Sepsis NeonatalSERVICIO DE PEDIATRÍA - INTERNADO

HOSPITAL DE VENTANILLA

WUINNY A. LI HOLGUÍN.

Lima, marzo del 2017

As part of this comprehensive approach, it is impossible to neglect the importance of infection as an underlying and contributing cause of maternal and newborn mortality. Deaths due to infection occur mainly through sepsis—a potentially life-threatening condition caused by a dysregulated host response to infection and organ dysfunction.2 Infections cause about 11% of maternal deaths, and are also a significant contributor to many deaths attributed to other conditions.3 The risk of early neonatal sepsis increases in the event of maternal infection.4 Early neonatal sepsis causes about 8% of all neonatal deaths, but the proportion of late neonatal deaths due to sepsis is four times higher.5 Deaths from maternal and neonatal sepsis expose broader health determinants and underlying issues of quality of care including infrastructureconstraints, inconsistent use of preventive measures, delayed diagnosis, and poor management of infection and its complications.

This year, the Initiative will launch a maternal and neonatal sepsis global mobilisation and awareness campaign, which will culminate in the week of Sept 13, 2017, with the Global Maternal Sepsis Study. During that week, a massive coordinated data collection effort will take place to assess the burden and current management of maternal and neonatal sepsis in hundreds of health facilities in approximately 50 countries around the world. The new maternal sepsis definition and potential identification criteria will be tested and validated in this large global study. That eff ort will be followed by the implementation of other specific projects and programmes targeting the prevention and successful management of maternaland newborn sepsis.

INFECCIONES EN EL NEONATO

• Estas infecciones son mas frecuentes en prematuros y en ellos reviste especial gravedad. Los microorganismos patógenos inicialmente contaminan la piel y/o mucosas del RN, llegando al torrente circulatorio tras atravesar la barrera cutaneo-mucosa.

• Canal genital materno

• Contaminación ascendente

• De la madre al RN

Sepsis de transmisión vertical

• UCI neonatal

• Personal sanitario (manos contaminadas)

Sepsis de transmisión horizontal nosocomial

• En su domicilio o en su comunidad

Sepsis de transmisión horizontal comunitaria

ETIOLOGÍA

ETIOLOGÍA

PATOGENIA

• Hematógena o Transplacentaria o Infección fonicular

• Sitios proximales: LA

Infecciones prenatales o congénitas

• Vía ascendente

• RPM 18 horas

• Aspiración / Deglución de secreciones por el canal post parto.

• Sepsis neonatal / Complicaciones obstétricas

Infecciones perinatales

• Ambiente

• Alimentos

• Ropa

Infecciones postnatales

Período embrionario:

Endoarteritis – Malformaciones

Período Fetal: Necrosis celular

PATOGENIA

ANTIINFLAMATORIO

• Parálisis inmunológica

• Sd rpta antiinflamatoria compensatoria

• Mayor riesgo de sobreinfecciones (catéter o heridas)

PRO INFLAMATORIA

• Choque profundo

• Fulminante

EFECTO DELETÉREO:

Activación SER

Pérdida de integridad

microvascular

Disfunción de órganos

distantes del sitio de

injuria inicial

SEPSIS NEONATAL

• Sintomatología clínica + Datos de Laboratorio (Leucocitosis, PCR, procalcitonina)

• SISR + evidencia de infección

Manifestaciones clínicas

Actividad espontánea

Inestabilidad de la T°

Dificultad en la alimentación

• Retención gástrica

• Regurgitación

• Reflejo de succión débil – abolido

PMT:

• Taquicardia

• Bradicardia

• Apnea

Manifestaciones digestivas

• Vómitos

• Distensión abdominal

• Diarrea

Cardiorrespiratoria:

• Taquicardia

• Taquipnea

• Distrés Respirtatorio

• Apnea

Neurológica

• Apatía

• Irritabilidad

• Convulsiones

TARDÍA

Movimiento espontáneo

Hipotonía

Ictericia “aspecto séptico”

CID: ptequias, equimosis, Hemorragia en mucosas.

CHOQUE SÉPTICO:

• Llenado capilar 2 segundos

• Taquicardia

• Pulso débil

• Hipotensión

SUPERPOSICIÓN DE DOS FENÓMENOS: CHOQUE FRÍO Y CHOQUE CALIENTE

SEPSIS NEONATAL

•1 FR + 1SCRIESGO DE INFECCIÓN

•+ alteraciones analíticas de sospecha

INFECCIÓN NEONATAL PROBABLE

•1 o más cultivos control (+)

INFECCIÓN NEONATAL

CIERTA

SEPSIS NEONATAL

•1 FR + 1SCRIESGO DE INFECCIÓN

•+ alteraciones analíticas de sospecha

INFECCIÓN NEONATAL PROBABLE

•1 o más cultivos control (+)

INFECCIÓN NEONATAL

CIERTA

SEPSIS CLÍNICA: Signos (+)

Cultivos (-). Probablemente por

virosis sistémica o porque la madre

recibió ATB previo

SEPSIS NEONATAL

SEPSIS NEONATAL

• The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network and the Vermont Oxford Network define neonatal early-onset sepsis (EOS) as the onset of signs and symptoms of sepsis with an associated positive culture result at or before age 72 hours. Late-onset sepsis (LOS) is defined as the onset of signs or symptoms of sepsis after age 72 hours.

• The diagnosis of neonatal sepsis is challenging because early signs and symptoms are often subtle and nonspecific, yet prognosis depends on early detection and treatment. Furthermore, the symptoms of many noninfectious common neonatal conditions can mimic those of sepsis, complicating the diagnosis of sepsis.

SEPSIS NEONATAL

• The gold standard for diagnosing sepsis is a positive result on culture from blood or another sterile body fluid, such as cerebrospinal fluid (CSF) or urine. It has been estimated that cases with a positive blood culture result represent less than 40% of all neonatal sepsis because of inadequate blood volume sampled, transient or low-grade bacteremia, or antibiotic transferred from a mother who received antibiotics during the intrapartum period. A single aerobic blood culture of sufficient volume (1 mL) has a 98% probability to isolate an organism even in infants with low-level bacteremia (4 CFU/mL).

• The complete white blood cell (WBC) count with differential is routinely used to assist in the diagnosis of sepsis; however, multiple studies have determined that the WBC, immature-to-total neutrophil (I/T) ratio, and platelet count have low sensitivities and specificities.

SEPSIS NEONATAL

• Two very large retrospective, multicenter database studies found that low WBC counts and high I/T ratios were associated with increasing odds of infection in EOS. High and low WBC counts, high absolute neutrophil count, high I/T ratios, and low platelet counts were associated with LOS.

• A single blood cellcount–derived index did not have proven sensitivity to reliably include or exclude EOS or LOS in neonates. The absolute immature neutrophilcount and absolute neutrophil count have suboptimal sensitivity and decreased predictive accuracy for EOS because elevation does not consistently distinguish an inflammatory response from a noninfectious origin. The I/T ratio is a more sensitive indicator of sepsis; however, single assessments have a better negative predictive value (NPV) (99%) than positive predictive value (PPV) (25%). The I/T ratio is elevated in a quarter to half of presumptively uninfected neonates. Overall, neutrophil indexes seem to be more helpful for excluding infants without infection than for including infants with infection.

SEPSIS NEONATAL

• Rapid diagnostic biomarkers of sepsis to differentiate septic from nonsepticneonates may allow timely discontinuation of antibiotic therapy, thus avoiding their prolonged use and preventing emergence of antibiotic resistant bacteria. In addition, prolonged empiric antibiotic use has been associated with increased risk of necrotizing enterocolitis, LOS, and death.

• Acute-phase proteins, components of the complement system, chemokines, cytokines, adhesion molecules, and cell surfacemarkers have all been investigated as biomarkers of neonatal sepsis. The most widely studied and most promising markers include C-reactive protein (CRP), interleukin (IL) 6, IL-8, procalcitonin (PCT), and tumor necrosis factor a (TNF-a).

SEPSIS NEONATAL

PROCALCITONINA

Aumenta de 6 – 18 horas después de la noxa y alcanza un pico en 8-60 horas después.

PCR es sintetizada por el feto y RN. Sin embargo, estudios han demostrado que sus niveles están disminuidos en los pretérmino. Hay un mínimo transporte de PCR materno al feto por eso es que es un marcador ideal para Sepsis de aparición temprana en neonatos.

EOS: Es el mejor marcador de sepsis neonatal entre las 24-48 h desde el inicio de la infección, con una sensibilidad de 84% y una especificidad del 96%.

LOS: PCR se usa como un biomarcador específico de infección neonatal. Esmás sensible y específico en el dx de Sepsis que el índice de I/T y el valor absolute de Neutrófilos. Sin embargo, también se eleva en otras condiciones no infecciosas como: Aspiración meconial, HIV, asfixia perinatal.

SEPSIS NEONATAL

IL-6

Aumenta de 2-3 horas y regresa a sus VN en 6-8 horas.

Producido por Macrófagos, células endoteliales y fibroblastos en respuesta la inflamación.

Es el mejor marcador inductor de la síntesis de proteínas de fase aguda pediátricas, incluyendo PCR y fibrinógeno.

Su concentración no está influenciada por la edad gestacional}

Presenta una alta sensibilidad en diagnosticar sepsis de aparición temprana y tardía.

SEPSIS NEONATAL

IL-8

Producido por Macrófagos, células endoteliales y fibroblastos en respuesta la inflamación, parecido a la IL-6.

Su concentración no está influenciada por la edad gestacional ni por infantes post-término.

Su sensibilidad y especificidad disminuyen tras 24-48 horas de la infección.

EOS: S-78%, E-91%, VPP-100% y VPN 84%.

SEPSIS NEONATAL

TNF-a

Citcina proinflamatoria que estimula la producción de IL-6 y que está aumentada en sepsis neonatal.

Es moderadamente adecuada para el dx de EOS (S:66% E:76%) y LOS (S:68%, E:89%).

Aunque es un buen marcador de sepsis neonatal, es menos útil que otras citosinas como IL-6 y la IL-8.

SEPSIS NEONATAL

Procalcitonina

Reactante de fase aguda roducida por monocitos y hepatocitos 4-6 horas después de la exposición a los antígenos bacterianos.

Sus valores incrementan en los primeros días después del nacimiento de forma fisiológica, su valor es limitado en el diagnóstico de EOS.

Los pretérmino tienen valores más elevados de PCT comparados con los infantes a término.

EOS: S-76% y E-76% y para LOS: S-90% y E-88%.

TERAPIA ANTIBIÓTICA EMPÍRICA:

Objetivo: erradicar lo más temprano posible el microorganismo causante.

R/B: Altera la microbiota neonatal, potencialmente torna más susceptible al neoanto de infecciones oportunistas, aumento del riego de Resistencia.

El ATB dirigido al microorganismo causante.

Previous infant with invasive GBS disease

- GBS bacteriuria during any trimester of the current pregnancy

- Positive GBS vaginal-rectal screening culture in late gestation during current pregnancy

- Unknown GBS status at the on set of labor (culture not done, incomplete, or results unknown)

and any of the following:

- Delivery at < 37 weeks’ gestation

- Amniotic membrane rupture ≥18 hours

- Intrapartum temperature ≥38.0°C

Intrapartum antibiotic prophylaxis during labor

- Penicillin G, 5 million units IV initial dose, then 2,5 - 3 million units IV every 4 hours until delivery

- OR Ampicillin, 2 g IV initial dose, then 1 g IV every 4 hours until delivery If patient has a history

of allergy (anaphylaxis, angioede ma, respiratory distress or urticaria) after receiving penicillin or

a cephalosporin - Clindamycin 900 mg IV every 8 hours until delivery

Intrapartum GBS prophylaxis not indicated- Negative vaginal-rectal GBS screening culture during the current pregnancy, regardless of intrapartum

risk factors

- Cesarean delivery per for med before onset of labor on a wo man with intact amniotic membranes,

regardless of GBS colonization status or gestational age

Observations - A negative GBS screen is considered valid for 5 weeks, after this time, repeat screening if the wo men

has not delivered

- If the women is receiving ampicillin and /or clindamycin for presumed chorioamnionitis or premature

rupture of membranes during labor, she does not need additional antibiotic

“Penicillin (the recommended agent for IAP) (1) is no produced in Italy. A standard dose of ampicillin (2 g intravenously plus 1 g intravenously every 4 h until delivery) is recommended during active Labor for IAP. Cefazolin is recommended for allergic women not at risk of anaphylaxis. Women with a positive prenatal screening and planned cesarean section do not receive IAP. According to a local protocol, which is consistent with CDC guidelines (1), IAP is given to women with (1) a previous GBS infected infant, (2) GBS bacteriuria during the current pregnancy, (3) GBS colonization in late pregnancy (35–37 weeks’ gestation), or (4) unknown GBS status and RFs (preterm birth, PROM and IF). Furthermore, regardless of antenatal screening results, we consider IF as an indication for giving broad spectrum antibiotics (usually ampicillin and gentamicin).”