Ocular penetration of topically applied 1% tigecycline in a rabbit model.

AIM: To evaluate ocular penetration of topically applied 1% tigecycline. METHODS: Forty-two New Zealand White rabbits were divided into 3 groups. A 50 µL drop of 1% tigecycline was administered in group 1. In groups 2 and 3, the drop was administered every 15min for 60min (keratitis protocol). Aqueous humor samples in groups 1 and 2 were collected under general anesthesia at 15, 30, 45, 60, 120, and 180min after the last drop. All animals in group 3 were euthanatized. Cornea, vitreous and blood samples were collected 60 and 120min after the last drop. Tigecycline concentrations were measured using high performance liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: The peak aqueous humor tigecycline concentration [mean 0.73±0.14 mg/L (SD) and 2.41±0.14 mg/L, respectively] occurred 45min after topical drug application in groups 1 and 2. Group 3 mean values in the cornea, and vitreous, were 3.27±0.50 µg/g, and 0.17±0.10 mg/L at 60min and 3.17±0.77 µg/g and 0.20±0.07 mg/L at 120min, respectively. Tigecycline serum concentrations were negligible. CONCLUSION: Tigecycline levels in the aqueous humor in groups 1 and 2, and in the cornea in group 3 exceeded the minimum inhibitory concentrations of most gram-positive organisms that cause bacterial keratitis and endophthalmitis.

Daptomycin versus Vancomycin in an Enterococcus faecalis Endophthalmitis Rabbit Model.

PURPOSE: To compare bactericidal activities of daptomycin (DAP) and vancomycin (VAN) in an experimental rabbit model of Enterococcus faecalis endophthalmitis. MATERIALS AND METHODS: The right vitreous cavities of 24 New Zealand rabbits were inoculated with 100 colony-forming units of E. faecalis; and after 24 h, rabbits were randomly divided into three groups. DAP group (n = 8, 0.2 mg/0.05 ml intravitreally), VAN group (n = 8, 1 mg/0.05 ml intravitreally) and balanced salt solution group (BSS, n = 8, 0.05 ml intravitreally). Clinical examination scores were recorded, and vitreous aspirates were obtained for microbiological analysis on days 0, 1, 2, 3 and 4. Rabbits were sacrificed, and the eyes were enucleated for histopathological assessment. RESULTS: There was no difference between the DAP, VAN and BSS groups in terms of the clinical grading of endophthalmitis 24 h after the inoculation. The bacterial counts were similar between the VAN and DAP groups except on day 1, where it was significantly lower than those in the VAN group (p = 0.003). On day 4, 62% of the eyes treated with DAP, and 50% of the eyes treated with VAN were sterilized. All of the eyes from the BSS group showed increasing bacterial growth from day 0 to day 4. There was no difference between the DAP and VAN groups in terms of the histopathological and clinical examination scores, while they were significantly lower than those in the BSS group. CONCLUSIONS: This study demonstrates evidence of the effectiveness of DAP for the treatment of experimental E. faecalis endophthalmitis.

Serum Levels of Annexin A2 as a Candidate Biomarker for Hepatic Fibrosis in Patients With Chronic Hepatitis B.

BACKGROUND: Hepatologists have studied serologic markers of liver injury for decades. Annexins are a prominent group of such markers and annexin A2 (AnxA2) is one of the best characterized annexins. AnxA2 inhibits HBV polymerase among other functions. Its expression is up-regulated in regenerative hepatocytes. OBJECTIVES: To determine if serum AnxA2 level has a role in estimating liver damage in chronic HBV infection and investigate whether AnxA2 levels correlate with hepatic fibrosis. PATIENTS AND METHODS: This study included 173 patients with chronic hepatitis B (CHB) and 51 healthy controls. Liver fibrosis was graded histologically on liver biopsy samples. Blood samples were taken from patients during biopsy and serum AnxA2 levels were measured with ELISA. RESULTS: In a group of adult patients with CHB, AnxA2 values were far higher than those of the control group (P = 0.001). When we assessed AnxA2 levels based on fibrosis stages, serum AnxA2 levels of patients with early stage fibrosis (stages 1 - 3) were significantly higher than those of patients with advanced stage fibrosis (stages 4 - 5; P = 0.001). CONCLUSIONS: AnxA2 is a useful biomarker for early stage fibrosis in patients with CHB.

Clearance of intravitreal daptomycin in uveitis-induced rabbit model.

PURPOSE: To investigate the elimination rate of daptomycin after intravitreal injection in uveitis-induced rabbits. MATERIALS AND METHODS: Intravitreal injection of the single dose of 200 µg/0.05 mL daptomycin was administered to rabbits starting 24 h after induction of uveitis by an intravitreal endotoxin injection. Aqueous humor and vitreous humor samples of eight eyes per time point were collected at selected time intervals (1, 3, 6, 24, 48, 72 and 96 h), and the in vitreous half-life was calculated. Daptomycin concentrations in vitreous and aqueous humor were assayed with high-performance liquid chromatography. RESULTS: The vitreous concentration was noted to decline slowly with time. The mean vitreous concentration was 23.25 ± 10.99 µg/mL and 11.10 ± 3.33 µg/mL at 96 h in inflamed and normal eyes, respectively. The vitreous daptomycin concentration showed an exponential decay with a half-life of 25.67 h in normal eyes and 34.6 h in inflamed eyes. The aqueous levels of daptomycin in normal eyes were low but remained significantly higher than those of inflamed eyes. CONCLUSIONS: Given that the injected dose corresponds to several times the minimum inhibitory concentrations of organisms most involved in endophthalmitis, and that therapeutic levels are present up to 96 h after injection, intravitreal daptomycin should be considered for the treatment of endophthalmitis caused by Gram-positive bacteria.

Evaluation of 48-week response of treatment-naive chronic hepatitis B patients to 0.5 mg/day entecavir.

AIM: The hepatitis B virus (HBV) is an important healthcare problem. Chronic hepatitis B infection may present with a wide range of manifestations from inactive carrier state to cirrhosis and hepatocellular cancer. Therefore, treatment is very important in chronic hepatitis B. In this study, the treatment results of 199 chronic hepatitis B patients taking entecavir 0.5 mg/day for 48 weeks were evaluated. MATERIALS AND METHODS: This study retrospectively evaluated data of 199 treatment-naive chronic hepatitis B patients who were treated with entecavir. RESULTS: Of the 199 treatment-naive chronic hepatitis B patients, 141 (70.9%) were males and 58 (29.1%) were females, and mean age of the whole group was 37.5 ± 12.1 years. HBeAg was positive in 91 (45.7%) and antiHBe was positive in 108 (54.3%) patients. Mean HBV DNA value was 666,449,365.5 ± 2,759,013,996.9 IU/mL, mean ALT value was 112.1 ± 95.7 U/L, and mean AST value was 95.3 _ 71.2 U/L. At week 24 of the treatment, HBV DNA levels were below 50 IU/mL in 56% of the HBeAg-positive and 76% of the HBeAg-negative patients. At week 48 of the treatment, HBV DNA levels were below 50 IU/mL in 79% of the HBeAg-positive and 87% of the HBeAg- negative patients. At week 24, ALT had normalized in 72% of the HBeAg-positive and 79% of the HBeAg-negative patients. At week 48, ALT had normalized in 89% of the HBeAg-positive and 88% of the HBeAg-negative patients. AntiHBe seroconversion was seen in 2 of 91 patients (2.2%), but the loss of HBsAg was never observed. CONCLUSION: The 48-week entecavir treatment at a dose of 0.5 mg/day was shown to be effective both for HBeAg-positive and negative patients.

Diagnostic clues for spondylitis in acute brucellosis.

OBJECTIVES: To determine the diagnostic factors for brucellar spondylitis. METHODS: This retrospective study included 227 consecutive brucellosis patients admitted to the Infectious Diseases and Clinical Microbiology clinics of Adiyaman State Hospital and Adiyaman 82 nd Year State Hospital, Adiyaman, Turkey between January 2010 and December 2012. Acute brucellosis was diagnosed by standard tube agglutination test and/or growth of Brucella spp. in appropriately prepared culture media (Bactec). Brucellar spondylitis was diagnosed and followed-up with contrast-enhanced magnetic resonance imaging. RESULTS: Among the 227 brucellosis patients included, 88 (38.8%) were male, and 139 (61.2%) were female. Brucellar spondylitis was detected in 54 patients (23.7%). Brucellar spondylitis patients had higher mean age, higher fever, and higher blood culture positivity rate when compared with brucellosis patients (p=0.001, p=0.001, and p=0.001). Logistical regression analysis determined that male gender (OR: 3.006), older age (OR: 1.025), erythrocyte sedimentation rate (ESR) (OR: 1.067), high fever at the time of admission (OR: 2.550), and positive blood cultures for Brucella spp. (OR: 4.003) values were independently associated with brucellar spondylitis. However, high C-reactive protein (CRP) levels (OR: 0.971) were not found as a risk factor for brucellar spondylitis. CONCLUSIONS: The results of this study shows that the risk of developing brucellar spondylitis is high in patients with acute brucellosis, who are at advanced age, who have high fever, that have Brucella spp. growth in their blood culture that has a high ESR value, and who are male.

Pharmacokinetics of intravenously administered tigecycline in eye compartments: an experimental study.

PURPOSE: The purpose of this study was to evaluate the ocular distribution of intravenously administered tigecycline in a rabbit uveitis model. METHODS: Tigecycline, which has a broad spectrum of activity against many gram-positive, gram-negative, and anaerobic organisms, was given intravenously to rabbits at 7 mg/kg of body weight starting 24 h after induction of uveitis by intravitreal endotoxin injection. Tigecycline concentrations were determined by high performance liquid chromatography-mass spectrometry (LC-MS/MS) assay in the aqueous humor, vitreous humor, and plasma 1, 3, 6, and 24 h after administration of a single dose. RESULTS: The maximum concentrations were found within 1 h after the end of the intravenously given tigecycline, and were 1,308.60 ± 301.76 ng/mL in plasma, 181.40 ± 51.32 ng/mL in vitreous humor and 145.00 ± 55.29 ng/mL in aqueous humor of the inflamed eye. After 24 h, no drug was detectable in the aqueous and vitreous of the normal eyes, whereas small amounts of drug were detectable in inflamed eyes and in plasma. CONCLUSIONS: Tigecycline did not reach therapeutically significant levels in the aqueous and the vitreous humor of rabbit eyes. The findings suggest a limited role for intravenously administered tigecycline in the treatment of bacterial endophthalmitis.

Ocular penetration of intravenously administered colistin in rabbit uveitis model.

PURPOSE: The purpose of this study was to evaluate the ocular distribution of intravenously administered colistin in a rabbit uveitis model. METHODS: Colistin, a polypeptide antibiotic against the multidrug-resistant (MDR) Gram-negative organisms, was given intravenously to rabbits at 5 mg/kg of body weight starting 24 h after induction of uveitis by intravitreal endotoxin injection. Colistin concentrations were determined by high-performance liquid chromatography-mass spectrometry assay in the aqueous humor, vitreous humor, and plasma 0.5, 3, 6, and 24 h after administration of a single dose. RESULTS: The maximum colistin concentrations (mean±standard deviation) were found 0.5 h after the end of the intravenous administration and were 9.48±2.0 µg/mL in plasma and 0.62±0.07 µg/mL in the aqueous humor of the inflamed eye. After 24 h, no drug was detectable in the aqueous of the inflamed eyes. Colistin was undetectable in the aqueous of contralateral normal eyes at all time points. Drug concentrations in all the vitreous samples from both inflamed and normal eyes were undetectable, except at the 3-h inflamed eye group, and a colistin concentration of 0.02±0.01 µg/mL was found. Plasma levels of colistin fell to 0.93±0.07 and 0.24±0.08 µg/mL, after 3 and 6 h, respectively, and were not detectable 24 h after the given dose. CONCLUSIONS: In our model, colistin did not reach therapeutically relevant levels in the aqueous and in the vitreous humor of rabbit eyes. The findings suggest a limited role for intravenously administered colistin in the treatment of Gram-negative bacterial endophthalmitis.

Evaluation of the relation between hepatic fibrosis and basic laboratory parameters in patients with chronic hepatitis B fibrosis and basic laboratory parameters.

BACKGROUND: The hepatitis B virus is an important healthcare problem. According to current clinical practice, a liver biopsy is required for the diagnosis and treatment of chronic liver disease. However, a liver biopsy is an invasive, inconvenient procedure, which requires an expert pathologist opinion. Therefore requirement of biochemical tests, which are considered to indicate hepatic fibrosis and may be repeated easily, increases gradually today. OBJECTIVES: This study evaluated the correlation between hepatic fibrosis and routine laboratory values in patients with chronic hepatitis B. PATIENTS AND METHODS: The files of 456 patients with CHB (chronic hepatitis B) who were referred to the infectious diseases and clinical microbiology clinic between January 2009 and March 2012 were screened retrospectively. Liver biopsy samples were examined according to Ishak scoring. Laboratory parameters and histopathology reports were recorded, and correlations between the fibrosis grade and laboratory parameters were analyzed. RESULTS: There were 320 male and 136 female patients, with a mean age 36.7 ± 12.1 years. According to liver biopsy results, a low fibrosis score (stage 0-2) was detected in 281 patients (61.6%), and a high fibrosis score (stage 3-5) was detected in 175 patients (38.4%). Patients with a high fibrosis score had significantly higher ALT (alanine amino transferase), AST (aspartate aminotransferase), and HBV-DNA values and a significantly lower platelet count compared with those with a low fibrosis score (P = 0.001, 0.001, 0.025, and 0.001, respectively). A positive correlation was detected between the fibrosis score and age, BMI, HAI, ALT, and AST values, and a negative correlation was detected between the fibrosis score and albumin and platelet counts. In the regression analysis performed to evaluate the factors associated with high-stage fibrosis, fibrosis was determined to be associated with thrombosis, ALT, and gender. The results of the regression analysis demonstrated that the risk of fibrosis was 4.6 fold higher in men. CONCLUSIONS: According to the results obtained in our study, advanced age, higher BMI, AST, ALT, and HBV-DNA levels, and low albumin and platelet levels are correlated with advanced fibrosis in patients with CHB.