Resistant Candida Strains Research Articles

Antifungal activity of a prenylated flavonoid from Dalea elegans against Candida albicans biofilms

BackgroundThe continuing emergence of infections with antifungal resistant Candida strains requires a constant search for new antifungal drugs, with the plant kingdom being an important source of chemical structures. PurposeThe present study investigated the antifungal effect of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-8-prenylpinocembrin (8PP, formerly 6PP), a natural prenylflavonoid, on Candida albicans biofilms, and compared this with an azole antifungal (fluconazole) by studying the cellular stress and antioxidant response. Study design/methodsThe fluconazole sensitive (SCa) and azole-resistant (RCa) C. albicans strains were used, with biofilm formation being studied using crystal violet (CV) and confocal scanning laser microscopy (CSLM). The minimal inhibitory concentration for sessile cells (SMIC) was defined as the concentration of antifungal that caused a 50% (SMIC 50) and 80% (SMIC 80) reduction of treated biofilms. The reactive oxygen species (ROS) were detected by the reduction of nitro blue tetrazolium (NBT), and reactive nitrogen intermediates (RNI) were determined by the Griess assay. The activities of the superoxide dismutase (SOD) and catalase (CAT) antioxidant enzymes and the total antioxidant capacity of the biofilms were measured by spectrophotometric methods. ROS accumulation was also detected inside biofilms by using the fluorogenic dye 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), which was visualized by CSLM. ResultsThe SCa and RCa biofilms were strongly inhibited by 8PP at 100 µM (SMIC 80). We observed that cellular stress affected biofilms growth, resulting in an increase of ROS and also of reactive nitrogen intermediates (RNI), with SOD and CAT being increased significantly in the presence of 8PP. The basal level of the biofilm total antioxidant capacity was higher in RCa than SCa. Moreover, in SCa, the total antioxidant capacity rose considerably in the presence of both 8PP and fluconazole. ConclusionOur data suggest that 8PP may be useful for the treatment of biofilm-related Candida infections, through an accumulation of endogenous ROS and RNI that can induce an adaptive response based on a coordinated increase in antioxidant defenses. 8PP may also have a therapeutic potential in C. albicans infections.

Effect of two monoterpene phenols on antioxidant defense system in Candida albicans

Thymol and carvacrol from the class of monoterpene phenols are one of the most potent plant essential oil components possessing antimicrobial effects. Known for their wide bioactive spectrum, these positional isomers of isopropyl cresol deplete ergosterol content, compromise membrane permeability, block efflux pumps and restore antifungal susceptibility to fluconazole in resistant Candida strains. Exposure to these natural compounds induces a cascade of stress responses, which are important to comprehend their microbicidal mechanisms. This study evaluates the antioxidant defense response to lower concentrations of thymol and carvacrol in Candida albicans. The antioxidant defense responses in C. albicans are important for developmental mechanisms pertaining to resistance against the immune system, infection establishment and drug resistance. In this view, primary and secondary antioxidant defense enzymes, and oxidative stress markers including glutathione and lipid peroxidation were determined in C. albicans cells exposed to lower concentrations of thymol and carvacrol. These compounds were found to induce oxidative stress and compromised the antioxidant defense system in C. albicans at lower concentrations. This study helps in understanding the ‘in cell’ antifungal mechanisms of natural monoterpene phenols originating from oxidative stress. Thymol and carvacrol induced membrane deterioration reported earlier, is further explained as a result of a toxic radical cascade mediated by lipid peroxidation. Findings reinforce the observed toxic oxidizing effects of these compounds as a consequence of direct damage to antioxidant components and not to their genetic manipulations.

Novel Macrocyclic Amidinoureas: Potent Non-Azole Antifungals Active against Wild-Type and Resistant Candida Species.

Novel macrocyclic amidinourea derivatives 11, 18, and 25 were synthesized and evaluated as antifungal agents against wild-type and fluconazole resistant Candida species. Macrocyclic compounds 11 and 18 were synthesized through a convergent approach using as a key step a ring-closing metathesis macrocyclization reaction, whereas compounds 25 were obtained by our previously reported synthetic pathway. All the macrocyclic amidinoureas showed antifungal activity toward different Candida species higher or comparable to fluconazole and resulted highly active against fluconazole resistant Candida strains showing in many cases minimum inhibitory concentration values lower than voriconazole.

Susceptibility profile of Candida spp. isolated from humans and dogs with stomatitis to the essential oil of Thymus vulgaris

Candida spp. form a part of human and animal oral cavity flora. However Candida spp. is the main cause of dental related stomatitis in humans and stomatitis in dogs. Stomatitis treatment implies the use of azoles and polyenes to which yeasts build up resistance. The research is directed to the use of natural compounds such as essential oils. The aim of this paper is to define the antifungal activity of thyme oil on 15 clinical strains of Candida spp., isolated from humans and dogs and to determine if there is a difference in susceptibility between human and dog isolates. Sampling in patients with stomatitis was done by swabbing the denture or oral mucosa swab while sampling in dogs was done by swabbing the oral cavity mucosa after stomatitis has been diagnosed. In order to investigate the antifungal activity of thyme oil in vitro, microdilution method was used. Thyme oil expressed antifungal effects on all investigated strains. Also, our data show that the values of minimum fungicide concentration (MFC) and minimum inhibitory concentration (MIC) are lower in human strains. Explanation is that in most cases, stomatitis in humans is asymptomatic and thus not treated, so Candida strains have not developed resistance. On the other hand, stomatitis in dogs is followed by a marked clinical picture and treated is by antimicotics (mostly by azoles), therefore resistant Candida strains are more likely to occur.

Invasive fungal infections following liver transplantation: Incidence, risk factors, survival, and impact of fluconazole-resistant Candida parapsilosis (2003-2007)

Invasive fungal infections (IFIs) are associated with a high mortality rate for liver transplantation (LT) recipients. To study the incidence of and risk factors for IFIs in LT recipients and the associated mortality rates, we retrospectively reviewed the records of first-time deceased donor LT recipients (January 2003 to December 2007). The incidence of IFIs was 12%. Non-albicans Candida species accounted for 55% of IFIs; 50% of these IFIs were Candida parapsilosis. Only 43% of Candida isolates were fluconazole-susceptible (minimum inhibitory concentration ≤ 8 μ/mL). All C. parapsilosis isolates were fluconazole-resistant, and this coincided with a surge of these isolates during a peak period of LT. Factors associated with IFIs included a creatinine level > 2 mg/mL [hazard ratio (OR) = 2.4, 95% confidence interval (CI) = 1.2-5.0, P = 0.01], a Model for End-Stage Liver Disease score > 25 (OR = 2.4, 95% CI = 1.2-4.9, P = 0.02), pretransplant fungal colonization (OR = 7.0, 95% CI = 3.2-15.3, P < 0.001), and a daily prophylactic fluconazole dosage < 200 mg (OR = 2.8, 95% CI = 1.1-7.4, P = 0.03). According to a multivariate analysis, only pretransplant fungal colonization was associated with IFIs (OR = 7.8, 95% CI = 3.9-16.2, P < 0.001). The 1-year patient survival rates with and without IFIs were 41% and 80%, respectively, and the survival rates with C. parapsilosis, other non-albicans Candida, and Candida albicans IFIs were 28%, 50%, and 75%, respectively. In conclusion, IFIs after LT (especially non-albicans Candida species and fluconazole-resistant C. parapsilosis) were associated with reduced survival. The risk factors highlight the importance of pretransplant risk assessments. The identification of pretransplant fungal colonization may allow for risk modifications before or at the time of LT. Additionally, the number of LT procedures and prophylactic strategies may affect institutional outbreaks of resistant Candida strains.

Azole‐resistant Candida spp. – emerging pathogens?

SummaryInvasive fungal infections cause significant morbidity and mortality in immunocompromised patients. Azoles, and fluconazole in particular, are very active against Candida albicans, and are used widely because of their good tolerability. However, the increasing use of azole antifungals for the treatment of mucosal and systemic Candida infections has resulted in the selection and/or emergence of resistant Candida strains. The main mechanisms of azole resistance among Candida species are the development of bypass pathways, alterations in the ERG 11 gene encoding the azole target enzyme, and the up‐regulation of genes encoding efflux pumps. A better understanding of the mechanisms and clinical impact of antifungal resistance is essential to prompt and efficient treatment of patients with invasive mycoses and to improve the outcome of such infections.

A Retrospective Analyses of Candida Spp. Infections in the Intensive Care Unit

Introduction: Systemic fungal disease, by Candida species, are a much feared complication in NICU.Objectives: We evaluated the higher incidence of Candida A. infection and not particularly in VLBW and ELBW infants.Methods: Infection cases by Candida albicans and not recorded in NICU of Messina.Results: The cases were reported 42/1839 (2%) 21 premature infants, G.A. 30.5± 3.78, weight 1550.4 ± 906.9, 14 term infants, G.A. 38.42 ± 1:45,weight 3128.9 ± 290.8, 7 pediatric patients. The fungus most frequently isolated was Candida parapsilosis (19/42- 46%), followed by C. albicans (13/42 - 32%), by C. lambica (5/42 - 12%), C. tropicalis (2/42 - 4%), C.zeylanoides (1/42 - 2%), C.krusei (1/42 - 2%), C.guillermondi (1/42- 2%). Of the 15 preterm with GA ≤ 32, in 8 / 15 (53%) was isolated C.parapsilosis, in 4 / 15 (27%) C. albicans, in 2 / 15 (13%) C.lambica, in one case (1 / 15 - 7%) C.zeylanoides. About patients studied 7 / 42 died (17%) which 6 / 21 preterm infants (28%), 1 / 7 pediatric patients (14%), no term baby died. We have registered two cases of mycetoma in a preterm baby.Conclusions: The increased incidence of Candida parapsilosis is a main cause of infections, linked to fungal adherence ability to prosthetic materials and to proliferate in presence of high glucose concentrations, especially in preterm infants in parenteral nutrition. Our study shown the problem of colonization,the selection of resistant strains of Candida in NICU and its new therapeutic options.

Chemical Composition and Anticandidal Properties of the Essential Oil Isolated from Aerial parts of Cotula cinerea: A Rare and Threatened Medicinal Plant in Morocco

The chemical composition and anticandidal properties of the essential oil of Moroccan Cotula cinerea aerial parts have been examined. GC-MS data were used to identify 24 constituents. Oxygenated monoterpenes constituted the main fraction with trans-thujone (41.4%), cis-verbenyl acetate (24.7%), 1,8-cineole (8.2%) and camphor (5.5%) as the major components. The anticandidal activity of the essential oil was evaluated using a panel of human pathogenic fungi (Candida albicans CCMM L4 and CCMM L5, C. krusei CCMM L10, C. glabrata CCMM L7 and C. parapsilosis CCMM L18). The oil showed high anticandidal activity against all investigated strains with minimal inhibitory concentrations of 3.2 to 4.7 mg/mL depending on the tested yeast and 5.9 mg/mL as a minimal candidicidal concentration value. These findings add significant information to the pharmacological activity of Cotula cinerea essential oil, which may present a good alternative to antibiotics for the treatment of resistant strains of Candida.

Latest developments in fungal lung infection in solid organ transplantation (SOT)

The incidence of invasive mycoses following solid organ transplant (SOT) ranges from 5 to 42% depending on the organ transplanted. Despite the increasing impact of viral infections in SOT, fungal infections still have a main role in transplant recipients. In fact, they remain a common cause of morbidity and mortality in the early and late post-transplant periods. Aspergillus spp. and Candida spp. account for most IFI, but recent epidemiological and clinical studies suggest the emergence of mycelia fungi other than Aspergillus as well as resistant strains of Candida in these patients. Due to the difficulty in making a definitive diagnosis, the treatment is sometimes delayed or is not prescribed (post-mortem diagnosis). Serological and molecular detection of Aspergillus antigens or fungal DNA, in blood and/or BAL samples, may improve the diagnosis of pulmonary aspergillosis, but in SOT the sensitivity is variable and more studies are needed. Another pendent issue is antifungal prophylaxis in SOT recipients; it is unknown which is the best agent or the time duration, and in which receptors must be applied. Treatment combining AmB preparations, newer antifungal drugs, early surgical resection of infected tissue and discontinuation or modulation of immunosuppressive treatment can to be necessary in selected patients and in certain occasions, and all of them may improve prognosis of IFI. However, there are two main handicaps in the management of FI in transplant recipients: firstly, to establish an early diagnosis, secondly, delays in applying early treatment with antifungal drugs. Development of new early diagnostic tools more precise and well-designed multicenter evaluations of diagnostic methods and therapeutic regimens available at present are the important work in the next 3-5 years. This review highlights changing spectrum of invasive fungal infections, risk factors, antifungal prophylaxis, and treatment following SOT.

In vitro activity of inexpensive topical alternatives against Candida spp. isolated from the oral cavity of HIV-infected patients

The use of inexpensive topical alternatives, e.g. oil of melaleuca (tea tree oil (TTO)), chlorhexidine (CHX), povidone iodine (PI) and gentian violet (GV), to treat oral candidiasis in human immunodeficiency virus (HIV)-infected patients has been proposed in resource-poor countries. However, pre-clinical studies comparing the antifungal activity of these agents are lacking. This study compared the minimal inhibitory concentrations (MICs) of TTO, GV, PI, CHX and fluconazole (FLZ) against 91 clinical Candida strains using Clinical and Laboratory Standard Institute (CLSI) methodology. Isolates were obtained from the oral cavity of acquired immune deficiency syndrome (AIDS) patients. Among the topical agents examined, GV showed the most potent activity against all Candida isolates tested (MIC range, MIC for 50% of the organisms (MIC 50) and MIC for 90% of the organisms (MIC 90) of 0.03–0.25 μg/mL, 0.06 μg/mL and 0.12 μg/mL, respectively). CHX was 64 times less active than GV (MIC range, MIC 50 and MIC 90 of 0.5–16 μg/mL, 4 μg/mL and 8 μg/mL, respectively). The lowest antifungal activity was seen for PI (MIC 90 = 0.25%). Moreover, GV, unlike the other topical agents tested, was fungicidal (minimum fungicidal concentration = 1 μg/mL) against Candida albicans isolates ( n = 83). In addition, GV showed activity against FLZ-resistant C. albicans ( n = 3). The combination of GV and FLZ was not antagonistic and there was no interaction between the two compounds. GV possesses potent antifungal activity against FLZ-susceptible and -resistant Candida strains and is not antagonistic when used in combination with FLZ. In vivo evaluation is warranted.

Increase of Virulence and Its Phenotypic Traits in Drug-Resistant Strains of Candida albicans

There is concern about the rise of antifungal drug resistance, but little is known about comparative biological properties and pathogenicity of drug-resistant strains. We generated fluconazole (FLC; CO23 RFLC)- or micafungin (FK; CO23 RFK)-resistant strains of Candida albicans by treating a FLC- and FK-susceptible strain of this fungus (CO23 S) with stepwise-increasing concentrations of either drug. Molecular analyses showed that CO23 RFLC had acquired markedly increased expression of the drug-resistance efflux pump encoded by the MDR1 gene, whereas CO23 RFK had a homozygous mutation in the FSK1 gene. These genetic modifications did not alter to any extent the growth capacity of the drug-resistant strains in vitro, either at 28 degrees C or at 37 degrees C, but markedly increased their experimental pathogenicity in a systemic mouse infection model, as assessed by the overall mortality and target organ invasion. Interestingly, no apparent increase in the vaginopathic potential of the strains was observed with an estrogen-dependent rat vaginal infection. The increased pathogenicity of drug-resistant strains for systemic infection was associated with a number of biochemical and physiological changes, including (i) marked cellular alterations associated with a different expression and content of major cell wall polysaccharides, (ii) more rapid and extensive hypha formation in both liquid and solid media, and (iii) increased adherence to plastic and a propensity for biofilm formation. Overall, our data demonstrate that experimentally induced resistance to antifungal drugs, irrespective of drug family, can substantially divert C. albicans biology, affecting in particular biological properties of potential relevance for deep-seated candidiasis.

Epidemiology and antifungal susceptibility of Candida species isolated from hospitalized patients

Objective Voricanozole and caspofungin are new antifungal agents used in the treatment of Candida infections. However, the susceptibility of Candida species to these antifungal agents could be variable. The aim of this study was to investigate the distribution of the Candida species isolated from hospitalized patients and to determine their susceptibilities to some antifungal agents including voriconazole, caspofungin, fluconazole and amphotericin B. Material and Methods A total of 164 Candida strains were isolated from clinical specimens obtained during the study period. Of 164 strains, 103 (62%) were C. albicans, followed by C. tropicalis (11%) and C. glabrata (8%). Other Candida species less frequently identified were C. parapsilosis, C. lusitaniae, C. kefyr, C. pelliculosa and C. norvegensis. Antifungal susceptibility testing of these isolates were performed according to the CLSI (formerly NCCLS) M27-A2 broth microdilution method and the results were read after 24 h. Results Fluconazole resistance was seen in 21 (13%) isolates. All fluconazole-resistant isolates showed low MICs to caspofungin and amphotericin B. MIC values of voriconazole for Candida isolates were between 0.125 and 4 μg/ml. Conclusion Amphotericin B is still the major therapeutic agent for azole resistant Candida strains and caspofungin seems to be a good alternative.

Fungal infections in solid organ transplantation

Fungal infections in solid organ transplant recipients continue to be a significant cause of morbidity and mortality. Candida spp. and Aspergillus spp. account for most invasive fungal infections. The incidence of fungal infection varies with type of solid organ transplant. Liver transplant recipients have highest reported incidence of candida infections while lung transplant recipients have highest rate of Aspergillus infections. Recent epidemiological studies suggest the emergence of resistant strains of candida as well as mycelial fungi other than Aspergillus in these patients. The current review incorporates the recent changes in the epidemiology of fungal infections in solid organ transplant recipients and highlights the newer data on the diagnosis, prophylaxis and treatment of fungal infections in these patients.

Invasive Pilzinfektionen bei Patienten nach Lebertransplantation

ZusammenfassungFortschritte bei chirurgischer Technik, Immunsuppression und medizinischem Management haben zu einer wesentlichen Verbesserung der Ergebnisse nach Lebertransplantation (LTx) geführt. Pilzinfektionen stellen bei LTx‐Patienten allerdings nach wie vor schwerwiegende Komplikationen mit signifikant verringertem Überleben dar. Der überwiegende Anteil von Pilzinfektionen nach LTx wird durch Candida spp. hervorgerufen, was sich aus dem großen abdominalchirurgischen Eingriff erklärt. Aspergillus‐Infektionen stellen die zweithäufigste Pilzinfektion dar, während andere Erreger wie Pneumocystis, Cryptococcus und Zygomyzeten nur in Einzelfällen eine Rolle spielen. Die hohe Letalität von invasiven Pilzinfektionen bei LTx‐Patienten ist durch den Schweregrad der Grunderkrankung sowie Schwierigkeiten bei Diagnose und medikamentöser Therapie bedingt. Mit den derzeitigen mikrobiologischen Testverfahren ist eine frühe und zuverlässige Diagnose nicht möglich. In der Therapie stellte Amphotericin B bislang das Mittel der Wahl dar, wobei Nebenwirkungen die Anwendung limitieren. Fluconazol weist eine größere therapeutische Breite und geringe Arzneimittelinteraktionen auf. Nachteile sind fehlende Wirksamkeit auf Aspergillus‐Spezies und die Selektion resistenter Candida‐Stämme. Eine Weiterentwicklung stellen aufgrund deutlich geringerer Toxizität und breitem Wirkspektrum neue Azolderivate (Voriconazol) und Echinocandinderivate (Caspofungin) dar. Durch die Identifikation prognostischer Faktoren für die Entwicklung von Pilzinfektionen bei LTx‐Patienten lassen sich Hochrisikogruppen definieren. Eine medikamentöse Prophylaxe bzw. eine präemptive Behandlung bei solchen Risikopatienten kann zu einer Verbesserung der klinischen Ergebnisse führen.

Dose-Dependent Preventive Effect ofSaccharomyces boulardiion clindamycin-induced Alterations in Intestinal Aerobic Flora of the Hamster

The impact of Saccharomyces boulardi i following disruption of flora homeostasis by clindamycin was investigated in the Syrian hamster model. The flora of control animals remained stable and the daily administration of S. boulardii (4x10 10 CFU/kg per day) did not alter this equilibrium. The comparison between control animals and those treated with one single clindamycin dose (10 mg/kg) showed that this antibiotic significantly modified the intestinal aerobic flora. In these animals, the daily administration of S. boulardii induced a dosedependent decrease of the amplitude of the changes associated with clindamycin. In particular a reduction of the resistant strains of streptococci, Enterobacteriaceae and Candida was noted. Moreover the decreased population of the sensitive staphylococcal strains recovered rapidly to their basal level under the yeast treatment. This direct effect of S. boulardii suggests that it can minimize the risk of development of potentially pathogenic strains. Key words: Saccharomyces boulardii , clindamyci n, intestinal microflora, hamster, antibioticassociated diarrhoea .

Voriconazole: The Newest Triazole Antifungal Agent

Fungal infections remain a significant cause of morbidity and mortality despite advances in medicine and the emergence of new antifungal agents (1). Immunocompromised patients are particularly at risk of developing these infections, with Candida and Aspergillus spp. being the mycoses most commonly identified (2). Patients who develop candidemia have a greater chance of prolonged hospitalization and have a mortality rate as high as 60%. In addition, the prevalence of Candida spp. that are resistant to triazole antifungal agents is increasing, making treatment options a concern. Aspergillosis carries a 100% mortality rate if left untreated (3). Although there are numerous treatment options, no broad-spectrum antifungal agents with an acceptable safety profile and with both intravenous and oral formulations are available at this time. Amphotericin B is currently the drug of choice for the treatment of systemic infections caused by Aspergillus and Candida spp. (2–4). However, the high incidence of toxicity associated with amphotericin B has limited its use in many patients. Lipid formulations of amphotericin B are better tolerated than conventional amphotericin B and have similar efficacy. However, these agents are costly and are generally reserved for second-line therapy in patients who did not respond to or could not tolerate conventional amphotericin B therapy. Caspofungin, an echinocandin antifungal agent, has in vitro activity against Aspergillus and Candida spp. However, due to a lack of clinical trials, it is generally reserved for aspergillosis that is refractory to other antifungal treatment. Fluconazole and itraconazole are triazole antifungal agents used in the treatment of fungal infections. They have both intravenous and oral formulations and favorable safety profiles. However, the triazoles' spectrum of activity is somewhat limited. Fluconazole is active mainly against Candida albicans and Cryptococcus neoformans. Itraconazole is most active against Aspergillus spp. and has greater activity than fluconazole against resistant strains of Candida spp. other than C. albicans (2). Voriconazole is the newest agent in the armamentarium against fungal infections. It is a triazole antifungal with a structure related to that of fluconazole and a spectrum of activity comparable to that of itraconazole. Voriconazole was approved by the Food and Drug Administration in May 2002 for the treatment of invasive aspergillosis and refractory infections of Scedosporium apiospermum and Fusarium spp. Studies have also shown it to be a promising agent for empiric treatment in febrile neutropenia.

Cross-Resistance of clinical isolates of Candida albicans and Candida glabrata to over-the-counter azoles used in the treatment of vaginitis.

Antifungal drug resistance in Candida spp. continues to increase in response to the widespread application of triazole therapeutics among immunosuppressed patients. Azole-based over-the-counter (OTC) antifungal agents used to treat vaginitis have the potential to exacerbate this problem by contributing to the selection of highly resistant strains of Candida in otherwise healthy women. In this study, we show that fluconazole-resistant (MIC > 64 microg/mL) blood stream isolates of Candida albicans and Candida glabrata obtained from cancer patients were cross-resistant to the root drugs miconazole, clotrimazole, and tioconazole (found in several over-the-counter products), but remained susceptible to butoconazole. We also provide evidence that spontaneous mutants of Candida glabrata selected for resistance to clotrimazole were cross-resistant to other azolebased drugs, including fluconazole. Our findings demonstrate cross-resistance of Candida strains to fluconazole and OTC azole antifungals, and support the notion that OTC drugs can promote azole resistance in Candida spp.

Glucan synthesis and its inhibition by cilofungin in susceptible and resistant strains of Candida albicans.

The lipopeptide antimycotic agent, cilofungin, at a dose of 20 micrograms ml-1, inhibited beta 1-3 glucan synthesis in a drug-susceptible strain (3153; minimum inhibitory concentration (MIC) < 1 microgram ml-1) as well as in a drug-resistant strain of Candida albicans (CA-2, derived from 3153 by nitrosoguanidine mutagenesis; MIC > 50 micrograms ml-1). This was demonstrated for both whole cells under growing and non-growing conditions, and during protoplast regeneration. However, time-effect experiments, during growth of a CA-2 culture initially exposed to an inhibitory dose of cilofungin, showed that this strain was able to progressively regain both glucan synthesis and a growth rate comparable to that of cultures that had not been treated with the drug. This recovery was not attributable to cilofungin instability or degradation within the CA-2 culture. Our study suggests the existence of an as yet unknown drug-related and/or cell-related factor(s) modulating the inhibition of glucan synthesis, and then contributing to the actual inhibitory effects of cilofungin in C. albicans.

Itraconazole Serum Levels in the Preterm Neonate

The increasing use of invasive procedures and antibiotic treatments has caused an increase in candidal infections in preterm neonates. Antifungal drugs currently used are toxic (amphotericin B) or lead to rapid development of resistant Candida strains (flucytosine). This has led to a search for new, less toxic, drugs. The bioavailability of itraconazole, an oral antifungal agent with broad-spectrum activity and low toxicity, was therefore investigated. Trough and peak serum levels of itraconazole were measured by high performance liquid chromatography in 6 preterm neonates (gestational age, 25.6 ± 0.8 weeks; weight, 760 ± 120 g), 48 h after initiating therapy with itraconazole, 5 mg/kg/day, in hydroxypropyl-Β-cyclodextrin solution. The area under the curve could be determined in 4 neonates (gestational age, 25.7 ± 1.0 weeks; weight, 825 ± 55 g) with a dose interval of 24 h. The parameters obtained were: trough, 85 + 18 ng/ml; peak, 276 ± 41 ng/ml; AUC (0-24 h), 5,138 ± 1,188 ng·h/ml. It was concluded that itraconazole, 5 mg/kg/day, is well absorbed and recommended levels are reached in preterm neonates of less than 32 weeks gestational age. No side-effects were seen. Itraconazole may be a useful antifungal drug in preterm neonates, but further studies on efficacy and safety are needed.

Interaction of polyene antibiotics with sensitive and resistant strains ofCandida albicons

Interaction of polyene antibiotics with sensitive and resistant strains ofCandida albicons