Challenges in Treatment Strategies for Management of Neonatal Sepsis

T. Amin, A. N. Nur, Imran Mahmud
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Materials and methods: The study was a prospective study done in the neonatal ward of a tertiary hospital in Bangladesh; total 100 neonates diagnosed as neonatal sepsis, were enrolled in this study. All study subjects were fully evaluated clinically, thoroughly investigated and properly treated as per protocol. Results: The sensitivity and specificity of clinical features and investigations were statistically significant (i.e. p <0.05) and etiologic agents were isolated by urine culture and sensitivity to antibiotics were shown and outcome measure e.g. mortality was 22% (OR 3.54; 95% CI 2.046.13; P <0.05). Conclusion: There are challenges in making diagnosis and treating neonatal sepsis, yet sincere approach to diagnosis and rational and appropriate use of antibiotics along with necessary adjuvant therapy can mitigate the challenges. DOI: https://doi.org/10.3329/jdmc.v29i1.51166 J Dhaka Med Coll. 2020; 29(1) : 23-28 1. Dr. Tahsinul Amin, Associate Professor, Dept. of Neonatology, Sher-e-Bangla Medical College, Barishal. 2. Dr. Ayesha Najma Nur, Consultant (Obstetrics and Gynecology), CWCH, Dhaka. 3. Dr. Imran Mahmud, Registrar, Department of Medicine, Dhaka Medical College, Dhaka Correspondence: Dr. Tahsinul Amin. Associate Professor, Dept. of Neonatology, Sher-e-Bangla Medical College, Barishal. E-mail :tahsinul_amin@yahoo.com. Mobile: 01715734232 Received: 05-12-2019 Revision: 15-01-2020 Accepted: 21-03-2020 Introduction Globally bacterial infection (sepsis, meningitis, pneumonia etc.) is a leading cause of 2.9 million neonatal deaths every year.1 Strategies to reduce preventable infection-related neonatal deaths by 2030 to meet the WHO Sustainable Development Goal (SDG) is a global health priority. Neonates are especially vulnerable to sepsis due to perinatal exposure to infective agents, compromised immune system and maternal and neonatal risk factors.1 In recent years neonatal mortality has decreased at much lower rates, and currently represents 40% of all childhood mortality.2 Three-fourths of these deaths occur in the first week of life.3 Neonatal sepsis is the third leading cause of neonatal mortality, only behind to prematurity and perinatal asphyxia.4 is responsible for 13% of all neonatal mortality, and 42% of deaths in the first week of life.5,6 In developing countries, clinically diagnosed sepsis is present in 49–170 per 1000 live births, culture-proven sepsis in 16 per 1000 live births and neonatal meningitis in 0.8–6.1 per 1000 live births.7 Infants with neonatal infections are more likely to have adverse neuro-developmental outcomes at follow up, including cerebral palsy, lower mental and psychomotor development index scores, visual impairment and impaired growth.8,9 Risk factors for early-onset neonatal sepsis (EOS) include prematurity, immunologic immaturity, maternal Group B streptococcal (GBS) colonization, prolonged rupture of membranes, and maternal intra-amniotic infection.10 Intra-partum antimicrobial prophylaxis administered to GBS-colonized women has reduced the burden of disease associated with early onset GBS invasive infections.11 Late-onset neonatal sepsis (LOS) attributable to Gram-positive organisms, including coagulase negative Staphylococci and Staphylococcus aureus, is associated with increased morbidity and mortality among premature infants.11 Invasive candidiasis is an emerging cause of late-onset sepsis, especially among infants who receive broad spectrum antimicrobial agents.12 Despite recent medical advances have improved neonatal care, yet many challenges remain in the diagnosis and management of neonatal infections.13 The diagnosis of neonatal sepsis is complicated by the non-specific signs and symptoms of sepsis, low sensitivity of the gold standard blood culture test (particularly following intra-partum antibiotic prophylaxis), delayed availability of culture results (approximately 48–72 hours after blood collection) and the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests.14 Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis.15 Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increased antimicrobial resistance.16 Given current challenges with diagnosis, and the high mortality and morbidity associated with neonatal sepsis, particularly in low-income countries, there is a need to develop novel approaches for identifying neonates at greatest risk.17 Although there are challenges in making the diagnosis and providing appropriate treatment for neonatal sepsis, we need to overcome those obstacles with rational approach to investigate and manage neonatal sepsis. The objective of this prospective study was to find out the etiology, sensitivity and specificity of the clinical features and investigations and optimal and effective treatment for neonatal sepsis.","PeriodicalId":320976,"journal":{"name":"Journal of Dhaka Medical College","volume":"33 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2021-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Dhaka Medical College","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3329/JDMC.V29I1.51166","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Neonatal sepsis is an important cause of morbidity and mortality in newborns. The symptoms and signs of neonatal sepsis are often non-specific and similar to other common neonatal diseases, investigation results are also non-specific and low sensitivity of blood culture also causes diagnostic dilemma and often empirical antibiotic treatment is given. This is why, there is challenges in making the diagnosis and treating neonatal sepsis. Objectives: To find the etiology, sensitivity and specificity of clinical features and investigations and optimal and effective treatment for neonatal sepsis. Materials and methods: The study was a prospective study done in the neonatal ward of a tertiary hospital in Bangladesh; total 100 neonates diagnosed as neonatal sepsis, were enrolled in this study. All study subjects were fully evaluated clinically, thoroughly investigated and properly treated as per protocol. Results: The sensitivity and specificity of clinical features and investigations were statistically significant (i.e. p <0.05) and etiologic agents were isolated by urine culture and sensitivity to antibiotics were shown and outcome measure e.g. mortality was 22% (OR 3.54; 95% CI 2.046.13; P <0.05). Conclusion: There are challenges in making diagnosis and treating neonatal sepsis, yet sincere approach to diagnosis and rational and appropriate use of antibiotics along with necessary adjuvant therapy can mitigate the challenges. DOI: https://doi.org/10.3329/jdmc.v29i1.51166 J Dhaka Med Coll. 2020; 29(1) : 23-28 1. Dr. Tahsinul Amin, Associate Professor, Dept. of Neonatology, Sher-e-Bangla Medical College, Barishal. 2. Dr. Ayesha Najma Nur, Consultant (Obstetrics and Gynecology), CWCH, Dhaka. 3. Dr. Imran Mahmud, Registrar, Department of Medicine, Dhaka Medical College, Dhaka Correspondence: Dr. Tahsinul Amin. Associate Professor, Dept. of Neonatology, Sher-e-Bangla Medical College, Barishal. E-mail :tahsinul_amin@yahoo.com. Mobile: 01715734232 Received: 05-12-2019 Revision: 15-01-2020 Accepted: 21-03-2020 Introduction Globally bacterial infection (sepsis, meningitis, pneumonia etc.) is a leading cause of 2.9 million neonatal deaths every year.1 Strategies to reduce preventable infection-related neonatal deaths by 2030 to meet the WHO Sustainable Development Goal (SDG) is a global health priority. Neonates are especially vulnerable to sepsis due to perinatal exposure to infective agents, compromised immune system and maternal and neonatal risk factors.1 In recent years neonatal mortality has decreased at much lower rates, and currently represents 40% of all childhood mortality.2 Three-fourths of these deaths occur in the first week of life.3 Neonatal sepsis is the third leading cause of neonatal mortality, only behind to prematurity and perinatal asphyxia.4 is responsible for 13% of all neonatal mortality, and 42% of deaths in the first week of life.5,6 In developing countries, clinically diagnosed sepsis is present in 49–170 per 1000 live births, culture-proven sepsis in 16 per 1000 live births and neonatal meningitis in 0.8–6.1 per 1000 live births.7 Infants with neonatal infections are more likely to have adverse neuro-developmental outcomes at follow up, including cerebral palsy, lower mental and psychomotor development index scores, visual impairment and impaired growth.8,9 Risk factors for early-onset neonatal sepsis (EOS) include prematurity, immunologic immaturity, maternal Group B streptococcal (GBS) colonization, prolonged rupture of membranes, and maternal intra-amniotic infection.10 Intra-partum antimicrobial prophylaxis administered to GBS-colonized women has reduced the burden of disease associated with early onset GBS invasive infections.11 Late-onset neonatal sepsis (LOS) attributable to Gram-positive organisms, including coagulase negative Staphylococci and Staphylococcus aureus, is associated with increased morbidity and mortality among premature infants.11 Invasive candidiasis is an emerging cause of late-onset sepsis, especially among infants who receive broad spectrum antimicrobial agents.12 Despite recent medical advances have improved neonatal care, yet many challenges remain in the diagnosis and management of neonatal infections.13 The diagnosis of neonatal sepsis is complicated by the non-specific signs and symptoms of sepsis, low sensitivity of the gold standard blood culture test (particularly following intra-partum antibiotic prophylaxis), delayed availability of culture results (approximately 48–72 hours after blood collection) and the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests.14 Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis.15 Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increased antimicrobial resistance.16 Given current challenges with diagnosis, and the high mortality and morbidity associated with neonatal sepsis, particularly in low-income countries, there is a need to develop novel approaches for identifying neonates at greatest risk.17 Although there are challenges in making the diagnosis and providing appropriate treatment for neonatal sepsis, we need to overcome those obstacles with rational approach to investigate and manage neonatal sepsis. The objective of this prospective study was to find out the etiology, sensitivity and specificity of the clinical features and investigations and optimal and effective treatment for neonatal sepsis.
新生儿脓毒症治疗策略的挑战
背景:新生儿脓毒症是新生儿发病和死亡的重要原因。新生儿脓毒症的症状和体征往往是非特异性的,与其他常见的新生儿疾病相似,调查结果也是非特异性的,血培养的低敏感性也造成诊断困境,往往给予经验性抗生素治疗。这就是为什么在诊断和治疗新生儿败血症方面存在挑战的原因。目的:探讨新生儿脓毒症的病因、临床特征的敏感性和特异性,探讨最佳有效的治疗方法。材料和方法:本研究是在孟加拉国一家三级医院新生儿病房进行的前瞻性研究;本研究共纳入100例诊断为新生儿败血症的新生儿。所有的研究对象都经过了充分的临床评估,彻底的调查,并按照方案进行了适当的治疗。结果:临床特征和调查的敏感性和特异性均有统计学意义(p <0.05),尿培养分离出病原,显示对抗生素的敏感性,结局指标如死亡率为22% (OR 3.54;95% ci 2.046.13;P < 0.05)。结论:新生儿脓毒症的诊断和治疗存在一定的挑战,正确诊断,合理合理使用抗生素,配合必要的辅助治疗,可缓解新生儿脓毒症的诊断和治疗挑战。DOI: https://doi.org/10.3329/jdmc.v29i1.51166 J Dhaka Med Coll. 2020;29(1): 23-28Tahsinul Amin博士,巴里沙尔Sher-e-Bangla医学院新生儿科副教授。Ayesha Najma Nur医生,妇产科顾问,达卡CWCH。Imran Mahmud医生,达卡医学院医学系注册主任通讯:Tahsinul Amin医生。巴里沙尔Sher-e-Bangla医学院新生儿科副教授。电子邮件:tahsinul_amin@yahoo.com。全球范围内,细菌感染(脓毒症、脑膜炎、肺炎等)是每年290万新生儿死亡的主要原因到2030年减少可预防的与感染有关的新生儿死亡以实现世卫组织可持续发展目标的战略是一项全球卫生优先事项。由于围产期暴露于感染因子、免疫系统受损以及孕产妇和新生儿的危险因素,新生儿特别容易患败血症近年来,新生儿死亡率以较低的速度下降,目前占所有儿童死亡率的40%其中四分之三的死亡发生在出生后的第一周新生儿败血症是新生儿死亡的第三大原因,仅次于早产和围产期窒息。13%的新生儿死亡率和42%的生命第一周死亡是由4造成的。在发展中国家,临床诊断的败血症发生率为每1000例活产49-170例,培养证实的败血症发生率为每1000例活产16例,新生儿脑膜炎发生率为每1000例活产0.8-6.1例新生儿感染的婴儿在随访中更有可能出现不良的神经发育结果,包括脑瘫、智力和精神运动发育指数得分较低、视力障碍和生长障碍。8,9早发性新生儿脓毒症(EOS)的危险因素包括早产、免疫不成熟、母体B群链球菌(GBS)定植、胎膜破裂时间延长和母体羊膜内感染对感染GBS的妇女进行产前抗菌预防可以减轻与早发性GBS侵袭性感染相关的疾病负担由革兰氏阳性菌(包括凝固酶阴性葡萄球菌和金黄色葡萄球菌)引起的迟发性新生儿败血症(LOS)与早产儿发病率和死亡率增加有关侵袭性念珠菌病是迟发性败血症的新病因,特别是在接受广谱抗菌药物治疗的婴儿中尽管最近的医学进步改善了新生儿护理,但在新生儿感染的诊断和管理方面仍存在许多挑战新生儿脓毒症的诊断因以下因素而复杂化:脓毒症的非特异性体征和症状、金标准血培养试验的低敏感性(特别是在产后抗生素预防后)、培养结果的可得性延迟(大约在采血后48-72小时)、与脓毒症相似的非传染性疾病的频繁出现(尤其是在早产儿中)以及缺乏最佳诊断试验由于新生儿脓毒症是一种高风险疾病,尤其是早产儿,临床医生不得不经验性地对有危险因素和/或疑似脓毒症体征的婴儿施用抗生素。 不幸的是,广谱抗生素和经验性抗生素的长期治疗都与不良后果和抗菌素耐药性增加有关鉴于目前诊断方面的挑战,以及与新生儿败血症相关的高死亡率和发病率,特别是在低收入国家,有必要开发新的方法来识别风险最大的新生儿尽管新生儿败血症的诊断和治疗存在诸多挑战,但我们需要通过合理的方法来克服这些障碍,对新生儿败血症进行调查和管理。本前瞻性研究的目的是了解新生儿脓毒症的病因、临床特征和调查的敏感性和特异性,以及最佳有效的治疗方法。
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