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Cystic fibrosis (CF) is a genetic and multisystemic disease that requires a high therapeutic demand for its control. The aim of this study was to assess therapeutic adherence (TA) to different treatments to study possible clinical consequences and clinical factors influencing adherence. This is an ambispective observational study of 57 patients aged over 18 years with a diagnosis of CF. The assessment of TA was calculated using the Medication Possession Ratio (MPR) index. These data were related to exacerbations and the rate of decline in FEV1 percentage. Compliance was good for all CFTR modulators, azithromycin, aztreonam, and tobramycin in solution for inhalation. The patients with the best compliance were older; they had exacerbations and the greatest deterioration in lung function during this period. The three variables with the highest importance for the compliance of the generated Random Forest (RF) models were age, FEV1%, and use of Ivacaftor/Tezacaftor. This is one of the few studies to assess adherence to CFTR modulators and symptomatic treatment longitudinally. CF patient therapy is expensive, and the assessment of variables with the highest importance for a high MPR, helped by new Machine learning tools, can contribute to defining new efficient TA strategies with higher benefits.

Current antifungal chemotherapy against the prevalent basidiomycete Cryptococcus neoformans displays some drawbacks. This pathogenic fungus is refractory to echinocandins, whereas conventional treatment with amphotericin B plus 5-fluorocytosine has a limited efficacy. In this study, we explored the potential cryptococcal activity of some natural agents. After conducting a screening test with a set of propolis from different geographical areas, we selected an extract from China, which displayed a certain cytotoxic activity against C. neoformans, due to this extract being cheap and easily available in large amounts. The combination of this kind of propolis with carnosic acid in a 1:4 ratio induced a stronger fungicidal effect, which occurred following a synergistic pattern, without visible alterations in external cell morphology. Furthermore, several carnosic acid–propolis formulations applied onto preformed biofilms decreased the metabolic activity of the sessile cells forming biofilms. These data support the potential application of mixtures containing these two natural extracts in the design of new antifungal strategies in order to combat opportunistic infections caused by prevalent pathogenic fungi.

Background: Leptospirosis is a worldwide zoonotic infection, and its management needs to be refined. This study aims to discern which antibiotic would be the best option to treat leptospirosis disease and analyze the efficacy of chemoprophylaxis regimens to prevent this illness. Methods: systematic review and meta-analysis on the efficacy of antibiotic treatment and chemoprophylaxis of leptospirosis in humans. Results: Ten clinical trials compared an antibiotic treatment with placebo or other antibiotic treatments in leptospirosis (the most recent one was published in 2007). The meta-analysis shows no effect of penicillin treatment on mortality compared to placebo (OR 1.65; 95% CI 0.76–3.57; p = 0.21). There are no differences between penicillin and cephalosporins or doxycycline. Penicillin does not reduce the time of defervescence (MD-0.16; 95% CI (−1.4) –1.08; p = 0.80) nor hospital stay (MD 0.15; 95% CI (−0.75)–1.06; p = 0.74). Besides, the data did not demonstrate any effectiveness of the use of penicillin in terms of the incidence of oliguria/anuria, the need for dialysis treatment, time to creatinine normalization, incidence of jaundice, or the liver function normalization time. Eight trials have assessed prophylactic treatment against leptospirosis with different strategies. A weekly dose of 200 mg of doxycycline does not show benefit versus placebo regarding the number of new cases of symptomatic leptospirosis (OR 0.20; 95% CI 0.02–1.87; p = 0.16). A single dose of doxycycline at exposure to flood water could have a beneficial effect (OR 0.23; 95% CI 0.07–0.77; p = 0.02). None of the other chemoprophylaxis regimens tested have shown a statistically significant effect on the number of new symptomatic cases. Conclusion: There is no evidence that antibiotics are a better treatment than placebo regarding mortality, shortening of fever, liver and kidney function, or reduction in the hospital stay. On the other hand, neither doxycycline nor penicillin, nor azithromycin have shown statistically significant differences in preventing symptomatic infection. Well-designed clinical trials, including other antibiotics such as quinolones or aminoglycosides, are urgently needed to improve our understanding of the treatment for this infection, which continues to be a neglected disease.

Clostridioides difficile is an anaerobic spore-forming Gram-positive bacterium. C. difficile carriage and 16S rDNA profiling were studied in three clinical groups at three different sampling times: inflammatory bowel disease (IBD) patients, C. difficile infection (CDI) patients and healthcare workers (HCWs). Diversity analysis was realized in the three clinical groups, the positive and negative C. difficile carriage groups and the three analysis periods. Concerning the three clinical groups, β-diversity tests showed significant differences between them, especially between the HCW group and IBD group and between IBD patients and CDI patients. The Simpson index (evenness) showed a significant difference between two clinical groups (HCWs and IBD). Several genera were significantly different in the IBD patient group (Sutterella, Agathobacter) and in the CDI patient group (Enterococcus, Clostridioides). Concerning the positive and negative C. difficile carriage groups, β-diversity tests showed significant differences. Shannon, Simpson and InvSimpson indexes showed significant differences between the two groups. Several genera had significantly different relative prevalences in the negative group (Agathobacter, Sutterella, Anaerostipes, Oscillospira) and the positive group (Enterococcus, Enterobacteriaceae_ge and Enterobacterales_ge). A microbiota footprint was detected in C. difficile-positive carriers. More experiments are needed to test this microbiota footprint to see its impact on C. difficile infection.

Clostridioides difficile is an anaerobic Gram-positive and spore-forming bacterium. The majority of C. difficile strains produce two toxins, A and B, associated with the development of acute diarrhea and/or colitis. In this review, two situations are distinguished: C. difficile infection (CDI) and asymptomatic colonization (AC). The main objective of this review is to explore the available data related to the link between the gut microbiota and the development of CDI. The secondary aim is to provide more information on why some people colonized with toxigenic C. difficile develop an infection while others show no signs of disease. Several factors, such as the use of antibiotics and proton pump inhibitors, hospitalization, and age, predispose individuals to C. difficile colonization and/or C. difficile infection. The gut microbiota of people with AC showed decreased abundances of Prevotella, Alistipes, Bacteroides, Bifidobacterium, Dorea, Coprococcus, and Roseburia. The gut microbiota of people suffering from CDI showed reductions in the abundances of Lachnospiraceae, Ruminococcaceae, Blautia spp., Prevotella spp., Dialister spp., Bifidobacterium spp., Roseburia spp., Anaerostipes spp., Faecalibacterium spp. and Coprococcus spp., in comparison with healthy people. Furthermore, increases in the abundances of Enterococcaceae and Enterococcus were associated with C. difficile infection.

Engineering of multifunctional drug nanocarriers combining stability and good release properties remains a great challenge. In this work, natural polymers κ-carrageenan (κ-CAR) and chitosan (CS) were deposited onto olive oil nanoemulsion droplets (NE) via layer-by-layer (LbL) self-assembly to study the release mechanisms of the anti-inflammatory diflunisal (DF) as a lipophilic drug model. The nano-systems were characterized by dynamic light scattering (DLS), zeta potential (ζ-potential) measurements, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (XEDS) and Fourier transform infrared spectroscopy (FTIR) to confirm the NE-coating with polymer layers. In addition, kinetic release studies of DF were developed by the dialysis diffusion bag technique. Mathematical models were applied to investigate the release mechanisms. The results showed that stable and suitably sized nanocapsules (~300 nm) were formed. Also, the consecutive adsorption of polyelectrolytes by charge reversal was evidenced. More interestingly, the drug release mechanism varied depending on the number of layers deposited. The nanosized systems containing up to two layers showed anomalous transport and first order kinetics. Formulations with three and four layers exhibited Case II transport releasing diflunisal with zero order kinetics. Hence, our results suggest that these polyelectrolyte nanocapsules have great potential as a multifunctional nanocarrier for drug delivery applications.