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新生儿细菌性感染的发生率和危险因素:来自马达加斯加的一项基于社区的队列研究(2018-2021 年)。

Incidence and risk factors of neonatal bacterial infections: a community-based cohort from Madagascar (2018-2021).

机构信息

CESP, Anti-infective evasion and pharmacoepidemiology team, Université Paris-Saclay, UVSQ, Inserm, Montigny-Le-Bretonneux, F- 78180, France.

Institut Pasteur, Université Paris Cité, Epidemiology and Modelling of Antibiotic Evasion (EMAE), Paris, F-75015, France.

出版信息

BMC Infect Dis. 2023 Oct 5;23(1):658. doi: 10.1186/s12879-023-08642-w.

Abstract

BACKGROUND

Few studies on neonatal severe bacterial infection are available in LMICs. Data are needed in these countries to prioritize interventions and decrease neonatal infections which are a primary cause of neonatal mortality. The BIRDY project (Bacterial Infections and Antimicrobial Drug Resistant among Young Children) was initially conducted in Madagascar, Senegal and Cambodia (BIRDY 1, 2012-2018), and continued in Madagascar only (BIRDY 2, 2018-2021). We present here the BIRDY 2 project whose objectives were (1) to estimate the incidence of neonatal severe bacterial infections and compare these findings with those obtained in BIRDY 1, (2) to identify determinants associated with severe bacterial infection and (3) to specify the antibiotic resistance pattern of bacteria in newborns.

METHODS

The BIRDY 2 study was a prospective community-based mother and child cohort, both in urban and semi-rural areas. All pregnant women in the study areas were identified and enrolled. Their newborns were actively and passively followed-up from birth to 3 months. Data on clinical symptoms developed by the children and laboratory results of all clinical samples investigated were collected. A Cox proportional hazards model was performed to identify risk factors associated with possible severe bacterial infection.

FINDINGS

A total of 53 possible severe bacterial infection and 6 confirmed severe bacterial infection episodes were identified among the 511 neonates followed-up, with more than half occurring in the first 3 days. For the first month period, the incidence of confirmed severe bacterial infection was 11.7 per 1,000 live births indicating a 1.3 -fold decrease compared to BIRDY 1 in Madagascar (p = 0.50) and the incidence of possible severe bacterial infection was 76.3, indicating a 2.6-fold decrease compared to BIRDY 1 in Madagascar (p < 0.001). The 6 severe bacterial infection confirmed by blood culture included 5 Enterobacterales and one Enterococcus faecium. The 5 Enterobacterales were extended-spectrum β-lactamases (ESBL) producers and were resistant to quinolones and gentamicin. Enterococcus faecium was sensitive to vancomycin but resistant to amoxicillin and to gentamicin. These pathogns were classified as multidrug-resistant bacteria and were resistant to antibiotics recommended in WHO guidelines for neonatal sepsis. However, they remained susceptible to carbapenem. Fetid amniotic fluid, need for resuscitation at birth and low birth weight were associated with early onset possible severe bacterial infection.

CONCLUSION

Our results suggest that the incidence of severe bacterial infection is still high in the community of Madagascar, even if it seems lower when compared to BIRDY 1 estimates, and that existing neonatal sepsis treatment guidelines may no longer be appropriate in Madagascar. These results motivate to further strengthen actions for the prevention, early diagnosis and case management during the first 3 days of life.

摘要

背景

在中低收入国家(LMICs),关于新生儿严重细菌感染的研究较少。这些国家需要相关数据来确定干预措施的优先级,以降低新生儿感染率,因为新生儿感染是导致新生儿死亡的主要原因之一。BIRDY 项目(儿童期细菌感染和抗菌药物耐药性)最初在马达加斯加、塞内加尔和柬埔寨进行(BIRDY 1,2012-2018 年),并在马达加斯加继续进行(BIRDY 2,2018-2021 年)。我们在此介绍 BIRDY 2 项目,其目标是:(1)估计新生儿严重细菌感染的发生率,并将这些发现与 BIRDY 1 进行比较;(2)确定与严重细菌感染相关的决定因素;(3)明确新生儿细菌的抗生素耐药模式。

方法

BIRDY 2 研究是一项前瞻性的社区为基础的母婴队列研究,同时在城市和半农村地区进行。研究区域内所有孕妇均被识别并纳入研究。对新生儿从出生到 3 个月进行主动和被动随访。收集儿童出现的临床症状和所有临床样本实验室检查结果的数据。采用 Cox 比例风险模型确定与可能的严重细菌感染相关的风险因素。

结果

在 511 名接受随访的新生儿中,共发现 53 例可能的严重细菌感染和 6 例确诊的严重细菌感染,其中一半以上发生在出生后的前 3 天。在第一个月期间,确诊的严重细菌感染发生率为每 1000 例活产 11.7 例,与马达加斯加的 BIRDY 1 相比,下降了 1.3 倍(p=0.50);可能的严重细菌感染发生率为 76.3,与马达加斯加的 BIRDY 1 相比,下降了 2.6 倍(p<0.001)。6 例经血培养确诊的严重细菌感染中,包括 5 例肠杆菌科和 1 例屎肠球菌。5 例肠杆菌科均为超广谱β-内酰胺酶(ESBL)产生菌,对喹诺酮类和庆大霉素耐药。屎肠球菌对万古霉素敏感,但对阿莫西林和庆大霉素耐药。这些病原体被归类为多重耐药菌,对世界卫生组织(WHO)新生儿败血症治疗指南推荐的抗生素耐药。然而,它们对碳青霉烯类药物仍敏感。羊水有臭味、出生时需要复苏和低出生体重与早期可能的严重细菌感染有关。

结论

我们的研究结果表明,即使与 BIRDY 1 的估计值相比,马达加斯加社区的严重细菌感染发生率似乎较低,但仍处于较高水平,并且现有的新生儿败血症治疗指南可能不再适用于马达加斯加。这些结果促使我们进一步加强行动,以预防、早期诊断和管理出生后前 3 天的病例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00a2/10552278/0b50a625e886/12879_2023_8642_Fig1_HTML.jpg

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