Systemic Antifungal Agents Research Articles

Vaginal Ozone Insufflation in the Treatment of Recurrent Candidal Vulvovaginitis: Randomized Control Trial

Background: O3 therapy induces moderate oxidative stress when interacting with lipids. Aim of the Work: to demonstrate the efficacy of the application of vaginal ozone insufflations in treatment of recurrent CANDIDAL vulvo-vaginitis , compared to combined vaginal and systemic antifungal agents. Patients and Methods: This randomized-controlled study was conducted on 50 women with recurrent vulvo-vaginitis, recruited from the outpatient gynecology clinic of Ain shams University Obstetrics and Gynecology Hospital, who were attending for outpatient consultation. Subjects were assigned randomly into two groups, group (A) 25 subjects, who were treated with traditional, combined, topical and systemic antifungal therapy, and (b) Group (B): 25 subjects, who were treated by vaginal ozone insufflations. Results: Twenty-two (88%) patients in the vaginal ozone group had clinical cure compared with only 14 (56%) patients in the traditional treatment group. This difference was statistically significant. Likewise, the microbiological cure rate was significantly higher in the vaginal ozone group compared with the traditional treatment group. Five out of 14 patients (35.7%) in the traditional treatment group suffered clinical recurrence compared with only 1 out of 22 patients (4.5%) in the vaginal ozone group. This difference was statistically significant. Likewise, the microbiological recurrence rate was significantly lower in the vaginal ozone group compared with the traditional treatment group. Conclusion: Ozone therapy has proven to be effective in treatment of the recurrent vulvovaginitis, where the persistence of clinical symptoms and positive culture exudates were measured.

Potential antibiofilm activity of farnesol-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles against Candida albicans

Candida species are ubiquitous fungal pathogens and are the most common causes of mucosal and invasive fungal infections in humans. Especially Candida albicans commonly resides as a commensal in the mucosal tissues of approximately half of the human population. When the balance of the normal flora is disrupted or the immune defenses are compromised, Candida species can become pathogenic, often causing recurrent disease in susceptible individuals.The treatments available for Candida infection are commonly drug-based and can involve topical and systemic antifungal agents. However, the use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. Candida species ability to produce drug-resistant biofilm is an important factor in human infections, because microorganisms within biofilm benefit from various advantages over their planktonic counterparts including protection from antimicrobials and chemicals. These limitations emphasize the need to develop new and more effective antifungal agents. Natural products are attractive alternatives for this purpose due to their broad spectrum of biological activities. Farnesol is produced by many microorganisms and found in some essential oils. It has also a great attention as a quorum-sensing molecule and virulence factor. It has also antimicrobial potential due to its inhibitory effects on various bacteria and fungi. However, as it is a hydrophobic component, its solubility and biofilm inhibiting properties are limited.To overcome these shortcomings, nanoparticle-based drug delivery systems have been successfully used. For this purpose, especially using biodegradable polymeric nanoparticles has gained increasing attention owing to their biocompatibility and minimal toxicity. Poly (DL-lactide-co-glycolide) (PLGA) is the most widely used polymer in this area. In this study, farnesol is loaded to PLGA nanoparticles (F-PLGA NPs) by emulsion evaporation method and characterized by DLS, TEM, and FT-IR analyses. Our TEM findings indicate that the sizes of F-PLGA NPs are approximately 140 nm. The effects of F-PLGA NPs on planktonic cells and biofilm formation of C. albicans were compared with effects of farnesol alone. Farnesol inhibits the growth at a range of 53% at a concentration of 2.5 μL compared to the control group. This rate is 45% for F-PLGA NPs at the same concentration. However, although farnesol amount in F-PLGA is approximately 22.5% of the total volume, the observed effect is significant. In TEM examinations, planktonic Candida cells treated with farnesol showed relatively regular ultrastructural morphology. Few membrane and wall damage and electron density in the cytoplasm were determined. In F-PLGA NP-treated cells, increased irregular cell morphology, membrane and wall damages, and large vacuoles are observed. Our SEM and XTT data suggest that F-PLGA NPs can reduce the biofilm formation at lower concentrations than farnesol alone 57%, and our results showed that F-PLGA NPs are effective and biocompatible alternatives for inhibiting growth and biofilm formation of C. albicans, but detailed studies are needed.

Antifungal drugs: An updated review of central nervous system pharmacokinetics.

Invasive fungal infections (IFIs) in the central nervous system (CNS) are particularly hard to treat and are associated with high morbidity and mortality rates. Four chemical classes of systemic antifungal agents are used for the treatment of IFIs (eg meningitis), including polyenes, triazoles, pyrimidine analogues and echinocandins. This review will address all of these classes and discuss their penetration and accumulation in the CNS. Treatment of fungal meningitis is based on the antifungal that shows good penetration and accumulation in the CNS. Pharmacokinetic data concerning the entry of antifungal agents into the intracranial compartments are faulty. This review will provide an overview of the ability of systemic antifungals to penetrate the CNS, based on previously published drug physicochemical properties and pharmacokinetic data, for evaluation of the most promising antifungal drugs for the treatment of fungal CNS infections. The studies selected and discussed in this review are from 1990 to 2019.

Successful treatment of resistant onychomycosis with voriconazole in a liver transplant patient.

Onychomycosis is a common chronic fungal infection of the nails caused by dermatophytes, yeasts, and non-dermatophyte filamentous fungi. A relatively high incidence of resistance and treatment failure of onychomycosis to traditional systemic antifungal agents such as terbinafine and itraconazole has been reported. Voriconazole is a novel broad spectrum systemic antifungal that has shown high efficacy against various types of dermatophytes including Trichophyton and Microsporum species in many in vitro and, recently, in two in vivo studies of resistant dermatophytosis. Herein, we report the successful treatment of a resistant case of finger nail onychomycosis by oral voriconazole in a liver transplant patient who failed to respond to traditional systemic antifungals.

Labeled use of efinaconazole topical solution 10% in treating onychomycosis in children and a review of the management of pediatric onychomycosis

Onychomycosis is a difficult to treat condition whose prevalence is increasing. Until recently, there was no FDA approved antifungal agent for the treatment of onychomycosis in children. Although systemic antifungal agents are effective, their use is restricted by the potential adverse events and drug-drug interactions. There is evidence regarding the safety and efficacy of topical antifungal agents for pediatric onychomycosis. We have summarized the results of a recently published study using efinaconazole topical solution 10% to treat onychomycosis in children and discuss management of pediatric onychomycosis. In a multicenter, open-label phase 4 study, efinaconazole 10% solution was applied topically once daily in children aged 6 to 16 years with mild to severe, culture positive, distal and lateral subungual onychomycosis. Treatment was for 48 weeks with a follow-up at week 52. Pharmacokinetics was performed in a subset of patients. There were 62 patients enrolled in the study. At week 52, the efficacy was mycological cure rate 65% and complete cure rate 40%. All treatment-emergent adverse events (TEAE) were mild to moderate in severity with none resulting in study discontinuation. The only treatment-related TEAE was ingrown toenail. Efinaconazole was detected at low levels in plasma. Efinaconazole topical solution 10% is effective and safe in treating onychomycosis in children age 6 to 16 years and was recently FDA-approved for this indication. The on-label use of other topical agents, tavaborole solution 5% and ciclopirox nail lacquer solution 8% is reviewed. We also briefly discuss the use of oral agents, terbinafine, itraconazole, and fluconazole in pediatric onychomycosis.

Identification of Fungi in Burn Wounds Using Conventional and Vitek System in Duhok City, Iraq

Background: Fungal burns and wounds infections are frequent but underestimated causing invasive infections with late-onset morbidity and mortality in patients suffering severe perturbed immune systems.
 Objectives: This study aimed to investigate fungal infections in clinical specimens by using conventional and Vitek system.
 Methods: A total of 123 swabs were obtained from wound and burns patients with different age, gender, burn degrees and nationality that admitted burns and emergency hospital in Duhok city, Iraq, from October 2019 till January 2020. All swabs screened by direct examination, fungal isolation then subjecting the purified colonies to Vitak system 2 to confirm the identification of fungal species.
 Results: Out of 123, 55.5% and 44.5% revealed fungal growth in wound and burn swab, respectively with more mono-fungal growth patterns. Male, middle ages group, Iraqi nationality and second-degree burn were more affected. Cryptococcus laurentii was the predominant (40%) followed by Stephanoascus ciferri (23%), Aspergillus nigar (11%) and Candida albicans was very low rate (1.1%), while other fungal specie’s were recorded in fewer rates. The present study demonstrated that the wound and burn fungal infection cases are relatively high in above mentioned hospitals with a variety of fungal pathogens. Unexpectedly, the Cryptococcus laurentii and Stephanoascus ciferri were highly predominant.
 Conclusions: The study concluded the necessity of using Vitak system for full identification and emphasize on the cleaning of surroundings of patients in the burn and wound units care, reduction of humidity, regular employment of topical and systemic antifungal agents that reduce morbidity and mortality in burn unit in this setting.

In vitro pharmacokinetics/pharmacodynamics modeling and efficacy against systemic candidiasis in Drosophila melanogaster of a bisaryloxypropanamine derivative.

The number of deaths due to systemic fungal infections is increasing alarmingly, which is aggravated by the limitations of traditional treatments and multidrug resistance. Therefore, the research and development of new therapeutic options against pathogenic fungi is an urgent need. To evaluate the fungicidal activity of a synthetic compound, 1,3-bis-(3,4-dichlorophenoxy)propan-2-aminium chloride (2j), through time-kill studies and pharmacokinetics/pharmacodynamics (PK/PD) modeling. The protective effect of the compound was also evaluated using the Drosophila melanogaster minihost model of candidiasis. Mathematical modeling of time-kill data of compound 2j was performed to obtain PD characteristics. Additionally, Toll-deficient D. melanogaster flies were infected with a Candida albicans strain and treated with 2j. We observed that compound 2j demonstrated a time- and dose-dependent fungicidal effect against Candida spp. and dermatophytes, even at low concentrations, and rapidly achieved kill rates reaching the maximum effect in less than one hour. The efficacy of the compound against systemic candidiasis in D. melanogaster flies was comparable to that achieved by fluconazole. These results support the potential of compound 2j as a systemic antifungal agent candidate and serve as a starting point for further studies involving mammalian animal models.

Fungal Periprosthetic Joint Infection of Hip – Report of 2 Cases

A 72-year old woman had revision unipolar hemiarthroplasty for AMA loosening with vertical split fracture of greater trochanter. This was complicated by PJI, treated with staged arthroplasty with articulated antibiotic loaded cement spacer. Revision of antibiotic loaded cement spacer for dislocation and cable plate fixation of greater trochanter was done. Then the tissue specimen grew Candida ablicans. Fluconazole was given. Repeated debridement and exchange of antibiotic loaded cement spacer was done twice again with amphoteric B and vancomycin added to the cement. Unfortunately, the frozen section was still positive despite the CRP was returned to normal for 1 month. Oral fluconazole was continued. Finally, revision total hip replacement was done 14 months after the initial insertion of antibiotic loaded cement spacer. The patient could manage to walk with frame indoor with no hip pain at 3 year follow-up. Another 80-year old woman had removal of AMA, debridement and antibiotics loaded cement spacer was done for PJI. This was complicated by breakage of the articulated cemented spacer during reduction and later hip dislocation despite of cemented acetabular liner. A total of 3 debridement and antibiotics loaded cement spacer were done. Besides Candida albicans, tissue also grew Enterobacter cloacae and Pseudomonas aeruginosa. Exchange of cement space loaded with gentamicin and voriconazole was done as the 4th reoperation 22 weeks after the debridement and antibiotics loaded cement spacer insertion. Intraoperatively, the patient developed haemorrhagic shock and complicated with myocardial infraction and pneumonia postoperatively and eventually succumbed 12 days after the last operation.The control rate of fungal PJI of only 36% was reported in the literature. The use of systemic and local antifungal agents, surgical treatment strategy and outcomes will be reviewed.

Lenticular fungal infection caused by Aspergillus in a patient with traumatic corneal laceration: a case report

BackgroundTo report a case of lenticular infection caused by Aspergillus, which was diagnosed 13 weeks after traumatic corneal laceration.Case presentationA 60-year-old woman presented with traumatic corneal laceration including anterior lens capsule rupture and traumatic cataract after being hit with a chestnut in the right eye. There were multiple injuries due to tiny thorns of the chestnut, including the conjunctiva, sclera, cornea, and anterior lens capsule. But no visible foreign body was detected by slit-lamp examination. Topical corticosteroid was prescribed to resolve the conjunctival inflammation induced by the thorns of chestnut, which could have caused persistent irritation. As conjunctival injection and edema being decreased during outpatient clinical follow-up, embedded conjunctival foreign body was detected and surgically removed (1st surgery). Approximately 10 weeks after the trauma, severe inflammation of the anterior segment accompanied with hypopyon developed suddenly and at the same time embedded scleral foreign body was revealed. After removal of scleral foreign body (2nd surgery), unspecified mold species was cultured from the scleral foreign body in SDA (Sabouraud dextrose agar) plate. Suspicious corneal foreign body was removed as 3rd surgery and phacoemulsification of traumatic cataract was planned as 4th surgery. Aspergillus was finally detected from removed anterior capsule and fibrotic membrane during the operation. Fungal infection resolved successfully after administration of topical (1% voriconazole and 5% natamycin) and systemic (fluconazole) antifungal agents and phacoemulsification of traumatic cataract.ConclusionChestnut thorns can damage multiple ocular tissues simultaneously. Lens capsular rupture could result in fungal inoculation and lead to delayed lenticular fungal infection with complicated cataract formation. In cases of ocular trauma due to organic substances such as thorns and branches, the possibility of fungal infection should be considered.

Probiotic Streptococcus salivarius Reduces Symptoms of Denture Stomatitis and Oral Colonization by Candida albicans

Denture stomatitis (DS) is an inflammatory status of oral mucosae frequently observed in denture wearers, and mainly associated with oral overgrowth of Candida albicans. DS is the cause of multiple visits to the dental office and is thought to enhance the risk of systemic infections. The treatment of DS mainly relies upon improvement of oral hygiene measures and prescription of topical or systemic antifungal agents, and disinfectants that, although effective, are not without drawbacks. Since, in recent years, some probiotics were investigated as a means to contrast oral colonization by Candida spp., this study was designed to preliminarily evaluate the effects of probiotic strain Streptococcus salivarius K12, in subjects affected by DS, and the duration of these effects. Fifty adult denture wearers affected by DS were enrolled and randomly divided into two groups: the experimental group was instructed to perform careful oral and denture hygiene and to assume the probiotic preparation for 30 days; the control group received only oral hygiene instructions. Patients were evaluated for signs of DS at the beginning of the study, at the end of treatment and 30 days later. Microbiological samples were obtained at the beginning of the study and at the end of treatment to quantify Candida albicans cells. Experimental treatment reduced clinical signs and symptoms of DS and the count of C. albicans. The clinical effects of experimental treatment were still evident after 30 days, suggesting that administration of probiotic strain Streptococcus salivarius K12 could be a promising approach in the treatment of DS.

Refractory keratitis from Beauveria bassiana—Successful treatment with intrastromal amphotericin B and micafungin

A case of Beauveria bassiana keratitis refractory to treatment with topical and systemic antifungal agents that demonstrated high-sensitivity profiles was presented. Clinical resolution was achieved within 1 month after the implementation of intrastromal injections of amphotericin B and micafungin. Keratitis from B. bassiana is a rare fungal species without a well-defined management strategy. To our knowledge, no previous reports have described the effectiveness or therapeutic use of intrastromal micafungin. This case report highlights a previously unreported treatment for cases of refractory keratitis from this rare fungal infection.

A Multicenter Study of Antifungal Use and Species Distribution and Antifungal usceptibilities of Candida Isolates in South Korea

Background: Candidiasis control should include monitoring the epidemiology and resistance to various antifungal agents. In this study, the researchers investigated the Candida species recovered from clinical specimens at particular geographic areas or hospitals. Objective: The present study is geared toward the evaluation of antifungal drug usage at Korean hospitals in 2016. It is also essential that species distribution and antifungal susceptibilities of Candida isolates should be looked into to provide important data that can help devise therapeutic strategies to control the disease. Methods: Systemic antifungal agent usage over a one-year period was investigated at 10 Korean hospitals. Identification and antifungal susceptibility tests were performed on clinical isolates of the Candida species, which were collected over a three-month period. Results: The total antifungal usage in each hospital ranged from 7.7 to 158.9 defined daily doses (DDDs) per 1,000 patient days. Fluconazole was most commonly used (37.1%), followed by amphotericin B (30.6%), itraconazole (9.7%), echinocandins (8.8%), voriconazole (7.5%), and posaconazole (6.3%), respectively. Among 274 Candida isolates, C. albicans was the most frequently recovered (51.1%), followed by C. glabrata (15.7%), C. tropicalis (15.0%), and C. parapsilosis (13.5%), respectively. Through the application of either species-specific clinical breakpoints or epidemiological cutoff values to Candida isolates, the non-susceptibility rates to fluconazole, voriconazole, amphotericin B, and micafungin were found in 20.7%, 5.6%, 0%, and 0% of isolates, respectively. Conclusion: This nationwide multicenter study showed that total antifungal use varied considerably according to each hospital. Non-susceptibility to fluconazole should be further monitored, considering the drug's frequent use in Korea.

509 Fungal Infections After Blast and Thermal Injury

Abstract Introduction Invasive fungal wound infections have been reported after combat-related blast injury sustained in recent conflicts. Systemic antifungal agents are commonly used as an adjunct to urgent surgical debridement. There is currently controversy in defining the depth of fungal invasion, which is the most critical factor that determines the treatment strategy. The objective of this study was to describe fungal infections in blast injury patients admitted to our burn center. Methods This was a retrospective chart review. Subjects who were admitted between January 2004 and February 2019, received a systemic antifungal agent, and experienced a blast injury were included. Culture and histopathology results were recorded. Results Eighty one patients were included. Seventy five subjects (92.6%) were active-duty service members at the time of injury and 79 (97.5%) subjects were male. On average, subjects were 27.4±7.8 years old with a burn size of 51.4±25.3% TBSA. Twenty seven subjects (33.3%) died during their hospital stay. The 75 subjects had 157 cultures positive for fungi, including 130 tissue cultures. The most common genera isolated was Aspergillus (n=148), Candida (n=106), Fusarium (n=16), and Mucor (n=12). Fifty seven percent of subjects who grew Mucor died, as compared to 52% who grew Aspergillus, 50% who grew Fusarium, and 32.3% who grew Candida. For histopathology, 33 subjects (40.7%) had results with fungus in non-viable tissue, 27 subjects (25.9%) had results with fungus in viable tissue, and 14 (17.3%) had results with angioinvasion. Subjects who had fungus in viable tissue had the highest mortality rate (71.4%), followed by angioinvasion (64.3%), and fungus in non-viable tissue (33.3%). The 75 subjects received 121 courses of systemic antifungals. The average duration of therapy was 12.3±13.6 days. The most common antifungals ordered were voriconazole (n=58), fluconazole (n=53), and liposomal amphotericin B (n=42). Conclusions Invasive fungal infection after blast injury had a high mortality rate. Early recognition and management of fungal infections is paramount to patient survival. A consensus is needed on how to best define the depth and level of invasion of fungal wound infections, and to determine the optimal treatment duration of systemic antifungal agents for these patients. Applicability of Research to Practice Invasive fungal wound infections carry a high mortality rate. A consensus is needed on the optimal systemic therapy.

508 Fungal Infections in Burn Patients from 2014–2019: A 5-year Retrospective Review

Abstract Introduction Topical and systemic antibiotic agents used to treat burn wounds allow for fungal growth. Fungal infections often occur later in the hospital course and carry a higher mortality rate than bacterial infections in critically ill burn patients. The primary objective of this study was to describe the incidence and characteristics of fungal infections in our burn center. Methods This was a retrospective chart review. Subjects who were admitted between January 2014 and February 2019 after sustaining a burn injury and received a systemic antifungal agent were included. All cultures and histopathology results that were positive for fungus were recorded. Results Ninety one subjects were included in this analysis. The average age was 42.3±16.9 years and 74 (81.3%) subjects were male. Seventy four (81.3%) subjects were admitted after flame burn. The average burn size was 40.1±24.2% TBSA. The average hospital length of stay was 57.2±44.8 days. Thirty eight (41.7%) subjects died during their hospital stay. The 91 subjects had 220 cultures positive for fungi: 29 blood cultures, 19 BAL cultures, 23 sputum cultures, 118 tissue cultures, and 31 urine cultures. The most common fungal genera isolated were: Candida (n=146), Aspergillus (n=55), and Fusarium (n=44). Twenty six (28.6%) subjects had histopathology results that showed fungus in non-viable tissue, with an average time from injury to fungus of 20.4±11.8 days. Twenty six (28.6%) subjects had histopathology results that showed fungus in viable tissue, with an average time from injury to fungus of 22.7±16.7 days. Of note, these were not the group that had fungus in non-viable tissue. Twelve (13.2%) subjects had angioinvasion, with an average time to angioinvasion of 26.6±22 days. The 91 subjects received 133 courses of antifungals. The average course of antifungal therapy was 7.8±8.9 days. The most common antifungals used were: micafungin (n=54), fluconazole (n=53), and liposomal amphotericin B (n=44). Conclusions Patients who were started on a systemic antifungal had a high mortality rate. Common fungi isolated included Candida and Aspergillus, which is consistent with previous literature. Further research is needed on the early recognition, accurate diagnosis, and timely management of fungal infections in this patient population. Applicability of Research to Practice Fungal infections after burn injury carry a high mortality rate. Early recognition and timely management of these infections is paramount.

Treatment of allergic bronchopulmonary aspergillosis: from evidence to practice.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder caused by dysregulated immune responses against Aspergillus fumigatus. The disorder usually complicates the course of patients with asthma and cystic fibrosis. Patients with ABPA most often present with asthma that is poorly controlled despite inhaled corticosteroids and long-acting β2 agonists. The treatment of ABPA is complicated due to the occurrence of recurrent exacerbations and spontaneous remissions. The drugs used for treating ABPA include systemic glucocorticoids, antifungal agents and biologics, each with its own benefits and drawbacks. In this review, we illustrate the treatment pathway for ABPA in different situations, using a case-based approach. In each case, we present the options for treatment based on the available evidence from recent clinical trials.

Prospective trial for the clinical efficacy of anogenital skin care with miconazole nitrate‐containing soap for diaper candidiasis

Anogenital skin care for the elderly remains an umbrella term concerning protective and non-interventional regimens, particularly for ordinary diaper users. Our recent investigation has demonstrated the preventive effect of daily anogenital washing with miconazole nitrate-containing soap to the development of diaper candidiasis. We extended this work to cover our hypothesis as to whether the miconazole soap has a therapeutic benefit in genital candidiasis. The study outline includes: (i) the enrollment of 21 bedridden inpatients (84 ± 9 years; eight men and 13 women) who were diagnosed clinically and mycologically with genital candidiasis, and who had never received topical and/or systemic antifungal agents; (ii) administration of anogenital washing with 0.75% miconazole-containing soap once daily for 4 weeks; and (iii) assessment of clinical symptoms and detection of Candida materials by culture and microscopic examination. As assessed by clinical symptom scoring for incontinence-associated dermatitis (IAD), the ratio of patients with severe to moderate symptoms dramatically decreased by 2 weeks and 10 of 21 patients became symptom-free at 4 weeks. The IAD clinical severity score was significantly decreased at 4 weeks. Compared with the baseline positivity, both microscopic and cultured Candida-positive rates were significantly decreased at 4 weeks after washing. All culture-detected fungi were Candida albicans. Severe adverse events did not occur in all participants. Individual medical and risk factors had no significant correlation with clinical severity and duration of candidiasis on variance analysis. In conclusion, topical washing with miconazole soap is a safe and reliable non-medical approach for soothing diaper-associated genital candidiasis in bedridden inpatients in whom it is difficult to perform prompt medical examination.

Administration and Dosing of Systemic Antifungal Agents in Pediatric Patients.

Neonates and immunosuppressed/immunocompromised pediatric patients are at high risk of invasive fungal diseases. Appropriate antifungal selection and optimized dosing are imperative to the successful prevention and treatment of these life-threatening infections. Conventional amphotericin B was the mainstay of antifungal therapy for many decades, but dose-limiting nephrotoxicity and infusion-related adverse events impeded its use. Despite the development of several new antifungal classes and agents in the past 20years, and their now routine use in at-risk pediatric populations, data to guide the optimal dosing of antifungals in children are limited. This paper reviews the spectra of activity for approved antifungal agents and summarizes the current literature specific to pediatric patients regarding pharmacokinetic/pharmacodynamic data, dosing, and therapeutic drug monitoring.

The effect of aqueous and ethanolic extract of Iranian propolis on Candida Albicans isolated from the mouth of patients with colorectal malignancy undergone chemotherapy: An in-vitro study.

Background:Candidiasis is one of the most common fungal infections in immunosuppressed patients. The condition is usually treated with local and systemic antifungal agents. Given the antifungal properties of propolis, it appears this natural resin material can be effective in treating this infection. The aim of the present in vitro study was to compare the effect of Iranian propolis with those of routine antifungal agents on Candida species isolated from the oral candida lesions of patients with cancer, who had undergone chemotherapy, and a standard strain of Candida albicans.Methods:A total of 23 samples were collected from the oral cavities of patients with colorectal cancer, who had undergone chemotherapy with 5-fu. The fungal species were determined based on the results of culture in C. albicans chromagar medium, formation of the germ tube and formation of vesicles. The MIC of aqueous extract propolis (AEP) and ethanolic extract of propolis (EEP) and amphotericin B (AMP-B), fluconazole (FL) and nystatin (NYS) were compared.Results:A total of 23 oral C. albicans samples were isolated. The MICs of FL and AMP- B were similar and less than those of EEP, AEP and NYS (P<0.001). In addition, the MIC of AEP was higher than EEP (P<0.001). The MIC of AMP- B on the strains isolated from the patients was more than that of the standard strain (P=0.012).Conclusion:The aqueous and ethanolic extracts of Iranian propolis exhibited antifungal activity, with a greater effect of the EEP compared to the AEP.

Pulmonary mycoses treated by topical amphotericin B

Since its discovery, amphotericin B (AmB) became a key management because it is the most common antifungal drug with activity to disrupt the fungal cell wall. Furthermore, it is the first-choice treatment in pulmonary mycoses that may consider lethal infection; the difference in lipid structure between fungal and mammalian cell membranes determines the effect of AmB. However, some fungal pulmonary diseases such as aspergillomas are partially contact with the blood and narrow touch the walls of the lung cavities, thus administration of systemic antifungal agents may be ineffective to eliminate these infections. Tissue penetration of systemic antifungal agents must be evaluated to get a proper appreciation of their antifungal activity, which may differ even within the same antifungal class. So, topical administration considered necessity in these situations. AmB belongs to the polyene group has a wide-spectrum in vitro and in vivo antifungal activity. All of the known available formulas of AmB are administrated through intravenous injection to treat severe systemic fungal infections, while the development of the topical formula of AmB is still under preliminary development, including topical pulmonary AmB. Due to the revealing of antimicrobial-resistant fungi in recent years and ineffective systemic management of pulmonary fungi, this study explains the role of topical AmB in treating refractory lung fungi that not response to other drugs that may help researchers to develop an effective topical formula of AmB regarding pulmonary mycosis.

Non-thermal atmospheric plasma treatment of onychomycosis in an in vitro human nail model.

SummaryBackgroundOnychomycosis affects almost 6% of the world population. Topical azoles and systemic antifungal agents are of low efficacy and can have undesirable side effects. An effective, non‐invasive therapy for onychomycosis is an unmet clinical need.ObjectiveDetermine the efficacy threshold of non‐thermal atmospheric plasma (NTAP) to treat onychomycosis in an in vitro model.MethodsA novel toe/nail‐plate model using cadaver nails and agarose media inoculated with Candida albicans was exposed to a range of NTAP doses.ResultsDirect exposure of C albicans and Trichophyton mentagrophytes to 12 minutes of NTAP results in complete killing at doses of 39 and 15 kPulses, respectively. Onset of reduced viability of C albicans to NTAP treatment through the nail plate occurs at 64 kPulses with 10× and 100× reduction at 212 and 550 kPulses, respectively.ConclusionsNTAP is an effective, non‐invasive therapeutic approach to onychomycosis that should be evaluated in a clinical setting.