Tigecycline therapy in pediatric patients with multidrug resistant bacteremia / Tratamiento con tigeciclina en pacientes pediátricos con bacteriemia multirresistente

INTRODUCTION: Multidrug resistance among bacteria increases the need for new therapeutic options. Tigecycline is one candidate drug, due to property of a wider anti-bacterial spectrum to multi-drug resistant (MDR) pathogens. However, it has still not been approved for use in pediatric patients. METHODS: In this study the effectiveness and safety of tigecycline in children was assessed retrospectively. RESULTS: A total of 36 pediatric patients, received tigecycline therapy with a median of 13 days (2-32 days). Tigecycline was used as a combination therapy in all cases. Microbiological eradication was achieved in 27 patients (75%) and clinical response was observed in 30 patients (83%). There were six cases (17%) of relapse. CONCLUSION: Our findings suggest that tigecycline may be an option for children with severe infections due to multidrug resistant bacteria

INTRODUCCIÓN: La multirresistencia por parte de las bacterias aumenta la necesidad de nuevas opciones de tratamiento. La tigeciclina es un fármaco candidato, debido a la propiedad de presentar un espectro antibacteriano más amplio frente a patógenos multirresistentes. Sin embargo, todavía no se ha aprobado para su uso en pacientes pediátricos. MÉTODOS: En este estudio se evaluó de forma retrospectiva la eficacia y la seguridad de la tigeciclina en niños. RESULTADOS: Un total de 36 pacientes pediátricos recibieron tratamiento con tigeciclina durante una mediana de 13 días (2-32 días). La tigeciclina se utilizó como parte de un tratamiento combinado en todos los casos. Se consiguió la erradicación microbiológica en 27 pacientes (75%) y se observó respuesta clínica en 30 pacientes (83%). Hubo 6 casos (17%) de recidiva. CONCLUSIÓN: Nuestros hallazgos sugieren que la tigeciclina puede ser una opción para niños con infecciones graves debidas a bacterias multirresistentes

Asociación entre la concentración de vitamina D y la sepsis neonatal extrahospitalaria de aparición tardía / Association between vitamin D level and community-acquired late-onset neonatal sepsis

Introducción. El objetivo fue determinar la relación entre la concentración materna e infantil de vitamina D y la sepsis de aparición tardía. Población y métodos. En este estudio se incluyó a los bebés nacidos con ≥ 37 semanas de gestación hospitalizados con diagnóstico de sepsis de aparición tardía. Se comparó la concentración de vitamina D de los niños y sus madres del grupo del estudio y del de referencia. Resultados. El grupo del estudio incluyó a 46 pacientes con sepsis de aparición tardía nacidos a término y el grupo de referencia, 46 pacientes con hiperbilirrubinemia. La suplementación con vitamina D durante el embarazo fue menor en las madres del grupo del estudio que en el de referencia (p = 0,001). La concentración sérica de 25-hidroxivitamina D [25(OH)D] de los niños y las madres del grupo del estudio fue significativamente menor que la del grupo de referencia (p < 0,001). Se observó una correlación positiva entre la 25(OH)D en las madres y los niños de ambos grupos (r: 0,38; p < 0,001). El valor de corte para la 25(OH)D, que determina el riesgo de sepsis neonatal de aparición tardía, se estableció en 15,45 ng/ml (sensibilidad: 91,3 %; especificidad: 71,7 %; área bajo la curva: 0,824; p < 0,001). Conclusiones. La concentración de 25(OH)D fue inferior en los bebés nacidos a término con sepsis de aparición tardía y sus madres en comparación con el grupo de referencia. La correlación entre la concentración sérica de 25(OH)D de los niños y sus madres fue positiva.

Introduction. The objective was to determine the relationship between mother and infant vitamin D levels and late onset sepsis. Population and methods.Infants born ≥37 weeks of gestational age who were hospitalized with the diagnosis of late-onset sepsis were enrolled to this prospective case control study. VitaminD levels of the infants and their mothers in the study and a control group were compared. Results. Fourty six term patients with lateonset sepsis composed the study group, 46 patients with hyperbilirubinemia as the control group. Vitamin D supplementation during pregnancy was lower in mothers of study group compared to the control group (p = 0.001). Serum 25-hydroxyvitamin D levels of infants and mothers in the study group were significantly lower than the control group (p < 0.001). There was a positive correlation between 25-hydroxyvitaminD levels of mothers and infants in both groups (r: 0.38, p < 0.001). The best cut off value of 25-hydroxyvitamin D, which determines the risk of late-onset sepsis in neonates, was detected as 15.45 ng/ml (sensitivity: 91.3 %, specificity: 71.7 %, area under the curve: 0.824, p < 0.001). Conclusions.In this study, 25-hydroxyvitaminD levels were found to be lower in term infants with late-onset sepsis and among their mothers compared to the control group. Positive correlation was found between serum 25(OH)D levels of infants and their mothers. Key words: newborn infant, sepsis,

Association between vitamin D level and community-acquired late-onset neonatal sepsis. / Asociación entre la concentración de vitamina D y la sepsis neonatal extrahospitalaria de aparición tardía.

INTRODUCTION: The objective was to determine the relationship between mother and infant vitamin D levels and late onset sepsis. POPULATION AND METHODS: Infants born > 37 weeks of gestational age who were hospitalized with the diagnosis of late-onset sepsis were enrolled to this prospective case control study. VitaminD levels of the infants and their mothers in the study and a control group were compared. RESULTS: Fourty six term patients with late-onset sepsis composed the study group, 46 patients with hyperbilirubinemia as the control group. Vitamin D supplementation during pregnancy was lower in mothers of study group compared to the control group (p = 0.001). Serum 25-hydroxyvitamin D levels of infants and mothers in the study group were significantly lower than the control group (p < 0.001). There was a positive correlation between 25-hydroxyvitamin D levels of mothers and infants in both groups (r: 0.38, p < 0.001). The best cut off value of 25-hydroxyvitamin D, which determines the risk of late-onset sepsis in neonates, was detected as 15.45 ng/ml (sensitivity: 91.3 %, specificity: 71.7 %, area under the curve: 0.824, p < 0.001). CONCLUSIONS: In this study, 25-hydroxyvitamin D levels were found to be lower in term infants with late-onset sepsis and among their mothers compared to the control group. Positive correlation was found between serum 25(OH)D levels of infants and their mothers.

Introducción. El objetivo fue determinar la relación entre la concentración materna e infantil de vitamina D y la sepsis de aparición tardía. Población y métodos. En este estudio se incluyó a los bebés nacidos con >37 semanas de gestación hospitalizados con diagnóstico de sepsis de aparición tardía. Se comparó la concentración de vitamina D de los niños y sus madres del grupo del estudio y del de referencia. Resultados. El grupo del estudio incluyó a 46 pacientes con sepsis de aparición tardía nacidos a término y el grupo de referencia, 46 pacientes con hiperbilirrubinemia. La suplementación con vitamina D durante el embarazo fue menor en las madres del grupo del estudio que en el de referencia (p = 0,001). La concentración sérica de 25-hidroxivitamina D [25(OH)D] de los niños y las madres del grupo del estudio fue significativamente menor que la del grupo de referencia (p < 0,001). Se observó una correlación positiva entre la 25(OH)D en las madres y los niños de ambos grupos (r: 0,38; p < 0,001). El valor de corte para la 25(OH)D, que determina el riesgo de sepsis neonatal de aparición tardía, se estableció en 15,45 ng/ml (sensibilidad: 91,3 %; especificidad: 71,7 %; área bajo la curva: 0,824; p < 0,001). Conclusiones. La concentración de 25(OH)D fue inferior en los bebés nacidos a término con sepsis de aparición tardía y sus madres en comparación con el grupo de referencia. La correlación entre la concentración sérica de 25(OH)D de los niños y sus madres fue positiva.

Tigecycline therapy in pediatric patients with multidrug resistant bacteremia.

INTRODUCTION: Multidrug resistance among bacteria increases the need for new therapeutic options. Tigecycline is one candidate drug, due to property of a wider anti-bacterial spectrum to multi-drug resistant (MDR) pathogens. However, it has still not been approved for use in pediatric patients. METHODS: In this study the effectiveness and safety of tigecycline in children was assessed retrospectively. RESULTS: A total of 36 pediatric patients, received tigecycline therapy with a median of 13 days (2-32 days). Tigecycline was used as a combination therapy in all cases. Microbiological eradication was achieved in 27 patients (75%) and clinical response was observed in 30 patients (83%). There were six cases (17%) of relapse. CONCLUSION: Our findings suggest that tigecycline may be an option for children with severe infections due to multidrug resistant bacteria.

Enzyme Replacement Therapy in Hypophosphatasia

Hypophosphatasia (HPP) is associated with significant morbidity and mortality in pediatric patients. The disease also imposes a high disease-burden in adult-onset HPP. Asfotase alfa (AA) is the first-in-class, bone-targeted, enzyme- replacement therapy designated to reverse the skeletal mineralisation defects in HPP. A male newborn presented with extreme fontanel gap and respiratory distress. He was diagnosed with perinatal lethal HPP thus AA treatment was started. Serum alkaline phosphatase (ALP) levels increased as high as 12,700 U/L during treatment. Any side effect related to AA was not observed. AA may be a valuable emerging therapy for the treatment of HPP.

Experience and Prognosis of Systemic Neonatal Thrombosis at a Level III NICU.

OBJECTIVE: The objective of this article was to evaluate neonates diagnosed systemic thrombosis and their outcomes. METHODS: We retrospectively evaluated data of neonatal systemic thrombosis between January 2011 and December 2016. RESULTS: Among 4376 hospitalized, 30 neonates (0.69%) were diagnosed systemic thrombosis. Their mean birth weight was 2422±1152 g (680 to 4750 g), gestational age was 35±5.4 weeks (25 to 41 wk). There were 25 neonates (83.3%) with venous, 5 patients (16.7%) with arterial thrombosis. The most common sites that thrombi localized were major vessels (n=11) and central nervous system (n=8). Central catheter insertion (76.7%) and prematurity (46.7%) were the most common risk factors. Congenital prothrombotic risk factors included G1691A mutation in factor V Leiden (n=1), mutation in factor XIII (n=1), C677T mutation in methylenetetrahydrofolate reductase (n=6). More than 1 congenital risk factor was identified in 5 patients. The patients were treated with low-molecular weight heparin. The mortality rate was 13.3% (n=4). Two patients required amputation (left foot, left upper extremity). Unilateral renal atrophy (n=1), cerebral palsy (n=2), hemiparesis (n=1) were identified among followed 24 patients. CONCLUSIONS: Critically ill neonates are at risk for thrombosis, and devastating consequences can result. As indwelling catheters and prematurity are important, careful monitorization, early diagnosis and therapy, cautious care of central catheter might reduce the incidence and adverse outcome.

A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus.

Congenital hyperinsulinism (CHI) is the most common cause of neonatal persistent hypoglycemia caused by mutations in nine known genes. Early diagnosis and treatment are important to prevent brain injury. The clinical presentation and response to pharmacological therapy may vary depending on the underlying pathology. Genetic analysis is important in the diagnosis, treatment, patient follow-up, and prediction of recurrence risk within families. Our patient had severe hypoglycemia and seizure following birth. His diagnostic evaluations including genetic testing confirmed CHI. He was treated with a high-glucose infusion, high-dose diazoxide, nifedipine, and glucagon infusion. A novel homozygous mutation (p.F315I) in the KCNJ11 gene, leading to diazoxide-unresponsive CHI, was identified. Both parents were heterozygous for this mutation. Our patient's clinical course was complicated by severe refractory hypoglycemia; he was successfully managed with sirolimus and surgical intervention was not required. Diazoxide, nifedipine, and glucagon were discontinued gradually following sirolimus therapy. The patient was discharged at 2 months of age on low-dose octreotide and sirolimus. His outpatient clinical follow-up continues with no episodes of hypoglycemia. We present a novel homozygous p.F315I mutation in the KCNJ11 gene leading to diazoxide-unresponsive CHI in a neonate. This case illustrates the challenges associated with the diagnosis and management of CHI, as well as the successful therapy with sirolimus.

Effects of Two Different Exogenous Surfactant Preparations on Serial Peripheral Perfusion Index and Tissue Carbon Monoxide Measurements in Preterm Infants with Severe Respiratory Distress Syndrome.

BACKGROUND: Administration of an exogenous surfactant may affect both ventilatory and hemodynamic parameters in preterm infants with respiratory distress syndrome (RDS). Peripheral perfusion may be expected to be influenced, and serial perfusion index (PI) values may show this effect. Noninvasive transcutaneous carbon monoxide (TCO) monitoring may show RDS severity, oxidative and inflammatory stress, and response to surfactant treatment. METHODS: This randomized controlled nonblinded study was performed in 30 preterm infants with RDS, treated with poractant alfa (n = 15) or beractant (n = 15); 18 preterm infants without RDS served as a control group. Oxygenation and hemodynamic parameters were recorded and compared through the first 6 hours of treatment. PI and TCO values were measured prior to (Tp), immediately after (T0), and at 5 minutes (T5), 30 minutes (T30), 60 minutes (T60), and 360 minutes (T360) after the bolus surfactant administration. The mean arterial pressure, oxygenation index, pH, and lactate levels were recorded simultaneously. RESULTS: Both study groups had lower Tp PI and higher Tp TCO levels than controls. Both surfactant preparations improved the PI, TCO, mean arterial pressure, oxygenation index, pH, and lactate levels at the end point of T360. However, the median Tp PI value of 1.3 first decreased to 0.86 at T0 (P < 0.001), and then it increased to 0.99 at T5 (p < 0.001) and to 1.25 at T30 (p = 0.037). The median Tp TCO value of 3 decreased to 2, 1.5, 0, and 0 at T0, T5, T30, and T60, respectively (p < 0.001). PI more quickly recovered to Tp values (30 minutes vs. 60 minutes) and reached the control group values (30 minutes vs. 360 minutes) with beractant compared to that with poractant alfa. TCO recovered to Tp values in both groups at the same time (5 minutes vs. 5 minutes), but reached the control group values more quickly (5 minutes vs. 30 minutes) with poractant alfa than with beractant. CONCLUSION: Patients with RDS had poor perfusion, and PI improved with both surfactant preparations only following a short decline in the 1(st) minute. The expected improvement of PI occurred earlier in the beractant subgroup. TCO declined in both groups, showing lung improvement and decreased oxidative/inflammatory stress, and it was normalized earlier with poractant alfa.

Optimal Time of Tracheotomy in Infants: Still a Dilemma.

Objective. Infants with respiratory failure may require prolonged intubation. There is no consensus on the time of tracheotomy in neonates. Methods. We evaluated infants applied tracheotomy, time of procedure, and early complications in our neonatal intensive care unit (NICU) retrospectively from January 2012 to December 2013. Results. We identified 9 infants applied tracheotomy with gestational ages 34 to 41 weeks. Their diagnoses were hypotonic infant, subglottic stenosis, laryngeal cleft, neck mass, and chronic lung disease. Age on tracheotomy ranged from 4 to 10 weeks. Early complication ratio was 33.3% with minimal bleeding (1), air leak (1), and canal revision requirement (1). We discharged 7 infants, and 2 infants died in the NICU. Conclusion. Tracheotomy makes infant nursing easy for staff and families even at home. If carried out by a trained team, the procedure is safe and has low complication. When to apply tracheotomy should be individualized, and airway damage due to prolonged intubation versus risks of tracheotomy should be taken into consideration.

Both parents of neonatal intensive care unit patients are at risk of depression.

Postpartum depression is a serious disorder that can be seen not only in mothers but also in fathers; therefore, it negatively affects the whole family. Hospitalization in the neonatal intensive care unit (NICU) is a stress factor for the parents and contributes to depression. We aimed to detect the frequency of postpartum depression and the contributing risk factors in parents of NICU patients. The Edinburgh Postnatal Depression Scale was used for mothers and the Beck Depression Inventory was performed for fathers in the 2nd and 6th weeks after delivery. At the 2nd week, maternal depression frequency was found as 38.3%, with a mean score [ms] of 10.97±6.93. At the 6th week, maternal depression frequency was 33.3% (ms: 9.57±5.78). Paternal depression was 11.7% (ms= 7.13±7.35) at the 2nd week and 10.0% (ms: 6.50±5.79) at the 6th week. The frequency of maternal depression remained stable, but mean maternal depression scores were decreased at the 6th week compared to the 2nd week (p=0.023). However, paternal depression scores were similar in both periods (p=0.428). The infants' disease severity at admission to the NICU, as shown by SNAPPE-II risk scores, was positively correlated with Edinburgh depression scores of the mothers at the postnatal 2nd week, but not at the 6th week. In conclusion, NICU stay of high-risk infants may cause depression in their mothers and fathers, even in the absence of any previous risk factor. Although at a lower rate than in mothers, fathers may also suffer from depression. Parental depression screening and whole family support during NICU hospitalization are strongly recommended.

LY96, UPKIB mutations and TLR4, CD14, MBL polymorphisms in children with urinary tract infection.

OBJECTIVE: To evaluate genetic variations of innate immune system such as mannose binding lectin (MBL), Toll like receptor 4 (TLR4), CD14, LY96 (MD2) and Uroplakin 1B (UPK1B) genes in children with recurrent urinary tract infection (UTI). METHODS: The study included 30 children with recurrent UTI and 30 healthy controls. Blood was drawn and analysed for genetic polymorphisms of MBL, TLR4 and CD14 genes by the PCR-RFLP method. Direct DNA sequencing analysis was performed for LY96 and UPK 1B gene mutation in 10 children from UTI group and 5 children from control group. RESULTS: TLR4 gene Thr399Ile polymorphism was not observed in any child. Genotype distribution and allele frequency of Asp299Gly polymorphism was similar in both groups (p = 0.55). Codon 54 polymorphism of the MBL gene was similar in UTI and control groups (p = 0.49). -159 CC/CT/TT genotypes of CD14 gene was similar between the two groups (p = 0.14). UPK1B and LY96 gene DNA sequence analysis was similar in UTI and control groups. CONCLUSIONS: This study is the first study in which different parts of the innate immune system were evaluated in UTI etiopathogenesis in Turkish children. The results did not point out a significant role of any of the genes evaluated in this study.