Impact of Long-Term Azithromycin Therapy on Carriage and Resistance of Respiratory Bacteria Among Children with HIV-Associated Chronic Lung Disease: A Randomised Controlled Trial

Selection for resistance to azithromycin (AZM) and other antibiotics such as tetracyclines and lincosamides remains a concern with long-term AZM use for treatment of chronic lung diseases (CLD). We investigated the impact of 48 weeks of AZM on the carriage and antibiotic resistance of common respiratory bacteria among children with HIV-associated CLD. Nasopharyngeal (NP) swabs and sputa were collected at baseline, 48 and 72 weeks from participants with HIV-associated CLD randomised to receive weekly AZM or placebo for 48 weeks and followed post-intervention until 72 weeks. The primary outcomes were prevalence and antibiotic resistance of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI) and Moraxella catarrhalis (MC) at these timepoints. Mixed-effects logistic regression and Fisher's exact test were used to compare carriage and resistance, respectively. Of 347 (174 AZM, 173 placebo) participants (median age 15 years (IQR 13–18), female 49%), NP carriage was significantly lower in the AZM (n=159) compared to placebo (n=153) arm for SP (18% versus 41%, p<0.001), HI (7% versus 16%, p=0.01) and MC (4% versus 11%, p=0.02); SP resistance to AZM (62% (18 out of 29) versus 13% (8 out of 63), p<0.0001) or tetracycline (60% (18 out of 29) versus 21% (13 out of 63), p<0.0001) was higher in the AZM arm. Carriage of SA resistant to AZM (91% (31 out of 34) versus 3% (1 out of 31), p<0.0001), tetracycline (35% (12 out of 34) versus 13% (4 out of 31), p=0.05) and clindamycin (79% (27 out of 34) versus 3% (1 out of 31), p<0.0001) was also significantly higher in the AZM arm and persisted at 72 weeks. Similar findings were observed for sputa. The persistence of antibiotic resistance and its clinical relevance for future infectious episodes requiring treatment needs further investigation

System-on-chips design using ISCAS benchmark circuits - an approach to fault injection and simulation based on Verilog HDL

The evolution of the embedded cores-based design paradigm in recent times has created numerous challenging problems for the test design community. To develop suitable test environment and appropriate test methodologies for digital cores-based-system-on-chip (SOC) is a fascinating area of research today. This paper attempts to develop viable solution option to these problems based on cores constructed from the International Symposium on Circuits and Systems (ISCAS) 85 combinational and ISCAS 89 sequential benchmark circuits. The wrapper that separates the core under test from other cores is assumed to be Institute of Electrical and Electronics Engineers P1500-compliant. The cores and test access mechanism (TAM) are described in the paper using Verilog hardware description language, while TAM is implemented as a plain signal transport medium, being shared by all the cores in the SOC. The fault injection is done by a simulator that also generates the tests for the core. The fault simulation process is carried out after successful compilation of the cores, the individual core selection being done by the program running in the background

Composition of gut microbiota of children and adolescents with perinatal HIV infection taking antiretroviral therapy in Zimbabwe

Background - Human immunodeficiency virus (HIV) infection causes impairment of the gastrointestinal barrier, with substantial depletion of CD4+ T cells in the gut. Antiretroviral therapy (ART) restores CD4+ counts and may have beneficial effects on gut microbiota in adults. Little is known about effect of long-term ART on gut microbiome in HIV-infected children. We investigated composition of gut microbiota in HIV-infected and -uninfected children and assessed associations between gut microbiota and patient characteristics. Methods - In a cross-sectional study, rectal swabs were collected from 177 HIV-infected and 103 HIV-uninfected controls. Gut microbial composition was explored using 16S ribosomal ribonucleic acid sequencing. Results - Human immunodeficiency virus-infected children had significantly lower alpha-diversity and higher beta-diversity compared to HIV-uninfected. No association was observed between microbiome diversity and CD4+ T-cell count, HIV viral load, or HIV-associated chronic lung disease. We found enriched levels of Corynebacterium (P Finegoldia (P Anaerococcus (P Enterobacteriaceae (P = .02) in participants with low CD4+ counts (3). Prolonged ART-treatment (≥10 years) was significantly associated with a richer gut microbiota by alpha diversity. Conclusions - Human immunodeficiency virus-infected children have altered gut microbiota. Prolonged ART may restore the richness of the microbiota closer to that of HIV-uninfected children

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

Selection for resistance to azithromycin (AZM) and other antibiotics such as tetracyclines and lincosamides remains a concern with long-term AZM use for treatment of chronic lung diseases (CLD). We investigated the impact of 48 weeks of AZM on the carriage and antibiotic resistance of common respiratory bacteria among children with HIV-associated CLD. Nasopharyngeal (NP) swabs and sputa were collected at baseline, 48 and 72 weeks from participants with HIV-associated CLD randomised to receive weekly AZM or placebo for 48 weeks and followed post-intervention until 72 weeks. The primary outcomes were prevalence and antibiotic resistance of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI) and Moraxella catarrhalis (MC) at these timepoints. Mixed-effects logistic regression and Fisher's exact test were used to compare carriage and resistance, respectively. Of 347 (174 AZM, 173 placebo) participants (median age 15 years (IQR 13-18), female 49%), NP carriage was significantly lower in the AZM (n=159) compared to placebo (n=153) arm for SP (18% versus 41%, p<0.001), HI (7% versus 16%, p=0.01) and MC (4% versus 11%, p=0.02); SP resistance to AZM (62% (18 out of 29) versus 13% (8 out of 63), p<0.0001) or tetracycline (60% (18 out of 29) versus 21% (13 out of 63), p<0.0001) was higher in the AZM arm. Carriage of SA resistant to AZM (91% (31 out of 34) versus 3% (1 out of 31), p<0.0001), tetracycline (35% (12 out of 34) versus 13% (4 out of 31), p=0.05) and clindamycin (79% (27 out of 34) versus 3% (1 out of 31), p<0.0001) was also significantly higher in the AZM arm and persisted at 72 weeks. Similar findings were observed for sputa. The persistence of antibiotic resistance and its clinical relevance for future infectious episodes requiring treatment needs further investigation