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

Prevalence and antimicrobial resistance profiles of respiratory microbial flora in African children with HIV-associated chronic lung disease.
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DOI:
10.1186/s12879-021-05904-3
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发表时间:
2021-02-25
影响因子:
3.7
通讯作者:
Dube FS
Dube FS
中科院分区:
医学3区
文献类型:
--
作者:
Abotsi RE;Nicol MP;McHugh G;Simms V;Rehman AM;Barthus C;Mbhele S;Moyo BW;Ngwira LG;Mujuru H;Makamure B;Mayini J;Odland JØ;Ferrand RA;Dube FS

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艾滋病毒相关性慢性肺病(CLD)在撒哈拉以南非洲的艾滋病毒携带者(CLWH)儿童中很常见,包括那些接受抗逆转录病毒治疗(ART)的儿童。然而,CLD的发病机制及其可能与微生物决定因素的关系仍然知之甚少。我们调查了津巴布韦和马拉维患有CLD(CLD+)和没有CLD(CLD-)的CLWH患者中肺炎链球菌(SP)、金黄色葡萄球菌(SA)、流感嗜血杆菌(HI)和卡他莫拉菌(MC)的患病率和对抗生素的敏感性。鼻咽拭子(NP)和痰来自慢性阻塞性肺疾病+慢性阻塞性肺疾病(CLD+CLWH)(定义为沙丁胺醇支气管扩张后无可逆性的z-Score < − 1),作为阿奇霉素随机、安慰剂对照试验(呼吸试验-NCT02426112)的一部分,以及年龄和性别匹配的CLD-CLWH。标本培养,药敏试验采用纸片扩散法。通过问卷调查确定细菌携带的危险因素,并进行多因素Logistic回归分析。共有410名参与者(CLD+336人,CLD-74人)入选(中位年龄15 岁[IQR = 13-18])。慢性阻塞性肺病患儿NP中SP和MC携带率分别为46%(15/336)和14%(49/74),明显高于非慢性阻塞性肺病患儿的26%(19/74)和14%(49/74),p = 分别为0.012和0.012。慢性阻塞性肺病患儿肺炎支原体对青霉素不敏感的可能性高于慢性阻塞性肺病患儿(36%vs11%[2/18],p = 0.036)。耐甲氧西林金黄色葡萄球菌不常见[4%(7/195)]。在多因素分析中,与NP细菌携带相关的关键因素包括有CLD(SP:调整后的优势比(AOR)2[95%CI 1.1-3.9]),较年轻的年龄(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])。两组的痰细菌携带率相似(50%),且与津巴布韦部位有关(SP:AOR 3.1[1.4-7.3],SA:2.1[1.1-4.2]),持续时间较长(SP:AOR 0.3[0.1-0.8]),与雨季相比炎热(SP:AOR 2.3[1.2-4.4])。CLD+CLWH比CLD-CLWH更容易被MC和SP定植,包括青霉素不敏感的SP菌株。这些细菌在CLD发病机制中的作用,包括急性加重的风险,应该进一步研究。网上版载有补充材料,可在10.1186/s12879-021-05904-3查阅。
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. 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. 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]). 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. The online version contains supplementary material available at 10.1186/s12879-021-05904-3.
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