Prevalencia de sepsis neonatal confirmada microbiológicamente en una maternidad de la Ciudad Autó noma de Buenos Aires / Prevalence of microbiologically confirmed neonatal sepsis at a maternity center in the City of Buenos Aires

Introducción. En neonatos internados es frecuente sospechar sepsis neonatal, pero solo en el 25 % al 30 % se confirma con cultivos positivos. La selección del esquema antibiótico basándose en la epidemiología local favorece el uso racional y minimiza sus efectos colaterales. Objetivo primario. Describir la prevalencia de sepsis precoz y tardía con rescate microbiológico y sus características clínicas. Población y método. Estudio transversal retrospectivo, realizado del 1 de enero de 2013 al 31 de diciembre de 2017, en una maternidad pública de Argentina, que incluyó todos los recién nacidos internados en la unidad con diagnóstico de sepsis precoz y tardía con rescate microbiológico, y aquellos reingresados dentro del mes de vida. Resultados. Ingresaron 3322 recién nacidos, 1296 evaluados por sospecha de sepsis precoz, cultivos positivos en 25 (1,9 %; tasa: 0,86 ‰). El 52 % eran menores de 33 semanas de edad gestacional. Microorganismos: Escherichia coli 5, Listeria monocytogenes 4, Streptococcus agalactiae (SGB) 3, Streptococcus pneumoniae 3. Sepsis tardía (tasa 8,73 ‰), el 68 % ocurridas en menores de 33 semanas. Microorganismos intrahospitalarios: Staphylococcus coagulasa negativos 115, Staphylococcus aureus 47, Escherichia coli 30, Cándida spp. 16, Enterococcus faecalis 13, Klebsiella pneumoniae 11 y Streptococcus agalactiae 10. En los reingresos: E. coli 11, S. aureus 12, SGB 3 y Haemophilus influenzae 3. Conclusiones. Se observa en el período estudiado una frecuencia de sepsis precoz similar a los reportes internacionales, con predominio de E. coli y L. monocytogenes. La tasa de sepsis tardía presentó una tendencia descendente en los años analizados, con predominio de los cocos grampositivos

Introduction. Neonatal sepsis is often suspected in hospitalized newborn infants, but only in 25­30% of cases it is confirmed via a positive culture. Selecting the antibiotics based on local epidemiology favors their rational use and minimizes their side effects. Primary objective. To describe the prevalence of early- and late-onset sepsis with microorganism isolation and their clinical characteristics. Population and method. Retrospective, cross-sectional study conducted between 01-01-2013 and 12-31-2017 in a public maternity center of Argentina in all hospitalized newborn infants with a diagnosis of early- and late-onset sepsis with microorganism isolation, and those re-admitted in their first month of life. Results. A total of 3322 newborn infants were admitted; 1296 were assessed for suspected early- onset sepsis; 25 had a positive culture (1.9%; rate: 0.86‰). Of these, 52% were born before 33 weeks of gestation. Microorganisms: Escherichia coli 5, Listeria monocytogenes 4, Streptococcus agalactiae (SGB) 3, Streptococcus pneumoniae 3. Also, 68% of late-onset sepsis cases (rate: 8.73‰) occurred in infants born before 33 weeks of gestation. Hospital-acquired microorganisms: coagulase-negative Staphylococcus 115, Staphylococcus aureus 47, Escherichia coli 30, Candida spp. 16, Enterococcus faecalis 13, Klebsiella pneumoniae 11, and Streptococcus agalactiae 10. In re-admissions: E. coli 11, S. aureus 12, SGB 3, and Haemophilus influenzae 3. Conclusions. During the study period, the frequency of early-onset sepsis was similar to international reports, with a predominance of E. coli and L. monocytogenes. The rate of late-onset sepsis showed a downward trend in the analyzed years, with a predominance of Gram-positive cocci.

Sepsis neonatal precoz: recomendaciones para su abordaje en la práctica clínica / Early neonatal sepsis: recommendations for approach in clinical practice / Sepse neonatal precoce: recomendações para sua abordagem na prática clínica

La sepsis neonatal precoz se define como la que se manifiesta en las primeras 72 horas de vida. Es una importante causa de morbilidad y mortalidad neonatal. Su incidencia es inversamente proporcional a la edad gestacional. Los microorganismos considerados como frecuentes son Streptoccocus del grupo B, Escherichia coli y Listeria monocytogenes. El diagnóstico de sepsis precoz se basa principalmente en la presencia de factores de riesgo como la corioamnionitis y la edad gestacional. Los signos clínicos son inespecíficos y los exámenes paraclínicos disponibles actualmente, como los reactantes de fase aguda (proteína C reactiva y procalcitonia) tienen escaso valor predictivo positivo. Se realizó una revisión bibliográfica de las últimas publicaciones disponibles sobre sepsis neonatal precoz en recién nacidos, en cuanto a su sospecha, confirmación diagnóstica y tratamiento. A partir de las últimas publicaciones se confeccionó una guía para el manejo clínico de los recién nacidos con sospecha de sepsis precoz.

Early neonatal sepsis is defined as that type of sepsis with an onset within the first 72 hours of life and that is a major cause of neonatal morbidity and mortality. Its incidence is inversely proportional to its gestational age. Frequent microorganisms are group B Streptococcus, Escherichia coli and Listeria monocytogenes. Early sepsis diagnosis is mainly based on the presence of risk factors such as chorioamnionitis and gestational age. Clinical signs are non-specific and currently available paraclinical tests such as acute phase reactants (C-reactive protein and procalcitonin) have little positive predictive value. A bibliographic review of the suspicion, diagnostic confirmation and treatment on Early Neonatal Sepsis in newborns in the latest papers and guidelines were prepared for the clinical treatment of newborns with suspected early sepsis.

A sepse neonatal precoce é definida como aquela que se manifesta nas primeiras 72 horas de vida e que é uma das principais causas de morbidade e mortalidade neonatal. Sua incidência é inversamente proporcional à idade gestacional. Os microrganismos considerados frequentes são o Streptococcus grupo B, Escherichia coli e Listeria monocytogenes. O diagnóstico de sepse precoce baseia-se principalmente na presença de fatores de risco como a coioamnionite e a idade gestacional. Os sinais clínicos são inespecíficos e os testes para-clínicos atualmente disponíveis, como reagentes de fase aguda (proteína C-reativa e procalcitonia) têm pouco valor preditivo positivo. Fizemos uma revisão bibliográfica das últimas publicações disponíveis sobre sepse neonatal precoce em recém-nascidos em termos de suspeita e confirmação diagnóstica e tratamento. Com base nas últimas publicações, elaboramos um guia para o manejo clínico de recém-nascidos com suspeita de sepse precoce.

Sepsis precoz, osteoartritis y meningitis: a propósito de un caso clínico / Early sepsis, osteoarthritis and meningitis: a clinical case / Sepse precoce, osteoartrite e meningite: relato de caso

Se expone el caso de un recién nacido que desarrolló sepsis connatal precoz a Streptococcus agalactiae, con meningitis aguda supurada y osteoartritis de rodilla izquierda. Como factor de riesgo la madre no tenía realizado el exudado rectovaginal, pesquisa que detecta la colonización por estreptococo del grupo B (EGB). Se aisló el germen en hemocultivo y en líquido de punción articular. Recibió tratamiento antibiótico adecuado a la sensibilidad del microorganismo y según pauta de sepsis con meningitis, evolucionando favorablemente. En este trabajo se describe la epidemiología de la sepsis neonatal y los cambios ocurridos luego de la implementación de la profilaxis antibiótica en el preparto.

We hereby present the case of a newborn with early connatal sepsis due to Streptococcus agalactiae, with acute suppurative meningitis and left knee osteoarthritis. As a risk factor, the mother had not performed the rectus vaginal exudate screening that detects colonization by Group B Streptococcus (GBS). The germ was isolated in blood culture and in joint puncture fluid. The patient received germ-sensitive antibiotic treatment for meningitis sepsis and evolved favorably. This paper describes the epidemiology of neonatal sepsis and the changes that have occurred after the administration of the antibiotic prophylaxis during pregnancy.

Apresentamos o caso de um recém-nascido com sepse neonatal precoce por Streptococcus agalactiae, com meningite supurativa aguda e osteoartrite de joelho esquerdo. Como fator de risco, a mãe não realizou teste de exsudato vaginal do reto que detecta a colonização por estreptococos do grupo B (SGB). O germe foi isolado em hemocultura e líquido de punção articular. A paciente recebeu tratamento com antibióticos germinativos para padrão meningite sepse e evoluiu favoravelmente. Este artigo descreve a epidemiologia da sepse neonatal e as mudanças ocorridas após a administração da profilaxia antibiótica durante a gravidez.

Sepsis risk calculator-guided antibiotic management in neonates with suspected early-onset sepsis / 中国当代儿科杂志

OBJECTIVE@#To evaluate the efficacy of sepsis risk calculator (SRC) in guiding antibiotic use in neonates with suspected early-onset sepsis (EOS).@*METHODS@#A total of 284 neonates with a gestational age of ≥ 35 weeks were enrolled as the control group, who were hospitalized in the Children's Hospital of Chongqing Medical University from March to July, 2019 and were suspected of EOS. Their clinical data were retrospectively collected and the use of antibiotics was analyzed based on SRC. A total of 170 neonates with a gestational age of ≥ 35 weeks were enrolled as the study group, who were admitted to the hospital from July to November, 2020 and were suspected of EOS. SRC was used prospectively for risk scoring to assist the decision making of clinical antibiotic management. The two groups were compared in terms of the rate of use of antibiotics, blood culture test rate, clinical outcome, and adherence to the use of SRC.@*RESULTS@#Compared with the control group, the study group had a significantly higher SRC score at birth and on admission (@*CONCLUSIONS@#The use of SRC reduces the rate of empirical use of antibiotics in neonates with suspected EOS and does not increase the risk of adverse outcomes, and therefore, it holds promise for clinical application.

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,

The challenges of neonatal sepsis management / Os desafios no manejo da sepse neonatal

Abstract Objectives To present current evidence on the etiology, risk factors, diagnosis, and management of early and late neonatal sepsis. Source of data Non-systematic review of the Medline (PubMed), Scopus, Web of Science, Cochrane, and Google Scholar databases regarding the following terms: neonatal sepsis, early neonatal sepsis, late neonatal sepsis, empirical antibiotic therapy, sepsis calculator, vancomycin, newborn, preterm newborn. Data synthesis Neonatal sepsis is a frequent cause of neonatal morbidity and mortality. Its diagnosis is difficult. Continuous observation of the patient is critical to diagnostic suspicion. When neonatal sepsis is suspected, bacteriological tests should be collected. Vancomycin should not be routinely using in the empirical antibiotic regimen in late neonatal sepsis, and the main protective mechanisms against neonatal sepsis are handwashing and the use of breast milk. Conclusions Newborns constitute a group that is more vulnerable to sepsis. Knowledge of risk factors and etiological agents allows a better approach to the newborn with sepsis.

Resumo Objetivos Apresentar evidências atuais na etiologia, fatores de risco, diagnóstico e manejo da sepse neonatal precoce e tardia. Fontes de dados Revisão não sistemática feita nas bases de dados Medline (PubMed), Scopus, Web of Science, Cochrane, Google Scholar sobre os temas sepse neonatal, sepse neonatal precoce, sepse neonatal tardia, antibioticoterapia empírica, sepsis calculator, vancomicina, recém-nascido, recém-nascido pré-termo. Síntese de dados A sepse neonatal é uma causa frequente de morbimortalidade neonatal. O seu diagnóstico é difícil. A observação contínua do paciente é fundamental para uma suspeição diagnóstica. Ao se suspeitar de sepse neonatal devem-se coletar exames bacteriológicos. Não usar, rotineiramente, vancomicina no esquema empírico de antibiótico na sepse neonatal tardia. Os principais mecanismos protetores da sepse neonatal são a lavagem de mãos e o uso do leite materno. Conclusões Os recém-nascidos constituem um grupo mais vulnerável à sepse. O conhecimento dos fatores de risco e dos agentes etiológicos permite uma melhor abordagem do recém-nascido séptico.

Uso de beta-lactámicos como alternativa del tratamiento empírico actual de sepsis neonatal tardía: revisión temática / Use of beta-lactams as an alternative to the current empirical treatment of late neonatal sepsis: review

OBJETIVO: Analizar el uso de beta-lactámicos en sepsis neonatal tardía, en comparación con el tratamiento empírico actual con vancomicina, mediante la revisión de artículos científicos. METODOLOGÍA: Revisión temática en Bases LILACS y PubMed. La selección de los artículos se realizó mediante la lectura de título, abstract y texto completo. Criterios de búsqueda: Estudios en humanos, artículos por abstract y texto completo, en inglés y español, y de no más de 10 años. RESULTADOS: No hay relación en la duración ni en la mortalidad de la sepsis al utilizar un betalactámico, o al utilizar vancomicina. Además, cepas resistentes a beta-lactámico, respondieron bien al usar un beta-lactámico como terapia empírica inicial, sin la necesidad de recurrir a vancomicina, excepto en casos de no mejoría clínica. CONCLUSIONES: Beta-lactámicos pueden ser utilizados como terapia empírica inicial en sepsis neonatal tardía como alternativa al tratamiento actual con vancomicina, restringiendo el uso de vancomicina a casos de resistencia, o cuando no haya mejoría clínica del recién nacido que está utilizando un beta-lactámico como tratamiento.

OBJECTIVE: To analyze the use of beta-lactams in late- onset neonatal sepsis, compared with empirical treatment with vancomycin used currently, through the revision of scientific articles. METHODOLOGY: Thematic review in LILACS and PubMed. The articles were selected by reading the title, abstract and full text. Searching criteria: Human studies, articles by abstract and full text, in English and Spanish, and no more than 10 years since published. RESULTS: There is no relationship in duration or mortality in Sepsis when using beta-lactam, or using vancomycin. In addition, resistant strains to beta-lactam responded well in using betalactam as initial empirical therapy, without the need to resort to vancomycin, except in cases of non-clinical improvement. CONCLUSIONS: Beta-lactams may be used as initial empirical therapy in late-onset neonatal sepsis as an alternative to current vancomycin therapy, restricting the use of vancomycin to resistance cases, or when there is no clinical improvement in the neonate, who is using a beta-lactam as a treatment.

Resistencia de Staphylococcus aureus frente a cefalosporinas en la sepsis neonatal y puerperal / Staphylococcus Aureus Resistance against Cephalosporins in Neonatal and Puerperal Sepsis

Introducción: El mecanismo más común de actividad antibiótica es la interferencia en la síntesis de la pared celular bacteriana. Las cefalosporinas tienen el mismo mecanismo de acción que las penicilinas; sin embargo, tienen un espectro antibacteriano más amplio, son resistentes a muchas b-lactamasas y tienen propiedades farmacocinéticas mejoradas. Objetivos: Identificar por servicios los gérmenes aislados y determinar la resistencia del Staphylococcus aureus a las cefalosporinas. Método: Se realizó un estudio retrospectivo, transversal y descriptivo en hospital Ginecobstétrico de Guanabacoa desde enero de 2014 hasta diciembre de 2016. Se seleccionaron como variables los gérmenes aislados y el patrón de resistencia del germen que predominó frente a todas las generaciones de cefalosporinas. Resultados: En el servicio de neonatología el mayor aislamiento fue en el hemocultivo seguido del catéter venoso (19 pacientes) y tubo endotraqueal. En el servicio de Obstetricia, los loquios y el sitio quirúrgico fue donde se aisló mayor número (69 y 31 pacientes, respectivamente). Conclusiones: El germen más frecuente aislado en ambos servicios fue el Staphylococcus aureus y la resistencia a las cefalosporinas fue muy elevado(AU)

Introduction: The synthesis interference of bacterial cell wall is the most common antibiotic mechanism. Cephalosporins have the same mechanism of action as penicillin. However, they have wider antibacterial spectrum, they are more resistant to B-lactamases and better pharmacokinetics properties. Additionally, cephalosporins have higher activity in front of gram-negative bacteria than penicillin. Objective: To identify isolated germs in these services and to determine the Staphylococcus aureus resistance to cephalosporins. Method: A retrospective, transversal and descriptive study was conducted in Guanabacoa Gynecobstetric hospital from January 2014 to December 2016. selected variables as isolated microorganism, and resistance pattern in front of cephalosporin generations. The isolated germs and the resistance pattern of the germ that prevailed against all generations of cephalosporins were selected as variables. In the Obstetrics Service, the largest number of germs was isolated in the lochia and surgical sites. (69 and 31, respectively). Results: In neonatology service, the most frequent isolation occurred in blood culture (35), venous catheter (19) and endotracheal tube (10). In Obstetric service, the most frequent isolation occurred in liquors (69) and the surgical site isolated (31). Conclusions: Staphylococcus Aureus was the main microorganism isolated in hospital and its cephalosporin resistance was very high(AU)

Síndrome celulitis-adenitis, una forma infrecuente de presentación de la sepsis neonatal tardía: A propósito de dos casos / Adenitis-cellulitis syndrome, an infrequent form of presentation of the late-onset neonatal septicemia: Report of two cases

La sepsis es la principal causa de mortalidad neonatal. La forma precoz, habitualmente, está relacionada con la colonización recto-vaginal u otros factores de riesgo materno. En la forma tardía, es difícil establecer su origen; por lo general, es nosocomial o de la comunidad. El Streptococcus agalactiae (Streptococcus beta-hemolítico del grupo B) es el germen implicado con más frecuencia en la sepsis neonatal en países desarrollados. La forma tardía, generalmente, se presenta con septicemia y meningitis, y, en ocasiones, pueden detectarse infecciones osteoarticulares o de piel y tejidos blandos. El síndrome celulitis-adenitis en la región cervical, forma poco frecuente de presentación, es causado por Staphylococcus aureus y, ocasionalmente, por Streptococcus agalactiae. Se reportan 2 casos de sepsis neonatal tardía con clínica de celulitis-adenitis cervical causados por Streptococcus beta-hemolítico del grupo B, con una evolución satisfactoria con terapia antibiótica de amplio espectro.

Septicemia is the main cause of neonatal mortality. The early-onset neonatal sepsis is usually related to maternal factor risks including recto-vaginal colonization. In the late-onset neonatal septicemia it is more difficult to establish the etiology because the majority of the cases are nosocomial or community related. The Streptococcus agalactiae (beta-hemolytic Streptococcus) is the most frequent germ associated with neonatal sepsis in developed countries. The late-onset form usually occurs with septic symptoms and meningitis and, in a few cases, with osteoarticular, skin and soft tissue infection. Adenitis-cellulitis syndrome is rarely seen, and its main cause is Staphylococcus aureus, followed by Streptococcus agalactiae. We report two cases of group B Streptococcus late-onset neonatal septicemia, both of them with adenitis-cellulitis syndrome. Patients recovered uneventfully after an adequate antibiotic therapy.

Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review

ABSTRACT Background Technologies and life support management have enhanced the survival of preterm infants. The immune system of newborns is immature, which contributes to the occurrence of healthcare-associated infections. The overlap of several conditions with neonatal sepsis and the difficulty of diagnosis and laboratory confirmation during this period result in a tendency to over-treat neonatal sepsis. The use of antimicrobial agents is a risk factor for multidrug-resistant bacterial infections. This work aimed to perform a systematic review of the relationship between inadequate use of antimicrobial agents and increase in neonatal sepsis related to healthcare assistance, due to bacterial resistance. Methods Our population, exposition, comparison, outcome and study type was as follows: P: hospitalized neonates with sepsis diagnosis, E: inappropriate use of antimicrobial agents, C: adequate use of antimicrobial agents or no indication of infection, O: resistant bacterial infection, and S: original studies. We performed searches in the PubMed, Scopus, Virtual Health Library (Scielo, LILACS, and MEDLINE), and Embase without limits on time, language, and the references of the articles found. Fourteen studies were included and assessed using the Grading of Recommendations, Assessment, Development, and Evaluation, Newcastle, and the Strengthening the Reporting of Observacional Studies in Epidemiology methodologies. Results All studies found were observational and started with a low-quality evidence level in the Grading of Recommendations, Assessment, Development, and Evaluation. Conclusions Despite their low-quality evidence, the studies demonstrated the association between inadequate use of antimicrobial agents and increase of neonatal resistant bacterial healthcare-associated infections in neonatal units. However, there is significant difficulty in conducting high-quality studies in this population due to ethical issues tied to randomized trials. Therefore, new studies should be encouraged to recommend adequate treatment of newborns without increasing the risk of healthcare-associated infections by multidrug-resistant bacteria.

Problemas relacionados a medicamentos antimicrobianos em unidade de terapia intensiva neonatal / Antimicrobial drug-related problems in a neonatal intensive care unit

RESUMO Objetivo: Determinar os principais problemas relacionados a medicamentos em neonatos sob uso de antimicrobianos. Métodos: Estudo observacional, prospectivo e longitudinal. Os problemas relacionados a medicamentos foram classificados de acordo com a versão 6.2 da Pharmaceutical Care Network Europe Foundation. Foi executada análise descritiva, na qual as variáveis clínicas e terapêuticas foram apresentadas por frequências absolutas e relativas, ou por média e desvio padrão, conforme apropriado. Resultados: Foram incluídos 152 neonatos com predomínio do sexo masculino (58,5%), idade gestacional de 32,7 ± 4,2 semanas e peso de 1.903,1 ± 846,9g. A principal hipótese diagnóstica de infecção foi a sepse precoce (66,5%), detectando-se que 71,7% dos neonatos apresentavam algum fator de risco para infecção. Dentre os neonatos, 33,6% apresentaram pelo menos um problema relacionado a medicamento. Destes, 84,8% estavam relacionados à efetividade do tratamento e 15,2% a reações adversas. A principal causa de problemas relacionados a medicamentos foi a escolha da dose, sobretudo dos aminoglicosídeos e das cefalosporinas. Conclusão: O uso de antimicrobianos em terapia intensiva neonatal relaciona-se principalmente a problemas relacionados a medicamentos de efetividade, predominando a prescrição de antimicrobianos em subdose, sobretudo os aminoglicosídeos.

ABSTRACT Objective: The goal was to determine the main drug-related problems in neonates who were using antimicrobials. Method: This was an observational, prospective and longitudinal study. Drug-related problems were classified according to version 6.2 of the Pharmaceutical Care Network Europe Foundation classification. A descriptive analysis was performed, in which the clinical and therapeutic variables were presented as absolute and relative frequencies or as the mean and standard deviation, as appropriate. Results: In total, 152 neonates with a predominance of males (58.5%), gestational age of 32.7 ± 4.2 weeks and weight of 1,903.1 ± 846.9g were included. The main diagnostic hypothesis of infection was early sepsis (66.5%), and 71.7% of the neonates had some risk factor for infection. Among the neonates, 33.6% had at least one drug-related problem. Of these, 84.8% were related to treatment effectiveness and 15.2% to adverse reactions. The main cause of drug-related problems was the selected dose, particularly for aminoglycosides and cephalosporins. Conclusion: The use of antimicrobials in the neonatal intensive care is mainly associated with problems related to medication effectiveness, predominantly the prescription of subdoses of antimicrobials, especially aminoglycosides.

Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m2/day for neonates?

Abstract Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m2/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m2/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m2/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p < 0.001). A dose of 27 mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.

Empirical antimicrobial therapy for late-onset sepsis in a neonatal unit with high prevalence of coagulase-negative Staphylococcus / Terapia antimicrobiana empírica para sepse tardia na unidade neonatal com alta prevalência de Staphylococcus coagulase negativo

Abstract Objective: The aim of this study was to compare two different empiric treatments for late-onset neonatal sepsis, vancomycin and oxacillin, in a neonatal intensive care unit with a high prevalence of coagulase-negative Staphylococcus. Methods: A cross-sectional study was conducted in an neonatal intensive care unit from 2011 to 2014. Data from the medical records of at-risk newborns were collected daily. Infections were defined according to the National Health Surveillance Agency criteria. Data analysis was performed using an internal program. Results: There was a significant reduction in the number of Staphylococcus aureus infections (p = 0.008), without endocarditis, meningitis, or lower respiratory tract infection, as well as a reduction in the frequency of deaths related to S. aureus infection. There were no significant changes in the incidence of Gram-negative bacterial or fungal infections. An increase in coagulase-negative Staphylococcus infections was observed (p = 0.022). However, there was no measured increase in related morbidity and mortality. There was a reduction in the median number of days of treatment with oxacillin from 11.5 to 6 days (p < 0.001) and an increase of one day in the median number of days of treatment with vancomycin (p = 0.046). Conclusions: Modification of the empiric treatment regimen for neonatal late-onset sepsis with use of oxacillin showed a significant reduction in S. aureus infections, as well as a reduction in the frequency of infections with major organ system involvement and mortality due to infection with this microorganism. As a result, oxacillin can be considered as an effective treatment for late-onset sepsis, making it possible to avoid broad-spectrum antibiotics.

Resumo Objetivo Comparar dois períodos com diferentes esquemas empíricos para tratamento de sepse neonatal tardia, incluindo vancomicina ou oxacilina respectivamente, em unidade neonatal de referência com alta prevalência de Staphylococcus coagulase negativo. Métodos Estudo transversal, feito em unidade neonatal de referência, de 2011 a 2014. Os dados foram coletados diariamente por vigilância ativa em prontuário de recém-nascidos de risco. As infecções foram notificadas conforme critérios definidos pela Agência Nacional de Vigilância Sanitária. O banco de dados e a análise foram feitos em programa interno. Resultados Ocorreu redução significativa da notificação de infecções por Staphylococcus aureus (p = 0,008), sem notificações de endocardite, meningite e infecções de vias aéreas inferiores, além de redução na frequência de óbitos pelo microrganismo e sem alteração significativa nas incidências de infecções por bactérias Gram negativas e fungos. Houve aumento de infecções S. aureus coagulase negativo (p = 0,022), mas sem aumento de morbidade e mortalidade. Ocorreu redução na mediana do tempo de uso de oxacilina, de 11,5 para 6 dias (p < 0,001), com aumento de mediana de um dia de uso de vancomicina (p = 0,046). Conclusões A modificação do esquema empírico com uso de oxacilina revelou redução significativa das infecções por S. aureus, além da redução na frequência de infecção de foco profundo e mortalidade pelo microrganismo. Considera-se que oxacilina pode ser usada como esquema de tratamento de sepse neonatal tardia para se evitar o uso de antibióticos de largo espectro.

Etiología y patrones de resistencia antimicrobiana en sepsis neonatal temprana y tardía, en una Unidad de Terapia Intensiva Neonatal / Etiology and antimicrobial resistance patterns in early and late neonatal sepsis in a Neonatal Intensive Care Unit

Introducción. La sepsis neonatal es una de las principales causas de muerte en recién nacidos. El tratamiento antimicrobiano empírico se sustenta en información epidemiológica y pruebas de susceptibilidad antimicrobiana. El objetivo del estudio fue describir los agentes etiológicos y su sensibilidad antimicrobiana enreciénnacidos con sepsis temprana (SNTe) o tardía (SNTa) de una Unidad de Terapia Intensiva Neonatal. Métodos. Estudio transversal realizado en un hospital de concentración del occidente de México. Se determinó la resistencia antimicrobiana de los gérmenes aislados en sangre o líquido cefalorraquídeo de pacientes con SNTe o SNTa nosocomial. Resultados. Se aislaron bacterias o levaduras en 235 cultivos de 67 eventos de SNTe y 166 eventos de SNTa. Del total de aislamientos, las bacterias más frecuentes fueron enterobacterias (51,5%), seguidas de Streptococcus spp. en SNTe y Staphylococcus spp. en SNTa. En cuanto a las enterobacterias de adquisición nosocomial, el 40% fueron productoras de betalactamasas de espectro extendido. En especies de Staphylococcus, la resistencia a oxacilina se registró en el 65,5%. En las enterobacterias (n: 121), la frecuencia de resistencia a amikacina, piperacilina-tazobactam y meropenem fue menor del 3%. En bacterias no fermentadoras, no se observó resistencia a amikacina, ciprofloxacino y cefepime; sin embargo, el número de aislamientos fue escaso. Conclusiones. Las bacterias identificadas con mayor frecuencia en SNTe fueron enterobacterias (67,6%) y Streptococcus spp. (17,6%), mientras que, en SNTa, fueron enterobacterias (44,9%) y Staphylococcus spp. (34,7%). El 40% de las enterobacterias de adquisición nosocomial fueron productoras de betalactamasas de espectro extendido y el 65,5% de Staphylococcus spp. mostraron resistencia a oxacilina.

Introduction. Neonatal sepsis is one of the main causes of death among newborn infants. Empirical antimicrobial treatment is based on epidemiological information and antimicrobial susceptibility tests. The objective of this study was to describe etiologic agents and their antimicrobial susceptibility among newborn infants with early-onset neonatal sepsis (EONS) or late-onset neonatal sepsis (LONS) at a Neonatal Intensive Care Unit. Methods. Cross-sectional study conducted at a tertiary referral hospital in Western Mexico. Determination of antimicrobial resistance of microorganisms isolated in blood or cerebrospinal fluid of patients with EONS or nosocomial LONS. Results. Yeasts and bacteria were isolated from 235 cultures corresponding to 67 events of EONS and 166 events of LONS. Of all isolates, the most common bacteria were Enterobacteriaceae (51.5%), followed by Streptococcus spp. in EONS, and by Staphylococcus spp. in LONS. Of all nosocomial Enterobacteriaceae, 40% were extended spectrum beta-lactamase producing bacteria. Among Staphylococcus species, resistance to oxacillin was recorded in 65.5%. Among Enterobacteriaceae (n: 121), resistance to amikacin, piperacillin-tazobactam, and meropenem was below 3%. Non-fermenting bacteria did not show resistance to amikacin, ciprofloxacin or cefepime; however, the number of isolates was scarce. Conclusions.The most commonly identified bacteria in EONS were Enterobacteriaceae (67.6%) and Streptococcus spp. (17.6%), and Enterobacteriaceae (44.9%) and Staphylococcus spp. (34.7%) in LONS. Forty percent ofnosocomial Enterobacteriaceae were extended spectrum beta-lactamase producing bacteria, and 65.5% of Staphylococcus spp. showed resistance to oxacillin.