Слайд 2Background
Neonatal sepsis may be categorized as early-onset or late-onset. Of newborns
with early-onset sepsis, 85% present within 24 hours, 5% present at 24-48 hours, and a smaller percentage present within 48-72 hours.
Onset is most rapid in premature neonates.
Early-onset sepsis is associated with acquisition of microorganisms from the mother.
Late-onset sepsis occurs at 4-90 days of life and is acquired from the caregiving environment.
Слайд 3Pathophysiology
1. Specific microbial factors - The bacterial capsule polysaccharide of Staphylococcus
epidermidis adheres well to the plastic polymers of the catheters; organism provides a barrier to the host defense
2. Host factors that predispose the newborn to sepsis
cellular immunity
-neonatal PMNs are deficient in chemotaxis and killing capacity
-neutrophil reserves are easily depleted because of the diminished response of the bone marrow, especially in the premature infant
-Formation of antigen-specific memory function after primary infection is delayed
humoral immunity
-lower levels of immunoglobulins are found with increasing prematurity
-Mature complement activity is not reached until infants are aged 6-10 months.
barrier function.
-Skin and mucous membranes are broken down easily in the premature infant.
-Neonates who are ill, premature, or both are at additional risk because of the invasive procedures that breach their physical barriers to infection.
Слайд 4The microorganisms most commonly associated with early-onset infection
Group B Streptococcus
(GBS)
Escherichia coli
Coagulase-negative Staphylococcus
Haemophilus influenzae
Listeria monocytogenes
Слайд 5Early onset sepsis in the United States
Слайд 6Early onset sepsis among very low birth weight infants in the
United States
Слайд 7Early onset sepsis in developing nations.
Слайд 8The most common risk factors associated with early-onset neonatal sepsis
Maternal
GBS colonization (especially if untreated during labor)
Premature rupture of membranes (PROM)
Preterm rupture of membranes
Prolonged rupture of membranes
Prematurity
Maternal urinary tract infection
Chorioamnionitis
Слайд 9Other factors that are associated with or predispose to early-onset neonatal
sepsis
Low Apgar score (< 6 at 1 or 5 minutes)
Maternal fever greater than 38°C
Maternal urinary tract infection (UTI)
Poor prenatal care
Poor maternal nutrition
Low socioeconomic status
History of recurrent abortion
Maternal substance abuse
Low birth weight
Difficult delivery
Birth asphyxia
Meconium staining
Congenital anomalies
Слайд 10Organisms that have been implicated in causing late-onset sepsis
Coagulase-negative Staphylococcus
Staphylococcus
aureus
E coli
Klebsiella
Pseudomonas
Enterobacter
Candida
GBS
Serratia
Acinetobacter
Anaerobes
Слайд 11Late-onset sepsis is associated with the following risk factors
Prematurity
Central venous
catheterization (duration >10 days)
Nasal cannula or continuous positive airway pressure (CPAP) use
H2 -receptor blocker or proton pump inhibitor (PPI) use
GI tract pathology
Слайд 12Factors that confer a greater risk for LOS in the neonate.
Слайд 13Meningitis
The principal pathogens in neonatal meningitis are GBS (36% of cases),
E coli (31%), and Listeria species (5-10%). Other organisms that may cause meningitis include the following:
S pneumoniae
S aureus
S epidermidis
H influenzae
Pseudomonas species
Klebsiella species
Serratia species
Enterobacter species
Proteus species
Слайд 14Meningitis
Ventriculitis
Arachnoiditis
Vasculitis
Cerebral edema
Infarction
Слайд 15Epidemiology
The incidence of culture-proven sepsis in the United States is approximately
2 per 1000 live births.
Of the 7-13% of neonates who are evaluated for neonatal sepsis, only 3-8% have culture-proven sepsis.
Because early signs of sepsis in the newborn are nonspecific, diagnostic studies are often ordered and treatment initiated in neonates before the presence of sepsis has been proved.
Слайд 16Incidence of early-onset and late-onset invasive group B Streptococcus (GBS) disease.
Слайд 17Age-, sex-, and race-related demographics
Black infants have an increased incidence of
GBS disease and late-onset sepsis.
In all races, the incidence of bacterial sepsis and meningitis, especially with gram-negative enteric bacilli, is higher in males than in females.
Premature infants have an increased incidence of sepsis.
The risk of death or meningitis from sepsis is higher in infants with low birth weight than in full-term neonates.
Слайд 18History
Maternal group B Streptococcus (GBS) status
Premature rupture of membranes (PROM)
Prematurity
Chorioamnionitis
Слайд 19Physical Examination
nonspecific clinical signs of early sepsis are also associated with
other neonatal diseases, such as respiratory distress syndrome (RDS), metabolic disorders, intracranial hemorrhage, and a traumatic delivery.
In view of the nonspecificity of these signs, it is prudent to provide treatment for suspected neonatal sepsis while excluding other disease processes.
Слайд 20Signs and symptoms of neonatal infection (most are NONSPECIFIC):
Apnea and
dusky episodes for no clear reason.
Lethargy, poor color, hypoactivity, poor capillary refill.
Feeding intolerance (more than usual spit-up), abdominal distention.
Clinical appearance; doesn't look "good".
Tachypnea, temperature instability, look of distress.
NO GOLD STANDARD for the diagnosis of neonatal infection
Слайд 21Congenital pneumonia and intrauterine infection
Tachypnea, irregular respirations, moderate retracting, apnea,
cyanosis, and grunting
The chest radiograph may depict bilateral consolidation or pleural effusions.
Klebsiella species and S aureus are especially likely to generate severe lung damage, producing microabscesses and empyema.
Early onset GBS pneumonia has a particularly fulminant course, with significant mortality in the first 48 hours of life.
Postnatally acquired pneumonia may occur at any age
If the infant has remained hospitalized in an NICU environment, especially with endotracheal intubation and mechanical ventilation, the organisms may include Staphylococcus or Pseudomonas species.
, these hospital-acquired organisms frequently demonstrate multiple antibiotic resistances.
Слайд 22Cardiac signs
In overwhelming sepsis, an initial early phase characterized by pulmonary
hypertension, decreased cardiac output, and hypoxemia may occur.
This phase is followed by further progressive decreases in cardiac output with bradycardia and systemic hypotension. The infant manifests overt shock with pallor, poor capillary perfusion, and edema.
Слайд 23Metabolic signs
Hypoglycemia
Hyperglycemia
metabolic acidosis
jaundice
Слайд 24Neurologic signs
Impairment of consciousness (ie, stupor with or without irritability)
Coma
Seizures
Bulging anterior
fontanelle
Extensor rigidity
Focal cerebral signs
Cranial nerve signs
Nuchal rigidity
Temperature instability
decreased tone
Lethargy
poor feeding
Слайд 25Differential Diagnoses
Bowel Obstruction in the Newborn
Congenital Diaphragmatic Hernia
Congenital Pneumonia
Heart Failure, Congestive
Hemolytic
Disease of Newborn
Meconium Aspiration Syndrome
Necrotizing Enterocolitis
Pericarditis, Bacterial
Pulmonary Hypoplasia
Respiratory Distress Syndrome
Слайд 26Laboratory studies used to evaluate for sepsis
complete blood count (CBC)
and differential: thrombocytopenia or neutropenia, a left shift, changes in the ratio of immature to total neutrophils.
blood and cerebrospinal fluid (CSF) cultures
measurement of levels of C-reactive protein (CRP) and other infection markers.
Coagulation studies (DIC - abnormalities in the prothrombin time (PT), the partial thromboplastin time (PTT), and fibrinogen and D-dimer levels)
Слайд 27Hematologic signs
Neutrophil ratios - the immature-to-total (I/T) ratio is the most
sensitive.
-the maximum acceptable ratio for excluding sepsis during the first 24 hours is 0.16.
-An I:T ratio of >0.2 has been considered abnormal
-Disseminated intravascular coagulation (DIC):abnormalities in prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen and D-dimer levels
If infants show signs consistent with impaired coagulation, including gastric blood, bleeding from intravenous or laboratory puncture sites, or other bleeding, evaluating coagulation by checking these values is important.
Слайд 28CSF findings in infective neonatal meningitis
Elevated WBC count (predominantly PMNs)
Elevated
protein level
Decreased glucose concentration
Positive culture results
Слайд 29Approach Considerations
When neonatal sepsis is suspected, treatment should be initiated immediately
because of the neonate’s relative immunosuppression.
Begin antibiotics as soon as diagnostic tests are performed
Monitoring of blood pressure, vital signs, hematocrit, platelets, and coagulation studies is vital.
An infant with temperature instability needs thermoregulatory support with a radiant warmer or incubator.
Слайд 30Antibiotic Therapy
In the United States and Canada, the current approach to
the treatment of early-onset neonatal sepsis includes combined IV aminoglycoside and expanded-spectrum penicillin antibiotic therapy.
This provides coverage for gram-positive organisms, especially group B Streptococcus (GBS), and gram-negative bacteria, such as Escherichia coli.
If an infection appears to be nosocomial (late-onset sepsis), antibiotic coverage should be directed at organisms implicated in hospital-acquired infections, including S aureus, S epidermidis, and Pseudomonas species. Vancomycin and oxacillin has been favored for this coverage
Aminoglycosides and vancomycin both have the potential to produce ototoxicity and nephrotoxicity and should therefore be used with caution.
Слайд 33The need for continued therapy should be based not on the
diagnostic data
Culture results
Maternal and intrapartum risk factors
CSF results
Complete blood cell (CBC) count and differential
C-reactive protein (CRP) trends
Radiographs
Clinical progress
Слайд 34Additional therapies that have been investigated for the treatment of neonatal
sepsis
Granulocyte transfusion
IVIg infusion
Exchange transfusion
Recombinant cytokine administration
Слайд 35Prevention
The Committee on Infectious Diseases of the AAP recommends that obstetric
care include a strategy for managing early-onset GBS disease.
Women with GBS bacteriuria should be treated during pregnancy when the condition is diagnosed and during the intrapartum period.
Слайд 38Imaging studies in the workup of neonatal sepsis
chest radiography to
evaluate pulmonary involvement
computed tomography (CT)
magnetic resonance imaging (MRI)
ultrasonography of the head in cases of meningitis.
Слайд 39Algorithm for secondary prevention of early-onset group B Streptococcal disease among
newborns.
Слайд 40Antibiotics
Ampicillin
Ampicillin is a beta-lactam antibiotic that is bactericidal for susceptible
organisms, such as group B Streptococcus (GBS), Listeria, non–penicillinase-producing Staphylococcus, some strains of Haemophilus influenzae, and meningococci. Some publications recommend ampicillin (in combination with gentamicin) as first-line therapy for suspected sepsis in the newborn.
Слайд 41Antibiotics
Gentamicin
Gentamicin is an aminoglycoside that is bactericidal for susceptible gram-negative organisms,
such as Escherichia coli and Pseudomonas, Proteus, and Serratia species. It is effective in combination with ampicillin for GBS and Enterococcus. Some publications recommend gentamicin (in combination with ampicillin) as first-line therapy for suspected sepsis in the newborn.
Слайд 42Antibiotics
Cefotaxime (Claforan)
Cefotaxime is a third-generation cephalosporin with excellent in vitro activity
against GBS and E coli and other gram-negative enteric bacilli. Good concentrations can be achieved in serum and cerebrospinal fluid (CSF). Concern exists that emergence of drug-resistant gram-negative bacteria may occur more rapidly with cefotaxime coverage than with traditional penicillin and aminoglycoside coverage.
Слайд 43Antibiotics
Vancomycin
Vancomycin is a bactericidal agent that is effective against most aerobic
and anaerobic gram-positive cocci and bacilli. It is especially important in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) and is recommended when coagulase-negative staphylococcal sepsis is suspected. However, therapy with rifampin, gentamicin, or cephalothin may be required in cases of endocarditis or CSF shunt infection with coagulase-negative staphylococci.
Слайд 44Antibiotics
Chloramphenicol
Chloramphenicol has been shown to be effective in the treatment of
highly resistant bacterial meningitis. It inhibits protein synthesis by binding reversibly to 50S ribosomal subunits of susceptible organisms, which, in turn, prevents amino acids from being transferred to growing peptide chains.
Oxacillin
Oxacillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is used in the treatment of infections caused by penicillinase-producing staphylococci. It may be given as initial therapy when a staphylococcal infection is suspected.
Слайд 45Antibiotics
Metronidazole (Flagyl)
Metronidazole is an antimicrobial that has been shown to be
effective against anaerobic infections, especially Bacteroides fragilis meningitis, ventriculitis, and endocarditis. This agent is also useful in the treatment of infections caused by Trichomonas vaginalis.
Piperacillin
Piperacillin is an acylampicillin with excellent activity against Pseudomonas aeruginosa. It is also effective against Klebsiella pneumoniae, Proteus mirabilis, B fragilis, Serratia marcescens, and many strains of Enterobacter. Administer it in combination with an aminoglycoside.
Слайд 46Antibiotics
Erythromycin base (Erythrocin, Ery-Tab, EryPed, E.E.S.)
Erythromycin is a macrolide antimicrobial agent
that is primarily bacteriostatic and is active against most gram-positive bacteria, such as Neisseria species, Mycoplasma pneumoniae, Ureaplasma urealyticum, and Chlamydia trachomatis. It is not well concentrated in the CSF.
Trimethoprim/sulfamethoxazole (Bactrim DS, Septra DS)
Trimethoprim-sulfamethoxazole has been shown to be effective in the treatment of highly resistant bacterial meningitis. Trimethoprim-sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. Trimethoprim-sulfamethoxazole should not be used if hyperbilirubinemia and kernicterus are of concern in the newborn.
Слайд 47Antivirals
Acyclovir (Zovirax)
Acyclovir is used for treatment of mucosal, cutaneous, and
systemic HSV-1 and HSV-2 infections.
Zidovudine (Retrovir)
Zidovudine is a thymidine analogue that inhibits viral replication. It is used to treat patients with HIV infection.
Слайд 48Antifungals
Fluconazole (Diflucan)
Fluconazole is used to treat susceptible fungal infections, including
oropharyngeal, esophageal, and vaginal candidiasis. It is also used for systemic candidal infections and cryptococcal meningitis. Fluconazole has fungistatic activity. It is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.
Amphotericin B (AmBisome)
Amphotericin B is used to treat severe systemic infections and meningitis caused by susceptible fungi, such as Candida and Aspergillus species, Histoplasma capsulatum, and Cryptococcus neoformans. This agent is a polyene produced by a strain of Streptomyces nodosus; it can be fungistatic or fungicidal. Amphotericin B binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak and subsequent fungal cell death.
Liposomal amphotericin B (AmBisome) may be considered for patients with systemic fungal infections resistant to amphotericin B or for patients with renal or hepatic failure. This product consists of amphotericin B within a single-bilayer liposomal drug delivery system.