Clostridioides difficile is an enteric pathogen that can cause a range of illnesses from mild diarrhea to pseudomembranous colitis and even death. This pathogen often takes advantage of microbial dysbiosis provoked by antibiotic use. With the increasing incidence and severity of infections, coupled with high recurrence rates, there is an urgent need to identify innovative therapies that can preserve the healthy state of the gut microbiota. In this study, we screened a microbial metabolite library against C. difficile. From a collection of 527 metabolites, we identified 18 compounds with no previously identified antimicrobial activity and metabolites that exhibited potent activity against C. difficile growth. Of these 18 hits, five drugs and three metabolites displayed the most potent anti-C. difficile activity and were subsequently assessed against 20 clinical isolates of C. difficile. These potent agents included ecteinascidin 770 (minimum inhibitory concentration against 50% of isolates [MIC50] ≤0.06 µg/mL); 8-hydroxyquinoline derivatives, such as broxyquinoline and choloroquinaldol (MIC50 = 0.125 µg/mL); ionomycin calcium salt, carbadox, and robenidine hydrochloride (MIC50 = 1 µg/mL); and dronedarone and milbemycin oxime (MIC50 = 4 µg/mL). Unlike vancomycin and fidaxomicin, which are the standard-of-care anti-C. difficile antibiotics, most of these metabolites showed robust bactericidal activity within 2-8 h with minimal impact on the growth of representative members of the normal gut microbiota. These results suggest that the drugs and microbial metabolite scaffolds may offer alternative avenues to address unmet needs in C. difficile disease prevention and treatment.
OBJECTIVE: The most frequent infection associated with hospital settings is Clostridioides difficile, which can cause fatal diarrhea and severe colitis, toxic megacolon, sepsis, and leaky gut. Those who have taken antibiotics for other illnesses that affect the gut\'s healthy microbiota are more susceptible to C. difficile infection (CDI). Recently, some reports showed higher recurrence rates and resistance to anti-C. difficile, which may compromise the efficacy of CDI treatment. Our study is significant because it is anticipated to discover novel microbial metabolites and drugs with microbial origins that are safe for the intestinal flora, effective against C. difficile, and reduce the risk of recurrence associated with CDI.

In response to the global rise in antibiotic resistance and the prevalence of bacterial biofilm-related infections, the antibacterial efficacy of methanolic, ethanolic, and aqueous extracts of 18 Lamiaceae plants from Serbia was evaluated. The total coumarins and triterpenes were detected spectrophotometrically, while a microdilution assay measured their effects on bacterial growth. Additionally, the impact of these extracts was assessed on Pseudomonas aeruginosa PAO1 adhesion and invasion in human fibroblasts and biofilm formation and degradation. The alcoholic extracts had the highest phytochemical content, with Teucrium montanum and Lavandula angustifolia being the richest in coumarins and triterpenes, respectively. Gram-positive bacteria, particularly Bacillus subtilis, were more susceptible to the extracts. Hyssopus officinalis ethanolic and Sideritis scardica methanolic extracts inhibited bacterial growth the most efficiently. Although the extracts did not inhibit bacterial adhesion, most ethanolic extracts significantly reduced bacterial invasion. Origanum vulgare and H. officinalis ethanolic extracts significantly inhibited biofilm formation, while Teucrium chamaedrys extract was the most active in biofilm degradation. This study significantly contributes to the literature by examining the antibacterial activity of Lamiaceae extracts, addressing major literature gaps, and underscoring their antibacterial potential, particularly Satureja montana and O. vulgare ethanolic extracts, linking their efficacy to coumarins and triterpenes.

BACKGROUND: The Patient and Observer Scar Assessment Scale (POSAS) is frequently used to assess scar quality after burns. It is important to be aware of the minimal important change (MIC) and the minimal clinically important difference (MCID) to establish if a POSAS score represents a clinically relevant change or difference. The aim of this study is to explore the MIC and MCID of POSAS version 2.0.
METHODS: This prospective study included 127 patients with deep dermal burns that underwent split thickness skin grafting with a mean age of 44 years (range 0 - 87) and total body surface area burned of 10 % (range 0.5 - 55). POSAS data was obtained for one burn scar area at three, six, and 12 months after split skin grafting. At the second and third visits, patients rated the degree of clinical change in scar quality in comparison to the previous visit. At 12 months, they completed the POSAS for a second burn scar area and rated the degree of clinical difference between the two scar areas. Two anchor-based methods were used to determine the MIC and MCID.
RESULTS: MIC values of the patient POSAS ranged from - 0.59 to - 0.29 between three and six months and from - 0.75 to - 0.38 between six and 12 months follow-up. Both had a poor discriminatory value. MCID values ranged from - 0.39 and - 0.08, with a better discriminatory value.
CONCLUSIONS: Results suggest that patients consider minor differences (less than 0.75 on the 1-10 scale) in POSAS scores as clinically important scar quality changes. MCID values can be used to evaluate the effects of burn treatment and perform sample-size calculations.

Herbal extracts have evoked interest owing to the small number of terpenoids and phenolic compounds, which impart antimicrobial, antioxidant, and anti-inflammatory properties. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) of four herbal extracts (lemon grass oil, basil oil, peppermint oil, and Obicure tea extract) against endodontic pathogens along with the MIC: MBC/MFC ratio were evaluated. The antimicrobial activity by detecting the MIC of three essential oils and tea extract was evaluated against eight common endodontic pathogens by the broth dilution method, while MBC was detected by subculturing onto blood agar from the first -three to five tubes from the MIC dilution tubes (showing no turbidity), which were plated on blood agar. All herbal extracts proved to be effective antimicrobials against tested endodontic pathogens. Basil oil had a bacteriostatic effect on all the organisms (P < 0.05). Mint oil showed bacteriostatic activity on Enterococcus (E.) faecalis and Peptostreptococcus (P > 0.05). Tea extract had a bacteriostatic effect (P > 0.05) against all tested microbes except Actinomyces, Lactobacilli, Staphylococcus (S.) aureus, and Fusobacterium (F.) nucleatum. Lemon grass oil had a bactericidal effect against all the organisms and a bacteriostatic effect against Peptostreptococcus (P > 0.05). It can be concluded that basil oil showed a strong bactericidal effect on the test organisms. The MIC for the organisms ranged from 0.2 to 50 μg/ml.

Click chemistry is widely used for the efficient synthesis of 1,4-disubstituted-1,2,3-triazole, a well-known scaffold with widespread biological activity in the pharmaceutical sciences. In recent years, this magic ring has attracted the attention of scientists for its potential in designing and synthesizing new antifungal agents. Despite scientific and medical advances, fungal infections still account for more than 1.5 million deaths globally per year, especially in people with compromised immune function. This increasing trend is definitely related to a raise in the incidence of fungal infections and prevalence of antifungal drug resistance. In this condition, an urgent need for new alternative antifungals is undeniable. By focusing on the main aspects of reaction conditions in click chemistry, this review was conducted to classify antifungal 1,4-disubstituted-1,2,3-triazole hybrids based on their chemical structures and introduce the most effective triazole antifungal derivatives. It was notable that in all reactions studied, Cu(I) catalysts generated in situ by the reduction in Cu(II) salts or used copper(I) salts directly, as well as mixed solvents of t-BuOH/H2O and DMF/H2O had most application in the synthesis of triazole ring. The most effective antifungal activity was also observed in fluconazole analogs containing 1,2,3-triazole moiety and benzo-fused five/six-membered heterocyclic conjugates with a 1,2,3-triazole ring, even with better activity than fluconazole. The findings of structure-activity relationship and molecular docking of antifungal derivatives synthesized with copper-catalyzed azide-alkyne cycloaddition (CuAAC) could offer medicinal chemistry scientists valuable data on designing and synthesizing novel triazole antifungals with more potent biological activities in their future research.

UNASSIGNED: Candida is the primary cause of invasive fungal disease, candidiasis, especially in developed nations. The increasing resistance observed in multiple antibiotics, coupled with the prolonged process of creating new antibiotics from the ground up, emphasizes the urgent requirement for innovative methods and new compounds to combat Candida infections. Employing a treatment strategy that combines antibiotics can improve efficacy, broaden the spectrum of targeted fungal, and reduce the chances of resistance emergence. This approach shows potential in tackling the escalating problem of antibiotic resistance. The objective of this research is to explore the potential synergistic effects of combining 3-hydrazinoquinoxaline-2-thiol and thymoquinone against a variety of Candida isolates. This investigation aims to offer an understanding of the collective antimicrobial action of these compounds.
UNASSIGNED: Broth microdilution was utilized to assess the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and thymoquinone for 22 clinical Candida isolates. Following this, a checkerboard assay was employed to analyze the interaction between 3-hydrazinoquinoxaline-2-thiol and thymoquinone, with a specific focus on the Fractional Inhibitory Concentration Index (FICI).
UNASSIGNED: The MICs of thymoquinone and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical Candida strains, with thymoquinone exhibiting MICs ranging from 64 to 8 µg/mL, and 3-hydrazinoquinoxaline-2-thiol displaying MICs varying from 64 to 8 µg/mL. Notably, the combination of 3-hydrazinoquinoxaline-2-thiol and thymoquinone resulted in a synergistic effect, leading to a significant reduction in MICs, with reductions of up to 64-fold with FICI below 0.5 against tested strains.
UNASSIGNED: The prospect of using 3-hydrazinoquinoxaline-2-thiol in combination with thymoquinone as an effective solution against Candida looks encouraging. Nevertheless, to validate its practical applicability, additional comprehensive testing and experiments are imperative.

The spread of antibiotic resistance is one of the biggest challenges of our time, making it difficult to treat bacterial diseases. Pasteurella multocida is a widespread facultative pathogenic bacterium, which causes a wide range of diseases in both mammals and birds. In the present study, antibiotic susceptibility of 155 P. multocida strains were tested using the broth microdilution method to obtain the minimum inhibitory concentration (MIC) values for 15 antibiotics. The most effective antibiotics against pasteurellosis were ceftiofur, tetracycline, doxycycline, florfenicol and tilmicosin. Of the strains, 12 proved to be multi-drug resistant (MDR). To combat antibiotic resistance, it is important to establish a pre-treatment antibiotic susceptibility profile. A well-chosen antibiotic would not only make the treatment more successful but may also slow down the spread of resistance and the evolution of MDR strains.

Biopreservation strategies such as the use of Mediterranean plant extracts to ensure food safety are promising to deal with the emergence of antimicrobial resistances and the overreliance on food chemical additives. In the last few decades, antimicrobial susceptibility testing (AST) for evaluating the in vitro antibacterial potential of plant extracts against the most relevant foodborne pathogens has been widely reported in the literature. The current meta-analysis aimed to summarise and analyse the extensive evidence available in the literature regarding the in vitro antimicrobial capability of Allium, Ocimum and Thymus spp. extracts against foodborne pathogens. A systematic review was carried out to gather data on AST results of these extracts against Listeria monocytogenes, Staphylococcus aureus, Salmonella spp., Escherichia coli and Bacillus cereus, including inhibition diameters (ID) and minimum inhibitory concentrations (MIC). A total of 742 records were gathered from a raw collection of 2,065 articles. Weighted mixed-effect linear models were adjusted to data to obtain pooled ID, pooled MIC and the relationship between both model estimations and observations. The pooled results revealed B. cereus as the most susceptible bacteria to Allium sativum (pooled ID = 20.64 ± 0.61 mm) by diffusion methods and S. aureus (pooled MIC = 0.146 mg/mL) by dilution methods. Diffusion methods did not yield conclusive results for Ocimum spp. extracts; however, the lowest pooled MIC was obtained for S. aureus (0.263 mg/mL). Among the foodborne pathogens evaluated, B. cereus showed the highest sensitivity to Thymus spp. extracts by both diffusion and dilution methods (pooled ID = 28.90 ± 2.34 mm and MIC = 0.075 mg/mL). The methodology used for plant extraction was found to not significantly affect MIC values (p > 0.05). Overall, the antimicrobial effectiveness of the studied extracts against Gram-positive and Gram-negative bacteria was demonstrated. Finally, the robustness of the meta-regression model was confirmed, also revealing an inversely proportional correlation between the ID and MIC measurements (p < 0.0001). These results provide a robust scientific basis on the factors affecting the in vitro antimicrobial efficacy of extracts from Mediterranean plants. They also provide valuable information for stakeholders involved in their industrial application in food, including producers, regulatory agencies and consumers which demand green-labelled foods.

In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC50 363.51 ± 2.54 µM and E. coli IC50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC50 3.51 ± 0.82 µM and E. coli IC50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.

UNASSIGNED: Several studies have shown that tranexamic acid (TXA), an antifibrinolytic, reduces postoperative infection rates. Recent in vitro research showed that TXA alone and in combination with vancomycin and gentamicin had a synergistic effect against some staphylococcal strains. In the present study, this synergistic effect was validated in samples from patients with staphylococcal periprosthetic infection (PPI) and in an in vivo model.
UNASSIGNED: We tested 19 clinical strains (5 Staphylococcus aureus and 14 coagulase-negative staphylococci [CoNS]) against 10 mg/ml TXA alone and in combination with serial dilutions of vancomycin and gentamicin. The standardized microtiter plate method was used. The minimal inhibitory concentration (MIC) were calculated using standard visualization of well turbidity. We also used an S. aureus (ATCC29213) murine subcranial PPI model to compare the synergistic effect of TXA and gentamicin with that of TXA or gentamicin alone after 4 days of monitoring. The mice were euthanized, and disks were removed for analysis of cfu/ml counts and cell viability rate. Biofilm structure of both in vitro and in vivo samples was also analyzed using scanning electron microscopy (SEM).
UNASSIGNED: When TXA was combined with vancomycin or gentamicin, the MIC decreased in 30% of the strains studied. According to species, the MIC50 for vancomycin and gentamicin alone and in combination with TXA against S. aureus strains was the same. This was also the case for CoNS with vancomycin and its corresponding combination, whereas with gentamicin and TXA, a reduction in MIC50 was observed (2 dilutions). In addition, in the in vivo model, the mean (SD) log cfu/ml and cell viability rate obtained from the implant was lower in the group of mice treated with TXA and gentamicin than in those treated only with TXA or gentamicin. SEM images also corroborated our findings in strains in which the MIC was reduced, as well as the in the mice implants, with the area occupied by biofilm being greater in samples treated only with gentamicin or TXA than in those treated with TXA+gentamicin.
UNASSIGNED: We confirm that combining TXA with vancomycin or gentamicin exerts a synergistic effect. However, this only occurs in selected strains.