ABSTRACT Objective To compare in-hospital outcomes between small-for-gestational-age and appropriate-for-gestational-age preterm neonates who needed intensive care. Methods A retrospective cohort study with preterm newborns, from January to December 2017. The results are presented as median, frequency, and odds ratio. Numerical variables were compared using the Wilcoxon test. Categorical variables were compared using the χ2 test. We considered p<0.05 as significant. Results Out of 129 preterm newborns included, 20.9% were small-for-gestational-age. Median gestational age was 31 2/7 weeks, birthweight was 1,450g, and length of hospital stay was 39 days. Preterm small-for-gestational-age newborns presented a higher chance of peri-intraventricular hemorrhage (odds ratio of 3.23; p=0.02), retinopathy of prematurity (odds ratio of 2.78 p=0.02), patent ductus arteriosus (odds ratio of 2.50; p=0.04) and a lower chance of presumptive early-onset sepsis (odds ratio of 0.37; p=0.03). Conclusion Preterm small-for-gestational-age neonates were associated with peri-intraventricular hemorrhage, retinopathy of prematurity and patent ductus arteriosus. This emphasizes the need of special care for these neonates.

OBJETIVO: O objetivo do presente estudo foi investigar a farmacocinética da vancomicina em neonatos pretermo, considerando a idade pós-conceptual e também a idade pós-natal para determinar se as alterações no volume aparente de distribuição, meia-vida biológica e depuração plasmática causam variação significativa no vale plasmático da vancomicina. MATERIAL E MÉTODO: Os vinte e cinco pacientes selecionados foram distribuídos em dois grupos, que diferiram significativamente em termos de idade pós-conceptualgrupo 1, n=13: 31,2-32,3 semanas; grupo 2, n=12: 33,5-34,1 semanas, IC95%, p<0,0001) e idade pós-natalgrupo 1: 12,0-18,5 dias; grupo 2: 18,0-34,0 dias, p<0,05). Todos os responsáveis foram informados sobre os detalhes do estudo e assinaram o termo de consentimento livre e esclarecido. O protocolo foi submetido e aprovado previamente pelo Comitê de Ética em Pesquisa do hospital. RESULTADO: O volume aparente de distribuição se mostrou significativamente aumentado no grupo 1 comparado aos pacientes do grupo 2 0,85 vs 0,56 L/kg, p=0,01). Adicionalmente, o teste de regressão linear múltipla mostrou boa correlação linear: 0,85) da concentração plasmática de vale com o volume aparente de distribuição, e também com a meia-vida biológica nos pacientes do grupo 1. Nas crianças do grupo 2 evidenciou-se boa correlação(r: 0,91) entre o vale e a depuração plasmática. A influência desses parâmetros farmacocinéticos sobre o vale nos prematuros parece variar de acordo com a idade pós-conceptual e a idade pós-natal. CONCLUSÃO: Concluindo, a concentração de vale para a vancomicina depende da farmacocinética e a correlação múltipla varia de acordo com a idade pós-conceptual e a idade pós-natal dos recém-nascidos pré-termos.

OBJETIVE: The objective of the present study was to evaluate the kinetic disposition of vancomycin in preterm infants with emphasis on the apparent volume of distribution, biological half-life, and total body clearance as well as whether their variations cause significant modification of the trough plasma concentration of the drug, depending on the postconceptional age (PCA) and the postnatal age (PNA). MATERIAL AND METHOD: Twenty-five selected patients were distributed into 2 groups which differed significantly in terms of mean PCA (31.2-32.3 weeks in group 1, n = 13; 33.5-34.1 weeks in group 2, n = 12: CI95%, P < .001) and PNA (group 1, 12.0-18.5 days; group 2, 18.0-34.0 days, CI95%, P < .05). The parents were informed and signed a written consent for participation of the infants in the protocol that had been previously approved by the Ethics Committee of the hospital. RESULTS: Apparent volume of distribution was significantly increased in group 1 compared with patients of group 2 (0.85 vs. 0.56 L/kg, respectively; P = .01,). Additionally multiple linear regression revealed a good linear correlation (r = 0.85) of trough plasma concentration of vancomycin with the apparent volume of distribution and also with the biological half-life in patients of group 1, while a good correlation (r = 0.91) was obtained for the trough plasma concentration with total body clearance in infants of group 2. The influence of these kinetic parameters on the trough concentration of vancomycin in preterm infants seems to vary according to PCA and PNA. CONCLUSION: In conclusion, the trough plasma concentration of vancomycin depends on the pharmacokinetics, and multiple linear correlation indicates that it varies according to the postconceptional and postnatal age of preterm infants.

INTRODUÇÃO: Foi realizada monitorização dos níveis séricos de vancomicina em recém-nascidos de termo com sepse ou suspeita de sepse Staphylococcus sp., através da cromatografia líquida de alta eficácia (HPLC) e imunoensaio por fluorescência polarizada (FPIA). OBJETIVO: Verificar a existência de correlação estatística entre os resultados obtidos pelas duas técnicas. MÉTODO E CASUÍSTICA: Foram obtidas dezoito e vinte concentrações séricas de vancomicina no pico e vale respectivamente, em recém-nascidos de termo, no período de outubro de 1995 a outubro de 1997. RESULTADO: O coeficiente de correlação linear para pico sérico foi de 0,27, p=0,110 e para vale sérico 0,26, p= 0,1045 não sendo estatisticamente significativo, não sendo estatisticamente significativo. CONCLUSÃO: Apesar da pequena casuística, não houve correlação estatisticamente significante entre os resultados obtidos pelos duas técnicas.

INTRODUCTION: Peak and trough serum concentrations of vancomycin were determined in term newborn infants with confirmed or suspected Staphylococcus sp sepsis by high performance liquid chromatography and flourescence polarization immunoassay. OBJECTIVE: To statistically compare the results of the high performance liquid chromatography and flourescence polarization immunoassay techniques for measuring serum vancomycin concentrations. METHODS: Eighteen peak and 20 trough serum samples were assayed for vancomycin concentrations using high performance liquid chromatography and flourescence polarization immunoassay from October 1995 to October 1997. RESULTS: The linear correlation coefficients for high performance liquid chromatography and flourescence polarization immunoassay were 0.27 (peak, P = 0.110) and 0.26 (trough, P = 0.1045) respectively, which were not statistically significant. CONCLUSION: There was wide variation in serum vancomycin concentrations determined by high performance liquid chromatography as compared with those determined by flourescence polarization immunoassay. There was no recognizable pattern in the variability; in an apparently random fashion, the high performance liquid chromatography measurement was sometimes substantially higher than the flourescence polarization immunoassay measurement, and at other times it was substantially lower.

Foi realizado um estudo prospectivo para verificar se as doses habituais de vancomicina determinam concentrações séricas adequadas em 25 recém - nascidos de termo com sepse. OBJETIVOS: Avaliou-se a resposta terapêutica da sepse neonatal por Staphylococcus sp., tratada com vancomicina, monitorizando além de sua concentração sérica, o poder bactericida do soro (PBS) e a concentração inibitória mínima (MIC). MÉTODO: Os níveis séricos do antibiótico foram obtidos através do imunoensaio por fluorescência polarizada, o MIC através de micro-difusão em ágar, e o PBS foi obtido por macro-diluição em caldo. RESULTADOS: Concentrações séricas no pico de vancomicina adequadas (20-40 mg/mL) ocorreram em 59,1% dos casos e um recém-nascido apresentou potencial risco de ototoxicidade (>40 mg/mL). Em 48% dos pacientes ocorreram vales séricos adequados (5-10 mg/mL) e 28% dos pacientes apresentaram potencial risco de nefrotoxicidade (>10mg/mL). Não houve concordância significante entre a normalidade determinada pelo pico e vale de vancomicina no método (prova de McNemar: p=0,7905). A concentração sérica no pico de vancomicina foi comparada com a evolução clínica dos recém-nascidos com sepse neonatal, não havendo diferença estatisticamente significante entre os picos séricos dos pacientes que apresentaram boa e má evolução (U=51,5; p=0,1947). Também não houve diferença estatisticamente significante entre os vales séricos dos pacientes que apresentaram boa e má evolução clínica ( U= 77,0; p=0,1710). Todos os MICs obtidos demonstraram sensibilidade à vancomicina. Metade dos pacientes que apresentou PBS no vale adequado (1/8), também tiveram concentração sérica de vancomicina adequada e boa evolução clínica. CONCLUSÕES: A recomendação de doses de vancomicina para recém-nascidos de termo deve ser baseada no peso e na idade pós-conceptual apenas para dar início à terapia antimicrobiana na sepse neonatal, não existindo um padrão de doses ideal. Logo, a dose deve ser individualizada. A utilização desses dados laboratoriais com a clínica favorecem a elucidação da provável causa da má evolução do paciente, facilitando o ajuste da droga e a menor chance de efeitos tóxicos ou sub-terapêuticos.

A prospective study was conducted to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 term newborn infants with sepsis. Purpose: The therapeutic response of neonatal sepsis by Staphylococcus sp. treated with vancomycin was evaluated through serum concentrations of vancomycin, serum bactericidal titers (SBT), and minimum inhibitory concentration (MIC). METHOD: Vancomycin serum concentrations were determined by the fluorescence polarization immunoassay technique , SBT by the macro-broth dilution method, and MIC by diffusion test in agar . RESULTS: Thirteen newborn infants (59.1%) had adequate peak vancomycin serum concentrations (20--40 mg/mL) and one had peak concentration with potential ototoxicity risk (>40 µg/mL). Only 48% had adequate trough concentrations (5--10 mg/mL), and seven (28%) had a potential nephrotoxicity risk (>10 µg/mL). There was no significant agreement regarding normality for peak and trough vancomycin method (McNemar test : p = 0.7905). Peak serum vancomycin concentrations were compared with the clinical evaluation (good or bad clinical evolution) of the infants, with no significant difference found (U=51.5; p=0.1947). There was also no significant difference between the patients' trough concentrations and good or bad clinical evolution (U = 77.0; p=0.1710). All Staphylococcus isolates were sensitive to vancomycin according to the MIC. Half of the patients with adequate trough SBT (1/8), also had adequate trough vancomycin concentrations and satisfactory clinical evolution. CONCLUSIONS: Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. SBT interpretation should be made in conjunction with the patient's clinical presentation and vancomycin serum concentrations. Those laboratory and clinical data favor elucidation of the probable cause of patient's bad evolution, which would facilitate drug adjustment and reduce the risk of toxicity or failing to achieve therapeutic doses.