[Mycoses and antifungals: What is the situation in Senegal in the current context?] / Mycoses et antifongiques : quelle est la situation du Sénégal dans le contexte actuel ?

In the context of increasing incidence of fungal infections worldwide, the availability of antifungal drugs was studied in Senegal, a country with limited resources where diagnosis of invasive fungal infections is not often established by lack of specialists and/or diagnostic tools. After a background on the country's situation with regard to fungal infections and the drug distribution network in Senegal, a compilation of the various available antifungals was presented before concluding with recommendations to prepare for a situation that could allow to treat appropriately invasive mycoses.

The yeast, the antifungal, and the wardrobe: a journey into antifungal resistance mechanisms of Candida tropicalis.

Candida tropicalis is a prominent non-Candida albicans Candida species involved in cases of candidemia, mainly causing infections in patients in intensive care units and (or) those presenting neutropenia. In recent years, several studies have reported an increase in the recovery rates of azole-resistant C. tropicalis isolates. Understanding C. tropicalis resistance is of great importance, since resistant strains are implicated in persistent or recurrent and breakthrough infections. In this review, we address the main mechanisms underlying C. tropicalis resistance to the major antifungal classes used to treat candidiasis. The main genetic basis involved in C. tropicalis antifungal resistance is discussed. A better understanding of the epidemiology of resistant strains and the mechanisms involved in C. tropicalis resistance can help improve diagnosis and assessment of the antifungal susceptibility of this Candida species to improve clinical management.

The pathogenicity of Aspergillus fumigatus, drug resistance, and nanoparticle delivery.

The genus Aspergillus includes fungal species that cause major health issues of significant economic importance. These microorganisms are also the culprit for production of carcinogenic aflatoxins in grain storages, contaminating crops, and economically straining the production process. Aspergillus fumigatus is a very important pathogenic species, being responsible for high human morbidity and mortality on a global basis. The prevalence of these infections in immunosuppressed individuals is on the rise, and physicians struggle with the diagnosis of these deadly pathogens. Several virulence determinants facilitate fungal invasion and evasion of the host immune response. Metabolic functions are also important for virulence and drug resistance, since they allow fungi to obtain nutrients for their own survival and growth. Following a positive diagnostic identification, mortality rates remain high due, in part, to emerging resistance to frequently used antifungal drugs. In this review, we discuss the role of the main virulence, drug target, and drug resistance determinants. We conclude with the review of new technologies being developed to treat aspergillosis. In particular, microsphere and nanoparticle delivery systems are discussed in the context of improving drug bioavailability. Aspergillus will likely continue to cause problematic infections in immunocompromised patients, so it is imperative to improve treatment options.

Synthesis of new oxadiazole, pyrazole and pyrazolin-5-one bearing 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide analogs as potential antibacterial and antifungal agents.

Two series of diversely substituted phenyldiazenyl(2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetyl)3,5-dimethyl-1H-pyrazole 11a-g and phenyldiazenyl-1-(2-(4-methyl-2-oxo-4-chromen-7-yloxy)acetyl)-3-methyl-1H-pyrazol-5(4)H-one 12a-j were synthesized. All these compounds were characterized by IR, NMR, mass spectra and elemental analyses. The compounds were evaluated for their in vitro antibacterial activity against some Gram-positive bacteria, Staphylococcus aureus, Bacillus subtilis, Gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and screened for antifungal activity against A. niger, U. maydis. The compounds showed moderate to very good antibacterial activities.

[Non-antibiotic anti-infectious treatments in urology]. / Les médicaments anti-infectieux non antibiotiques en urologie.

OBJECTIVE: To define the terms of use of pesticides, antifungal, antiviral and antiseptic treatments in urology. MATERIALS AND METHODS: A literature search was conducted on MEDLINE for all these treatments used in urology. The molecules were classified by family. Modes of action, indications in urology and adverse effects have been detailed. Authorisation files were consulted and then complemented by a literature analysis. RESULTS: Although parasitic or viral diseases are uncommon in urology, their specific treatment deserves a thorough knowledge of pesticide and antiviral molecules. Antifungal treatments are regularly used in urology with special features to know to improve the efficacy/safety ratio. Antiseptics are used daily in urology and a better understanding of these molecules allows better use. CONCLUSION: Beyond antibiotics, antiviral, antiparasitic and antifungal deserve a thorough knowledge. Antiseptic although used daily have features little known.

Thesaurus for off-label indications for systemic antifungal agents.

OBJECTIVES: Following the removal of temporary treatment protocol procedures, we developed a thesaurus for off-label indications for systemic antifungals at our facility to update clinical practices and to control off-label prescriptions. MATERIALS AND METHODS: Clinical practice guidelines and literature data were analyzed. This work was part of an antifungal stewardship program. RESULTS: Off-label wording (prophylaxis, preemptive, empirical, curative) and corresponding antifungals and references were validated by the multidisciplinary group for antifungal agents under the aegis of the Commission for the use of drugs and sterile medical devices and of the anti-infective committee. CONCLUSION: Considering the complexity of invasive fungal infection management, this thesaurus needs to be shared and used as a helping tool to review off-label situations.

From phaeohyphomycosis to disseminated chromoblastomycosis: A retrospective study of infections caused by dematiaceous fungi.

OBJECTIVE: Infections caused by dematiaceous fungi are more common in tropical and subtropical areas. We aimed to describe the clinical, microbiological and therapeutic aspects of case patients diagnosed at a University Hospital located on an Indian Ocean island. PATIENTS AND METHODS: We performed an observational retrospective study of infections caused by dematiaceous fungi diagnosed at the University Hospital of Saint-Pierre, Reunion, from 2000 to 2015. Mycological identifications were performed at the National Reference Center for Invasive Mycosis and Antifungal Agents (Paris). RESULTS: The review of clinical and microbiological data of 11 patients identified revealed that five were infected by dematiaceous fungi. Two had cutaneous phaeohyphomycosis, two had cerebral phaeohyphomycosis and one had cutaneous chromoblastomycosis with brain and potentially medullary dissemination. Skin lesions and cerebral abscesses were quite varied. CONCLUSION: Infections caused by dematiaceous fungi are rare. Medullary and brain localizations are extremely rare, especially for chromoblastomycosis. Cutaneous manifestations of phaeohyphomycosis are varied; diagnosis is thus more difficult. It is therefore important, when confronted with a chronic tumor-like lesion in endemic areas, to perform a biopsy for pathology and fungal culture. While surgical excision is not always sufficient, medical treatment of these infections is not standardized, but relies on an azole, which can be associated with another antifungal agent.

[Post-traumatic pulmonary aspergilloma]. / Aspergillome pulmonaire sur corps étranger résiduel post-traumatique. Diagnostic et prise en charge.

INTRODUCTION: Aspergillomas occur due to colonization of a pre-existing pulmonary, bronchial or pleural cavity by Aspergillus spp. Often asymptomatic, this pathology can reveal itself by recurrent haemoptysis or when bacterial superinfections occur. Aspergillomas occurring in post-traumatic cavities are rare and their management is poorly codified. CASE REPORT: A child suffered from a chest wound at the age of 13 years. Two years later, investigation of recurrent haemoptysis revealed a residual pneumatocele in the right lower lobe colonized by Aspergillus spp. Initial treatment with systemic azole antifungals was unsuccessful because of digestive and ophthalmological intolerance. Surgical treatment by right lower lobectomy was finally decided on by the multidisciplinary team. This revealed an intrabronchial foreign body of vegetal type with cellulosic reinforcement, causing a polymorphic granulomatous reaction around, and associated with a proliferation of filamentous fungi including Aspergillus fumigatus. Surgery was followed by liposomal amphotericin B treatment for three weeks with a favourable outcome. CONCLUSIONS: This clinical case illustrates the benefits of surgical management of post-traumatic aspergillomas, even in children, in order to eradicate the aspergillus implant and to remove any foreign body to prevent recurrence.

Assessment of high-priced systemic antifungal prescriptions.

OBJECTIVES: To assess compliance with international guidelines for costly antifungal prescriptions and to compare these results with a first study performed in 2007. METHODS: Retrospective study including all costly antifungal prescriptions made in surgical and medical intensive care units and in a hepatobiliary, pancreatic, and digestive surgery unit. Prescriptions were assessed in terms of indication, dosage, and antifungal de-escalation. RESULTS: Seventy-four treatments were analyzed. Treatments were prescribed for prophylactic (1%), empirical (22%), pre-emptive (16%), or targeted therapy (61%). Caspofungin accounted for 68% of prescriptions, followed by voriconazole (20%) and liposomal amphotericin B (12%). Indication was appropriate in 91%, debatable in 1%, and inappropriate in 8%. Dosage was appropriate in 69%, debatable in 8%, and inappropriate in 23%. Prescriptions were inappropriate for the following reasons: lack of dosage adjustment in light of the hepatic function (10 cases), underdosage or excessive dosage by>25% of the recommended dose in seven cases. De-escalation to fluconazole was implemented in 40% of patients presenting with a fluconazole-susceptible candidiasis. CONCLUSION: The overall incidence of appropriate use was higher in 2012 compared with 2007 (62% and 37% respectively, P=0.004). Nevertheless, costly antifungal prescriptions need to be optimized in particular for empirical therapy, dosage adjustment, and potential de-escalation to fluconazole.

Holothurians antifungal and antibacterial activity to human pathogens in the Persian Gulf.

Pharmaceutical industries now accept that oceans contain a vast array of organisms with unique biological properties. As investigation of antimicrobial activity, three species of Holothuria sea cucumbers (Holothuria scabra, Holothuria parva and Holothuria leucospilota) from the Persian Gulf, Iran, were obtained, their different organs: gonads (G), body wall (BW), intestine tract (IT), respiratory tree (RT) were isolated and extracted with organic solvents: ethyl acetate and methanol. Antifungal and antibacterial activities of each fraction was estimated with a minimum inhibitory concentration (MIC) and disk-diffusion method against the number (i.e. n=10) of human pathogenic microbes (eight pathogenic Gram-positive/negative bacteria strains and two fungi). All the sea cucumbers extracts confirmed their strong potential antagonistic effect against the bacterial and fungal indicators, except for three relatively resistant microbial strains: Candida albicans and Pseudomonas aeruginosa and Klebsiella pneumonia. Most effective antifungal and antibacterial activities were recorded for methanolic extract of intestine tract organs of H. parva against Saccharomyces cerevisiae (MIC=0.09mg/ml, IZ=22±0.8mm) and Staphylococcus epidermidis (MIC=0.04mg/ml and IZ=30±0.9mm), compared the other extracts. Nevertheless, the differences between species can result from a variety of their natural habits. The finding suggests that marine Holothuria sea cucumber specie, especially H. parva, has a potential source for the discovery of natural antibiotic compounds and drug development.

[Not Available]. / Spécificités pédiatriques de l'utilisation des antifongiques.

Specificity of antifungals use in paediatric patients is linked to mycoses epidemiology in this population. Pharmacokinetics vary with patient age. Although studies are in progress, pharmacokinetic data in children are limited in number for most antifungals. Among antifungal agents, those approved in France for use in children are rare. Adverse event frequency can differ in children, as compared to frequency in adults, and drug interaction should be a major worry. Relative interest and cost of available forms in the paediatric population in not always taken into account. For each different situation, an optimal strategy of antifungals use in children should be determined.

Rhodotorula fungemia: Report of two cases in Sfax (Tunisia).

Rhodotorula is emerging as an important cause of nosocomial and opportunistic infections. We present two cases of Rhodotorula mucilaginosa fungemia diagnosed at our hospital during the last decade. The first case was of a term neonate who presented congenital heart disease (interventricular communication) and body dysmorphic disorder. He was admitted for respiratory failure and sepsis. The second case involved in a 33-year-old woman that had Hodgkinien lymphoma associated to tuberculosis. Identification was performed using commercial systems and confirmed by PCR sequencing of internal transcribed spacer, ITS1 and ITS2 regions of rDNA. Antifungal susceptibility tested by sensititre yeast revealed susceptibility to amphotericin B and resistance to fluconazole for the two strains. These cases emphasize the emerging importance of Rhodotorula sp. as a pathogen and it must be considered a potential pathogen in patients with immunosupression and with central venous catheters. Correct identification is mandatory for appropriate management, as Rhodotorula spp. are resistant to antifungal agents, such as fluconazole.

In vitro activities of five antifungal agents against 199 clinical and environmental isolates of Aspergillus flavus, an opportunistic fungal pathogen.

Aspergillus flavus is the second leading cause of invasive and non-invasive aspergillosis, as well as the most common cause of fungal sinusitis, cutaneous infections, and endophthalmitis in tropical countries. Since resistance to antifungal agents has been observed in patients, susceptibility testing is helpful in defining the activity spectrum of antifungals and determining the appropriate drug for treatment. A collection of 199 clinical and environmental strains of Aspergillus flavus consisted of clinical (n=171) and environmental (n=28) were verified by DNA sequencing of the partial b-tubulin gene. MICs of amphotericin B, itraconazole, voriconazole, posaconazole, and MEC of caspofungin were determined in accordance with the Clinical and Laboratory Standards Institute M38-A2 document. Caspofungin, followed by posaconazole, exhibited the lowest minimum inhibitory concentrations (MIC). All isolates had caspofungin MEC90 (0.063µg/ml) lower than the epidemiologic cutoff values, and 3.5% of the isolates had amphotericin B MIC higher than the epidemiologic cutoff values. However, their clinical effectiveness in the treatment of A. flavus infection remains to be determined.

Comparison of two antifungal susceptibility testing of Candida sp. isolates using agar diffusion method: Neo-sensitabs® tablets and Bio-rad® disks.

INTRODUCTION: The aim of our study was to evaluate the concordance between the two antifungal susceptibility testing of Candida sp. isolates using agar diffusion method: Neo-Sensitabs(®) tablets and Bio-Rad(®) disks. MATERIALS AND METHODS: This is a prospective study conducted in the Laboratory of Parasitology and Mycology of the Mohammed V military teaching hospital from February to August 2012. Upon receiving blood cultures and peripheral sites samples, the identification of Candida isolates performed using routine phenotypic standard tests and the realization of the antifungal susceptibility was carried out on Neo-sensitabs(®) tablets and Bio-Rad(®) disks. RESULTS: A total of 38 Candida strains were isolated: 15 C. albicans (39%), 13 C. glabrata (34%), 5 C. tropicalis (13%), 4 C. krusei (11%) and 1 C. dubliniensis (3%). There were no significant difference (P>0.05) in susceptibility rate between both methods for all antifungal agents tested except for 5-fluorocytosine. The concordance percentage between two methods was 100% for amphotericin B, 97.4% for fluconazole, 94.7% for voriconazole and 73% for 5-fluorocytosine. CONCLUSION: Both methods are easy to perform, rapid and cost effective. Our results showed the best agreement between the two methods for testing the susceptibility of Candida isolates to amphotericin B, fluconazole and voriconazole while for the 5-fluorocytosine, the concordance rate was low.

Evaluation of antifungal activity of standardized extract of Salvia rhytidea Benth. (Lamiaceae) against various Candida isolates.

OBJECTIVES: Salvia species have long been described in traditional medicine for various indications. Owing to the widespread use of this genus by ethnic populations, especially for various infections ranging from skin disease to gastrointestinal disorders, we were encouraged to determine whether Salvia rhytidea could be effective against fungal infections. Given the increased incidence of candidiasis in the past decade, limits on the use of antifungal drugs, emergence of azole-resistant Candida species and increased incidence of treatment failures, it is necessary to identify a novel agent with antifungal properties. Aim of the study was to evaluate the antifungal properties of S. rhytidea against various Candida isolates. MATERIALS AND METHODS: In this study, at first rosmarinic acid content of plant extract was determined. A total of 96 Candida isolates were tested, including the following species: Candida albicans (n=42), Candida glabrata (n=16), Candida tropicalis (n=11), Candida krusei (n=9), Candida parapsilosis (n=9), Candida lusitaniae (n=7) and Candida guilliermondii (n=2). The in vitro antifungal activity of methanolic extracts of S. rhytidea Benth. was evaluated against Candida isolates and compared with that of the standard antifungal drug nystatin by using a broth microdilution method, according to CLSI. RESULTS: Phytochemical screening results showed that the methanolic extract of S. rhytidea Benth. was rich in flavonoids and tannins. The minimal inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of S. rhytidea Benth. ranged from 3.125 to>100µg/ml and 6.25 to>100µg/ml respectively. The growth inhibition value displayed that C. tropicalis, C. krusei and C. albicans isolates were most susceptible to S. rhytidea. CONCLUSIONS: Findings show that S. rhytidea possesses an antifungal effect against Candida isolates.

In vitro antifungal susceptibility of clinical species belonging to Aspergillus genus and Rhizopus oryzae.

OBJECTIVE: Among filamentous fungal pathogens, Aspergillus spp. and zygomycetes account for highest rates of morbidity and mortality among immunocompromised patients. Recently developed antifungal drugs offer the potential to improve management and therapeutic outcomes of fungal infections. The aim of this study was to analyse the in vitro activities of voriconazole, itraconazole, amphotericin B and caspofungin against clinical isolates of Aspergillus spp. and Rhizopus oryzae. MATERIAL AND METHODS: The in vitro antifungal susceptibility of 54 isolates belonging to different clinical isolates of Aspergillus spp. and R. oryzae was tested for four antifungal agents using a microdilution reference method (CLSI, M38-A2). All isolates were identified by typical colony and microscopic characteristics, and also characterized by molecular methods. RESULTS: Caspofungin (MEC range: 0.008-0.25 and MEC50: 0.0023µg/mL) was the most active drug in vitro against Aspergillus spp., followed by voriconazole (MIC range: 0.031-8 and MIC50: 0.5µg/mL), itraconazole (MIC range: 0.031-16 and MIC50: 0.25µg/mL), and amphotericin B (MIC range: 0.125-4 and MIC50: 0.5µg/mL), in order of decreasing activity. The caspofungin, voriconazole, and itraconazole demonstrated poor in vitro activity against R. oryzae isolates evaluated, followed by amphotericin B. CONCLUSION: This study demonstrates that caspofungin had good antifungal activity and azole agents had better activity than amphotericin B against Aspergillus species. Although, azole drugs are considered ineffective against R. oryzae. This result is just from a small scale in vitro susceptibility study and we did not take other factors into consideration.

Role of a NSAID in the apparent cure of a fungal mycetoma.

UNLABELLED: We report the case of a fungal mycetoma due to Madurella mycetomatis that failed to respond to surgery and antifungal treatment but responded strongly to the addition of a non-steroidal anti-inflammatory drug (NSAID). This African patient was born in Mauritania in 1972. He was a herdsman, living close to the Senegal River. The first nodules appeared on the left foot at the age of 13years (1985). The patient suffered frequent flare-ups with the appearance of black grains and underwent surgery in 1988 and 1992 in Senegal. After remission for several months after surgery, new fistulae occurred. The patient emigrated to France in 1995 and underwent a third surgical intervention in 1996. M. mycetomatis was cultured from the black grains. The patient was otherwise in good health, with no diabetes, and HIV tests were negative. We saw the patient for the first time in 2005, at which time he had flare-ups every two to three months. Imaging disclosed an absence of bone involvement. The patient underwent a fourth operation in October, 2005, and voriconazole treatment was initiated. A new flare-up occurred in February, 2006. CT, MRI, and PET scans revealed calcaneus and tarsal involvement, and posaconazole then replaced voriconazole. Flucytosine was added four months later, due to an absence of improvement. New flares-ups occurred and a fifth surgical intervention was performed in September, 2006. The pain, which had been present for three years, worsened; the patient had to stop working and was no longer able to walk without crutches. Amputation of the foot was considered. Empiric treatment with a NSAID, diclofenac (Voltaren(®); 100mg/day), was added to the antifungal treatment in November 2006, to treat the patient's pain and inflammation. A major improvement was observed within one week. The patient was able to walk without crutches one month later. After two months, clinical examination was normal: no pain, inflammation, nodules or fistulae. Flucytosine was stopped after six months of treatment, in January 2007, diclofenac after 10months, in October 2007, and posaconazole after 18.5months, also in October 2007. No relapse has occurred during the eight years of follow-up since treatment ended. The patient seems to have been cured and has normal CT, MRI, and PET scans. IN SUMMARY: This eumycetoma, which had progressed over 20years despite surgery and antifungal treatments, seems to have been cured by the addition of a NSAID. This observation suggests that inflammation plays a major role in the pathogenesis of fungal mycetoma. Clinical studies of treatments including an NSAID should be conducted to confirm this finding.

Prevalence of Candida species in the buccal cavity of diabetic and non-diabetic individuals in and around Pondicherry.

OBJECTIVES: The aim of the present study was to determine the prevalence of Candida in the buccal cavity of diabetic and non-diabetic individuals in and around Pondicherry, India and to analyse the antifungal susceptibility profile of the selected isolates. MATERIALS AND METHODS: A total of 400 buccal samples, 200 each from diabetic and non-diabetic healthy individuals were included in the study. Sabouraud's dextrose agar was used for isolation of Candida species. Identification was performed through microscopy, germ tube test, sugar fermentation test, sugar assimilation test and by using Hichrome agar. Distinct and phenotypically representative colonies were selected and subjected to ITS analysis. In vitro antifungal susceptibility testing for the isolated Candida species was performed using E-test. RESULTS: Results revealed that the prevalence of Candida species in diabetic individuals was higher when compared with non-diabetic healthy individuals. The most predominantly isolated species in diabetic and non-diabetic individuals from buccal cavity was Candida albicans. C. tropicalis was predominant among the non-albicans Candida isolated from both diabetic and non-diabetic individuals. Among denture wearers C. glabrata was predominant. In vitro antifungal susceptibility testing shows that ketoconazole, fluconazole and itraconazole were effective against the isolated Candida species. CONCLUSIONS: The rate of candidal carriage in diabetic individuals is higher. Different species of Candida are present in the oral cavity of diabetic individuals. There may be a positive correlation between glycemic control and candidal colonization. In vitro antifungal susceptibility testing of Candia species are required for proper management and treatment of candidal infections.

Species spectrum and antifungal susceptibility profile of vaginal isolates of Candida in Kuwait.

OBJECTIVE: The study was undertaken to determine the prevalence of vulvovaginal candidiasis (VVC) among patients with vaginitis, frequency of different Candida species, and their susceptibility profile. PATIENTS AND METHODS: Over six months period, high vaginal swabs were cultured on Sabouraud's dextrose agar and isolates were identified by culture on CHROMagar Candida and Vitek2 yeast identification system or/and API 20C (BioMerieux, France). Antifungal susceptibility of the Candida isolates was determined by E-test against amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole and caspofungin. RESULTS: One thousand seven hundred and fifty-two women with vaginitis were screened for the prevalence of Candida spp. Vaginal swab cultures of 231 (13.2%) women yielded Candida spp. The isolation rates of different species were as follows: Candida albicans (73.9%), Candida glabrata (19.8%), Candida kefir (1.94%), Candida tropicalis (0.96%), Candida parapsilosis (0.96%), Candida krusei (0.96%), Candida guilliermondii (0.96%), and Saccharomyces cerevisiae (0.52%). All strains of C. albicans and non-C. albicans were susceptible to most of the antifungal agents tested. CONCLUSION: The high frequency with which C. albicans was recovered and its azole susceptibility support the continued use of azole agents for empirical therapy of uncomplicated VVC. However, a larger controlled study is required to determine the role of non-C. albicans in recurrent VVC.

Candida infection in the intensive care unit: A study of antifungal susceptibility pattern of Candida species in Milad hospital, Tehran, Iran.

OBJECTIVE: The occurrence of Candida infections has improved during the past two decades as a result of increase in the number of immunocompromised patients. In this study the antifungal susceptibility patterns of Candida species isolated from sterile body sites of patients admitted in Milad Intensive Care Unit (ICU) during 6 months were determined. METHODS: Candidal isolates were obtained from 50 patients admitted in Milad ICUs from April to September 2013. Identification of the isolates was performed by using morphological and polymerase chain reaction assay. Resistance to the antifungal agents containing caspofungin, posoconazole, voriconazole and amphotericin B was determined using E-test method. RESULTS: Out of 67 Candida isolates 47.8% were Candida glabrata, 28.3% were C. albicans, 7.5% were C. tropicalis, 7% were C. guilliermondii, 3% were C. krusei and 2% were C. dubliniensis. C. glabrata was the least susceptible species, with 9.4% of the isolates resistant to amphotericin B and 6.3% resistant to posoconazole and voriconazole. No resistance to caspofungin was observed among C. glabrata isolates. One of the C. krusei isolates was resistant to amphotericin B while no resistance to voriconazole, caspofungin and posoconazole was detected among C. krusei strains. Increase in the prevalence of antifungal-resistant non-C. albicans species in recent years has become a problematic event amongst clinicians caring for ICU patients. C. glabrata as the most common species isolated from ICU patients in this study indicated higher levels of antifungal resistance in comparison with other species. This observation accentuates the importance of managing preventive treatments to avoid development of resistance to the current antifungal drugs.