Introduction: Klebsiella pneumoniae is one of the most important infectious agents in neonates. There are “classic” and hypervirulent strains of K. pneumoniae. The “classic” non-virulent strain of K. pneumoniae, producing extended-spectrum beta-lactamases (ESBLs), is associated with nosocomial infections. Hypervirulent K. pneumoniae strains are associated with invasive infections in previously healthy adult people, and most of them exhibit antimicrobial susceptibility. The role of virulent strains of K. pneumoniae (including hv-KP) in neonatal infections is unknown. The aim of the study was the assessment of the impact of virulence factors and antibiotic resistance of K. pneumoniae strains on clinical features and outcomes of neonatal infection.Materials and Methods: Two groups of infants were enrolled. The first group consisted of 10 neonates with sepsis caused by K. pneumoniae. The second group consisted of 10 neonates with urinary tract infection (UTI) caused by K. pneumoniae. We investigated the susceptibility of K. pneumoniae isolates to antibiotics, the ability of the microorganism to produce ESBL, and virulence factors, including the rmpA gene, aerobactin, and colibactin genes. In neonates with sepsis, we investigated K. pneumoniae isolates, which was taken from the blood, in neonates with UTI—from the urine.Results: In neonates with sepsis testing of K. pneumoniae isolates for ESBL production was positive in 60% of cases, in neonates with UTI—in 40% of cases. All blood and urine ESBL producing K. pneumoniae isolates were resistant to ampicillins, including protected ones, and third-generation cephalosporins. At the same time, these isolates were sensitive to meropenem, amikacin, and ciprofloxacin. The rmpA gene was detected in four blood, and three urine K. pneumoniae isolates. In neonates with sepsis rmpA gene in two cases was detected in ESBL-producing K. pneumoniae isolates. They were infants with meningitis, and both cases were fatal. In the group of infants with UTI, the rmpA gene was detected only in K. pneumoniae isolates not producing ESBL. Aerobactin and colibactin genes were detected in two neonates with sepsis and in three neonates with UTI. In all cases, aerobactin and colibactin genes were detected only in rmpA-positive K. pneumoniae isolates. Out of three fatal outcomes, two cases were caused by hv-KP producing ESBL.Conclusion: The prevalence of virulent strains of K. pneumoniae among neonates with sepsis and other neonatal infection is higher than we think. The most severe forms of neonatal sepsis with an unfavorable outcome in our study were due to virulent strains of K. pneumoniae.

Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-β, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS), as well as those with early onset of sepsis (EOS), had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted.

Klebsiella pneumoniae is one of the most important infectious agents among neonates. This pathogen has a potential to develop an increased antimicrobial resistance and virulence. The classic non-virulent strain of K. pneumoniae, producing an extended-spectrum beta-lactamases (ESBL), is associated with nosocomial infection mainly in preterm neonates. Hypervirulent K. pneumoniae strains are associated with invasive infection among previously healthy ambulatory patients, and most of them exhibit antimicrobial susceptibility. During the last few years, several cases of diseases caused by hypervirulent K. pneumoniae producing ESBL have been registered in different geographical regions of the world. However, reports of such cases in neonates are rare. Here, we reported that this pathogen can cause pyogenic meningitis in full-term neonate with poor prognosis. A previously healthy, full-term, 12-day-old neonate was admitted to the infectious diseases hospital with suspected meningitis. The clinical symptoms included loss of appetite, irritability, fever, seizures, and a bulging anterior fontanelle. The analysis of the cerebrospinal fluid confirmed the diagnosis of meningitis. Blood and cerebrospinal fluid cultures were positive for K. pneumoniae, producing ESBL. K. pneumoniae isolates were resistant to aminopenicillins, 3rd generation cephalosporins but were sensitive to imipenem and meropenem. The “string test” was positive. The study of the virulence factors of K. pneumoniae by PCR revealed the presence of the rmpA gene. A combination of K. pneumoniae virulence and drug resistance complicated by cerebral oedema led to the death of the neonate. We concluded that both the risk of developing severe forms of infection and the outcome of the disease due to K. pneumonia are associated with the phenotypic features of the pathogen such as its antibiotic susceptibility and virulence factors. Emergence of the ESBL-producing strain of hypervirulent K. pneumoniae could represent a new serious threat to public health, suggesting an urgent need to enhance clinical awareness and epidemiological surveillance.

Purpose. To evaluate clinical and epidemiological features of neonatal sepsis and assess the impact of organ dysfunction on its outcome.Characteristics of children and research methods. The authors carried out a retrospective analysis of 66 patients with neonatal sepsis hospitalized to the neonatal intensive care unit of the Kazan City Children’s Hospital No. 1 from 2013 to 2017. The diagnosis was based on the development of a systemic inflammatory response syndrome, an increase in C-reactive protein concentration in the blood more than 1 mg/dl, the presence of one or more foci of infection, the development of organ dysfunction and the isolation of the microorganism from venous blood. Bacteremia was a mandatory inclusion criterion.Results. In the most cases (54.5%) neonatal sepsis was caused by gram-negative bacteria. 41 and 4.5% of cases were caused by gram-positive bacteria and fungi, respectively. Among the gram-negative bacteria, the main causative agents of sepsis were Klebsiella pneumoniae (27 cases, 41%), among the gram-positive bacteria –staphylococci (24 cases, 36.5%). Fungal sepsis was caused by Candida kruzei (2 cases) and Candida albicans (1 case). In 11 (17%) cases there was a dysfunction of a single organ, in 31 (47%) cases – dysfunction of 2 organs and in 24 (36%) cases – dysfunction of more than 2 organs. The most common impairments were respiratory dysfunction (86%) and hemostatic disorders in the form of thrombocytopenia (58%). Neonatal sepsis was fatal in 11 (17%) cases. It was found that the multiple organ dysfunction was associated with a risk of death (odds ratio – OR = 29.3; 95% CI 3.4–249.7). Among the signs of organ dysfunction, coma (OR = 30.8; 95% CI 3.0–316.6), elevated blood lactate level of more than 5 mmol/l (OR = 22.1; 95% CI 3.5–139,6) and a low platelet count of less than 50 · 109/l (OR = 5; 95% CI 1.2–21.3) had the prognostic significance.Conclusion. Modern neonatal sepsis has a diverse etiology with gram-negative bacteria as causative agents in half of the cases. Despite modern treatment methods, neonatal sepsis remains a formidable infectious pathology. The risk of fatal outcome is associated with organ dysfunction. Coma, elevated blood lactate level and severe thrombocytopenia are the most significant predictors of fatal outcome in neonatal sepsis.

миляуша ильдуСовна иСмагилова, врач-педиатр изоляционно-диагностического отделения Детской республиканской клинической больницы, Казань, Россия Реферат. В статье описан клинический случай развития синдрома токсического шока у девочки 7 лет на фоне скарлатины. Рассмотрены возможные причины развития синдрома токсического шока и его клинические проявления. Ключевые слова: стрептококковая инфекция, скарлатина, синдром токсического шока.