بسم الله بسم الله الرحمن الرحيمالرحمن الرحيم

PROLONGED RUPTURE PROLONGED RUPTURE OF MEMBRANESOF MEMBRANES

ANDANDNEONATAL INFECTIONNEONATAL INFECTION

Ayman Abou Mehrem, MD, CABPAyman Abou Mehrem, MD, CABPStaff PhysicianStaff Physician

Department of PediatricsDepartment of PediatricsKing Abdulaziz National Guard HospitalKing Abdulaziz National Guard Hospital

Pathogenesis of Ascending Pathogenesis of Ascending Bacterial InfectionBacterial Infection

In most casesIn most cases the fetus or neonate is the fetus or neonate is not exposed to potentially pathogenic not exposed to potentially pathogenic bacteria until the membranes rupture bacteria until the membranes rupture

and the infant passes through the birth and the infant passes through the birth canal and/or enters the extra uterine canal and/or enters the extra uterine

environmentenvironment

TheThe human birth canal is colonized with human birth canal is colonized with aerobic and anaerobic organisms that aerobic and anaerobic organisms that

may result in ascending amniotic may result in ascending amniotic infection and/or colonization of the infant infection and/or colonization of the infant

at birthat birth

VERTICAL TRANSMISSIONVERTICAL TRANSMISSION of bacterial of bacterial agents that infect the amniotic fluid agents that infect the amniotic fluid

and/or vaginal canal may occur in utero and/or vaginal canal may occur in utero or or more commonlymore commonly during labor and/or during labor and/or

deliverydelivery

CHORIOAMNIONITISCHORIOAMNIONITIS results from results from microbial invasion of amniotic fluid as a microbial invasion of amniotic fluid as a

result of prolonged rupture of the result of prolonged rupture of the chorioamniotic membranechorioamniotic membrane

On occasionOn occasion, , amniotic infection occurs with apparently amniotic infection occurs with apparently

intact membranes or with a relatively intact membranes or with a relatively brief duration of membrane rupturebrief duration of membrane rupture

Amniotic fluid infection may be Amniotic fluid infection may be asymptomatic or may produce maternal asymptomatic or may produce maternal fever with or without local or systemic fever with or without local or systemic

signs of chorioamnionitissigns of chorioamnionitis

THE DURATION OF MEMBRANE THE DURATION OF MEMBRANE RUPTURERUPTURE is directly correlated with the is directly correlated with the

development of chorioamnionitisdevelopment of chorioamnionitis

LONGER THAN 18 HOURSLONGER THAN 18 HOURS is the is the current cut off for increased risk of current cut off for increased risk of

neonatal infectionneonatal infection

OTHER FACTORSOTHER FACTORS that associated with that associated with increased frequency of increased frequency of NEONATAL NEONATAL

INFECTIONINFECTION

Difficult DeliveryDifficult Delivery Traumatic DeliveryTraumatic Delivery Preterm DeliveryPreterm Delivery Resuscitation at BirthResuscitation at Birth

In most casesIn most cases, , bacterial colonization of the newborn bacterial colonization of the newborn

does notdoes not result in disease result in disease

What are the factors influencing which What are the factors influencing which colonized infant will develop diseasecolonized infant will develop disease??

These are not well understood, but include:These are not well understood, but include:PrematurityPrematurityUnderlying illnessUnderlying illness Invasive proceduresInvasive procedures Inoculum sizeInoculum sizeVirulence of infecting organismVirulence of infecting organismTransplacental maternal antibodiesTransplacental maternal antibodies

AspirationAspiration or or ingestion ingestion of bacteria in of bacteria in amniotic fluid may lead to congenital amniotic fluid may lead to congenital pneumonia or systemic infection, with pneumonia or systemic infection, with manifestations become apparent before manifestations become apparent before delivery or after a latent period of a few delivery or after a latent period of a few hours. Aspiration or ingestion of bacteria hours. Aspiration or ingestion of bacteria during the birth process may lead to during the birth process may lead to infection after an interval of 1-2 days.infection after an interval of 1-2 days.

Prematurity and InfectionPrematurity and Infection

Preterm infants have 3- to 10-fold Preterm infants have 3- to 10-fold higher incidence of infection than full higher incidence of infection than full term, normal birth weight infants doterm, normal birth weight infants do

is considered to be an important is considered to be an important cause of preterm labor with an cause of preterm labor with an

increased risk of vertical increased risk of vertical transmission to the newborntransmission to the newborn

Maternal genital tract infectionMaternal genital tract infection

gestational agegestational age

The frequency of intra-amniotic The frequency of intra-amniotic infection is inversely related toinfection is inversely related to

immune dysfunctionimmune dysfunctionPremature infants have documentedPremature infants have documented

Premature infants often require Premature infants often require prolonged intravenous access, prolonged intravenous access,

endotracheal intubation or other endotracheal intubation or other invasive procedures that provide ainvasive procedures that provide a

portal of entry or impair portal of entry or impair clearance mechanismsclearance mechanisms

The most common bacterial organisms The most common bacterial organisms causing neonatal infection are:causing neonatal infection are:

Group B streptococcus (Streptococcus Group B streptococcus (Streptococcus agalactiae)agalactiae)

Enteric organismsEnteric organismsListeria monocytogenesListeria monocytogenesGonococciGonococciChlamydiaChlamydia

Group B StreptococcusGroup B StreptococcusGBSGBS

GBS is encapsulated Gram positive GBS is encapsulated Gram positive coccus colonizes the gastrointestinal coccus colonizes the gastrointestinal

and genital tracts in the humansand genital tracts in the humans

Approximately Approximately 25%25% of pregnant women of pregnant women carried this organism in their genital carried this organism in their genital and/or gastrointestinal tracts and this and/or gastrointestinal tracts and this

carriage was the most critical carriage was the most critical determinant of risk for early onset GBS determinant of risk for early onset GBS

infection in their offspringinfection in their offspring

Approaches for GBS Prevention in the NewbornApproaches for GBS Prevention in the Newborn

Eradication of colonizationEradication of colonization in pregnant women in pregnant women with antibiotics given during pregnancywith antibiotics given during pregnancy

Active screeningActive screening of pregnant women with of pregnant women with antibiotics during labor only for those with positive antibiotics during labor only for those with positive screening culturesscreening cultures

AntibioticsAntibiotics during labor for all pregnant women during labor for all pregnant women with one or more factors leading to an increased with one or more factors leading to an increased risk for GBS infection in their offspringrisk for GBS infection in their offspring

Development of vaccinesDevelopment of vaccines which could be which could be administered to women before pregnancyadministered to women before pregnancy

The first guidelines for Intrapartum Antibiotic The first guidelines for Intrapartum Antibiotic Prophylaxis (IAP) were published by the Prophylaxis (IAP) were published by the AAP in 1992AAP in 1992

A CDC survey of a population of almost 30 A CDC survey of a population of almost 30 million documented a significant decrease in million documented a significant decrease in early onset infection (i.e. < 7 days of age) early onset infection (i.e. < 7 days of age) between 1993 and 1998 (1.7 to 0.6 cases between 1993 and 1998 (1.7 to 0.6 cases per 1000 births)per 1000 births)

2002 Revised IAP Guidelines2002 Revised IAP Guidelines

All pregnant womenAll pregnant women should be screened should be screened for GBS colonization with swabs of both for GBS colonization with swabs of both the lower vagina and rectum at 35 to 37 the lower vagina and rectum at 35 to 37 weeks of gestation. The only patients who weeks of gestation. The only patients who are are excludedexcluded from screening are those from screening are those with GBS bacteriuria earlier in the current with GBS bacteriuria earlier in the current pregnancy or those who gave birth to a pregnancy or those who gave birth to a previous infant with invasive GBS disease. previous infant with invasive GBS disease. These are not included in the screening These are not included in the screening recommendation because they should recommendation because they should receive IAP regardless of the colonization receive IAP regardless of the colonization statusstatus

SwabsSwabs should be obtained from the lower should be obtained from the lower vagina vagina (not cervix)(not cervix) and rectum and rectum (not anal (not anal orifice)orifice) and should be promptly placed into and should be promptly placed into non-nutrient transport medianon-nutrient transport media

Susceptibility testingSusceptibility testing to erythromycin and to erythromycin and clindamycin, if feasible, should be performed clindamycin, if feasible, should be performed for GBS isolates for GBS isolates

Patients recommended for Patients recommended for IAPIAP

Pregnant women with a positive screening culture from Pregnant women with a positive screening culture from either vagina or rectum either vagina or rectum unlessunless a planned cesarean delivery a planned cesarean delivery is performed in the absence of labor or membrane ruptureis performed in the absence of labor or membrane rupture

Pregnant women who gave birth to a previous infant with Pregnant women who gave birth to a previous infant with invasive GBS diseaseinvasive GBS disease

Pregnant women with documented bacteriuria during the Pregnant women with documented bacteriuria during the current pregnancycurrent pregnancy

Pregnant women whose culture status is unknown (culture Pregnant women whose culture status is unknown (culture not performed or results not available) and who have any of not performed or results not available) and who have any of the following:the following:

Delivery at <37 weeks of gestationDelivery at <37 weeks of gestation Amniotic membrane rupture for ≥18 hoursAmniotic membrane rupture for ≥18 hours Intrapartum temperature ≥38°CIntrapartum temperature ≥38°C

Patients not recommended Patients not recommended for IAPfor IAP

Positive GBS screening culture in a previous Positive GBS screening culture in a previous pregnancy (unless the infant had invasive GBS pregnancy (unless the infant had invasive GBS disease or the screening culture is also positive in disease or the screening culture is also positive in the current pregnancy)the current pregnancy)Patient who undergoes a planned cesarean Patient who undergoes a planned cesarean delivery without labor or rupture of membranesdelivery without labor or rupture of membranesPregnant women with negative GBS screening Pregnant women with negative GBS screening culture at 35 to 37 weeks of gestation even if they culture at 35 to 37 weeks of gestation even if they have one or more of the above intrapartum risk have one or more of the above intrapartum risk factors.factors.

The use of broad spectrum intrapartum The use of broad spectrum intrapartum antibiotics for the treatment of presumed antibiotics for the treatment of presumed chorioamnionitis in febrile women in labor chorioamnionitis in febrile women in labor is left to the discretion of the obstetricianis left to the discretion of the obstetrician

IAP IAP regimensregimensPenicillin GPenicillin G (5 million units IV initial dose, then (5 million units IV initial dose, then 2.5 million units IV Q4h)2.5 million units IV Q4h)Ampicillin Ampicillin (2 g IV initial dose, then 1 g IV Q4h). (2 g IV initial dose, then 1 g IV Q4h). Penicillin is preferred based upon its narrower Penicillin is preferred based upon its narrower spectrum of activity and theoretical reduced spectrum of activity and theoretical reduced opportunity for development of ampicillin-opportunity for development of ampicillin-resistant organismsresistant organismsCefazolin Cefazolin (2 g initial dose, then 1 g Q8h) is (2 g initial dose, then 1 g Q8h) is recommended for women with a history of non-recommended for women with a history of non-immediate-type penicillin-allergy, i.e. at low risk immediate-type penicillin-allergy, i.e. at low risk for anaphylaxisfor anaphylaxis

Clindamycin Clindamycin (900 mg IV Q8h) or(900 mg IV Q8h) or Erythromycin Erythromycin (500 mg IV Q6h) are recommended for patients (500 mg IV Q6h) are recommended for patients at high risk for anaphylaxis to penicillins at high risk for anaphylaxis to penicillins only ifonly if their GBS culture screening isolate is their GBS culture screening isolate is documented to be susceptible to one of themdocumented to be susceptible to one of them

Vancomycin Vancomycin (1 g Q12h) is recommended for (1 g Q12h) is recommended for patients at high risk for anaphylaxis and a GBS patients at high risk for anaphylaxis and a GBS isolate resistant to clindamycin or erythromycin; isolate resistant to clindamycin or erythromycin; or with unknown susceptibilityor with unknown susceptibility

IAP is continued from hospital IAP is continued from hospital admission through deliveryadmission through delivery

The greatest efficacy is achieved The greatest efficacy is achieved if penicillin G, ampicillin, or if penicillin G, ampicillin, or

theoretically cefazolin is theoretically cefazolin is administered ≥4 hours before administered ≥4 hours before

deliverydelivery

Approach to Threatened Preterm DeliveryApproach to Threatened Preterm Delivery

No GBS cultureNo GBS culture GBS +

Onset of labor or rupture of membranes at <37 weeks gestationOnset of labor or rupture of membranes at <37 weeks gestationwith significant risk for imminent preterm delivery with significant risk for imminent preterm delivery

GBS -

Penicillin IV

for >=48 hrs

(during tocolysis)

Obtain vaginal

and rectal GBS

culture and

initiate IV penicillin

No GBS

prophylaxis

IAP at delivery

Stop penicillin

GBS +

No growth at 48 hrs

Management of the infant Management of the infant whose mother has whose mother has

received IAPreceived IAP

Any gestational ageAny gestational age

If the infant is ill-appearing or sepsis is If the infant is ill-appearing or sepsis is otherwise strongly suspected, a full diagnostic otherwise strongly suspected, a full diagnostic evaluation including a CBC with differential, a evaluation including a CBC with differential, a blood culture, and a lumbar puncture (unless blood culture, and a lumbar puncture (unless the clinical status dictates otherwise) should be the clinical status dictates otherwise) should be done and empiric antibiotic treatment initiated done and empiric antibiotic treatment initiated using ampicillin and gentamicin until laboratory using ampicillin and gentamicin until laboratory results are known. A chest radiograph should be results are known. A chest radiograph should be obtained if respiratory symptoms are presentobtained if respiratory symptoms are present

Infants born at <35 wks of gestationInfants born at <35 wks of gestation

there is a clinical suspicion for sepsisthere is a clinical suspicion for sepsis a change occurs in clinical statusa change occurs in clinical status the blood culture yields GBSthe blood culture yields GBS IAP administered <4 hrs prior to delivery IAP administered <4 hrs prior to delivery

If the infant is healthy-appearing and IAP with If the infant is healthy-appearing and IAP with penicillin, ampicillin, or cefazolin was penicillin, ampicillin, or cefazolin was administered to the mother at least 4 hrs prior administered to the mother at least 4 hrs prior to delivery, a CBC with diff. and blood culture to delivery, a CBC with diff. and blood culture should be obtained and the infant observed should be obtained and the infant observed without antibiotic treatment for at least 48 hrswithout antibiotic treatment for at least 48 hrsEmpiric antibiotics are initiated if:Empiric antibiotics are initiated if:

Infants born at ≥35 wks of gestationInfants born at ≥35 wks of gestationIf the infant is healthy-appearing and IAP with If the infant is healthy-appearing and IAP with penicillin, ampicillin, or cefazolin was penicillin, ampicillin, or cefazolin was administered to the mother at less than 4 hrs administered to the mother at less than 4 hrs prior to delivery, a CBC with diff. and blood prior to delivery, a CBC with diff. and blood culture should be obtained and the infant culture should be obtained and the infant observed without antibiotic treatment for at least observed without antibiotic treatment for at least 48 hrs48 hrsEmpiric antibiotics are initiated if:Empiric antibiotics are initiated if: a change occurs in clinical statusa change occurs in clinical status the blood culture yields GBS the blood culture yields GBS

If the infant is healthy-appearing and IAP with If the infant is healthy-appearing and IAP with penicillin, ampicillin, or cefazolin was penicillin, ampicillin, or cefazolin was administered to the mother at least 4 hrs prior administered to the mother at least 4 hrs prior to delivery, the infant does not need further to delivery, the infant does not need further evaluation but should be observed in the evaluation but should be observed in the hospital without antibiotic treatment for at least hospital without antibiotic treatment for at least 48 hrs48 hrs

Maternal IAP for GBS?

Maternal antibiotics for suspected

chorioamnionitis?

Limited evaluationObserve ≥48hrs

If sepsis is suspected, full diagnostic evaluation and

empiric therapy

Full diagnostic evaluationEmpiric therapy

Signs of neonatal sepsis?

GA <35 weeks?

No evaluationNo therapy

Observe ≥48 hrs

Duration of IAP before delivery <4 hrs?

Yes

Yes

Yes

YesYes

No

No

No

Management of the infant Management of the infant whose mother has whose mother has

received IAPreceived IAP

Management of the infant whose mother has Management of the infant whose mother has prolonged rupture of membranesprolonged rupture of membranes

Rupture of Membranes ≥ 18 hrs

Mother has Chorioamnionitis?

Sings of Neonatal Sepsis?

GBS Screening at 35-37 wks gestation

Negative

No EvaluationNo Therapy

Observe ≥ 48 hrs

Positiveor Unknown

Mother received IAP ≥ 4 hrs prior to delivery

GA < 35 wks

Limited Evaluation (CBC with differential, and blood culture)Observe ≥ 48 hrsFull Septic Screen and Start I.V. Antibiotics if: 1- Change in clinical status2- Blood culture yields GBS

GA < 35 wks

Full Septic Screen: CBC with differential, blood culture, LP, and chest X-ray (if indicated).Start I.V. Antibiotics

Yes

Yes

Yes

Yes

Yes

No

No

No

No

No

Prepared by:Dr. Ayman Abu Mehrem

Approved by:Dr. Hesham Al-Girim

Reference: