The crucial relationship between vancomycin minimum inhibitory concentration and therapeutic efficacy against methicillin-resistant coagulase-negative staphylococci.

The area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio was used as an indicator of the clinical efficacy of vancomycin. However, the target AUC/MIC has not been set for methicillin-resistant coagulase-negative staphylococci (MR-CNS), and the effectiveness of vancomycin in strains with high MIC is unknown. Therefore, we aimed to investigate the relationship between the vancomycin MIC and therapeutic efficacy in patients with MR-CNS bacteremia. The primary outcome was the difference in treatment failure rate when the MR-CNS vancomycin MIC was 1 or 2 µg/mL. The treatment failure rate did not significantly differ between the two groups (MIC 1 vs. MIC 2: 27.0% vs. 31.0%; p = 0.779). As a result of multivariate analysis, AUC/MIC0-24 h ≤230 was extracted as risk factor for treatment failure, suggesting the importance of a sufficient initial loading dose and early blood concentration monitoring to increase AUC/MIC0-24 h for successful treatment.

Antibacterial Activity of Ethanol Extract from Australian Finger Lime.

Australian finger lime (Citrus australasica L.) has become increasingly popular due to its potent antioxidant capacity and health-promoting benefits. This study aimed to determine the chemical composition, antibacterial characteristics, and mechanism of finger lime extract. The finger lime extracts were obtained from the fruit of the Australian finger lime by the ethanol extraction method. The antibacterial activity of the extract was examined by detecting the minimum inhibitory concentration (MIC) for two Gram-positive and four Gram-negative bacterial strains in vitro, as well as by assessing variations in the number of bacteria for Candidatus Liberibacter asiaticus (CLas) in vivo. GC-MS analysis was used to identify the antibacterial compounds of the extract. The antibacterial mechanisms were investigated by assessing cell permeability and membrane integrity, and the bacterial morphology was examined using scanning electron microscopy. The extract demonstrated significant antibacterial activity against Staphylococcus aureus, Bacillus subtilis, and Gram-negative bacterial species, such as Escherichia coli, Agrobacterium tumefaciens, Xanthomonas campestris, Xanthomonas citri, and CLas. Among the six strains evaluated in vitro, B. subtilis showed the highest susceptibility to the antimicrobial effects of finger lime extract. The minimum inhibitory concentration (MIC) of the extract against the tested microorganisms varied between 500 and 1000 µg/mL. In addition, the extract was proven effective in suppressing CLas in vivo, as indicated by the lower CLas titers in the treated leaves compared to the control. A total of 360 compounds, including carbohydrates (31.159%), organic acid (30.909%), alcohols (13.380%), polyphenols (5.660%), esters (3.796%), and alkaloids (0.612%), were identified in the extract. We predicted that the primary bioactive compounds responsible for the antibacterial effects of the extract were quinic acid and other polyphenols, as well as alkaloids. The morphology of the tested microbes was altered and damaged, leading to lysis of the cell wall, cell content leakage, and cell death. Based on the results, ethanol extracts from finger lime may be a fitting substitute for synthetic bactericides in food and plant protection.

Terpenoids from Marine Sources: A Promising Avenue for New Antimicrobial Drugs.

Currently, there is an urgent need for new antibacterial and antifungal agents to combat the growing challenge of antibiotic resistance. As the largest ecosystem on Earth, the marine ecosystem includes a vast array of microorganisms (primarily bacteria and fungi), plants, invertebrates, and vertebrates, making it a rich source of various antimicrobial compounds. Notably, terpenoids, known for their complex structures and diverse bioactivities, are a significant and promising group of compounds in the battle against bacterial and fungal infections. In the past five years, numerous antimicrobial terpenoids have been identified from marine organisms such as bacteria, fungi, algae, corals, sea cucumbers, and sponges. This review article provides a detailed overview of 141 terpenoids with antibacterial and/or antifungal properties derived from marine organisms between 2019 and 2024. Terpenoids, a diverse group of natural organic compounds derived from isoprene units, are systematically categorized based on their carbon skeleton structures. Comprehensive information is provided about their names, structures, biological sources, and the extent of their antibacterial and/or antifungal effectiveness. This review aims to facilitate the rapid identification and development of prospective antimicrobials in the pharmaceutical sector.

Comparative Evaluation of the Antimicrobial Efficacy of Elettaria cardamomum (0.5%) Mouthwash, Camellia sinensis (0.5%) Mouthwash, and 0.12% Chlorhexidine Gluconate Mouthwash against Streptococcus mutans: An In Vitro Study.

Aim: The in vitro study aimed to evaluate and compare the antimicrobial efficacy of Elettaria cardamomum (0.5%) mouthwash, Camellia sinensis (0.5%) mouthwash, and 0.12% chlorhexidine gluconate mouthwash against Streptococcus mutans. Materials and methods: A total of 60 samples of the five mouthwash preparations were prepared to check for their antimicrobial efficacy. The zone of inhibition (ZOI) against S. mutans was measured as a diameter in mm, and the minimum inhibitory concentration (MIC) of mouthwash preparations was measured as µg/mL. All the groups were compared statistically using the Mann-Whitney U test and the Kruskal-Wallis test. Results: The highest ZOI was observed in group V chlorhexidine gluconate [mean: 20.8, standard deviation (SD): 0.58], followed by group III C. sinensis (alcohol-free) (mean: 15.5, SD: 0.67), group IV C. sinensis (alcohol-based) (mean: 14.08, SD: 0.66), and group II E. cardamomum (alcohol-based) (mean: 13.2, SD: 0.45). The least ZOI was observed in group I E. cardamomum (alcohol-free) (mean: 10.7, SD: 0.45). This difference was statistically significant (p < 0.01). The MIC was similar in all the groups (p = 0.13). Conclusion: Chlorhexidine gluconate 0.12% mouthwash showed the best antimicrobial action; however, C. sinensis mouthwash showed potential against S. mutans. E. cardamomum mouthwash exhibited limited antimicrobial activity. How to cite this article: Deolikar S, Jawdekar A, Saraf T, et al. Comparative Evaluation of the Antimicrobial Efficacy of Elettaria cardamomum (0.5%) Mouthwash, Camellia sinensis (0.5%) Mouthwash, and 0.12% Chlorhexidine Gluconate Mouthwash against Streptococcus mutans: An In Vitro Study. Int J Clin Pediatr Dent 2024;17(4):461-466.

Comparative study of the antibacterial effects of wound secretions of different cultivars of Chinese fir.

Background: The bark of Chinese fir (Cunninghamia lanceolata), the largest afforestation tree species in the forest areas of southern China, is susceptible to injuries and bites from small animals. The population of small animals has recently increased owing to improvements in the ecological environment across various forested areas, thus increasing the incidence of injuries in the bark of Chinese fir. Following such injuries, the bark secretes light yellow or milky white secretions, the function of which remains unclear. The present study aimed to reveal the antibacterial effect of exudates of different Chinese fir cultivars on five bacterial species. Methods: The research involved three-year-old plantations of Taxus chinensis var. koraiensis and Yangkou3 and three-year-old container plantations of Taxus chinensis var. pendula, Yang 061, and Yang 020. The antibacterial effects of exudates were analyzed using the filter paper diffusion method. The minimum inhibitory concentration for each secretion and the bacterial inhibition zone were determined. Results: The exudates of the different Chinese fir bark exhibited notable antibacterial effects on Bacillus subtilis, Salmonella paratyphi B, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. However, the extent of these antibacterial effects varied among the different Chinese fir cultivars, as the minimum inhibitory concentrations (MICs) of the exudates against the five bacterial species varied. The mean MIC of Pseudomonas aeruginosa was lower potency, whereas that of Escherichia coli was the lowest. Notably, the antibacterial efficacy of the exudates was mainly influenced by the composition of the secretions rather than the number of secretions, with organic acid compounds and terpenoids potentially contributing to the antibacterial effects against E. coli and Bacillus subtilis, respectively. Conclusion: This study demonstrates the antibacterial effect of wound secretion of different Chinese fir cultivars, highlighting their varying efficacy on different bacterial species. Moreover, the antibacterial ability of the exudates of the strains was mainly determined by the composition of the wound secretions, and there was no noticeable relationship with the number of wound secretions. The results of this study offers a theoretical basis for screen Chinese fir cultivars with high-disease-resistant.

Synergistic potential of essential oil combinations against Microsporum, Trichophyton, and Epidermophyton.

Dermatophyte infections globally account for 20 to 25% of fungal infections. Dermatophytes have begun exhibiting antifungal drug resistance, making it challenging to treat this particular infection. Essential oils could be used as alternative solutions as they have been used for a long period to treat different infections. The research has demonstrated the antifungal efficacy of cinnamon, clove, lemongrass, tea tree, thyme, and garlic essential oils, and the impact of their combinations was assayed against Microsporum canis, Trichophyton tonsurans, T. violaceum, T. verrucosum, and Epidermophyton floccosum. Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) was used to identify the most prevalent M. canis. The accession number of M. canis was obtained as ON007275. All tested essential oils exhibited antidermatophytic action except garlic. A synergistic effect was attained by cinnamon + clove, cinnamon + lemongrass, clove + lemongrass, clove + tea tree, and thyme + tea tree combinations. Concerning antifungal activity, M. canis was the most susceptible dermatophytic species, except in the case of thyme T. violaceum, which was the most susceptible dermatophytic species. The maximum inhibition was recorded in the cases of cinnamon and cinnamon + lemongrass combination against M. canis. The least minimum inhibitory concentrations were attained by cinnamon and clove against M. canis, cinnamon + clove against M. canis and T. violaceum, and cinnamon + lemongrass against M. canis, T. violaceum, T. verrucosum, and E. floccosum. The least minimum fungicidal concentration showed by cinnamon against M. canis, cinnamon + clove against M. canis and T. violaceum, cinnamon + lemongrass against M. canis, T. violaceum, T. verrucosum, and E. floccosum, and clove + lemongrass against M. canis.

Genetic and phenotypic of Pseudomonas aeruginosa sensitive to meropenem antibiotics after exposure to meropenem.

Background and Objectives: Pseudomonas aeruginosa, drug-resistant, causes health infections. Resistance to the preferred therapy meropenem is a serious threat. This study aimed to analyze changes in meropenem minimum inhibitory concentration (MIC), changes in ampC, mexA, and oprD gene expression, and the correlation between MIC and ampC, mexA, and oprD gene expression after meropenem exposure. Materials and Methods: Ten isolates of P. aeruginosa from the Clinical Microbiology Department, Faculty of Medicine, Universitas Indonesia were used. After the bacteria were shown to be sensitive to meropenem phenotypically, intrinsic resistance genes were detected using PCR. After meropenem exposure on Days 5 and 12, sensitivity testing was carried out with the concentration gradient method and RNA was detected using real-time RT-PCR. Results: All P. aeruginosa isolates that were phenotypically sensitive to meropenem had the ampC, mexA, and oprD genes. An increase in MIC, an increase in ampC and mexA gene expression, and a decrease in oprD gene expression were observed after meropenem exposure. There was a very strong and significant correlation (p ≤ 0.05) between MIC and oprD gene expression after Day 12 of meropenem exposure. Conclusion: Although there were no significant differences in MIC and ampC, mexA, and oprD gene expression between Day 5 and Day 12, there was a very strong and significant correlation between MIC and oprD gene expression on Day 12 (p ≤ 0.05). This indicates that decreasing oprD gene expression has the potential to increase meropenem resistance in Pseudomonas aeruginosa.

Antimicrobial Susceptibility of Various MRSA Clinical Isolates and the Impact of Glycopeptide MICs on Clinical and Microbiological Outcomes.

Objective: While vancomycin has remained the mainstay of the treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, there is growing evidence of the clinical impact of increased glycopeptide minimum inhibitory concentrations (MICs) in MRSA isolates. This study aimed to determine the susceptibility of various MRSA isolates to different antibiotics with antistaphylococcal activity and the impact of glycopeptide MICs on clinical and microbiological outcomes. Materials and Methods: This retrospective cohort study, conducted between 2013 and 2017, evaluated the susceptibility of MRSA strains isolated from various clinical samples to antistaphylococcal antibiotics using the gradient strip method. The clinical and laboratory features of patients infected with MRSA isolates with elevated glycopeptide MICs (>1 mg/L) and with isolates that had low glycopeptide MICs (≤1 mg/L) were compared. Results: A total of 104 patients infected with MRSA strains were included in this study. Male sex (odds ratio [OR]=2.48, 95% confidence interval [CI]=1.01-6.10, p=0.048), two or more comorbidities (OR=2.48, 95% CI=1.03-6.50, p=0.044), history of MRSA infection (OR=4.91, 95% CI=1.70-14.28, p=0.003) and a longer hospital stay prior to MRSA infection (OR=2.32, 95% CI=1.05-7.85, p=0.040) were independent risk factors for high glycopeptide MICs. In MRSA infections with a teicoplanin MIC of >0.75mg/L, the microbiological and treatment failures were 46.2% (p=0.044) and 60.6% (p=0.042), respectively. Conclusion: This study showed that the critical MIC value, which suggested treatment failure as well as microbiological failure in the teicoplanin-treated MRSA infections, was >0.75 mg/L rather than >1 mg/L in our study cohort. The identification of high-risk patients;for treatment failures and mortality considering gradient strip method MIC values is crucial for the effective management of MRSA infections.

Different Contributions of embB and ubiA Mutations to Variable Level of Ethambutol Resistance in Mycobacterium tuberculosis Isolates.

Objective: To explore the association between the variant mutations within embB and ubiA, and the degree of ethambutol (EMB) resistance of Mycobacterium tuberculosis (M. tuberculosis) isolates. Methods: A total of 146 M. tuberculosis isolates were used to determine the minimum inhibitory concentrations (MICs) of EMB with a 96-well microplate-based assay. The mutations within embB and ubiA among these isolates were identified with DNA sequencing. Moreover, a multivariate regression model and a computer model were established to assess the effects of mutations on EMB resistance. Results: Our data showed that overall 100 isolates exhibited 28 mutated patterns within the sequenced embB and ubiA. Statistical analysis indicated that embB mutations Met306Val, Met306Ile, Gly406Ala, and Gln497Arg, were strongly associated with EMB resistance. Of these mutations, Met306Val and Gln497Arg were significantly associated with high-level EMB resistance. Almost all multiple mutations occurred in high-level EMB-resistant isolates. Although the mutation within ubiA accompanied with embB mutation presented exclusively in EMB-resistant isolates, four single ubiA mutations (Ala39Glu, Ser173Ala, Trp175Cys, and Val283Leu) leading to protein instability were observed in EMB-susceptible isolates. Conclusion: This study highlighted the complexity of EMB resistance. Some individual mutations and multiple mutations within embB and ubiA contributed to the different levels of EMB resistance.

Trends in the antimicrobial susceptibility among Chinese neonates from 2012 to 2021: a multicenter study.

BACKGROUND: Antibiotic resistance is a serious global public health issue. However, there are few reports on trends in antimicrobial susceptibility in Chinese neonates, and most of the existing evidence has been derived from adult studies. We aimed to assess the trends in antimicrobial susceptibility of common pathogens in full-term neonates with invasive bacterial infections (IBIs) in China. METHODS: This cross-sectional survey study analyzed the antimicrobial susceptibility in Chinese neonates with IBIs from 17 hospitals, spanning from January 2012 to December 2021. Joinpoint regression model was applied to illustrate the trends and calculate the average annual percentage change (AAPC). Using Mantel-Haenszel linear-by-linear association chi-square test, we further compared the antibiotic minimum inhibitory concentrations (MICs) by pathogens between 2019 and 2021 to provide precise estimates of changes. RESULTS: The proportion of Escherichia coli with extended-spectrum-beta-lactamase-negative strains increased from 0.0 to 88.5% (AAPC = 62.4%, 95% confidence interval (CI): 44.3%, 82.9%), with two breakpoints in 2014 and 2018 (p-trend < 0.001). The susceptibility of group B Streptococcus (GBS) to erythromycin and clindamycin increased by 66.7% and 42.8%, respectively (AAPC = 55.2%, 95% CI: 23.2%, 95.5%, p-trend = 0.002; AAPC = 54.8%, 95% CI: 9.6%, 118.6%, p-trend < 0.001), as did Staphylococcus aureus to penicillin (AAPC = 56.2%; 95% CI: 34.8%, 81.0%, p-trend < 0.001). However, the susceptibility of Enterococcus spp. to ampicillin declined from 100.0 to 25.0% (AAPC = - 11.7%, 95% CI: - 15.2%, - 8.1%, p-trend < 0.001), and no significant improvement was observed in the antibiotic susceptibility of Escherichia coli to ampicillin, gentamicin, and cephalosporin. Additionally, the proportion of GBS/Staphylococcus aureus with relatively low MIC values for relevant antibiotics also increased in 2021 compared to 2019. CONCLUSIONS: Antimicrobial susceptibility of the most prevalent pathogens in full-term neonates seemed to have improved or remained stable over the last decade in China, implying the effectiveness of policies and practice of antibiotic stewardship had gradually emerged.

In Vitro Antibacterial Activities of Fosfomycin against Escherichia coli Isolates from Canine Urinary Tract Infection.

Fosfomycin is a bactericidal drug recommended as an alternative treatment for canine bacterial cystitis, particularly in cases involving multidrug-resistant (MDR) infections when no other options are available. In this study, minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of fosfomycin were determined against 79 clinical E. coli isolates using the agar dilution method. The susceptibility rate of E. coli to fosfomycin was 86.06%, with MIC50 and MIC90 values of 4 mg/L and 96 mg/L, respectively. MPC50 and MPC90 values were 64 mg/L and 192 mg/L. Using pharmacokinetic (PK) data from dogs given a single 80 mg/kg oral dose of fosfomycin, the area under the curve per MIC50 (AUC0-24/MIC50) was 85.79 with time above MIC50 (T > MIC50) exceeding 50%. In urine, the AUC0-24/MIC50 was 10,694.78, and the AUC0-24/MPC90 was 222.81, with T > MPC90 extending beyond 24 h. Therefore, fosfomycin exhibited significant antibacterial activity against canine uropathogenic E. coli, including MDR strains, at concentrations below the susceptible MIC breakpoint. However, the high MPC values, especially the MPC90, indicate the critical importance of performing susceptibility testing for fosfomycin and maintaining ongoing resistance monitoring.

Antimicrobial Activity of Positively Charged Oligopeptides with Theoretical High α-Helix Content against Cutibacterium acnes.

Cutibacterium acnes is abundant and commonly exists as a superficial bacteria on human skin. Recently, the resistance of C. acnes to antimicrobial agents has become a serious concern, necessitating the development of alternative pharmaceutical products with antimicrobial activity against C. acnes. To address this need, we evaluated the antimicrobial activity of CKR-13-a mutant oligopeptide of FK-13 with increased net charge and theoretical α-helical content-against C. acnes in modified Gifu Anaerobic Medium broth by determining the minimum inhibitory concentration (MIC). CKR-13 exerted greater antimicrobial activity against C. acnes than FK-13 in the broth at pH 7.0. The antimicrobial activity of CKR-13 with RXM against C. albicans was pH-dependent. The ionization of CKR-13 and pH-dependent growth delay of C. albicans was suggested to be associated with the increase in CKR-13 antimicrobial activity.

Antifungal Activity of Morinda citrifolia Methanolic Extract against Candida albicans: An In Vitro Study.

Aim: Natural medicine used as an alternative and/or complementary treatment to counteract diseases is of great importance in public health. Therefore, the purpose of the present study was to assess the in vitro antifungal activity of Morinda citrifolia methanolic extract of peel, pulp, and seed against Candida albicans. Materials and Methods: The present study was experimental in vitro and cross-sectional. Eight replicates were prepared in Sabouraud dextrose agar with five wells each, where 0.12% chlorhexidine, distilled water, and methanolic extract of seed, peel, and pulp of Morinda citrifolia fruit were placed at concentrations of 10,690, 8,270, and 6,430 mg/mL, respectively, to evaluate sensitivity according to Duraffourd's scale. In addition, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined by dilution and agar seeding method. Statistical analysis was performed by analysis of variance (ANOVA) and Tukey's post hoc test, considering a significance level of P < 0.05. Results: The inhibition halos of Morinda citrifolia methanolic extract of seed, peel, and pulp against Candida albicans measured on average 15.94, 11.94, and 11.56 mm, respectively. The MIC of seed, peel, and pulp extract were 1366.25, 2067.5, and 1607.5 mg/mL respectively, whereas the MFC for seed, peel, and pulp extract were 2672.50, 2067.5, and 3215 mg/mL, respectively. Moreover, seed extract presented significantly higher antifungal activity than peel and pulp (P < 0.001). Conclusions: Morinda citrifolia methanolic extract of peel, pulp, and seed showed fungistatic and fungicidal effect against Candida albicans, being this very sensitive to seed extract with a MIC of 1366.25 mg/mL and a MFC of 2672.5 mg/mL, which allows recommending the development of effective pharmacological formulations for the control of candidiasis.

Group A streptococcus isolated in Guyana with reduced susceptibility to ß-lactam antibiotics.

Introduction. Streptococcus pyogenes [group A streptococci (GAS)] is the causative agent of pharyngitis and various other syndromes involving cellulitis, streptococcal toxic shock syndrome (STSS), and necrotising fasciitis. Although the prevalence of GAS infections globally remains high, necessitating the widespread use of ß-lactam antibiotics, GAS have remained largely susceptible to these agents. However, there have been several reports of GAS with reduced susceptibility harbouring mutations in genes for penicillin-binding proteins (PBPs). The objectives of this study were to examine the in vitro ß-lactam susceptibility patterns of group A streptococci, determine the prevalence of drug resistance, and ascertain whether such resistance could be attributed to mutations in specific PBP genes. Methods. In this study, we sought to use Sanger sequencing to identify mutations in PBP genes of Streptococcus pyogenes isolated from patients that required inpatient and outpatient care that could confer reduced PBP affinity for penicillin and/or cephalosporin antibiotics. All isolates were screened for susceptibility to penicillin, amoxicillin, and cefazolin using E-test strips. Results. While there were no documented cases of reduced susceptibility to penicillin or amoxicillin, 13 isolates had reduced susceptibility to cefazolin. Examination of pbp1a by Sanger sequencing revealed several isolates with single amino acid substitutions, which could potentially reduce the affinity of PBP 1A for cefazolin and possibly other first-generation cephalosporins. Conclusion. Penicillin and penicillin-derived antibiotics remain effective treatment options for GAS infections, but active surveillance is needed to monitor for changes to susceptibility patterns against these and other antibiotics and understand the genetic mechanisms contributing to them.

Implications of silver nanoparticles for H. pylori infection: modulation of CagA function and signaling.

Background: Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis. Methods: In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated. Results: AGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function. Conclusion: Our study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.

High-Throughput Monitoring of Pathogenic Fungal Growth Using Whole Slide Imaging for Rapid Antifungal Susceptibility Assessment.

Invasive fungal infections are a major health threat with high morbidity and mortality, highlighting the urgent need for rapid diagnostic tools to detect antifungal resistance. Traditional culture-based antifungal susceptibility testing (AFST) methods often fall short due to their lengthy process. In our previous research, we developed a whole-slide imaging (WSI) technique for the high-throughput assessment of bacterial antibiotic resistance. Building on this foundation, this study expands the application of WSI by adapting it for rapid AFST through high-throughput monitoring of the growth of hundreds of individual fungi. Due to the distinct "budding" growth patterns of fungi, we developed a unique approach that utilizes specific cell number change to determine fungi replication, instead of cell area change used for bacteria in our previous study, to accurately determine the growth rates of individual fungal cells. This method not only accelerates the determination of antifungal resistance by directly observing individual fungal cell growth, but also yields accurate results. Employing Candida albicans as a representative model organism, reliable minimum inhibitory concentration (MIC) of fluconazole inhibiting 100% cells of Candida albicans (denoted as MIC100) was obtained within 3h using the developed method, while the modified broth dilution method required 72h for the similar reliable result. In addition, our approach was effectively utilized to test blood culture samples directly, eliminating the need to separate the fungi from whole blood samples spiked with Candida albicans. These features indicate the developed method holds great potential serving as a general tool in rapid antifungal susceptibility testing and MIC determination.

Pyrimidine-based sulfonamides and acetamides as potent antimicrobial Agents: Synthesis, Computational Studies, and biological assessment.

A series of novel sulfonamide and acetamide derivatives of pyrimidine were synthesized and their antimicrobial activities were assessed. Based on the Microbroth dilution method, the minimum inhibitory concentration (MIC) of the synthesized compounds demonstrated moderate to good levels of antifungal and antibacterial activity. Structure-activity relationship analysis suggested that the presence of electron-withdrawing groups, such as halogens, nitrile, and nitro groups, on the pyrimidine ring contributed to the enhanced antimicrobial potency, while electron-donating substituents led to a decrease in activity. Computational studies, including density functional theory (DFT), frontier molecular orbitals (FMO), and molecular electrostatic potential (MEP) analysis, provided insights into the electronic properties and charge distribution of the compounds. Drug-likeness evaluation using ADME/Tox analysis indicated that the synthesized compounds possess favorable physicochemical properties and could be potential drug candidates. Molecular docking against the Mycobacterium TB protein tyrosine phosphatase B (MtbPtpB) revealed that the synthesized compounds exhibited strong binding affinities (-46 kcal/mol to - 61 kcal/mol) and formed stable protein-ligand complexes through hydrogen bonding and π-π stacking interactions with key residues in the active site. The observed interactions from the docking simulations were consistent with the predicted interaction sites identified in the FMO and MEP analyses. These findings suggest that the synthesized pyrimidine derivatives could serve as promising antimicrobial agents and warrant further investigation for drug development.

Genetic diversity and antifungal susceptibilities of environmental Cryptococcus neoformans and Cryptococcus gattii species complexes.

Cryptococcosis is an opportunistic systemic mycosis caused by Cryptococcus neoformans and C. gattii species complexes and is of increasing global importance. Maintaining continued surveillance of the antifungal susceptibility of environmental C. neoformans and C. gattii isolates is desirable for better managing cryptococcosis by identifying resistant isolates and revealing the emergence of intrinsically resistant species. Relevant research data from Egypt are scarce. Thus, this study aimed to report the genetic diversity of C. neoformans and C. gattii species complexes originating from different environmental sources in Egypt, antifungal susceptibility profiles, antifungal combinations, and correlations of susceptibility with genotypes. A total of 400 environmental samples were collected, 220 from birds and 180 from trees. Cryptococcus spp. were found in 58 (14.5%) of the samples, 44 (75.9%) of the isolates were recovered from birds and 14 (24.1%) from trees. These isolates were genotyped using M13 polymerase chain reaction-fingerprinting and URA5 gene restriction fragment length polymorphism analysis. Of the 31 C. neoformans isolates, 24 (77.4%), 6 (19.4%) and one (4.4%) belonged to VNI, VNII, and VNIII genotypes, respectively. The 27 C. gattii isolates belonged to VGI (70.4%), VGII (18.5%), and VGIII (11.1%) genotypes. Non-wild type C. neoformans and C. gattii isolates that may have acquired resistance to azoles, amphotericin B (AMB), and terbinafine (TRB) were observed. C. gattii VGIII was less susceptible to fluconazole (FCZ) and itraconazole (ITZ) than VGI and VGII. C. neoformans isolates showed higher minimum inhibitory concentrations (MICs) to FCZ, ITZ, and voriconazole (VRZ) than those of C. gattii VGI and VGII. Significant (P < 0.001) correlations were found between the MICs of VRZ and ITZ (r = 0.64) in both C. neoformans and C. gattii isolates, FCZ and TRB in C. neoformans isolates, and FCZ and TRB (r = 0.52) in C. gattii isolates.There is no significant differences in the MICs of TRB in combination with FCZ (P = 0.064) or in combination with AMB (P = 0.543) and that of TRB alone against C. gattii genotypes. By calculating the fractional inhibitory concentration (FIC) index, the combination of FCZ + AMB was synergistic against all tested genotypes. These findings expand our knowledge of ecological niches, genetic diversity, and resistance traits of C. neoformans and C. gattii genotypes in Egypt. Further investigations into how they are related to clinical isolates in the region are warranted.

An In Vitro Study to Evaluate the Antimicrobial Activity of a Zinc Citrate, Sodium Fluoride, Alum and Xylitol-Based Toothpaste Formulation.

INTRODUCTION: Periodontitis is a prevalent condition significantly affecting oral health. Comorbid conditions, such as diabetes, can heighten the severity of periodontal disease and overall oral health. Therefore, to enhance oral health and manage comorbid conditions, comprehensive periodontal care is essential. This approach could involve using toothpaste containing antimicrobial ingredients in routine oral care. This paper presents the results of an in vitro study analysing the antimicrobial properties of the test formulation containing zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste (Stolin-R). These ingredients work together to help in providing comprehensive oral care by controlling growth of bacteria majorly responsible for periodontal disease and thus maintaining optimal oral hygiene. AIM: To determine the antimicrobial properties of zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste formulation against key periodontal pathogens through in vitro analyses. MATERIALS AND METHODS: The antimicrobial efficacy of test formulation is evaluated through minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-dependent antibacterial assessment against key periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, Prevotella intermedia, Streptococcus mutans, and Bacteroides fragilis. RESULTS: The test formulation demonstrated potent antimicrobial effectiveness against Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Streptococcus mutans, and Tannerella forsythia, by exhibiting low MIC and MBC. Additionally, significant bacterial reduction, exceeding 99.99%, was observed within five minutes, emphasising its potential as an effective adjunct in combating periodontal infection. CONCLUSION: Zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste formulation demonstrates significant antimicrobial activity against key periodontal pathogens, suggesting its potential as an effective agent for maintaining oral health and combating gingival infection.

Antifungal Susceptibility and Genotypic Analysis of cyp51A Mutations in Aspergillus fumigatus Isolates in Malaysia.

Purpose: Azole resistance in Aspergillus fumigatus poses a significant challenge in the management of invasive aspergillosis. This study aimed to investigate the antifungal susceptibility and cyp51A mutation profiles of A. fumigatus isolates in Malaysia. Patients and Methods: Sixty clinical A. fumigatus isolates were collected and subjected to antifungal susceptibility testing (AFST) and molecular analysis. The antifungal susceptibility testing was performed according to CLSI M38 guideline. The geometric mean (GM) minimum inhibitory concentration (MIC), MIC50/MIC90 for voriconazole, itraconazole, posaconazole, amphotericin B, and isavuconazole against A. fumigatus in non-invasive cases and invasive cases were calculated. In addition, the presence of cyp51A mutations was also identified. Results: The present study revealed an overall resistance rate of 6.7% among the isolates. In non-invasive cases, isavuconazole and posaconazole demonstrated the lowest GM MIC of 0.08 µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.15µg/mL, 0.16µg/mL and 0.90µg/mL, respectively. Similarly, in invasive cases, isavuconazole and posaconazole exhibited the lowest GM MIC of 0.09µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.14µg/mL, 0.17µg/mL and 0.80µg/mL, respectively. Genotypic analysis revealed various cyp51A mutations, including F46Y, M172V, N248K, R34L, V244A, V244S, and E427K. However, not all mutations corresponded to antifungal resistance. Conclusion: The majority of clinical Aspergillus fumigatus isolates demonstrated susceptibility to the antifungal agents tested, with isavuconazole and posaconazole demonstrating the lowest MIC values. However, cyp51A mutations were discovered without a consistent correlation to antifungal resistance, emphasising the need for additional research.