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印度德里三级保健中心出生的新生儿败血症病原体的特征和抗菌药物耐药性:一项队列研究。

Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study.

出版信息

Lancet Glob Health. 2016 Oct;4(10):e752-60. doi: 10.1016/S2214-109X(16)30148-6.

DOI:10.1016/S2214-109X(16)30148-6
PMID:27633433
Abstract

BACKGROUND

Sepsis is one of the most common causes of neonatal deaths globally. Most sepsis-related deaths occur in low-income and middle-income countries, where the epidemiology of neonatal sepsis remains poorly understood. Most of these countries lack proper surveillance networks, hampering accurate assessment of the burden of sepsis, implementation of preventive measures, and investment in research. We report results of neonates born in hospital from a multicentre collaboration on neonatal sepsis.

METHODS

In this cohort study, dedicated research teams prospectively followed up neonates born in one of three tertiary care centres in Delhi, India (Vardhaman Mahavir Medical College, Maulana Azad Medical College, and All India Institute of Medical Sciences [coordinating centre]) and subsequently admitted to the intensive care unit. Neonates were followed up daily until discharge or death. On clinical suspicion, neonates underwent sepsis work-up including blood cultures. The isolated organisms were identified and tested for antimicrobial susceptibility. We defined Gram-negative isolates resistant to any three of five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) as multidrug resistant.

FINDINGS

13 530 neonates of 88 636 livebirths were enrolled between July 18, 2011, and Feb 28, 2014. The incidence of total sepsis was 14·3% (95% CI 13·8-14·9) and of culture-positive sepsis was 6·2% (5·8-6·6). Nearly two-thirds of total episodes occurred at or before 72 h of life (defined as early onset; 1351 [83%] of 1980). Two-thirds (645 [64%]) of 1005 isolates were Gram-negative including, Acinetobacter spp (22%), Klebsiella spp (17%), and Escherichia coli (14%). The pathogen mix in early-onset sepsis did not differ from that of late-onset sepsis (ie, after 72 h). High rates of multidrug resistance were observed in Acinetobacter spp (181/222, 82%), Klebsiella spp (91/169, 54%), and Escherichia coli (52/137, 38%) isolates. Meticillin resistance prevailed in 61% (85/140) of coagulase-negative staphylococci and 38% (43/114) of Staphylococcus aureus isolates. Nearly a quarter of the deaths were attributable to sepsis. The population-attributable risks of mortality were 8·6% in culture-negative sepsis, 15·7% in culture-positive sepsis by multidrug-resistant organisms, and 12·0% in culture-positive sepsis by non-multidrug-resistant organisms.

INTERPRETATION

The high incidence of sepsis and alarming degree of antimicrobial resistance among pathogens in neonates born in tertiary hospitals underscore the need to understand the pathogenesis of early-onset sepsis and to devise measures to prevent it in low-income and middle-income countries.

FUNDING

Indian Council of Medical Research.

摘要

背景

败血症是全球新生儿死亡的最常见原因之一。大多数与败血症相关的死亡发生在低收入和中等收入国家,这些国家的新生儿败血症流行病学仍未得到充分了解。这些国家大多缺乏适当的监测网络,这阻碍了对败血症负担的准确评估、预防措施的实施以及对研究的投资。我们报告了在一项关于新生儿败血症的多中心合作中,在三家三级保健中心(印度德里的 Vardhaman Mahavir 医学院、Maulana Azad 医学院和全印度医学科学研究所[协调中心])出生的新生儿的结果。

方法

在这项队列研究中,专门的研究小组前瞻性地随访了在这三家三级保健中心中的一家出生的、随后入住重症监护病房的新生儿。新生儿每天进行随访,直到出院或死亡。在出现临床疑似病例时,对新生儿进行败血症检查,包括血培养。对分离的病原体进行鉴定和药敏试验。我们将对五类抗生素中的任何三种具有耐药性的革兰氏阴性分离株(广谱头孢菌素、碳青霉烯类、氨基糖苷类、氟喹诺酮类和哌拉西林-他唑巴坦)定义为多药耐药。

结果

2011 年 7 月 18 日至 2014 年 2 月 28 日期间,共有 88636 例活产儿中纳入了 13530 例新生儿。总败血症的发生率为 14.3%(95%CI 13.8-14.9),培养阳性败血症的发生率为 6.2%(5.8-6.6)。总发病例中近三分之二发生在出生后 72 小时内(定义为早发性;1980 例中 1351 例[83%])。1005 株分离株中,645 株(64%)为革兰氏阴性菌,包括不动杆菌属(22%)、克雷伯菌属(17%)和大肠埃希菌(14%)。早发性败血症和晚发性败血症(即 72 小时后)的病原体组合没有差异(即 72 小时后)。不动杆菌属(181/222,82%)、克雷伯菌属(91/169,54%)和大肠埃希菌属(52/137,38%)分离株的多药耐药率较高。凝固酶阴性葡萄球菌中 61%(85/140)和金黄色葡萄球菌中 38%(43/114)的耐甲氧西林率较高。近四分之一的死亡归因于败血症。阴性培养败血症的人群归因风险为 8.6%,多药耐药菌阳性培养败血症为 15.7%,非多药耐药菌阳性培养败血症为 12.0%。

结论

在三级医院出生的新生儿中,败血症的发病率很高,病原体对抗菌药物的耐药程度令人震惊,这突显出需要了解早发性败血症的发病机制,并制定措施在低收入和中等收入国家预防它。

资助

印度医学研究理事会。

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