The subjects were those who had clinical signs of infection and/or elevated C-reactive protein (CRP) among the patients who were identified with causative organisms in blood cultures within 72 hours of life [1,3]. In patients with skin flora, including coagulase-negative staphylococci, the diagnosis of sepsis was based on both the presence of clinical signs of infection and elevated CRP, or the same bacteria were continuously detected in the blood culture performed within 48 hours. Among patients who were positive for microorganisms in their blood specimens within 3 days of life, those with contaminants were excluded from the study. The following were assessed as contamination: if contaminants (Corynebacterium, Diphtheroids, Micrococci, and Propionibacterium) or more than one organism were detected in the blood culture and antibiotics were discontinued within 5 days in the surviving patient [1,5]. Using the medical data of patients with EOS, the incidence of sepsis and clinical findings of infections, including causative organisms, symptoms and signs, laboratory findings, mortality, and risk factors associated with fatality, were investigated.

Clinical symptoms associated with sepsis were limited to the following: decreased activity, fever, tachycardia, bradycardia, apnea, abdominal distension, and hypotension. Clinical symptoms and laboratory tests in the early phase of infection were limited to findings within the first 48 hours from the time of blood culture. Chorioamnionitis included both a clinical and histological diagnosis [8]. Maternal hypertension included all four types of hypertension in pregnancy classified as gestational hypertension, preeclampsia, eclampsia, and chronic hypertension of any etiology [17]. The use of antenatal steroids was limited to 2 or more doses of dexamethasone. The use of antenatal antibiotics was limited to the administration of drugs for more than 3 days. Apnea was defined as temporary cessation of breathing for a duration of >20 seconds or when accompanied by bradycardia and desaturation, even though the duration was <20 seconds [18]. Hypotension was defined as a mean blood pressure of <30 mmHg [19]. Neutropenia was defined as a neutrophil count of <1,000/μL [20]. Respiratory distress syndrome (RDS) was limited to the cases undergoing surfactant replacement treatments. Pneumothorax was limited to cases with chest tube insertion. Pulmonary hemorrhage was limited to cases that required interventional therapies, including tracheal instillation of epinephrine. Patent ductus arteriosus (PDA) was limited to cases with hemodynamic significance confirmed by echocardiography and associated symptoms. Acute kidney injury was defined as both oliguria (<1 mL/kg/hr) and elevated serum creatinine (>1.5 mg/dL) [21]. Empirical antimicrobial therapy for EOS was based on the use of ampicillin and gentamicin. Also, the results of culture test for maternal specimens were considered. The empirical antimicrobial regimen was considered appropriate if at least one antibiotic is susceptible to the causative organism; otherwise, it was assessed to be inappropriate. Fulminant infection was defined as deaths within 48 hours after the onset of sepsis [22]. Fatality in patients with sepsis was limited to death within 14 days after infection.

Data were analyzed using IBM SPSS Statistics ver. 20.0 (IBM Co., Armonk, NY, USA). The chi-square test and Fisher exact test were used for categorical variables, and the Man-Whitney U test and t test were used for continuous variables. Multiple logistic regression analysis was performed to detect the risk factors associated with the prognosis of EOS. P values less than 0.05 were considered statistically significant.

Of the total 3,862 patients, microorganisms were identified in the blood samples of 167 babies (4.3%). Among the infants with identified microbes in their blood specimens, 45 were diagnosed as infected, and the remaining 122 were classified as cases with contaminants. Among the babies with contaminants, mixed bacteria were detected in 2 cases, and 2 different contaminants were detected in blood culture tests at intervals of 48 hours in another. The EOS group was classified into 17 deaths and 28 survivors (Fig. 1).

In a total of 45 subjects, the most common pathogen responsible for EOS was GBS in 10 cases (22.2%), followed by E. coli in 9 cases (20%). The rate of gram-positive sepsis was higher in term than in preterm infants (85.7% vs. 51.6%) (P<0.05). In contrast, the rate of gram-negative infection was higher in preterm than in term infants (45.2% vs. 14.3%) (P<0.05) (Table 1).

The overall mortality within 14 days after the infection was 37.8 % (17 of 45). The number of deaths was the highest at 8 (47.1%) during the first 3 days after infection, 4 (23.5%) after 4–7 days, and 5 (29.4%) after 8–14 days (Table 2). Fulminant infections occurred in 7 cases (15.6%), and all were preterm infants. In detail, 3 cases occurred in patients with Pseudomonas aeruginosa and E. coli sepsis, respectively; the remaining 1 developed in infants with Staphylococcus aureus sepsis.

The rate of fatality in patients with P. aeruginosa, E. coli and GBS sepsis was 100%, 77.8%, and 10%, respectively. The overall rate of fatal infections in infants with gram-negative sepsis was 68.8%, which was higher than the 21.4% for patients with gram-positive infections (P<0.005) (Table 3).

There was a significant difference in terms of gestational age (26.8±3.3 weeks vs. 35.1±4.3 weeks) and birth weight (957.1±542.4 g vs. 2,520.4±924.4 g) between the death and survival groups (P< 0.001). Furthermore, the proportion of VLBWI was higher in the death group than in the survival group (82.4% vs. 14.3%) (P<0.001). The 1-min and 5-min Apgar scores were lower in the death group (P<0.001). The frequency of chorioamnionitis, antenatal steroid and antibiotic therapy was also higher in the death group (P<0.05). In a comparison of clinical symptoms during the early phase of infection, the frequencies of several variables, including decreased activity, bradycardia, hypotension, and fever, were different between the death and survival groups (P<0.05). Among the laboratory findings, elevated CRP and leukopenia were the most common findings (64.4% and 33.3%, respectively); however, there were no differences between the 2 groups. The rate of neutropenia was significantly higher in the death group than in the survival group (P<0.005). Moreover, in a comparison of comorbid diseases in the early phase of infection, several factors, including RDS, PDA, and pulmonary hemorrhage, were more common in the death group than in the survival group (P<0.05). Meningitis was complicated in 2 term infants with GBS sepsis, both of whom survived. The appropriateness of empiric antimicrobial therapy was not different between the 2 groups (Table 4).

Logistic regression analysis of individual variables was performed to adjust for differences in gestational age and birth weight between the death and survival groups. Gram-negative pathogens (odds ratio [OR], 42; 95% confidence interval [CI], 1.4–1,281.8) and some clinical findings, such as neutropenia (OR, 46; 95% CI, 1.3–1,628.7) and decreased activity (OR, 34; 95% CI, 1.8–633.4), were associated with fatality of sepsis after adjusting for these differences (Table 5).