BackgroundEpidemic outbreaks of multi-drug resistant (MDR) Acinetobacter baumannii (AB) in intensive care units (ICUs) are increasing. The incidence of MDR AB bacteremia, which develops as a result of colonization, is increasing through widespread dissemination of the pathogen, and further colonization. We sought to determine risk factors for MDR AB bacteremia in patients colonized with MDR AB in the ICU.MethodsWe conducted a retrospective, observational study of 200 patients colonized with MDR AB in the ICU at Severance Hospital, South Korea during the outbreak period between January 2008 and December 2009.ResultsOf the 200 patients colonized with MDR AB, 108 developed MDR AB bacteremia, and 92 did not. APACHE II scores were higher in bacteremic than non-bacteremic patients at the time of ICU admission and colonization (24.0 vs. 21.6; P = 0.035, 22.9 vs. 16.8; P < 0.001, respectively). There was no difference between the two groups in the duration of time from ICU admission to colonization (7.1 vs. 7.2 days; P = 0.923), but the duration of time at risk was shorter in bacteremic patients (12.1 vs. 6.0 days; P = 0.016). A recent invasive procedure was a significant risk factor for development of bacteremia (odds ratio = 3.85; 95% CI 1.45-10.24; P = 0.007). Multivariate analysis indicated infection and respiratory failure at the time of ICU admission, maintenance of mechanical ventilation, maintenance of endotracheal tube instead of switching to a tracheostomy, recent central venous catheter insertion, bacteremia caused by other microorganism after colonization by MDR AB, and prior antimicrobial therapy, were significant risk factors for MDR AB bacteremia.ConclusionsPatients in the ICU, colonized with MDR AB, should be considered for minimizing invasive procedures and early removal of the invasive devices to prevent development of MDR AB bacteremia.
Purpose We aimed to investigate the effects of dupilumab on 1) the permeability and antimicrobial barrier, 2) the composition of the skin microbiome, and 3) the correlation between changes in skin barrier properties and microbiota in atopic dermatitis (AD) patients. Methods Ten patients with severe AD were treated with dupilumab for 12 weeks. Disease severity was assessed using the Eczema Area and Severity Index (EASI). Skin barrier function was evaluated by measuring transepidermal water loss, stratum corneum (SC) hydration, and pH. The following parameters were analyzed in the pre- and post-treatment SC samples; 1) skin microbiota using 16S rRNA gene sequencing, 2) lipid composition using mass spectrometry, and 3) human β-defensin 2 (hBD-2) expression using quantitative reverse transcription polymerase chain reaction. Results SC hydration levels in the lesional and non-lesional skin increased after 12-week dupilumab therapy (24.2%, P < 0.001 and 59.9%, P < 0.001, respectively, vs. baseline) and correlated with EASI improvement ( r = 0.90, P < 0.001 and r = 0.85, P = 0.003, respectively). Dupilumab increased the long-chain ceramide levels in atopic skin (118.4%, P = 0.028 vs. baseline) that correlated with changes in SC hydration ( r = 0.81, P = 0.007) and reduced the elevated hBD-2 messenger RNA levels (−15.4%, P = 0.005 vs. baseline) in the lesional skin. Dupilumab decreased the abundance of Staphylococcus aureus. In contrast, the microbial diversity and the abundance of Cutibacterium and Corynebacterium species increased, which were correlated with an increase in SC hydration levels (Shannon diversity, r = 0.71, P = 0.027; Cutibacterium , r = 0.73, P = 0.017; Corynebacterium , r = 0.75, P = 0.012). Increased abundance of Cutibacterium species was also correlated with EASI improvement ( r = 0.68, P = 0.032). Conclusions Th2 blockade-induced normalization of skin microbiome in AD patients is associated with increased SC hydration.
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