pediatrics
Neonatal Sepsis
Diagnosis of Neonatal Sepsis
High index of suspicion Blood, cerebrospinal fluid (CSF), and sometimes urine culture Early diagnosis of neonatal sepsis is important and requires awareness of risk factors (particularly in LBW neonates) and a high index of suspicion when any neonate deviates from the norm in the first few weeks of life. should have a complete blood count (CBC), differential with smear, blood culture, urine culture (not necessary for evaluation of early-onset sepsis), and lumbar puncture (LP), if clinically feasible, as soon as possible. Neonates with respiratory symptoms require chest x-ray. Diagnosis is confirmed by isolation of a pathogen in culture. Other tests may have abnormal results but are not necessarily diagnostic. Infants should be given broad-spectrum Antimicrobials . are managed depending on several factors as discussed below under Prevention . The total white blood cell count and absolute band count in neonates are poor predictors of early-onset sepsis. However, an elevated ratio of immature:total polymorphonuclear leukocytes of > 0.16 is sensitive, and values below this cutoff have a high negative predictive value. However, specificity is poor; up to 50% of term neonates have an elevated ratio. Values obtained after 6 hours of life are more likely to be abnormal and clinically useful than those obtained immediately after birth. The platelet count may fall hours to days before the onset of clinical sepsis but more often remains elevated until a day or so after the neonate becomes ill. This fall is sometimes accompanied by other findings of DIC (eg, increased fibrin degradation products, decreased fibrinogen, prolonged international normalized ratio [INR]). Given the timing of these changes, the platelet count is not typically helpful in evaluating a neonate for sepsis. Because of large numbers of circulating bacteria, organisms can sometimes be seen in or associated with polymorphonuclear leukocytes by applying Gram stain,methylene blue, or acridine orange to the buffy coat. Regardless of the results of the CBC or LP, in all neonates with suspected sepsis (eg, those who look sick or are febrile or hypothermic), antibiotics should be started immediately after cultures (eg, blood and CSF [if possible]) are taken. There is a risk of increasing hypoxia during an LP in already hypoxemic neonates. However, LP should be done in neonates with suspected sepsis as soon as they are able to tolerate the procedure (see also Diagnosis under Neonatal Bacterial Meningitis). Supplemental oxygen is given before and during LP to prevent hypoxia. Because GBS pneumonia manifesting in the first day of life can be confused with Umbilical vessels are frequently contaminated by organisms on the umbilical stump, especially after a number of hours, so blood cultures from umbilical venous lines may not be reliable. Therefore, blood for culture should be obtained by venipuncture, preferably at 2 peripheral sites. Although the optimal skin preparation to do before obtaining blood cultures in neonates is not defined, clinicians can apply an iodine-containing liquid and allow the site to dry. Alternatively, blood obtained soon after placement of an umbilical arterial catheter may also be used for culture if necessary. Blood should be cultured for both aerobic and anaerobic organisms. However, the minimum amount of blood per blood culture bottle is 1.0 mL; if < 2 mL is obtained, it should all be placed in a single aerobic blood culture bottle. If catheter-associated sepsis is suspected, a culture specimen should be obtained through the catheter as well as peripherally. In>90% of positive bacterial blood cultures, growth occurs within 48 hours of incubation. Data on capillary blood cultures are insufficient to recommend them. Candidaspecies grow in blood cultures and on blood agar plates, but if other fungi are suspected, a fungal culture medium should be used. For species other thanCandida, fungal blood cultures may require 4 to 5 days of incubation before becoming positive and may be negative even in obviously disseminated disease. Proof of colonization (in mouth or stool or on skin) may be helpful before culture results are available. Neonates with candidemia should undergo LP to identify candidal meningitis. Indirect ophthalmoscopy with dilation of the pupils is done to identify retinal candidal lesions. Renal ultrasonography is done to detect renal mycetoma. Urine testing is needed only for evaluation of late-onset sepsis. Urine should be obtained by catheterization or suprapubic aspiration, not by urine collection bags. Although only culture is diagnostic, a finding of≥5 white blood cells/high-power field in the spun urine or any organisms in a fresh unspun gram-stained sample is presumptive evidence of a urinary tract infection (UTI). Absence of pyuria does not rule out UTI. Numerous tests are often abnormal in sepsis and have been evaluated as possible early markers. In general, however, sensitivities tend to be low until later in illness, and specificities are suboptimal. Biomarkers are not considered useful for determining when to initiate antibiotics for neonatal sepsis because of their poor positive predictive value, but they may have an adjunctive role in determining when it may be acceptable to stop antibiotics if cultures remain negative in suspected early-onset sepsis. Acute-phase reactantsare proteins produced by the liver under the influence of IL-1 when inflammation is present. The most studied of these is quantitative C-reactive protein. A concentration of ≥ 1 mg/dL (9.52 nmol/L) (measured by nephelometry) is generally considered abnormal. Elevated levels occur within 6 to 8 hours of developing sepsis and peak at 1 day. The sensitivity of C-reactive protein measurements is higher if measured after 6 to 8 hours of life. Two normal values obtained between 8 hours and 24 hours after birth and then 24 hours later have a negative predictive value of 99.7%. Procalcitonin is being investigated as an acute-phase reactant marker for neonatal sepsis. Although procalcitonin appears more sensitive than C-reactive protein, it is less specific ( Diagnosis references ). A combination of biomarkers that includes procalcitonin and C-reactive protein may prove to be more useful for determining antibiotic duration ( 1.Pontrelli G, De Crescenzo F, Buzzetti R, et al: Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: A meta-analysis.BMC Infect Dis17(1):302, 2017. doi: 10.1186/s12879-017-2396-7 2.Stocker M, van Herk W, El Helou S, et al: C-reactive protein, procalcitonin, and white blood count to rule out neonatal early-onset sepsis within 36 hours: A secondary analysis of the neonatal procalcitonin intervention study.Clin Infect Dis73(2):e383–e390, 2021. doi: 10.1093/cid/ciaa876 