Late-Onset Sepsis in Very Low Birth Weight Premature Infants: A 10-Year Review of a Brazilian Tertiary University Hospital-the Challenge Remains.

OBJECTIVES: This study aimed to assess the incidence of late-onset sepsis (LOS), associated risk factors, and short-term prognosis in very low birth weight (VLBW) infants in a 10-year period. STUDY DESIGN: A cohort study was conducted with 752 VLBW preterm infants-23 to 33 gestational weeks and 400 to 1,500 g birth weight-admitted to a neonatal intensive care unit from 2008 to 2017 and who survived over 72 hours. LOS was defined as clinical and laboratory signs of infection, whether or not confirmed by blood culture. VLBW infants were divided into groups and compared: no LOS versus proven LOS versus clinical LOS. Study variables included maternal, birth, and neonatal data, morbidities, procedures, etiological agents, and outcome-death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, and retinopathy of prematurity (ROP). Analysis of variance with multiple Tukey's or Wald's comparison with gamma distribution, and stepwise multiple logistic regression model, adjusted for year, and gestational age, were used for statistical analysis. RESULTS: LOS incidence was 39% (proven LOS: 29%; clinical LOS: 10%). Septic VLBW infants showed higher mortality (proven LOS: 23.2%; clinical LOS: 41.9%) compared with no LOS (8.9%). Coagulase-negative staphylococci (56%), Gram-negative (26%), and fungi (8%) were the most frequent etiological agents. In comparing the groups, septic VLBW infants had lower gestational age and birth weight, presented more morbidities, and underwent more invasive procedures. The risk factors for proven and clinical LOS were days of mechanical ventilation and parenteral nutrition. LOS was associated with increased risk of death, BPD, and ROP. CONCLUSION: LOS showed high incidence and mortality, often caused by Gram-positive bacteria. Care interventions were the main risk factors associated. LOS had a major negative impact on short-term prognosis in VLBW infants. LOS reduction strategies are necessary and urgent. KEY POINTS: · LOS is associated with clinically significant neonatal morbidities and death in VLBW premature infants.. · There is association between LOS and duration of intensive care interventions.. · Quality improvement initiatives can be a pathway for LOS reduction..

Admission hypothermia, neonatal morbidity, and mortality: evaluation of a multicenter cohort of very low birth weight preterm infants according to relative performance of the center.

This prospective cohort study aimed to assess the association of admission hypothermia (AH) with death and/or major neonatal morbidities among very low birth weight (VLBW) preterm infants based on the relative performance of 20 centers of the Brazilian Network of Neonatal Research. This is a retrospective analysis of prospectively collected data using the database registry of the Brazilian Network on Neonatal Research. Center performance was defined by the relative mortality rate using conditional inference trees. A total of 4356 inborn singleton VLBW preterm infants born between January 2013 and December 2016 without malformations were included in this study. The centers were divided into two groups: G1 (with lower mortality rate) and G2 (with higher mortality rate). Crude and adjusted relative risks (RR) and 95% confidence intervals (95%CI) were estimated by simple and multiple log-binomial regression models. An AH rate of 53.7% (19.8-93.3%) was significantly associated with early neonatal death in G1 (adjusted RR 1.41, 95% CI 1.09-1.84) and G2 (adjusted RR 1.29, 95%CI 1.01-1.65) and with in-hospital death in G1 (adjusted RR 1.29, 95%CI 1.07-1.58). AH was significantly associated with a lower frequency of necrotizing enterocolitis (adjusted RR 0.58, 95%CI 38-0.88) in G2.Conclusion: AH significantly associated with early neonatal death regardless of the hospital performance. In G2, an unexpected protective association between AH and necrotizing enterocolitis was found, whereas the other morbidities assessed were not significantly associated with AH. What is Known: • Admission hypothermia is associated with early neonatal death. • The association of admission hypothermia with major neonatal morbidities has not been fully established. What is New: • Admission hypothermia was significantly associated with early neonatal and in-hospital death in centers with the lowest relative mortality rates. • Admission hypothermia was not associated with major neonatal morbidities and with in-hospital death but was found to be a protective factor against necrotizing colitis in centers with the highest relative mortality rates.

Risk factors for infection with coagulase-negative staphylococci in newborns from the neonatal unit of a brazilian university hospital.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are one of the most frequent causative agents of neonatal nosocomial infections, especially in premature and low-weight newborns. Risk factors for infection include extracellular polysaccharide production and consequent biofilm formation that permit adhesion to the smooth surface of catheters and other medical devices. The objective of this study was to identify CoNS strains isolated from 105 newborns admitted to the Neonatal Unit of our hospital, and to evaluate the association of biofilm production and host risk factors with the occurrence of infection. METHODS: CoNS isolates were identified and classified as significant or contaminant based on clinical and laboratory data of the newborn medical records. Perinatal risk factors for infection, neonatal clinical evolution, and antibiotic treatment were analysed. In addition, the presence of genes (icaA, icaC and icaD) responsible for biofilm production in CoNS was investigated. RESULTS: Among the 130 CoNS strains studied, 66 (50.8%) were classified as clinically significant and 64 (49.2%) as contaminant. There was no difference in the detection of biofilm-specific genes between CoNS strains isolated from newborns with (81.8%) and without infection (84.3%), although 11 (91.7%) of the 12 children whose death was related to CoNS were infected with strains that were positive for these genes. Forty-five (83.3%) of the 54 newborns infected with CoNS were premature and 33 (61.1%) had a birth weight ≤ 1,500 g. Most newborns infected with CoNS had been submitted to invasive procedures, including catheter use (85.2%), parenteral nutrition (61.1%), and mechanical ventilation (57.4%). S. epidermidis was the most frequently isolated species (81.5%) and was more related to infection (86.3%) than to contamination (76.5%). CONCLUSION: Most newborns infected with CoNS presented factors that contributed to the colonization and development of infection with these microorganisms, including a birth weight ≤ 1,500 g, catheter complications, use of a drain, and previous antibiotic treatment. The fact that most children who died of CoNS-related infection carried strains positive for biofilm-specific genes indicates the importance of this virulence factor for the outcome of staphylococcal infections.

Conductive hearing loss in children with bronchopulmonary dysplasia: a longitudinal follow-up study in children aged between 6 and 24 months.

AIMS: To determine the occurrence of isolated and recurrent episodes of conductive hearing loss (CHL) during the first two years of life in very low birth weight (VLBW) infants with and without bronchopulmonary dysplasia (BPD). STUDY DESIGN, SUBJECTS AND OUTCOME MEASURES: In a longitudinal clinical study, 187 children were evaluated at 6, 9, 12, 15 18 and 24 months of age by visual reinforcement audiometry, tympanometry and auditory brain response system. RESULTS: Of the children with BPD, 54.5% presented with episodes of CHL, as opposed to 34.7% of the children without BPD. This difference was found to be statistically significant. The recurrent or persistent episodes were more frequent among children with BPD (25.7%) than among those without BPD (8.3%). The independent variables that contributed to this finding were small for gestational age and a 5 min Apgar score. CONCLUSIONS: Recurrent CHL episodes are more frequent among VLBW infants with BPD than among VLBW infants without BPD.

Utilidade da cultura da ponta de cateter no diagnóstico de infecção neonatal / Usefulness of catheter tip culture in the diagnosis of neonatal infections

OBJETIVO: Determinar o número de unidades formadoras de colônias que melhor correlaciona com a infecção relacionada a cateter em recém-nascidos. MÉTODOS: Este foi um estudo prospectivo de culturas semiquantitativas de pontas de cateteres de recém-nascidos da unidade neonatal da Faculdade de Medicina de Botucatu. Os microrganismos isolados de cateteres e hemoculturas periféricas foram identificados e submetidos ao teste de sensibilidade a drogas. O ponto de corte ótimo foi determinado pela curva receiver operating characteristic (ROC). RESULTADOS: Foram estudados 85 cateteres de 63 recém-nascidos. A espécie Staphylococcus epidermidis foi prevalente (75 por cento) nos cateteres. Dos 11 episódios de infecção diagnosticados, oito (72,7 por cento) foram associados aos estafilococos coagulase-negativa, dos quais seis pertenciam à espécie S. epidermidis. Pela curva ROC, o ponto de corte ótimo para o diagnóstico de infecção relacionada a cateter foi 122 unidades formadoras de colônias. CONCLUSÃO: O ponto de corte 122 unidades formadoras de colônias melhor se correlacionou com o diagnóstico de infecção relacionada a cateter em recém-nascidos.

OBJECTIVE: To determine the number of colony-forming units (CFU) that best correlates with catheter-related infections (CRI) in newborns. METHODS: This was a prospective study of semiquantitative cultures of catheter tips obtained from newborns in the neonatal unit at Faculdade de Medicina de Botucatu, state of São Paulo, Brazil. The microorganisms isolated from catheter and peripheral blood cultures were identified and submitted to a drug susceptibility test. The optimal cutoff point was determined by the receiver operating characteristic (ROC) curve. RESULTS: A total of 85 catheters obtained from 63 newborns were studied. Staphylococcus epidermidis was the predominant species in the catheters (75 percent). Eight of 11 (72.7 percent) CRI episodes were associated with coagulase-negative staphylococci, six of which were of the S. epidermidis type. ROC curve analysis indicated that the optimal cutoff point for the diagnosis of CRI was 122 CFU. CONCLUSION: The cutoff point of 122 CFU correlated best with the diagnosis of CRI in newborns.

Usefulness of catheter tip culture in the diagnosis of neonatal infections.

OBJECTIVE: To determine the number of colony-forming units (CFU) that best correlates with catheter-related infections (CRI) in newborns. METHODS: This was a prospective study of semiquantitative cultures of catheter tips obtained from newborns in the neonatal unit at Faculdade de Medicina de Botucatu, state of São Paulo, Brazil. The microorganisms isolated from catheter and peripheral blood cultures were identified and submitted to a drug susceptibility test. The optimal cutoff point was determined by the receiver operating characteristic (ROC) curve. RESULTS: A total of 85 catheters obtained from 63 newborns were studied. Staphylococcus epidermidis was the predominant species in the catheters (75%). Eight of 11 (72.7%) CRI episodes were associated with coagulase-negative staphylococci, six of which were of the S. epidermidis type. ROC curve analysis indicated that the optimal cutoff point for the diagnosis of CRI was 122 CFU. CONCLUSIONS: The cutoff point of 122 CFU correlated best with the diagnosis of CRI in newborns.

Comparison between qualitative and semiquantitative catheter-tip cultures: laboratory diagnosis of catheter-related infection in newborns / Comparação entre culturas qualitativa e semiquantitativa de ponta de cateter: diagnóstico laboratorial de infecção relacionada a cateter em recém-nascidos

This prospective study evaluated semiquantitative and qualitative catheter-culture methods for diagnosis of catheter-related infection (CRI) in newborns. Catheter tips from newborns admitted to the Neonatal Unit of the University Hospital of the Botucatu Medical School, UNESP were included in the study. Catheter cultures were performed with both semiquantitative and qualitative techniques. For CRI diagnosis, microorganisms isolated from catheter cultures and from peripheral blood cultures were identified and submitted to agent susceptibility test. The gold standard was the certain CRI diagnosis when same microorganism (specie and profile of susceptibility to agents) was isolated from both catheter tips and peripheral blood culture. A total of 85 catheters from 63 newborns were included in the study. The semiquantitative culture method, despite presenting lower sensitivity (90 percent), showed higher specificity (71 percent) when compared to 100 percent of sensitivity and 60 percent of specificity in the qualitative method. The identification of the microorganisms obtained from the catheter cultures showed a prevalence of coagulase-negative staphylococci(CNS) species. The specie Staphylococcus epidermidis (77.5 percent) was the prevalent in the catheters with positive semiquantitative cultures. Among 11 episodes with CRI diagnosis, 8 (72.7 percent) were associated with CNS species, of which 6 were S. epidermidis. Two episodes of CRI by S. aureus and one by Candida parapsilosis were also detected. The semiquantitative catheter-culture method showed advantages for CRI diagnosis in newborns when compared to the conservative qualitative method.

Este estudo prospectivo avaliou os métodos semiquantitativo e qualitativo de cultura de cateter para o diagnóstico de infecção relacionada a cateter (IRC) em recém-nascidos (RN). Foram incluídas pontas de cateteres provenientes de recém-nascidos internados na Unidade Neonatal do Hospital das Clínicas da Faculdade de Medicina de Botucatu, UNESP. Foram utilizadas as técnicas semiquantitativa e qualitativa de cultura de cateter. Para o diagnóstico de IRC, os microrganismos isolados das culturas de cateteres e de hemoculturas periféricas foram identificados e submetidos ao teste de sensibilidade a antimicrobianos. O padrão ouro correspondeu ao diagnóstico de certeza de IRC, com o isolamento do mesmo microrganismo (espécie e perfil de sensibilidade a antimicrobianos) isolado em hemocultura periférica. Foram estudados 85 cateteres provenientes de 63 RN. A cultura semiquantitativa, embora tenha apresentado menor sensibilidade (90 por cento), apresentou uma maior especificidade (71 por cento) em comparação à sensibilidade de 100 por cento e especificidade de 60 por cento encontradas na cultura qualitativa. Através da identificação dos microrganismos obtidos nas culturas de cateteres, observou-se uma predominância de espécies de Estafilococos coagulase-negativa (ECN). A espécie Staphylococcus epidermidis foi a prevalente (77,5 por cento) nos cateteres com culturas semiquantitativas positivas. Dos 11 episódios de IRC diagnosticados, 8 (72,7 por cento) foram associados a espécies de ECN, dos quais 6 eram da espécie S. epidermidis. Também foram detectados dois casos de IRC por S. aureus e um caso por Candida parapsilosis. O método de cultura semiquantitativo cateter apresentou vantagens para o diagnóstico de IRC em RN quando comparado com o método qualitativo tradicional.

Comparison between qualitative and semiquantitative catheter-tip cultures: laboratory diagnosis of catheter-related infection in newborns.

This prospective study evaluated semiquantitative and qualitative catheter-culture methods for diagnosis of catheter-related infection (CRI) in newborns. Catheter tips from newborns admitted to the Neonatal Unit of the University Hospital of the Botucatu Medical School, UNESP were included in the study. Catheter cultures were performed with both semiquantitative and qualitative techniques. For CRI diagnosis, microorganisms isolated from catheter cultures and from peripheral blood cultures were identified and submitted to agent susceptibility test. The gold standard was the certain CRI diagnosis when same microorganism (specie and profile of susceptibility to agents) was isolated from both catheter tips and peripheral blood culture. A total of 85 catheters from 63 newborns were included in the study. The semiquantitative culture method, despite presenting lower sensitivity (90%), showed higher specificity (71%) when compared to 100% of sensitivity and 60% of specificity in the qualitative method. The identification of the microorganisms obtained from the catheter cultures showed a prevalence of coagulase-negative staphylococci (CNS) species. The specie Staphylococcus epidermidis (77.5%) was the prevalent in the catheters with positive semiquantitative cultures. Among 11 episodes with CRI diagnosis, 8 (72.7%) were associated with CNS species, of which 6 were S. epidermidis. Two episodes of CRI by S. aureus and one by Candida parapsilosis were also detected. The semiquantitative catheter-culture method showed advantages for CRI diagnosis in newborns when compared to the conservative qualitative method.