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

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.

The impact of long-term azithromycin on antibiotic resistance in HIV-associated chronic lung disease

“…Nasopharyngeal (NP) swabs and sputa were collected from participants at baseline, 48- and 72-week visits. Details of sample collection, handling and transport, culture and antibiotic susceptibility testing (AST) for SP, SA, HI and MC have previously been described [ 10 ]. Briefly, susceptibility to AZM, tetracycline and cotrimoxazole was conducted for all four bacterial species using the Kirby–Bauer disk diffusion method.…”

“…42) 0.81 [0.47-1.42] 0.469 #Missing values: Weight-for-age-z-score(5), Viral load suppression at enrolment(5), ART regimen(1), Duration of ART at baseline(10), BMI-for-age z-score (5), Height-for-age z-score(5). *Missing values: Weightfor-age-z-score (3), Viral load suppression at enrolment (1), Duration of ART at baseline (4), BMI-for-age z-score (3), Height-for-age z-score(3).…”

“…Missing values: Weight-for-age-z-score(5), Viral load suppression at enrolment(5), ART regimen (1), Duration of ART at baseline(10), Cotrimoxazole prophylaxis (2), BMI-for-age z-score (5), Height-for-age zscore(5). *Missing values: Viral load suppression at enrolment (1), Duration of ART at baseline (2), Cotrimoxazole prophylaxis(1).…”

Sputum bacterial load and bacterial composition correlate with lung function and are altered by long term azithromycin treatment in children with HIV-associated chronic lung disease

“…We previously observed that a Haemophilus, Moraxella or Neisseria (HMN)-dominant sputum bacteriome was associated with a 1.5-fold increased risk of HCLD, compared to a Streptococcus or Prevotella-dominant bacteriome [10]. We also showed an association between HCLD and respiratory carriage of Streptococcus pneumoniae and Moraxella catarrhalis [11]. The therapeutic effect of AZM in COPD may be mediated by changes in the lung bacteriome along with associated changes in microbial metabolites that interact with the host immune system [2].…”

Effect of azithromycin on incidence of acute respiratory exacerbations in children with HIV taking antiretroviral therapy and co-morbid chronic lung disease: a secondary analysis of the BREATHE trial

“…Detailed microbiological procedures and results have been reported previously [7,8]. Conventional culture was performed for common bacterial pathogens at baseline, 12 and 18 months on sputum and nasopharyngeal samples.…”