The importance of defining the age-specific TREC/KREC levels for detection of various inborn errors of immunity in pediatric and adult patients.

This study aimed to establish physiological TREC/KREC values in a healthy population of different ages to create cut-offs and analyze pediatric patients with various inborn errors of immunity. Dry blood spots and DNA samples purified from whole blood were used for TREC/KREC quantification using real-time PCR. Observed difference (p < 0.001) between methods revealed the isolation method as a factor we need to consider when determinating cut-offs. Data of 713 healthy individuals showed a negative correlation (p < 0.001) between age and TREC/KREC levels with gender difference observed only for KREC in a group of 51-60 years old (p < 0.001). The 5th percentile cut-off values were set for age groups, which allowed us to identify 25% of patients with immunodeficiencies in case of non-zero, borderline values of TREC/KREC. Screening of infants with congenital heart disease identified 11% of patients with lowered TREC/KREC and shows potential for newborn screening of specific groups of patients.

Tigecycline Therapy for Multi-drug-Resistant Pseudomonas aeruginosa Sepsis Associated with Multi-organ Failure in an Infant with Persistent Arterial Duct. Case Report.

Sepsis is the leading cause of death in infants and children worldwide. The growing drug resistance in nosocomial gram-negative bacteria has resulted in treatment challenges. One of the most common multi-drug-resistant bacteria is Pseudomonas aeruginosa. Resistance to antibiotics used in Pseudomonas aeruginosa infections limits the therapeutic options. We present a tigecycline administration in a 5-month-old infant with patent arterial duct, heart failure, and respiratory failure due to respiratory syncytial virus bronchiolitis with subsequent respiratory distress syndrome and severe sepsis caused by multi-drug-resistant Pseudomonas aeruginosa. Despite combined antibiotic therapy with meropenem, amikacin, and colistin, inflammatory markers increased. Because of life-threatening condition, tigecycline was added to the therapy and was administered intravenously twice daily. Within 48 h, inflammatory markers started to decrease and tigecycline therapy continued for 13 days without adverse effects. Tigecycline used in combination with other antibiotics might be a valuable therapeutic approach in the management of multi-drug-resistant bacteria infections in pediatric patients when conventional antibiotics have failed. Further studies are needed to evaluate the efficacy and safety of tigecycline administration in critically ill pediatric patients.

Immune Abnormalities in Patients With Single Ventricle Circulation Precede the Fontan Procedure.

BACKGROUND: Immune abnormalities are common in Fontan patients with protein-losing enteropathy. Limited data exist on immune function of other patients with single ventricle circulation. METHODS: This prospective cohort study evaluated immunologic characteristics of children with single ventricle circulation from neonatal age up to early post-Fontan period. RESULTS: Low leukocyte counts were observed in half of the patients prior to bidirectional Glenn and Fontan surgery. Total lymphocyte counts were below normal range in 36% to 63% of patients across all groups except patients following Fontan procedure who had normal counts. Typical lymphocyte subpopulation patterns were (1) high counts of total and helper T lymphocytes (CD3+ and CD4+ cells), low B lymphocytes (CD19+ cells), and increased CD4/CD8 ratio in neonates and (2) low T lymphocytes (CD3+, CD4+, CD8+ cells) with high natural killer cells (CD16+) and B lymphocytes (CD19+ cells) in other groups. Low preoperative total lymphocyte counts were associated with longer intensive care unit stay in patients after bidirectional Glenn and Fontan procedure ( P = .03 and P = .01, respectively) and low leukocyte counts with higher incidence of pleural effusions and chylothorax after Fontan procedure ( P = .005 and P = .002, respectively). CONCLUSIONS: Single ventricle patients display several immunological abnormalities. Beyond the neonatal age, an immune pattern includes CD3+, CD4+, CD8+ lymphopenia, and CD16+ and CD19+ lymphocytosis. B-cell lymphocytosis compensates T-cell lymphopenia, producing normal total lymphocyte counts in patients early after Fontan surgery. Low preoperative total lymphocyte counts may be associated with longer postoperative intensive care unit stay in patients with bidirectional Glenn and Fontan procedure and leukopenia with pleural effusions in Fontan patients.