Neonatal sepsis

Classification according to ICD-10
P36	Bacterial sepsis in the newborn
ICD-10 online (WHO version 2019)

In the neonatal sepsis is a systemic infection of the newborn , the colloquially called, septicemia is called. It particularly affects premature babies and children with a very low birth weight. Sepsis in the newborn is favored by the immaturity of the child's immune system . The WHO estimates that around 5% of deaths in children under the age of 5 in 2011 were due to neonatal sepsis.

to form

The division of neonatal sepsis depends on the time of its occurrence: If the diagnosis is made within the first 72 hours after birth, one speaks of congenital or congenital sepsis, which is known in English as Early-Onset Neonatal Sepsis (EONS). If the infection of the newborn occurs at a later point in time, it is referred to as acquired sepsis, which is referred to in English as Late-Onset Neonatal Sepsis (LONS). In the majority of cases, this is a nosocomial infection . However, the early and late forms of neonatal sepsis do not only differ in terms of their temporal occurrence, but also in terms of their characteristic spectrum of pathogens.

causes

Early sepsis

In early sepsis, the causative pathogens are transmitted from the mother to the child before or during the birth. Most commonly these pathogens are beta-hemolytic streptococci of group B or Escherichia coli . But also Staphylococcus aureus , Klebsiella , enterococci , streptococci of other groups, Listeria monocytogenes and anaerobes such as Bacteroides fragilis can cause early sepsis.

These pathogens usually originate from the mother's rectum and rise through the vagina into the uterine canal and into the uterus. There they cause inflammation of the membranes and subsequently get into the amniotic fluid that surrounds the not yet born child. The pathogens are swallowed by the affected children with the amniotic fluid and can get into the lungs, where they can cause pneumonia . However, the pathogens can also be absorbed by the newborn in the birth canal during the birth process and cause an infection.

During pregnancy, children receive immune bodies, a so-called loan immunity, from their mother via the placenta, and after pregnancy anti-infectious substances to fight infections via breast milk, but these are not always sufficient to successfully combat an infection and the pathogens that cause it. In this way, the pathogens can spread with the blood over the whole body of the newborn and also lead to further infections in other places. The immune system tries to react to this and causes an excessive inflammatory reaction, which leads to the loss of function of vital organs and thus to septic shock, from which the newborns die without timely treatment. The transition from healthy-looking newborns to seriously ill newborns and even death can often only take a few hours.

Late sepsis

In the late sepsis ( Late onset sepsis (LOS)), in contrast to the first signs of illness in newborns only after five to seven days of life show. Here, the causative pathogens mostly come from the birth canal as well, but were either suppressed for longer by the immune system so that only a latent infection was present or the symptoms arise from the colonization of the pathogen. A typical example of late-onset infection / sepsis is B-streptococcal meningitis. In general, healthy newborns can also develop LOS at home (about 10% of streptococcal infections are LOS according to the National Reference Center for Streptococci). Therefore, here from a nosocomial sepsis z. B. urgently differentiate by venous catheter. Even with late sepsis, the newborn's immune system cannot fight the pathogens and the infection effectively, so that these can spread over the whole body with the blood. The immune system tries to react to this and causes an excessive inflammatory reaction, which leads to the loss of function of vital organs and thus to septic shock, from which the newborns die without timely treatment. The transition from healthy-looking newborns to seriously ill newborns and even death can often only take a few hours.

Risk factors

Risk factors for the development of early or late sepsis in newborns are known.

For example, the risk of early sepsis in a newborn increases significantly if the child is born too early, i.e. before reaching the 37th week of pregnancy, and / or has a low birth weight, in the vagina and / or in the rectum of the mother Group B beta-hemolytic streptococci are present, the mother has amniotic infection syndrome , premature rupture of the bladder (≥ 18 hours before birth), bacteriuria or a urinary tract infection with group B beta-hemolytic streptococci in the mother during pregnancy has occurred or the mother has previously given birth to a child who suffered from early sepsis after birth. Amniotic infection syndrome is inflammation of the membranes, also called chorioamnionitis. Typical signs of chorioamnionitis in the mother can be a fever (≥ 38 ° C) during childbirth, a uterus that hurts when the abdomen is pressed, green, foul-smelling amniotic fluid, and an increase in white blood cells and the inflammatory parameter CRP in the blood be the mother. In addition, a prolonged acceleration of the child's heartbeat in the mother's womb prior to birth may indicate the presence of amniotic infection syndrome.

The risk of developing late-stage sepsis is also increased in a newborn if it was born prematurely, but also if it needs an infusion, artificial feeding, or ventilation. In addition, a lack of space and staff increase the risk of late sepsis in a newborn.

frequency

The incidence of neonatal sepsis is between 0.1 and 0.8%, with a negative correlation between birth weight and the incidence of neonatal sepsis: the lower the birth weight, the higher the risk of neonatal sepsis. Premature babies and children with a very low birth weight are therefore much more likely to be affected by newborn sepsis than children born mature who are born with a normal birth weight. In Germany, around 17% of children with a very low birth weight (<1500 g) develop newborn sepsis. In the group of children with a birth weight of less than 500 g, the incidence is approximately 40%.

Symptoms

In early sepsis, changes in the affected newborns usually appear on the first day of life, in late sepsis usually only after the fifth to seventh day of life. Depending on the location of the initial infection, i.e. where the pathogens entered the newborn's body, and the spread of the invaded pathogen in the newborn's body, various changes can occur in the respiratory, skin, digestive tract, nerves and circulatory system as well general changes in a newborn indicate the presence of neonatal sepsis. These changes are also referred to as signs of infection.

General indications of the presence of an infection in a newborn include poor drinking, low body temperature or less frequent fever, increased sensitivity to touch, and the impression that the child does not look good.

In the area of breathing , pauses in breathing (apnea) and / or respiratory distress syndrome indicate neonatal sepsis. Respiratory distress syndrome manifests itself as an increase in the respiratory rate, cyanosis with purple to bluish discoloration of the skin, mucous membranes, lips and fingernails as well as retraction of the skin in the area of ​​the sternum or between the ribs, nostrils and groans when exhaling. The respiratory distress syndrome in newborn sepsis does not differ from a respiratory distress syndrome that occurs for another reason, for example a surfactant deficiency or meconium aspiration .

In the area of ​​the skin there are paleness, the already mentioned cyanosis, punctiform hemorrhages in the skin , pus vesicles , encapsulated pus collections , inflammation of the umbilical cord , inflammation of the nail wall (circulation), yellowing of the skin, mucous membranes or the conjunctiva of the eyes and fluid accumulations in the Tissue possible signs of infection.

In the digestive tract , vomiting, a distended abdomen, delayed emptying of the stomach with increasing amounts of gastric remains, constipation, diarrhea, refusal to eat and the absence of intestinal noises are indications of neonatal sepsis. An enlargement of the liver and spleen, a so-called hepatosplenomegaly , are possible as a late sign of newborn sepsis in the digestive tract .

Possible signs of infection in the nervous system are apathy , a disorder of consciousness with drowsiness , decreased or increased muscle tone , seizures and tense fontanelles . In this case have hyperextension , seizures, and a protrusion of the fontanelle for the presence of meningitis out. Newborn sepsis is particularly common in late sepsis, that is, in up to 25 percent, with meningitis.

In the area of ​​the circulatory system , the signs of neonatal sepsis consist of an increase in heart rate, paleness and poor blood flow to the skin with a prolonged capillarization time. With a prolonged capillary refill, it takes longer after pressure on the fingernail or an area of ​​skin through which the small blood vessels empty and the surface becomes pale for the vessels to refill and for the area to return to normal color. The drop in blood pressure, which is another sign of infection, only occurs in an advanced stage of neonatal sepsis, when the sepsis continues without treatment and the condition and circulation of the affected newborns worsen until septic shock occurs.

The transition from healthy-looking newborns to seriously ill newborns with septic shock that dies without immediate treatment often takes just a few hours.

Diagnosis

If a newborn has risk factors for newborn sepsis, the newborn should be closely monitored. The presence of newborn sepsis must be immediately considered if the newborns show signs of infection or their general condition deteriorates, so that one has the impression that something is wrong with the child.

If signs of infection appear in a newborn, blood should be taken from the child immediately and blood cultures should be created. The blood culture, in which pathogens can be detected in the blood, would prove the presence of a neonatal sepsis. Since the result of the blood cultures is usually only available after 48 to 72 hours, but therapy must be started immediately, the blood cultures do not primarily help in the decision for or against a treatment. Changes in the blood that can be measured in a short time can, however, help with the decision. For example, a deficiency in white blood cells, known as leukopenia , with a shift to the left indicates the presence of newborn sepsis. Leukopenia occurs when the white blood cells are used up to fight off pathogens and infection. However, leukocytosis with an increased number of white blood cells in the newborn's blood can also be measured as more white blood cells are produced to fight the infection. A shift to the left means that more immature than mature granulocytes , certain white blood cells, than are normally present in the blood, also because of the increased consumption to ward off infection and thus the increased production of new white blood cells. In addition, the inflammatory parameter CRP may have increased in the blood. However, this usually rises too late to be of importance for the diagnosis and the timely start of treatment. In addition, other factors such as procalcitonin , interleukin-6 or interleukin-8 in the blood can be changed, although their significance in the diagnosis of neonatal sepsis is still unclear.

Furthermore, if late sepsis is suspected in the urine of the affected newborn, the causative pathogens can be searched for by examining the urine and taking urine cultures.

If meningitis is suspected in a newborn, a so-called lumbar puncture should be carried out in addition to the blood samples, blood cultures and urine tests . Here, brain fluid is taken from the lumbar spine and then examined for cell count, protein content and sugar content. In addition, a Gram stain should be carried out and cultures should be set up in order to determine whether and, if so, which pathogens are present in the cerebrospinal fluid and thus responsible for the meningitis.

Based on the symptoms of the newborn, its risk of infection, the risk factors and the results of its blood, urine and / or cerebral fluid tests, it is important to weigh up whether a newborn has neonatal sepsis and whether treatment should be started immediately or if it is missing Suspicions can still be awaited.

Differential diagnosis

The following diseases in newborns can lead to symptoms similar to those of neonatal sepsis:

• Respiratory distress syndrome from another cause, such as surfactant deficiency or meconium aspiration
• persistent fetal circulation
• Hyperviscosity syndrome
• Heart defect
• necrotizing enterocolitis (NEK)
• Cerebral hemorrhage
• Metabolic disorder
• other infections acquired in the womb

therapy

If neonatal sepsis is suspected, intravenous, calculated therapy with antibiotics must be started immediately . It is a medical emergency.

Antibiotics are chosen for treatment, which are effective against the pathogens that usually cause neonatal sepsis. It is important that blood cultures are taken from the newborn before the start of antibiotic treatment in order to determine whether newborn sepsis is really present and which pathogens are responsible for the newborn sepsis.

If the symptoms subside under treatment and the condition of the newborn improves, this speaks in favor of a diagnosis of neonatal sepsis and the continuation of treatment. If the condition of the newborn continues to deteriorate, it must be remembered that in rare cases other pathogens that do not respond to treatment could also be responsible for the newborn sepsis, and the treatment started should be supplemented with antibiotics against such pathogens. If the blood, urine or cerebral fluid cultures taken confirm the suspicion of neonatal sepsis, antibiotic treatment should be continued. If no pathogens can be found in the bacteriological cultures taken, the other examinations are also normal and have found other explanations for the initial indications of the presence of neonatal sepsis, the treatment should be stopped immediately, since any unnecessary antibiotic treatment can contribute to the development of antibiotic resistance . However, if the affected newborns continue to show signs of neonatal sepsis and therefore newborn sepsis cannot be ruled out with certainty, antibiotic treatment should be continued, even if no pathogens were found in the bacteriological cultures.

In early sepsis , antibiotic treatment can be started with an aminopenicillin / aminoglycoside or a cephalosporin (third generation) / aminopenicillin combination, with an aminopenicillin / cephalosporin (third generation) / aminoglycoside combination recommended if meningitis is present or suspected . However, these combinations usually do not work against anaerobes. If the condition of the newborn worsens despite the antibiotic treatment started, it must be taken into account that anaerobes may have caused the newborn sepsis and the treatment should be supplemented with metronidazole .

In late nosocomial sepsis , antibiotic treatment can be started with a cephalosporin (third generation) / aminoglycoside or cephalosporin (third generation) / vancomycin combination. An alternative is the combination of a carbapenem and vancomycin. In the presence or suspicion of meningitis, a vancomycin / cephalosporin (third generation) / aminoglycoside combination is recommended. If a fungus is suspected to be the cause of neonatal sepsis, an amphotericin B / flucytosine combination or fluconazole can be used. If the bacteriological examinations carried out prove the pathogen, the treatment that has been started should be switched to a targeted and efficient treatment against the pathogen.

In addition to treatment to specifically combat the causative pathogens, measures must be taken to stabilize the condition of the newborn. This includes ventilation if breathing is difficult so that all cells in the newborn's body receive enough oxygen. Blood pressure can be stabilized by giving fluids via an infusion and, if necessary, by administering medication to support the circulation ( catecholamines ). If the bleeding tendency increases due to the excessive consumption of blood coagulation factors in the context of disseminated intravascular coagulopathy (DIC), the affected newborns can be given vitamin K , antithrombin III or fresh frozen plasma . If the number of platelets is too low and the amount of bleeding is too low , the missing platelets can be replaced by giving blood platelets. A hypo , a hyperacidity , a displacement of the salts or anemia must be balanced.

In addition, various measures, such as the administration of immunoglobulins , can be used to try to strengthen the newborn's immune system.

However, an international study in the New England Journal of Medicine found no improvement in the prognosis of infants suffering from neonatal sepsis from intravenous immunoglobulin therapy (IVIG).

forecast

If newborn sepsis is suspected early on and appropriate antibiotic treatment is started, the symptoms of the newborn usually subside quickly and their general condition improves. However, in ten to twenty-five percent of newborns with neonatal sepsis, treatment is initiated too late and the newborns die. In the surviving newborns, so-called pulmonary hypertension , i.e. high blood pressure in the area of ​​the blood vessels in the pulmonary circulation, can persist and lead to serious health consequences. After neonatal sepsis with inflammation of the meninges caused by beta-hemolytic streptococci of group B or by gram-negative bacteria, damage to the nervous system can persist in a high proportion of those affected.

Prevention

In some countries, such as Switzerland, Austria and Germany, shortly before delivery, between about the 35th and 37th week of pregnancy, swabs are taken from pregnant women in the vagina and rectum to determine whether they have beta-hemolytic streptococci of the group B are present that could trigger early sepsis in the newborn. If the smear is positive, the mother is given antibiotics via an infusion, usually penicillin G or, as an alternative, ampicillin , starting at least four hours before the actual birth . If you are allergic to penicillin, a second generation cephalosporin can be used, and if you are allergic to penicillin and cephalosporins, clindamycin can be used. These antibiotics can significantly reduce the risk of early sepsis with beta-hemolytic group B streptococci. In addition, the mother will be given antibiotics via an infusion during childbirth if the swab results are unknown or are more than five weeks old and premature rupture of the bladder (≥ 18 hours before birth) has occurred, the mother has a fever during labor (≥ 38 ° C), which indicates an amniotic infection syndrome, or a premature birth, i.e. a birth before the end of the 37th week of pregnancy, is threatened. Also, women who have given birth to a child who suffered from neonatal sepsis with beta-hemolytic group B streptococci after birth are treated with antibiotics during childbirth. Smears from the vagina and rectum are not necessary for them. Likewise, swabs are not necessary in women who suffered from bacteriuria or urinary tract infection with beta-hemolytic group B streptococci during pregnancy. These women should be treated with antibiotics during pregnancy if bacteriuria or urinary tract infection is discovered and during childbirth. If a cesarean section is primarily performed for the birth of the child in a pregnant woman, i.e. without rupture of the bladder or labor, antibiotics are not required, as there is a risk of early sepsis with beta-hemolytic streptococci during the birth Case is low.

The prophylactic administration of antibodies (immunoglobulins) to premature babies in order to reduce the frequency of infections in them is controversial and is not recommended, as it is likely that only very immature premature babies will benefit from it and the occurrence of serious side effects cannot be ruled out with certainty.

In order to prevent nosocomially acquired late sepsis in newborns, it is important to strictly follow the hygiene measures when dealing with newborns, especially careful washing and disinfection of hands.

literature

• Friedrich Carl Sitzmann: Pediatrics. (= Dual row ). 2nd Edition. Georg Thieme Verlag, 2002, ISBN 3-13-125332-0 , pp. 117–126.
• Manfred Stauber, Thomas Weyerstahl: Gynecology and Obstetrics. (= Dual row ). Georg Thieme Verlag, 2001, ISBN 3-13-125341-X , pp. 706-707.
• CM Stan, M. Meisser, M. Boulvain: Newborn sepsis from group B streptococci. A critical consideration of current and future strategies for their prevention. In: The gynecologist. Volume 35, Number 7, 2002, pp. 674-679. ISSN  0017-5994
• Hubert Schneemann, L. Young, MA Koda-Kimble: Applied Drug Therapy: Clinical-Pharmaceutical Care in Case Studies. Springer Verlag, 2001, ISBN 3-540-41356-1 , pp. 742-746.
• Karl Werdan, HP Schuster, U. Müller-Werdan: Sepsis and MODS. 4th edition. Springer Verlag, 2005, ISBN 3-540-00004-6 , pp. 557-572.
• Berthold Koletzko: Pediatric and Adolescent Medicine. 13th edition. Springer Verlag, 2007, ISBN 978-3-540-48632-9 , pp. 91-94.
• Björn Hoffmann: Pediatrics crash course. 2nd Edition. Urban & Fischer Verlag, 2007, ISBN 978-3-437-43201-9 , pp. 36-37.
• Dietrich Reinhardt: Therapy of diseases in childhood and adolescence. 8th edition. Springer Verlag, 2007, ISBN 978-3-540-71898-7 , pp. 411-416.
• Centers for Disease Control and Prevention, S. Schrag, R. Gorwit, K. Fultz-Butts, A. Schuchat: Prevention of Perinatal Group B Streptococcal Disease. In: MMWR. 51 (RR-11), 2002, pp. 1-22. (Preview)
• DM Money, S. Dobson: The Prevention of Early-Onset Neonatal Group B Streptococcal Disease. In: Journal of Obstetrics and Gynaecology, Canada. Volume 26, 2004, pp. 826-832.
• Royal College of Obstetricians and Gynecologists : Prevention of early onset neonatal group B streptococcal disease. In: Guideline. No. 36, Nov 2003, pp. 1-10. (on-line)

Web links

• Pschyrembel
• D. Surbek, A. Gross, J. Seydoux, Ch. Honegger, O. Irion, G. Drack: Expert Letter No. 19: Prophylaxis of early-onset neonatal sepsis due to group B streptococci.
• Recommendations of the Swiss Society of Neonatology for the care of newborns from mothers colonized with group B streptococci
• Prophylaxis of neonatal sepsis - early form - by streptococci of group B, German Society for Gynecology and Obstetrics, guidelines, recommendations, statements, status August 2008

Individual evidence

1. ^ BJ Stoll, T. Gordon, SB Korones et al.: Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. In: J Pediatr . 129, 1996, pp. 72-80.
2. ↑ WHO-UNICEF Child Health Epidemiology Reference Group (CHERG) estimates, 2103.
3. ^ BJ Stoll, T. Gordon, SB Korones et al.: Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. In: J Pediatr. 129, 1996, pp. 72-80.
4. ↑ K. Faust, W. Göpel, E. Herting, C. Härtel: Sepsis in premature babies with a very low birth weight. Epidemiology, Risk Factors, and Prevention Strategies. In: Chemother J. 20, 2011, pp. 1-8. (Data from the Federal Statistical Office and the GNN preliminary study 2003-2008)
5. ^ New England Journal of Medicine. 365, 2011, pp. 1201-1211.
6. ↑ nejm.org
7. ↑ H. Burchardi, R. Larsen, R. Kuhlen, KW Jauch, J. Schölmerich: Die Intensivmedizin. 10th edition. Springer Verlag, 2008, p. 1108.

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