艾滋病毒相关慢性肺部疾病非洲儿童呼吸道微生物菌群的流行状况和抗微生物耐药谱。

Prevalence and antimicrobial resistance profiles of respiratory microbial flora in African children with HIV-associated chronic lung disease.

机构信息

Department of Molecular and Cell Biology & Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

Department of Pharmaceutical Microbiology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana.

出版信息

BMC Infect Dis. 2021 Feb 25;21(1):216. doi: 10.1186/s12879-021-05904-3.

DOI:10.1186/s12879-021-05904-3

PMID:33632144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7908671/

Abstract

BACKGROUND

HIV-associated chronic lung disease (CLD) is common among children living with HIV (CLWH) in sub-Saharan Africa, including those on antiretroviral therapy (ART). However, the pathogenesis of CLD and its possible association with microbial determinants remain poorly understood. We investigated the prevalence, and antibiotic susceptibility of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC) among CLWH (established on ART) who had CLD (CLD+), or not (CLD-) in Zimbabwe and Malawi.

METHODS

Nasopharyngeal swabs (NP) and sputa were collected from CLD+ CLWH (defined as forced-expiratory volume per second z-score < - 1 without reversibility post-bronchodilation with salbutamol), at enrolment as part of a randomised, placebo-controlled trial of azithromycin (BREATHE trial - NCT02426112 ), and from age- and sex-matched CLD- CLWH. Samples were cultured, and antibiotic susceptibility testing was conducted using disk diffusion. Risk factors for bacterial carriage were identified using questionnaires and analysed using multivariate logistic regression.

RESULTS

A total of 410 participants (336 CLD+, 74 CLD-) were enrolled (median age, 15 years [IQR = 13-18]). SP and MC carriage in NP were higher in CLD+ than in CLD- children: 46% (154/336) vs. 26% (19/74), p = 0.008; and 14% (49/336) vs. 3% (2/74), p = 0.012, respectively. SP isolates from the NP of CLD+ children were more likely to be non-susceptible to penicillin than those from CLD- children (36% [53/144] vs 11% [2/18], p = 0.036). Methicillin-resistant SA was uncommon [4% (7/195)]. In multivariate analysis, key factors associated with NP bacterial carriage included having CLD (SP: adjusted odds ratio (aOR) 2 [95% CI 1.1-3.9]), younger age (SP: aOR 3.2 [1.8-5.8]), viral load suppression (SP: aOR 0.6 [0.4-1.0], SA: 0.5 [0.3-0.9]), stunting (SP: aOR 1.6 [1.1-2.6]) and male sex (SA: aOR 1.7 [1.0-2.9]). Sputum bacterial carriage was similar in both groups (50%) and was associated with Zimbabwean site (SP: aOR 3.1 [1.4-7.3], SA: 2.1 [1.1-4.2]), being on ART for a longer period (SP: aOR 0.3 [0.1-0.8]), and hot compared to rainy season (SP: aOR 2.3 [1.2-4.4]).

CONCLUSIONS

CLD+ CLWH were more likely to be colonised by MC and SP, including penicillin-non-susceptible SP strains, than CLD- CLWH. The role of these bacteria in CLD pathogenesis, including the risk of acute exacerbations, should be further studied.

摘要

背景

在撒哈拉以南非洲地区，HIV 相关的慢性肺部疾病（CLD）在感染 HIV 的儿童（CLWH）中很常见，包括接受抗逆转录病毒治疗（ART）的儿童。然而，CLD 的发病机制及其与微生物决定因素的可能关联仍知之甚少。我们调查了津巴布韦和马拉维接受抗逆转录病毒治疗（ART）的 CLD+（定义为用力呼气量每秒 z 评分 < -1 且沙丁胺醇支气管扩张后无逆转）和无 CLD（CLD-）CLWH 中肺炎链球菌（SP）、金黄色葡萄球菌（SA）、流感嗜血杆菌（HI）和卡他莫拉菌（MC）的流行率和抗生素药敏性。

方法

在 BREATHE 试验（NCT02426112）中，作为随机、安慰剂对照试验的一部分，在 CLD+ CLWH 入组时收集鼻咽拭子（NP）和痰液，以及年龄和性别匹配的 CLD- CLWH。使用纸片扩散法进行培养和抗生素药敏试验。使用问卷调查确定细菌携带的危险因素，并使用多变量逻辑回归进行分析。

结果

共纳入 410 名参与者（336 名 CLD+，74 名 CLD-）（中位年龄 15 岁 [IQR 13-18]）。CLD+儿童 NP 中 SP 和 MC 的携带率高于 CLD-儿童：46%（154/336）与 26%（19/74），p=0.008；14%（49/336）与 3%（2/74），p=0.012。CLD+儿童 NP 中 SP 分离株对青霉素的耐药率高于 CLD-儿童（36%[53/144]与 11%[2/18]，p=0.036）。耐甲氧西林的 SA 较为罕见[4%（7/195）]。多变量分析显示，与 NP 细菌携带相关的关键因素包括患有 CLD（SP：调整后的优势比（aOR）2 [95%CI 1.1-3.9]）、年龄较小（SP：aOR 3.2 [1.8-5.8]）、病毒载量抑制（SP：aOR 0.6 [0.4-1.0]，SA：0.5 [0.3-0.9]）、发育迟缓（SP：aOR 1.6 [1.1-2.6]）和男性（SA：aOR 1.7 [1.0-2.9]）。两组的痰液细菌携带率相似（50%），与津巴布韦的地点有关（SP：aOR 3.1 [1.4-7.3]，SA：2.1 [1.1-4.2]）、接受 ART 的时间较长（SP：aOR 0.3 [0.1-0.8]）和与雨季相比处于旱季（SP：aOR 2.3 [1.2-4.4]）。