Search Results (21)

Ocular fungal diseases are associated with severe infection and pain and, in advanced stages, can lead to vision loss. Current treatment options are limited to the topical application of conventional drugs, and the bioavailability of these drugs is quite limited due to ocular barriers. In this study, a dual-drug nanodelivery system was developed to improve intraocular drug delivery by combining antifungal and anti-inflammatory therapies. Posaconazole (PSC), a broad-spectrum triazole antifungal agent, and dexketoprofen trometamol (DKP), a rapidly acting nonsteroidal anti-inflammatory drug, were co-loaded onto polymeric micelles and then incorporated into electrospun poly(vinyl alcohol)/poly(vinylpyrrolidone) (PVA/PVP) nanofiber intraocular implants. DSC, XRD, FTIR, and FESEM analyses showed that both APIs were successfully converted into nanofiber form without disrupting the micelle structure. Comparative studies with DKP solution and PSC commercial oral suspension (Noxafil^® 40 mg/mL) showed that the produced micelle-loaded nanofibers provided sustained release and significantly increased ex vivo ocular permeation and penetration. In vitro antifungal activity tests demonstrated efficacy against Candida albicans, and HET-CAM toxicity tests showed that the micelle-loaded nanofibers were non-irritating and suitable for ocular application. Overall, the micelle-loaded electrospun nanofiber ocular inserts developed in this study represent a promising platform for combined antifungal and anti-inflammatory ocular therapy. Full article

Background: Transrectal ultrasound-guided prostate biopsy remains the gold standard in diagnosing prostate cancer, but is associated with infectious and non-infectious complications. Increasing fluoroquinolone resistance and regulatory restrictions have prompted evaluation of alternative prophylactic strategies, including fluoroquinolone-sparing agents and targeted prophylaxis. This study compared ciprofloxacin and fosfomycin as empirical prophylactic agents, focusing on microbiological concordance, clinical outcomes, and patient-reported outcomes. Methods: In this prospective observational study, 265 men undergoing transrectal ultrasound-guided prostate biopsy received empirical antibiotic prophylaxis with either ciprofloxacin (n = 146) or fosfomycin trometamol (n = 119). Rectal swabs were obtained prior to biopsy, and antimicrobial susceptibility was analyzed post hoc. Infectious and non-infectious complications were recorded. Lower urinary tract symptoms (IPSS), erectile function (IIEF-5), and patient-reported quality of life were assessed before and after biopsy. Results: Microbiological concordance between administered prophylaxis and rectal flora susceptibility was higher in the ciprofloxacin group than in the fosfomycin group (80.1% vs. 65.0%, p = 0.007), while resistance rates were similar (10.9% vs. 10.2%). Post-biopsy fever occurred in 5.3% of patients, and hospitalization was required in 3.1%, with no significant differences between prophylaxis groups. IPSS increased significantly after biopsy (p < 0.001), while IIEF-5 scores remained unchanged. Patients with microbiological concordance reported significantly better post-biopsy quality of life (p = 0.006). Conclusions: Ciprofloxacin and fosfomycin showed similar safety profiles as empirical prophylaxis before transrectal prostate biopsy. Although ciprofloxacin achieved higher microbiological concordance, fosfomycin remains a viable alternative. The link between microbial concordance and improved patient-reported quality of life underscores the importance of targeted prophylaxis and supports antimicrobial stewardship in prostate cancer diagnostics. Full article

Background: Antibiotics are commonly used in gynecology, yet only limited outpatient prescribing data are available in Germany. The aim of this study is to estimate the prevalence of antibiotic prescriptions in gynecological practices and to identify patient and diagnostic factors. Methods: A retrospective cross-sectional analysis was conducted using anonymized electronic records from the IQVIA Disease Analyzer, including 344,187 women aged ≥16 years who had at least one gynecological visit in 2024. The primary outcome of interest was the prescription of an antibiotic. Consequently, the prevalence of antibiotic prescriptions was calculated overall and stratified by age group. Associations between potential factors and antibiotic prescriptions were assessed using multivariable logistic regression. Results: The overall prescription prevalence was 8.4% (29,007/344,187). Regarding the age distribution within the prescribed sample, the highest percentages were observed among women aged 31–40 years (25.6%) and 16–30 years (25.4%), while those aged 51–60 and >60 made up 12.9% and 19.1%, respectively. The most commonly prescribed agents were fosfomycin trometamol (35.9%), clindamycin (17.6%), and pivmecillinam (10.7%). Mastitis (OR 63.54, 95% CI 55.79–72.38), acute cystitis (OR 43.67, 95% CI 41.63–45.80), and unspecified urinary tract infection (OR 31.58, 95% CI 20.11–33.12) were strongly positively associated with AB prescription. Positive associations were also observed for acute vaginitis (OR 3.44, 95% CI 3.30–3.58), chlamydial infection (OR 6.27, 95% CI 5.77–6.81), and pregnancy (OR 1.95, 95% CI 1.85–2.05). Negative associations were observed for dysmenorrhea (OR 0.52, 95% CI 0.48–0.56), irregular menstruation (OR 0.65, 95% CI 0.60–0.71), menopausal disorders (OR 0.51, 95% CI 0.48–0.53), and ovarian cysts (OR 0.78, 95% CI 0.72–0.84). Conclusions: Antibiotic use in gynecology is low and strongly diagnosis-driven, primarily for urogenital infections. Signals of inappropriate prescribing in patients with candidiasis suggest a need for improved diagnostic accuracy and guideline adherence. Full article

Naproxen (NAP) is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the arylpropionic acid class. Classified as a Biopharmaceutical Classification System (BCS) class II drug, NAP exhibits low water solubility, thus resulting in restricted oral bioavailability. This study aimed to evaluate the effectiveness of pharmaceutical salts in enhancing the solubility and oral bioavailability of NAP. Two novel NAP salts, specifically naproxen-ethylenediamine (NAP-EDA) and naproxen-trometamol (NAP-TRIS), were synthesized using a 2:1 and 1:1 stoichiometric ratio, respectively. The NAP-EDA and NAP-TRIS powders were thoroughly characterized using single-crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC), providing a comprehensive understanding of their structural and thermal properties. Additionally, the solubilities and dissolution rates of NAP-EDA and NAP-TRIS salts were assessed in water and a pH 6.86 phosphate buffer. Notably, the solubility of NAP-TRIS salt increased markedly, by 397.5-fold in water and 6.2-fold at pH 6.86. Furthermore, in vivo pharmacokinetic studies in rats revealed that NAP-TRIS salt displayed faster absorption and higher peak blood concentrations compared to NAP. These results indicate that the NAP-TRIS salt effectively enhanced the solubility and oral bioavailability of naproxen. In conclusion, this study underscores the potential of pharmaceutical salts, particularly NAP-TRIS, in improving the solubility and oral bioavailability of drugs with low aqueous solubility, presenting a promising avenue for advancing drug delivery and therapeutic outcomes. Full article

Dendrobium stem is a valuable food with medicinal and edible properties. Due to its high medicinal value and price, closely related Dendrobium varieties are often sold as imitations on the market. Therefore, there is an urgent need to develop new methods that can quickly identify Dendrobium stem and its closely related species. The Heracles Neo ultra-fast gas phase electronic nose was used in this study to determine and analyze the composition and contents of volatile organic compounds (VOCs) in Dendrobium stem and samples of five other species closely related to it. A total of 20 VOCs were identified, and a fingerprint map of the VOCs was constructed. Principal component analysis (PCA), Euclidean distance, and other methods were used to comprehensively process and analyze the obtained VOC information. The AroChemBase database was also used for qualitative analysis of the compounds. The results showed that there are significant differences in the odor fingerprint spectra of Dendrobium stem and the five other closely related species. The main types of compounds in Dendrobium stem and its five closely related species were organic esters, aldehydes, ketones, and olefins. Among them, 3-methylbutanal and n-butanol were characteristic compounds of the Dendrobium stem sample, while the VOCs acetonitrile and trometamol were present in the five related Dendrobium species samples. The Heracles Neo ultra-fast gas phase electronic nose can quickly and accurately identify Dendrobium stem and its five closely related species. It can also be used for the quality evaluation of Dendrobium stem, providing a theoretical reference for reducing the phenomenon of medicinal confusion in the Dendrobium stem market. Full article

This study aimed to assess the efficacy of a novel prophylactic scheme of fosfomycin trometamol in patients undergoing elective HoLEP (holmium laser enucleation of the prostate) or TURP (transurethral resection of the prostate) procedures for treating benign prostatic hyperplasia. Patients affected by benign prostatic hyperplasia and undergoing elective HoLEP or TURP procedures during the period February 2022–June 2023 were prospectively enrolled. Two 3 g oral fosfomycin trometamol doses 12 h apart were administered at 8.00 p.m. on day −1 (i.e., the day before HoLEP or TURP procedure) and at 8.00 a.m. on day 0 (i.e., the day of the surgical procedure). The following outcomes were assessed: prevalence of fever occurring in the first 48 h after surgical procedure; prevalence of urological complications occurring after the surgical procedure; prevalence of proven urinary tract infections (UTIs) and/or bloodstream infections (BSIs) at 14 days post-procedure; and prevalence of emergency department admission for UTI-related sepsis at 14 days post-procedure. Univariate analysis comparing patients with and without proven UTI, BSI, or emergency department admission at 14 days post-procedure was carried out. Overall, 96 patients (median age 70 years) undergoing HoLEP (82.3%) or TURP (17.7%) were prospectively included. Median (IQR) time of surgical procedure after the morning fosfomycin dose was 226.5 min (range 88.5–393.75 min). Fever in the post-surgical 48 h occurred in 3/96 patients (3.1%). Prevalence of proven UTI at 14 days was as low as 1.0% (1/96), whereas no patient had proven BSI or UTI-related sepsis requiring emergency department admission at 14 days. Our findings support the contention that a prophylactic scheme based on two doses of fosfomycin trometamol 12 h apart before surgical intervention may represent a valuable strategy for preventing infectious complications in urologic patients undergoing HoLEP or TURP. Larger definitive confirmatory studies are warranted. Full article

Orally disintegrating granules (ODGs) are a pharmaceutical form commonly used for the administration of NSAIDs because of their easy assumption and fast dispersion. The development of ODGs is not easy for drugs like dexketoprofen trometamol (DXKT), which have a bitter and burning taste. In this work, high-shear coating (HSC) was used as an innovative technique for DKXT taste masking. This study focused on coating DXKT granules using the HSC technique with a low-melting lipid excipient, glyceryl distearate (GDS). The HSC technique allowed for the coating to be developed through the thermal rise resulting from the friction generated by the granules movement inside the equipment, causing the coating excipient to soften. The design of the experiment was used to find the best experimental coating conditions in order to gain effective taste masking by suitably reducing the amount of drug released in the oral cavity. The influence of the granule dimensions was also investigated. Coating effectiveness was evaluated using a simulated saliva dissolution test. It was found that low impeller speed (300 rpm) and a 20% coating excipient were effective in suitably reducing the drug dissolution rate and then in taste masking. The coated granules were characterized for their morphology and solid-state properties by SEM, BET, XRPD, DSC, and NIR analyses. A human taste panel test confirmed the masking of DXKT taste in the selected batch granules. Full article

Introduction and hypothesis: Urinary tract infections (UTIs) are one of the most common complications of urogynecological surgeries. The risk of UTIs is increased by the catheterization of the bladder, intraoperative cystoscopy, and urine retention after the procedure. Due to increasing antibiotic resistance, there is a need to search for new methods of postoperative UTI prevention. Canephron is a mixture of century herbs, lovage roots, and rosemary leaves with diuretic, spasmolytic, anti-inflammatory, antibacterial, and nephroprotective properties. The aim of this study is to demonstrate the noninferiority of Canephron versus antibiotic prophylaxis with fosfomycin trometamol (FT), based on the collective results of postoperative urine culture analyses. Methods: One hundred and twenty-five female patients were randomized into two groups before undergoing urogynecological surgeries, including a control group (n = 67), which received one dose of 3 g of FT the day after the procedure, and a study group (n = 58), which received Canephron three times a day for 14 days, starting the day after the procedure. All the patients were assessed using the Acute Cystitis Symptom Score (ACSS). Results: UTIs were observed in 6.4% of the patients. There was no statistically significant difference between the use of FT and Canephron in terms of UTIs (Chi^2 N-1 = 0.8837; p = ns). Additional factors, such as menopausal status and the type of procedure performed, increased the risk of developing a UTI. Factors such as the body mass index (BMI) and parity had no correlation. Conclusions: Canephron is noninferior to FT in the prevention of postoperative UTIs. The use of such a phytotherapeutic drug may help to decrease antibiotic consumption, which is closely connected to the growing trend of antibiotic resistance. Full article

Background: Skin local reactions to mRNA COVID-19 vaccines have been linked to the use of vaccine excipients. The aim of the study is to evaluate the role of skin testing excipients in delayed skin reactions due to mRNA COVID-19 vaccines. Methods: Skin testing among a group of healthcare workers with skin reactions due to mRNA vaccines was performed. Patch testing and intradermal testing (IDT) with polyethylene glycol (PEG)-400, PEG-2000, trometamol, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine were performed. Healthcare workers without skin reactions to vaccines were used for skin testing as controls. Results: Thirty-one healthcare workers (from a total of 4315 vaccinated healthcare workers) experienced cutaneous adverse vaccine reactions. Skin testing was performed in sixteen of the healthcare workers (11 delayed large local reactions (DLLR) and 5 widespread reactions). Positive IDT for PEG-2000 1% in DLLR was seen in 10 (90.9%) patients, in comparison with one (16.6%) individual with a delayed widespread reaction. Delayed positive IDT reactions for PEG-2000 1% on day 2 were observed in three (27.3%) patients with DLLR. Patch testing of the excipients was negative. Among 10 controls, only one exhibited a transient positive IDT reaction to PEG-2000 1%. Conclusions: Immediate and delayed reactions to IDT are frequently detected in patients with DLLR. The observation of positive delayed intradermal reactions to PEG disclosed only in patients with DLLR reinforces a possible role of PEG in the development of these reactions. Skin testing of other excipients is of little importance in clinical practice. Full article

The present Phase I study investigated, for the first time, fosfomycin pharmacokinetics in humans after two 3 g doses of fosfomycin trometamol administered 27 h apart, according to the dose regimen recommended for the prophylactic indication for transrectal prostate biopsy in adult men. Plasma, urine and seminal plasma concentrations were measured after one and two consecutive doses in 24 healthy men, representative of the target population of the prophylactic indication. Prostate and seminal vesicle concentrations were estimated based on seminal plasma concentrations using a one-step regression method. The exposure to fosfomycin was very similar in rate (C_max, t_max) after one and two doses. The AUC showed a minimal increment. On average, the apparent volume of distribution was high (>100 L), and the mean clearance had an intermediate value. The total amount and dose fraction of fosfomycin excreted in urine showed a small increment after two doses. The renal clearance was about 5 L/h. The fosfomycin concentration in the prostate and seminal vesicles showed that the antibiotic increased on average after two consecutive doses. This result confirmed the ability of fosfomycin to distribute into the prostate and into seminal vesicles after one single dose and that a two consecutive dose regimen increases the antibiotic availability inside these peripheral tissues. Full article

This study proposes a simple and effective method to obtain ultra-thin membranes based on κ-carrageenan. Two types of membranes were obtained, one based on κ-carrageenan and the second type based on κ-carrageenan, hydroxyethyl cellulose and the plasticizer (glycerol). Three non-steroidal anti-inflammatory drugs (Dexketoprofen trometamol, Meloxicam, Diclofenac sodium) and a glucocorticoid (Dexamethasone) were introduced, looking for the best option for incorporation. The obtained membranes were characterized by FTIR, TG/DTG and UV-VIS methods and the data collected following these methods indicated success in terms of the incorporation of the active substance, as well as the high thermal stability in the temperature range 37–100 °C of both the matrices of membrane types, as well as the membranes with the drug incorporated. All the studies carried out led to the conclusion that within all the membranes the anti-inflammatory substances were intact and, thus we can say that these membranes can be used for transdermal administration of the studied anti-inflammatory substances. Full article

Urinary tract infections, especially cystitis, are common infections; they are the second most prevalent cause of antibiotic prescriptions in community pharmacies. To reduce antimicrobial resistance, guidelines are revised regularly. This study aims to assess compliance between prescriptions collected in community pharmacies and French cystitis guidelines. A treatment is considered compliant if the nature, dosage, and duration of the antibiotics are correct. Only women aged 18–65 years with a diagnosis of cystitis were eligible. The participation of 16 pharmacies resulted in 303 prescriptions. Most infections were classified as uncomplicated cystitis (79.2%), general practitioners were the prescribers in more than 9 out of 10 cases, and fosfomycin trometamol was the antibiotic dispensed for 1 in 2 women. An average compliance of 66% was observed, but with disparities according to the type of cystitis. Two-thirds of cases of uncomplicated cystitis and recurrent cystitis followed the recommendations, whereas only 15% of cystitis cases that were at risk of complication did so. The inclusion of a urine examination in uncomplicated cystitis decreased the overall compliance rate to 5.8%. These results show the essential role played by pharmacists; they are the last line of defence before dispensing antibiotics. They must know the recommendations in order to apply them. Full article

Two different concepts for developing direct HPLC-UV methods for quantifying fosfomycin trometamol were developed without any derivatization and modification of the analyte. In the first concept, without the use of alkylamines as ion-pairs in the mobile phase, by using cyanopropyl CN and a strong anion-exchanger column, we investigated the possibility of their highly polar and anion-exchanging forces and mechanisms to retain, separate and detect trometamol without the help of additional agents or modifiers. In the second concept, the most frequent reversed-phase C18 columns with different characteristics and vendors were tested in combination with different length-based alkylamines with 3–10 C atoms in their chains. In our research, we found that the ion-pairing of fosfomycin with 6–10 C-atom-based alkyl-length of aliphatic chains manifested the most appropriate strength of interactions between alkyl-paired trometamol molecules and octadecylsilane or C18 bonded RP column to achieve optimal retention, selectivity and peak shape on chromatograms, with the possibility for the fine-tuning of elution time. The simplicity of our method concept omits the need for expensive and sophisticated columns like HILIC, C30 graphite carbon, and mixed-mode-based columns for easier retaining, separation, and determination of fosfomycin, and for its quantification purposes, especially in high-throughput analyses in regular quality-control laboratories. Full article

Background: Antimicrobial drugs to treat male urinary tract infection (UTI) with multidrug-resistant Enterobacterales are limited. We studied oral fosfomycin-trometamol (FT) in this situation. The objective was to assess the clinical cure rate in patients presenting UTIs treated with oral FT. Methods: We conducted a single-center observational retrospective study from January 2017 to August 2018. The primary endpoint was clinical cure; and the secondary endpoints were incidence of recurrences, oral FT safety, and microbiological cure. Results: Sixteen male patients were included, presenting 21 UTI episodes. Fourteen patients (88%) have at least one underlying urologic disorder. We described 4 episodes of acute UTI and 17 episodes of chronic bacterial prostatitis (CBP). Sixteen out of twenty-one Enterobacterales were extended spectrum beta-lactamase (ESBL)-producers and all the patients presented a resistance to fluoroquinolones and trimethoprim/sulfamethoxazole. In acute UTI, the regimen was a daily dose of oral FT for a mean duration of 2.5 weeks (+/−7.0 days). Clinical and microbiological recovery was achieved in all patients, with no recurrence after 5.3 months follow-up on average (+/−10.4 days). In CBP, the regimen was one oral dose of fosfomycin every 24–48 h, for a mean duration of 5.5 weeks/UTI episodes (+/−15.3 days). Clinical and microbiological recovery was found in 16/17 cases. Seven of the twelve patients with CBP had relapsed and 3/12 had had a new episode of infection after an average follow-up of 5.8 months. Only 6/21 of patients presented minor or moderate adverse effects, such as digestive disorders. Conclusions: FT could be an alternative option to carbapenems in the treatment of multidrug-resistant Enterobacterales infections for male UTIs. Full article

Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improving patient compliance. Concerning that, this work aims to develop a suitable chitosan-based thermo-responsive scaffold to provide 24 h controlled release of Dexketoprofen trometamol (DKT). Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and FT-IR. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C, and the profiles were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 h (77.75 ± 2.72%) and reduced the burst release in the initial 6 h (40.18 ± 1.00%). The formulation exhibited a lower critical solution temperature (LCST) at 34.96 °C, and due to this phase transition, an increased release was observed at 38 °C (88.52 ± 2.07% at 12 h). The release profile for this formulation fits with Hixson–Crowell and Korsmeyer–Peppas kinetic models at both temperatures. Therefore, the developed scaffold for DKT delivery performs adequate controlled release, thereby; it can potentially overcome adherence issues and complications in wound healing applications. Full article