Evaluación del consumo de antimicrobianos en una Unidad de Neonatologia: un trabajo en equipo para promover el uso racional de antimicrobianos / Evaluation of antimicrobial consumption in a Neonatology Unit: a team work to promote the rational use of antibiotics

Resumen Antecedentes: Los antimicrobianos (ATM) son uno de los medicamentos más utilizados en recién nacidos (RN) hospitalizados. El uso indiscriminado de ATM trae consecuencias negativas como son el predominio de bacterias resistentes a los ATM usualmente utilizados y asociaciones individuales a morbilidad relevante como son la displasia broncopulmonar, enterocolitis necrosante, sepsis tardía y/o muerte. Objetivo: Registrar y evaluar las tendencias del uso de ATM a lo largo del tiempo en RN hospitalizados en el Servicio de Neonatología (SRN) del Complejo Asistencial Dr. Sótero del Río, con el fin de objetivar los cambios en la práctica habitual de la indicación de ATM. Un objetivo secundario fue evaluar el impacto de estas conductas sobre la resistencia antimicrobiana. Métodos: Estudio de cohorte, prospectivo, observacional, unicéntrico, en todos los pacientes hospitalizados entre enero de 2011 y diciembre de 2014. Se registró el peso al nacer, días de hospitalización, indicación y días de uso de ATM para cada paciente. El uso de ATM fue cuantificado por medio de distintas tasas: días de indicación de un o más ATM para el consumo global (TUA), sumatoria total de días de uso (STUA) como para los ATM más frecuentemente utilizados. Cada tasa calculada por 100 días hospitalizados. Además, se registró la susceptibilidad antimicrobiana de las bacterias más frecuentemente aisladas en nuestro servicio: Staphylococcus coagulasa negativa (SCN) y bacilos gramnegativos (BGNs). Resultados: El 34,7% de los pacientes hospitalizados recibió algún tipo de antimicrobiano, correspondiendo 32,3% a antibacterianos. El ATM más utilizado fue ampicilina (20,2% del total) y luego cefadroxilo (11,6%). El TUA no cambió entre 2011 y 2014. La STUA disminuyó en 10,7% entre 2011 y 2014 (p < 0,05). En el análisis por rangos de peso, en el grupo < 750 g disminuyó la tendencia de uso de vancomicina (descenso de uso en 9,9%) y un aumento de 18,8% para metronidazol. Por otra parte, hubo un aumento en el uso del régimen de piperacilina/tazobactam en el grupo > 1.500 g. Al evaluar la susceptibilidad antimicrobiana, hubo una disminución de la susceptibilidad a cloxacilina en SCN entre 2011 y 2014 desde 27 a 10,3%, respectivamente. Para BGN hubo una disminución desde 76,9 a 40,5% en la susceptibilidad a cefalosporinas de tercera generación, principalmente debido a Klebsiella pneumoniae que pasó a ser el BGN predominante, con un aumento de 6,7 a 50% en los años 2011 y 2014, respectivamente. Para Klebsiella pneumoniae la susceptibilidad a cefalosporinas de tercera generación descendió desde 77 a 22%. Por último, amikacina mostró una actividad sobre 85% en todos los BGNs entre 2011 y 2014. Conclusiones: Es recomendable planificar y mantener un registro continuo del consumo de ATM tanto como terapia y profilaxis, idealmente llevar el TUA, el STUA y siendo categorizado por tipo de ATM y rango de peso de los RN. En forma concomitante, es de considerable importancia analizar y evaluar la susceptibilidad de microorganismos. Es esencial que un equipo interdisciplinario prepare este registro, y que continuamente proporcione retroalimentación a los profesionales que mantienen el funcionamiento de las unidades de cuidados neonatales.

Background: Antibiotics (ATB) are drugs widely used in hospitalized newborns. The indiscriminate use of ATBs promote the rise of resistant bacteria to the most commonly indicated antimicrobials. In addition, ATB prescription presents associations to morbidity, such as bronchopulmonary dysplasia, necrotizing enterocolitis, late sepsis and even death. All of the above leads to an increase in health care costs. Aim: To record and to evaluate trends of antibiotic use over time in hospitalized NB in the Neonatology Unit at Dr. Sótero del Río Hospital, in order to objectify the changes in the usual practice of the ATM indication. A secondary objective was to assess its impact on antimicrobial resistance. Methods: Cohort, observational, prospective unicenter study which included all hospitalized patients between January 2011 and December 2014. Birth weight, hospitalization days, ATB indication and days of ATB use were recorded for each patient. The use of ATB was quantified by means of different rates; days of indication of one or more ATBs for global consumption (RUA), total sum of days of use (TSUA) and for the most frequently used ATBs. Each calculated rate for 100 days hospitalized. In addition, the antimicrobial susceptibility of the most frequently isolated bacteria in our service: coagulase-negative Staphylococcus (SCN) and Gram-negative bacilli (BGN) were recorded continuously. Results: The 34.7% of the hospitalized patients received some type of antimicrobial agent. ATBs were 32.3% of medicines used. The most widely used was ampicillin (with 20.2% of the total) and cefadroxyl (with 11.6%). The RUA did not change during the study time, but STUA decreased by 10.7% between 2011 and 2014 with p < 0.05. When subgroup analyzes were divided by weight ranges, in the < 750 g group, the use of vancomycin decreased in use by 9.9% and an increase of 18.8% for metronidazole was observed. On the other hand, there was an increase in the use of the piperacillin-tazobactam regimen in the range > 1,500 g. When evaluating antimicrobial susceptibility, there was a decrease in susceptibility for oxacillin in SCN between 2011 and 2014 from 27% to 10.3% respectively. In addition, for Gram negative there was a decrease from 76.9% to 40.5% in susceptibility to third generation cephalosporins, mainly due to Klebsiella pneumoniae, which became the predominantly isolated BGN with an increase of 6.7% to 50% between 2011 and 2014, respectively. For K. pneumoniae the loss of susceptibility to third generation cephalosporins decreased from 77% to 22%. Finally, amikacin showed an activity over 85% in all BGNs between 2011 and 2014. Conclusions: It is advisable to plan and to maintain a continuous record of ATB consumption, as well as therapy and prophylaxis, being categorized by ATB type and range of newborn weight. It is of considerable importance to analyze and to evaluate the susceptibility of microorganisms. It is essential that an interdisciplinary team prepare this recording, and to continuously provide feedback to professionals who maintain the functioning of neonatal care units.

[Evaluation of antimicrobial consumption in a Neonatology Unit: a team work to promote the rational use of antibiotics]. / Evaluación del consumo de antimicrobianos en una Unidad de Neonatologia: un trabajo en equipo para promover el uso racional de antimicrobianos.

BACKGROUND: Antibiotics (ATB) are drugs widely used in hospitalized newborns. The indiscriminate use of ATBs promote the rise of resistant bacteria to the most commonly indicated antimicrobials. In addition, ATB prescription presents associations to morbidity, such as bronchopulmonary dysplasia, necrotizing enterocolitis, late sepsis and even death. All of the above leads to an increase in health care costs. AIM: To record and to evaluate trends of antibiotic use over time in hospitalized NB in the Neonatology Unit at Dr. Sótero del Río Hospital, in order to objectify the changes in the usual practice of the ATM indication. A secondary objective was to assess its impact on antimicrobial resistance. METHODS: Cohort, observational, prospective unicenter study which included all hospitalized patients between January 2011 and December 2014. Birth weight, hospitalization days, ATB indication and days of ATB use were recorded for each patient. The use of ATB was quantified by means of different rates; days of indication of one or more ATBs for global consumption (RUA), total sum of days of use (TSUA) and for the most frequently used ATBs. Each calculated rate for 100 days hospitalized. In addition, the antimicrobial susceptibility of the most frequently isolated bacteria in our service: coagulase-negative Staphylococcus (SCN) and Gram-negative bacilli (BGN) were recorded continuously. RESULTS: The 34.7% of the hospitalized patients received some type of antimicrobial agent. ATBs were 32.3% of medicines used. The most widely used was ampicillin (with 20.2% of the total) and cefadroxyl (with 11.6%). The RUA did not change during the study time, but STUA decreased by 10.7% between 2011 and 2014 with p < 0.05. When subgroup analyzes were divided by weight ranges, in the < 750 g group, the use of vancomycin decreased in use by 9.9% and an increase of 18.8% for metronidazole was observed. On the other hand, there was an increase in the use of the piperacillin-tazobactam regimen in the range > 1,500 g. When evaluating antimicrobial susceptibility, there was a decrease in susceptibility for oxacillin in SCN between 2011 and 2014 from 27% to 10.3% respectively. In addition, for Gram negative there was a decrease from 76.9% to 40.5% in susceptibility to third generation cephalosporins, mainly due to Klebsiella pneumoniae, which became the predominantly isolated BGN with an increase of 6.7% to 50% between 2011 and 2014, respectively. For K. pneumoniae the loss of susceptibility to third generation cephalosporins decreased from 77% to 22%. Finally, amikacin showed an activity over 85% in all BGNs between 2011 and 2014. CONCLUSIONS: It is advisable to plan and to maintain a continuous record of ATB consumption, as well as therapy and prophylaxis, being categorized by ATB type and range of newborn weight. It is of considerable importance to analyze and to evaluate the susceptibility of microorganisms. It is essential that an interdisciplinary team prepare this recording, and to continuously provide feedback to professionals who maintain the functioning of neonatal care units.

Bronchopulmonary dysplasia: incidence, risk factors and resource utilization in a population of South American very low birth weight infants.

OBJECTIVE: To determine the incidence of bronchopulmonary dysplasia, its risk factors and resource utilization in a large South American population of very low birth weight infants. METHODS: Prospectively collected data in infants weighing 500 to 1,500 g born at 16 NEOCOSUR Network centers from 10/2000 through 12/2003. Multivariate relative risk and 95% confidence intervals were estimated by Poisson regression with robust error variance to find factors that affected the risk of bronchopulmonary dysplasia. RESULTS: 1,825 very low birth weight infants survivors were analyzed. Mean birth weight and gestational age were 1085+/-279 g and 29+/-3 weeks respectively. Bronchopulmonary dysplasia incidence averaged 24.4% and survival without bronchopulmonary dysplasia augmented with increasing gestational age. A higher birth weight and gestational age and a female gender all decreased the risk for bronchopulmonary dysplasia. Factors that independently increased that risk were surfactant requirement, mechanical ventilation, airleak, patent ductus arteriosus, late onset sepsis and necrotizing enterocolitis. Bronchopulmonary dysplasia infants had more days of hospitalization (91+/-27 vs. 51+/-19), of mechanical ventilation (19+/-20 vs. 4+/-7) and oxygen therapy (72+/-30 vs. 8+/-14) in comparison with non BPD infants. CONCLUSIONS: Bronchopulmonary dysplasia incidence was 24.4% in a large South American population and is related to greater resource utilization. Risk factors for bronchopulmonary dysplasia in this study were: surfactant requirement, mechanical ventilation, airleak, patent ductus arteriosus, late onset sepsis and necrotizing enterocolitis. These studies may provide useful information in the design of effective preventive perinatal strategies.

Bronchopulmonary dysplasia: incidence, risk factors and resource utilization in a population of South-American very low birth weight infants

OBJECTIVE: To determine the incidence of bronchopulmonary dysplasia, its risk factors and resource utilization in a large South American population of very low birth weight infants. METHODS: Data were prospectively collected from infants weighing 500 to 1,500 g born at 16 NEOCOSUR Network centers from 10/2000 through 12/2003. Multivariate relative risk and 95% confidence intervals were estimated by Poisson regression with robust error variance to find factors that affected the risk of bronchopulmonary dysplasia. RESULTS: 1,825 very low birth weight infant survivors were analyzed. Mean birth weight and gestational age were 1085+279 g and 29+3 weeks respectively. Bronchopulmonary dysplasia incidence averaged 24.4% and survival without bronchopulmonary dysplasia augmented with increasing gestational age. Higher birth weight and gestational age and a female gender all decreased the risk for bronchopulmonary dysplasia. Factors that independently increased that risk were surfactant requirement, mechanical ventilation, air leak, patent ductus arteriosus, late onset sepsis and necrotizing enterocolitis. Bronchopulmonary dysplasia infants had more days of hospitalization (91±27 vs. 51±19), on mechanical ventilation (19±20 vs. 4±7) and oxygen therapy (72±30 vs. 8±14) in comparison with non BPD infants. CONCLUSIONS: Bronchopulmonary dysplasia incidence was 24.4% in a large South American population and is related to greater resource utilization. Risk factors for bronchopulmonary dysplasia in this study were: surfactant requirement, mechanical ventilation, air leak, patent ductus arteriosus, late onset sepsis and necrotizing enterocolitis. These studies may provide information useful to the design of effective preventive perinatal strategies.

A new score for predicting neonatal very low birth weight mortality risk in the NEOCOSUR South American Network.

OBJECTIVE: To develop and validate a model for very low birth weight (VLBW) neonatal mortality prediction, based on commonly available data at birth, in 16 neonatal intensive care units (NICUs) from five South American countries. STUDY DESIGN: Prospectively collected biodemographic data from the Neonatal del Cono Sur (NEOCOSUR) Network between October 2000 and May 2003 in infants with birth weight 500 to 1500 g were employed. A testing sample and crossvalidation techniques were used to validate a statistical model for risk of in-hospital mortality. The new risk score was compared with two existing scores by using area under the receiver operating characteristic curve (AUC). RESULTS: The new NEOCOSUR score was highly predictive for in-hospital mortality (AUC=0.85) and performed better than the Clinical Risk Index for Babies (CRIB) and the NICHD risk models when used in the NEOCOSUR Network. The new score is also well calibrated - it had good predictive capability for in-hospital mortality at all levels of risk (HL test=11.9, p=0.85). The new score also performed well when used to predict in hospital neurological and respiratory complications. CONCLUSIONS: A new and relatively simple VLBW mortality risk score had a good prediction performance in a South American network population. This is an important tool for comparison purposes among NICUs. This score may prove to be a better model for application in developing countries.

Determinants of insulin sensitivity and secretion in very-low-birth-weight children.

In prepubertal children, low birth weight is related to reduced insulin sensitivity, particularly if a history of rapid postnatal weight gain is present. We sought to determine whether these associations were also evident in premature, very-low-birth-weight (VLBW) children. We studied 60 VLBW prepubertal children aged 5-7 yr (mean age 5.7 +/- 0.7 yr). Birth weights ranged from 690 to 1500 g (mean 1195 +/- 31 g), with gestational ages between 25 and 34 wk (median 29 wk). A short iv glucose tolerance test was carried out to assess fasting insulin sensitivity and glucose-stimulated insulin secretion. The effects of current body mass index, birth weight (SD scores), postnatal growth rates, and indicators of postnatal morbidity were evaluated by analysis of covariance. Twenty children were born small for gestational age, and 40 were appropriate for gestational age. Ninety-eight percent of them had attained a height within target range. Children who were small for gestational age had lower insulin sensitivity than children who were appropriate for gestational age (homeostasis model assessment insulin resistance index 1.24 +/- 0.17 vs. 0.94 +/- 0.08, P < 0.05). Moreover, birth weight SD scores correlated significantly with homeostasis model assessment insulin resistance index (r = -0.326, P = 0.01). This effect persisted after adjustment for current body mass index, gestational age, and perinatal morbidity. In addition, fasting and postload insulin secretion during the short iv glucose tolerance test correlated significantly with early postnatal growth rates, independently of birth weight SD scores. Our findings in a cohort of VLBW prepubertal children indicate that growth in utero as well as postnatal growth rates are independent determinants of subsequent insulin sensitivity and secretion.

Glucose and lipid metabolism in small for gestational age infants at 48 hours of age.

OBJECTIVE: To study the consequences of low birth weight on glucose and lipid metabolism 48 hours after delivery. METHODS: We studied 136 small for gestational age (SGA) and 34 appropriate for gestational age (AGA) term neonates who were born in Santiago, Chile. Prefeeding venous blood was obtained 48 hours after birth for determination of glucose, free fatty acids, beta-hydroxy butyrate, insulin, C-peptide, leptin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 (IGFBP-1), and cortisol. RESULTS: SGA newborns had lower glucose (SGA versus AGA, median [interquartile range]: 3.6 mmol/L [2.9-4.1 mmol/L] vs 3.9 mmol/L [3.6-4.6 mmol/L]) and insulin levels (31.3 pmol/L [20.8-47.9 pmol/L] vs 62.5 pmol/L [53.5-154.9]) than AGA infants, and they had higher glucose/insulin ratios (13.9 mg/dL/uIU/mL [8.6-19.1 mg/dL/uIU/mL] vs 8.2 mg/dL/uIU/mL [4.6-14.1 mg/dL/uIU/mL]). SGA infants also had higher levels of IGFBP-1 (5.1 nmol/L [4.4-6.7 nmol/L] vs 2.9 nmol/l [1.4-4.2 nmol/L]), free fatty acids (0.72 mEq/L [0.43-1.00 mEq/L] vs 0.33 mEq/L [0.26-0.54 mEq/L]) and beta-hydroxy butyrate (0.41 mEq/L [0.15-0.91 mEq/L] vs 0.09 mEq/L [0.05-0.13 mEq/L]). Sex-hormone binding globulin levels were not significantly different between the 2 groups. CONCLUSIONS: In early postnatal life, SGA infants display an increased insulin sensitivity with respect to glucose disposal but not with respect to suppression of lipolysis, ketogenesis, and hepatic production of IGFBP-1. It will be important to determine how these differential sensitivities to insulin vary with increasing age.