Antimicrobial and Anti-Infective Activity of Natural Products-Gaining Knowledge from Novel Studies.

Despite advances in the development of antimicrobial drugs in the last centuries, antimicrobial resistance has consistently raised in the last decades, compromising their effectiveness. Novel antimicrobial compounds, especially from natural sources, including plants, microorganisms, and animals, have since become a growing area of research. In this context, studies covering the investigation of their ability to combat resistant microorganisms, either by neutralization or inactivation of pathogen resistance mechanisms and virulence properties, have gained attention. Herein, a collection of 19 manuscripts focused on the antimicrobial and anti-infective activity of natural products, including their mechanisms of action, in silico evidence of antimicrobial activity, synergistic associations with antibiotics, and other aspects, will be discussed.

In Silico and In Vitro Analysis of Sulforaphane Anti-Candida Activity.

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous vegetables, is an antimicrobial with yet controversial activities and mechanisms on fungi. Herein, the in silico and antifungal activities of SFN against C. albicans were investigated. In silico analyzes for the prediction of the biological activities and oral bioavailability of SFN, its possible toxicity and pharmacokinetic parameters, as well as the estimates of its gastrointestinal absorption, permeability to the blood-brain barrier and skin, and similarities to drugs, were performed by using different software. SFN in vitro anti-Candida activities alone and in combination with fluconazole (FLZ) were determined by the broth microdilution method and the checkerboard, biofilm and hyphae formation tests. Amongst the identified probable biological activities of SFN, nine indicated an antimicrobial potential. SFN was predicted to be highly absorbable by the gastrointestinal tract, to present good oral availability, and not to be irritant and/or hepatotoxic. SFN presented antifungal activity against C. albicans and prevented both biofilm and hyphae formation by this microorganism. SFN was additive/synergistic to FLZ. Overall, the data highlights the anti-Candida activity of SFN and its potential to be used as an adjuvant therapy to FLZ in clinical settings.

In Vitro Antimicrobial Activity and Probiotic Potential of Bifidobacterium and Lactobacillus against Species of Clostridium.

Many Clostridium species are found as commensal members of the intestinal microbiota. However, imbalances of the microbiota may lead to certain infections caused by these microorganisms, mainly Clostridium butyricum, Clostridium difficile, and Clostridium perfringens. In many cases, infection recurrence can occur after antibiotics, indicating the need for novel therapeutic options that act on the pathogens and also restore the microbiota. Herein, the in vitro antimicrobial activity and probiotic potential of clinical and reference strains of Bifidobacterium and Lactobacillus were investigated against Clostridium species. Antimicrobial activity was evaluated by the agar spot test and inhibition of gas production. Then, the probiotic potential of selected strains was assessed by analyzing their coaggregation ability, adhesive properties to host cells and mucin, tolerance to acidic pH and bile salts, and antimicrobial susceptibility profiles. Lactobacillus plantarum ATCC 8014 was the most promising strain based on its inhibitory activity against Clostridium spp. Also, this strain met criteria to be considered a probiotic based on its coaggregation ability, adhesive properties, and tolerance to harsh pH and bile acid salt conditions. The results indicate that among the studied strains, L. plantarum ATCC 8014 presents probiotic potential for controlling infections induced by the studied Clostridium species and should be further evaluated in in vivo animal models.

Treatment with either leflunomide or adalimumab reduces anaemia in patients with rheumatoid arthritis.

Rheumatoid arthritis is a chronic disease of the joints, which causes joint pain and disability. Anaemia is a frequent extra-articular manifestation in rheumatoid arthritis, affecting 30-70% of the patients; presenting a negative impact on patient´s quality of life. Some of the drugs used in rheumatoid arthritis treatment improve anaemia; but little is known on the beneficial effects of the anti-rheumatic leflunomide or the anti-TNFα adalimumab, in this parameter. We investigated the incidence of anaemia in rheumatoid arthritis patients treated or not with leflunomide or adalimumab. We also assessed whether anaemia correlates with disease activity. Anaemia was present in patients who had just been diagnosed with rheumatoid arthritis and had never taken disease modifying agents or biologicals (non-specific therapy group), but not in those taking either leflunomide or adalimumab. The erythrocyte sedimentation rate was increased in patients with non-specific therapy in comparison with those taking either leflunomide or adalimumab. Anaemia correlated with increased erythrocyte sedimentation rate. We suggest that leflunomide and adalimumab may be useful in treating anaemia in patients with rheumatoid arthritis.

Transient Receptor Potential Ankyrin 1 Channel Expression on Peripheral Blood Leukocytes from Rheumatoid Arthritic Patients and Correlation with Pain and Disability.

Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA). We also assessed whether TRPA1 expression correlates with joint pain and disability, in addition to the immune changes in RA. TRPA1 expression on peripheral blood leukocytes correlated with pain severity and disability. TRPA1 levels on these cells were associated with the numbers of polymorphonuclear and the activation of CD14+ cells. No correlations were found between the lymphocyte population and TRPA1 expression, pain or disability. Patients recently diagnosed with RA expressed increased levels of TRPA1 on their leukocytes whilst treatment with either LFN or ADA down-regulated this receptor probably by reducing the numbers of polymorphonuclears and the activation of CD14+ cells. We suggest that the activation levels of CD14+ cells, the numbers of PMNs in the peripheral blood and the expression of TRPA1 on peripheral blood leukocytes correlate with RA progression, affecting joint pain sensitivity and loss of function.

Epidemiology and outcomes of ventilator-associated pneumonia in northern Brazil: an analytical descriptive prospective cohort study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is considered the most common nosocomial infection in the intensive care unit (ICU), but its features are not fully known in many hospitals in Brazil. We identified clinical and epidemiological aspects associated with VAP in an intensive care unit (ICU) in a general public hospital in northern Brazil and performed an analytical descriptive prospective cohort study. METHODS: We analyzed data from thirty-three patients who developed VAP while in the ICU. Clinical and epidemiological data of patients were obtained and tracheal secretions were submitted to culture. Microbial isolates were identified and evaluated for resistance against antimicrobial agents by using the automated Vitek 2 system. RESULTS: The frequency of VAP was 26.2% in patients submitted to invasive mechanical ventilation for at least 48 hours, and death occurred in 78.8% of cases. Only the presence of comorbidity showed a significant association (P = 0.029) with death. The most commonly found bacteria were Pseudomonas aeruginosa, Acinetobacter spp., and Enterobacteriaceae. We also found a frequency of 54.5% of multiresistant bacteria associated with VAP, and previous antibiotic therapy was used in 97% of patients. CONCLUSIONS: VAP in our ICU presented with a high frequency and was mainly caused by multiresistant bacteria. Implementation of rational protocols for the use of antibacterial agents and rapid delivery of culture and susceptibility test results are essential. This may help decrease VAP-related mortality rates by multiresistant bacteria in the ICU.