Neonatal septicemia refers to a systemic infection caused by bacteria invading the bloodstream during the neonatal period, where they multiply and produce toxins, sometimes leading to metastatic lesions within the body. It remains a significant disease in the neonatal period, with an incidence rate of about 1-10% among live births, and a higher incidence among premature infants. Bacteremia refers to the presence of bacteria in the bloodstream that are quickly cleared without causing toxemia or any symptoms.

bubble_chart Etiology

Pathogenic bacteria have continuously evolved with the application of antibiotics. In the 1940s, Group A hemolytic streptococci were predominant in Europe and America. By the 1950s, Staphylococcus aureus became the main pathogen. In the 1960s, large intestine bacilli took the lead. After the 1970s, Group B hemolytic streptococci (GBS) became the most common bacteria, followed by large intestine bacilli, with Klebsiella, Pseudomonas aeruginosa, and Salmonella also being significant. In recent years, Staphylococcus epidermidis has become the most common cause of hospital-acquired infections in the United States. In China, large intestine bacilli (mostly possessing the K₁ antigen) and Staphylococcus aureus remain the most common, with frequent reports of Klebsiella, Pseudomonas aeruginosa, and L bacteria (named by the Lister Institute) infections. Staphylococcus epidermidis infections are increasing, and although GBS has been reported, it is not common. The above-mentioned bacteria can cause infections before or after birth, but mainly after birth. Postpartum infections often invade through neonatal skin injuries, umbilical cord contamination, or the mucous membranes of the mouth, respiratory tract, or digestive tract.

The infection site of bacterial invasion is not obvious and often difficult to locate. Sometimes, due to incomplete examination, it is missed, especially in areas covered by clothing such as the back, sacrococcygeal region, limbs, and armpits.

Full-term infants and advanced stage newborns (2-4 weeks after birth) may exhibit clinical symptoms such as fever, refusal to eat, lethargy, or dysphoria. Premature infants and low birth weight infants may show atypical symptoms, including refusal to feed, spitting up, not crying, not moving, pale complexion, failure to gain weight, unstable body temperature, and sometimes no rise in body temperature.

In addition to the above symptoms, the following manifestations may suggest sepsis: ① Jaundice worsens or reappears after subsiding. Sometimes, jaundice may be the main manifestation of the condition. ② Grade I or Grade II hepatosplenomegaly without other explainable causes. ③ Petechiae or ecchymoses that cannot be explained by neonatal purpura or trauma.

Severe sepsis may lead to toxic intestinal paralysis, presenting as abdominal distension and fullness, and reduced borborygmus. It may also result in disseminated intravascular coagulation, hematemesis, hematochezia, or pulmonary hemorrhage.

Group B hemolytic streptococcus (GBS) sepsis, common in Europe and America, has also been reported in China. The GBS carriage rate in the vagina and rectum of pregnant women in the United States is as high as 20-35%, and about 40-75% of infants born carry the same bacteria within 3 days after birth, but only 1-2% develop the disease. GBS sepsis is divided into early-onset and delayed-onset types. Early-onset infection comes from intrauterine or during delivery, and GBS types Ia, Ib, Ic, II, and III may all be disease causes, mainly affecting the lungs. Infants develop the disease within 0-4 days after birth, and the clinical manifestations and lung X-rays are similar to neonatal hyaline membrane disease, even the pathological changes are similar. Delayed-onset infections mostly come from medical staff, with 90% caused by GBS type III, usually starting more than 5 days after birth, and about 80% are complicated by purulent meningitis.

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1. Peripheral blood white blood cell count: The count may vary, being high, low, or normal, thus it is not very significant. However, a ratio of band neutrophils to total neutrophils ≥0.2 is of reference value.

2. Culture: It is best to perform blood culture before using antibiotics. Skin disinfection and operation must be strictly aseptic to avoid culturing contaminating bacteria. If penicillin or cephalosporin has been used for treatment, a hypertonic medium can be used for L-form bacterial culture. The culture of pus from a sexually transmitted disease lesion, if positive, has significant diagnostic value.

3. Rapid diagnosis: Enzyme-linked immunosorbent assay (ELISA) can be selected (see diagnosis in neonatal infectious diseases).

4. Direct smear for bacteria: If intrauterine infection is suspected, fluid from the external auditory canal or gastric fluid should be taken within 1 hour after birth for a smear to look for bacteria. A positive result indicates contamination of the amniotic fluid, but the infant may not necessarily develop the disease. {|103|}

bubble_chart Diagnosis

1. Medical History: The possibility of bacterial infection should be considered in the presence of the following risk factors: ① Rupture of membranes for more than 12-24 hours; ② Maternal history of fever and chorioamnionitis in the late stage [third stage] of pregnancy; ③ Low Apgar score at birth and a history of resuscitation; ④ Premature labor, twins.

Nosocomial infections are prone to occur under the following circumstances: ① Infants treated in the neonatal intensive care unit (NICU); ② Infants undergoing invasive treatments such as tracheal intubation, umbilical vein catheterization, etc.; ③ Long hospital stays; ④ Infants undergoing surgical treatment; ⑤ Crowded wards; ⑥ Long-term use of broad-spectrum antibiotics, etc.

(1) Respiratory distress: The most common, accounting for 90% in septic infants, with varying severity: such as mild tachypnea, nasal flaring, retractions, increased need for oxygen, apnea, dyspnea, and even respiratory failure requiring mechanical ventilation.

(2) Tachycardia and poor peripheral circulation perfusion, cyanosis.

(3) Hypotension.

(4) Acidosis (metabolic), hypoglycemia or hyperglycemia.

(5) Temperature instability: 10-30% of neonates may have fever and hypothermia.

(6) Gastrointestinal symptoms: including vomiting, diarrhea, abdominal distension and fullness, poor appetite.

(7) Decreased activity or drowsiness, dysphoria, moaning.

(8) Convulsions.

(9) Petechiae or ecchymosis.

(10) Others such as jaundice, hepatosplenomegaly, etc.

3. Laboratory Tests

(1) Peripheral white blood cell count and differential: White blood cell count <5×10⁹/L, immature white blood cells and neutrophil ratio >0.2 suggest bacterial infection.

(2) Platelet count: Platelet count <100×10⁹/L suggests neonatal sepsis.

(3) Acute phase proteins: ① C-reactive protein >15μg/ml suggests bacterial infection, ② ESR >15^mm/h.

(4) Blood culture: Positive blood culture can establish the diagnosis of disease cause. Suspected infected infants should have peripheral blood cultures taken before antibiotics are administered after admission, and strict aseptic techniques should be followed to prevent contamination. If the infant has been treated with antibiotics that act on the cell wall, such as penicillin, cephalosporins, L-form bacterial culture can be performed using hypertonic medium. If anaerobic infection is suspected, anaerobic culture can be performed.

(5) Cultures from other sites: Umbilical, urine, stool, or other local infection sites.

(6) Radiological examination: Chest X-ray should be performed in infants with respiratory symptoms.

(7) Pathogen antigen detection: Such as counterimmunoelectrophoresis, latex agglutination test, hemagglutination inhibition test, etc.

bubble_chart Treatment Measures

1. Antibiotics Neonatal sepsis requires antibiotic treatment before blood culture results are obtained. Subsequently, antibiotics are chosen based on blood culture results and bacterial sensitivity tests. Typically, a combination of a penicillin and an aminoglycoside antibiotic is used as the initial choice because this combination has a broad antibacterial spectrum and can produce synergistic effects. In cases of severe infection, a third-generation cephalosporin combined with a penicillin can be used.

(1) Large intestine bacillus sepsis It is generally believed that infections occurring within 3 days after birth, due to prolonged rupture of membranes, prolonged labor, intrapartum infection, are mainly caused by large intestine bacillus. Ampicillin combined with gentamicin or amikacin can be used. Ampicillin is commonly used for bacterial infections in neonates, not only having strong antibacterial effects against cocci but also high antibacterial activity against common pathogens in neonatal infections such as large intestine bacillus and Haemophilus influenzae. Dose: For infants ≤7 days old, 50mg/(kg·d) divided into 2 intravenous infusions; for infants >7 days old, 75mg/(kg·d) divided into 3 intravenous administrations. Gentamicin dose: <1500g: 3mg/(kg·d), once daily; 1500～2500g: 3mg/(kg·d) divided into 12-hourly doses; >2500g: 5mg/(kg·d) divided into 8-hourly doses. Due to the ototoxic side effects of gentamicin, blood concentration monitoring should be performed during use. Since the sensitivity of large intestine bacillus strains varies greatly, antibiotic selection should be based on sensitivity tests combined with clinical judgment. If resistance to the above antibiotics or poor clinical efficacy is observed, third-generation cephalosporins can be used. Third-generation cephalosporins are effective in treating sepsis caused by various gram-negative and gram-positive aerobic bacteria, especially showing outstanding efficacy against gram-negative bacteria, with effectiveness rates of 84～97%. For example, cefotaxime and ceftriaxone not only have significant bactericidal effects but can also penetrate the inflamed blood-brain barrier. The doses for these two cephalosporins are: Cefotaxime: <7 days old, 100mg/(kg·d) divided into 2 intravenous doses; >7 days old, 150mg/(kg·d) divided into 3 intravenous doses. Ceftriaxone: 50mg/(kg·d) divided into 1～2 intravenous doses. The treatment course is about 2～3 weeks.

(2) Staphylococcus aureus sepsis Neonates with skin or mucous membrane purulent infections, and those born in hospitals with long hospital stays are often primarily infected with Staphylococcus aureus. Penicillin can be used for treatment, but most Staphylococcus aureus strains are resistant to penicillin, so acid-resistant penicillins such as oxacillin, cloxacillin, dicloxacillin, or vancomycin combined with the above enzyme-resistant penicillins are commonly used. The doses for these three enzyme-resistant penicillins are: <2000g: 0～7 days old, 50mg/(kg·d) divided into 2 doses; >7 days old, 100mg/(kg·d) divided into 3 doses; >2000g: 0～7 days old, 75mg/(kg·d) divided into 3 doses; >7 days old, 150mg/(kg·d) divided into 4 doses, all administered intravenously. Vancomycin dose: For preterm infants <37 weeks, 15mg/kg every 12 hours; for full-term infants, 10～15mg/kg every 8 hours, all administered intravenously. The treatment course is 7～10 days. Second-generation cephalosporins such as cefuroxime can also be used, with a dose of 50～100mg/(kg·d) divided into 2 intravenous doses.

(3) Streptococcus sepsis The early clinical manifestations of group B streptococcus sepsis are similar to neonatal respiratory distress syndrome and are difficult to distinguish. Treatment involves high-dose penicillin 200,000～400,000 U/(kg·d) divided into 2～3 intravenous doses.

(4) Anaerobic sepsis In recent years, the incidence of anaerobic infections in newborns has been gradually increasing, commonly seen in cases of premature rupture of membranes and postoperative complications. Metronidazole is the drug of choice for treatment. Dose: For infants ≤7 days old, 15mg/(kg·d) divided into 2 intravenous doses. For infants >7 days old, 30mg/(kg·d) divided into 2-3 intravenous doses. The treatment course is 7-10 days.

(5) Sepsis caused by nosocomial infection: Invasive treatments after hospitalization (such as umbilical vein catheterization, tracheal intubation, etc.), long-term use of broad-spectrum antibiotics, and crowded wards can easily lead to nosocomial infections. For nosocomial sepsis caused by coagulase-negative staphylococci, vancomycin should be used, with the dose as mentioned above, and the treatment course is 7-10 days.

For nosocomial sepsis caused by Gram-positive bacteria, aminoglycoside antibiotics such as gentamicin should be used, with the dose as mentioned above. However, the resistance to gentamicin is widespread, while amikacin has lower resistance and is often chosen. Amikacin dose: <1500g: 10mg/(kg·d) once daily; >1500g <2500g: 10mg/(kg·d) divided into 12h intervals; >2500g: 20mg/(kg·d) divided into 12h intervals, administered intravenously. Since aminoglycoside antibiotics commonly have ototoxic and nephrotoxic side effects, serum drug concentrations need to be monitored.

2. General treatment: Pay attention to warmth, maintain water and electrolyte balance, and supplement calories. Correct acidosis and hypoxia promptly, and manage local infection sites such as the umbilical area and skin.

3. Symptomatic treatment: Use sedatives and anticonvulsants for convulsions, provide blue light therapy for jaundice, and promptly reduce intracranial pressure for cerebral edema.

4. Supportive treatment: Administer small, frequent blood or plasma transfusions to enhance the body's resistance.

5. Immunotherapy: The immune system of newborns is not fully developed at birth, especially in low birth weight infants, and their response to various antigenic stimuli is not sensitive. Infections further weaken their immunity. Therefore, immunotherapy can improve the immunity of newborns and enhance their ability to fight infections.

(1) Immunoglobulin therapy: Premature infants have low immunoglobulin levels and are highly susceptible to hypogammaglobulinemia, leading to severe infections. The incidence and mortality of sepsis are higher in premature infants compared to full-term infants. Although full-term infants do not have significant hypogammaglobulinemia, they may still lack specific antibodies such as those against Escherichia coli and Salmonella, which can lead to uncontrolled infections. Intravenous immunoglobulin contains a large amount of immunoglobulins and specific antibodies, making it useful as an adjunctive treatment for sepsis. Recommended dose: 0.2-0.5g/kg per week for 4 weeks.

(2) Leukocyte transfusion: For severe sepsis in children, if the neutrophil count is low and bone marrow reserves cannot replenish the granulocyte deficiency, transfusing polymorphonuclear leukocytes isolated from normal adult blood can enhance the phagocytic and bactericidal activity of leukocytes, thereby reducing mortality.

(3) Exchange transfusion: Severe sepsis in children can be treated by exchanging blood to remove bacteria, toxins, and acidic metabolites; clear abnormal blood clotting substances, correct abnormal blood clotting processes, and provide a large amount of antibodies, complement, and phagocytes that newborns lack, enhancing the body's resistance. Fresh whole blood is recommended for exchange transfusion, with a transfusion volume of 160ml/kg. However, complications such as electrolyte imbalance, infection, and graft-versus-host reaction should be monitored. Exchange transfusion is suitable for severe neonatal sepsis that does not respond to antibiotic treatment.

bubble_chart Complications

Neonatal sepsis is most likely to be complicated by purulent meningitis, where neurological symptoms may not be obvious, yet the condition has already developed. Therefore, it is crucial to remain vigilant and conduct cerebrospinal fluid tests early. Another common complication is pneumonia or lung abscess, presenting with respiratory symptoms. Other metastatic infections such as cellulitis, osteomyelitis, and pyelonephritis may also occasionally occur.