Efficacy of Calcium-EDTA as an Inhibitor for Metallo-β-Lactamase in a Mouse Model of Pseudomonas aeruginosa Pneumonia▿

In this study, we have evaluated the efficacy of calcium-EDTA (Ca-EDTA) as an inhibitor of bacterial metalloenzymes, such as metallo-β-lactamase (MBL) and other proteases, in a mouse model of Pseudomonas aeruginosa pneumonia. The simultaneous presence of Ca-EDTA (32 μg/ml) reduced the MICs of imipenem (IPM) in all MBL-producing P. aeruginosa isolates (IMP-1, -2, -7, and -10 and VIM-2) but not non-MBL-producing strains. In the pneumonia model, mice were intranasally infected with MBL-producing P. aeruginosa and then kept under conditions of hyperoxia to mimic ventilator-associated pneumonia. With both intranasal and subcutaneous administrations, Ca-EDTA significantly potentiated survival benefits of IPM compared to those of IPM alone. Ca-EDTA combination therapy induced a significant reduction of the bacterial burden in the lungs (P < 0.05). Furthermore, the inhibition activity of Ca-EDTA against MBL activity was confirmed by using the purified IMP-1 enzyme, which was characterized by a 50% inhibitory concentration (IC50) of 55 ± 8.2 μM. Finally, the protective effects of Ca-EDTA were demonstrated by culture supernatant-induced epithelial cell damage and acute lung injury in mice. These data suggest the therapeutic potential of Ca-EDTA not only by the blocking of MBLs but also by neutralizing tissue-damaging metalloproteases in P. aeruginosa infections

Analysis of the Influenza A (H1N1) 2009 Pandemic Infection in Japanese Asthmatic Patients: Using a Questionnaire-Based Survey

Background: Influenza infection is known to be an exacerbating factor in the control of asthma, therfore its prevention is critical in managing asthma. The aim of this study was to investigate the influenza A H1N1 2009 pandemic virus (H1N1 pdm09) infection in adult asthmatic patients. Methods: Data were obtained from a questionnaire-based survey of asthmatic patients conducted from September to October 2010 in Niigata Prefecture. Patient background, H1N1 pdm09 infection, vaccination status, and asthma exacerbation due to influenza infection were analyzed. Results: In total, 2,555 cases were analyzed. The incidence of the infection was 6.7% (95% confidence interval [CI]: 5.7-7.6), and the rate of vaccination was 63.9% (95% CI: 62.1-65.8). The odds ratio (OR) for vaccination against the infection among adult patients and younger patients (≤ the median age) were 0.61 (95% CI: 0.45-0.84) and 0.62 (95% CI: 0.42-0.90), respectively. However, OR among the older patient (> median age) were 1.38 (95%CI: 0.66-2.89). The rate of infection-induced asthma exacerbation was 23.2% (95% CI: 18.6-29.6), and the OR for vaccination against the infection-induced asthma exacerbation was 1.42 (95% CI: 0.69-2.92). Conclusions: The effectiveness of the vaccination against the H1N1 pdm09 virus was confirmed during the first pandemic season, but it was limited. Further investigation on H1N1 pdm09 virus infection in asthmatics will be required