Screening for COPD in primary care, involving dentists, pharmacists, physiotherapists, nurses and general practitioners (the UNANIME pilot study).

BACKGROUND: COPD is underdiagnosed and is projected to be the third cause of death in 2030. However, recent reviews do not recommend screening for COPD in the general population. METHODS: We conducted a prospective study to assess the feasibility of implementing COPD screening in a high-risk COPD population, with the help of various healthcare professionals (General practitioners, pharmacists, dentists, physiotherapists, and nurses). Participants filled out a questionnaire, performed a spirometry (COPD6™) and counselling was performed, including smoking cessation and chest physician referral. Participants were contacted at two months to evaluate the effect of the intervention. RESULTS: Between April 7th, 2017 and July 30th, 2018, 157 participants filled out the questionnaires, performed spirometry and were contacted at two months. Thirty-five out of 157 (22% [95% CI, 15.8-28.8]) participants were detected with an airflow obstruction (FEV1/FEV6 < 0.7), using COPD6™ device. At the two-month-contact, 68 participants (43%, [95%CI 35.5-51.1]) were engaged in a smoking cessation program and 22 (14% [95 % CI, 8.6-19.4]) reported having quit smoking. CONCLUSION: This pilot study suggested that a predefined screening of COPD by different healthcare professionals could be implemented in primary care and might be part of counselling for smoking cessation (NCT03104348 on ClinicalTrials.gov).

High-performance liquid chromatography assay for moxifloxacin in brain tissue and plasma: validation in a pharmacokinetic study in a murine model of cerebral listeriosis.

Moxifloxacin is a broad-spectrum antibacterial 8-methoxy-fluoroquinolone. In order to evaluate the pharmacokinetic properties of moxifloxacin in mouse plasma and brain tissue, we developed a high-performance liquid chromatography (HPLC) method. This study was based on single-drug delivery, intravenously dosed in a central listeriosis murine model. The method employed a reversed-phase Lichrospher RP-18 with a precolumn (250 × 4.6 mm) and a mobile phase composed of a mixture of acetonitrile, methanol, and citric buffer (pH = 3.5) with sodium dodecyl sulfate and tetrabutylammonium bromide. Fluorescence detection was performed at an excitation wavelength of 290 nm and an emission wavelength of 550 nm. The relative standard deviation of intra- and inter-day assays was <10%. This validated method led to a short retention time (8.0 min) for moxifloxacin. The standard curves were linear from 5-250 µg/L in plasma and from 0.1-2.5 µg/g of brain tissue. The limits of quantification were 5 µg/L in plasma and 0.1 µg/g in brain tissue. The method enabled the detection of systemic antimicrobial in plasma and in CNS in Listeria-infected mice. Injected moxifloxacin passed through the encephalic barrier within a 30 to 60 min after injection time frame. Moxifloxacin pharmacokinetics are modeled in an infected model compared to control mice.

Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model.

The prevalence of extensively drug-resistant tuberculosis (XDR-TB), defined as TB that is resistant to isoniazid, rifampin, fluoroquinolones, and aminoglycosides, is rising worldwide. The extent of Mycobacterium tuberculosis resistance to fluoroquinolones depends on the mutation in the DNA gyrase, the only target of fluoroquinolones. The MIC of moxifloxacin, the most active fluoroquinolone against M. tuberculosis, may be lower than its peak serum level for some ofloxacin-resistant strains of Mycobacterium tuberculosis. Therefore, if the MIC of moxifloxacin is lower than its peak serum level, it may be effective against XDR-TB. Our objective was to determine the efficacy of moxifloxacin in treating ofloxacin-resistant TB. We selected isogenic fluoroquinolone-resistant mutants of M. tuberculosis H37Rv in vivo. We infected Swiss mice with either wild-type H37Rv or one of three mutant strains with different MICs that are commonly seen in clinical practice. The MICs of the mutant strains ranged from below to above the peak moxifloxacin level seen in humans (3 µg/ml). Each mouse was treated with one of four moxifloxacin doses for 1 month. Moxifloxacin was effective against mutant strain GyrB D500N, with the lowest MIC (0.5 µg/ml), when the standard dose was doubled. Moxifloxacin reduced mortality in mice infected with mutant strain GyrA A90V with an intermediate MIC (2 µg/ml). However, it had no impact on the mutant strain GyrA D94G with the highest MIC (4 µg/ml). Our study underscores current WHO recommendations to use moxifloxacin when there is resistance to early-generation fluoroquinolones such as ofloxacin, restricting this recommendation to strains with moxifloxacin MICs of less than or equal to 2 µg/ml.