scholarly journals Topical Caspofungin for Treatment of Keratitis Caused by Candida albicans in a Rabbit Model

2005 ◽  
Vol 49 (4) ◽  
pp. 1359-1363 ◽  
Author(s):  
David Goldblum ◽  
Beatrice E. Frueh ◽  
Gian-Marco Sarra ◽  
Konstantinos Katsoulis ◽  
Stefan Zimmerli
Keyword(s):  
Candida Albicans ◽  
Drug Treatment ◽  
Clinical Assessment ◽  
Rabbit Model ◽  
Fungal Keratitis ◽  
Saline Control ◽  
Fungal Culture ◽  
Treatment Groups ◽  
Treatment Regimens ◽  
Hyphal Density

ABSTRACT Candida albicans is the most frequent cause of fungal keratitis in temperate regions. Caspofungin has potent activity against Candida spp. in a variety of clinical settings. Little is known, however, about its activity against fungal keratitis. We compared the efficacy of topical caspofungin with that of topical amphotericin B (AMB) in a rabbit model of experimental keratomycosis. Keratitis was induced with a standardized inoculum of Candida albicans (SC 5314) placed on the debrided cornea. Twenty-four hours after infection, animals were randomly assigned to treatment with 0.15% caspofungin, 0.5% caspofungin, 0.15% AMB, and a saline control (n = 12 rabbits in each group). For the first 12 h, treatment was repeated every 30 min and, after a 12-h pause, was resumed at hourly intervals for another 12 h. The animals were examined and killed 12 h after administration of the last dose. Treatment effects were evaluated by clinical assessment, fungal culture, and histopathology. Drug treatment significantly reduced corneal fungal recovery from 3.78 log10 CFU in saline-treated animals to 2.97, 1.76, and 1.18 log10 CFU in animals treated with 0.15% caspofungin, 0.5% caspofungin, and 0.15% AMB, respectively. By histopathology, the mean hyphal density was significantly lower in the corneas of treated animals than in those of the controls; there was no difference in hyphal densities between the different treatment groups. The depth of corneal invasion was not significantly reduced by the antifungal treatments. By clinical assessment, keratitis progressed in animals treated with saline, whereas disease progression was inhibited by all drug treatment regimens. In our rabbit model, 0.5% caspofungin was as effective as 0.15% AMB for the topical treatment of Candida keratitis. The potential clinical efficacy of caspofungin awaits further investigation.

scholarly journals Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Increased Fluconazole Efficacy against Experimental Endocarditis Due to Candida albicans

2004 ◽  
Vol 48 (8) ◽  
pp. 3051-3056 ◽  
Author(s):  
Michael R. Yeaman ◽  
Darwin Cheng ◽  
Bhavesh Desai ◽  
Leon I. Kupferwasser ◽  
Yan-Qiong Xiong ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Host Defense ◽  
Rabbit Model ◽  
Fungal Burden ◽  
Treatment Groups ◽  
Time Points ◽  
Platelet Microbicidal Protein ◽  
The Relationship

ABSTRACT Platelet microbicidal proteins (PMPs) are believed to be integral to host defense against endovascular infection. We previously demonstrated that susceptibility to thrombin-induced PMP 1 (tPMP-1) in vitro negatively influences Candida albicans virulence in the rabbit model of infective endocarditis (IE). This study evaluated the relationship between in vitro tPMP-1 susceptibility (tPMP-1s) or resistance (tPMP-1r) and efficacy of fluconazole (FLU) therapy of IE due to C. albicans. Candida IE was established in rabbits with either tPMP-1s or tPMP-1r strains. Treatment groups received FLU (100 mg/kg/day) intraperitoneally for 7 or 14 days; control animals received no therapy. At these time points, cardiac vegetations, kidneys, and spleens were quantitatively cultured to assess fungal burden. At both 7 and 14 days and in all target tissues, the extent of candidal clearance by FLU was greater in animals infected with the tPMP-1s strain than in those infected with the tPMP-1r strain. These differences were statistically significant in the spleen and kidney. Corroborating these in vivo data, FLU (a candidastatic agent), in combination with tPMP-1, exerted an enhanced fungicidal effect in vitro against tPMP-1s and tPMP-1r C. albicans, with the extent of this effect greatest against the tPMP-1s strain. Collectively, these results support the concept that tPMP-1 susceptibility contributes to the net efficacy of FLU against C. albicans IE in vivo, particularly in tissues in which platelets and tPMP-1 likely play significant roles in host defense.

scholarly journals Comparative study of oral terbinafine vs. oral griseofulvin in the management of tinea capitis

2019 ◽  
Vol 5 (3) ◽  
pp. 629
Author(s):  
Anjani Kumar Shukla ◽  
Bibhuti Bhushan ◽  
Dharmendra Kumar Mishra ◽  
Shyam Sundar Chaudhary ◽  
Mihir Kumar Jha ◽  
...  
Keyword(s):  
Clinical Assessment ◽  
Tinea Capitis ◽  
Fungal Culture ◽  
Treatment Groups ◽  
The Mean ◽  
To Receive ◽  
Tissue Effect ◽  
Dermatophyte Infection ◽  
Oral Terbinafine

<p class="abstract"><strong>Background:</strong> Tinea capitis (TC) is a common dermatophyte infection affecting primarily prepubertal children. The present study has been designed to assess the clinico-etiological profile of the T capitis and to compare the efficacy and tolerability of terbinafine with griseofulvin.</p><p class="abstract"><strong>Methods:</strong> One hundred fifty eight patients of T. capitis were divided into two groups of 79 patients each to receive either oral griseofulvin or terbinafine (according to weight). Patients in both the groups were followed up at 2, 4, 12 and 36 weeks. At every visit, clinical improvement was evaluated using clinical assessment severity score and the compliance, tolerability and side effects of the drugs were assessed along with KOH microscopy, fungal culture from the lesion and relevant blood investigations.<strong></strong></p><p class="abstract"><strong>Results:</strong> The clinical assessment score were statistically similar in group G and group T at the start of therapy. The decline in scores in both treatment groups was statistically significant at each follow up visit. In griseofulvin group, the mean score was declined from 5.9 at baseline to 4.24 at week 2 and 2.79 at week 4, 0.82 at week 12 and 1.24 at 36 week. In the terbinafine group, the score had a mean of 6.23 at 0 week and 4.03 at week 2, 2.32 at week 4, 0.69 at week 12 and 0.83 at week 36.</p><p><strong>Conclusions:</strong> At follow up study long lasting tissue effect of terbinafine was found but effect of griseofulvin was waned at 36 week. So terbinafine may be better option with similar side effect profile but it is better in residual clinical and mycological effect at higher cost.</p>

scholarly journals Efficacies of High-Dose Fluconazole plus Amphotericin B and High-Dose Fluconazole plus 5-Fluorocytosine versus Amphotericin B, Fluconazole, and 5-Fluorocytosine Monotherapies in Treatment of Experimental Endocarditis, Endophthalmitis, and Pyelonephritis Due to Candida albicans

1999 ◽  
Vol 43 (12) ◽  
pp. 2831-2840 ◽  
Author(s):  
Arnold Louie ◽  
Weiguo Liu ◽  
Dorothy A. Miller ◽  
Alana C. Sucke ◽  
Qing-Feng Liu ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Rabbit Model ◽  
Vitreous Humor ◽  
The Other ◽  
High Dose ◽  
Central Nervous System Toxicity ◽  
Time Curve ◽  
Treatment Groups ◽  
Days Of Therapy

ABSTRACT We compared the efficacies of fluconazole (Flu), amphotericin B (AmB), and 5-fluorocytosine (5FC) monotherapies with the combination of Flu plus 5FC and Flu plus AmB in a rabbit model of Candida albicans endocarditis, endophthalmitis, and pyelonephritis. The dose of Flu used was that which resulted in an area under the concentration-time curve in rabbits equivalent to that seen in humans who receive Flu at 1,600 mg/day, the highest dose not associated with central nervous system toxicity in humans. Quantitative cultures of heart valve vegetations, the choroid-retina, vitreous humor, and kidney were conducted after 1, 5, 14, and 21 days of therapy. All untreated controls died within 6 days of infection; animals treated with 5FC monotherapy all died within 18 days. In contrast, 93% of animals in the other treatment groups appeared well and survived until they were sacrificed. At day 5, the relative decreases in CFU per gram in the vitreous humor were greater in groups that received Flu alone and in combination with 5FC or AmB than in groups receiving AmB or 5FC monotherapies (P< 0.005) but were similar thereafter. In the choroid-retina, 5FC was the least-active drug. However, there were no differences in choroidal fungal densities between the other treatment groups. On days 5 and 14 of therapy, fungal densities in kidneys of AmB recipients were lower than those resulting from the other therapies (P< 0.001 and P ≤ 0.038, respectively) and AmB-plus-Flu therapy was antagonistic; however, all therapies for fungal pyelonephritis were similar by treatment day 21. While fungal counts in cardiac valves of Flu recipients were similar to those of controls on day 5 of therapy and did not change from days 1 to 21, AmB therapy significantly decreased valvular CFUs versus Flu at days 5, 14, and 21 (P < 0.005 at each time point). 5FC plus Flu demonstrated enhanced killing in cardiac vegetations compared with Flu or 5FC as monotherapies (P < 0.03). Similarly, the combination of AmB and Flu was more active than Flu in reducing the fungal density in cardiac vegetations (P < 0.03). However, as in the kidney, AmB plus Flu demonstrated antagonism versus AmB monotherapy in the treatment of C. albicansendocarditis (P < 0.05, P = 0.036, and P < 0.008 on days 5, 14, and 21, respectively).

scholarly journals Fungal Keratitis in Northern Thailand: Spectrum of Agents, Risk Factors and Putative Virulence Factors

2021 ◽  
Vol 7 (6) ◽  
pp. 475
Author(s):  
Siriporn Chongkae ◽  
Sirida Youngchim ◽  
Joshua D. Nosanchuk ◽  
Angkana Laliam ◽  
Chulaluck Tangmonkongvoragul ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Vision Loss ◽  
Proteolytic Enzymes ◽  
Tertiary Care ◽  
Fungal Keratitis ◽  
High Rate ◽  
Ocular Infection ◽  
Fungal Culture ◽  
Care Hospital ◽  
Northern Thailand

Fungal keratitis (FK) is a serious ocular infection that can result in various degrees of vision loss, including blindness. The aim of the study was to identify and retrospectively review all FK cases diagnosed between August 2012 and December 2020 at a tertiary care hospital in northern Thailand with a specific focus on epidemiologic features, including season, patient sex and age, the spectrum of pathogens, and presence of certain putative virulence factors. Of 1237 patients with corneal ulcers, 294 (23.8%) were confirmed by direct microscopic examination and/or fungal culture. For the positive cases, direct examinations of Calcofluor white (CW) stains and KOH mounts were found in 97.3% (286/294) and 76.5% (225/294), respectively (p < 0.05). Of the cases diagnosed by microscopy and culture, fungi were isolated in 152 (51.7%), with Fusarium spp. being the most frequently identified (n = 69, 45.5%) followed by dematiaceous fungi (n = 45, 29.6%) and Aspergillus spp. (n = 18, 11.8%). The incidence of FK was higher in the rainy season of July to October. The mean age was 54.4 ± 14.4 (SD) years, with a range of 9–88 years. Males (75.8%) were affected significantly more than females (24.2%) (p < 0.05). Of 294 patients, 132 (44.9%) were middle-aged adults (41–60 years) and 107 (36.4%) were older than 60 years. Trauma to the eye by soil or vegetative matter were the most common preceding factors (188/294; 64.0%). We assessed two virulence factors. First, 142 of the 152 culture-positive FK cases were due to molds, indicating that hyphal morphogenesis is extremely important in disease. We also demonstrated that fungal melanization occurs in the molds during the course of FK by applying a melanin-specific monoclonal antibody (MAb) that labeled fungal elements in corneal samples of patients, and melanin particles derived from the hyphae were also recovered after treatment of the samples with proteolytic enzymes, denaturant and hot concentrated acid. In summary, we demonstrate that northern Thailand has a high rate of FK that is influenced by season and males engaged in outside activities are at highest risk for disease. Moulds are significantly more commonly responsible for FK, in part due to their capacity to form hyphae and melanins. Future studies will examine models of fungal corneal interactions and assess additional factors of virulence, such as secreted enzymes, to more deeply decipher the pathogenesis of FK.

scholarly journals Immune Responses and Protection against Experimental Brucella suis Biovar 1 Challenge in Nonvaccinated or B. abortus Strain RB51-Vaccinated Cattle

2010 ◽  
Vol 17 (12) ◽  
pp. 1891-1895 ◽  
Author(s):  
S. C. Olsen ◽  
S. G. Hennager
Keyword(s):  
Immune Responses ◽  
Experimental Infection ◽  
Brucella Abortus ◽  
Agglutination Test ◽  
Saline Control ◽  
Infected Cattle ◽  
Infection Rates ◽  
Treatment Groups ◽  
Brucella Suis ◽  
Fluorescence Polarization Assay

ABSTRACT Twenty Hereford heifers approximately 9 months of age were vaccinated with saline (control) or 2 × 1010 CFU of the Brucella abortus strain RB51 (RB51) vaccine. Immunologic responses after inoculation demonstrated significantly greater (P < 0.05) antibody and proliferative responses to RB51 antigens in cattle vaccinated with RB51 than in the controls. Pregnant cattle received a conjunctival challenge at approximately 6 months of gestation with 107 CFU of B. suis bv. 1 strains isolated from naturally infected cattle. The fluorescence polarization assay and the buffered acid plate agglutination test had the highest sensitivities in detecting B. suis-infected cattle between 2 and 12 weeks after experimental infection. Serologic responses and lymphocyte proliferative responses to B. suis antigens did not differ between control and RB51 vaccinees after experimental infection. No abortions occurred in cattle in either treatment group after challenge, although there appeared to be an increased incidence of retained placenta after parturition in both the control and the RB51 vaccination treatment groups. Our data suggest that the mammary gland is a preferred site for B. suis localization in cattle. Vaccination with RB51 did not reduce B. suis infection rates in maternal or fetal tissues. In conclusion, although B. suis is unlikely to cause abortions and fetal losses in cattle, our data suggest that RB51 vaccination will not protect cattle against B. suis infection after exposure.

Refinement and reduction through application of a quantitative score system for estimation of TB-induced disease burden using computed tomography

2018 ◽  
Vol 52 (6) ◽  
pp. 599-610 ◽  
Author(s):  
Sally A Sharpe ◽  
Donna Smyth ◽  
Anthony McIntyre ◽  
Fergus Gleeson ◽  
Mike J Dennis
Keyword(s):  
Computed Tomography ◽  
Disease Burden ◽  
Test Model ◽  
Score System ◽  
Global Epidemic ◽  
Treatment Groups ◽  
Additional Tool ◽  
Treatment Regimens ◽  
Improved Outcomes ◽  
Quantitative Score

Until validated correlates of protection are identified, animal models remain the only way to test the efficacy of the new vaccines and drugs urgently needed to fight the global epidemic caused by infection with Mycobacterium tuberculosis. Non-human primates (NHP) offer the most relevant models of human tuberculosis (TB) and are central to the development process for new interventions. Efficacy evaluations are dependent on the capability of the test model to discriminate improved outcomes between treated groups after experimental exposure to M. tuberculosis and therefore the ability to measure TB-induced disease burden is central to the process. We have developed a score system that allows us to quantify the disease burden induced in macaques by infection with M. tuberculosis, based on the extent and features of disease visible on computed tomography (CT) images. The CT determined disease burden was then verified against that obtained using an established pathology-based approach. Trials of the system as a tool to measure disease burden have shown the approach capable of revealing differences between treatment groups in order to: (a) characterise outcome of infection and enable model refinement; (b) demonstrate the efficacy of drug treatment regimens by showing differences in outcome between test groups. Initial trials suggest that the imaging-based score system provides a valuable additional tool for the measurement of TB-induced disease burden that offers the opportunity to apply both refinement and reduction within studies.

Divergent Effects of Leptin on Luteinizing Hormone and Insulin Secretion are Dose Dependent

2003 ◽  
Vol 228 (3) ◽  
pp. 325-330 ◽  
Author(s):  
Dorota A. Zieba ◽  
Marcel Amstalden ◽  
Marlon N. Maciel ◽  
Duane H. Keisler ◽  
Nina Raver ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Luteinizing Hormone ◽  
Plasma Insulin ◽  
Beef Cows ◽  
Saline Control ◽  
Free Access ◽  
Treatment Groups ◽  
Positive Effects ◽  
Pulse Characteristics ◽  
Dose Dependent

We have shown recently that fasting permits leptin to modulate both luteinizing hormone (LH) and insulin secretion in cows. In rodents, leptin causes divergent effects on LH and insulin release that are dose dependent. To test the hypothesis that leptin effects on LH and insulin secretion in fasted cows are dose related, we examined the effects of various doses of recombinant ovine leptin (oleptin) in mature cows. Twenty ovariectomized beef cows, each bearing an estradiol implant to maintain basal estradiol concentrations, were used. All cows were fasted for 60 hr with free access to water and were assigned randomly to one of four groups (n = 5/group): 1) saline control; 2) leptin, 0.2 μg/kg; 3) leptin, 2.0 μg/kg; and 4) leptin, 20 μg/kg body wt. Blood samples were collected at 10-min intervals for 6 hr on Days 0 and 2, with saline or oleptin injected intravenously immediately after the first intensive sample on Day 2 (54 hr). Leptin caused a dose-related increase (P < 0.001) in mean concentrations of circulating LH. Stimulation of LH release by leptin was significant at the lowest (141% of control) and middle (122% of control) doses used, but no increase was observed for the highest dose. Increased mean concentrations of LH appeared to result from an augmentation of basal secretion, as pulse characteristics were not affected. After 54 hr of fasting, plasma insulin concentrations were lowered (P < 0.01) in all treatment groups compared to Day 0. After leptin injections, plasma insulin concentrations increased (P < 0.01) and reached highest concentrations during the first hour of sampling. However, this increase was sustained for several hours only in the intermediate (2.0 μg/kg) dose group. Collectively, our results show that leptin has potent positive effects on both LH and insulin secretion in fasted cows, but the anterior pituitary and endocrine pancreas appear to become downregulated in the presence of excess ligand.

scholarly journals Comparison of fluconazole and amphotericin B for treatment of experimental Candida albicans endocarditis in rabbits.

1996 ◽  
Vol 40 (1) ◽  
pp. 263-266 ◽  
Author(s):  
K Chemlal ◽  
L Saint-Julien ◽  
V Joly ◽  
R Farinotti ◽  
N Seta ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Rabbit Model

Amphotericin B (AmB) and fluconazole, administered intraperitoneally for 7 days, were compared in a rabbit model for Candida albicans endocarditis. When given early, AmB was more effective than fluconazole for reducing CFU counts in vegetations (P < 0.01) and kidneys. Forty-eight hours after the last dose, AmB was still detected in all vegetations whereas fluconazole was detected in only one case.

scholarly journals Comparative study utilizing different post-breeding treatment regimens in cyclic Arabian mares

2021 ◽  
pp. 2863-2868
Author(s):  
Khalid Mohammed Karam ◽  
Ahmed Saed Alebady ◽  
Haitham O. Alhilfi ◽  
Dhia Hussain Al-Delemi
Keyword(s):  
Treatment Regimen ◽  
Normal Saline ◽  
Prophylactic Treatment ◽  
Treatment Protocols ◽  
Treatment Groups ◽  
Treatment Regimens ◽  
Reproductive Management ◽  
Natural Breeding ◽  
Uterine Lavage ◽  
Age Category

Background and Aim: Post-breeding treatment is the most common practice in the reproductive management of mares. Oxytocin, uterine lavage, and intrauterine (I/U) antibiotic are usually used as prophylactic therapy. This study aimed to determine the most efficient prophylactic treatment regimen among six treatment protocols applied during natural breeding of cyclic Arabian mares. Materials and Methods: The current study was conducted on cyclic Arabian mares that were subdivided into three age categories (n=968): Category I (5-10 years, n=380), Category II (11-15 years, n=361), and Category III (≥16 years, n=227). Six prophylactic treatments were applied after 4 h of breeding. According to the treatment regimen, treated mares (n=483) were divided into six treatment groups: A (n=80), treated with I/U antibiotic (1 g gentamicin); B (n=81), I/U lavage (normal saline 500 mL); C (n=83), intramuscular (I/M) oxytocin (10 IU); D (n=82), I/U antibiotic and I/M oxytocin; E (n=78), I/U lavage and I/M oxytocin; and F (n=79), I/U lavage with I/U antibiotic and I/M oxytocin. Non-treated mares were classified as controls (n=485). Ultrasonography was performed to monitor pregnant mares 30 and 60 days after mating, and mares were followed until foaling. Results: Pregnancy and foaling results reveals that in age Category I, treatment with oxytocin alone or oxytocin with I/U lavage showed the highest pregnancy and foaling rates (p<0.01). In age Category II, the highest pregnancy and foaling rates were observed in lavage treatment (p<0.01), whereas, in age Category III, the good pregnancy and foaling rates were monitored in treatment with oxytocin and I/U lavage (p<0.01). Conclusion: Treatment with systemic I/M oxytocin is ideal in early age group mares (5-10 years of age). However, irrespective of the age categories, all mares exhibited high pregnancy and foaling rates after treatment with systemic I/M oxytocin and I/U lavage with normal saline (0.9%) 4 h post-breeding.

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