Inappropriate antimicrobial use in Turkish pediatric hospitals: A multicenter point prevalence survey

Objectives: Although well-defined principles of rational antimicrobial use are available, inappropriate prescribing patterns are reported worldwide. Accurate information on the usage of antimicrobials, including factors associated with and influencing their use, is valuable for improving the quality of prescription practices. Methods: In this cross-sectional point prevalence survey, data on patients hospitalized in 12 different children's hospitals were collected on a single day. Appropriateness of prescription was compared between the types of antimicrobials prescribed, indications, wards, and presence of/consultation with an infectious disease physician (IDP). Results: A total 711 of 1302 (54.6%) patients evaluated were receiving one or more antimicrobial drugs. The antimicrobial prescription rate was highest in pediatric intensive care (75.7%) and lowest in the surgery wards (37.0%). Of the 711 patients receiving antimicrobials, 332 patients (46.7%) were found to be receiving at least one inappropriately prescribed drug. Inappropriate use was most frequent in surgery wards (80.2%), while it was less common in oncology wards (31.8%; p < 0.001). Respiratory tract infection was the most common indication for antimicrobial use (29.4%). Inappropriate use was more common in deep-seated infections (54.7%) and respiratory infections (56.5%). Fluoroquinolones were used inappropriately more than any other drugs (81.8%, p = 0.021). Consultation with an IDP appears to increase appropriate antimicrobial use (p = 0.008). Conclusions: Inappropriate antimicrobial use remains a common problem in Turkish pediatric hospitals. Consultation with an IDP and prescribing antimicrobial drugs according to microbiological test results could decrease the inappropriate use of antimicrobials

In a real-life setting, direct-acting antivirals to people who inject drugs with chronic hepatitis c in Turkey

Background: People who inject drugs (PWID) should be treated in order to eliminate hepatitis C virus in the world. The aim of this study was to compare direct-acting antivirals treatment of hepatitis C virus for PWID and non-PWID in a real-life setting. Methods: We performed a prospective, non-randomized, observational multicenter cohort study in 37 centers. All patients treated with direct-acting antivirals between April 1, 2017, and February 28, 2019, were included. In total, 2713 patients were included in the study among which 250 were PWID and 2463 were non-PWID. Besides patient characteristics, treatment response, follow-up, and side effects of treatment were also analyzed. Results: Genotype 1a and 3 were more prevalent in PWID-infected patients (20.4% vs 9.9% and 46.8% vs 5.3%). The number of naïve patients was higher in PWID (90.7% vs 60.0%), while the number of patients with cirrhosis was higher in non-PWID (14.1% vs 3.7%). The loss of follow-up was higher in PWID (29.6% vs 13.6%). There was no difference in the sustained virologic response at 12 weeks after treatment (98.3% vs 98.4%), but the end of treatment response was lower in PWID (96.2% vs 99.0%). In addition, the rate of treatment completion was lower in PWID (74% vs 94.4%). Conclusion: Direct-acting antivirals were safe and effective in PWID. Primary measures should be taken to prevent the loss of follow-up and poor adherence in PWID patients in order to achieve World Health Organization’s objective of eliminating viral hepatitis

Cyclodextrine Based Nanogels and Phase Solubility Studies of Flurbiprofen as a Chemopreventive Agent

Abstract: Flurbiprofen (FB) is one of the nonsteroidal anti-inflammatory drugs (NSAIDs) which has low water solubility (1). In recent studies it is shown that NSAIDs tend to demonstrate chemopreventive activity and chemoprotective agents frequently show low water solubility (2). In this study FB was selected as a model drug. Cyclodextrins (CDs) which are natural products and have special structure (hydrophobic inner phase and hydrophilic outer phase), have been widely used to enhance solubility and stability of drug substances (3). The objective of this study was to prepare CD based nanogels for increasing solubility and stability of FB. Nanogels were prepared with two different ratio (0.02 and 20%) and type of CD (βCD and HPβCD) using emulsification-solvent evaporation technique. Particle size (PS), polydispersity index (PDI), zeta potential (ZP) were investigated and phase solubility studies were performed to optimize CD based nanogels. According to results of phase solubility studies; it was achieved to enhance water solubility of FB with HPβCD 56.7 fold. PS, PDI and ZP were found as 154.5 ± 3.1 nm, 0.25 ± 0.01, −60 ± 2 mV for 0.02% HPβCD and 270.7 ± 58.2nm, 0.52 ± 0.06, −28.9 ± 2.3 mV for 20% HPβCD respectively. It can be concluded that HPβCD based nanogels can be promising carriers for FB as a chemopreventive agent

A new nanosuspension prepared with wet milling method for oral delivery of highly variable drug Cyclosporine A: development, optimization and in vivo evaluation

Cyclosporine A (CsA) is a cyclic polypeptide, that has been widely used for immunosuppression. This study aims to develop nanosuspension for oral administration of CsA using the wet milling (WM) method one of the top-down technologies. The WM method was optimized by studying the effects of critical process parameters for WM on the particle size (PS), particle size distribution (PDI), and zeta potential (ZP) of nanosuspensions using the Design of Experiment (DoE) approach. Nanosuspension was developed using hydroxypropyl methylcellulose (HPMC) and sodium dodecyl sulfate (SDS) and in vitro characterization studies were performed. In vitro dissolution and in vivo pharmacokinetic studies were conducted with biorelevant media (fasted and fed state simulated fluids) and fasted and fed states in rats, respectively. In vivo immunological studies were also performed. PS, PDI, and ZP values for nanosuspension were approximately 600 nm, 0.4, -25 mV, respectively. The solubility of CsA was increased by 4.5-folds by nanosuspensions. Dissolution studies showed that nanosuspension had higher dissolution than the commercial product in the FeSSIF medium. The pharmacokinetic study indicated that AUC0–24 values of CsA nanosuspension were to be 2.09 and 5.51-fold higher than coarse powder in fasted and fed conditions, respectively. Immunological studies were carried out after oral administration of nanosuspension for 21 days, the ratio of CD4+/CD8+ was found to be more acceptable than the commercial product. These results demonstrated that nanosuspension is a promising approach for increasing the bioavailability and avoiding the food effect on absorption of CsA which one of the highly variable drugs