The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens\' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Antimicrobial susceptibility testing is an essential task for selecting appropriate antimicrobial agents to treat infectious diseases. Constant evolution has been observed in methods used in the diagnostic microbiology laboratories. Disc diffusion or broth microdilution are classical and conventional phenotypic methods with long turnaround time and labour-intensive but still widely practiced as gold-standard. Scientists are striving to develop innovative, novel and faster methods of antimicrobial susceptibility testing to be applicable for routine microbiological laboratory practice and research. To meet the requirements, there is an increasing trend towards automation, genotypic and micro/nano technology-based innovations. Automation in detection systems and integration of computers for online data analysis and data sharing are giant leaps towards versatile nature of automated methods currently in use. Genotypic methods detect a specific genetic marker associated with resistant phenotypes using molecular amplification techniques and genome sequencing. Microfluidics and microdroplets are recent addition in the continuous advancement of methods that show great promises with regards to safety and speed and have the prospect to identify and monitor resistance mechanisms. Although genotypic and microfluidics methods have many exciting features, however, their applications into routine clinical laboratory practice warrant extensive validation. The main impetus behind the evolution of methods in antimicrobial susceptibility testing is to shorten the overall turnaround time in obtaining the results and to enhance the ease of sample processing. This comprehensive narrative review summarises major conventional phenotypic methods and automated systems currently in use, and highlights principles of some of the emerging genotypic and micro/nanotechnology-based methods in antimicrobial susceptibility testing.

Studies are being carried out on achieving the maximum quality of garlic through various approaches. In Bangladesh, new garlic varieties (BARI 1-4, BAU-1, BAU-2, BAU-5) have been recently developed by artificial selection to enhance their quality. The present study aimed to evaluate their potency in terms of bioactive properties and organosulfur compounds content using different bioassay and GC-MS techniques while comparing them with other accessible varieties (Chinese, Indian, Local). The new variety, BARI-3 showed the highest antioxidant activity and total phenolic content. It was also found with the highest level of a potent blood pressure-lowering agent, 2-vinyl-4H-1,3-dithiine (78.15 %), which is never reported in any garlic at this percentage. However, the local variety exhibited greater inhibitory properties against the tested organisms including multidrug-resistant pathogens compared to other varieties. This study primarily shows the potential of these two kinds of garlic for their further utilization and development.

Fungal peritonitis (FP) is usually associated with poor patient outcomes and is mostly caused by non-albicans Candida species. We present a Candida nivariensis-associated peritonitis in a 68-year-old woman with end-stage kidney disease on peritoneal dialysis (PD). Biochemical profiling of the cultured yeast of the effluent sample did not adequately identify the yeast. Hence, molecular phylogeny and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) mass spectroscopy were employed which correctly identified the causative species, C. nivariensis. PD catheter was removed and oral fluconazole was promptly started according to the 2022 International Society for PD (ISPD) Peritonitis Guidelines. However, the patient achieved only a partial clinical response and eventually died. The susceptibility test showed that the pathogen was susceptible to amphotericin B and voriconazole but resistant to other triazoles. This report underlines the importance of identifying the species, though rarely reported, and the drug susceptibility of the organism.

UNASSIGNED: The rapid emergence of antibiotic resistance among various bacterial pathogens has been one of the major concerns of health organizations across the world. In this context, for the development of novel inhibitors against antibiotic-resistant bacterial pathogens, UDP-N-Acetylmuramoyl-L-Alanine-D-Glutamate Ligase (MurD) enzyme represents one of the most apposite targets.
UNASSIGNED: The present review focuses on updated advancements on MurD-targeted inhibitors in recent years along with genetic regulation, structural and functional characteristics of the MurD enzyme from various bacterial pathogens. A concise account of various crystal structures of MurD enzyme, submitted into Protein Data Bank is also discussed.
UNASSIGNED: MurD, an ATP dependent cytoplasmic enzyme is an important target for drug discovery. The genetic organization of MurD enzyme is well elucidated and many crystal structures of MurD enzyme are submitted into Protein Data bank. Various inhibitors against MurD enzyme have been developed so far with an increase in the use of in-silico methods in the recent past. But cell permeability barriers and conformational changes of MurD enzyme during catalytic reaction need to be addressed for effective drug development. So, a combination of in-silico methods along with experimental work is proposed to counter the catalytic machinery of MurD enzyme.

UNASSIGNED: Optimizing antimicrobial therapy to attain drug exposure that limits the emergence of resistance, effectively treats the infection, and reduces the risk of side effects is of a particular importance in critically ill patients, in whom normal functions are augmented or/and are infected with pathogens less sensitive to treatment. Achievement of these goals can be enhanced by therapeutic drug monitoring (TDM) for many antibiotics. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method is presented here for simultaneous quantification of ten antimicrobials: cefazolin (CZO), cefepime (CEP), cefotaxime (CTA), ceftazidime (CTZ), ciprofloxacin (CIP), flucloxacillin (FLU), linezolid (LIN), meropenem (MER), piperacillin (PIP) and tazobactam (TAZ) in human plasma.
UNASSIGNED: Plasma samples were precipitated with acetonitrile and injected into the LC-MS/MS. Chromatographic separation was on a Waters Acquity BEH C18 column. Compounds were eluted with water and acetonitrile containing 0.1 % formic acid, using a gradient (0.5-65 % B), in 3.8 min. The flow rate was 0.4 mL/min, and the run time was 5.8 min.
UNASSIGNED: The calibration curves were linear across the tested concentration ranges (0.5-250, CZO, CEP, CTA, CTZ and FLU; 0.2-100, MER and TAZ; 0.1-50, CIP and LIN and 1-500 mg/L, PIP). The intra and inter-day imprecision was < 11 %. Accuracy ranged from 95 to 114 %. CTZ and MER showed ionization suppression while CIP showed ionization enhancement, which was normalized with the use of the internal standard.
UNASSIGNED: An LC-MS/MS method for simultaneous quantification of ten antimicrobials in human plasma was developed for routine TDM.

The leaf of Chinese prickly ash, a unique spice having typical pungent sensation, is a popular food in Southwest China with antipruritic, insecticidal and fungicidal functions, but its bioactive constituents of fungistatic capacity remain unknown. In present investigation, twenty-nine compounds were isolated from leaf of Chinese prickly ash, and their antifungal bioactivity against drug-resistant Candida albicans were evaluated in vitro and in vivo. As a result, three compounds 3, 10, 29 showed antifungal bioactivity by damage of the fungal biofilm, and they might recover sensitive of drug resistant C. albicans to Fluconazole. Then Chinese prickly ash leaf was proved to be a functional food against fungus for the first time in experiment.

UNASSIGNED: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients with cirrhosis represent a significant therapeutic challenge as they are associated with poor outcomes due to high rates of treatment failure, and frequently induce liver decompensation.
UNASSIGNED: To evaluate treatment failure and in-hospital mortality in two cohorts of patients with cirrhosis and with CRKP infections treated with antibiotic regimens including or excluding Ceftazidime-avibactam.
UNASSIGNED: Data from hospitalized patients with liver cirrhosis and CRKP infections were extracted and retrospectively analyzed.
UNASSIGNED: During the study period, 39 cirrhotic patients with confirmed invasive CRKP infections were enrolled. Overall, the median age was 60 years with a median MELD score of 16 points. Urinary tract infections were diagnosed in 46%, followed by pneumonia in 23%, and primary bacteremia in 18% of patients. Treatment failure was reported in 10 patients (26%), while in-hospital mortality in 15 patients (38%). A monotherapy was used in 8 patients (20.5%), while a combination therapy was required in 31 patients (79.5%). Ceftazidime-avibactam therapy was associated with lower rates of treatment failure (7% vs. 38%, P = 0.032) independent of severity of liver disease (Child Class) and mono or combination antibiotic therapy. Acute kidney injury, hepatorenal syndrome, and acute-on-chronic liver failure were the consequences more frequently observed in patients with treatment failure. In-hospital mortality was associated with treatment failure, and Ceftazidime-avibactam therapy improved in-hospital survival (log rank test: P = 0.035) adjusted for Child class and mono or combination therapy.
UNASSIGNED: Treatment including ceftazidime-avibactam was associated with a lower rate of treatment failure in cirrhotic patients with CRKP infections. Considering the favorable efficacy and outcomes of ceftazidime-avibactam, this drug should be considered for the treatment of these severe infections in patients with liver cirrhosis, though further investigation is required.

UNASSIGNED: Medicinal plants have been used as traditional treatments for various human diseases for many years and they are still widely practiced throughout the world. Due to the long history of the practice, medicinal plants have become an integral part of the Ethiopian culture. This study aimed to evaluate the antibacterial activities of Vernonia auriculifera Hiern and Buddleja polystachya Fresen leaf extracts and their synergistic effect against some selected human pathogenic bacteria.
UNASSIGNED: Ethanol, methanol, and n-hexane crude extracts of Vernonia auriculifera, Buddleja polystachya, and a mixture of the two-plant respective of each solvent were evaluated against tested pathogenic bacteria using the agar well diffusion method; the inhibition zones were recorded in millimeters. Gentamycin was used as a positive control, while dimethyl sulfoxide served as a negative control. The minimum inhibitory concentration of the plant extracts against test bacteria was evaluated using two-fold broth dilution methods and then Minimum bactericidal concentration was determined by sub-culturing the test dilutions from minimum inhibitory concentration tubes onto fresh Muller Hinton Agar plates incubated at 37 °C for 24 h.
UNASSIGNED: Maximum antibacterial inhibition zone was observed on methanol extracts of synergism against S. Typhimurium (ATCC 1333) (31.00 ± 1.73 mm) while, a minimum inhibition zone was observed on methanol extract of Buddleja polystachya, against E. coli (ATCC 35218) (5.67 ± 0.57). Minimum inhibitory concentration and minimum bactericidal concentration values of the crude extracts of Vernonia auriculifera, Buddleja polystachya, and their mixture lies between (3.125%-12.5%) and (6.25%-25%) respectively. The data were analyzed using the SPSS software package version 20 for windows.
UNASSIGNED: The present study revealed that ethanol and methanol extracts of Vernonia auriculifera and Buddleja polystachya possess significant inhibitory effects against tested pathogens and the antibacterial activity of both plants leaf extracts was greater than the activity of currently used antibiotics (Gentamycin) against some selected organisms.

Antimicrobial resistance is increasing in prevalence and there is a clear need for the development of rapid detection methods in clinical diagnostics. This review explores -omics studies utilising mass spectrometry to investigate the molecular phenotype associated with carbapenem resistance. Whilst the specific mechanisms of carbapenem resistance are well characterised, the resistant phenotype is poorly understood. Understanding how the acquisition of resistance affects cellular physiology and cell metabolism through molecular phenotyping is a necessary step towards detecting resistance by diagnostic means. In addition, this article examines the potential of mass spectrometry for the identification of resistance biomarkers through molecular profiling of bacteria. Developments in mass spectrometry platforms are expanding the biomarker-based diagnostic landscape. Targeted measures, such as high-resolution mass spectrometry coupled with chromatographic separation show considerable promise for the identification of molecular signatures and the development of a rapid diagnostic assay for the detection of carbapenem resistance.