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Sepsis neonatal

Article Last Updated: Aug 18, 2006 Artículo Última actualización: Aug 18, 2006

AUTHOR AND EDITOR INFORMATION Autor y


editor de la información
Section 1 of 11 Sección 1 de 11

• Authors and Editors Autores y Editores


• Introduction Introducción
• Clinical Clínica
• Differentials Diferencias
• Workup Workup
• Treatment Tratamiento
• Medication Medicación
• Follow-up Seguimiento
• Miscellaneous Miscellaneous
• Multimedia Multimedia
• References Referencias

Author: Ann L Anderson-Berry, MD, Assistant Professor of Pediatrics, Joint Division


of Newborn Medicine, Creighton University, University of Nebraska Medical Center
Autor: Ann Anderson L-Berry, MD, Profesor Adjunto de Pediatría, División Mixta del
Recién Nacido de Medicina, Universidad de Creighton, Universidad de Nebraska
Medical Center

Ann L Anderson-Berry is a member of the following medical societies: American


Academy of Pediatrics and Nebraska Medical Association Ann-L Anderson Berry es
miembro de las siguientes sociedades médicas: Academia Americana de Pediatría y la
Asociación Médica de Nebraska

Coauthor(s): Linda L Bellig, MA, RN, NNP, Track Coordinator, Instructor, Neonatal
Nurse Practitioner Program, Medical University of South Carolina College of Nursing;
Bryan L Ohning, MD, PhD, Clinical Associate Professor of Pediatrics, Medical
University of South Carolina; Medical Director, NICU and Neonatal Transport Team,
Department of Neonatology, Greenville Children's Hospital Coautor (s): Linda L Bellig,
MA, RN, NNP, Coordinador de pista, Instructor, enfermera de práctica neonatal
Programa de Medicina de la Universidad de Carolina del Sur Escuela de Enfermería;
Ohning Bryan L, MD, PhD, Profesor Clínico Asociado de Pediatría, Universidad de
Medicina de Carolina del Sur; Director Médico, UCIN y Equipo de Transporte Neonatal
del Departamento de Neonatología, Greenville Children's Hospital

Editors: Scott S MacGilvray, MD , Associate Professor, Department of Pediatrics, East


Carolina University School of Medicine; Mary L Windle, PharmD , Adjunct Assistant
Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy
Editor, eMedicine.com, Inc; David A Clark, MD , Chairman, Professor, Department of
Pediatrics, Albany Medical College; Carol L Wagner, MD , Professor of Pediatrics,
Medical University of South Carolina; Neil N Finer, MD, Professor, Department of
Pediatrics, University of California at San Diego School of Medicine; Program Director,
Division of Neonatology, University of California San Diego Medical Center Editores: S
MacGilvray Scott, MD, Profesor Asociado, Departamento de Pediatría, East Carolina
University School of Medicine; María L Windle, PharmD, Profesor Asistente Adjunto
de la Universidad de Nebraska Medical Center College de Farmacia, Farmacia Editor,
eMedicine.com, Inc; A David Clark, MD, Presidente, Profesor del Departamento de
Pediatría, Albany Medical College; Carol L Wagner, MD, Profesor de Pediatría,
Universidad Médica de Carolina del Sur; Neil N fina, MD, Profesor del Departamento de
Pediatría, Universidad de California en San Diego School of Medicine; Programa
Director de la División de Neonatología, Universidad de California San Diego Medical
Center

Author and Editor Disclosure Autor y editor de divulgación

Synonyms and related keywords: neonatal sepsis, neonatal infection, early-onset


neonatal sepsis, late-onset neonatal sepsis, early-onset sepsis syndrome, late-onset sepsis
syndrome, neonatal bacteremia Sinónimos y palabras clave relacionadas: sepsis
neonatal, infección neonatal, a principios de inicio sepsis neonatal, de aparición tardía
sepsis neonatal, a principios de sepsis de aparición de síndrome de aparición tardía,
síndrome de sepsis, bacteriemia neonatal

INTRODUCTION INTRODUCCIÓN
Section 2 of 11 Sección 2 de 11

• Authors and Editors Autores y Editores


• Introduction Introducción
• Clinical Clínica
• Differentials Diferencias
• Workup Workup
• Treatment Tratamiento
• Medication Medicación
• Follow-up Seguimiento
• Miscellaneous Miscellaneous
• Multimedia Multimedia
• References Referencias

Background Fondo

Neonatal sepsis may be categorized as early or late onset. Sepsis neonatal puede ser
categorizada como principios o de inicio tardío. 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. Ochenta y cinco por
ciento de los recién nacidos con inicio temprano de la infección presente en las 24 horas,
5% actual al 24-48 horas, y un menor porcentaje de pacientes presentan entre 48 horas y
6 días de vida. Onset is most rapid in premature neonates. El inicio es más rápido en los
recién nacidos prematuros. Early-onset sepsis syndrome is associated with acquisition of
microorganisms from the mother. A principios de sepsis de aparición de síndrome se
asocia con la adquisición de los microorganismos de la madre. Transplacental infection
or an ascending infection from the cervix may be caused by organisms that colonize in
the mother's genitourinary tract, with acquisition of the microbe by passage through a
colonized birth canal at delivery. Infección transplacentaria o una infección ascendente
desde el cuello del útero puede ser causada por organismos que colonizan a la madre del
tracto genitourinario, con la adquisición de los microbios de paso a través de un canal de
nacimiento colonizados en el momento del parto. The microorganisms most commonly
associated with early-onset infection include group B Streptococcus (GBS), Escherichia
coli, Haemophilus influenzae, and Listeria monocytogenes. Los microorganismos más
comúnmente asociados con la aparición temprana de la infección incluyen Streptococcus
del grupo B (GBS), Escherichia coli, Haemophilus influenzae y Listeria monocytogenes.

Late-onset sepsis syndrome occurs at 7-90 days of life and is acquired from the
caregiving environment. De aparición tardía, síndrome de sepsis se produce en 7-90 días
de vida y se adquiere desde el entorno de asistencia a otras personas. 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. Los organismos que han estado
implicados en el origen de aparición tardía, síndrome de sepsis incluyen coagulasa-
negativos estafilococos, Staphylococcus aureus, E coli, Klebsiella, Pseudomonas,
Enterobacter, Candida, GBS, Serratia, Acinetobacter, y anaerobios. 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. La piel del bebé, las vías respiratorias, conjunctivae, tracto
gastrointestinal, ombligo y puede llegar a ser colonizada desde el medio ambiente, dando
lugar a la posibilidad de aparición tardía de la sepsis microorganismos invasores. Vectors
for such colonization may include vascular or urinary catheters, other indwelling lines, or
contact from caregivers with bacterial colonization. Los vectores de esas colonización
puede incluir vascular o catéteres urinarios, inhabitación otras líneas, o póngase en
contacto con cuidadores de colonización bacteriana.

Pneumonia is more common in early-onset sepsis, whereas meningitis and bacteremia are
more common in late-onset sepsis. La neumonía es más común en los principios de sepsis
de aparición, mientras que la meningitis y la bacteriemia son más comunes a finales de
sepsis de aparición. 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. Prematuros y recién nacidos enfermos,
tienen una mayor susceptibilidad a la sepsis y sutil presentaciones iniciales inespecíficos,
por lo que requieren mucha vigilancia a fin de que la sepsis puede ser identificada y
tratada con eficacia.

Pathophysiology Fisiopatología

The infectious agents associated with neonatal sepsis have changed over the past 50
years. S aureus and E coli were the most common bacterial infectious hazards for
neonates during the 1950s in the United States. Los agentes infecciosos asociados con la
sepsis neonatal han cambiado en los últimos 50 años. S aureus y E coli son los más
comunes de bacterias infecciosas riesgos para los recién nacidos durante la década de
1950 en los Estados Unidos. Over the ensuing decades, GBS replaced S aureus as the
most common gram-positive organism that caused early-onset sepsis. Durante los
decenios subsiguientes, GBS sustituirá S aureus como el más común gram-positivos
organismo que causaron a principios de sepsis de aparición. During the 1990s, GBS and
E coli continued to be associated with neonatal infection; however, coagulase-negative S
aureus is now more frequently observed. Durante el decenio de 1990, GBS y E coli sigue
siendo asociado a infección neonatal, sin embargo, coagulasa-negativos S aureus es ahora
más frecuentemente observada. Additional organisms, such as L monocytogenes,
Chlamydia pneumoniae, H influenzae, Enterobacter aerogenes , and species of
Bacteroides and Clostridium have also been identified in neonatal sepsis. Organismos
adicionales, tales como L. monocytogenes, Chlamydia pneumoniae, H influenzae,
Enterobacter aerogenes, y las especies de Bacteroides y Clostridium también han sido
identificados en la sepsis neonatal.

Meningoencephalitis and neonatal sepsis syndrome can also be caused by infection with
adenovirus, enterovirus, or coxsackievirus. Meningoencefalitis y sepsis neonatal,
síndrome también puede ser causada por infección con adenovirus, enterovirus, o
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 in neonatal infection. Además, las enfermedades de transmisión sexual y las
enfermedades víricas, tales como la gonorrea, sífilis, virus herpes simplex (HSV),
citomegalovirus (CMV), hepatitis, VIH, rubéola, toxoplasmosis, Trichomonas vaginalis,
Candida y especies, han sido implicados en infección neonatal. Bacterial organisms with
increased antibiotic resistance have also emerged and have further complicated the
management of neonatal sepsis. Bacteriana organismos con una mayor resistencia a los
antibióticos también han surgido y se han complicado aún más la gestión de la sepsis
neonatal. The colonization patterns in nurseries and personnel are reflected in the
organisms currently associated with nosocomial infection. Los patrones de colonización
en los viveros y el personal se reflejan en los organismos que actualmente está asociada a
infecciones nosocomiales. In today's neonatal intensive care units (NICUs), infants with
lower birth weight and infants who are less mature have an increased susceptibility to
these organisms. En la situación actual de cuidados intensivos neonatales unidades
(NICUs), los bebés con menor peso al nacer y bebés que son menos maduros tienen una
mayor susceptibilidad a estos organismos.

Staphylococcus epidermidis , a coagulase-negative Staphylococcus , is increasingly seen


as a cause of nosocomial or late-onset sepsis, especially in the premature infant, in whom
it is considered the leading cause of late-onset infections. Staphylococcus epidermidis, un
coagulasa-negativos Staphylococcus, es cada vez más como una causa de infección
nosocomial o de aparición tardía sepsis, especialmente en el recién nacido prematuro, en
los cuales se considera la principal causa de aparición tardía infecciones. Its prevalence is
likely related to several intrinsic properties of the organism that allow it to readily adhere
to the plastic mediums found in intravascular catheters and intraventricular shunts. Su
prevalencia está probablemente relacionado con varias propiedades intrínsecas del
organismo que le permiten adherirse fácilmente a los medios de plástico se encuentran en
los catéteres intravasculares intraventricular y derivaciones. The bacterial capsule
polysaccharide adheres well to the plastic polymers of the catheters. La cápsula de
polisacáridos bacterianos se adhiere así a los polímeros de plástico de los catéteres. Also,
proteins found in the organism (AtlE and SSP-1) enhance attachment to the surface of the
catheter. Además, las proteínas se encuentran en el organismo (Atle y SSP-1) aumentar la
adhesión a la superficie del catéter. The adherence creates a capsule between microbe and
catheter, preventing C3 deposition and phagocytosis. La adhesión crea una cápsula entre
el microbio y el catéter, evitando la deposición de C3 y fagocitosis.

Biofilms are formed on indwelling catheters by the aggregation of organisms that have
multiplied with the protection provided by the adherence to the catheter. Biopelículas se
forman en los catéteres inhabitación de la agregación de los organismos que se han
multiplicado con la protección proporcionada por la adhesión al catéter. Slimes are
produced at the site from the extracellular material formed by the organism, which
provides a barrier to the host defense, as well as antibiotic action, making coagulase-
negative staphylococcal septicemia more difficult to treat. Slimes se producen en el lugar
de la material extracelular formado por el organismo, que proporciona una barrera para la
defensa de acogida, así como antibiótico de acción, haciendo coagulasa-negativos toxina
septicemia más difícil de tratar. The toxins formed by this organism have also been
associated with necrotizing enterocolitis. Las toxinas formado por este organismo
también se han asociado con la enterocolitis necrotizante. In addition to being a cause of
neonatal sepsis, the ubiquitous nature of coagulase-negative Staphylococcus as part of the
normal skin flora makes it a frequent contaminant of blood and cerebrospinal fluid (CSF)
cultures; therefore, a culture growing coagulase-negative Staphylococcus may represent a
contaminated sample rather than true coagulase-negative staphylococcal septicemia.
Además de ser una causa de sepsis neonatal, el carácter omnipresente de coagulasa-
negativos Staphylococcus como parte de la flora normal de la piel lo convierte en un
contaminante frecuente de la sangre y líquido cefalorraquídeo (LCR) las culturas, por lo
que una cultura cada vez más coagulasa-negativos Staphylococcus Mayo representan una
muestra contaminados en lugar de verdaderas coagulasa-negativos toxina septicemia.

In addition to the specific microbial factors mentioned above, a number of host factors
predispose the newborn infant to sepsis. Además de los factores específicos microbiana
se ha mencionado anteriormente, una serie de factores que predisponen a acoger al niño
recién nacido a la sepsis. These factors are especially prominent in the premature infant
and involve all levels of host defense, including cellular immunity, humoral immunity,
and barrier function. Estos factores son especialmente importantes en el recién nacido
prematuro e implicar a todos los niveles de defensa de acogida, incluidos la inmunidad
celular, inmunidad humoral, y la función barrera.

Cellular immunity Inmunidad celular

The neonatal neutrophil or polymorphonuclear (PMN) cell, which is vital for effective
killing of bacteria, is deficient in chemotaxis and killing capacity. El neonatal o
neutrófilos polimorfonucleares (PMN) de células, que es vital para la eficacia de
asesinato de bacterias, es deficiente en la quimiotaxis y la capacidad de matar. Decreased
adherence to the endothelial lining of blood vessels reduces their ability to marginate and
leave the intravascular space to migrate into the tissues. Disminución de la adhesión al
revestimiento del endotelio de los vasos sanguíneos reduce su capacidad de marginate y
dejar el espacio intravascular a emigrar en los tejidos. Once in the tissues, they may fail
to degranulate in response to chemotactic factors. Una vez en los tejidos, pueden dejar de
degranulate en respuesta a chemotactic factores. Also, neonatal PMNs are less
deformable; therefore, they are less able to move through the extracellular matrix of
tissues to reach the site of inflammation and infection. Por otra parte, neonatal PMNs son
menos deformables y, en consecuencia, son menos capaces de moverse a través de la
matriz extracelular de los tejidos para llegar al lugar de la inflamación e infección. The
limited ability of neonatal PMNs for phagocytosis and killing of bacteria is further
impaired when the infant is clinically ill. La limitada capacidad de PMNs neonatal para la
fagocitosis y muerte de las bacterias se altera cuando el bebé está clínicamente enfermos.
Lastly, neutrophil reserves are easily depleted because of the diminished response of the
bone marrow, especially in the premature infant. Por último, los neutrófilos son
fácilmente reservas agotadas a causa de la disminución de la respuesta de la médula ósea,
especialmente en el recién nacido prematuro.

Neonatal monocyte concentrations are at adult levels; however, macrophage chemotaxis


is impaired and continues to exhibit decreased function into early childhood. Neonatal
monocitos son las concentraciones en los niveles de adultos, sin embargo, los macrófagos
se perjudica la quimiotaxis y sigue exposición disminuyó en función de la primera
infancia. The absolute numbers of macrophages are decreased in the lungs and are likely
decreased in the liver and spleen, as well. El número absoluto de los macrófagos se
redujo en los pulmones y es probable disminución en el hígado y el bazo, también. The
chemotactic and bacteriocidal activity and the antigen presentation by these cells are also
not fully competent at birth. El chemotactic y bacteriocidal actividad y la presentación de
antígenos por estas células tampoco son plenamente competentes en el momento del
nacimiento. Cytokine production by macrophages is decreased, which may be associated
with a corresponding decrease in T-cell production. La producción de citocinas por los
macrófagos se redujo, lo que puede estar asociado con una correspondiente disminución
en las células T de producción.

Although T cells are found in early gestation in fetal circulation and increase in number
from birth to about age 6 months, these cells represent an immature population. Aunque
las células T se encuentran en la gestación temprana en la circulación fetal y aumento del
número desde el nacimiento hasta alrededor de edad de 6 meses, estas células representan
una población inmadura. These naive cells do not proliferate as readily as adult T cells
when activated and do not effectively produce the cytokines that assist with B-cell
stimulation and differentiation and granulocyte/monocyte proliferation. Estos ingenuos
células no proliferan como fácilmente como adultos cuando las células T activadas y no
producir eficazmente el citoquinas que ayudan a las células B-estimulación y la
diferenciación y de granulocitos / monocitos proliferación. A delay occurs in the
formation of antigen specific memory function following primary infection, and the
cytotoxic function of neonatal T cells is 50-100% as effective as adult T cells. Un retraso
se produce en la formación de antígenos específicos de la función de la memoria después
de la infección primaria, y la función citotóxica de las células T neonatal 50-100% es tan
efectivo como las células T de adultos. At birth, neonates are deficient in memory T cells.
Al nacer, los recién nacidos son deficientes en células T de memoria. As the neonate is
exposed to antigenic stimuli, the number of these memory T cells increases. A medida
que el recién nacido está expuesto a estímulos antigénicos, el número de estas células T
de memoria se incrementa.

Natural killer (NK) cells are found in small numbers in the peripheral blood of neonates.
Natural killer (NK), las células se encuentran en pequeñas cantidades en la sangre
periférica de los recién nacidos. These cells are also functionally immature in that they
produce far lower levels of interferon-gamma upon primary stimulation than do adult NK
cells. Estas células son también funcionalmente inmaduros en el sentido de que producen
muy por debajo de los niveles de interferón-gamma primaria a la estimulación que los
adultos, las células NK. This combination of findings may contribute to the severity of
HSV infections in the neonatal period. Esta combinación de hallazgos pueden contribuir
a la gravedad de las infecciones por HSV en el período neonatal.

Humoral immunity Inmunidad humoral

The fetus has some preformed immunoglobulin present, primarily acquired through
nonspecific placental transfer from the mother. El feto tiene algunas preformados
inmunoglobulina presente, principalmente adquiridos a través de la transferencia
placentaria inespecífico de la madre. Most of this transfer occurs in late gestation, such
that lower levels are found with increasing prematurity. La mayor parte de esta
transferencia se produce a finales de la gestación, de tal forma que los niveles inferiores
se encuentran con el aumento de la prematuridad. The neonate's ability to generate
immunoglobulin in response to antigenic stimulation is intact; however, the magnitude of
the response is initially decreased, rapidly rising with increasing postnatal age. El recién
nacido de la capacidad de generar inmunoglobulina en respuesta a la estimulación
antigénica está intacta, sin embargo, la magnitud de la respuesta se redujo inicialmente,
que aumentan rápidamente con el aumento de la edad postnatal.

The neonate is also capable of synthesizing immunoglobulin M (IgM) in utero at 10


weeks' 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. El recién nacido también es capaz de sintetizar la inmunoglobulina M (IgM)
en el útero a las 10 semanas de gestación, sin embargo, los niveles de IgM son
generalmente bajos en el momento del nacimiento, a menos que el niño estuvo expuesto a
un agente infeccioso durante el embarazo, estimulando así el aumento de la producción
de IgM. Immunoglobulin G (IgG) and immunoglobulin E (IgE) may be synthesized in
utero; however, only traces are found in cord blood at delivery, as most of the IgG is
acquired from the mother during late gestation. Inmunoglobulina G (IgG) y la
inmunoglobulina E (IgE) puede ser sintetizada en el útero, sin embargo, sólo los rastros
se encuentran en la sangre del cordón umbilical durante el parto, ya que la mayoría de la
IgG se adquiere de la madre durante la gestación tardía. The neonate may receive
immunoglobulin A (IgA) from breastfeeding but does not secrete IgA until 2-5 weeks
after birth. El recién nacido puede recibir la inmunoglobulina A (IgA) de la lactancia
materna pero no secretan IgA hasta 2-5 semanas después del nacimiento. Response to
bacterial polysaccharide antigen is diminished and remains so during the first 2 years of
life. La respuesta a antígenos polisacáridos bacterianos ha disminuido y sigue siendo así
durante los 2 primeros años de vida.

Complement protein production can be detected as early as 6 weeks' gestation; however,


the concentration of the various components of the complement system widely varies
among individual neonates. Complementar la producción de proteínas puede ser
detectado tan pronto como 6 semanas de gestación, sin embargo, la concentración de los
diversos componentes del sistema del complemento varía ampliamente entre los recién
nacidos. While some infants have had complement levels comparable with those in
adults, deficiencies appear to be greater in the alternative pathway than in the classic
pathway. Aunque algunos niños han tenido complementar los niveles comparables con
las de los adultos, las deficiencias parecen ser mayores en la vía alterna que en el clásico
itinerario. The terminal cytotoxic components of the complement cascade that leads to
killing of organisms, especially gram-negative bacteria, are deficient. La terminal
citotóxica componentes de la cascada del complemento que lleva a la muerte de los
organismos, especialmente bacterias gram-negativas, son deficientes. This deficiency is
more marked in preterm infants. Esta deficiencia es más marcada en los recién nacidos
prematuros. Mature complement activity is not reached until infants are aged 6-10
months. Pareja complementar la actividad no se alcanza hasta los bebés tienen edades 6-
10 meses. Neonatal sera have reduced opsonic efficiency against GBS, E coli , and S
pneumoniae because of decreased levels of fibronectin, a serum protein that assists with
neutrophil adherence and has opsonic properties. Suero neonatal han reducido la
eficiencia opsonic contra GBS, E coli, S pneumoniae y debido a la disminución de los
niveles de fibronectina, una proteína de suero que ayuda con la adhesión de neutrófilos y
ha opsonic propiedades.

Barrier function Función de barrera

The physical and chemical barriers to infection in the human body are present in the
newborn but are functionally deficient. La física y química barreras a la infección en el
cuerpo humano están presentes en el recién nacido, pero son funcionalmente deficientes.
Skin and mucus membranes are broken down easily in the premature infant. La piel y
membranas mucosas se desglosan fácilmente en el recién nacido prematuro. Neonates
who are ill and/or premature are additionally at risk because of the invasive procedures
that breach their physical barriers to infection. Los recién nacidos que están enfermos y /
o prematuro son, además, en situación de riesgo debido a los procedimientos invasivos
que el incumplimiento de sus barreras físicas a la infección. 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. Debido a la interdependencia de la respuesta
inmune, cada una de estas deficiencias de los distintos componentes de la actividad
inmune en el recién nacido conspirar para crear una situación peligrosa para el recién
nacido expuesto a amenazas infecciosas.

Frequency Frecuencia

United States Estados Unidos

The incidence of culture-proven sepsis is approximately 2 per 1000 live births. La


incidencia de la cultura de la sepsis probada es de aproximadamente 2 por cada 1000
nacidos vivos. Of the 7-13% of neonates who are evaluated for neonatal sepsis, only 3-
8% have culture-proven sepsis. De los 7-13% de los recién nacidos que son evaluados
para la sepsis neonatal, sólo el 3-8% han probado la cultura de la sepsis. The early signs
of sepsis in the newborn are nonspecific; therefore, many newborns undergo diagnostic
studies and the initiation of treatment before the presence of sepsis has been proven. Los
primeros signos de sepsis en el recién nacido son inespecíficos, por lo que muchos recién
nacidos se someten a estudios de diagnóstico y el inicio de tratamiento antes de la
presencia de sepsis se ha demostrado. Additionally, because the American Academy of
Pediatrics (AAP), American Academy of Obstetrics and Gynecology (AAOG), and
Centers for Disease Control and Prevention (CDC) all have recommended sepsis
screening and/or treatment for various risk factors related to GBS diseases, many
asymptomatic neonates now require evaluation. Además, debido a que la Academia
Americana de Pediatría (AAP), Academia Americana de Obstetricia y Ginecología
(AAOG), y los Centros para el Control y Prevención de Enfermedades (CDC) han
recomendado todas las sepsis detección y / o tratamiento de diversos factores de riesgo
relacionados con enfermedades GBS, muchos recién nacidos asintomáticos ahora
requieren evaluación. Because the mortality rate of untreated sepsis can be as high as
50%, most clinicians believe that the hazard of untreated sepsis is too great to wait for
confirmation based on positive culture results; therefore, most clinicians initiate treatment
while awaiting culture results. Debido a que la tasa de mortalidad de la sepsis no tratada
puede ser tan alta como 50%, la mayoría de los médicos creen que el riesgo de sepsis no
tratada es demasiado grande para esperar la confirmación sobre la base de la cultura
resultados positivos, por lo que la mayoría de los médicos iniciar el tratamiento a la
espera de los resultados de la cultura.

Mortality/Morbidity Mortalidad / morbilidad

The mortality rate in neonatal sepsis may be as high as 50% for infants who are not
treated. La tasa de mortalidad en la sepsis neonatal puede ser tan alto como el 50% de los
lactantes que no son tratados. Infection is a major cause of fatality during the first month
of life, contributing to 13-15% of all neonatal deaths. La infección es una de las
principales causas de mortalidad durante el primer mes de vida, contribuyendo al 13-15%
de todas las muertes neonatales. 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 in neonatal sepsis; it is responsible for 4% of all neonatal deaths. Neonatal
meningitis, una grave morbilidad de la sepsis neonatal, se produce en 2-4 casos por cada
10000 nacidos vivos y contribuye significativamente a la tasa de mortalidad en la sepsis
neonatal, es responsable de un 4% de todas las muertes neonatales. In the preterm infant,
inflammatory mediators associated with neonatal sepsis may contribute to brain injury
and poor neurodevelopmental outcomes. En los lactantes prematuros, los mediadores de
la inflamación asociada a la sepsis neonatal puede contribuir a la lesión cerebral y los
pobres resultados del neurodesarrollo.

Race Raza

Black infants have an increased incidence of GBS disease and late-onset sepsis. Negro
lactantes tienen una mayor incidencia de la enfermedad y GBS de aparición tardía sepsis.
This is observed even after controlling for risk factors of low birth weight and decreased
maternal age. Esto se observa incluso después de controlar factores de riesgo de bajo
peso al nacer y la disminución de la edad materna.

Sex Sexo

The incidence of bacterial sepsis and meningitis, especially for gram-negative enteric
bacilli, is higher in males than in females. La incidencia de sepsis bacteriana y la
meningitis, especialmente para los gram-negativos bacilos entéricos, es mayor en
hombres que en mujeres.

Age Edad

Premature infants have an increased incidence of sepsis. Recién nacidos prematuros


tienen una mayor incidencia de sepsis. The incidence of sepsis is significantly higher in
infants with very low birth weight (<1000 g), at 26 per 1000 live births, than in infants
with a birth weight of 1000-2000 g, at 8-9 per 1000 live births. La incidencia de sepsis es
significativamente mayor en los recién nacidos con muy bajo peso al nacer (<1000 g), a
26 por 1000 nacidos vivos, que en los lactantes con un peso al nacer de 1000-2000 g, a 8-
9 por cada 1000 nacidos vivos. The risk for death or meningitis from sepsis is higher in
infants with low birth weight than in full-term neonates. El riesgo de muerte o la
meningitis de sepsis es mayor en lactantes con bajo peso al nacer que en pleno plazo de
los recién nacidos.

CLINICAL CLÍNICA
Section 3 of 11 Sección 3 de 11

• Authors and Editors Autores y Editores


• Introduction Introducción
• Clinical Clínica
• Differentials Diferencias
• Workup Workup
• Treatment Tratamiento
• Medication Medicación
• Follow-up Seguimiento
• Miscellaneous Miscellaneous
• Multimedia Multimedia
• References Referencias

History Historia

The most common risk factors associated with early-onset neonatal sepsis include
maternal GBS colonization (especially if untreated during labor), premature rupture of
membranes (PROM), preterm rupture of membranes, prolonged rupture of membranes,
prematurity, maternal urinary tract infection, and chorioamnionitis. La mayoría de los
factores de riesgo comunes asociados con la aparición temprana de la sepsis neonatal
incluyen la colonización materna GBS (sobre todo si no reciben tratamiento durante el
parto), rotura prematura de membranas (PROM), ruptura prematura de membranas,
rotura prolongada de membranas, prematuridad, la maternidad infección del tracto
urinario, y corioamnionitis.

Risk factors also associated with early-onset neonatal sepsis include low Apgar score (<6
at 1 or 5 min), maternal fever greater than 38°C, maternal urinary tract infection, poor
prenatal care, poor maternal nutrition, low socioeconomic status, recurrent abortion,
maternal substance abuse, low birth weight, difficult delivery, birth asphyxia, meconium
staining, and congenital anomalies. Los factores de riesgo también se asocia con inicio
temprano de la sepsis neonatal incluyen puntuación de Apgar baja (<6 a 1 o 5 min),
fiebre materna superior a 38 ° C, la maternidad infección del tracto urinario, la mala
atención prenatal, la mala nutrición materna, nivel socioeconómico bajo, periódicos el
aborto, el abuso de sustancias materna, bajo peso al nacer, parto difícil, la asfixia,
manchas de meconio, y las anomalías congénitas. Risk factors implicated in neonatal
sepsis reflect the stress and illness of the fetus at delivery, as well as the hazardous
uterine environment surrounding the fetus before delivery. Los factores de riesgo
implicados en la sepsis neonatal reflejar el estrés y la enfermedad del feto durante el
parto, así como el medio ambiente uterino peligrosos que rodean el feto antes del parto.

Late onset sepsis is associated with the following risk factors: prematurity, central venous
catheterization (duration of >10 d), nasal cannula continuous positive airway pressure
use, H2 blocker/proton pump inhibitor use, and gastrointestinal tract pathology. Sepsis de
aparición tardía se asocia con los siguientes factores de riesgo: prematuridad, cateterismo
venoso central (duración de> 10 d), cánula nasal positiva continua en las vías
respiratorias uso de presión, bloqueador H2 / inhibidor de la bomba de protones uso, y
patología del tracto gastrointestinal.

An awareness of the many risk factors associated with neonatal sepsis prepares the
clinician for early identification and effective treatment, thereby reducing mortality and
morbidity. La conciencia de los muchos factores de riesgo asociados con la sepsis
neonatal se prepara para el clínico de diagnóstico precoz y un tratamiento eficaz,
reduciendo así la mortalidad y la morbilidad.

• Maternal GBS status GBS condición materna



o The most common etiology of neonatal bacterial sepsis is GBS. La
etiología más común de sepsis bacteriana neonatal es GBS. Nine serotypes
exist, and each is related to the polysaccharide capsule of the organism.
Nueve serotipos existen, y cada una está relacionada con la cápsula de
polisacárido del organismo. Types I, II, and III are commonly associated
with neonatal GBS infection. Los tipos I, II y III son comúnmente
asociados con la infección por SGB neonatal. The type III strain has been
shown to be most highly associated with CNS involvement in early-onset
infection, whereas type V has been associated with early-onset disease
without CNS involvement. El tipo III cepa ha demostrado ser más
asociados con afectación del sistema nervioso central a principios de
aparición de infección, mientras que el tipo V se ha asociado con la
aparición temprana de la enfermedad sin afectación del sistema nervioso
central.
o The GBS organism colonizes the maternal gastrointestinal tract and birth
canal. El GBS organismo coloniza el tracto gastrointestinal materna y el
nacimiento del canal. Approximately 30% of women have asymptomatic
GBS colonization during pregnancy. Aproximadamente el 30% de las
mujeres tienen colonización asintomática GBS durante el embarazo. GBS
is responsible for approximately 50,000 maternal infections per year in
women, but only 2 neonates per 1000 live births are infected. GBS es
responsable de aproximadamente 50000 infecciones maternas por año en
mujeres, pero sólo el 2 recién nacidos por cada 1000 nacidos vivos están
infectados. Women with heavy GBS colonization and culture results that
are chronically positive for GBS have the highest risk of perinatal
transmission. Las mujeres con GBS pesados colonización y la cultura que
los resultados son positivos para crónicamente GBS tienen el mayor riesgo
de transmisión perinatal. Also, heavy colonization at 23-26 weeks of
gestation is associated with prematurity and low birth weight. Por otra
parte, la colonización pesados en 23-26 semanas de gestación se asocia
con prematuridad y el bajo peso al nacer. Colonization at delivery is
associated with neonatal infection. La colonización en el momento del
parto se asocia con infección neonatal. Intrapartal chemoprophylaxis of
women with positive culture results for GBS has been shown to decrease
the transmission of the organism to the neonate during delivery. Intrapartal
quimioprofilaxis de las mujeres con resultados positivos para la cultura
GBS ha demostrado que disminuye la transmisión del organismo para el
recién nacido durante el parto.
• PROM may occur in response to an untreated infection of the urinary tract or birth
canal and is also associated with previous preterm delivery, uterine bleeding in
pregnancy, and heavy cigarette smoking during pregnancy. PROM puede ocurrir
en respuesta a una infección no tratada del tracto urinario o el nacimiento del
canal y también está asociada con parto prematuro previo, sangrado uterino
durante el embarazo, pesados y el hábito de fumar cigarrillos durante el embarazo.

o Rupture of membranes without other complications for more than 24
hours prior to delivery is associated with a 1% increase in the incidence of
neonatal sepsis; however, when chorioamnionitis accompanies the rupture
of membranes, the incidence of neonatal infection is quadrupled. Ruptura
de membranas sin otras complicaciones durante más de 24 horas antes del
parto se asocia con un aumento del 1% en la incidencia de sepsis neonatal,
sin embargo, cuando corioamnionitis acompaña a la ruptura de
membranas, la incidencia de infección neonatal se cuadruplicó.
o A recent multicenter study demonstrated that clinical chorioamnionitis and
maternal colonization with GBS are the most important predictors of
subsequent neonatal infection following PROM. Un reciente estudio
multicéntrico demostró que corioamnionitis clínica materna y la
colonización con SGB son los predictores más importantes de infección
neonatal posterior siguientes PROM.
o When membranes have ruptured prematurely before 37 weeks' gestational
age, a longer latent period precedes vaginal delivery, increasing the
likelihood that the infant will be infected. Cuando las membranas se han
roto prematuramente antes de las 37 semanas de edad gestacional, un largo
período de latencia precede a parto vaginal, lo que aumenta la
probabilidad de que el bebé se infecte. The relationship between duration
of membrane rupture and neonatal infection is inversely related to
gestational age. La relación entre la duración de ruptura de membrana y la
infección neonatal es inversamente proporcional a la edad gestacional.
Therefore, the more premature an infant, the longer the delay between
rupture of membranes and delivery, and the higher the likelihood of
neonatal sepsis. Por tanto, cuanto más prematuro un niño, cuanto más
largo sea el plazo transcurrido entre la ruptura de membranas y parto, y
cuanto más alto es el riesgo de sepsis neonatal.
o A study by Seaward et al found that more than 6 vaginal digital
examinations, which may occur as part of the evaluation for PROM, were
associated with neonatal infection even when considered separately from
the presence of chorioamnionitis. Un estudio realizado por Seaward et al
encontró que más de 6 exámenes vaginales digital, lo que puede ocurrir
como parte de la evaluación de PROM, se asociaron a infección neonatal
aun cuando se considere por separado de la presencia de corioamnionitis.
• Prematurity: The relationship between preterm PROM and neonatal sepsis has
already been described; however, other associations between prematurity and
neonatal sepsis increase the risk for premature infants. Prematuro: La relación
entre parto prematuro y PROM sepsis neonatal ya se ha descrito, sin embargo,
otras asociaciones entre la prematuridad y sepsis neonatal aumentar el riesgo para
los bebés prematuros.

o Preterm infants are more likely to require invasive procedures, such as
umbilical catheterization and intubation. Los recién nacidos prematuros
tienen más probabilidades de requerir procedimientos invasivos, como la
cateterización umbilical y la intubación.
o Prematurity is associated with infection from CMV, HSV, hepatitis B,
toxoplasmosis, Mycobacterium tuberculosis , Campylobacter fetus , and
Listeria species. La prematuridad está asociada con la infección de CMV,
HSV, la hepatitis B, toxoplasmosis, Mycobacterium tuberculosis,
Campylobacter fetus, y especies de Listeria.
o Intrauterine growth retardation and low birth weight are also observed in
CMV and toxoplasmosis infections. Retardo del crecimiento intrauterino y
bajo peso al nacer también se observó en el CMV y las infecciones de
toxoplasmosis.
o Premature infants have less immunologic ability to resist and combat
infection. Recién nacidos prematuros tienen menos capacidad
inmunológica para resistir y combatir la infección.
• Chorioamnionitis: The relationship between chorioamnionitis and other risk
variables is strong. Corioamnionitis: La relación entre corioamnionitis y otras
variables de riesgo es fuerte. Suspect chorioamnionitis in the presence of fetal
tachycardia, uterine tenderness, purulent amniotic fluid, elevated maternal WBC
count, and unexplained maternal temperature above 100.4°F (38°C). Sospechoso
corioamnionitis en la presencia de taquicardia fetal, uterina ternura, purulenta
líquido amniótico, elevación de WBC contar materna, y sin explicación materna
temperatura superior a 100,4 ° F (38 ° C).

Physical Física
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. Los
signos clínicos de sepsis neonatal son inespecíficos y se asocian con las características de
la causa y la respuesta del organismo a la invasión. 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. Estos signos clínicos inespecíficos del síndrome de sepsis temprana
también se asocian con otras enfermedades neonatales, tales como el síndrome de
dificultad respiratoria (SDR), trastornos metabólicos, hemorragia intracraneal, y una
traumática del parto. Given the nonspecific nature of these signs, providing treatment for
suspected neonatal sepsis while excluding other disease processes is prudent. Dado el
carácter inespecífico de los síntomas, el tratamiento para la sospecha de sepsis neonatal,
mientras que con exclusión de otros procesos de enfermedad es prudente.

• Congenital pneumonia and intrauterine infection: Inflammatory lesions are


observed postmortem in the lungs of infants with congenital and intrauterine
pneumonia. Neumonía congénita y la infección intrauterina: lesiones
inflamatorias postmortem se observan en los pulmones de los lactantes con
congénita intrauterina y la neumonía. 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. Esto puede no ser causada por
la acción de los microorganismos, pero sí puede ser causada por la aspiración de
líquido amniótico que contiene leucocitos materna y restos celulares. Tachypnea,
irregular respirations, moderate retracting, apnea, cyanosis, and grunting may be
observed. Taquipnea, irregular respirations, retracción moderada, apnea, cianosis,
y grunting puede observarse. Neonates with intrauterine pneumonia may also be
critically ill at birth and require high levels of ventilatory support. Los recién
nacidos con neumonía intrauterino también puede ser crítico en el momento del
nacimiento y que requieren altos niveles de soporte ventilatorio. The chest
radiograph may depict bilateral consolidation or pleural effusions. La radiografía
de tórax se presentan como si fuesen bilaterales consolidación o derrame pleural.
• 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. Neumonía congénita y la infección
intraparto: Los recién nacidos que se infectan durante el proceso de nacimiento
pueden adquirir a través de la neumonía por aspiración de los microorganismos
durante el proceso de entrega. The aspiration may lead to infection with
pulmonary changes, infiltration, and destruction of bronchopulmonary tissue. La
aspiración puede dar lugar a una infección pulmonar con cambios, la infiltración y
destrucción de tejido broncopulmonar. This damage is partly due to the
granulocytes' release of prostaglandins and leukotrienes. Este daño se debe en
parte a los granulocitos "liberación de prostaglandinas y leucotrienos. Fibrinous
exudation into the alveoli leads to inhibition of pulmonary surfactant function and
respiratory failure with an RDS-like presentation. Fibrinous exudado en los
alvéolos conduce a la inhibición de la función de surfactante pulmonar y la
insuficiencia respiratoria con un RDS-como presentación. Vascular congestion,
hemorrhage, and necrosis may occur. La congestión vascular, hemorragia,
necrosis y puede ocurrir lo contrario.

o Klebsiella species and S aureus are especially likely to generate severe
lung damage, producing microabscesses and empyema. Klebsiella
especies y S aureus son especialmente susceptibles de generar grave daño
pulmonar, la producción de micro y empiema.
o Early-onset GBS pneumonia has a particularly fulminant course, with
significant mortality in the first 48 hours of life. A principios de inicio
GBS tiene una neumonía fulminante curso en particular, con una
mortalidad significativa en las primeras 48 horas de vida.
o Infectious pneumonia is also characterized by pneumatoceles within the
pulmonary tissue. Infecciosas neumonía se caracteriza también por
pneumatoceles en el tejido pulmonar. Coughing, grunting, costal and
sternal retractions, nasal flaring, tachypnea and/or irregular respiration,
rales, decreased breath sounds, and cyanosis may be observed. Tos,
grunting, costales y esternales retracciones, quema nasal, taquipnea y / o
respiración irregular, rales, disminución de la respiración sonidos, cianosis
y puede observarse.
o Radiographic evaluation may demonstrate segmental or lobar atelectasis
or a diffuse reticulogranular pattern, much like what is observed in RDS.
Evaluación radiográfica puede demostrar segmentaria o lobar atelectasia o
un patrón reticulogranular difuso, al igual que lo observado en SDR.
o Pleural effusions may be observed in advanced disease. Derrame pleural
puede observarse en la enfermedad en estado avanzado.
• Postnatal infection: Postnatally acquired pneumonia may occur at any age.
Infección posnatal: después del neumonía adquirida puede ocurrir a cualquier
edad. Because these infectious agents exist in the environment, the likely cause
depends heavily on the infant's recent environment. Debido a que estos agentes
infecciosos existentes en el medio ambiente, la causa más probable depende en
gran medida en los últimos infantil del medio ambiente. 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. Si el bebé ha permanecido hospitalizado en una UCIN
medio ambiente, sobre todo con la intubación endotraqueal y ventilación
mecánica, los organismos pueden incluir Pseudomonas o Staphylococcus
especies. Additionally, these hospital-acquired organisms frequently demonstrate
multiple antibiotic resistances. Además, estos hospitales adquirido con frecuencia
los organismos demuestran múltiples resistencias a antibióticos. Therefore, the
choice of antibiotic agents in such cases requires knowledge of the likely
causative organisms and the local antibiotic-resistance patterns. Por lo tanto, la
elección de agentes antibióticos en estos casos requiere el conocimiento de la
probable causante y los organismos locales de resistencia a los antibióticos
patrones.
• Cardiac signs: In overwhelming sepsis, an initial early phase characterized by
pulmonary hypertension, decreased cardiac output, and hypoxemia may occur.
Signos cardíacos: En la sepsis abrumadora, una primera fase inicial se caracteriza
por hipertensión pulmonar, disminución del gasto cardíaco, hipoxemia y puede
ocurrir lo contrario. These cardiopulmonary disturbances may be due to the
activity of granulocyte-derived biochemical mediators, such as hydroxyl radicals
and thromboxane B2, an arachidonic acid metabolite. Estos disturbios
cardiopulmonar puede deberse a la actividad de los granulocitos y derivados
mediadores bioquímicos, como los radicales hidroxilo y de tromboxano B2, un
metabolito ácido araquidónico. These biochemical agents have vasoconstrictive
actions that result in pulmonary hypertension when released in pulmonary tissue.
Estos agentes bioquímicos han vasoconstrictive acciones que se traducen en la
hipertensión pulmonar cuando se libera en los tejidos pulmonares. A toxin derived
from the polysaccharide capsule of type III Streptococcus has also been shown to
cause pulmonary hypertension. Una toxina derivada de la cápsula de polisacáridos
de Streptococcus tipo III también ha sido demostrado que causa hipertensión
pulmonar. The early phase of pulmonary hypertension is followed by further
progressive decreases in cardiac output with bradycardia and systemic
hypotension. La fase inicial de la hipertensión pulmonar es seguido por una
disminución progresiva del gasto cardíaco con bradicardia y la hipotensión
sistémica. The infant manifests overt shock with pallor, poor capillary perfusion,
and edema. El infantil se manifiesta abierto choque con la palidez, mala perfusión
capilar, y edema. These late signs of shock are indicative of severe compromise
and are highly associated with mortality. Estos fines de signos de shock son
indicativos de una grave compromiso y están muy asociados con la mortalidad.
• Metabolic signs: Hypoglycemia, hyperglycemia, metabolic acidosis, and jaundice
all are metabolic signs that commonly accompany neonatal sepsis syndrome.
Señales metabólicas: hipoglucemia, hiperglucemia, acidosis metabólica, ictericia
y metabólicos son todos signos que comúnmente acompañan el síndrome de
sepsis neonatal. The infant has an increased glucose requirement because of
sepsis. El infantil tiene un aumento de glucosa requisito debido a sepsis. The
infant may also have impaired nutrition from a diminished energy intake. El bebé
también puede tener problemas de nutrición de la disminución de la ingesta
energética. Metabolic acidosis is due to a conversion to anaerobic metabolism
with the production of lactic acid. La acidosis metabólica se debe a una
conversión del metabolismo anaeróbico con la producción de ácido láctico. When
infants are hypothermic or they are not kept in a neutral thermal environment,
efforts to regulate body temperature can cause metabolic acidosis. Cuando los
bebés son hipotermia o que no se mantienen en un ambiente térmico neutro, los
esfuerzos para regular la temperatura corporal puede causar acidosis metabólica.
Jaundice occurs in response to decreased hepatic glucuronidation caused by both
hepatic dysfunction and increased erythrocyte destruction. La ictericia se produce
en respuesta a una disminución de la glucuronidación hepática causada por ambos
disfunción hepática y el aumento de eritrocitos destrucción.
• Neurologic signs: Meningitis is the common manifestation of infection of the
CNS. Signos neurológicos: La meningitis es común la manifestación de la
infección del SNC. 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, H influenzae , and species of
Pseudomonas, Klebsiella, Serratia, Enterobacter, and Proteus may cause
meningitis. Se asocia principalmente con GBS (36%), E coli (31%), y especies de
Listeria (5-10%), infecciones, aunque otros organismos tales como S
pneumoniae, S aureus, Staphylococcus epidermis, H influenzae, y especies de
Pseudomonas , Klebsiella, Serratia, Enterobacter, Proteus y puede causar
meningitis. Acute and chronic histologic features are associated with specific
organisms. Aguda y crónica características histológicas están asociadas con
organismos específicos.

o Ventriculitis
 Ventriculitis is the initiating event, with inflammation of the
ventricular surface. Ventriculitis es iniciar el evento, con
inflamación de la superficie ventricular. Exudative material usually
appears at the choroid plexus and is external to the plexus.
Exudativa material generalmente aparece en el plexo coroideo y es
ajena a la del plexo. Then, ependymitis occurs with disruption of
the ventricular lining and projections of glial tufts into the
ventricular lumen. A continuación, ependymitis ocurre con los
trastornos de la mucosa del ventrículo y proyecciones de bucles
gliales en el lumen ventricular. Glial bridges may develop by these
tufts and cause obstruction, particularly at the aqueduct of Sylvius.
Gliales pueden desarrollar puentes de estos bucles y causa la
obstrucción, en particular en el acueducto de Sylvius.
 The lateral ventricles may become multiloculated, which is similar
to forming abscesses. Los ventrículos laterales pueden llegar a ser
multiloculated, que es similar a la formación de abscesos.
Multiloculated ventricles can isolate organisms in an area, making
treatment more difficult. Multiloculated ventrículos pueden aislar
los organismos en una zona, haciendo más difícil el tratamiento.
 Meningitis is likely to arise at the choroid plexus and extend via
the ventricles through aqueducts into the subarachnoid space to
affect the cerebral and cerebellar surfaces. La meningitis es
probable que surjan en el plexo coroideo y ampliar a través de los
ventrículos a través de acueductos en el espacio subaracnoideo a
afectar a la cerebral y cerebeloso superficies. The high glycogen
content in the neonatal choroid plexus provides an excellent
medium for the bacteria. El alto contenido de glucógeno en el
plexo coroideo neonatal constituye un medio excelente para las
bacterias. When meningitis develops from ventriculitis, it
complicates effective treatment because achieving adequate
antibiotic levels in the cerebral ventricles is difficult. Cuando la
meningitis se desarrolla a partir de ventriculitis, se complica un
tratamiento eficaz, porque el logro de adecuados niveles de
antibióticos en los ventrículos cerebrales es difícil.
 When present, ventricular obstruction causes additional problems.
Cuando la actualidad, la obstrucción ventricular causa problemas
adicionales.
o Arachnoiditis is the next phase and is the hallmark of meningitis. La
aracnoiditis es la próxima etapa y es el sello distintivo de la meningitis.
The arachnoid is infiltrated with inflammatory cells that produce an
exudate that is thick over the base of the brain and more uniform over the
rest of the brain. El aracnoideo es infiltrados de células inflamatorias que
producen un exudado que es más gruesa la base del cerebro y más
uniforme durante el resto del cerebro. Early in the infection, the exudate is
primarily PMNs, bacteria, and macrophages. A principios de la infección,
el exudado es ante todo PMNs, bacterias y los macrófagos. Exudate is
prominent around the blood vessels and extends into the brain
parenchyma. Exudado es prominente alrededor de los vasos sanguíneos y
se extiende hasta el parénquima cerebral. 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. En la
segunda y tercera semanas de la infección, el porcentaje de PMNs
disminuye, la dominante son las células histiocitos, macrófagos y algunos
linfocitos y células plasmáticas. Exudate infiltration of cranial roots 3-8
occurs. Exudado infiltración de raíces craneal se produce 3-8. After this
period, the exudate decreases. Después de este período, el exudado
disminuye. Thick strands of collagen form, and arachnoid fibrosis occurs,
which is responsible for obstruction. Líneas gruesas de colágeno, y
aracnoideo fibrosis ocurre, que es responsable de la obstrucción.
Hydrocephalus results. Hidrocefalia resultados. Early-onset GBS
meningitis is characterized by much less arachnoiditis than late-onset GBS
meningitis. A principios GBS de aparición de meningitis se caracteriza por
mucho menos que aracnoiditis de aparición tardía GBS meningitis.
o Vasculitis extends the inflammation of the arachnoid and ventricles to the
blood vessels surrounding the brain. Vasculitis se extiende la inflamación
de la aracnoideo y ventrículos a los vasos sanguíneos que rodean el
cerebro. Occlusion of the arteries rarely occurs; however, venous
involvement is more severe. Oclusión de las arterias rara vez ocurre, sin
embargo, afectación venosa es más severa. Phlebitis may be accompanied
with thrombosis and complete occlusion. Flebitis puede ir acompañada
con trombosis y oclusión completa. Multiple fibrin thrombi are especially
associated with hemorrhagic infarction. Múltiples fibrina sobre todo de
trombosis asociado con infarto hemorrágico. This vascular involvement is
apparent within the first days of meningitis and becomes more prominent
during the second and third weeks. Esta participación vascular es evidente
en los primeros días de la meningitis y se hace más prominente durante la
segunda y tercera semanas.
o Cerebral edema may occur during the acute state of meningitis. Edema
cerebral puede ocurrir durante el estado agudo de meningitis. The edema
may be severe enough to greatly diminish the ventricular lumen. El edema
puede ser lo suficientemente graves como para disminuir en gran medida
el lumen ventricular. The cause is unknown, but it is likely related to
vasculitis and the increased permeability of blood vessels. La causa es
desconocida, pero es probable relacionados con vasculitis y la mayor
permeabilidad de los vasos sanguíneos. It may also be related to
cytotoxins of microbial origin. También puede estar relacionado con
cytotoxins de origen microbiano. Herniation of edematous supratentorial
structures does not generally occur in neonates because of the cranium's
distensibility. Hernia de edematous supratentorial estructuras no suele
ocurrir en los recién nacidos a causa del cráneo del distensibility.
o Infarction is a prominent and serious feature of neonatal meningitis.
Infarto es un grave y característica de la meningitis neonatal. It occurs in
30% of infants who die. Ocurre en el 30% de los lactantes que mueren.
Lesions occur because of multiple venous occlusions, which are frequently
hemorrhagic. Las lesiones se producen a causa de múltiples oclusiones
venosas, que son con frecuencia hemorrágico. 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. El loci de infartos son la
mayoría de las veces en la corteza cerebral y sustancia blanca subyacente,
pero también puede ser subependymal dentro de la materia blanca
profunda. Neuronal loss occurs, especially in the cerebral cortex, and
periventricular leukomalacia may subsequently appear in areas of neuronal
cell death. Pérdida neuronal se produce, especialmente en la corteza
cerebral, y periventricular leukomalacia podrá posteriormente aparecen en
las zonas de muerte celular neuronal.
o Meningitis due to early-onset neonatal sepsis usually occurs within 24-48
hours and is dominated by nonneural signs. La meningitis debido a la
temprana aparición de sepsis neonatal por lo general ocurre dentro de 24-
48 horas y está dominado por nonneural signos. Neurologic signs may
include stupor and irritability. Signos neurológicos pueden incluir estupor
e irritabilidad. Overt signs of meningitis occur in only 30% of cases.
Signos de meningitis ocurren en sólo el 30% de los casos. Even culture-
proven meningitis may not demonstrate white cell changes in the CSF.
Incluso la cultura demostrado la meningitis no pueden demostrar cambios
de células blancas en el MCA. Meningitis due to late-onset disease is more
likely to demonstrate neurologic signs (80-90%). La meningitis debido a
la tardía aparición de la enfermedad es más probable que demostrar signos
neurológicos (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.
In the neonate, many of these physical examination findings are subtle or
nonapparent.
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 culture results. 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 may also have decreased tone, lethargy, and poor
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/µL in
the first 10 days of life. Thrombocytopenia with counts less than 100,000
may occur in neonatal sepsis in response to the cellular products of the
microorganisms. These cellular products cause platelet clumping and
adherence leading to platelet destruction. Thrombocytopenia may be a
presenting sign and 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 in neonatal sepsis after
3 days. Because of the myriad of causes of thrombocytopenia and its late
appearance in neonatal sepsis, the presence of thrombocytopenia does not
aid the diagnosis of neonatal sepsis.
o Although WBC counts and ratios are more sensitive for determining sepsis
than platelet counts, they remain very nonspecific and have low positive
predictive value. 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 or
several other factors. A differential may be of 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, limiting the positive predictive value of these ratios;
therefore, when diagnosing sepsis, the elevated I/T ratio should be used in
combination with other signs.
o Disseminated intravascular coagulation (DIC) can occur in infected
infants. Predicting which infants will be affected at the onset of sepsis is
difficult. Affected infants show abnormalities in prothrombin time (PT),
partial thromboplastin time (PTT), and fibrinogen and D-dimer levels and
may need blood products, including fresh frozen plasma (FFP) and
cryoprecipitate, to replace coagulation factors consumed in association
with DIC. If infants show signs consistent with impaired coagulation,
including gastric blood, bleeding intravenous or laboratory puncture sites,
or other bleeding, evaluating coagulation by checking these values is
important.
• Gastrointestinal signs: The intestinal tract can be colonized by organisms in utero
or at delivery by swallowing infected amniotic fluid. The immunologic defenses
of the intestinal tract are not mature, especially in the preterm infant.
Lymphocytes proliferate in the intestines in response to mitogen stimulation;
however, this proliferation is not fully effective in responding to a microorganism
because antibody response and cytokine formation is immature until
approximately 46 weeks. Necrotizing enterocolitis has been associated with the
presence of a number of species of bacteria in the immature intestine, and
bacterial overgrowth of these organisms in the neonatal lumen is a component of
the multifactorial pathophysiology of NEC.

DIFFERENTIALS
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Acidosis, Metabolic
Bowel Obstruction in the Newborn
Coarctation of the Aorta
Congenital Diaphragmatic Hernia
Congenital Lung Malformations
Congenital Pneumonia
Heart Failure, Congestive
Hemolytic Disease of Newborn
Hemorrhagic Disease of Newborn
Hypoglycemia La hipoglucemia
Hypoplastic Left Heart Syndrome
Meconium Aspiration Syndrome
Meningitis, Bacterial
Necrotizing Enterocolitis
Osteomyelitis
Pericarditis, Bacterial
Pulmonary Atresia With Intact Ventricular Septum
Pulmonary Hypertension, Persistent-Newborn
Pulmonary Hypoplasia
Pulmonary Sequestration
Respiratory Distress Syndrome
Single Ventricle
Urinary Tract Infection

WORKUP
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Lab Studies

• Blood, CSF, and urine cultures



o Aerobic cultures are appropriate for most of the bacterial etiologies
associated with neonatal sepsis; however, anaerobic cultures are indicated
in neonates with abscess formation, processes with bowel involvement,
massive hemolysis, and refractory pneumonia.
o A Gram stain provides early identification of the gram-negative or gram-
positive status of the organism for preliminary identification.
o Bacterial culture results 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. Single-site blood cultures are
effective in isolating bacteria in the neonate with sepsis.
o Urine cultures are most appropriate when investigating late-onset sepsis.
o Blood and CSF cultures are appropriate for early- and late-onset sepsis.
o Because of the low incidence of meningitis in the newborn infant with
negative culture results, clinicians may elect to culture the CSF of only
those infants with documented or presumed sepsis. However, recent data
in large numbers of patients show a 38% rate of culture-positive
meningitis in neonates with negative blood culture results and suspected
sepsis.
• A CBC count 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 count may be useful in aiding the differentiation of sepsis
syndrome from nonspecific abnormalities due to the stress of delivery.

o The platelet count in the healthy newborn is rarely less than 100,000/µL in
the first 10 days of life. Thrombocytopenia with counts less than 100,000
may occur in neonatal sepsis. 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.
o WBC counts and ratios may be helpful in determining sepsis, although
normal WBC counts may be observed in as many as 50% of culture-
proven sepsis cases. WBC counts and ratios remain very nonspecific and
have low positive predictive value. Infants who are not infected may also
have abnormal WBC counts related to the stress of delivery. A differential
may be of use in diagnosing sepsis; however, these counts are laboratory
technician–dependent. 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.
o 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, limiting the
positive predictive value of these ratios; 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 count
(predominately PMNs), an elevated protein level, a depressed glucose level, and
positive culture results. 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 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 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 elevated
at some point 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 the infection has been present over a period of
time.
• Current evidence on the use of infection markers such as CD11b, CD64,
interleukin-6, and interleukin-8 for evaluation of sepsis in neonates shows that
they may be helpful as adjunctive markers. Serial measurements and use of
combinations of tests may improve their value. However, at this time, these tests
should not be used alone to determine the need for antibiotic therapy. In some
cases, they may prove useful in determining when to stop antibiotic therapy.

Imaging Studies

• Chest radiographs may depict segmental or lobar infiltrate but they more
commonly reveal a diffuse, fine, reticulogranular pattern, much like what is
observed in RDS. Pleural effusions may also be observed.
• A CT scan may be needed late in the course of complex neonatal meningitis to
document obstructive hydrocephalus, the site where the obstruction is occurring,
and the occurrence of major infarctions or abscesses. Signs of chronic disease,
such as ventricular dilation, multicystic encephalomalacia, and atrophy, may also
be demonstrated on CT scan.
• Head ultrasonograms in neonates with meningitis may 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 sit with support. The insertion site
should be between L3 and L4 in order to be below the lowest point of the spinal
cord in infants. If positive culture results are demonstrated, a follow-up lumbar
puncture is often performed within 24-36 hours after antibiotic therapy is initiated
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.

TREATMENT
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Medical Care

When neonatal sepsis is suspected, treatment should be initiated immediately because of


the neonate's relative immunosuppression. Begin antibiotics as soon as diagnostic tests
are performed. Additional therapies have been investigated for the treatment of neonatal
sepsis; however, no substantial clinical trials have shown that these treatments are
beneficial. These additional therapies include granulocyte transfusion, intravenous
immune globulin (IVIG) replacement, exchange transfusion, and the use of recombinant
cytokines.
• In the United States and Canada, the current approach to treat early-onset neonatal
sepsis syndrome includes combined IV aminoglycoside and expanded-spectrum
penicillin antibiotic therapy. This provides coverage for gram-positive organisms,
especially GBS, and gram-negative bacteria, such as E coli . The specific
antibiotics to be used are chosen on the basis of maternal history and prevalent
trends of organism colonization and antibiotic susceptibility in individual
nurseries.

o If an infection appears to be nosocomial, antibiotic coverage should be
directed 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. Use ceftriaxone with
caution in infants with hyperbilirubinemia because it displaces bilirubin
from serum albumin. Resistance and sensitivities for the organism isolated
from cultures are used to select themosteffectivedrug.
o Aminoglycosides and vancomycin both have the potential to produce
ototoxicity and nephrotoxicity and should therefore be used with caution.
The serum drug level is assessed 48 hours after starting treatment to
determine if levels are within the therapeutic range. The drug dosage or
interval may need to be changed to optimize the drug serum levels. A
serum level may also be warranted if the infant's clinical condition has not
improved to ensure that a therapeutic level has been reached. In addition,
renal function and hearing screening should be considered after
completion of the therapeutic course to determine if any short- or long-
range toxic effects of these drugs have occurred.
o If culture results are negative but the infant has significant risk or clinical
signs for sepsis, the clinician must decide whether to provide continued
treatment. Three days of negative culture results should provide
confidence in the data; however, a small number of infants documented to
have had sepsis by postmortem examination had negative culture results
during their initial sepsis evaluation.
o Management is further complicated if the mother received antibiotic
therapy before delivery, especially if she received the therapy within
several hours of delivery. This may result in negative culture results in an
infant who actually has bacteremia or sepsis. With this in mind, the need
for continued therapy should be based not on a single test, but on a review
of all diagnostic data, including culture results, maternal and intrapartal
risk factors, CSF results, the CBC count and differential radiographs, and
the clinical picture. Treatment for 7-10 days may be appropriate, even if
the infant has negative culture results at 48 hours.
o Infants with bacterial meningitis often require different dosages of
antibiotics and longer courses of treatment. These infants may also require
a different drug that has better penetration of the blood-brain barrier to
achieve therapeutic drug concentrations in the CSF. 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.
• IVIG infusion has been studied as a possible therapy 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 in neonatal populations. At present, the data do not support
the routine use of IVIG in neonatal sepsis.
• 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, platelets, and coagulation
studies 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.

If an abscess is present, surgical drainage may be necessary because intravenous


antibiotic therapy cannot adequately penetrate an abscess and because antibiotic
treatment alone is ineffective.

Consultations

• Infectious disease consultation is useful, especially if the infant is not responding


to treatment, is infected with an unusual organism, or has had a complicated
clinical course.
• If neonatal meningitis is identified, consultation with a pediatric neurologist may
be necessary for assistance with outpatient follow-up of neurologic sequelae.
Inpatient consultation may be necessary if meningitis is complicated by seizures.
• Consultation with a pediatric pharmacologist may be helpful for advice on the
most appropriate antibiotic or dosage to use should changes prove necessary
because of inadequate or toxic drug levels obtained with therapeutic monitoring.

Diet

The neonate may need to be given nothing by mouth (NPO) during the first days of
treatment because of gastrointestinal symptoms, feeding intolerance, 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. For most infants, breast milk is
the enteral diet recommended by the AAP.

Activity

The infant with temperature instability needs thermoregulatory support with a radiant
warmer or incubator. Once the infant is stable from a cardiopulmonary standpoint,
parental contact is important.
MEDICATION
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Some of the antibiotics commonly used to treat neonatal sepsis syndrome are ampicillin,
gentamicin, cefotaxime, vancomycin, metronidazole, erythromycin, and piperacillin. The
choice of antibiotic agents should be based on the specific organisms associated with
sepsis, sensitivities of the bacterial agent, and prevalent nosocomial infection trends in
the nursery. Viral infections such as herpes and fungal infections can masquerade as
bacterial infections.

Drug Category: Antibiotics


Empiric antimicrobial therapy must be comprehensive and should cover all likely
pathogens in the context of the clinical setting. Neonatal doses for antibiotics may be
based on several variables (eg, postmenstrual age [PMA], postnatal age, weight).

Ampicillin (Marcillin, Omnipen, Polycillin,


Drug Name
Principen, Totacillin)
A beta-lactam antibiotic that is bacteriocidal
for susceptible organisms, such as GBS,
Listeria , non–penicillinase-producing
Description Staphylococcus , some strains of H influenzae ,
Descripción and meningococci. Recent publications
indicate ampicillin (in combination with
gentamicin) is the first-line therapy for
suspected sepsis in the newborn.
< 29 weeks PMA and 0-28 days: 50-100
mg/kg/dose IV/IM q12h
< 29 weeks PMA and >28 days: 50-100
mg/kg/dose IV/IM q8h
30-36 weeks PMA and 0-14 days: 50-100
mg/kg/dose IV/IM q12h
30-36 weeks PMA and >14 days: 50-100
mg/kg/dose IV/IM q8h
Pediatric Dose
37-44 weeks PMA and 0-7 days: 50-100
mg/kg/dose IV/IM q12h
37-44 weeks PMA and > 7 days: 50-100
mg/kg/dose IV/IM q8h
> 45 weeks PMA: 50-100 mg/kg/dose IV/IM
q6h
Higher dosage may be used with meningitis
and GBS
Contraindications Documented hypersensitivity
Aminoglycosides reduce effectiveness when
coadministered; probenecid and disulfiram
Interactions
elevate levels; allopurinol decreases effects
and has additive effects on ampicillin rash
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
Adjust dose in renal failure; evaluate rash and
Precautions
differentiate from hypersensitivity reaction
Drug Name Gentamicin (Garamycin)
Description An aminoglycoside that is bacteriocidal for
Descripción susceptible gram-negative organisms, such as
E coli and Pseudomonas, Proteus, and
Serratia species. Effective in combination with
ampicillin for GBS and Enterococcus . Recent
publications indicate gentamicin (in
combination with ampicillin) is the first-line
therapy for suspected sepsis in the newborn.
< 29 weeks PMA and 0-7 days: 5 mg/kg/dose
IV/IM q48h
< 29 weeks PMA and 8-28 days: 4 mg/kg/dose
IV/IM q36h
< 29 weeks PMA and >29 days: 4 mg/kg/dose
IV/IM q24h
Pediatric Dose 30-34 weeks PMA and 0-7 days: 4.5
mg/kg/dose IV/IM q36h
30-34 weeks PMA and > 7 days: 4 mg/kg/dose
IV/IM q24h
> 35 weeks PMA: 4 mg/kg/dose IV/IM q24h
IV dosage preferred; IM may be used if IV
access is difficult
Documented hypersensitivity;
Contraindications a relative contraindication is severe renal
disease
Coadministration with other aminoglycosides,
cephalosporins, penicillins, indomethacin, and
amphotericin B may increase nephrotoxicity;
because aminoglycosides enhance effects of
neuromuscular blocking agents prolonged
Interactions
respiratory depression may occur;
coadministration with loop diuretics may
increase auditory toxicity of aminoglycosides;
possible irreversible hearing loss of varying
degrees may occur (monitor levels regularly)
Pregnancy D - Unsafe in pregnancy
Neonates with renal immaturity, renal disease,
auditory impairment, vestibular impairment,
hypocalcemia, or who are receiving ECMO;
Precautions monitoring levels is important to avoid
possible renal and auditory damage (normal
peaks 5-12 mcg/mL, normal troughs 0.5-1
mcg/mL)
Drug Name Cefotaxime (Claforan)
Description Third-generation cephalosporin with excellent
Descripción in vitro activity against GBS and E coli and
other gram-negative enteric bacilli. Has good
serum and CSF concentrations. Concern exists
about the emergence of drug-resistant gram-
negative bacteria at a more rapid rate than with
traditional penicillin and aminoglycoside
coverage. Ineffective against Listeria and
enterococci. Use in combination with
ampicillin. In most recent publications, this is
not a first-line agent for neonatal sepsis
because of its association with increased
mortality.
< 29 weeks PMA and 0-28 days: 50
mg/kg/dose IV/IM q12h
< 29 weeks PMA and >28 days: 50
mg/kg/dose IV/IM q8h
30-36 weeks PMA and 0-14 days: 50
mg/kg/dose IV/IM q12h
Pediatric Dose 30-36 weeks PMA and >14 days: 50
mg/kg/dose IV/IM q8h
37-44 weeks PMA and 0-7 days: 50
mg/kg/dose IV/IM q12h
37-44 weeks PMA and > 7 days: 50
mg/kg/dose IV/IM q8h
> 45 weeks PMA: 50 mg/kg/dose IV/IM q6h
Contraindications Documented hypersensitivity
Probenecid decreases renal elimination of
cefotaxime and prolongs therapeutic half-life;
Interactions
coadministration with furosemide and
aminoglycosides may increase nephrotoxicity
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
History of penicillin hypersensitivity, impaired
Precautions
renal function, or history of colitis
Drug Name Vancomycin (Lyphocin, Vancocin, Vancoled)
Bacteriocidal agent against most aerobic and
anaerobic gram-positive cocci and bacilli.
Especially important in the treatment of
MRSA. Recommended therapy when
Description
coagulase-negative staphylococcal sepsis is
Descripción
suspected. Therapy with rifampin, gentamicin,
or cephalothin may be required with
endocarditis or CSF shunt infection by
coagulase-negative staphylococcus.
Pediatric Dose < 29 weeks PMA and 0-14 days: 10-15
mg/kg/dose IV/IM q18h
< 29 weeks PMA and >14 days: 10-15
mg/kg/dose IV/IM q12h
30-36 weeks PMA and 0-14 days: 10-15
mg/kg/dose IV/IM q12h
30-36 weeks PMA and >14 days: 10-15
mg/kg/dose IV/IM q8h
37-44 weeks PMA and 0-7 days: 10-15
mg/kg/dose IV/IM q12h
37-44 weeks PMA and > 7 days: 10-15
mg/kg/dose IV/IM q8h
> 45 weeks PMA: 10-15 mg/kg/dose IV/IM
q6h
Use higher dosing range in meningitis
Documented hypersensitivity; hearing
Contraindications
impairment
Concurrent ototoxic or nephrotoxic drugs (eg,
aminoglycosides, loop diuretics); erythema,
histaminelike flushing and anaphylactic
reactions may occur when administered with
Interactions
anesthetic agents; effects in neuromuscular
blockade may be enhanced when
coadministered with nondepolarizing muscle
relaxants
C - Safety for use during pregnancy has not
Pregnancy
been established.
Administer over 60 min to avoid possibility of
histamine reaction, which is characterized by a
Precautions rash; levels greater than therapeutic trough (5-
10 mg/dL) may be associated with ototoxicity;
caution in renal failure or neutropenia
Drug Name Metronidazole (Flagyl)
Antimicrobial that has shown effectiveness
against anaerobic infections, especially
Description
Bacteroides fragilis meningitis, ventriculitis,
Descripción
and endocarditis. Also useful in treatment of
infections caused by T vaginalis .
Pediatric Dose Loading dose: 15 mg/kg PO/IV
Maintenance dose:
< 29 weeks PMA and 0-28 days: 7.5
mg/kg/dose IV/PO q48h
< 29 weeks PMA and >28 days: 7.5
mg/kg/dose IV/PO q24h
30-36 weeks PMA and 0-14 days: 7.5
mg/kg/dose IV/PO q24h
30-36 weeks PMA and >14 days: 7.5
mg/kg/dose IV/PO q12h
37-44 weeks PMA and 0-7 days: 7.5
mg/kg/dose IV/PO q24h
37-44 weeks PMA and > 7 days: 7.5
mg/kg/dose IV/PO q12h
> 45 weeks PMA: 7.5 mg/kg/dose IV/PO q8h
Documented hypersensitivity; first trimester of
Contraindications
pregnancy
May increase levels of phenytoin;
phenobarbital and rifampin may increase
Interactions metabolism of metronidazole; when
administered with food, a decrease and/or
delay in reaching peak levels may occur
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
Liver impairment, blood dyscrasias, CNS
disease; inject with caution in patients
Precautions receiving corticosteroids or patients
predisposed to edema because the drug
molecule contains sodium
Drug Name Erythromycin (E-Mycin, Erythrocin)
Macrolide antimicrobial agent that is primarily
bacteriostatic and is active against most gram-
Description positive bacteria, such as Neisseria species,
Descripción Mycoplasma pneumoniae, Ureaplasma
urealyticum, and Chlamydia trachomatis . Not
well concentrated in the CSF.
<7 days and <2000 g: 5 mg/kg/dose PO/IV/IM
q12h
<7 days and >2000 g: 5 mg/kg/dose PO/IV/IM
q8h
Pediatric Dose
> 7 days and <1200 g: 5 mg/kg PO/IV/IM
q12h
> 7 days and >1200 g: 10 mg/kg PO/IV/IM
q8h
Documented hypersensitivity; hepatic
Contraindications
impairment
CYP1A2 and CYP3A4 inhibitor;
coadministration may increase toxicity of
Interactions theophylline, digoxin, carbamazepine, and
cyclosporine; may potentiate anticoagulant
effects of warfarin
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
Monitor parenteral administration closely
because of associated tissue damage; caution
in liver disease; estolate formulation may
Precautions cause cholestatic jaundice; GI adverse effects
are common (give doses pc); discontinue use if
nausea, vomiting, malaise, abdominal colic, or
fever occur
Drug Name Piperacillin (Pipracil)
An acylampicillin with excellent activity
against Pseudomonas aeruginosa . Effective
Description against Klebsiella pneumonia, Proteus
Descripción mirabilis, B fragilis, S marcescens, and many
strains of Enterobacter . Administer in
combination with an aminoglycoside.
<7 days and 1200-2000 g: 75 mg/kg IV/IM
q12h
<7 days and >2000 g: 75 mg/kg IV/IM q8h
Pediatric Dose > 7 days and 1200-2000 g: 75 mg/kg IV/IM
q8h
> 7 days and >2000 g: 75 mg/kg/dose IV/IM
q6h
Contraindications Documented hypersensitivity
Synergic and antagonistic interactions
observed when combined with various
cephalosporins; piperacillin at high
Interactions
concentrations may physically inactivate
aminoglycosides; coadministration with
aminoglycosides has synergistic effects
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
Dosage modification required in patients with
Precautions
impaired renal function

Drug Category: Antivirals

A viral infection, such as HSV, may masquerade as bacterial sepsis. At the onset of the
infection, treatment must be initiated promptly to effectively inhibit the replicating virus.

Drug Name Acyclovir (Zovirax)


Description Used for treatment of mucosal, cutaneous, and
Descripción systemic HSV-1 and HSV-2 infections.
20 mg/kg/dose q8h IV; may increase dosing
interval in patients <34 weeks PMA or in
patients with significant hepatic or renal
Pediatric Dose failure
Treatment duration for localized infections is
14 d; for disseminated disease or CNS
infections, treat for 21 d
Contraindications Documented hypersensitivity
Concomitant use of probenecid or zidovudine
Interactions prolongs half-life and increases CNS toxicity
of acyclovir
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
Renal disease, dehydration, underlying
neurologic disease, patients with hypoxia and
hepatic or electrolyte abnormalities
Precautions
Periodic monitoring of CBC count is indicated

Follow renal and hepatic function


Drug Name Zidovudine (Retrovir, ZDV, AZT)
Description A thymidine analog that inhibits viral
Descripción replication. Used to treat patients with HIV.
< 29 weeks PMA and 0-28 days: 1.5
mg/kg/dose IV q12h or 2 mg/kg/dose PO q12h

< 29 weeks PMA and >28 days: 1.5


mg/kg/dose IV q8h or 2 mg/kg/dose PO q8h
30-34 weeks PMA and 0-14 days: 1.5
Pediatric Dose
mg/kg/dose IV q12h or 2 mg/kg/dose PO q12h

30-34 weeks PMA and >14 days: 1.5


mg/kg/dose IV q8h or 2 mg/kg/dose PO q8h
> 35 weeks PMA: 1.5 mg/kg/dose IV q6h or 2
mg/kg/dose PO q6h
Contraindications Documented hypersensitivity
Acyclovir, ganciclovir, or coadministration
with drugs that inhibit glucuronidation (eg,
Interactions
acetaminophen, cimetidine, indomethacin)
may increase toxicity
C - Safety for use during pregnancy has not
Pregnancy
been established.
Precautions Do not administer IM; bone marrow
compromise or impaired renal function; rare
severe lactic acidosis and hepatomegaly with
steatosis, including fatal cases, reported

Drug Category: Antifungals

Fungal infections can masquerade as bacterial infections and/or may appear at the end of
prolonged antibacterial therapy. Their mechanism of action may involve an alteration of
RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to
the fungal cell.

Drug Name Fluconazole (Diflucan)


Used to treat susceptible fungal infections,
including oropharyngeal, esophageal, and
vaginal candidiasis. Also used for systemic
candidal infections and cryptococcal
Description meningitis. Fungistatic activity. Synthetic oral
Descripción antifungal (broad-spectrum bistriazole) that
selectively inhibits fungal CYP450 and sterol
C-14 alpha-demethylation, which prevents
conversion of lanosterol to ergosterol, thereby
disrupting cellular membranes.
Systemic infections and meningitis:
Loading dose: 12 mg/kg IV
Maintenance dose:
< 29 weeks PMA and 0-14 days: 6 mg/kg/dose
IV q72h
< 29 weeks PMA and >14 days: 6 mg/kg/dose
IV q48h
30-36 weeks PMA and 0-14 days: 6
mg/kg/dose IV q48h
30-36 weeks PMA and >14 days: 6
Pediatric Dose
mg/kg/dose IV q24h
37-44 weeks PMA and 0-7 days: 6 mg/kg/dose
IV q48h
37-44 weeks PMA and > 7 days: 6 mg/kg/dose
IV q24h
> 45 weeks PMA: 6 mg/kg/dose IV q24h
Prophylaxis for ELBW infants in the NICU: 3
mg/kg/dose IV 2 times/wk
Thrush: 6 mg/kg PO on day 1, then 3
mg/kg/dose PO q24h
Contraindications Documented hypersensitivity
Interactions CYP2C19 and CYP3A4 inhibitor; levels may
increase with hydrochlorothiazide; long-term
coadministration of rifampin may decrease
levels; may decrease phenytoin clearance; may
increase concentrations of theophylline,
tolbutamide, glyburide, and glipizide; may
increase effects of anticoagulants; may
increase cyclosporine concentrations
C - Safety for use during pregnancy has not
Pregnancy
been established.
Perform periodic liver function and renal
Precautions function tests; dosage modification required in
patients with impaired renal function
Drug Name Amphotericin B (Amphocin, Fungizone)
Used to treat severe systemic infections and
meningitis caused by susceptible fungi, such as
Candida and Aspergillus species, H
capsulatum, and C neoformans . Polyene
Description
antibiotic produced by a strain of S nodosus;
Descripción
can be fungistatic or fungicidal. Binds to
sterols, such as ergosterol, in fungal cell
membrane, causing intracellular components
to leak and subsequent fungal cell death.
Pediatric Dose 0.5-1 mg/kg IV q24h infused over 2-6 h
Contraindications Documented hypersensitivity
Coadministration with other nephrotoxic drugs
(eg, antineoplastic agents, aminoglycosides,
vancomycin, cyclosporine) may enhance renal
Interactions toxicity; antineoplastic agents may increase
risk of bronchospasm and hypotension;
corticosteroids, digitalis, and thiazides may
potentiate hypokalemia
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
Decrease dose with renal impairment;
determine BUN and serum creatinine levels
weekly; monitor serum potassium and
magnesium closely; check electrolytes, CBC,
Precautions
liver function studies, input and output, BP,
and temperature regularly; administer slowly
because cardiovascular collapse reported after
rapid injection
Drug Name Amphotericin B, liposomal (AmBisome)
Used to treat severe systemic infections and
meningitis caused by susceptible fungi, such as
Candida and Aspergillus species, H
capsulatum, and C neoformans . Used in
systemic fungal infections resistant to
amphotericin B or in patients with renal or
Description hepatic failure. Consists of amphotericin B
Descripción within a single bilayer liposomal drug delivery
system. Polyene antibiotic produced by a strain
of S nodosus; can be fungistatic or fungicidal.
Binds to sterols, such as ergosterol, in fungal
cell membrane, causing intracellular
components to leak and subsequent fungal cell
death.
Pediatric Dose 5-7 mg/kg/dose IV q24h infused over 2 h
Contraindications Documented hypersensitivity
Coadministration with other nephrotoxic drugs
(eg, antineoplastic agents, aminoglycosides,
vancomycin, cyclosporine) may enhance renal
Interactions toxicity; antineoplastic agents may increase
risk of bronchospasm and hypotension;
corticosteroids, digitalis, and thiazides may
potentiate hypokalemia
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
Can lead to anemia, thrombocytopenia,
Precautions hypokalemia, nausea/vomiting, fever, and
chills

Further Outpatient Care

• The primary care provider (PCP) should evaluate the infant within one week of
discharge from the hospital. The infant can be evaluated for superinfection and
bacterial colonization associated with antibiotic therapy, especially if the therapy
was prolonged. The PCP should evaluate growth and determine if the feeding
regimen and activity have returned to normal.
• If neonatal sepsis was associated with meningitis, prolonged hypoxia,
extracorporeal membrane oxygenation (ECMO) therapy, or brain abscess
formation, the infant should be observed for several years to assess their
neurodevelopment and should receive appropriate early intervention services and
therapies when appropriate.

Transfer
• The infant may require transfer to a level III perinatal center, especially if he or
she requires cardiopulmonary support, parenteral nutrition, or prolonged
intravenous access.
• Multidisciplinary services available at larger centers may be necessary when
treating an acutely compromised neonate.

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 invasive GBS disease receive antibiotic prophylaxis during labor and
delivery. To minimize the risk of early-onset GBS disease, practitioners should
obtain screening vaginal and rectal cultures at 35-37 weeks' gestation for all
pregnant women unless they have had GBS bacteriuria in the current pregnancy
or a previous child with invasive GBS disease. The implementation of a screening
protocol has led to a significant decrease in the incidence of neonatal GBS disease
(see Image 1 ).
• Intrapartum antibiotic prophylaxis is indicated for all of the following (see Image
2 ):

o Previous infant with GBS disease
o GBS bacteriuria in the current pregnancy
o Positive GBS screening culture results during the current pregnancy
(unless a planned cesarean delivery, in the absence of labor or amniotic
membrane rupture, is performed)
o Unknown GBS status (culture not done, or results unknown) and any of
the following:
o
Delivery earlier than 37 weeks' gestation
Amniotic membrane rupture at 18 hours or later
Intrapartum temperature of 100.4°F or higher ( > 38°C)
• See Image 3 for recommended antibiotic prophylaxis regimens.

Complications

• Infants with meningitis may acquire hydrocephalus and/or periventricular


leukomalacia. They may also have complications associated with the use of
aminoglycosides, such as hearing loss and/or nephrotoxicity.

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.

Patient Education

• For excellent patient education resources, visit eMedicine's Blood and Lymphatic
System Center . Also, see eMedicine's patient education article Sepsis (Blood
Infection) .

MISCELLANEOUS
Section 9 of 11

• Authors and Editors


• Introduction Introducción
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous Miscellaneous
• Multimedia Multimedia
• References Referencias

Medical/Legal Pitfalls

• Delay in diagnosis and initiation of proper treatment may result in morbidity and
mortality.
• Failure to provide prophylaxis to women with GBS infection may create liability
if the infant subsequently becomes ill.

Special Concerns

• The Joint Commission on Infant Hearing of the AAP recommends that infants
who received aminoglycosides should have audiology screening before discharge.
Screen these infants again at 3 months, but no later than 6 months, to determine
whether damage has occurred.
MULTIMEDIA
Section 10 of 11

• Authors and Editors


• Introduction Introducción
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous Miscellaneous
• Multimedia Multimedia
• References Referencias

Media file 1: Incidence of early- and late-onset invasive group B Streptococcus (GBS)
disease