Transferosomes stabilized hydrogel incorporated rhodomyrtone-rich extract from Rhodomyrtus tomentosa leaf fortified with phosphatidylcholine for the management of skin and soft-tissue infections.

Rhodomyrtus tomentosa leaf (RT)-incorporated transferosomes were developed with lecithin and cholesterol blends with edge activators at different ratios. RT-transferosomes were characterized and employed in transferosomal gel formulations for the management of skin and soft-tissue infections. The optimized formulation entrapped up to 81.90 ± 0.31% of RT with spherical vesicles (405.3 ± 2.0 nm), polydispersity index value of 0.16 ± 0.08, and zeta potential of - 61.62 ± 0.86 mV. Total phenolic and flavonoid contents of RT-transferosomes were 15.65 ± 0.04 µg GAE/g extract and 43.13 ± 0.91 µg QE/g extract, respectively. RT-transferosomes demonstrated minimum inhibitory and minimum bactericidal concentrations at 8-256 and 64-1024 µg/mL, respectively. Free radical scavenging assay showed RT-transferosomes with high scavenging activity against DPPH and ABTS radicals. Moreover, RT-transferosomes demonstrated moderate activity against mushroom tyrosinase, with IC50 values of 245.32 ± 1.32 µg/mL. The biocompatibility results against L929 fibroblast and Vero cells demonstrated IC50 at 7.05 ± 0.17 and 4.73 ± 0.13 µg/mL, respectively. In addition, nitric oxide production significantly decreased by 6.78-88.25% following the treatment with 31.2-500 ng/mL RT-transferosomes (p < 0.001). Furthermore, the freeze-thaw stability study displayed no significant change in stability in the sedimentation and pH of gel fortified with RT-transferosomes. The results suggested that RT-transferosome formulation can be effectively employed as natural biomedicines for scar prevention and the management of skin soft-tissue infections.

Advanced biomaterial agent from chitosan/poloxamer 407-based thermosensitive hydrogen containing biosynthesized silver nanoparticles using Eucalyptus camaldulensis leaf extract.

CONTEXT: The emergence of multidrug-resistant (MDR) pathogens poses a significant challenge for global public health systems, increasing hospital morbidity and mortality and prolonged hospitalization. OBJECTIVE: We evaluated the antimicrobial activity of a thermosensitive hydrogel containing bio-synthesized silver nanoparticles (bio-AgNPs) based on chitosan/poloxamer 407 using a leaf extract of Eucalyptus calmadulensis. RESULTS: The thermosensitive hydrogel was prepared by a cold method after mixing the ingredients and left at 4°C overnight to ensure the complete solubilization of poloxamer 407. The stability of the hydrogel formulation was evaluated at room temperature for 3 months, and the absorption peak (420 nm) of the NPs remained unchanged. The hydrogel formulation demonstrated rapid gelation under physiological conditions, excellent water retention (85%), and broad-spectrum antimicrobial activity against MDR clinical isolates and ATCC strains. In this regard, minimum inhibitory concentration and minimum microbial concentration values of the bio-AgNPs ranged from 2-8 µg/mL to 8-128 µg/mL, respectively. Formulation at concentrations <64 µg/mL showed no cytotoxic effect on human-derived macrophages (THP-1 cells) with no induction of inflammation. CONCLUSIONS: The formulated hydrogel could be used in biomedical applications as it possesses a broad antimicrobial spectrum and anti-inflammatory properties without toxic effects on human cells.

In vitro and in vivo comparative analysis of antibacterial activity of green-synthesized silver nanoparticles.

This study aims to compare antibacterial effects of green-synthesized silver nanoparticles (AgNPs) with silver nitrate (AgNO3 ). AgNPs were successfully synthesized using Eucalyptus camaldulensis leaf extract as a reducing and stabilizing agent. Minimum inhibitory concentrations (MIC) of AgNPs and AgNO3 against Staphylococcus aureus and Pseudomonas aeruginosa ranged between 4.8 and 6.75 µg mL-1 . Growth curves demonstrated that inhibition of P. aeruginosa occurred right after AgNPs were added and throughout the period of the study (72 h). Antibacterial effects of both AgNPs and AgNO3 could be abrogated by cysteine and 2-mercaptoethanol, thiol-containing compounds. Galleria mellonella model revealed relatively low toxic effects of both AgNPs and AgNO3 . At 20MIC of AgNPs (≈137.8 mg kg-1 ), more than 80% survival of G. mellonella was observed. Unexpectedly, silver-containing agents could not rescue larvae after S. aureus infection. Further ex vivo experiments in the presence of coelomic larval fluid demonstrated the reduction of antibacterial activity of both AgNPs and AgNO3 . It was speculated that anionic molecules present in the coelomic fluid might neutralize the action of Ag ions. Binding of AgNPs or AgNO3 to albumin, a major protein in human blood which transport several endogenous compounds was not detected, indicating that the silver-containing agents could be applied as an antimicrobial agent.

Camaldulensals A-C, the First Meroterpenoids Possessing Two Spatially Separated Formyl Phloroglucinols Conjugated to a Terpene Core from the Leaves of Eucalyptus camaldulensis Dehnh.

Three new bis-formyl phloroglucinol-meroterpenoids (1-3), three new euglobal type formyl phloroglucinol-meroterpenoids (4-6), and one new dimeric formyl phloroglucinol (7) were isolated from the leaves of Eucalyptus camaldulensis. Camaldulensal A (1) is the first bis-isovaleryl-formyl-phloroglucinol-sesquiterpenoid. It features a novel 6/6/10/3/6/6 fused ring system and contains six stereogenic centers. Camaldulensals B (2) and C (3) are the first bis-isovaleryl-formyl-phloroglucinols, each conjugated to a monoterpene. Formyl phloroglucinol compounds (FPCs) containing two spatially separated formyl phloroglucinols conjugated to a terpene core such as 1-3 have not been reported previously. The structures of these compounds were elucidated by spectroscopic methods and computational analysis. Camaldulensals B (2) and C (3) exhibited significant antibacterial activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Structure activity relationships are discussed in relation to previously reported antibacterial activities of other molecules from the FPC structure class.

Rifampicin Enhanced Carbapenem Activity with Improved Antibacterial Effects and Eradicates Established Acinetobacter baumannii Biofilms.

Biofilm-mediated infections are critical to public health and a leading cause of resistance among pathogens, amounting to a prolonged hospital stay and increased mortality rate in the intensive care unit. In this study, the antibacterial and antibiofilm activities of rifampicin or carbapenem monotherapies were compared with rifampicin and carbapenem combination therapies against rifampicin-resistant and carbapenem-resistant Acinetobacter baumannii isolates. Among 29 CRAB isolates, 24/29 (83%) were resistant to rifampicin, with MIC values between 2-256 µg/mL. Checkerboard assays disclosed that combination therapies at FICIs between 1/8 and 1/4 improved the activity of carbapenems at subinhibitory concentrations. Time-kill kinetics indicated a 2- to 4-log reduction at 1/2 MIC rifampicin + 1/4 MIC carbapenem and 1/4 MIC rifampicin + 1/4 MIC carbapenem against the isolates, with the MIC values ranging from 2-8 µg/mL. The MTT assay revealed a dose-dependent decrease of the cell viability of established bacterial biofilm at 4 MIC rifampicin + 2 MIC carbapenems, with a percentage reduction of 44-75%, compared with monotherapies at 16 MIC. Scanning electron microscopy further confirmed bacterial cell membrane disruption, suggesting a synergism between carbapenem and rifampicin against a representative isolate. The findings demonstrated that the combination of rifampicin with carbapenems could improve antibacterial activities and eradicate established Acinetobacter baumannii biofilm.

Biogenic nanosilver-fabricated endotracheal tube to prevent microbial colonization in a veterinary hospital.

COVID-19 patients have often required prolonged endotracheal intubation, increasing the risk of developing ventilator-associated pneumonia (VAP). A preventive strategy is proposed based on an endotracheal tube (ETT) modified by the in situ deposition of eucalyptus-mediated synthesized silver nanoparticles (AgNPs). The surfaces of the modified ETT were embedded with AgNPs of approximately 28 nm and presented a nanoscale roughness. Energy dispersive X-ray spectroscopy confirmed the presence of silver on and inside the coated ETT, which exhibited excellent antimicrobial activity against Gram-positive and Gram-negative bacteria, and fungi, including multidrug-resistant clinical isolates. Inhibition of planktonic growth and microbial adhesion ranged from 99 to 99.999% without cytotoxic effects on mammalian cells. Kinetic studies showed that microbial adhesion to the coated surface was inhibited within 2 h. Cell viability in biofilms supplemented with human tracheal mucus was reduced by up to 95%. In a porcine VAP model, the AgNPs-coated ETT prevented adhesion of Pseudomonas aeruginosa and completely inhibited bacterial invasion of lung tissue. The potential antimicrobial efficacy and safety of the coated ETT were established in a randomized control trial involving 47 veterinary patients. The microbial burden was significantly lower on the surface of the AgNPs-coated ETT than on the uncoated ETT (p < 0.05). KEY POINTS: • Endotracheal tube surfaces were modified by coating with green-synthesized AgNPs • P. aeruginosa burden of endotracheal tube and lung was reduced in a porcine model • Effective antimicrobial activity and safety was demonstrated in a clinical trial.

Eucalyptus-Mediated Synthesized Silver Nanoparticles-Coated Urinary Catheter Inhibits Microbial Migration and Biofilm Formation.

Catheter-associated urinary tract infections (CAUTIs) are significant complications among catheterized patients, resulting in increased morbidity, mortality rates, and healthcare costs. Foley urinary catheters coated with synthesized silver nanoparticles (AgNPs) using Eucalyptus camaldulensis leaf extract were developed using a green chemistry principle. In situ-deposited AgNPs with particle size ranging between 20 and 120 nm on the catheter surface were illustrated by scanning electron microscopy. Atomic force microscopy revealed the changes in surface roughness after coating with nanoparticles. The coated catheter could significantly inhibit microbial adhesion and biofilm formation performed in pooled human urine-supplemented media to mimic a microenvironment during infections (p 0.05). AgNPs-coated catheter exhibited broad-spectrum antimicrobial activity against important pathogens, causing CAUTIs with no cytotoxic effects on HeLa cells. A reduction in microbial viability in biofilms was observed under confocal laser scanning microscopy. A catheter bridge model demonstrated complete prevention of Proteus mirabilis migration by the coated catheter. Significant inhibition of ascending motility of Escherichia coli and P. mirabilis along the AgNPs-coated catheter was demonstrated in an in vitro bladder model (p 0.05). The results suggested that the AgNPs-coated urinary catheter could be applied as an alternative strategy to minimize the risk of CAUTIs by preventing bacterial colonization and biofilm formation.

A new alkaloid and a new benzaldehyde derivative from the twig of Zanthoxylum rhetsa (Roxb.) DC.

A new alkaloid, 2-acetyl-4-methoxyfuro[2,3-b]quinoline (1), and a new benzaldehyde derivative, (2'S)-4-(2'-hydroxy-3'-methyl-3'-butenoxy)benzaldehyde (2), were isolated from the twig of Zanthoxylum rhetsa (Roxb.) DC. along with twenty-six known compounds (3-28). Their structures were determined by spectroscopic analysis (1D and 2D NMR spectroscopy and HRMS analysis) and comparison with data reported in the literature. Thirteen of the known compounds were evaluated for their cytotoxic activities against human cancer cell lines that included MDA-MB-231, SW1353, A549, and HCT116. (±)-8-Acetonyldihydronitidine (15) showed moderate cytotoxicity toward the SW1353 cancer cell line with an IC50 value of 18.90±0.39 µg/mL, and exhibited weak cytotoxic activity against MDA-MB-231, A549 and HCT116 cell lines with IC50 values of 49.86-71.32 µg/mL.

New acylphloroglucinols from a crude acetone extract of Eucalyptus camaldulensis Dehnh. leaf.

Acylphloroglucinols are well-known Eucalyptus secondary metabolites which exhibit a variety of structures and bioactivities. The investigation of a crude acetone extract of Eucalyptus camaldulensis leaves led to the isolation of two new acylphloroglucinols, eucalypcamals O and P (1 and 2) together with seven phloroglucinols (3-9), and a benzene derivative (10). Their chemical structures were elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and mass spectroscopy. The absolute configurations of compounds 1 and 2 were established by comparison of experimental and calculated electronic circular dichroism (ECD) data. In the putative biosynthetic pathway, eucalypcamals O and P should be derived from hetero-Diels-Alder reaction between grandinol and trans-isoeugenol.

Poly (vinyl alcohol) copolymerized with xanthan gum/hypromellose/sodium carboxymethyl cellulose dermal dressings functionalized with biogenic nanostructured materials for antibacterial and wound healing application.

Effective treatment of infected wounds requires a comprehensive wound dressing with a combination of antibacterial, antioxidative, and anti-inflammatory effects. Biodegradable wound dressings incorporating nanostructured material were developed using polyvinyl alcohol with xanthan gum, hypromellose, or sodium carboxymethyl cellulose and extensively evaluated for antibacterial and wound healing efficacy. Synthesized silver nanoparticles and wound dressings displayed λmax at 420 nm with zeta potential ≈ - 35 mV. Significant growth inhibition with >99 % reduction in CFU/ml (p < 0.05) against important wound pathogens including Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were observed. Within 1 h of treatment, hypromellose nanocomposite demonstrated excellent bactericidal effects with a 99.9 % of reduction in growth. In addition, wound dressings demonstrated inhibitory activities against free radical scavengers. Wound dressings demonstrated a significant reduction in the inflammatory response in RAW 264.7 macrophages (p < 0.001). Ex-vivo diffusion demonstrated zero-order release and steady-state flux between 0.1571-0.2295 µg/ml/cm2h with 0.124-0.144 permeability coefficient after 10 h. Usage in animals further confirmed that the hypromellose nanocomposite accelerated the wound healing process with biocompatibility. The results suggested that hybrid biodegradable dressings can be effectively applied to treat infected wounds and attenuate inflammatory responses.

Isolation and Characterisation of Bacteriophage Selective for Key Acinetobacter baumannii Capsule Chemotypes.

Nineteen bacteriophages against five main capsular types of multidrug-resistant Acinetobacter baumannii were isolated from tertiary care hospital sewage. Eight representative phages from each capsular type were characterized and tested for their biological properties. The biological features revealed that phages T1245, T444, and T515 had a large burst size of more than 420 pfu/mL, together with a short latent period lasting less than 6 min, and were readily adsorbed to a bacterial host within 10 min. Moreover, these phages demonstrated host specificity and stability over a broad range of temperatures (-20 to 60 °C) and pH (5.0-9.0). A whole-genome analysis of six lytic and two temperate phages revealed high genomic similarity with double-stranded DNA between 40 and 50 kb and G + C content of 38-39%. The protein compositions disclosed the absence of toxin-coding genes. The phylogenic results, together with morphological micrographs, confirmed that three selected phages (T1245, T444, and T515) belong to the Podoviridae family within the order Caudovirales. The biological data and bioinformatics analysis indicated that these novel A. baumannii phages possess important enzymes, including depolymerase and endolysin, which could be further developed as promising alternative antibacterial agents to control A. baumannii infections.

Phloroglucinol-meroterpenoids from the leaves of Eucalyptus camaldulensis Dehnh.

Fourteen undescribed phloroglucinol-meroterpenoids, namely eucalypcamals A-N, were isolated from a CH2Cl2 extract of the leaves of Eucalyptus camaldulensis Dehnh. In addition, from the same extract, twelve known phloroglucinols, three known flavonoids, and four known phenolic compounds were also isolated. The structures of the undescribed compounds were analyzed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and high resolution electrospray ionization mass spectrometry (HRESIMS). The assignments of the absolute configurations were performed by comparing the experimental electronic circular dichroism (ECD) data with the calculated values. Eucalyprobusal E was found to be cytotoxic against HCT116, Jurkat, and MDA-MB-231 cell lines with IC50 values of 17.6, 9.44, and 17.9 µM, respectively. Eucalrobusone F exhibited antibacterial activity against methicillin-resistant S. aureus (MRSA) and S. aureus with minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values of 4/4 µg/mL while euglobal Ia1 showed antifungal activity with MIC/MFC values of 16/16 µg/mL.

Synergistic Antibacterial Effects of Meropenem in Combination with Aminoglycosides against Carbapenem-Resistant Escherichia coli Harboring blaNDM-1 and blaNDM-5.

Infections due to carbapenem-resistant Escherichia coli (CREC) are problematic due to limitation in treatment options. Combination therapies of existing antimicrobial agents have become a reliable strategy to control these infections. In this study, the synergistic effects of meropenem in combination with aminoglycosides were assessed by checkerboard and time-kill assays. Of the 35 isolates, 19 isolates (54.3%) were resistant to carbapenems (imipenem and meropenem) with the MIC ranges from 16 to 128 µg/mL. These isolates were resistant to almost all antibiotic classes. Molecular characteristics revealed co-harboring of carbapenemase (blaNDM-1, blaNDM-5 and blaOXA-48) and extended-spectrum ß-lactamases (ESBL) genes (blaCTX-M, blaSHV and blaTEM). The checkerboard assay displayed synergistic effects of meropenem and several aminoglycosides against most CREC isolates. Time-kill assays further demonstrated strong synergistic effects of meropenem in combination with either amikacin, gentamicin, kanamycin, streptomycin, and tobramycin. The results suggested that meropenem in combination with aminoglycoside therapy might be an efficient optional treatment for infections cause by CREC.

Characterisation of Bacteriophage-Encoded Depolymerases Selective for Key Klebsiella pneumoniae Capsular Exopolysaccharides.

Capsular polysaccharides enable clinically important clones of Klebsiella pneumoniae to cause severe systemic infections in susceptible hosts. Phage-encoded capsule depolymerases have the potential to provide an alternative treatment paradigm in patients when multiple drug resistance has eroded the efficacy of conventional antibiotic chemotherapy. An investigation of 164 K. pneumoniae from intensive care patients in Thailand revealed a large number of distinct K types in low abundance but four (K2, K51, K1, K10) with a frequency of at least 5%. To identify depolymerases with the capacity to degrade capsules associated with these common K-types, 62 lytic phage were isolated from Thai hospital sewage water using K1, K2 and K51 isolates as hosts; phage plaques, without exception, displayed halos indicative of the presence of capsule-degrading enzymes. Phage genomes ranged in size from 41-348 kb with between 50 and 535 predicted coding sequences (CDSs). Using a custom phage protein database we were successful in applying annotation to 30 - 70% (mean = 58%) of these CDSs. The largest genomes, of so-called jumbo phage, carried multiple tRNAs as well as CRISPR repeat and spacer sequences. One of the smaller phage genomes was found to contain a putative Cas type 1E gene, indicating a history of host DNA acquisition in these obligate lytic phage. Whole-genome sequencing (WGS) indicated that some phage displayed an extended host range due to the presence of multiple depolymerase genes; in total, 42 candidate depolymerase genes were identified with up to eight in a single genome. Seven distinct virions were selected for further investigation on the basis of host range, phage morphology and WGS. Candidate genes for K1, K2 and K51 depolymerases were expressed and purified as his6-tagged soluble protein and enzymatic activity demonstrated against K. pneumoniae capsular polysaccharides by gel electrophoresis and Anton-Paar rolling ball viscometry. Depolymerases completely removed the capsule in K-type-specific fashion from K. pneumoniae cells. We conclude that broad-host range phage carry multiple enzymes, each with the capacity to degrade a single K-type, and any future use of these enzymes as therapeutic agents will require enzyme cocktails for utility against a range of K. pneumoniae infections.

A Bibliometric Meta-Analysis of Colistin Resistance in Klebsiella pneumoniae.

Colistin is a last resort antibiotic medication for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae. In recent years, various mechanisms have been reported to mediate colistin resistance in K. pneumoniae. This study reports a bibliometric analysis of published articles retrieved from the Scopus database relating to colistin resistance in K. pneumoniae. The research trends in colistin resistance and mechanisms of resistance were considered. A total of 1819 research articles published between 1995 and 2019 were retrieved, and the results indicated that 50.19% of the documents were published within 2017-2019. The USA had the highest participation with 340 (14.31%) articles and 14087 (17.61%) citations. Classification based on the WHO global epidemiological regions showed that the European Region contributed 42% of the articles while the American Region contributed 21%. The result further indicated that 45 countries had published at least 10 documents with strong international collaborations amounting to 272 links and a total linkage strength of 735. A total of 2282 keywords were retrieved; however, 57 keywords had ≥15 occurrences with 764 links and a total linkage strength of 2388. Furthermore, mcr-1, colistin resistance, NDM, mgrB, ceftazidime-avibactam, MDR, combination therapy, and carbapenem-resistant Enterobacteriaceae were the trending keywords. Concerning funders, the USA National Institute of Health funded 9.1% of the total research articles, topping the list. The analysis indicated poor research output, collaboration, and funding from Africa and South-East Asia and demands for improvement in international research collaboration.

Rhodomyrtone Accumulates in Bacterial Cell Wall and Cell Membrane and Inhibits the Synthesis of Multiple Cellular Macromolecules in Epidemic Methicillin-Resistant Staphylococcus aureus.

As the burden of antibacterial resistance worsens and treatment options become narrower, rhodomyrtone-a novel natural antibiotic agent with a new antibacterial mechanism-could replace existing antibiotics for the treatment of infections caused by multi-drug resistant Gram-positive bacteria. In this study, rhodomyrtone was detected within the cell by means of an easy an inexpensive method. The antibacterial effects of rhodomyrtone were investigated on epidemic methicillin-resistant Staphylococcus aureus. Thin-layer chromatography demonstrated the entrapment and accumulation of rhodomyrtone within the bacterial cell wall and cell membrane. The incorporation of radiolabelled precursors revealed that rhodomyrtone inhibited the synthesis of macromolecules including DNA, RNA, proteins, the cell wall, and lipids. Following the treatment with rhodomyrtone at MIC (0.5-1 µg/mL), the synthesis of all macromolecules was significantly inhibited (p ≤ 0.05) after 4 h. Inhibition of macromolecule synthesis was demonstrated after 30 min at a higher concentration of rhodomyrtone (4× MIC), comparable to standard inhibitor compounds. In contrast, rhodomyrtone did not affect lipase activity in staphylococci-both epidemic methicillin-resistant S. aureus and S. aureus ATCC 29213. Interfering with the synthesis of multiple macromolecules is thought to be one of the antibacterial mechanisms of rhodomyrtone.

Nationwide Surveillance and Molecular Characterization of Critically Drug-Resistant Gram-Negative Bacteria: Results of the Research University Network Thailand Study.

A large-scale surveillance is an important measure to monitor the regional spread of antimicrobial resistance. We prospectively studied the prevalence and molecular characteristics of clinically important Gram-negative bacilli, including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii complex (ABC), and Pseudomonas aeruginosa, from blood, respiratory tract, urine, and sterile sites at 47 hospitals across Thailand. Among 187,619 isolates, 93,810 isolates (50.0%) were critically drug resistant, of which 12,915 isolates (13.8%) were randomly selected for molecular characterization. E. coli was most commonly isolated from all specimens, except the respiratory tract, in which ABC was predominant. Prevalence of extended-spectrum cephalosporin resistance (ESCR) was higher in E. coli (42.5%) than K. pneumoniae (32.0%), but carbapenem-resistant (CR)-K. pneumoniae (17.2%) was 4.5-fold higher than CR-E. coli (3.8%). The majority of ESCR/CR-E. coli and K. pneumoniae isolates carried blaCTX-M (64.6% to 82.1%). blaNDM and blaOXA-48-like were the most prevalent carbapenemase genes in CR-E. coli/CR-K. pneumoniae (74.9%/52.9% and 22.4%/54.1%, respectively). In addition, 12.9%/23.0% of CR-E. coli/CR-K. pneumoniae cocarried blaNDM and blaOXA-48-like. Among ABC isolates, 41.9% were extensively drug resistant (XDR) and 35.7% were multidrug resistant (MDR), while P. aeruginosa showed XDR/MDR at 6.3%/16.5%. A. baumannii was the most common species among ABC isolates. The major carbapenemase gene in MDR-A. baumannii/XDR-A. baumannii was blaOXA-23-like (85.8%/93.0%), which had much higher rates than other ABC species. blaIMP, blaVIM, blaOXA-40-like, and blaOXA-58-like were also detected in ABC at lower rates. The most common carbapenemase gene in MDR/XDR-P. aeruginosa was blaIMP (29.0%/30.6%), followed by blaVIM (9.5%/25.3%). The findings reiterate an alarming situation of drug resistance that requires serious control measures.

Evaluation of the Synergistic Antibacterial Effects of Fosfomycin in Combination with Selected Antibiotics against Carbapenem-Resistant Acinetobacter baumannii.

The spread of multi-drug resistant (MDR) pathogens and the lagging pace in the development of novel chemotherapeutic agents warrant the use of combination therapy as a reliable, cost-effective interim option. In this study, the synergistic effects of fosfomycin in combination with other antibiotics were assessed. Of the 193 isolates, 90.6% were non-susceptible to fosfomycin, with minimum inhibitory concentrations (MICs) of ≥128 µg/mL. Antibacterial evaluation of fosfomycin-resistant isolates indicated multi-drug resistance to various antibiotic classes. Combinations of fosfomycin with 12 commonly used antibiotics synergistically inhibited most fosfomycin-resistant isolates. The fractional inhibitory concentration index indicated that combining fosfomycin with either aminoglycosides, glycylcyclines, fluoroquinolones, or colistin resulted in 2- to 16-fold reduction in the MIC of fosfomycin. Time-kill kinetics further confirmed the synergistic bactericidal effects of fosfomycin in combination with either amikacin, gentamicin, tobramycin, minocycline, tigecycline, or colistin, with more than 99.9% reduction in bacterial cells. Fosfomycin-based combination therapy might serve as an alternative option for the treatment of MDR A. baumannii. Further steps including in vivo efficacy and toxicity in experimental models of infection are required prior to clinical applications.

Rhodomyrtone as a New Natural Antibiotic Isolated from Rhodomyrtus tomentosa Leaf Extract: A Clinical Application in the Management of Acne Vulgaris.

Rhodomyrtone, a plant-derived principal compound isolated from Rhodomyrtus tomentosa (Myrtaceae) leaf extract, was assessed as a potential natural alternative for the treatment of acne vulgaris. The clinical efficacy of a 1% liposomal encapsulated rhodomyrtone serum was compared with a marketed 1% clindamycin gel. In a randomized and double-blind controlled clinical trial, 60 volunteers with mild to moderate acne severity were assigned to two groups: rhodomyrtone serum and clindamycin gel. The volunteers were instructed to apply the samples to acne lesions on their faces twice daily. A significant reduction in the total numbers of acne lesions was demonstrated in both treatment groups between weeks 2 and 8 (p < 0.05). Significant differences in acne numbers compared with the baseline were evidenced at week 2 onwards (p < 0.05). At the end of the clinical trial, the total inflamed acne counts in the 1% rhodomyrtone serum group were significantly reduced by 36.36%, comparable to 34.70% in the clindamycin-treated group (p < 0.05). Furthermore, a commercial prototype was developed, and a clinical assessment of 45 volunteers was performed. After application of the commercial prototype for 1 week, 68.89% and 28.89% of volunteers demonstrated complete and improved inflammatory acne, respectively. All of the subjects presented no signs of irritation or side effects during the treatment. Most of the volunteers (71.11%) indicated that they were very satisfied. Rhodomyrtone serum was demonstrated to be effective and safe for the treatment of inflammatory acne lesions.

Biologically rapid synthesized silver nanoparticles from aqueous Eucalyptus camaldulensis leaf extract: Effects on hyphal growth, hydrolytic enzymes, and biofilm formation in Candida albicans.

Bionanotechnology has increasingly gained attention in biomedical fields as antifungal and antibiofilm agents. In this study, biosynthesized silver nanoparticles (bio-AgNPs) using aqueous Eucalyptus camaldulensis leaf extract were successfully performed by a one-step green approach. Spherical-shaped nanoparticles, approximately 8.65 nm, exhibited noncytotoxicity to erythrocytes, HeLa, and HaCaT cells. The synthesized nanoparticles showed strong fungicidal activity ranging from 0.5 to 1 µg/ml. The nanoparticles affected Candida adhesion and invasion into host cells by reduced germ tube formation and hydrolytic enzyme secretion. Inhibitory effects of bio-AgNPs on Candida biofilms were evaluated by the prevention of yeast-to-hyphal transition. A decrease in cell viability within mature biofilm demonstrated the ability of bio-AgNPs to penetrate into the extracellular matrix and destroy yeast cell morphology, leading to cell death. Molecular biology study on biofilms confirmed downregulation in the expression of genes ALS3, HWP1, ECE1, EFG1, TEC1, ZAP1, encoding hyphal growth and biofilm development and PLB2, LIP9, SAP4, involved in hydrolytic enzymes. In addition to candida treatment, the bio-AgNPs could be applied as an antioxidant to protect against oxidative stress-related human diseases. The findings concluded that bio-AgNPs could be used as an antifungal agent for candida treatment, as well as be incorporated in medical devices to prevent biofilm formation.