Development and Evaluation of Combined Effect Buccal Films for Treatment of Oral Candidiasis.

Buccal film formulations, including antifungal nystatin, anti-inflammatory agent hydrocortisone acetate, and local anesthetic lidocaine hydrochloride for pain relief, were developed. Bioadhesive films were fabricated with hydrophilic polymers, hydroxyethyl cellulose (HEC), and xanthan gum (XG) and dried in the incubator. Textural, swelling, and bioadhesive properties, physicochemical and in vitro release characteristics, and antifungal activities of bioadhesive films were evaluated.Bioadhesive films significantly extended nystatin release by prolonging retention time of the target area formulation while rapidly releasing hydrocortisone acetate and lidocaine HCl, reducing drug administration. The polymer type affected bioadhesion strength and erosion ratio, and XG formulations had more polymer suitability. Consequently, XT-O2 formulation that was prepared with xanthan gum and tween 80, was best for its highest antifungal film activity (20.00 ± 0.07 mm), released nystatin (44.296% ± 1.695), and lowest erosion matrix (36.719% ± 0.249). The selected formulation can be used for compatibility, stability and in vivo studies targeted oral candidiasis infections.

Sequential Measurements of Pentraxin 3 Serum Levels in Patients with Ventilator-Associated Pneumonia: A Nested Case-Control Study.

PURPOSE: The main purpose of this study was to investigate the dynamics of pentraxin 3 (PTX3) compared with procalcitonin (PCT) and C-reactive protein (CRP) in patients with suspicion of ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: We designed a nested case-control study. This study was performed in the Surgical Intensive Care Unit of a tertiary care academic university and teaching hospital. Ninety-one adults who were mechanically ventilated for >48 hours were enrolled in the study. VAP diagnosis was established among 28 patients following the 2005 ATS/IDSA guidelines. RESULTS: The median PTX3 plasma level was 2.66 ng/mL in VAP adults compared to 0.25 ng/mL in non-VAP adults (p < 0.05). Procalcitonin and CRP levels did not significantly differ. Pentraxin 3, with a 2.56 ng/mL breakpoint, had 85% sensitivity, 86% specificity, 75% positive predictive value, and 92.9% negative predictive value for VAP diagnosis (AUC = 0.78). CONCLUSIONS: With the suspicion of VAP, a pentraxin 3 plasma breakpoint of 2.56 ng/mL could contribute to the decision of whether to start antibiotics.

Epidemiology and susceptibility of pathogens from SMART 2011-12 Turkey: evaluation of hospital-acquired versus community-acquired urinary tract infections and ICU- versus non-ICU-associated intra-abdominal infections.

Objectives: To describe the epidemiology and susceptibility of pathogens (including ESBL producers) from hospital-acquired (HA) versus community-acquired (CA) urinary tract infections (UTIs) and ICU- versus non-ICU-associated intra-abdominal infections (IAIs) in Turkey as a part of the SMART study. Methods: : For this report, Gram-negative pathogens (363 from UTIs and 458 from IAIs) were collected in 2011 and 2012 at six hospitals in Turkey. HA versus CA UTIs and ICU- versus non-ICU-associated IAIs were compared for the species isolated, percentage of ESBL-positive isolates by species and susceptibility for overall and individual Gram-negative species. Results: : Escherichia coli was the most common pathogen identified in HA (40.2%) and CA (73.9%) UTIs and ICU-associated (25.8%) and non-ICU-associated (43.3%) IAIs. The rate of ESBL-positive E. coli was significantly higher in HA than in CA UTIs (50.5% versus 38.2%, P < 0.001) and in non-ICU-associated than in ICU-associated IAIs (52.5% versus 29.2%, P = 0.029). Of the drugs studied, only amikacin was active against ≥90% of pathogens in UTIs, while ertapenem, imipenem and amikacin were active against ≥90% of E. coli ; and imipenem, amikacin and cefoxitin were active against ≥90% of Klebsiella pneumoniae in IAIs. Conclusions: Our findings demonstrated that E. coli continues to be the principal pathogen of UTIs and IAIs in Turkey. Along with a high rate of ESBL-positive isolates, high antimicrobial resistance among Gram-negative bacilli from either UTIs or IAIs was noted particularly in the case of HA UTIs and ICU-associated IAIs, with a higher likelihood of carbapenem- or amikacin-based therapy to provide the broadest activity against bacterial pathogens.

Delftia acidovorans: A rare pathogen in immunocompetent and immunocompromised patients.

Delftia acidovorans is an aerobic, nonfermenting Gram-negative bacillus. It is usually a nonpathogenic environmental organism and is rarely clinically significant. Although D acidovorans infection most commonly occurs in hospitalized or immunocompromised patients, there are also several reports documenting the infection in immunocompetent patients. The present article describes a B cell lymphoblastic leukemia patient with D acidovorans pneumonia who was successfully treated with antibiotic therapy. The present report indicates that unusual pathogens may be clinically significant in both immunocompromised and immunocompetent patients. D acidovorans is often resistant to aminoglycosides; therefore, rapid detection of this microorganism is important.

Le Delftia acidovorans est un bacille aérobie à Gram négatif sans pouvoir de fermentation. C'est un organisme généralement non pathogène présent dans l'environnement, qui est rarement significatif sur le plan clinique. Même si l'infection à D acidovorans s'observe surtout chez des patients hospitalisés ou immunodéprimés, plusieurs rapports le signalent chez des patients immunocompétents. Le présent article décrit un patient atteint d'une leucémie lymphoïde de type B compliquée par une pneumonie à D acidovorans éradiquée par antibiothérapie. D'après le présent rapport, des agents pathogènes inhabituels peuvent être cliniquement significatifs à la fois chez les patients immunodéprimés et chez les patients immunocompétents. Puisque le D acidovorans résiste souvent aux aminosides, il est important de le déceler rapidement.

Biodegradable microspherical implants containing teicoplanin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis.

BACKGROUND: The aim of this study was to prepare poly(d,l-lactide-co-glycolide) (PLGA) microspherical implants containing teicoplanin (TCP) using a double emulsion solvent evaporation method and to evaluate its efficacy for the local treatment of chronic osteomyelitis. METHODS: The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency and in vitro release assessments of the formulations were carried out. Sterile TCP­PLGA microspheres were implanted in the proximal tibia of rats with methicillin resistant Staphylococcus aureus (MRSA) osteomyelitis. After 3 weeks of treatment, bone samples were analysed with a microbiological assay and evaluated histopathologically. RESULTS: Microspheres between the size ranges of 2.01 and 3.91 µm were obtained. Production yield of all formulations was found to be higher than 82% and encapsulation efficiencies of 33.6­69.8% were obtained. DSC thermogram showed that the TCP was in an amorphous state in microspheres. In vitro drug release studies had indicated that the drug release rate of microspheres was decreased upon increasing the polymer:drug ratio. Based on the in vivo data, rats treated with implants and intramuscular injection showed 1.7 × 10(3) ± 1.3 × 10(3) and 5.8 × 10(4) ± 5.3 × 10(4) colony forming unit of MRSA in 1 g bone samples (CFU/g), respectively (P < 0.01). CONCLUSIONS: The in vitro and in vivo studies had shown that the TCP­PLGA microspheres were effective for the treatment of chronic osteomyelitis in an animal experimental model. Hence, these microspheres may be potentially useful in the clinical setting with the need for further investigation for optimal dosing of TCP­PLGA microspheres.

Preparation and Characterization of Doripenem-Loaded Microparticles for Pulmonary Delivery.

Background: Pneumonia is a bacterial lower respiratory tract infection that has a high morbidity rate. The gram-negative pathogen Pseudomonas aeruginosa is a significant cause of nosocomial infections and ventilator-associated pneumonias and is mainly treated by carbapenems. Doripenem is a carbapenem drug, which has a broad-spectrum antibacterial activity. The aim of this study was to develop doripenem-loaded chitosan microparticles for pulmonary administration to provide more efficient treatment for pneumonia. Methods: Ionotropic gelation and the spray-drying method were used to obtain doripenem-loaded chitosan microparticles with different lactose, trehalose, and L-leucine concentrations. Physicochemical characteristics, in vitro drug release properties, and aerodynamics properties were investigated and in vitro antimicrobial susceptibility tests of the formulations were performed. Assessment of aerodynamic properties of the powders, including Mass Median Aerodynamic Diameter, size distribution, and fine particle fraction (FPF), were performed using a Next Generation Impactor. Cytotoxicity of the fabricated microparticles was assessed using the Calu-3 cell airway epithelial cell line. Results: Optimum microparticles were produced using a combination of ionotropic gelation and spray-drying methods. Spray-dried microparticle production yield was relatively high (74.03% ± 3.88% to 98.23% ± 1.70%). Lactose, trehalose, and L-leucine were added to the formulation to prevent aggregation produced by the ionotropic gelation spray-drying method. Each formulation's encapsulation efficiency was above 78.98% ± 2.37%. The doripenem-loaded microparticle mean diameter ranged from 3.8 ± 0.110 to 6.9 ± 0.090 µm. Microparticles with 20% (w/w) L-leucine had the highest FPF ratio indicating the best aerosolization properties of the formulations. The efficacy of the formulations as an antibacterial agent was increased by forming doripenem-loaded microparticles compared to blank microparticles. P. aeruginosa showed the same susceptibility to all doripenem-loaded microparticle formulations. Cell viability of microparticles was between 70% ± 0.08% and 90% ± 0.04% at 0.5 and 10 mg/mL concentration, respectively. Conclusions: Doripenem-loaded microparticles, produced using a combination of ionotropic gelation and spray-drying methods, are suitable for pulmonary drug delivery based on their particles size, zeta potential, cytotoxicity and high production yield. To our knowledge, this is the first study that microparticles containing doripenem were produced and characterized.

Influence of multidrug resistant organisms on the outcome of diabetic foot infection.

OBJECTIVES: We described the clinical outcomes of the diabetic patients who had foot infections with multidrug resistant organisms. METHODS: We included the patients with diabetic foot infections (DFI) from 19 centers, between May 2011 and December 2015. Infection was defined according to IDSA DFI guidelines. Patients with severe infection, complicated moderate infection were hospitalized. The patients were followed-up for 6 months after discharge. RESULTS: In total, 791 patients with DFI were included, 531(67%) were male, median age was 62 (19-90). Severe infection was diagnosed in 85 (11%) patients. Osteomyelitis was diagnosed in 291(36.8%) patients. 536 microorganisms were isolated, the most common microorganisms were S. aureus (20%), P. aeruginosa (19%) and E. coli (12%). Methicillin resistance (MR) rate among Staphylococcus aureus isolates was 31%. Multidrug resistant bacteria were detected in 21% of P. aeruginosa isolates. ESBL (+) Gram negative bacteria (GNB) was detected in 38% of E. coli and Klebsiella isolates. Sixty three patients (8%) were re-hospitalized. Of the 791 patiens, 127 (16%) had major amputation, and 24 (3%) patients died. In multivariate analysis, significant predictors for fatality were; dialysis (OR: 8.3, CI: 1.82-38.15, p=0.006), isolation of Klebsiella spp. (OR:7.7, CI: 1.24-47.96, p=0.028), and chronic heart failure (OR: 3, CI: 1.01-9.04, p=0.05). MR Staphylococcus was detected in 21% of the rehospitalized patients, as the most common microorganism (p<0.001). CONCLUSION: Among rehospitalized patients, methicillin resistant Staphylococcus infections was detected as the most common agent, and Klebsiella spp. infections were found to be significantly associated with fatality.

A case of Budd-Chiari syndrome with Behcet's disease and oral contraceptive usage.

We present a case of Budd-Chiari syndrome (BCS) having two risk factors, Behcet's disease (BD) and oral contraceptive (OC) usage. A 33-year-old woman with BD was admitted to the Emergency Unit with nausea, vomiting, abdominal pain, abdominal distention, and confusion started 12 days ago before admission. Since the patient was in a shock state, she was taken to the Intensive Care Unit (ICU) with the suspicion of abdomen-originated sepsis. Abdominal ultrasound showed massive hepatosplenomegaly and moderate ascites. Abdominal MRI revealed an inferior vena cava (IVC) obstruction starting above the renal veins and diffuse thrombosis of the right and medial hepatic veins. An extensive thrombosis of the IVC and the hepatic veins (BCS) which led to shock was diagnosed. In addition to BD, the unnotified OC usage for a year by the patient without her doctor's knowledge was recognized as possible precipitating factor of BCS. Pulse methylprenisolone was started for three consecutive days to treat active BD-induced vasculitis. IVC digital subtraction angiography (DSA) showed occlusion of the IVC below the hepatic veins with extensive collateral circulation originating at the occlusion level suggesting that obliteration had a subacute or chronic course. Since intralesional thrombolytic therapy failed, the patient was transferred to a liver transplantation center. While waiting for an appropriate donor, the patient died due to hepatic failure. Since BCS is mortal and deemed multi-factorial, every patient with a thrombotic risk factor such as BD should be questioned for other possible causes of thrombosis.

[In vitro susceptibility of respiratory isolates of Streptococcus pneumoniae and Streptococcus pyogenes to telithromycin and 11 other antimicrobial agents: Turkish results of e-BASKETT-II surveillance study]. / Solunum yolu enfeksiyonu etkenleri Streptococcus pneumoniae ve Streptococcus pyogenes'in telitromisin ve 11 antimikrobik ilaca in vitro duyarliligi: e-BASKETT-II sürveyans çalismasinin Türrkiye sonuçlari.

In respiratory tract infections, therapy is often empirical and there is a need for local data on the rate of resistance to available antimicrobials. In this multicentre study which is a part of the international e-BASKETT-II surveillance study, respiratory isolates of Streptococcus pneumoniae (n=260) and Streptococcus pyogenes (n=312) collected between September 2002 and June 2003 from 18 hospitals in Turkey were tested against penicillin G, amoxicillin, cefuroxime, ceftriaxone, erythromycin, clarithromycin, azithromycin, clindamycin, telithromycin, tetracycline, levofloxacin and vancomycin. Antibiotic susceptibilities were determined with disk diffusion method and confirmed with broth dilution method following the CLSI guidelines. Isolates which were resistant to erythromycin were genotyped by polymerase chain reaction. In S. pneumoniae 11.5% of the isolates were highly and 22.7% were intermediately resistant to penicillin. Rate of resistance to erythromycin, clarithromycin, azithromycin was 17.3%, and 21.5% of the isolates were resistant to tetracycline. Resistance to levofloxacin and vancomycin was not observed and only one isolate was found intermediately resistant (MIC=2 microg/mL) to telithromycin. Genotypes in erythromycin-resistant isolates were ermB (77.8%), mefA (17.8%) and ermB+mefA (2.2%). S. pyogenes isolates were uniformly susceptible to beta-lactams and vancomycin, and only one isolate was intermediately resistant to levofloxacin. Macrolide resistance was observed in 1.3% of the isolates and three out of these harboured the mefA gene. One isolate with an MIC of 4 microg/mL for telithromycin had ermB gene. Telithromycin has demonstrated a good in vitro activity against macrolide-resistant respiratory tract isolates. As a result, e-BASKETT-II surveillance study has been one of the most extensive in vitro studies comparing telithromycin to available antimicrobial agents for respiratory tract infections in Turkey.

Characterization of biodegradable chitosan microspheres containing vancomycin and treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with prepared microspheres.

The biodegradable chitosan microspheres containing vancomycin hydrochloride (VANCO) were prepared by spray drying method with different polymer:drug ratios (1:1, 2:1, 3:1 and 4:1). Thermal behaviour, particle size and distribution, morphological characteristics, drug content, encapsulation efficiency, in vitro release assessments of formulations have been carried out to obtain suitable formulation which shows sustained-release effect when implanted. Sterilized VANCO loaded microspheres were implanted to proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. Intramuscular (IM) injection of VANCO for 21 days was applied to another group for comparison. After 3 weeks of treatment, bone samples were analysed with a microbiological assay. According to the results, encapsulation efficiency and yield of microspheres in all formulations were higher than 98% and 47%, respectively. Particle sizes of microspheres were smaller than 6 microm. All microsphere formulations have shown sustained-release effect. In vitro drug release rate decreased due to the increase in polymer:drug ratio but no significant difference was seen between these results (p>0.05). Based on our in vivo data, rats implanted VANCO-loaded chitosan microspheres and administered IM injection showed 3354+/-3366 and 52500+/-25635 colony forming unit of MRSA in 1g bone samples (CFU/g), respectively. As a result, implanted VANCO-loaded microspheres were found to be more effective than IM route for the treatment of experimental osteomyelitis.

International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections.

BACKGROUND: Commonly encountered nosocomially acquired gram-negative bacteria, especially Klebsiella pneumoniae, produce extended-spectrum beta-lactamases (ESBLs) as an antibiotic resistance mechanism. OBJECTIVE: To determine whether microbiology laboratories should report the presence of ESBLs and to establish the infection-control implications of ESBL-producing organisms. DESIGN: Prospective observational study. SETTING: 12 hospitals in South Africa, Taiwan, Australia, Argentina, the United States, Belgium, and Turkey. PATIENTS: 440 patients with 455 consecutive episodes of K. pneumoniae bacteremia between 1 January 1996 and 31 December 1997; of these, 253 episodes were nosocomially acquired. MEASUREMENTS: The K. pneumoniae isolates were examined for the presence of ESBLs. Pulsed-field gel electrophoresis was used to analyze the molecular epidemiology of nosocomial bacteremia with ESBL-producing K. pneumoniae. RESULTS: Overall, 30.8% (78 of 253) episodes of nosocomial bacteremia and 43.5% (30 of 69) episodes acquired in intensive care units were due to ESBL-producing organisms. After adjustment for potentially confounding variables, previous administration of beta-lactam antibiotics containing an oxyimino group (cefuroxime, cefotaxime, ceftriaxone, ceftazidime, or aztreonam) was associated with bacteremia due to ESBL-producing strains (risk ratio, 3.9 [95% CI, 1.1 to 13.8]). In 7 of 10 hospitals with more than 1 ESBL-producing isolate, multiple strains with the same genotypic pattern were observed, indicating patient-to-patient spread of the organism. CONCLUSIONS: Production of ESBLs by Klebsiella pneumoniae is a widespread nosocomial problem. Appropriate infection control and antibiotic management strategies are needed to stem the spread of this emerging form of resistance.

Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases.

The prevalence of extended-spectrum beta -lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL-producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem (primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.

A prospective study: inflammation, infection and comorbidity in patients on long-term dialysis.

BACKGROUND: The goal of this study was to identify inflammatory and infectious markers and their roles in mortality. METHODS: We enrolled 111 patients on haemodialysis (HD) and collected data at three time points (baseline, 33 and 76 months). RESULTS: Rates of Chlamydophila pneumoniae IgG, CRP ≥3 mg/l, ESR >50 mm/hour and fibrinogen >4 g/l were, respectively, 63.1%, 60.4%, 48.6% and 42.3%. Mortality was 21.6% and 43.2% at 33 and 76 months where 58.3% of all deaths were cardiocerebrovascular (CCV) related. Non-survivors were older than survivors. Univariate analysis showed diabetes mellitus (DM) and cerebrovascular accident (CVA) as important for the 33-month all-cause mortality, and CRPlog , fibrinogen, ESR >50 mm/hour, cardiovascular disease (CVD) and DM for the 76-month all-cause mortality. CVA was meaningful for the 33-month CCV mortality, and CVD, DM and ESR >50 mm/hour for the 76-month CCV mortality. Kaplan-Meier revealed poorer survival for patients with ESR >50 mm/hour at 76 months. Cox regression showed CVD, CVA and age as mortality predictors. CONCLUSION: Age, CVD and CVA are predictors for mortality in patients on HD patients, but the presence of C. pneumoniae IgG and inflammation are not.

Bioadhesive tablets containing cyclodextrin complex of itraconazole for the treatment of vaginal candidiasis.

Itraconazole (ITR) is commonly used in the treatment of Candida infections. It has a nephrotoxic effect and low bioavailability in patients who suffer from renal insufficiency, and its poor solubility in water makes ITR largely unavailable. Cyclodextrins (CyDs) are used to form inclusion complexes with drugs to improve their aqueous solubility and to reduce their side effects. In this study, ITR was complexed with γ-cyclodextrin (γ-CyD), hydroxypropyl-ß-cyclodextrin (HP-ß-CyD), methyl-ß-cyclodextrin (Met-ß-CyD) and sulphobutyl ether-ß-cyclodextrin (SBE7-ß-CyD) to increase its water solubility and to reduce the side effects of the drug without decreasing antifungal activity. Complex formation between ITR and CyDs was evaluated using SEM, (1)H NMR and XRD studies. The antifungal activity of the complexes was analyzed on Candida albicans strains, and the susceptibility of the strains was found to be higher for the ITR-SBE7-ß-CyD complex than for the complexes that were prepared with other CyDs. Vaginal bioadhesive sustained release tablet formulations were developed using the ITR-SBE7-ß-CyD inclusion complex to increase the residence time of ITR in the vagina, thereby boosting the efficacy of the treatment. The swelling, matrix erosion and bioadhesion properties of formulations and the drug release rate of these tablets were analyzed, and the most therapeutically effective vaginal formulation was determined.

Outcomes of fecal carriage of extended-spectrum ß-lactamase after transrectal ultrasound-guided biopsy of the prostate.

OBJECTIVE: To determine the prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (PE) fecal carriage in patients that undergo transrectal ultrasonography-guided biopsy (TRUSbx) and its relationship with post-biopsy infections. METHODS: A prospective clinical study in 4 different tertiary hospitals between 2008 and 2010 was conducted. Four hundred men with sterile urine who were to undergo a TRUSbx because of the suspicion of prostate cancer were included and followed for 14 days after biopsy. Rectal swab culture specimens were acquired immediately before the procedure. Demographic data, prophylaxis choice, quinolone or any other antibiotic consumption within the past 2 months, history of prostatitis, repeat biopsy, intensive care unit admission, hospitalization, urethral catheterization, diabetes mellitus (DM), and steroid usage were recorded. RESULTS: ESBL carriage was detected in 19% of patients and quinolone use within the last 2 months; other antibiotic use within the last 2 months and DM were found to be significantly associated (P <.05). Symptomatic urinary tract infection (UTI) on the third day after biopsy was seen in 9% of patients and was associated with fluoroquinolone (FQ) consumption before biopsy. Although ESBL-PE carriage was associated with post-biopsy UTI symptoms, it was not found to be associated with post-biopsy symptomatic UTI. Urosepsis was seen in 2 patients (0.5%) after biopsy, and both the patients were ESBL-PE carriers. CONCLUSION: The presence of ESBL-PE was associated with DM and FQ consumption before biopsy. ESBL-PE carriage was associated with a high rate of post-biopsy UTI symptoms requiring further elucidation; however, it was not associated with microbiologically proven infections. FQ consumption before TRUSbx was also associated with post-biopsy infections.

Preparation and characterisation of natamycin: gamma-cyclodextrin inclusion complex and its evaluation in vaginal mucoadhesive formulations.

Novel formulations of vaginal bioadhesive tablets were prepared where the natamycin was complexed with gamma-cyclodextrin (NT-gamma CyD) to increase the solubility and stability of NT in aqueous solutions and reduce the side effects of the drug without decreasing antimycotic activity. Favourable interactions between the NT and gamma CyD and formation of the 1:1 inclusion complex were observed. The MIC(90) of both NT alone and NT-gamma CyD complexes were below 0.0313 microg mL(-1), suggesting that complexation with gamma CyD has effectively increased the antimycotic activity of NT, thus indicating the clinical usefulness of NT-gamma CyD complexes. The sustained drug release of NT was achieved to over 8 h periods by altering the polymer component of formulations which was responsible for differences in water absorption and erosion behaviour of the tablets. Bioadhesion studies have clearly indicated that enhancement of mucoadhesion was achieved by inclusion of Carbopol 934P and by tailoring the ratio of Carbopol 934P in the formulation, a high mucoadhesion to vaginal mucosa can be achieved. Hence, the formation of complex between NT and gamma CyD and effective combination with polymers attain a bioadhesive and sustained release formulation of NT suitable for vaginal delivery and the effective treatment of Candida infections.

Sodium fusidate-poly(D,L-lactide-co-glycolide) microspheres: preparation, characterisation and in vivo evaluation of their effectiveness in the treatment of chronic osteomyelitis.

PURPOSE: The aim of this study was to prepare poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing sodium fusidate (SF) using a double emulsion solvent evaporation method with varying polymer:drug ratios (1:1, 2.5:1, 5:1) and to evaluate its efficiency for the local treatment of chronic osteomyelitis. METHODS: The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency and in vitro release assessments of the formulations had been carried out. Sterilized SF-PLGA microspheres were implanted in the proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. After 3 weeks of treatment, bone samples were analysed with a microbiological assay. RESULTS: PLGA microspheres between the size ranges of 2.16-4.12 microm were obtained. Production yield of all formulations was found to be higher than 79% and encapsulation efficiencies of 19.8-34.3% were obtained. DSC thermogram showed that the SF was in an amorphous state in the microspheres and the glass transition temperature (T(g)) of PLGA was not influenced by the preparation procedure. In vitro drug release studies had indicated that these microspheres had significant burst release and their drug release rates were decreased upon increasing the polymer:drug ratio (p < 0.05). Based on the in vivo data, rats implanted with SF-PLGA microspheres and empty microspheres showed 1987 +/- 1196 and 55526 +/- 49086 colony forming unit of MRSA in 1 g bone samples (CFU/g), respectively (p < 0.01). CONCLUSION: The in vitro and in vivo studies had shown that the implanted SF loaded microspheres were found to be effective for the treatment of chronic osteomyelitis in an animal experimental model. Hence, these microspheres may be potentially useful in the clinical setting.

A survey of antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae in Turkey, 2004 2005.

OBJECTIVES: To determine the prevalence of antimicrobial resistance among Streptococcus pneumoniae and Haemophilus influenzae isolated in Turkey as part of Survey Of Antibiotic Resistance, a surveillance programme in the Africa and Middle East region examining the antimicrobial susceptibility of key bacterial pathogens involved in community-acquired respiratory tract infections (CARTIs). METHODS: Susceptibility was evaluated against a range of antimicrobial agents using disc diffusion and Etest methods. RESULTS: Six centres in five cities collected 301 S. pneumoniae and 379 H. influenzae isolates between October 2004 and November 2005. Among S. pneumoniae, the prevalence of isolates with intermediate susceptibility (MICs 0.12-1 mg/L) and resistance to penicillin (MICs >or=2 mg/L) was 24.6% and 7.6%, respectively; there was a wide variation between cities (2.4% to 36.9% intermediate and 0% to 23.8% resistant phenotypes). Macrolide-azalide resistance rates exceeded those of penicillin resistance in all cities. Overall, 5.0% of isolates were co-resistant to penicillin and erythromycin and 10.0% were multidrug-resistant (joint resistance to erythromycin, co-trimoxazole and tetracycline). Agents tested to which over 90% of countrywide S. pneumoniae isolates remained susceptible were amoxicillin/clavulanate (98.7%), chloramphenicol (94.7%) and cefprozil (90.6%). Overall, the percentage of H. influenzae isolates producing beta-lactamase was 5.5%, differing widely across the country with the highest prevalence of beta-lactamase production detected in Trabzon (14.0%) and no beta-lactamase-positive isolates found in Izmir. H. influenzae had the highest per cent susceptibility to amoxicillin/clavulanate (99.5%) and ofloxacin (99.2%) while >20% were resistant to co-trimoxazole. CONCLUSIONS: Prevalence of penicillin and macrolide-azalide resistance among S. pneumoniae appears to be on the increase in Turkey while overall beta-lactamase production in H. influenzae remains relatively low. To adequately monitor the spread of drug-resistant phenotypes among these two important CARTI pathogens, ongoing collection of resistance surveillance data is required-where possible locally as resistance patterns can vary substantially between cities and institutions.

Antibiotics are not needed during tube thoracostomy for spontaneous pneumothorax: an observational case study.

BACKGROUND: Usefulness of prophylactic antibiotics following tube thoracostomy remains controversial in the literature. In this study, we aimed to investigate the consequences of closed tube thoracostomy for primary spontaneous pneumothorax without the use of antibiotics. METHODS: One-hundred and nineteen patients underwent tube thoracostomy for primary spontaneous pneumothorax. None of them received prophylactic antibiotic treatment. Eight patients with prolonged air leak undergoing either video assisted thoracoscopic surgery or thoracotomy were excluded. RESULTS: Of the remaining 111 (104 male and 7 female), 28 (25%) patients developed some induration around the entry site of chest tube that settled without further treatment. White blood cell count was high without any other evidence of infection in 12 (11%) patients and returned to its normal levels before discharge home in all. There was also some degree of fever not lasting for more than 48 hours in 8 (7%) patients. Bacterial cultures from suspected sites did not reveal any significant growth in these patients. CONCLUSION: Prophylactic antibiotic treatment seems avoidable during closed tube thoracostomy for primary spontaneous pneumothorax. This policy was not only cost-effective but also prevented our patients from detrimental properties of unnecessary antibiotic use, such as development of drug resistance and undesirable side effects.