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Lec:7 Pediatric Dr:Eman Isam

Neonatology

INFECTIONS IN THE NEWBORN (Neonatal )

The incidence of sepsis is approximately:

 1:1500 in full-term  1:250 in preterm infants. There is sixfold-higher rate of sepsis in preterm infants compared with term infants due to:

 the more immature immunologic systems of preterm infants and deficient transfer of antibodies from the mother to the fetus (which occurs mostly after 32 weeks' gestation).  their prolonged periods of hospitalization, in the neonatal intensive care unit, with exposure to endotracheal tubes, central arterial and venous catheters, and blood draws all increase risk of nosocomially acquired infectious diseases (bacteremia and ).

Routes: The major routes of :

 Infection may be acquired in utero through : . transplacental like(Syphilis and ) . transcervical routes: Ascending infection through the cervix, with or without rupture of the amniotic fluid membranes, may result in amnionitis, funisitis (infection of the ), congenital , and sepsis.  during birth. Infection upon infant passage through an infected birth canal or exposure to infected blood at delivery

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The bacteria responsible are common bacterial organisms of the maternal genitourinary tract.

 Nosocomial: (hospital-acquired) infections:

After birth, neonates are exposed to infectious agents in the nursery or in the community. Postnatal infections may be transmitted by . Direct contact with hospital personnel, the mother, or other family members; . Contaminated equipment. The most common source of postnatal infections in hospitalized newborns is hand contamination of health care personnel.

Classification of neonatal sepsis Neonatal sepsis presents during three periods.

Early-onset sepsis : (birth to 7 days usually>72hr):  Are acquired before or during delivery( often begins in utero) .  Usually is a result of infection caused by the bacteria in the mother's genitourinary tract. Organisms related to this sepsis include:

1. group B streptococci, 2. E. coli, 3. Listeria monocytogenes, 4. nontypable H. influenzae. 5. Klebsiella,

Aspiration or ingestion of bacteria in amniotic fluid may lead to pneumonia or systemic infection.

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Clinical manifestations: Early manifestations-grunting, poor feeding, pallor, apnea, lethargy, hypothermia, or an abnormal cry

Or may present as an overwhelming multiorgan system disease as , shock, meningitis (in 30% of cases), disseminated intravascular coagulation, acute tubular necrosis

The premature infants show nonspecific cardiorespiratory signs, such as grunting, tachypnea, and cyanosis at birth.

Risk factors for early-onset sepsis include;

1. vaginal colonization with group B streptococci, 2. prolonged rupture of the membranes (>18 hours), 3. amnionitis,( maternal fever or leukocytosis, fetal tachycardia), 4. . 5. African-American race and male sex are unexplained additional risk factors

Investigations:

1. blood culture: Documentation of a positive blood culture is the first diagnostic criterion for sepsis. 2. CSF examination,: Gram stain,. CSF culture and antigen, or the use of PCR 3. Chest radiograph :should be obtained to determine the presence of pneumonia. 4. Complete blood counts : Neutropenia is more common than neutrophilia in severe neonatal sepsis, thrombocytopenia. signs of DIC. 5. Arterial blood gases to detect hypoxemia and metabolic acidosis 6. Electrolytes, glucose, Calcium and levels Treatment :

Admission:

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1. Supportive measures, such as fluid ,correct electrolyte disturbance glucose ,acid –base balance, temperature control, nutrition.may need assisted ventilation and cardiovascular support 2. Antibiotic therapy: Once appropriate cultures have been obtained, Initial empirical treatment of early-onset bacterial infections should consist of: intravenous (100 mg/kg/day) and an (usually 5 mg/kg/day),is effective treatment against most organisms responsible for early-onset sepsis..

Once the pathogen has been identified and antibiotic sensitivities determined, the most appropriate drug or drugs should be selected.

Duration of Treatment : 10 to 14 days

If meningitis is present, the treatment should be cephalosporine &gentamicine &extended to 21 days

3. Inhaled nitric oxide, ECMO [Extracorporeal membrane oxygenation](in term infants), or both may improve the outcome of sepsis-related pulmonary hypertension. 4. Intratracheal surfactant may reverse respiratory failure. Prophylaxis:

Intrapartum IV penicillin empirical prophylaxis for group B streptococcal colonized mothers or mothers with risk factors (e.g., fever, preterm labor, previous infant with group B streptococci, and amnionitis) has reduced the rate of early-onset infection.

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Late-onset sepsis: (8 to 28 days) Usually occurs in a healthy full-term infant who was discharged in good health from the normal newborn nursery.

Late-onset sepsis may be caused by the same pathogens as early-onset sepsis, but infants exhibiting sepsis late in the neonatal period also may have infections caused by the pathogens usually found in older infants

1. H. influenzae, 2. S. pneumoniae 3. 4. S. aureus Clinical manifestations: may include lethargy, poor feeding, , apathy, seizures, bulging fontanel, fever, and direct-reacting hyperbilirubinemia.

In addition hematogenous seeding may result in focal infections, such as

1. Meningitis (in 75% of cases), 2. Osteomyelitis (group b streptococci, s. Aureus), 3. Arthritis (gonococcus, s. Aureus, , gram-negative bacteria) 4. Urinary tract infection (gram-negative bacteria).

Investigation: is similar to that for infants with early-onset sepsis, with special attention given to a careful physical examination of the :

 Bones (infants with osteomyelitis may exhibit pseudoparalysis)  Urine examination and culture obtained by sterile supra- pubic aspiration or urethral catheterization. Treatment:

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Because of the increased rate of resistance of H. influenzae and pneumococcus to ampicillin some centers begin treatment with vancomycin and aminoglycoside.

Consider cephalosporine if meningitis is suspected

Duration of Treatment the same as in Early-onset sepsis iii.Nosocomially acquired sepsis (8 days to discharge) occurs predominantly in premature infants in the neonatal intensive care unit; many of these infants have been colonized with the multidrug-resistant bacteria in the neonatal intensive care unit.

Risk factors for nosocomially acquired sepsis include:

1. Prematurity,LBW 2. frequent treatment with broad-spectrum antibiotics for sepsis 3. Invasive procedures: central venous indwelling catheters, endotracheal tubes, umbilical vessel catheters, and electronic monitoring devices. 4. Prolonged hospital stay

 Coagulase-negative staphylococci are the most frequent neonatal nosocomial pathogens followed by gram-negative bacteria and Pseudomonas species

The initial clinical manifestations: of nosocomial infection in a premature infant

 May be non specific and include apnea and , temperature instability, abdominal distention, and poor feeding.  In the later stages, signs of infection are shock, DIC, worsening respiratory status,  local reactions, such as omphalitis, eye discharge, diarrhea, and staphylococcal bullous impetigo

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Treatment:

Treatment of Nosocomially acquired sepsis depends on the indigenous microbiologic flora of the particular hospital and the antibiotic sensitivities.

An antistaphylococcal drug include (cloxacillin ,methicillin or nafcillin for S. Aureus or, vancomycin for coagulase-negative staphylococci ) with aminoglycoside(gentamycin or tobramycin) may be appropriate initial treatment.

PREVENTION OF NOSOCOMIAL INFECTION

1. Strict compliance with handwashing: Handwashing remains the most important and effective means of reducing nosocomial infections .Antimicrobial soaps or alcohol-based preparations are recommended. Proper handwashing is essential before entering the NICU and before each patient contact. 2. Reduce catheter-related infections 3. Decreasing the number of venipunctures and heelsticks

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TORCHS INFECTION

TOXOPLASMOSIS

Vertical transmission of Toxoplasma gondii occurs by transplacental from the mother to the fetus after an acute maternal infection. Transmission of infection rare after reactivation of infection .The severity of fetal disease varies inversely with the gestational age at which maternal infection occurs. High-risk exposure at 10-24 wk gestation

Clinical feature :

1. Many infants asymptomatic at birth 2. present with the classical findings of hydrocephalus, chorioretinitis, and intracerebral calcifications suggest the diagnosis of congenital 3. Non specific : IUGR , jaundice, hepatosplenomegaly, fever,generalized maculopapular rash. Seizures are common, and skull films may reveal diffuse cortical calcifications in contrast to the periventricular pattern observed with CMV.

Diagnosis:in infected infant seroconversion( IGg –ve change to+ve) or four fold rise in IGg titer need determination of specific IgM to confirm the DX .

Treatment: pyrimethamine(supplemented with folic acid) plus sulfadiazine

RUBELLA

With the widespread use of vaccination, congenital rubella is rare in developed countries. Early infection result in sever defect

 Infection is acquired during the first 4 weeks of gestation congenital defects approaches 85%.

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 Infection occurs during weeks 13 to 16, 35% of infants can have abnormalities.  Infection after 4 months' gestation does not seem to cause disease.

The most common characteristic abnormalities associated with congenital rubella include:

. ophthalmologic (microphthalmia, cataracts, glaucoma, "salt and pepper" chorioretinitis, ) . cardiac (patent ductus arteriosus and peripheral pulmonary artery stenosis), . auditory (sensorineural hearing loss), . purpuric skin lesions ("blueberry muffin" appearance from dermal erythropoiesis) . neurologic (microcephaly, meningoencephalitis, and mental retardation) . infants can present with growth retardation, hepatosplenomegaly, early-onset jaundice,thrombocytopenia, radiolucent bone disease.

Infants with congenital rubella are chronically and persistently infected and tend to shed live virus in urine, stools, and respiratory secretions for 1 year. Infants should be isolated while in the hospital and kept away from susceptible pregnant women when sent home.

Diagnosis:by identification of specific rubella IgM ab.

Prevention by vaccination.No specific treatment available.

CYTOMEGALOVIRUS

CMV is the most common congenital infection and the leading cause of sensorineural hearing loss, mental retardation, retinal disease, and cerebral palsy

Sources for primary infections of CMV during :

 sexual contacts 9

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 contact with infected young children.

Clinical features

10% of infected infants are small for gestational age and have symptoms at birth. Findings include microcephaly, thrombocytopenia, hepatosplenomegaly, hepatitis, intracranial calcifications, chorioretinitis, and hearing abnormalities. Some infants can present with a blueberry muffin appearance as the result of dermal erythropoiesis

. Skull films may reveal periventricular calcifications.

An additional 10% of infected infants may not present until later in infancy or early childhood, when they are found to have sensorineural hearing loss and developmental delays

Diagnosis : detection of virus in the urine or saliva. by traditional virus culture , monoclonal antibody or PCR

Treatment : trial of antiviral agent ganciclovir under study.

HERPES SIMPLEX VIRUS

HSV-2 accounts for 90% of primary genital herpes. neonatal infections are acquired from the mother by ascending infection(after rupture of membrane) or during passage through the birth canal at delivery.

Clinical manifestations: most infants are normal at birth, and symptoms of infection develop at 5 to 10 days of life. Symptoms of neonatal HSV infection include :

 disseminated disease involving multiple organ systems, mostly the liver and lungs; Disseminated infection should be considered in any infant with symptoms of sepsis, liver dysfunction, and negative bacteriological cultures  localized infection to the CNS  localized infection to the skin, eyes, and mouth 10

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Diagnosis :  viral culture should be obtained from any skin vesicle,eyes, urine, blood, CSF, stool  PCR is a sensitive method for detectingviral DNA in blood, skin lesions, and CSF.

Treatment :parenteral acyclovir is the treatment of choice for neonatal HSV infections

Prognosis is excellant for infants with disease limited to the skin, eyes, and mouth.

Treponema pallidum (syphilis) :sexually transmitted disease .

Mode of transmission include:

 transplacental infection of the fetus  direct contact with maternal primary asymptomatic painless "hidden" chancre at birth. clinical manifestations:

1. Intrauterine infection can result in , , or prematurity. 2. Many infants are asymptomatic at the time of diagnosis. If untreated, symptoms appear within the first 5 weeks of life. The most striking lesions affect the mucocutaneous tissues and bones.

a)Muco cutaneous poor feeding and snuffles (syphilitic rhinitis). Snuffles are more severe and persistent than the common cold and are often bloody.

A maculopapular desquamative rash develops over the palms and soles and around the mouth and anus.

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b)Bone :more than 90% of symptomatic infants exhibit radiographic abnormalities osteochondritis and perichondritis of the long bone.

3. Late onset: Untreated infants may develop late symptoms, which appear after 2 years of age and involve the CNS, bones, joints, teeth, eyes, and skin. such as interstitial keratitis, eighth cranial nerve deafness, Hutchinson teeth, frontal bossing, mulberry molars, saddle nose,Clutton joints

Diagnosis: Dark-field examination of direct fluorescent antibody staining of organisms obtained by scraping a skin or mucous membrane lesion is the quickest and most direct method of diagnosis. serological testing including the nontreponemal reaginic antibody assays—the Venereal DiseaseResearch Laboratory (VDRL)

Treatment :Parenteral Penicillin G for 10 to 14 days is the only documented effective therapy for infants who have and neurosyphilis .

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