Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis

PER-1 production in a urinary isolate of Providencia rettgeri

A Providencia rettgeri strain resistant to extended-spectrum cephalosporins and intermediate to aztreonam was isolated from the urine of a patient hospitalized in the urology clinic of SSK Educational Hospital in Ankara. Clavulanic acid restored the activity of extended-spectrum cephalosporins, suggesting that the strain was harboring an extended-spectrum beta-lactamase. Since the PER-1 enzyme is widespread in Turkey, and had been already detected in a related species such as Proteus mirabilis, the Providencia strain was suspected of harboring a PER-1 enzyme, which was indeed detected by PCR. This is the first description in a P. rettgeri isolate of a PER-1 enzyme which is widespread among Acinetobacter baumanni and Pseudomonas aeruginosa strains in Turkey

Evaluation of chitosan based vaginal bioadhesive gel formulations for antifungal drugs

The aim of the present study was to evaluate chitosan as a vaginal mucoadhesive gel base for econazole nitrate and miconazole nitrate. To this aim, different types of chitosan with different molecular masses and viscosity properties [low molecular mass chitosan (viscosity: 20,000 mPa s), medium molecular mass chitosan (viscosity: 200,000 mPa s), high molecular mass chitosan (viscosity: 800,000 mPa s)] have been used. First, rheological studies were conducted on chitosan gels. Mechanical, syringeability and mucoadhesive properties of chitosan gels were determined. Release profiles of econazole nitrate and miconazole nitrate from chitosan gels were obtained and evaluated kinetically. In addition, anticandidal activities of formulations were determined. Finally, vaginal retention of chitosan gels in rats was evaluated by in vivo distribution studies. Based on the results, it can be concluded that gels prepared with medium molecular mass chitosan might be effectively used for different antifungal agents in the treatment of vaginal candidiosis, since it has high mucoadhesiveness, suitable mechanical and release properties with good vaginal retentio

The evaluation of clusters of hospital infections due to multidrug-resistant Salmonella enterica serovar typhimurium in the neonatal unit: a two-year experience

Seven clusters of hospital infection due to Salmonella enterica serovar typhimurium were documented in the neonatology clinic of a children's hospital between April 2002 and March 2004. Eighty-one neonates were infected. Three cases were asymptomatic, 73 cases had gastroenteritis as the only clinical condition, and 5 cases had bacteremia associated with gastroenteritis. All isolates from stool and blood samples (n=86) were identified as Salmonella enterica serovar typhimurium

RESISTANCE TO NEWER BETA-LACTAMS AND RELATED ESBL TYPES IN GRAM-NEGATIVE NOSOCOMIAL ISOLATES IN TURKISH HOSPITALS: RESULTS OF THE MULTICENTRE HITIT STUDY

Increasing resistance due to extended-spectrum beta-lactamases (ESBLs) and multiple resistance mechanisms in gram-negative hospital isolates restrict the role of R-lactam antibiotics in empirical treatment of serious infections. As the prevalence of ESBL producing strains and resistance rates to antimicrobial agents can vary in each center, local surveillance studies are required to guide therapy. In this study, in vitro rates of resistance to ceftriaxone, ceftazidime, cefepime, imipenem, cefoperazone/sulbactam and piperacillin/tazobactam were evaluated in 1196 gram-negative hospital isolates in a multicenter in vitro study with the participation of six different centers in Turkey between the period of June 2004-January 2005. The isolates included Escherichia coli (n= 457), Klebsiella pneumoniae (n= 390), Pseudomonas aeruginosa (n= 194) and Acinetobacter baumannii (n= 155). In addition, frequency of ESBL production and types of enzymes were determined in blood isolates of E.coli and K.pneumoniae. MICs and ESBL production were investigated by E-test (AB Biodisk, Solna) and the results were evaluated by using CLSI breakpoints. PCR analysis was used for typing of the ESBLs. In E.coli, 26% and in K.pneumoniae 32% of the isolates were ESBL producers. Among the blood isolates of E.coli and K.pneumoniae, 31.7% and 33.3% produced ESBLs, respectively. CTX-M (71.4%) was the most prevalent enzyme, followed by TEM (49.4%) and SHV (46,7%) derived enzymes. CTX-M-15 (69.4%) was the most frequent CTX-M type in blood isolates followed by CTX-M-3 (28.6%) and CTX-M-1 (2%). Resistance to imipenem was not observed in E.coli isolates, however it was 1.3% in K.pneumoniae, 28.9% in P.aeruginosa and 52.2% in A.baumannii strains. Resistance to cefoperazone/sulbactam was found as 6%, 17.7%, 27.9% and 41.3% in E.coli, K.pneumoniae, P.aeruginosa and A.baumannii isolates, respectively, whereas resistance rates to piperacillin/tazobactam were 10.2%, 22.3%, 22.7% and 78.7%, respectively. These results indicate that ESBL production and rates of resistance to R-lactam antibiotics are high in hospital isolates of gram-negative bacteria in Turkey, however, they show variations in different hospitals and CTX-M enzymes are prevalent in these isolates

qnrA prevalence in extended-spectrum β-lactamase-positive enterobacteriaceae isolates from Turkey

Quinolone resistance mostly originates from chromosomal mutations. In recent years, however, plasmid-mediated quinolone resistance has been reported in several parts of the world. Plasmid-borne qnrA, qnrB, or qnrS genes are responsible for this kind of resistance. Little is known about the diversity, type, and species range of the qnr genes in Turkey. We screened qnrA, qnrB, and qnrS genes in quinolone-resistant blood culture isolates collected from six different medical centers in Turkey which produced extended-spectrum β-lactamases (ESBLs). Atotal of 78 ESBL-positive isolates were enrolled in this study. Of these, 37 (47.4%) were nalidixic-acid resistant or intermediate. qnrA was found on large plasmids isolated from five (6.4%) of the NalI/R isolates. In three of these, the same plasmid also carried blacCTX-M. Four of the qnrA-positive isolates were Klebsiella pneumoniae from Dokuz Eylul University Hospital, Izmir, and the fifth isolate was Escherichia coli from Istanbul University Hospital. Two of the isolates from Izmir were found by enterobacterial repetitive intergenic consensus sequpnce-PCR to be clonally related, This is the first report on the qnrA prevalence among ESBL-positive blood culture isolates collected from different regions in Turkey. According to our results, plasmid-mediated resistance is a potential problem for the spread of quinolone resistance, and this mechanism could be emerging strongly among the ESBL-positive Enterobacteriaceae in Turkey