What is sepsis of newborns?
Neonatal sepsis is a bacterial infection that develops during the first 90 days of life. Manifestations of it are diverse and include a decrease in spontaneous activity, sucking energy, apnea, bradycardia, instability of temperature, respiratory failure, vomiting, diarrhea, an increase in the abdomen, anxiety, seizures and jaundice. The diagnosis is made clinically, with advanced laboratory tests. Initial treatment is carried out with ampicillin plus gentamicin or cefotaxime, as quickly as possible with the transition to antibiotics, taking into account the sensitivity of the pathogen.
Neonatal sepsis occurs with a frequency of 0.5-8.0 cases per 1000 births. The highest incidence rate is observed among newborns with low birth weight, with inhibition of respiratory function at birth and in the presence of perinatal risk factors from the mother. The risk is higher in male infants and newborns with congenital malformations.
Obstetric complications, such as premature rupture of the membranes, which occurred 18 hours before the birth of the child, bleeding in the mother, toxinemia, rapid delivery or infectious diseases in the mother can predispose to the development of sepsis in the newborn.
Early sepsis is usually the result of infection of the newborn during labor. In more than 50% of cases of early sepsis, clinical manifestations develop within 6 hours after birth, and within 72 hours in most patients. In the late sepsis of newborns, infection often occurs from the environment.
Streptococcus group B and literate intestinal microorganisms cause 70% of early sepsis. When crops from the vagina and rectum in women at the time of delivery, 30% can reveal the colonization of HBV. At least 35% of their children will also be colonized. The massiveness of colonization determines the degree of risk of invasion of the microorganism, which is 40 times higher with massive colonization. Although only 1 in 100 newborns colonized with GBS develop an invasive disease, more than 50% of them develop the disease in the first 6 hours of life.Non-typable strains of Haemophilus influenzae are increasingly causative agents of sepsis in newborns, especially premature ones.
Other gram-negative intestinal rods and gram-positive microorganisms-Listeria monocytogenes, enterococci, group D streptococci, alpha-hemolytic streptococci and staphylococci cause the majority of other cases. Streptococcus pneumoniae of H. influenzae type b and less commonly Neisseria meningitidis are also isolated. Asymptomatic gonorrhea occurs in 5-10% of pregnancies, so N. gonorrhoeae can also be the causative agent of neonatal sepsis.
Staphylococci cause 30–50% of late neonatal sepsis, most often due to the use of intra-vascular devices. Isolation of Enterobactercloacae £ Sakazakii from blood or liquor implies contamination of food. In outbreaks of intra-hospital pneumonia or sepsis caused by Pseudomonas aeruginosa, contamination of ventilator equipment is suggested.
The role of anaerobes remains unclear, although deaths were associated with anaerobic bacteremia. Anaerobes can cause some cases of sepsis with negative results of seeding blood, but the presence of changes characteristic of sepsis during autopsy.
Candida sp are becoming more and more important causes of late sepsis, developing in 12-13% of babies with very low birth weight.
Some viral infections can manifest as early or late neonatal sepsis.
The most important risk factor in the development of late sepsis is the long-term use of intravascular catheters. Other causes of neonatal sepsis include comorbidities, antibiotic therapy, prolonged hospitalization, and contaminated equipment or solutions for intravenous or oral administration. Infection with gram-microorganisms can occur from the environment. Gram-negative intestinal bacteria, as a rule, are the patient's own flora, which could change under the influence of previous antibiotic therapy or be populated by resistant organisms through the hands of staff or contaminated equipment. Therefore, situations in which the risk of contamination with these microorganisms increases, lead to an increase in the incidence of intra-hospital infections. Risk factors for the development of sepsis in newborns caused by Candida sp are long-term use of central venous catheters, parenteral nutrition, prior use of antibiotics, necrotizing ulcerative enterocolitis, and previous operations.
Hematogenous and transplacental dissemination of the mother's infection occurs when certain viral, protozoal, and trimonomer pathogens are transmitted. A small number of microorganisms can be transmitted to the fetus transplacental, but in most cases, the infection occurs in utero or as an intra-natal route through the birth canal colonized by the pathogen.
Although the intensity of colonization of the mother is directly related to the risk of developing invasive diseases of newborns, many mothers with a low density of colonization give birth to infants with high colonization density, which in this connection are at risk. Amniotic fluid containing meconium or a primordial lubricant promotes the growth of glucocorticoids and E. co. Thus, several bacteria in the vagina are able to multiply rapidly with a prolonged anhydrous period, which probably explains this paradox. Microorganisms usually enter the bloodstream of the fetus during aspiration or ingestion of contaminated amniotic fluid, which leads to bacteremia. The upstream route of infection helps to explain such phenomenaas a high incidence of premature rupture of the membranes in neonatal infections, the value of inflammation of the membranes, an increased risk of infection in a twin closer to the birth canal, and bacteriological characteristics of neonatal sepsis, which reflect the flora of the vaginal vagina of the mother.
The primary focus of inflammation can be localized in the paranasal sinuses, middle ear, lungs, gastrointestinal tract and can spread to the meninges, kidneys, bones, joints, peritoneum and skin. Pneumonia is the most common invasive bacterial infection after primary sepsis.
Early manifestations are often non-specific and erased and do not differ according to etiology. Especially often there is a decrease in spontaneous activity, vigor of sucking, apnea, bradycardia, temperature instability. Fever is noted only in 10-50%, but if it persists, it usually indicates an infectious disease. Other manifestations include respiratory failure, neurological disorders, jaundice, vomiting, diarrhea, and an increase in the abdomen.The presence of an anaerobic infection is often indicated by the unpleasant putrid odor of amniotic fluid at birth.
Specific signs of damage to a particular organ may indicate a primary or metastatic focus. In most newborns with early sepsis caused by hypertension, the disease manifests itself as respiratory failure, which is difficult to distinguish from hyaline membrane disease. Redness of the skin, discharge or bleeding from the umbilical wound in the absence of hemorrhagic diathesis suggests omphalitis. Coma, convulsions, opisthotonus or bulging fontanelle suggest meningitis or brain abscess. A decrease in spontaneous movements of the limb and its swelling, erythema and local fever or soreness in the joint area indicate osteomyelitis or purulent arthritis. An unexplained bloating may indicate peritonitis or necrotic ulcerative enterocolitis. Skin vesicles, oral ulcers, and hepatosplengomegaly [especially in disseminated intravascular coagulation syndrome] may indicate generalized forms of herpes viral infection of the blood smear.The normal number of leukocytes in newborns fluctuates, but values less than 4,000 in μl or more than 25,000 in μl are abnormal. The determination of the absolute number of leukocytes is not sensitive enough to judge the presence of sepsis, but the ratio of juvenile forms and the total number of neutrophilic leukocytes of less than 0.2 has a pronounced negative prognostic value. The rapid decrease in the absolute number of neutrophil eosinophilovymorphological changes [for example, toxic granularity of neutrophils, corpus Dele and vacuolization of cytoplasm in the blood without the addition of citrate or ethylenediamine tetraacetyl acid] suggest sepsis.
The number of platelets may decrease several hours or days before the onset of the onset of the disease, but more often it remains elevated for a day or so after the onset of clinical manifestations in the newborn. This decrease is sometimes accompanied by changes in other indicators of coagulogram characteristic of DIC-sind-rum [for example, an increase in fibrin degradation products, a decrease in fibrinogen, a lengthening of the international normalized ratio.
Because of the large number of circulating bacteria, microorganisms can sometimes be seen associated with neutrophilic leukocytes when examining a thick drop smear when stained by Gram, methylene blue, or orange acridine.
There is a risk of increasing hypoxia during LP in a newborn with an existing hypoxia. Therefore routine carrying out of LP is not obligatory if confidence in presence of a sepsis is low. However, the LP should be carried out on a newborn with suspected sepsis as soon as the child is able to transfer the procedure. Respiratory support is carried out before and during the PL to prevent the development of hypoxia. Since pneumonia caused by GHV, which is a cli
Early-onset HBV infections can manifest as fulminant pneumonia. Obstetric complications are often noted. In more than 50% of cases, HBV infection occurs within 6 hours after birth; 45% of newborns have an Apgar score of less than 5. Meningitis is often absent. In cases of late onset of HBV infection, meningitis is common. Late-onset HBV infections are usually not associated with perinatal risk factors and obvious colonization of the cervix in the mother and can be acquired after delivery.
Early diagnosis is important and requires awareness of risk factors as well as alertness if the newborn has abnormalities in the first few weeks of life. For newborns with suspected sepsis and those whose mothers allegedly had chorioamnionitis, a complete blood count should be taken with a leukocyte count and platelet count, blood and urine cultures, and lumbar puncture should be performed if the condition of the child allows. If there are symptoms of the respiratory system, an X-ray of the chest organs is required. The diagnosis is confirmed by the release of the pathogen by the bacteriological method. Other tests can give abnormalities, but they are not specific.
For premature newborns who look healthy, but whose mother did not receive adequate anti-streptococcal treatment during childbirth, the American Pediatric Academy recommends limited screening.
Complete blood count with a count of leukocyte formula and is evident on the first day of life, can be mistaken for a disease of hyaline membranes,Often, drugs are routinely administered to newborns suspected of having these diseases.
Isolation of the pathogen from the blood
Umbilical vessels are often contaminated with microorganisms from the surface of the umbilical wound, especially after a few hours, so blood cultures from umbilical vessels may be unreliable. Consequently, blood samples for seeding should be taken during venipuncture, preferably from two peripheral veins, and the venipuncture site should be thoroughly treated with iodine-containing fluid, then with 95% alcohol and finally drying. Blood should be sown both on the aerobic flora and on anaerobic pathogens. If catheterization sepsis of newborns is suspected, samples for seeding should be obtained through the catheter, as well as during peripheral venipuncture. In more than 90% of the positive results of blood culture, growth occurs within 48 hours of incubation; in 50% of cases of positive results, blood samples contain more than 50 colony-forming units / ml. Because this is massive bacteremia, usually a small amount of blood is enough to detect microorganisms.Data on the results of capillary blood culture is not enough to recommend their holding.
Candida sp grows in hemoculture and on blood agar, however, if other fungi are suspected, the medium should be used for the cultivation of fungi with medium acidity. For other species of fungi other than Candida, it may be necessary to incubate blood cultures for 4–5 days until a positive result is obtained, and it is possible that a negative result is obtained even in the case of obvious signs of a generalized infection. Evidence of colonization may be helpful before obtaining the results of blood culture. If generalized candidiasis is suspected, an indirect ophthalmoscopy with dilated pupil is performed to detect a candidal retinal lesion. Ultrasound of the kidneys is performed to detect kidney mitosis.
Analysis and culture of urine. Urine should be obtained by catheterization or suprapubic puncture, and not using urine collection bags. Although only the results of urine culture are of diagnostic value, the detection of more than 5 leukocytes in the field of view at high magnification in centrifuged urine or any number of microorganisms in fresh non-centrifuged urine, gram-stained,is a preliminary indication of the presence of a urinary tract infection. The absence of pyuria does not exclude IC.
Other tests for infection and inflammation
Changes in sepsis are noted in many laboratory tests, which are evaluated as possible early markers. In general, however, their sensitivity, as a rule, remains low until the clinical picture of sepsis develops in newborns, and their specificity is not optimal.
The reactions of counter-immunoelectrophoresis and latex-agglutination make it possible to detect antigens in biological fluids; they can be used when preliminary antibacterial therapy makes the results of crops unreliable. They can also detect capsular polysaccharide antigen GBS, E. coli K1, N. Meningitidis type B, S. pneumoniae, H. influenzae type b.
Acute phase indicators are proteins produced by the liver under the influence of IL-1 in the presence of inflammation. The most significant are the tests for the quantitative determination of C-reactive protein. The concentration of 1 mg / dL gives a false-positive and false-negative results of 10%. The increase in C-reactive protein occurs during the day with a peak on the 2-3rd day and decreases to the sensitivity of the pathogen and the localization of the source of infection.If bacteriological examination shows no growth of the pathogen within 48 hours and the newborn feels good, the antibacterial therapy is stopped.
General supportive measures, including respiratory and hemodynamic support, are combined with antibacterial therapy.
Antibiotics for sepsis in newborns
In early sepsis, initial treatment should include ampicillin or penicillin G plus an amino glycoside. Instead of aminoglycoside, you can designate cefotaxime. When the putrid odor of amniotic fluid should be added anti-anaerobic therapy. Antibiotics can be changed as soon as the pathogen is isolated.
When arriving from home before healthy babies with suspected late sepsis, they should also receive therapy with ampicillin with gentamicin or ampicillin with cefotaxime. In late nosocomial sepsis, initial treatment should include vancomycin plus an aminoglycoside. If Pseudomonas aeruginosa prevails in the unit, ceftazidime can be used instead of an aminoglycoside. Newborns who have previously received a full 7-14-day course of aminoglycosides should be given another third-generation aminoglycoside or cephalosporin if they need to repeat a course of antibiotic therapy.
If an infection caused by coagulase-negative staphylococci or coagulase-negative staphylococci is isolated from blood or another normally sterile biological fluid, and they are considered to be the causative agent, initial therapy for late sepsis of the newborn should include vancomycin. However, if the microorganism is sensitive to nafcillin, this drug should be prescribed. Removing the intended source of infection and slowly returns to normal, much later than clinical recovery occurs. IL-6 and other inflammatory cytokines are currently being studied as markers of sepsis.
Sepsis of newborns - prognosis
Mortality is 2-4 times higher among low birth weight infants than among full-term newborns. The general lethality at early sepsis makes 15 - 40% and at late sepsis - 10 - 20%.
Septic newborns with granulocytopenia are less likely to survive, especially if their bone marrow neutrophil pool is reduced to less than 7% of the total number of nuclear cells. Since these data may not be available, the ratio of the number of adolescents and the total number of neutrophils in peripheral blood can give an approximate idea of the bone marrow neutrophil pool.The ratio U: 0 greater than 0.80 correlates with the depletion of the bone marrow neutrophil pool and death; This relationship can be used to identify patients for whom granulocyte transfusion may be indicated.
Treatment of sepsis in newborns
Since sepsis can manifest nonspecific clinical signs, and its consequences can be catastrophic, rapid administration of empirical antibiotic therapy is recommended; later, correction of therapy with regard to the catheter is carried out) may be necessary for treatment, since coagulase-negative staphylococci may be protected by glycocalix.
Since the growth of candidates can be observed only after 2–3 days, the start of therapy with amphotericin B and the removal of an infected catheter without obtaining a positive result of sowing blood or cerebrospinal fluid can save the patient's life.
Other treatments for sepsis in newborns
Replaceable blood transfusions were used in patients in serious condition. The goal was to increase the level of circulating immunoglobulins, reduce the level of circulating endotoxins, increase the level of hemoglobin and improve the perfusion.However, controlled prospective studies were not conducted to assess the results of the use of replacement transfusions in the treatment of sepsis.
Fresh frozen plasma can help reduce the deficiency of thermolabile and thermostable opsonins, which is observed in newborns with low birth weight, but it is impossible to conduct controlled studies of its use, and the risk associated with transfusion of blood components should be taken into account.
Granulocyte transfusions were used in newborns with sepsis and granulocytopenia, but no conclusive evidence was obtained of the improved prognosis.
Recombinant colony-stimulating factors [granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor] increased the number of neutrophils and their function in newborns with suspected sepsis, but apparently not necessarily effective in newborns with severe neutropenia; further study of their application is required.
Prevention of sepsis in newborns
Intravenous administration of immunoglobulin at birth can prevent the development of sepsis in certain newborns from high-risk groups with low birth weight.However, it is ineffective with an already proven infection.
Since the invasive disease caused by HBV often manifests during the first 6 hours of life, women who have previously given birth to a child with hepatitis B caused by the disease should receive antibiotic therapy during childbirth, and women with clinical or asymptomatic bacteriuria during pregnancy should receive antibiotics at the time of diagnosis, and during childbirth.
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