Authored by Augusto Sola*
Abstract
Unreasonable use of antibiotics occurs in about 25-30% of the population. The neonatal period is among the highest group where antibiotic abuse occurs, as high as 40% in some hospitals. This is particularly apparent in newborn intensive care units (NICU), where 70-80% of the admitted infants receive antibiotics. The main motive for this is that clinicians suspect neonatal sepsis very frequently, but only about 3-5% or less of the time infants have blood culture proven sepsis. The neonatal sepsis calculator, described some years ago and validated by several studies, is extremely useful in allowing care givers to assess risk factors and combine them with the clinical evaluation of the newborn to make a more adequate decision and decrease utilization of unnecessary antibiotics. On the other hand, nonspecific inflammatory markers, like C-reactive protein (CRP) and procalcitonin (PCT), are relied upon to make clinical decisions about antibiotic initiation and discontinuation. However, they have very bad specificity for early and late neonatal sepsis, and their sensitivity is not very adequate either. Relying on them in suspicion of neonatal sepsis is a “hazardous waste”. Antibiotic abuse is associated with short- and long-term adverse effects. In preterm infants in NICU, length of hospital stay, bronchopulmonary dysplasia, necrotizing enterocolitis and mortality are increased. In addition to this and to the concomitant increase in health care expenditures, there are long lasting consequences of antibiotic misuse in the neonatal period. They include development of antibiotic resistance, with the emergence of multi resistant organisms, and alterations to the microbiota and microbiome. This has been linked to various disease states later in life, such as abnormal brain development, infections during childhood, asthma, obesity, diabetes, atherosclerosis and autoimmune disorders, among others. The need to apply clinical measures to modify current neonatal practices and improve outcomes has never been more urgent.
Keywords: Antibiotics; Abuse; Newborn; Neonatal; Microbiome
Abbreviations: NICU: Newborn intensive care unit; CRP: C-reactive protein; PCT: Procalcitonin; EOBS: Early onset bacterial sepsis; WHO: World Health Organization; NEC: Necrotizing enterocolitis; BPD: Bronchopulmonary dysplasia; AMR: Antimicrobial resistance; NNT: Number needed to treat; SIBEN: Ibero american society of neonatology
Introduction
“The rational use of drugs requires that patients receive medications appropriate to their clinical needs, in doses that meet their individual requirements, for an adequate period of time, and at the lowest cost to them and their community” was affirmed by the Conference of Experts on the Rational Use of Drugs convened by the World Health Organization (WHO) in Nairobi in 1985 [1]. WHO estimates that more than half of all medicines are prescribed inappropriately, and antibiotics are among the most frequent ones that are used incorrectly [2]. Furthermore, it has become apparent that newborn infants are exposed to the highest abuse rate of antibiotics. For example, more than to 70% of neonates admitted to some neonatal intensive care units (NICU’s) are prescribed antibiotics [3,4]. In the USA, data from 297 centers with 40,364 infants <1,500 grams [5] showed that the majority of infants born prematurely infants are exposed to early antibiotic initiation and this occurred in 78.6% of infants with birth weight <1,500 grams and in 87% of those <1,000 grams at birth. Furthermore, many of them had subsequent prolonged antibiotic administration for more than 5 days. However, extremely few babies (1-3%) with suspected neonatal early-onset bacterial sepsis (EOBS) are actually proven to have blood culture positive sepsis.
In this manuscript we focus on the irrational uses of antibiotics in the neonatal period, particularly when EOBS is suspected. Clinical indications for initiation and discontinuation of antibiotics are described, together with the potential severe consequences of antibiotic abuse. These include, among others, higher prevalence of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and mortality, in addition to development of antimicrobial resistance (AMR) and microbiome alterations. AMR and the emergence of multiresistant bacteria is an epidemic in public health. Neonatal microbiome influences immune cell ontogeny [6] and early exposure to antibiotics affect the composition of the intestinal microbiota [7-11].
The purpose of this manuscript is to review some of the current neonatal practices related to antibiotic indication and discontinuation and present a current summary of most of the untoward effects of antibiotic abuse in neonatal medicine. Hopefully, this review will be useful for implementation of changes that would ultimately lead to improved neonatal outcomes.
Discussion
Use of antibiotics in the neonatal period
Neonatal bacterial sepsis is a grave condition that may lead to death if untreated or if initiation of treatment is delayed. Antibiotics do save newborns’ lives.
In the NICU, suspected EOBS is one of the most common diagnoses and antibiotics are the most frequently used medications. The antibiotics for treatment of neonatal sepsis must be given intravenously and never PO or intramuscularly. The more frequently used are ampicillin and gentamycin. Their discontinuation should occur in 36-72 hours if the blood cultures are negative and the infant is asymptomatic.
In asymptomatic newborns, with suspected EOBS decisions to start antibiotics should be mainly based on the newborn’s clinical condition and not solely on risks or on inflammatory markers.
The risk of EOBS is very low in well appearing, asymptomatic newborns, about 0.21‰ live births [12-14]. The number needed to treat (NNT) for this group has been estimated at 9,370. What needs to be done in these cases is clinical assessment and risk assessment, with routine observation of the infants together with their mothers, and discharge home as per usual guidelines. On the other hand, when there are clinically evident signs in the first 12-24 hours of life, the risk is > 11‰ live births, with NNT of about 118. In these cases, a blood culture and empirical antibiotics should be started immediately without delay, with admission to the NICU. In cases of equivocal or doubtful clinical early presentation, the risk is about 2.6‰ live births, with NNT of 823. In these doubtful cases a blood culture can be obtained, and the vital signs must be carefully monitored every 4 hours for 24 hours at least, without initiation of antibiotics. Treatment with antibiotics will be according to the persistence of suggestive symptoms.
Risk scores and clinical assessment should guide the practice of antibiotic utilization, and not simply suspecting EOBS. In a study conducted on 608.014 newborns > 34 weeks in 14 hospitals [15] it was possible to stratify the risk of neonatal sepsis according to several maternal and labor and delivery variables, together with the newborn’s clinical presentation . Three groups were identified:
1. Treat empirically with antibiotics: 4.1%
2. Study them, with frequent observation and conditional treatment: 11.1%
3. Only continuous observation: 84.8%.
The incidence of sepsis with positive blood cultures was 8.4%, 1.2% and 0.11% respectively for groups 1, 2 and 3. This has led to a decrease in the use and time of antibiotics in the network of participating hospitals. These authors created the neonatal sepsis calculator, a software that calculates an individual risk or score in relation to some prenatal factors and the baby’s clinical signs and evolution in the first 12 to 72 hours [16]. This neonatal sepsis calculator, validated by several studies, is extremely useful in allowing clinicians to assess risk factors and combine them with the clinical evaluation of the newborn to make a more adequate decision in clinical care [12-14,17-23]. In an asymptomatic infant without any risk, or even with some risks, appropriate care is to observe, evaluate and not interfere with the mother-child bonding, unless the a priori risk is high or very high. When in doubt, take blood cultures, do not start antibiotics but implement detailed clinical observation every 2-4 hours of the infant while she or he is with the mother. If something changes clinically, start antibiotics promptly. However, in symptomatic newborns, even if the risk score is low, obtain blood cultures and start antibiotics quickly. If the symptoms disappear after several hours and blood cultures are negative, antibiotics could be discontinued in 48-72 hours.
Chorioamnionitis and prolonged rupture of the membranes
Routine antibiotics had been initiated in many, if not all neonates exposed to chorioamnionitis. However, in mothers with clinical chorioamnionitis, the incidence of EOBS in neonates has been reported as low as 1‰ to about 4-7‰ live births. In newborns > 35 weeks’ gestation, only about 1.25% of the infants born to mothers with chorioamnionitis have positive cultures. The rate is higher in newborns <35 weeks (4.8% to 16.9%). This is clear proof that routine antibiotics should not be initiated in all neonates exposed to chorioamnionitis. Doing so would mean treating hundreds of infants to find one that really has an infection. The NNT in the group of infants >35 weeks exposed to chorioamnionitis is from 80 to 210. Additionally, studying the placenta histologically does not add substantial information to decide to start treatment or to prolong the use of antibiotics. All this suggests that we should abandon the recommendation to treat with antibiotics asymptomatic newborns >34 weeks with a history of chorioamnionitis [24-29]. Even in symptomatic infants born to mothers with chorioamnionitis, the NNT in order to identify one infant with EOBS is high, 23 or greater. However, in the case preterm infants with maternal chorioamnionitis, the NNT is from 6 to 20; in this group it would be justified to obtain blood cultures and start antibiotics.
To read more about this article...Open access Journal of Pediatrics & Neonatal Care
To know more about our Journals....Iris Publishers
No comments:
Post a Comment