Neonatology. Lesson 10. Topis:
1. Generalized infections in neonates. Neonatal sepsis.
Background: Neonatal sepsis may be categorized as early or late onset. Eighty-five percent of newborns with early-onset infection present within 24 hours, 5% present at 24-48 hours, and a smaller percentage of patients present between 48 hours and 6 days of life. Onset is most rapid in premature neonates. Early-onset sepsis syndrome is associated with acquisition of microorganisms from the mother. Transplacental infection or an ascending infection from the cervix may be caused by organisms that colonize in the mother’s genitourinary tract. The infant may acquire the microbe by passage through a colonized birth canal at delivery. The microorganisms most commonly associated with early-onset infection include group B Streptococcus (GBS), Escherichia coli, Haemophilus influenzae, and Listeria monocytogenes.
Late-onset sepsis syndrome occurs at 7-90 days of life and is acquired from the caregiving environment. Organisms that have been implicated in causing late-onset sepsis syndrome include coagulase-negative staphylococci, Staphylococcus aureus, E coli, Klebsiella, Pseudomonas, Enterobacter, Candida, GBS, Serratia, Acinetobacter, and anaerobes. The infant’s skin, respiratory tract, conjunctivae, gastrointestinal tract, and umbilicus may become colonized from the environment, leading to the possibility of late-onset sepsis from invasive microorganisms. Vectors for such colonization may include vascular or urinary catheters, other indwelling lines, or contact from caregivers with bacterial colonization.
Pneumonia is more common in early-onset sepsis, whereas meningitis and/or bacteremia are more common in late-onset sepsis. Premature and ill infants have an increased susceptibility to sepsis and subtle nonspecific initial presentations; therefore, they require much vigilance so that sepsis can be identified and treated effectively.
Pathophysiology: The infectious agents associated with neonatal sepsis have changed over the past 50 years. S aureus and E coli were the most common infectious hazards for neonates in the 1950s in the
Meningoencephalitis and neonatal sepsis syndrome can also be caused by infection with adenovirus, enterovirus, or coxsackievirus. Additionally, sexually transmitted diseases and viral diseases, such as gonorrhea, syphilis, herpes simplex virus (HSV), cytomegalovirus (CMV), hepatitis, HIV, rubella, toxoplasmosis, Trichomonas vaginalis, and Candida species, have all been implicated ieonatal infection. Bacterial organisms with increased antibiotic resistance have also emerged and have further complicated the management of neonatal sepsis. The colonization patterns iurseries and personnel are reflected in the organisms currently associated with nosocomial infection. Infants with lower birth weight and infants who are less mature in today’s neonatal intensive care units (NICUs) have increased susceptibility to these organisms.
Staphylococcus epidermidis, or coagulase-negative Staphylococcus is increasingly seen as a cause of nosocomial or late-onset sepsis, especially in the premature infant. It is considered the leading cause of late-onset infections for this population.
The neonate is unable to respond effectively to infectious hazards because of deficits in the physiological response to infectious agents.
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Fig. 7. Spread of Infection Via the Blood to the Entire Body in an Infant.
The fetus has some preimmune immunoglobulin present; however, preimmune immunoglobulin is relatively limited in fetuses compared to adults. The infant receives immunoglobulin G (IgG) prenatally after 16 weeks of gestation; however, the infant born prematurely has less IgG due to the shorter period of placental transmission of immunoglobulin.
Additionally, if the mother is immunosuppressed, it is possible that less IgG can be transmitted to the infant. The neonate is capable of synthesizing immunoglobulin M (IgM) in utero at 10 weeks of gestation; however, IgM levels are generally low at birth, unless the infant was exposed to an infectious agent during the pregnancy, thereby stimulating increased IgM production. IgG and immunoglobulin E (IgE) may be synthesized in utero; however, only traces are found in cord blood at delivery. The neonate may receive immunoglobulin A (IgA) from breastfeeding but does not secrete IgA until 2-5 weeks after birth. Response to bacterial polysaccharide antigen is diminished and remains so during the first 2 years of life.
The physical and chemical barriers to infection in the human body are present in the newborn but are functionally deficient. Skin and mucus membranes are broken down easily in the premature infant. Neonates who are ill and/or premature are additionally at risk because of the invasive procedures that breach their physical barriers to infection. Because of the interdependence of the immune response, these individual deficiencies of the various components of immune activity in the neonate conspire to create a hazardous situation for the neonate exposed to infectious threats.
Scheme of sepsis pathogenesis
pathogen, toxins, ferments
distortion of hemostasis, changes of immunogenesis
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macrophages endothelial thrombocytes complement T, В–lymphocytes coagulation
cells system system
mediators of inflammation: ТNА, interleukins– IL 1,6,8, NO, prostaglandins, thromboxan А2, prostacyclin
increase of penetrate ability, vasodilatation, blood depot, hypovolemia, metabolic disorders
polyorganic insufficiency
septic shock
Mortality/Morbidity: The mortality rate ieonatal sepsis may be as high as 50% for infants who are not treated. Infection is a major cause of fatality during the first month of life, contributing to 13-15% of all neonatal deaths. Neonatal meningitis, a serious morbidity of neonatal sepsis, occurs in 2-4 cases per 10,000 live births and significantly contributes to the mortality rate ieonatal sepsis; it is responsible for 4% of all neonatal deaths.
Age: Studies have shown that premature infants have an increased incidence of sepsis. The incidence of sepsis is significantly higher in infants with very low birth weight (<
Classification of sepsis
1. Time of beginning:
· antenatal
· postnatal
o early
o late
· nosocomeal
2. Etiology: streptococcal, staphylococcal, Klebsiella’s, Escherichia’s, Candida’s, mixed etiology.
3. Clinical forms: septicemia, septicopyemia.
4. Entrance region: umbilical, pulmonary, bowel, otogenic, cryptogenic.
5. Duration:
o fulminant – few hours–1-3 days
o acute – 4-8 weeks
o prolonged – more than 8 weeks
6. Periods: initial, significant clinical signs, recovery, period of rehabilitation.
7. Complications: DIC–syndrome, thrombosis, hypotrophy, endomyocarditis, renal failure etc.
Diagnosis example: postnatal umbilical, staphylococcal sepsis, septicopyemia: (omphalitis, bilateral pneumonia with cardiovascular syndrome, respiratory failure ІІ grade, right shoulder proximal epiphysial osteomyelitis), acute duration, DIC-syndrome.
The risk factors that are associated most highly with neonatal sepsis include:
1. maternal GBS colonization (especially if untreated during labor),
2. premature rupture of membranes (PROM),
3. preterm rupture of membranes,
4. prolonged rupture of membranes,
5. prematurity,
6. and chorioamnionitis.
Predisposing risk factors also are associated with neonatal sepsis. They include:
1. maternal urinary tract infection, maternal fever greater than
2. poor maternal nutrition, low socioeconomic status,
3. poor prenatal care,
4. maternal substance abuse,
5. recurrent abortion,
6. difficult delivery,
7. low Apgar score (<6 at 1 or 5 min), birth asphyxia,
8. meconium staining,
9. low birth weight, and congenital anomalies.
An awareness of the myriad of risk factors associated with neonatal sepsis prepares the clinician for early identification and effective treatment, thereby reducing mortality and morbidity.
Physical: The clinical signs of neonatal sepsis are nonspecific and are associated with characteristics of the causative organism and the body’s response to the invasion.
· Congenital pneumonia and intrauterine infection: Inflammatory lesions are observed postmortem in the lungs of infants with congenital and intrauterine pneumonia. This may not be caused by the action of the microorganisms themselves but may be caused by aspiration of amniotic fluid containing maternal leukocytes and cellular debris. Tachypnea, irregular respirations, moderate retracting, apnea, cyanosis, and grunting may be observed. Neonates with intrauterine pneumonia may also be critically ill at birth and require high levels of ventilatory support. The chest radiograph may depict bilateral consolidation or pleural effusions.
· Congenital pneumonia and intrapartum infection: Neonates who are infected during the birth process may acquire pneumonia through aspiration of the microorganisms during the delivery process. The colonization may lead to infection with pulmonary changes, infiltration, and destruction of bronchopulmonary tissue. This damage is partly due to the granulocytes’ release of prostaglandins and leukotrienes. Fibrinous exudation into the alveoli leads to inhibition of pulmonary surfactant function and respiratory failure with an RDS-like presentation. Vascular congestion, hemorrhage, and necrosis may occur.
o Klebsiella species and S aureus are especially capable of considerably damaging the lungs, producing microabscesses and empyema.
o Infectious pneumonia is also characterized by pneumatoceles within the pulmonary tissue. Coughing, grunting, costal and sternal retractions, nasal flaring, tachypnea and/or irregular respiration, rales, decreased breath sounds, and cyanosis may be observed.
o On radiography, segmental or lobar atelectasis or a diffuse reticulogranular pattern may exist, much like what is observed in RDS.
o Pleural effusions may be observed in advanced disease.
· Congenital pneumonia and postnatal infection: Postnatally acquired pneumonia may occur at any age. Because these infectious agents exist in the environment, the likely cause depends heavily on the infant’s recent environment. 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. Additionally, these hospital-acquired organisms frequently demonstrate multiple antibiotic resistances. Therefore, the choice of antibiotic agents in such cases requires knowledge of the likely causative organisms and the antibiotic-resistance patterns of the hospital.
· Cardiac signs: In overwhelming sepsis, an initial early phase characterized by pulmonary hypertension, decreased cardiac output, and hypoxemia is postulated to occur. These cardiopulmonary disturbances may be due to the activity of granulocyte biochemical mediators, such as hydroxyl radicals and thromboxane B2, an arachidonic acid metabolite. These biochemical agents have vasoconstrictive actions that result in pulmonary hypertension when released in pulmonary tissue. A toxin derived from the polysaccharide capsule of type III Streptococcus has also been shown to cause pulmonary hypertension. The early phase of pulmonary hypertension 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. These late signs of shock are indicative of severe compromise and are highly associated with mortality.
· Metabolic signs: Hypoglycemia, metabolic acidosis, and jaundice all are metabolic signs that commonly accompany neonatal sepsis syndrome. The infant has an increased glucose requirement because of sepsis. The infant may also have impaired nutrition from a diminished energy intake. Metabolic acidosis is due to a conversion to anaerobic metabolism with the production of lactic acid. When infants are hypothermic or they are not kept in a neutral thermal environment, efforts to regulate body temperature can cause metabolic acidosis. Jaundice occurs in response to decreased hepatic glucuronidation caused by both hepatic dysfunction and increased erythrocyte destruction.
· Neurologic signs: Meningitis is the common manifestation of infection of the central nervous system. It is primarily associated with GBS (36%), E coli (31%), and Listeria species (5-10%) infections, although other organisms such as S pneumoniae, S aureus, Staphylococcus epidermis, Haemophilus influenzae, and species of Pseudomonas, Klebsiella, Serratia, Enterobacter, and Proteus may cause meningitis. Acute and chronic histologic features are associated with specific organisms.
o Ventriculitis is the initiating event with inflammation of the ventricular surface. Exudative material usually appears at the choroid plexus and is external to the plexus. Then, ependymitis occurs with disruption of the ventricular lining and projections of glial tufts into the ventricular lumen. Glial bridges may develop by these tufts and cause obstruction, particularly at the aqueduct of Sylvius. The lateral ventricles may become multiloculated, which is similar to forming abscesses. Multiloculated ventricles can isolate organisms in an area, making treatment more difficult. Meningitis is likely to arise at the choroid plexus and extend via the ventricles through aqueducts into the arachnoid to affect the cerebral and cerebellar surfaces. The high glycogen content in the neonatal choroid plexus provides an excellent medium for the bacteria. Ventricular origination of meningitis causes significant treatment problems because the areas are inaccessible. Ventricular obstruction causes an additional problem.
o Arachnoiditis is the next phase and is the hallmark of meningitis. The arachnoid is infiltrated with inflammatory cells producing an exudate that is thick over the base of the brain and more uniform over the rest of the brain. Early in the infection, the exudate is primarily PMNs, bacteria, and macrophages. Exudate is prominent around the blood vessels and extends into the brain parenchyma. In the second and third weeks of infection, the proportion of PMNs decreases; the dominant cells are histiocytes, macrophages, and some lymphocytes and plasma cells. Exudate infiltration of cranial roots 3-8 occurs. After this period, the exudate decreases. Thick strands of collagen form, and arachnoid fibrosis occurs, which is responsible for obstruction. Hydrocephalus results. Early-onset GBS meningitis is characterized by much less arachnoiditis than late-onset GBS meningitis.
o Vasculitis extends the inflammation of the arachnoid and ventricles to the blood vessels surrounding the brain. Occlusion of the arteries rarely occurs; however, venous involvement is more severe. Phlebitis may be accompanied with thrombosis and complete occlusion. Multiple fibrin thrombi are especially associated with hemorrhagic infarction. This vascular involvement is apparent within the first days of meningitis and becomes more prominent during the second and third weeks.
o Cerebral edema may occur during the acute state of meningitis. The edema may be severe enough to greatly diminish the ventricular lumen. The cause is unknown, but it is likely related to vasculitis and the increased permeability of blood vessels. It may also be related to the cytotoxins of microorganisms. Herniation of edematous supratentorial structures does not occur ieonates because of the cranium’s distensibility.
o Infarction is a prominent and serious feature of neonatal meningitis. It occurs in 30% of infants who die. Lesions occur because of multiple venous occlusions, which are frequently hemorrhagic. The loci of infarcts are most often in the cerebral cortex and underlying white matter but may also be subependymal within the deep white matter. Neuronal loss occurs, especially in the cerebral cortex, and periventricular leukomalacia may subsequently appear in areas of neuronal cell death.
o Meningitis due to early-onset neonatal sepsis usually occurs within 24-48 hours and is dominated by nonneural signs. Neurologic signs may include stupor and irritability. Overt signs of meningitis occur in only 30% of cases. Even culture-proven meningitis may not demonstrate white cell changes in the CSF. Meningitis due to late-onset disease is more likely to demonstrate neurologic signs (80-90%). Impairment of consciousness (ie, stupor with or without irritability), coma, seizures, bulging anterior fontanel, extensor rigidity, focal cerebral signs, cranial nerve signs, and nuchal rigidity occur.
o The CSF findings in infectious neonatal meningitis are an elevated WBC count (predominately PMNs), an elevated protein level, a decreased CSF glucose concentration, and positive cultures. The decrease in CSF glucose concentration does not necessarily reflect serum hypoglycemia. Glucose concentration abnormalities are more severe in late-onset disease and with gram-negative organisms. The CSF WBC count is within the reference range in 29% of GBS meningitis infections; in gram-negative meningitis, it is within the reference range in only 4%. Reference range CSF protein and glucose concentrations are found in about 50% of patients with GBS meningitis; however, in gram-negative infections, reference range CSF protein and glucose concentrations are found in only 15-20%.
o Temperature instability is observed with neonatal sepsis and meningitis, either in response to pyrogens secreted by the bacterial organisms or from sympathetic nervous system instability. The neonate is most likely to be hypothermic. The infant is also floppy, lethargic, and disinterested in feeding. Signs of neurologic hyperactivity are more likely when late-onset meningitis occurs.
· Hematologic signs
o The platelet count in the healthy newborn is rarely less than 100,000 per mm3 in the first 10 days of life. Thrombocytopenia with counts less than 100,000 may occur ieonatal sepsis in response to the cellular products of the microorganisms. These cellular products cause platelet clumping and adherence leading to platelet destruction. Thrombocytopenia is generally observed after sepsis has been diagnosed and usually lasts 1 week, though it can last as long as 3 weeks. Only 10-60% of infants with sepsis have thrombocytopenia. Because of the appearance of newly formed platelets, mean platelet volume (MPV) and platelet distribution width (PDW) are shown to be significantly higher ieonatal sepsis after 3 days. Because of the myriad of causes of thrombocytopenia and its late appearance ieonatal sepsis, the presence of thrombocytopenia does not aid the diagnosis of neonatal sepsis.
o WBC counts and ratios are more sensitive for determining sepsis than platelet counts, although normal WBC counts may be observed in as many as 50% of cases of culture-proven sepsis. Infants who are not infected may also demonstrate abnormal WBC counts related to the stress of delivery. A differential may be of more use in diagnosing sepsis. Total neutrophil count (PMNs and immature forms) is slightly more sensitive in determining sepsis than total leukocyte count (percent lymphocyte + monocyte/PMNs + bands). Abnormal neutrophil counts, taken at the time of symptom onset, are only observed in two thirds of infants; therefore, the neutrophil count does not provide adequate confirmation of sepsis. Neutropenia is observed with maternal hypertension, severe perinatal asphyxia, and periventricular or intraventricular hemorrhage.
o Neutrophil ratios have been more useful in diagnosing or excluding neonatal sepsis; the immature-to-total (I/T) ratio is the most sensitive. All immature neutrophil forms are counted, and the maximum acceptable ratio for excluding sepsis during the first 24 hours is 0.16. In most newborns, the ratio falls to 0.12 within 60 hours of life. The sensitivity of the I/T ratio has ranged from 60-90%, and elevations may be observed with other physiological events; therefore, when diagnosing sepsis, the elevated I/T ratio should be used in combination with other signs.
· Gastrointestinal signs: The gut can be colonized by organisms in utero or at delivery by swallowing infected amniotic fluid. The immunologic defenses of the gut are not mature, especially in the preterm infant. Lymphocytes proliferate in the gut in response to mitogen stimulation; however, this proliferation is not fully effective in responding to a microorganism because antibody formation and cytokine formation is immature until approximately 46 weeks. Necrotizing enterocolitis (NEC) has been associated with the presence of a number of species of bacteria in the immature gut, and bacterial overgrowth of these organisms in the neonatal lumen is a component of the multifactorial pathophysiology of NEC.
Lab Studies:
Blood, CSF, and urine cultures
· Aerobic cultures are appropriate for most of the bacterial etiologies associated with neonatal sepsis; however, anaerobic cultures are indicated ieonates with abscess formation, processes with bowel involvement, massive hemolysis, and refractory pneumonia.
· A Gram stain provides early identification of the gram-negative or gram-positive status of the organism for preliminary identification.
· Bacterial cultures should generally reveal the organism of infection within 36-48 hours; the subsequent initial identification of the organism occurs within 12-24 hours of the growth.
· Urine cultures are most appropriate when investigating late-onset sepsis.
· Blood and CSF cultures are appropriate for early and late-onset sepsis.
· Because of the low incidence of meningitis in the newborn infant with negative cultures, clinicians may elect to culture the CSF of only those infants with documented or presumed sepsis.
A CBC and differential may be ordered serially to determine changes associated with the infection, such as thrombocytopenia or neutropenia, or to monitor the development of a left shift or an elevated I/T ratio. Such serial monitoring of the CBC may be useful in aiding the differentiation of sepsis syndrome from nonspecific abnormalities due to the stress of delivery.
· The platelet count in the healthy newborn is rarely less than 100,000 per mm3 in the first 10 days of life. Thrombocytopenia with counts less than 100,000 may occur ieonatal sepsis, although this sign is usually observed late in the infection. MPV and PDW have been shown to be significantly elevated in infants with sepsis after 2-3 days of life. These measures may assist in determining the etiology of thrombocytopenia.
· WBC counts and ratios are more sensitive in determining sepsis, although normal WBC counts may be observed in culture-proven sepsis in as many as 50% of cases. Infants who are not infected may also have abnormal WBC counts related to the stress of delivery. A differential may be of more use in diagnosing sepsis. Total neutrophil count (PMNs and immature forms) is slightly more sensitive in determining sepsis than total leukocyte count (percent lymphocyte + monocyte/PMNs + bands). Abnormal neutrophil counts at the time of symptom onset are only observed in two thirds of infants; therefore, neutrophil count does not provide adequate confirmation of sepsis. Neutropenia is also observed with maternal hypertension, severe perinatal asphyxia, and periventricular or intraventricular hemorrhage.
· Neutrophil ratios have been more useful in diagnosing neonatal sepsis; the I/T ratio is the most sensitive. All immature neutrophil forms are counted, and the maximum acceptable ratio for excluding sepsis in the first 24 hours is 0.16. In most newborns, the ratio falls to 0.12 within 60 hours of life. The sensitivity of the I/T ratio has ranged from 60-90%, and elevations may be observed with other physiological events; therefore, when diagnosing sepsis, the elevated I/T ratio should be used in combination with other signs.
The CSF findings in infectious neonatal meningitis are an elevated WBC (predominately PMNs), an elevated protein level, a depressed glucose level, and positive cultures. The decrease in glucose is not reflective of serum hypoglycemia. The CSF abnormalities are more severe in late onset and with gram-negative organisms. The WBC is within the reference range in 29% of GBS meningitis infections; in gram-negative meningitis, it is within the reference range in only 4%. Reference range protein and glucose concentrations are found in about 50% of patients with GBS meningitis; however, in gram-negative infections, reference range protein and glucose concentration are found in only 15-20%.
C-reactive protein, an acute phase protein associated with tissue injury, is eventually elevated in 50-90% of infants with systemic bacterial infections. This is especially true of infections with abscesses or cellulitis of deep tissue. C-reactive protein usually rises within 24 hours of infection, peaks within 2-3 days, and remains elevated until the inflammation is resolved. The C-reactive protein level is not recommended as a sole indicator of neonatal sepsis, but it may be used as part of a sepsis workup or as a serial study during infection to determine response to antibiotics, duration of therapy, and/or relapse of infection.
IgM concentration in serum may be helpful in determining the presence of an intrauterine infection, especially if present over a period of time.
Imaging Studies:
· Chest radiographs may depict segmental or lobar atelectasis, but they more commonly reveal a diffuse, fine, reticulogranular pattern, much like what is observed in RDS. Hemothorax and pleural effusions may also be observed.
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scan may be needed late in the course of complex neonatal meningitis to document any occurrence of blocks to CSF flow, the site where the blocks are occurring, and occurrence of major infarctions or abscesses. Signs of chronic stage disease, such as ventricular dilation, multicystic encephalomalacia, and atrophy, are also demonstrated on CT scan.
· Head ultrasonograms in neonates with meningitis show evidence of ventriculitis, abnormal parenchymal echogenicities, extracellular fluid, and chronic changes. Serially, head ultrasonograms can demonstrate the progression of complications.
Procedures: Lumbar puncture is warranted for early- and late-onset sepsis, although clinicians may be unsuccessful in obtaining sufficient or clear fluid for all the studies. Infants may be positioned on their side or sitting with support, but adequate restraint is needed to avoid a traumatic tap. Because the cord is lower in the spinal column in infants, the insertion site should be between L3 and L4. If positive cultures are demonstrated, a follow-up lumbar puncture is often performed within 24-36 hours after antibiotic therapy to document CSF sterility. If organisms are still present, modification of drug type or dosage may be required to adequately treat the meningitis. An additional lumbar puncture within 24-36 hours is necessary if organisms are still present.
Complications
1. Septic shock is sepsis with uncorrected hypotension, hypoperfusion of tissues, acidosis, oliguria, conscious changes.
o Early septic shock is sepsis with hypotension, hypoperfusion of capillaries; which may be corrected in the short period of time by fluids or/and medicine.
o Refractive septic shock is sepsis with hypotension, hypoperfusion of capillaries; which is not corrected by fluids or/and medicine more than 1 hour; need dopamine, adrenalin or noradrenalin correction.
Septic shock’s stages: І – decreasing of blood circulation; ІІ – early decompensation; ІІІ – late decompensation; IV – irreversible (agonizing).
2. DIC–syndrome, stages: І – hypercoagulation; ІІ – hypocoagulation; ІІІ – consume coagulopathy; IV – restoring.
DIFFERENTIALS These nonspecific clinical signs of early sepsis syndrome are also associated with other neonatal diseases, such as Respiratory Distress Syndrome (RDS), metabolic disorders, intracranial hemorrhage, and a traumatic delivery. Therefore, diagnose neonatal sepsis by excluding other disease processes, performing an examination, and testing for more specific indications of neonatal sepsis.
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Criteria
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Meningitis
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Localized forms of infection
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Congenital infections
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Birth trauma |
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1. Anamnesis:
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Acute and chronic maternal diseases during the pregnancy
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+
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+ |
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Mastitis during breastfeeding period
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+
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Umbilical late epithelization |
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+
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Purulent changes of the skin
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+
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+
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Rapid delivery
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+ |
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Complicated delivery of shoulders
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+
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Using of forceps, vacuum extraction |
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+ |
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2.Prolonged intoxication:
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+
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+ |
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-increased body temperature
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+
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–loss of appetite
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+
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+
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+ |
+
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–vomiting,
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+
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–
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+ |
+
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–skin color:
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–pale-pink
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+
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–pallor
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+ |
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+
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–pale-grey
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–yellow |
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+ |
+ |
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–weight gain: –slow
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+ |
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+
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–absent
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+ – |
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+ |
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– jaundice:
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+
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+ |
+
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–conjugated
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+ |
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–parenchimatous |
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З.Presence of hematogenous methastatic sites of infection
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+
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–hepatosplenomegaly
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+
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4.Positive cultures
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–blood
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+
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–from sites of infection |
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+
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5. CSF: |
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– transparent
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+
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–muddy – hemorrhagic – pleocytosis – proteinorrhachia 6. Disappearance of the clinical signs during treatment: – slow – rapid – absent |
+ –– ++ +
+ –– –– –– |
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+ –– + +
+ –– + + |
–– + –– ––
+ –– –– –– |
TREATMENT Medical Care: Initiate treatment immediately because of the neonate’s immunologic weaknesses for fighting infection. Begin antibiotics as soon as diagnostic tests are performed. Additional therapies have been investigated for the treatment of neonatal sepsis; however, no unequivocal proof that these treatments are beneficial exists. These additional therapies include granulocyte transfusion, intravenous immune globulin (IVIG) replacement, exchange transfusion, and the use of recombinant cytokines.
Antibiotic therapy In the
· If infection appears to be nosocomial, direct coverage at organisms implicated in hospital-acquired infections, including S aureus, S epidermis, and Pseudomonas species. Most strains of S aureus produce beta-lactamase, which makes them resistant to penicillin G, ampicillin, carbenicillin, and ticarcillin. Vancomycin has been favored for this coverage; however, concern exists that overuse of this drug may lead to vancomycin-resistant organisms, thereby eliminating the best response to these resistant organisms. Cephalosporins are attractive in the treatment of nosocomial infection because of their lack of dose-related toxicity and adequate serum and CSF concentration; however, resistance by gram-negative organisms has occurred with their use. Do not use ceftriaxone in infants with hyperbilirubinemia because it displaces bilirubin from serum albumen. Resistance and sensitivities for the organism are used to indicate the most effective drug.
· Aminoglycosides and vancomycin are both ototoxic and nephrotoxic; have caution when using them. Check the serum level after 48 hours of treatment to determine if levels are above those required for a therapeutic effect. The dosage amount or interval may need to be changed to ensure adequate but nontoxic coverage. A serum level may be warranted when the infant’s clinical condition has not improved to ensure that a therapeutic level has been reached. In addition, perform renal function and hearing screening to determine any short- or long-range toxic effects of these drugs.
· If cultures are negative but the infant has significant risk for sepsis and/or clinical signs, the clinician must decide whether to provide continued treatment. Three days of negative cultures should provide confidence in the data; however, a small number of infants with proven sepsis at postmortem had negative cultures during their initial sepsis workup. Management is further complicated if the mother received antibiotic therapy before delivery, especially close to delivery. This may result iegative cultures in the infant who is still ill. Review all diagnostic data, including cultures, maternal and intrapartal risk factors, CSF results, the CBC and differential radiographs, and the clinical picture to determine the need for continued therapy. Treatment for 7-10 days may be appropriate, even if the infant has negative cultures at 48 hours.
· The clinician may require different antibiotic choice, dosage, and/or treatment time if the infant has bacterial meningitis. Perform a follow-up lumbar puncture within 24-36 hours after antibiotic therapy has been initiated to determine if the CSF is sterile. If organisms are still present, modification of drug type or dosage is required to adequately treat the meningitis. Continue antibiotic treatment for 2 weeks after sterilization of the CSF or for a minimum of 2 weeks for gram-positive meningitis and 3 weeks for gram-negative meningitis, whichever period is longest. Chloramphenicol or trimethoprim-sulfamethoxazole has been shown to be effective in the treatment of highly resistant bacterial meningitis.
Granulocyte transfusion has been shown to be suitable for infants with significant depletion of the storage neutrophil pool; however, the documentation of storage pool depletion requires a bone marrow aspiration, and the granulocyte transfusion must be administered quickly to be beneficial. The number of potential adverse effects, such as graft versus host reaction, transmission of CMV or hepatitis B, and pulmonary leukocyte sequestration, is considerable. Therefore, this therapy remains an experimental treatment.
Intravenous immune globuline has been considered for neonatal sepsis to provide type-specific antibodies to improve opsonization and phagocytosis of bacterial organisms and to improve complement activation and chemotaxis of neonatal neutrophils; however, difficulties with IVIG therapy for neonatal sepsis exist. The effect has been transient, and adverse effects associated with the infusion of any blood product can occur. Dose-related problems with this therapy decrease its usefulness ieonatal populations.
Recombinant human cytokine administration to stimulate granulocyte progenitor cells has been studied as an adjunct to antibiotic therapy. These therapies have shown promise in animal models, especially for GBS sepsis, but require pretreatment or immediate treatment to demonstrate efficacy. The use of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) has been studied in clinical trials, but their use in clinical neonatology remains experimental.
The infant with sepsis may require treatment aimed at the overwhelming systemic effects of the disease. Cardiopulmonary support and intravenous nutrition may be required during the acute phase of the illness until the infant’s condition stabilizes. Monitoring of blood pressure, vital signs, hematocrit, and platelets is vital.
Surgical Care: If hydrocephalus associated with neonatal meningitis occurs, and progressive accumulation of CSF is present, placing a ventriculoperitoneal (VP) shunt may be necessary to drain off the excess fluid. The immediate complications of shunt placement are overdrainage, equipment failure, disconnection, migration of catheter, or shunt infection. Abdominal obstruction, omental cysts, and perforation of the bladder, gall bladder, or bowel occur infrequently. The VP shunt may cause long-term neurologic complications, including slit-ventricle syndrome, seizures, neuro-ophthalmological problems, and craniosynostosis; however, the outcome for children with VP shunt placement is generally good with careful follow-up.
Diet: The neonate may need to be given nothing by mouth (NPO) during the first days of treatment because of gastrointestinal symptoms or poor feeding. Consider parenteral nutrition to ensure that the patient’s intake of calories, protein, minerals, and electrolytes is adequate during this period. Feeding may be restarted via a nasogastric tube for the infant with serious compromise. Encourage that breast milk be given because of the immunologic protection it provides.
Activity: The infant with temperature instability needs thermoregulatory support with a radiant warmer or incubator. Also, encouraging parental contact is important to ease the stress for parents and continue the bonding between the parents and child.
|
Drug Name |
Ampicillin (Marcillin, Omnipen, Polycillin, Principen, Totacillin) |
|
Pediatric Dose |
<7 days and <2000 g: 50 mg/kg/dose IV/IM q12h |
|
Drug Name |
Gentamicin (Garamycin) |
|
Pediatric Dose |
0-4 weeks and <1200 g: 2.5 mg/kg/dose IV/IM q18h |
|
Drug Name |
Cefotaxime (Claforan) |
|
Pediatric Dose |
<7 days: 50 mg/kg/dose IV/IM q12h |
|
Drug Name |
Vancomycin (Lyphocin, Vancocin, Vancoled) — |
|
Pediatric Dose |
<1 month: |
|
Drug Name |
Metronidazole (Flagyl) — Antimicrobial that has shown effectiveness against anaerobic infections, especially Bacteroides fragilis meningitis. |
|
Pediatric Dose |
<4 weeks and <1200 g: 7.5 mg/kg/dose PO/IV q2d |
|
Drug Name |
Erythromycin (E-Mycin, Erythrocin) –. |
|
Pediatric Dose |
<7 days and <2000 g: 5 mg/kg/dose PO/IV/IM q12h |
|
Drug Name |
Piperacillin (Pipracil) |
|
Pediatric Dose |
<7 days and 1200-2000 g: 75 mg/kg IV/IM q12h |
Drug Category: Antifungals — Fungal infections can masquerade as bacterial infections and/or may appear at the end of prolonged antibacterial therapy.
|
Drug Name |
Fluconazole (Diflucan) — Used to treat susceptible fungal infections, including oropharyngeal, esophageal, and vaginal candidiasis. Also used for systemic candidal infections and cryptococcal meningitis. |
|
Pediatric Dose |
0-14 days: Oropharyngeal candidiasis: 6 mg/kg PO/IV initial dose; after 3 d, 3 mg/kg q3d for a total of 14 d |
|
Drug Name |
Amphotericin B (Amphocin, Fungizone) |
|
Pediatric Dose |
Test dose: 0.1 mg/kg/dose IV; not to exceed 1 mg/dose infused over 20-60 min or 0.25 mg/kg infused over 6 h; if tolerated, administer 0.25 mg/kg/d; gradually increase dose by 0.25-mg/kg/d increments until desired daily dose reached |
Deterrence/Prevention: The Committee on Infectious Diseases of the AAP recommends that obstetric care include a strategy to manage early-onset GBS disease. Treat women with GBS bacteriuria during pregnancy when it is diagnosed and at delivery. The committee also recommends that women who have previously given birth to an infant with GBS disease be intrapartally treated. Practitioners should use either a strategy based on screening the mother or a strategy based on the presence of intrapartum risk factors to minimize the risk of early-onset GBS disease.
Prognosis: With early diagnosis and treatment, infants are not likely to experience long-term health problems associated with neonatal sepsis; however, if early signs and/or risk factors are missed, the mortality rate increases. Residual neurologic damage occurs in 15-30% of neonates with septic meningitis. Infants with meningitis may acquire hydrocephalus and/or periventricular leucomalacia. They may also have complications associated with the use of aminoglycosides, such as hearing loss and/or nephrotoxicity.
Management of Neonates With Suspected or Proven Early-Onset Bacterial Sepsis
1. Richard A. Polin, MD and
2. the COMMITTEE ON FETUS AND NEWBORN
Abstract
With improved obstetrical management and evidence-based use of intrapartum antimicrobial therapy, early-onset neonatal sepsis is becoming less frequent. However, early-onset sepsis remains one of the most common causes of neonatal morbidity and mortality in the preterm population. The identification of neonates at risk for early-onset sepsis is frequently based on a constellation of perinatal risk factors that are neither sensitive nor specific. Furthermore, diagnostic tests for neonatal sepsis have a poor positive predictive accuracy. As a result, clinicians often treat well-appearing infants for extended periods of time, even when bacterial cultures are negative. The optimal treatment of infants with suspected early-onset sepsis is broad-spectrum antimicrobial agents (ampicillin and an aminoglycoside). Once a pathogen is identified, antimicrobial therapy should be narrowed (unless synergism is needed). Recent data suggest an association between prolonged empirical treatment of preterm infants (≥5 days) with broad-spectrum antibiotics and higher risks of late onset sepsis, necrotizing enterocolitis, and mortality. To reduce these risks, antimicrobial therapy should be discontinued at 48 hours in clinical situations in which the probability of sepsis is low. The purpose of this clinical report is to provide a practical and, when possible, evidence-based approach to the management of infants with suspected or proven early-onset sepsis.
Key Words:
· Abbreviations: CFU — colony-forming units CRP — C-reactive protein CSF —cerebrospinal fluid GBS — group B streptococci I/T — immature to total neutrophil (ratio) PMN — polymorphonuclear leukocyte PPROM — preterm premature rupture of membranes
Introduction
“Suspected sepsis” is one of the most common diagnoses made in the NICU.1 However, the signs of sepsis are nonspecific, and inflammatory syndromes of noninfectious origin mimic those of neonatal sepsis. Most infants with suspected sepsis recover with supportive care (with or without initiation of antimicrobial therapy). The challenges for clinicians are threefold: (1) identifying neonates with a high likelihood of sepsis promptly and initiating antimicrobial therapy; (2) distinguishing “high-risk” healthy-appearing infants or infants with clinical signs who do not require treatment; and (3) discontinuing antimicrobial therapy once sepsis is deemed unlikely. The purpose of this clinical report is to provide a practical and, when possible, evidence-based approach to the diagnosis and management of early-onset sepsis, defined by the National Institute of Child Health and Human Development and Vermont Oxford Networks as sepsis with onset at ≤3 days of age.
Pathogenesis and Epidemiology of Early-Onset Sepsis
Before birth, the fetus optimally is maintained in a sterile environment. Organisms causing early-onset sepsis ascend from the birth canal either when the amniotic membranes rupture or leak before or during the course of labor, resulting in intra-amniotic infection.2 Commonly referred to as “chorioamnionitis,” intra-amniotic infection indicates infection of the amniotic fluid, membranes, placenta, and/or decidua. Group B streptococci (GBS) can also enter the amniotic fluid through occult tears. Chorioamnionitis is a major risk factor for neonatal sepsis. Sepsis can begin in utero when the fetus inhales or swallows infected amniotic fluid. The neonate can also develop sepsis in the hours or days after birth when colonized skin or mucosal surfaces are compromised. The essential criterion for the clinical diagnosis of chorioamnionitis is maternal fever. Other criteria are relatively insensitive. When defining intra-amniotic infection (chorioamnionitis) for clinical research studies, the diagnosis is typically based on the presence of maternal fever of greater than
At term gestation, less than 1% of women with intact membranes will have organisms cultured from amniotic fluid.6 The rate can be higher if the integrity of the amniotic cavity is compromised by procedures before birth (eg, placement of a cerclage or amniocentesis).6 In women with preterm labor and intact membranes, the rate of microbial invasion of the amniotic cavity is 32%, and if there is preterm premature rupture of membranes (PPROM), the rate may be as high as 75%.7 Many of the pathogens recovered from amniotic fluid in women with preterm labor or PPROM (eg, Ureaplasma species or Mycoplasma species) do not cause early-onset sepsis.8–10 However, both Ureaplasma and Mycoplasma organisms can be recovered from the bloodstream of infants whose birth weight is less than
The major risk factors for early-onset neonatal sepsis are preterm birth, maternal colonization with GBS, rupture of membranes >18 hours, and maternal signs or symptoms of intra-amniotic infection.14–16 Other variables include ethnicity (ie, black women are at higher risk of being colonized with GBS), low socioeconomic status, male sex, and low Apgar scores. Preterm birth/low birth weight is the risk factor most closely associated with early-onset sepsis.17 Infant birth weight is inversely related to risk of early-onset sepsis. The increased risk of early-onset sepsis in preterm infants is also related to complications of labor and delivery and immaturity of innate and adaptive immunity.18
Diagnostic Testing for Sepsis
The clinical diagnosis of sepsis in the neonate is difficult, because many of the signs of sepsis are nonspecific and are observed with other noninfectious conditions. Although a normal physical examination is evidence that sepsis is not present,19,20 bacteremia can occur in the absence of clinical signs.21 Available diagnostic testing is not helpful in deciding which neonate requires empirical antimicrobial therapy but can assist with the decision to discontinue treatment.22
Blood Culture
A single blood culture in a sufficient volume is required for all neonates with suspected sepsis. Data suggest that 1.0 mL of blood should be the minimum volume drawn for culture when a single pediatric blood culture bottle is used. Dividing the specimen in half and inoculating aerobic and anaerobic bottles is likely to decrease the sensitivity. Although 0.5 mL of blood has previously been considered acceptable, in vitro data from Schelonka et al demonstrated that 0.5 mL would not reliably detect low-level bacteremia (4 colony-forming units [CFU]/mL or less).23 Furthermore, up to 25% of infants with sepsis have low colony count bacteremia (≤4 CFU/mL), and two-thirds of infants younger than 2 months of age have colony counts <10 CFU/mL.24,25 Neal et al demonstrated that more than half of blood specimens inoculated into the aerobic bottle were less than 0.5 mL.26 A study by Connell et al indicated that blood cultures with an adequate volume were twice as likely to yield a positive result.27 A blood culture obtained through an umbilical artery catheter shortly after placement for other clinical indications is an acceptable alternative to a culture drawn from a peripheral vein.28 The risk of recovering a contaminant is greater with a blood culture drawn from an umbilical vein.29 There are, however, data to suggest that a blood culture drawn from the umbilical vein at the time of delivery using a doubly clamped and adequately prepared segment of the cord is a reliable alternative to a culture obtained peripherally.30
Urine Culture
A urine culture should not be part of the sepsis workup in an infant with suspected early-onset sepsis.31 Unlike urinary tract infections in older infants (which are usually ascending infections), urinary tract infections in newborn infants are attributable to seeding of the kidney during an episode of bacteremia.
Gastric Aspirates
The fetus swallows 500 to 1000 mL of amniotic fluid each day. Therefore, if there are white blood cells present in amniotic fluid, they will be present in gastric aspirate specimens at birth. However, these cells represent the maternal response to inflammation and have a poor correlation with neonatal sepsis.32 Gram stains of gastric aspirates to identify bacteria are of limited value and are not routinely recommended.33
Body Surface Cultures
Bacterial cultures of the axilla, groin, and the external ear canal have a poor positive predictive accuracy. They are expensive and add little to the evaluation of an infant with possible bacterial sepsis.34,35
Tracheal Aspirates
Cultures and Gram stains of tracheal aspirate specimens may be of value if obtained immediately after endotracheal tube placement.36 Once an infant has been intubated for several days, tracheal aspirates are of no value in the evaluation of sepsis.37
Lumbar Puncture
The decision to perform a lumbar puncture in a neonate with suspected early-onset sepsis remains controversial. In the high-risk, healthy-appearing infant, data suggest that the likelihood of meningitis is extremely low.38 In the infant with clinical signs that are thought to be attributable to a noninfectious condition, such as respiratory distress syndrome, the likelihood of meningitis is also low.39 However, in bacteremic infants, the incidence of meningitis may be as high as 23%.40,41 Blood culture alone cannot be used to decide who needs a lumbar puncture, because blood cultures can be negative in up to 38% of infants with meningitis.42,43 The lumbar puncture should be performed in any infant with a positive blood culture, infants whose clinical course or laboratory data strongly suggest bacterial sepsis, and infants who initially worsen with antimicrobial therapy. For any infant who is critically ill and likely to have cardiovascular or respiratory compromise from the procedure, the lumbar puncture can be deferred until the infant is more stable.
Cerebrospinal fluid (CSF) values indicative of neonatal meningitis are controversial. In studies that have excluded infants with “traumatic taps” (or nonbacterial illnesses), the meaumber of white blood cells in uninfected preterm or term infants was consistently <10 cells/mm3.44–50 Cell counts 2 standard deviations from the mean were generally less than 20 cells/mm3.46 In a study by Garges et al, the median number of white blood cells in infants who were born at greater than 34 weeks’ gestation and had bacterial meningitis was 477/mm3.43 In contrast, the mediaumber of white blood cells in infants who were born at less than 34 weeks’ gestation and had meningitis was 110/mm3.51 Infants with meningitis attributable to Gram-negative pathogens typically have higher CSF white blood cell counts than do infants with meningitis attributable to Gram-positive pathogens.52 Adjusting the CSF white blood cell count for the number of red blood cells does not improve the diagnostic utility (loss of sensitivity with marginal gain in specificity).53 In addition, the number of bands in a CSF specimen does not predict meningitis.54 With a delay in analysis (>2 hours), white blood cell counts and glucose concentrations decrease significantly.55
Protein concentrations in uninfected, term newborn infants are <100 mg/dL.44–50 Preterm infants have CSF protein concentrations that vary inversely with gestational age. In the normoglycemic newborn infant, glucose concentrations in CSF are similar to those in older infants and children (70%–80% of a simultaneously obtained blood specimen). A low glucose concentration is the CSF variable with the greatest specificity for the diagnosis of meningitis.43,51 Protein concentrations are higher and glucose concentrations are lower in term than in preterm infants with meningitis. However, meningitis occurs in infants with normal CSF values, and some of these infants have high bacterial inocula.43,51
Peripheral White Blood Cell Count and Differential Count
Total white blood cell counts have little value in the diagnosis of early-onset sepsis and have a poor positive predictive accuracy.56,57 Many investigators have analyzed subcomponents of the white blood cell count (neutrophil indices)—absolute neutrophil count, absolute band count, and immature to total neutrophil (I/T)ratio—to identify infected infants. Like most diagnostic tests for neonatal sepsis, neutrophil indices have proven most useful for excluding infants without infection rather than identifying infected neonates. Neutropenia may be a better marker for neonatal sepsis and has better specificity than an elevated neutrophil count, because few conditions besides sepsis (maternal pregnancy-induced hypertension, asphyxia, and hemolytic disease) depress the neutrophil count of neonates.58 The definitions for neutropenia vary with gestational age,58–61 type of delivery (infants born by cesarean delivery without labor have lower counts than infants delivered vaginally),61 site of sampling (neutrophil counts are lower in samples from arterial blood),62 and altitude (infants born at elevated altitudes have higher total neutrophil counts).63 In late preterm and term infants, the definition for neutropenia most commonly used is that suggested by Manroe et al (<1800/mm3 at birth and <7800/mm3 at 12–14 hours of age).58 Schmutz et al reinvestigated these reference ranges using modern cell-counting instrumentation in 30 254 infants born at 23 to 42 weeks’ gestation.61 Infants with diagnoses known to affect neutrophil counts (eg, those born to women with pregnancy-induced hypertension or those with early-onset sepsis) were excluded. In this study, the lower limits of normal for neutrophil values at birth were 3500/mm3 in infants born at >36 weeks’ gestation, 1000/mm3 in infants born at 28 through 36 weeks’ gestation, and 500/mm3 in infants born at <28 weeks’ gestation. Peak values occurred at 6 to 8 hours after birth; the lower limits of normal at that time were 7500/mm3, 3500/mm3, and 1500/mm3 for infants born at >36 weeks’ gestation, 28 to 36 weeks’ gestation, and <28 weeks’ gestation, respectively.61 It is noteworthy that the study by Schmutz et al was performed at
The absolute immature neutrophil count follows a similar pattern to the absolute neutrophil count and peaks at approximately 12 hours of life. The number of immature neutrophils increases from a maximal value of 1100 cells/mm3 at birth to 1500 cells/mm3 at 12 hours of age.58 Absolute immature counts have a poor sensitivity and positive predictive accuracy for early-onset sepsis.22 Furthermore, if exhaustion of bone marrow reserves occurs, the number of immature forms will remain depressed.64
The I/T ratio has the best sensitivity of any of the neutrophil indices. However, with manual counts, there are wide interreader differences in band neutrophil identification.65 The I/T ratio is <
Exhaustion of bone marrow reserves will result in low band counts and lead to falsely low ratios. The timing of the white blood cell count is critical.68 Counts obtained 6 to 12 hours after birth are more likely to be abnormal than are counts obtained at birth, because alterations in the numbers (and ratios) of mature and immature neutrophils require an established inflammatory response. Therefore, once the decision is made to start antimicrobial therapy soon after birth, it is worth waiting 6 to 12 hours before ordering a white blood cell count and differential count.68,69
Platelet Counts
Despite the frequency of low platelet counts in infected infants, they are a nonspecific, insensitive, and late indicator of sepsis.70,71 Moreover, platelet counts are not useful to follow clinical response to antimicrobial agents, because they often remain depressed for days to weeks after a sepsis episode.
Acute-Phase Reactants
A wide variety of acute-phase reactants have been evaluated ieonates with suspected bacterial sepsis. However, only C-reactive protein (CRP) and procalcitonin concentrations have been investigated in sufficiently large studies.72,73 CRP concentration increases within 6 to 8 hours of an infectious episode ieonates and peaks at 24 hours.74,75 The sensitivity of a CRP determination is low at birth, because it requires an inflammatory response (with release of interleukin-6) to increase CRP concentrations.76 The sensitivity improves dramatically if the first determination is made 6 to 12 hours after birth. Benitz et al have demonstrated that excluding a value at birth, 2 normal CRP determinations (8–24 hours after birth and 24 hours later) have a negative predictive accuracy of 99.7% and a negative likelihood ratio of 0.15 for proveeonatal sepsis.76 If CRP determinations remain persistently normal, it is strong evidence that bacterial sepsis is unlikely, and antimicrobial agents can be safely discontinued. Data are insufficient to recommend following sequential CRP concentrations to determine the duration of antimicrobial therapy in an infant with an elevated value (≥1.0 mg/dL).
Procalcitonin concentrations increase within 2 hours of an infectious episode, peak at 12 hours, and normalize within 2 to 3 days in healthy adult volunteers.77 A physiologic increase in procalcitonin concentration occurs within the first 24 hours of birth, and an increase in serum concentrations can occur with noninfectious conditions (eg, respiratory distress syndrome).78 Procalcitonin concentration has a modestly better sensitivity than does CRP concentration but is less specific.73 Chiesa and colleagues have published normal values for procalcitonin concentrations in term and preterm infants.79 There is evidence from studies conducted in adult populations, the majority of which focused on patients with sepsis in the ICU, that significant reductions in use of antimicrobial agents can be achieved in patients whose treatment is guided by procalcitonin concentration.80
Sepsis Screening Panels
Hematologic scoring systems using multiple laboratory values (eg, white blood cell count, differential count, and platelet count) have been recommended as useful diagnostic aids. No matter what combination of tests is used, the positive predictive accuracy of scoring systems is poor unless the score is very high. Rodwell et al described a scoring system in which a score of 1 was assigned to 1 of 7 findings, including abnormalities of leukocyte count, total neutrophil count, increased immature polymorphonuclear leukocyte (PMN) count, increased I/T ratio, immature to mature PMN ratio >0.3, platelet count ≤150 000/mm3, and pronounced degenerative changes (ie, toxic granulations) in PMNs.81 In this study, two-thirds of preterm infants and 90% of term infants with a hematologic score ≥3 did not have proven sepsis.81 Furthermore, scores obtained in the first several hours after birth have been shown to have poorer sensitivity and negative predictive value than scores obtained at 24 hours of age.67 Sepsis screening panels commonly include neutrophil indices and acute-phase reactants (usually CRP concentration). The positive predictive value of the sepsis screen ieonates is poor (<30%); however, the negative predictive accuracy has been high (>99%) in small clinical studies.22 Sepsis screening tests might be of value in deciding which “high-risk” healthy-appearing neonates do not need antimicrobial agents or whether therapy can be safely discontinued.
Treatment of Infants With Suspected Early-Onset Sepsis
In the
The duration of antimicrobial therapy in infants with negative blood cultures is controversial. Many women receive antimicrobial agents during labor as prophylaxis to prevent early-onset GBS infections or for management of suspected intra-amniontic infection or PPROM. In those instances, postnatal blood cultures may be sterile (false negative). When considering the duration of therapy in infants with negative blood cultures, the decision should include consideration of the clinical course as well as the risks associated with longer courses of antimicrobial agents. In a retrospective study by Cordero and Ayers, the average duration of treatment in 695 infants (<
Prevention Strategies for Early-Onset Sepsis
The only intervention proven to decrease the incidence of early-onset neonatal sepsis is maternal treatment with intrapartum intravenous antimicrobial agents for the prevention of GBS infections.93 Adequate prophylaxis is defined as penicillin (the preferred agent), ampicillin, or cefazolin given for ≥4 hours before delivery. Erythromycin is no longer recommended for prophylaxis because of high resistance rates. In parturients who have a nonserious penicillin allergy, cefazolin is the drug of choice. For parturients with a history of serious penicillin allergy (anaphylaxis, angioedema, respiratory compromise, or urticaria), clindamycin is an acceptable alternative agent, but only if the woman’s rectovaginal GBS screening isolate has been tested and documented to be susceptible. If the clindamycin susceptibility is unknown or the GBS isolate is resistant to clindamycin, vancomycin is an alternative agent for prophylaxis. However, neither clindamycior vancomycin has been evaluated for efficacy in preventing early-onset GBS sepsis ieonates. Intrapartum antimicrobial agents are indicated for the following situations93:
1. Positive antenatal cultures or molecular test at admission for GBS (except for women who have a cesarean delivery without labor or membrane rupture)
2. Unknown maternal colonization status with gestation <37 weeks, rupture of membranes >18 hours, or temperature >
3. GBS bacteriuria during the current pregnancy
4. Previous infant with invasive GBS disease
Management guidelines for the newborn infant have been published93 and are available online (http://www.cdc.gov/groupbstrep/guidelines/index.html).
Clinical Challenges
Challenge 1: Identifying Neonates With Clinical Signs of Sepsis With a “High Likelihood” of Early-Onset Sepsis Who Require Antimicrobial Agents Soon After Birth
Most infants with early-onset sepsis exhibit abnormal signs in the first 24 hours of life. Approximately 1% of infants will appear healthy at birth and then develop signs of infection after a variable time period.21 Every critically ill infant should be evaluated and receive empirical broad-spectrum antimicrobial therapy after cultures, even when there are no obvious risk factors for sepsis. The greatest difficulty faced by clinicians is distinguishing neonates with early signs of sepsis from neonates with noninfectious conditions with relatively mild findings (eg, tachypnea with or without an oxygen requirement). In this situation, data are insufficient to guide management. In more mature neonates without risk factors for infection who clinically improve over the first 6 hours of life (eg, need for oxygen is decreasing and respiratory distress is resolving), it is reasonable to withhold antimicrobial therapy and monitor the neonates closely. The 6-hour window should not be considered absolute; however, most infants without infection demonstrate some improvement over that time period. Any worsening of the infant’s condition should prompt starting antimicrobial agents after cultures have been obtained.
Challenge 2: Identifying Healthy-Appearing Neonates With a “High Likelihood” of Early-Onset Sepsis Who Require Antimicrobial Agents Soon After Birth
This category includes infants with 1 of the risk factors for sepsis noted previously (colonization with GBS, prolonged rupture of membranes >18 hours, or maternal chorioamnionitis). GBS is not a risk factor if the mother has received adequate intrapartum therapy (penicillin, ampicillin, or cefazolin for at least 4 hours before delivery) or has a cesarean delivery with intact membranes in the absence of labor.93 The risk of infection in the newborn infant varies considerably with the risk factor present. The greatest risk of early-onset sepsis occurs in infants born to women with chorioamnionitis who are also colonized with GBS and did not receive intrapartum antimicrobial agents. Early-onset sepsis does occur in infants who appear healthy at birth.21 Therefore, some clinicians use diagnostic tests with a high negative predictive accuracy as reassurance that infection is not present (allowing them to withhold antimicrobial agents). The decision of whether to treat a high-risk infant depends on the risk factors present, the frequency of observations, and gestational age. The threshold for initiating antimicrobial treatment generally decreases with increasing numbers of risk factors for infection and greater degrees of prematurity. Suggested algorithms for management of healthy-appearing, high-risk infants are shown in Figs 1, 2, and 3. Screening blood cultures have not been shown to be of value.21
l
FIGURE 1
Evaluation of asymptomatic infants <37 weeks’ gestation with risk factors for sepsis. aThe diagnosis of chorioamnionitis is problematic and has important implications for the management of the newborn infant. Therefore, pediatric providers are encouraged to speak with their obstetrical colleagues whenever the diagnosis is made. bLumbar puncture is indicated in any infant with a positive blood culture or in whom sepsis is highly suspected on the basis of clinical signs, response to treatment, and laboratory results. IAP, intrapartum antimicrobial prophylaxis; WBC, white blood cell; Diff, differential white blood cell count.
FIGURE 2
Evaluation of asymptomatic infants ≥37 weeks’ gestation with risk factors for sepsis. aThe diagnosis of chorioamnionitis is problematic and has important implications for the management of the newborn infant. Therefore, pediatric providers are encouraged to speak with their obstetrical colleagues whenever the diagnosis is made. bLumbar puncture is indicated in any infant with a positive blood culture or in whom sepsis is highly suspected on the basis of clinical signs, response to treatment, and laboratory results. WBC, white blood cell; Diff, differential white blood cell count.
FIGURE 3
Evaluation of asymptomatic infants ≥37 weeks’ gestation with risk factors for sepsis (no chorioamnionitis). aInadequate treatment: Defined as the use of an antibiotic other than penicillin, ampicillin, or cefazolin or if the duration of antibiotics before delivery was <4 h. bDischarge at 24 h is acceptable if other discharge criteria have been met, access to medical care is readily accessible, and a person who is able to comply fully with instructions for home observation will be present. If any of these conditions is not met, the infant should be observed in the hospital for at least 48 h and until discharge criteria are achieved. IAP, intrapartum antimicrobial prophylaxis; WBC, white blood cell; Diff, differential white blood cell count.
Conclusions
The diagnosis and management of neonates with suspected early-onset sepsis are based on scientific principles modified by the “art and experience” of the practitioner. The following are well-established concepts related to neonatal sepsis:
1. Neonatal sepsis is a major cause of morbidity and mortality.
2. Diagnostic tests for early-onset sepsis (other than blood or CSF cultures) are useful for identifying infants with a low probability of sepsis but not at identifying infants likely to be infected.
3. One milliliter of blood drawn before initiating antimicrobial therapy is needed to adequately detect bacteremia if a pediatric blood culture bottle is used.
4. Cultures of superficial body sites, gastric aspirates, and urine are of no value in the diagnosis of early-onset sepsis.
5. Lumbar puncture is not needed in all infants with suspected sepsis (especially those who appear healthy) but should be performed for infants with signs of sepsis who can safely undergo the procedure, for infants with a positive blood culture, for infants likely to be bacteremic (on the basis of laboratory data), and infants who do not respond to antimicrobial therapy in the expected manner.
6. The optimal treatment of infants with suspected early-onset sepsis is broad-spectrum antimicrobial agents (ampicillin and an aminoglycoside). Once the pathogen is identified, antimicrobial therapy should be narrowed (unless synergism is needed).
7. Antimicrobial therapy should be discontinued at 48 hours in clinical situations in which the probability of sepsis is low.
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The localized forms of infections: skin diseases, subcutaneous fat diseases, and umbilical wound infection.
Problem of the newborns’ localized purulent infection is topical question because of frequent severe consequences. This pathology is more common in premature, low weight children, newborns with birth asphyxia, birth injury. The life prognosis depends on in time diagnosis and effective treatment. That’s why doctors of different specializations have to know this pathology.
The newborn infant is more vulnerable than the older child to certain infections. The preterm baby is even less able to withstand infection and more liable to suffer serious complications.
· Humoral antibodies
o IgG is transferred across the placenta especially in the last trimester, and protects the baby against specific infections to which the mother has been immunized, e.g. measles, mumps, polio, diphtheria, tetanus, typhoid.
o This passive immunity wanes after four to six months, but may persist to 9 months e.g. measles.
o Neither IgM nor IgA cross the placenta. They are normally only produced by the infant after birth. (Note: the fetus can produce IgM in response to an intra-uterine infection e.g. congenital syphilis)
· Cell-mediated immunity:
o Lymphocytes are involved in the killing of bacteria
o The lymphocytes have not been exposed previously to antigens
· Inflammatory reaction:
o In the newborn the inflammatory response is poor and phagocytosis of bacteria by leucocytes is inefficient (due to reduced opsonins and delayed chemotaxis)
· Antenatal:
o The placenta filters out most organisms but not rubella virus, HIV, Toxoplasma, CMV and Treponema pallidum
o amniotic fluid contains lysozymes and other antibacterial agents to reduce the risk of infection
· Postnatal:
· Breast feeding:
o breast milk has IgG, IgM, IgA, macrophages and lysozymes
o lactoferrin and transferrin protect against gram negative organisms
o breast feeding promotes growth of Lactobacilli and inhibits E.coli
· Nursery care:
o Infection may be prevented by hand-washing, bathing baby and cord and eye care.
· Antenatal:
o Syphilis, HIV, rubella, CMV, varicella and bacterial chorioamnionitis
· Intranatal:
o Herpes, Streptococci, Gonococci, Candida, Chlamydia (increased risk with prolonged labour)
· Postnatal:
o Cross-infection: hands, feeds, inhalation.
· Antenatal :
o Stillbirth, fetal anomalies (e.g. rubella), congenital infections (e.g. syphilis, amniotic fluid infection syndrome with pneumonia).
· Postnatal :
o Common: conjunctivitis, oral thrush.
o Less common: cord infection, skin sepsis.
o Uncommon: urinary infection, pneumonia, septicaemia, meningitis.
· Clinical:
o superficial infection: usually obvious
o generalised infections: may present with poor feeding, lethargy, failure to gain weight, jaundice, anaemia, rash, hepatosplenomegaly, diarrhoea, vomiting, etc
o The temperature may be raised but is more ofteormal or sub-normal.
· Viral infections:
o isolate the virus, or demonstrate a rise in antibody titre
o total or specific IgM levels
o demonstrate organism, e.g. Candida, on slide using Gram stain, or culture on special agar
o obtain cultures from mother
o gastric aspirate M/C/S
o white blood count (normal 5000 to 20 000)
o immature/total neutrophil ratio (normal 0-12%)
o C reactive protein
o pus, urine, CSF, blood culture
o x-rays of chest or bones
o ECG (? myocarditis)
Scalded skin syndrome (Ritter’s disease).
Conjunctivitis. Gonococcal conjunctivitis is a serious acute inflammation which may damage the cornea leading to blindness. The onset is often rapid with red swollen mucus membranes and a copious purulent discharge. The diagnosis can be made quickly with a Gram stain on a smear of pus (Gram negative diplococci in leucocytes).
Treatment involves the instillation of Penicillin eyedrops (20,000 units/ml), frequently enough to keep eye free of pus. Repeated irrigation of the eye with saline can be used if penicillin drops are not available.
It is essential to give an additional 100,000 units of intramuscular procaine penicillin daily for 3 days in severe gonococcal conjunctivitis. Don’t forget to also treat the mother and have her VDRL checked.
Gonococcal conjunctivitis can be prevented by putting chloromycetin eye ointment into both eyes routinely after delivery.
Non-Gonococcal Conjunctivitis: Chloramphenicol ointment or drops applied 8 hourly for a week is usually sufficient for most infections aquired after delivery.
Use tetracycline or erythromycin ointment if Chlamydia infection is suspected or if inflammation recurs after chloramphenicol therapy. Proven Chlamydia infections should also be treated with oral erythromycin for 10 days.
Thrush:
Moniliasis is caused by the fungus Candida albicans and commonly affects the mouth or the nappy area. The source is usually mother’s vagina or nipples, or contaminated hands, bottles, etc.
Small white patches are found on the tongue and may spread to the inside of the cheeks and lips. These white plaques resemble curds of milk but are difficult to dislodge. The underlying mucosa is inflammed and sucking is often painful. The diagnosis is proved by the identification of spores and hyphae on microscopy. In the nappy area, the insides of skin folds (groin) are affected.
Treatment:
Mycostatin suspension (Nystatin) 1 ml (100,000 units) after each feed for 7-10 days. If mother is breast feeding, mycostatin should be applied to the nipples while vaginal infection should be eradicated. Dummies, teats and bottle must be boiled.
Skin Infections: Mostly due to Staph. aureus and may present as one or more pustules, infected vesicles, abscesses, etc. The diagnosis is made on Gram stain and culture, the results of which will determine the form of treatment. Mild superficial infection may be treated with chlorhexidine (Hibiscrub). Abscesses need incision and drainage. More severe infections, e.g. cellulitis require systemic antibiotic therapy.
Phlegmona of the newborn: local signs + expressed intoxication.
There are 4 clinical stages: incidence, alterative-necrotic, declination, reparation.
This is a local hyperemia, infiltration with distinct margins, it enlarges quickly ® infiltration became cyanotic with softening in the center ® formation of the wound surface with digger margins ® granulations, epithelization with scars formation.
Localization: chest, back, buttocks, arms and legs.
Treatment: surgical + conservative (antibiotics, desintoxication, immune therapy, symptomatic).
Mastitis of the newborn
Local signs: enlargement of the breast, condensation, local hyperthermia, hyperemia, tenderness, later – fluctuation;
Expressed intoxication (high body temperature, lost of appetite, poor sucking);
Treatment: conservative in the infiltrative stage (antibiotics), surgical in case of abscess formation).
Umbilical Infection (Omphalitis):
Causes: Omphalitis is a polymicrobial infection typically caused by a mixture of aerobic and anaerobic organisms. Associated risk factors include the following:
o Low birthweight (<
o Prior umbilical catheterization
o Septic delivery (as suggested by premature rupture of membranes, nonsterile delivery, or maternal infection)
o Prolonged rupture of membranes
Omphalitis occasionally manifests from an underlying immunologic disorder.
Rarely, an anatomic abnormality may be present, such as a patent urachus or patent omphalomesenteric duct.
Serous omphalitis: serous discharge from the umbilical stump, prolonged epithelization; symptoms from organs and systems, intoxication are absent.
Treatment: local (3% Hydrogen peroxide, Spiritus camphoratus, Viridis nitens, xerophormum).
Purulent omphalitis Local disease: Physical signs vary with the extent of disease. Signs of localized infection include the following:
o Purulent or malodorous discharge from the umbilical stump
o Periumbilical erythema
o Edema
o Tenderness
Extensive local disease: The following signs indicate more extensive local disease, such as fasciitis or myonecrosis. These signs also may suggest infection by both aerobic and anaerobic organisms and include the following:
o Periumbilical ecchymoses
o Crepitus
o Bullae
o Progression of cellulitis despite antimicrobial therapy
Fig. 1. Purulent omphalytis.
Lab Studies:
· Obtain specimens from umbilical infection routinely, and submit specimens for Gram stain and culture for aerobic and anaerobic organisms. If myonecrosis is suspected, obtain specimens from the involved muscle rather than the wound surface.
· Obtain a blood culture for aerobic and anaerobic organisms.
· Obtain a complete blood count with manual differential.
o Neutrophilia or neutropenia may be present in acute infection. An immature-to-total neutrophil ratio greater than 0.2 may be a useful indicator of systemic bacterial infection in the first few days of life.
o Thrombocytopenia may be present.
TREATMENT Medical Care: Treatment of omphalitis (periumbilical edema, erythema, and tenderness) in the newborn includes antimicrobial therapy and supportive care.
Antimicrobial therapy
o Include parenteral antimicrobial coverage for gram-positive and gram-negative organisms. A combination of an antistaphylococcal penicillin and an aminoglycoside antibiotic is recommended.
o Some believe that anaerobic coverage is important in all patients. Omphalitis complicated by necrotizing fasciitis or myonecrosis requires a more aggressive approach, with antimicrobial therapy directed at anaerobic organisms as well as gram-positive and gram-negative organisms.
§ Metronidazole may provide anaerobic coverage.
§ Clindamycin may be substituted for the antistaphylococcal penicillin.
§ As with antimicrobial therapy for other infections, consider local antibiotic susceptibility patterns.
§ Pseudomonas species have been implicated in particularly rapid or invasive disease.
o Expect erythema of the umbilical stump to improve within 12-24 hours after the initiation of antimicrobial therapy.
Supportive care: In addition to antimicrobial therapy, supportive care is essential to survival. These measures include the following:
o Provide ventilatory assistance and supplementary oxygen for hypoxemia or apnea unresponsive to stimulation.
o Administer fluid, vasoactive agents, or both for hypotension.
o Administration of platelets, fresh frozen plasma, or cryoprecipitate for DIC and clinical bleeding is suggested.
o Treat infants at centers capable of supporting cardiopulmonary function.
Management of necrotizing fasciitis and myonecrosis involves early and complete surgical debridement of the affected tissue and muscle.
Staphylococcus Aureus Infection
· Skin and soft tissue (impetigo) (Fig. 1, 2, 3, 4): Generally, this starts as a small area of erythema that progresses into bullae (filled with cloudy fluid) that rupture and heal with the formation of a crust, previously described as honey-colored. Although group A Streptococcus was considered the primary agent, S aureus has become the major pathogen since the 1980s. Bullous impetigo is caused exclusively by S aureus and is observed less frequently in the
· Initial appearance is a small area of erythema. Bullae, ie, blisterlike lesions filled with cloudy fluid, appear as the disease progresses. As bullae heal, a honey-colored crust develops.
Fig. 2. Impetigo in infant.
Fig. 3,4,5. Bullous impetigo.
· Folliculitis/furuncle/carbuncle: This is a series of progressively severe staphylococcal skin infections. Folliculitis is a tender pustule that involves the hair follicle. A furuncle involves both the skin and the subcutaneous tissues in areas with hair follicles, such as the neck, axillae, and buttocks. They actually are small abscesses characterized by exuding purulent material from a single opening. A carbuncle is an aggregate of connected furuncles and has several pustular openings. Skin infections can be self-limited, but they can also disseminate hematogenously and cause life-threatening septicemia.
Fig. 6. The superficial pustule in axillar region.
· Folliculitis is the appearance of a tender pustule involving a hair follicle. Furuncle is an apparent small abscess that exudes purulent material from a single opening. Carbuncle is an aggregate of furuncles with several openings.
· Laboratory studies: Make the diagnosis based on clinical appearance and occasionally on results of aspiration and culture of purulent material from the lesion.
· Medical Care: Impetigo/folliculitis/furuncle/carbuncle: Treatment of impetigo and other minor skin infections (ie, superficial or localized infections) can be with a topical agent such as mupirocin. Treat more extensive skin disease and bullous impetigo with oral antistaphylococcal agents.
· Scalded skin syndrome (Ritter disease (Fig. 7): A relatively rare syndrome caused by exfoliative toxin takes the form of superficial fragile blisters that burst, leaving a tender base. The patient often is febrile and occasionally has mucopurulent eye discharge. Place special emphasis in making this diagnosis because it can often be mistaken for erythema multiforme and/or toxic epidermal necrolysis, which are treated with corticosteroids. Misdiagnosis delays treatment and allows exfoliation to progress, and corticosteroid therapy could potentiate bacterial superinfection. Although the mortality rate is low in children with this entity, most fatalities are caused by delays in diagnosis.
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Fig. 7. Baby with Ritter’s disease.
· Examination shows superficial fragile blisters that burst, leaving a tender base. Skin sloughs easily when touched, called Nikolsky sign (Fig. 8). Fever is often present. A mucopurulent eye discharge may be present. As discussed above, it can often be mistaken for erythema multiforme and/or toxic epidermal necrolysis. Misdiagnosis must be avoided.
Fig. 8. Nikolsky sign.
· Therapy for this, as with any S aureus toxin–mediated disease, should be aimed at eradicating the focus of infection and ending toxin production. Administer large doses of intravenous antistaphylococcal agents, such as oxacillin (150 mg/kg/d) or a first-generation cephalosporin, such as cefazolin (100 mg/kg/d). In vitro, clindamycin has been shown to inhibit the synthesis of TSST-1, and personal experience has shown it to be extremely effective in combination with one of the above agents. Children with denuded skin should be touched as little as possible. Topical antimicrobial agents have little utility because skin damage is self-limited once systemic antibiotics are administered.
· Bone infections (osteomyelitis) Children often present with a sudden onset of fever and bony tenderness or a limp. The pain can be throbbing and quite severe; however, presentation ieonates can be quite subtle. Infants can appear well except for failure to move an extremity or pain on movement. Redness or swelling indicates that infection has spread into the subperiosteal space. Rupture of a focus of osteomyelitis into a joint space can result in septic arthritis. This is often observed ieonates.
· Bone infections are indicated by fever and bony tenderness or limp. Infants can appear well except for failure to move an extremity or pain on movement. Children with vertebral osteomyelitis present with back pain, and those younger than 3 years present with refusal to walk or with a limp. Occasionally, children with vertebral osteomyelitis may have incontinence as a presenting symptom. Children with discitis tend to present with less fever and often appear less ill than those children with vertebral osteomyelitis.
· Laboratory studies: Blood cultures are positive only in 50% of pediatric patients. Therefore, cultures of bone aspirate are useful in obtaining the organism and planning for long-term therapy. In addition, C-reactive protein or erythrocyte sedimentation rate are generally elevated in acute disease.
· Imaging Studies: On plain film radiographs, destructive bone changes are usually observed 2 weeks after infection. This is because a 30-50% reduction in bone calcium content is required before demonstration of an osteolytic lesion. Clinical diagnosis of osteomyelitis is most often supported by findings on bone scan with technetium diphosphonate. Increased tracer uptake reflects the inflammatory process in the bone lesion. However, this modality is not as useful ieonates or after trauma or surgery. MRI is the best imaging modality for defining purulent collections and for planning surgery.
· Differential diagnosis
Signs |
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History |
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Time of appearing |
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Changes of the movements |
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Intoxication |
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Local infiltration |
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Active movements in the arm |
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Passive movements in the arm |
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Blood count (leucocytosis, formula left shift) |
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Roentgenologic signes |
· Therapy: Starting a semisynthetic penicillin, such as oxacillin (150 mg/kg/d), empirically is a good choice for most cases of community-acquired osteomyelitis. In patients with allergy to penicillin, a first-generation cephalosporin and lyncomycin (40 mg/kg/d) are both excellent alternatives. Cefuroxime (150 mg/kg/d) is a good alternative in younger children who are incompletely immunized because it covers H influenzae type B as well as S aureus. Only use vancomycin when the other drugs mentioned are absolutely not tolerated or when a possibility of a methicillin-resistant strain exists. The duration of therapy is a controversial topic in the literature, but the consensus among multiple authors is that the minimum effective treatment time is 4-6 weeks. A switch to oral therapy is acceptable if the child is able to take oral antibiotics, is afebrile, and if an etiologic agent is found after a good clinical response to parenteral antibiotics has been shown. Absorption of the antibiotic should be measured using serum bactericidal peaks and troughs.
· Surgical Care: Surgery is usually indicated to drain purulent material from the subperiosteal space or if infected foreign material is present.
· Septic arthritis: Typical findings include warmth, erythema, and tenderness of the joint together with constitutional symptoms and fever. An important exception to this is in infants (in whom the hip is the most commonly involved joint), where these signs may be absent. The child typically lies with the involved joint abducted and externally rotated. Because pain fibers are located within the joint capsule, movements, such as changing a diaper, that compress the head of the femur into the acetabulum cause pain. A portal of infection is almost never found, and the infection is nearly always unilateral. Patients with infection of the sacroiliac joint present with tenderness elicited during digital rectal examination and with pain during flexion, abduction, and external rotation of the hip.
· Examination shows warmth, erythema, and tenderness of the joint. Constitutional symptoms and fever are frequent. These findings may be absent in an infant. Children with infection of the sacroiliac joint present with tenderness elicited during digital rectal examination.
· Laboratory studies: Joint fluid, when obtained, is the primary means of diagnosis. The fluid should be Gram stained and cultured. In addition, the number and type of leukocytes should be determined. Median cell count in bacterial arthritis is 60.5 X 109 cells with a neutrophil predominance of greater than 75%.
· Imaging Studies: Plain radiographs show capsular swelling. They are most useful in identifying other causes of hip pain, such as Legg-Calve-Perthes disease. They should be obtained with the child in the frog leg position as well as with the legs extended and slightly internally rotated. Displacement of gluteal fat lines because of the swelling of the joint capsule is an early radiologic sign of septic arthritis. If a bone scan is performed, increased uptake on either side of the joint is visible. Pyogenic sacroiliitis is difficult to diagnose, and the radiologic method of choice is computerized tomography imaging.
· Therapy: As in osteomyelitis, start an appropriate antistaphylococcal drug (eg, oxacillin, which is penicillinase resistant; clindamycin; cefazolin) parenterally. These antibiotics reach joint fluid readily, and the concentration in the joint fluid is 30% the serum value. Therapy usually is for at least 4 weeks. Duration of parenteral therapy is often debated. Some authors have demonstrated efficacy with 1 week of parenteral therapy followed by 3 weeks of oral therapy. Make the decision to switch to oral therapy based on the ability to reliably administer a drug dosage with a peak bactericidal titer of at least 1:8. Any reaccumulation of joint fluid should be removed and cultured to assess the efficacy of therapy as well as to make the patient more comfortable.
· Surgical care: In an infant, septic arthritis of the hip and shoulder is a surgical emergency because these joints should be drained as soon as possible to prevent bony destruction. In addition, any joint should be surgically drained if a large amount of fibrin, tissue debris, or loculation is present, preventing adequate drainage by needle aspiration.
· Thrombophlebitis: Usually occurring in a hospitalized patient, the patient develops fever, pain, and sometimes erythema at the insertion site of an intravenous catheter. Occasionally, pus can be expressed. Severe suppurative thrombophlebitis can occur in burn patients, with fewer than half of diagnoses made while patients are alive.
· Patients usually have a fever and sometimes have cutaneous involvement such as erythema, induration, or tenderness. Occasionally, pus can be expressed at the insertion site of the catheter. Commonly, the exit site does not show signs of infection. Establishing infection of an intravascular device as the cause of fever in a hospitalized patient is a diagnosis of exclusion.
· Laboratory studies: Thrombophlebitis: Although management is sometimes controversial, obtaining a blood culture through the line and a peripheral blood culture is usually recommended.
· Therapy: Immediately remove the lines in any patient who is immunocompromised or severely ill. In mildly-to-moderately ill patients, a trial of antibiotic therapy, usually vancomycin and gentamicin, may be attempted. However, if the infecting organism is S aureus, such trials are usually unsuccessful.
· Surgical care: Remove the infected line in immunocompromised or severely ill patients or when infection is impossible to eradicate medically.
NECROTISING ENTEROLOCITIS Necrosis of the bowel wall may complicate bowel ischaemia after asphyxia, infection or shock iewborn infants.
Stages of the necrotizing enterocolitis
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Stage |
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І – incidence |
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ІІ – height |
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ІІІ – progressive |
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ІV – complications |
· Complications:
o perforation, later – stenosis
· Treatment:
o nasogastric drainage
o total parenteral nutrition
o penicillin, gentamicin and metronidazole IV
o may need bowel resection
MENINGITIS Usually presents as in septicaemia. Later may show local signs e.g. full tense fontanelle, squint, convulsions, etc. Neck stiffness is unusual.
· Diagnosis:
o confirmed by lumbar puncture
· Treatment:
o suitable antibiotics given intravenously for 3 weeks e.g. Cefotaxime or Ceftriaxone or combination of ampicillin, cotrimoxazole and chloramphenicol.
URINARY TRACT INFECTION: Infection usually blood-borne. Commonest pathogen E.coli. Predisposed to by urinary tract anomalies e.g. pelvi-ureteric junction obstruction, vesico-ureteric reflux. Signs of infection are usually non-specific. The kidneys may be enlarged.
