles in the evaluation of EOS. Although

both methicillin-sensitive and methicillin-resistant S au-

reus (MRSA) cause a large proportion of hospital-

acquired infection in VLBW infants and represent an

increasing issue in community-acquired pediatric infec-

tions, they remain a rare cause of neonatal EOS. A recent

study of 5,732 pregnant women documented a 3.5%

incidence of MRSA in GBS rectovaginal screening cul-

tures but found no cases of MRSA neonatal EOS in

delivered infants. (22) Finally, fungal organisms (primar-

ilyCandidasp) rarely cause neonatal EOS. Fungal EOS

is found largely in preterm and VLBW infants and in ourcenter is associated with very prolonged antibiotic (24

h) exposure of pregnant mothers prior to delivery.

Clinical Risk Factors for EOSMaternal and infant characteristics associated with the

development of EOS have been studied most rigorously

with respect to GBS EOS, but much of these data were

obtained prior to the implementation of IAP for GBS

prevention. Perhaps the most challenging clinical issue in

the era of GBS prophylaxis is the identification and

evaluation of the initially asymptomatic term and late

preterm infant at risk for EOS. Escobar and associates(23) studied a cohort of more than 18,000 infants born

in 1995 to 1996, cared for in a single health-care plan,

whose birthweights were at least 2,000 g, and who had

no major anomalies. Of these, 2,785 infants were evalu-

ated for EOS with a complete blood count and blood

culture. Multivariate analyses of predictors of EOS ac-

counted for intrapartum antibiotic exposure and mod-

eled maternal chorioamnionitis either as a clinical obstet-

ric diagnosis or as an entity defined by prolonged rupture

of membranes and maternal fever. Results of the latter

model are shown in Table 4, but the overall findings were

the same in each model: maternal intrapartum fever, the





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clinical diagnosis of chorioamnionitis, low absolute neu-

trophil count, and the presence of meconium-stained

amniotic fluid each were associated with increased risk of

EOS, with some modification of these factors in the

presence of maternal intrapartum antibiotic exposure.

Although this study aids in our understanding the issues

of overall EOS risk in the era of GBS prophylaxis, it also

underscores the challenge of evaluating the initiallyasymptomatic infant. Only 1% of the initially asymptom-

atic infants in this study had EOS, and asymptomatic

status predicted against infection. Yet, this incidence is

10-fold higher than the population risk of 1 to 2 cases per

1,000 live births, pointing out the importance of the

clinical factors that prompted the evaluation for infection

and confirming the concept that asymptomatic status

alone cannot rule out infection.

Algorithm for the Evaluation ofAsymptomatic Infants at Risk for EOS

The CDC 2002 guidelines for the use of IAP to preventearly-onset GBS disease address the evaluation of infants

at risk for GBS-specific EOS. Other microbiologic causes

of EOS also must be considered in evaluating the asymp-

tomatic infant at risk for infection. Many centers develop

protocols to standardize the decision to evaluate an

asymptomatic infant for EOS. We use a protocol for

evaluation of the asymptomatic infant born at 35 or more

weeks gestation who is at risk for EOS (Figure). This

protocol takes into account the 2002 CDC guideline for

GBS prophylaxis as well as the existing literature on the

risk of overall EOS. In addition, it accounts for center-

specific factors (including the primary role of pediatric

resident housestaff in conducting

EOS evaluations at our center and

the use of epidural analgesia in most

deliveries). A total white blood cell

count less than 5.0103/mcL

(5.0109/L) or an immature to

total neutrophil ratio greater than

0.2 is used to guide treatment de-

cisions in the evaluation of the

well-appearing infant at risk for

sepsis. A single white blood cell

determination is used in most cases

to avoid multiple blood collections

from otherwise asymptomatic in-

fants. This particular algorithm maynot be ideal for all centers and only

is included as a model protocol.

A quality improvement study con-

ducted at our institution compared

the rate of compliance with CDC recommendations

for the evaluation of infants at risk for early-onset GBS

disease between hospitals within our health-care system

that did or did not have a mandated protocol and found

significantly greater compliance in the hospitals that used

a specific protocol.

Current Clinical Challenges in EOSEOS remains an infrequent but potentially devastating

clinical issue for term and preterm infants. The wide-

spread implementation of IAP for the prevention of

GBS early-onset disease has resulted in an overall de-

crease in neonatal EOS in the United States. There

remain, however, a number of research questions that

need to be addressed to optimize neonatal care further

with respect to EOS. Considerable clinical time and

economic resources are expended in the identification

and evaluation of infants at risk for EOS. A multicenter

reassessment of the clinical risk factors for EOS in the

setting of proper implementation of a screening-basedprogram for IAP should be performed. Such a study may

allow clinicians to identify more accurately the initially

asymptomatic infant who needs to be evaluated for in-

fection in the era of GBS prophylaxis. The utility of

real-time PCR-based GBS diagnostics, used either as a

substitute for third trimester culture-based GBS screen-

ing or as an addition to culture-based screening, needs to

be assessed on a national basis to determine if this test can

lower the national incidence of early-onset GBS disease

further. Finally, the CDC has endorsed the need for

continued surveillance to assess the impact of GBS pro-

phylaxis practices on the microbiology of EOS, particu-

Table 4.Risk Factors for All Causes of Early-onset

Sepsis in Infants Weighing Less than 2,000 gAt Birth in the Era of Intrapartum AntibioticProphylaxis

Multivariate Odds Ratio (95% ConfidenceInterval)

Predictor

No IntrapartumAntibiotics(n1,568)

IntrapartumAntibiotics(n1,217)

Temperature >101.5F (38.6C) 5.78 (1.57 to 21.29) 3.50 (1.30 to 9.42)Rupture of membranes >12 h 2.05 (1.06 to 3.96) Not significantLow absolute neutrophil count

for age

2.82 (1.50 to 5.34) 3.60 (1.45 to 8.96)

Infant asymptomatic 0.27 (0.11 to 0.65) 0.42 (0.16 to 1.11)Meconium in amniotic fluid 2.24 (1.19 to 4.22) Not significant

Adapted from Escobar et al.Pediatrics.2000;106:256263.





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larly among VLBW infants. Research into individual

center obstetric practices as well as national surveillance

may help identify the risks that may be associated with

IAP to allow neonates to continue to benefit from this

important advance in the prevention of EOS.

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IAPintrapartum antibiotic prophylaxis, I:Timmature to total, PMNpolymorphonuclear lymphocytes, PTDprior to delivery,

ROMrupture of membranes, WBC-white blood cell.





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5. Widespread implementation of intrapartum antibiotic prophylaxis has altered the epidemiology of early-onset sepsis (occurring at less than 72 hours after birth) in the newborn. The incidence of group BStreptococcus (GBS) early-onset sepsis has decreased; the incidence of non-GBS early-onset sepsis isunchanged or decreasing. Of the following, the national incidence of GBS early-onset sepsis, as estimatedin 2003 through 2005, is closestto:

A. 0.03 per 1,000 live births.B. 0.30 per 1,000 live births.C. 0.60 per 1,000 live births.D. 0.90 per 1,000 live births.E. 0.20 per 1,000 live births.

6. The spectrum of microorganisms causing early-onset sepsis in the era of intrapartum antibiotic prophylaxisis different between term neonates (>2,000 g birthweight) and very low-birthweight neonates (2,000 g birthweight) and very low-birthweight (VLBW) neonates(18 hours).





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DOI: 10.1542/neo.9-12-e5712008;9;e571NeoReviews

Karen M. PuopoloEpidemiology of Neonatal Early-onset Sepsis

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DOI: 10.1542/neo.9-12-e5712008;9;e571NeoReviews

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