Pseudozyma aphidis fungaemia with invasive fungal pneumonia in a patient with acute myeloid leukaemia: case report and literature review

Pseudozyma species rarely cause invasive diseases in humans, which are usually isolated from plants. There have been anecdotal reports regarding Pseudozyma species infections in patients with underlying diseases or in neonates. However, clinical data and the pathogenicity in humans are still insufficient. We experienced a case of Pseudozyma aphidis fungaemia with invasive fungal pneumonia that developed during reinduction chemotherapy in a 51‐year‐old male with acute myeloid leukaemia (AML). P. aphidis was suspected based on the morphology of the yeast isolated from the blood and was confirmed via rDNA gene sequencing analysis. The patient successfully underwent stem cell transplantation with continuing antifungal treatment and finally completely recovered from both the AML and infectious complications. Here, we report a case of P. aphidis infection that developed during neutropenia in an AML patient and review the global literature.     

In vitro antifungal susceptibilities of isolates of Candida spp. and Aspergillus spp. from China to nine systemically active antifungal agents: data from the SENTRY antifungal surveillance program, 2010 through 2012

We report the in vitro activity of nine systemically active antifungal agents against 237 contemporary clinical isolates of yeast and moulds obtained from 13 laboratories in China during 2010 through 2012. Susceptibility testing was performed using CLSI methods. Sequencing of fks hot spots was performed for echinocandin non‐wild‐type (WT) strains. Isolates included 220 from eight species of Candida, 15 from four species of Aspergillus and one isolate each of Rhodotorula mucilaginosa and Trichosporon asahii. Resistance to amphotericin B (0.0%), flucytosine (0.0–1.7%) and the echinocandins (0.0–3.4%) was distinctly uncommon among C. albicans, C. parapsilosis, C. tropicalis, C. glabrata and C. pelliculosa. Three C. albicans isolates showed resistance to echinocandins and one harboured a mutation in HS1 of fks1. Resistance to the azoles was much more common with resistance to fluconazole, voriconazole and posaconazole detected among isolates of C. glabrata and C. tropicalis. Both C. parapsilosis and C. pelliculosa exhibited decreased susceptibility to fluconazole. Amphotericin B, the mould‐active azoles and the echinocandins were all quite active against isolates of A. fumigatus and A. flavus. Consistent with previous studies from China, resistance to fluconazole is prominent among Candida spp. isolates in this country.     

Isolation of Rhodotorula mucilaginosa from blood cultures in a tertiary care hospital

Rhodotorula species have traditionally been considered as one of common non‐virulent environmental inhabitant. They have emerged as an opportunistic pathogen, particularly in immunocompromised hosts and most infections have been associated with intravenous catheters in these patients. We review the isolates in blood cultures of Rhodotorula mucilaginosa in our Hospital. We describe the demographic and clinical features of the cases and the antifungal susceptibility profiles of the isolates. Selected patients had an isolation of R. mucilaginosa in blood cultures in our tertiary care Hospital. All data were collected retrospectively from clinical records during 5 years. We report 8 isolates in blood, two of them were considered contaminants. Immunosuppression, surgery, previous antibiotic therapy were common clinical features. For all the isolates, minimum inhibitory concentration (MIC) values were high for echinocandins and azoles and low for amphotericin B and 5‐flucytosine. One strain showed atypical susceptibility profile. Rhodotorula mucilaginosa may be present on the skin and blood cultures can be contaminated. Fungaemia due to R. mucilaginosa is a rare clinical entity which requires risk factors but clinically relevant because of the multiresistant profile. Rhodotorula mucilaginosa shows high MIC values for azoles and echinocandins, therefore amphotericin B and flucytosine must be administered as antifungal therapy.     

Invasive infections due to Saprochaete and Geotrichum species: Report of 23 cases from the FungiScope Registry

Saprochaete and Geotrichum spp. are rare emerging fungi causing invasive fungal diseases in immunosuppressed patients and scarce evidence is available for treatment decisions. Among 505 cases of rare IFD from the FungiScope^? registry, we identified 23 cases of invasive infections caused by these fungi reported from 10 countries over a 12‐year period. All cases were adults and previous chemotherapy with associated neutropenia was the most common co‐morbidity. Fungaemia was confirmed in 14 (61%) cases and deep organ involvement included lungs, liver, spleen, central nervous system and kidneys. Fungi were S. capitata (n=14), S. clavata (n=5), G. candidum (n=2) and Geotrichum spp. (n=2). Susceptibility was tested in 16 (70%) isolates. All S. capitata and S. clavata isolates with the exception of one S. capitata (MIC 4 mg/L) isolate had MICs>32 mg/L for caspofungin. For micafungin and anidulafungin, MICs varied between 0.25 and >32 mg/L. One case was diagnosed postmortem, 22 patients received targeted treatment, with voriconazole as the most frequent first line drug. Overall mortality was 65% (n=15). Initial echinocandin treatment was associated with worse outcome at day 30 when compared to treatment with other antifungals (amphotericin B ± flucytosine, voriconazole, fluconazole and itraconazole) (P=.036). Echinocandins are not an option for these infections.     

Rhodotorula minuta as onychomycosis agent in a Chinese patient: first report and literature review

Onychomycosis is a common superficial fungal infection, which usually caused by dermatophytes, yeast and non‐dermatophytic moulds. Recently, we isolated a Rhodotorula minuta isolate from a 15‐year‐old immunocompetent girl student in Hangzhou (China) that was identified using microscopy, culture morphology, histological diagnosis, API 20C AUX Yeast Identification Kit and sequencing of the Internal Transcribed Spacer region. In vitro, antifungal susceptibility tests showed that this yeast isolate was susceptible to low concentrations of amphotericin B, itraconazole, voriconazole and 5‐flvoriconaz but that it appeared to be dose‐dependent susceptible to fluconazole(MIC = 16 μg/ml). Furthermore, the effective result of therapy with itraconazole against R. minuta was consistent with that of susceptibility tests.     

Candida glabrata – unique features and challenges in the clinical management of invasive infections

Candida glabrata is a pathogenic yeast with several unique biological features. This article provides an up‐to‐date review on current data and reasoning aspects of this clinically problematic organism. Haploidy, absence of pseudohyphae, facultative anaerobe growth of C. glabrata, as well as its intrinsically low susceptibility to azole antifungals require specific consideration in diagnosis and treatment approaches. As C. glabrata today represents a sizeable percentage of pathogens in candidaemia, the use of azole antifungals in upfront therapy of invasive yeast infections is discouraged by recent guidelines. While the selection of C. glabrata mutants with impaired susceptibility to echinocandins has been described, analyses of several clinical studies indicate an association of improved outcomes with the use of echinocandins as the primary treatment for invasive yeast infections with potential or documented involvement of C. glabrata.     

In vitro interactions between amphotericin B and other antifungal agents and rifampin against Fusarium spp.

Fusarium species are common hyaline soil saprophytes and plant pathogens that are opportunistic fungal pathogens of immunocompromised patients. The treatment for fusariosis remains uncertain with an unfavourable prognosis; new possibilities for treatment, such as various synergistic drug interactions, must be uncovered. In this study, we evaluated the in vitro interactions of amphotericin B with caspofungin, ketoconazole, 5‐flucytosine, itraconazole, miconazole, rifampin, fluconazole, terbinafine and voriconazole against isolates of Fusarium spp. using the chequerboard method with interactions evaluated by fractional inhibitory concentration indices. The highest percentages of synergistic interactions were observed for the combinations of amphotericin B and caspofungin (68.7%), amphotericin B and rifampin (68.7%), amphotericin B plus 5‐flucytosine (59.3%) and amphotericin B with voriconazole (37.5%). The pattern of susceptibility to antifungal agents among Fusarium species and their consequence on the effects of drug combinations are also discussed.     

In vitro activities of new and conventional antimycotics against fluconazole-susceptible and non-susceptible Brazilian Candida spp. isolates

The substantial increase in the rate of azole resistant Candida spp. yeast infections has become a serious treatment problem requiring new and more active antifungal agents. In this study, the in vitro activities of ravuconazole and albaconazole were compared with those of amphotericin B, flucytosine, itraconazole and fluconazole against 162 Brazilian isolates of Candida spp. from which 48 isolates had previously shown lower susceptibility or resistance to fluconazole. Ravuconazole susceptibility ranged from 84.6% (Candida albicans) to 100% for other species and albaconazole MIC(90) was < or =1.0 microg ml(-1) for all the species emphasising the potent activity of these triazoles. To our knowledge this is the first study evaluating the susceptibility of C. dubliniensis to albaconazole.     

An outbreak due to Candida auris with prolonged colonisation and candidaemia in a tertiary care European hospital

Multidrug‐resistant Candida auris has emerged as a cause of insidious hospital outbreaks and complicated infections. We present the analysis of an ongoing C. auris outbreak including the largest published series of C. auris bloodstream infection. All C. auris‐positive patients from April‐2016 to January‐2017 were included. Environmental, clinical and microbiological data were recorded. Definitive isolate identification was performed by ITS‐rDNA sequencing, and typing by amplified fragment length polymorphism fingerprinting. One hundred and forty patients were colonised by C. auris during the studied period (68% from surgical intensive care). Although control measures were implemented, we were not able to control the outbreak. Forty‐one invasive bloodstream infections (87.8% from surgical intensive care) were included. Clinical management included prompt intravascular catheter removal and antifungal therapy with echinocandins. All isolates were fluconazole‐ and voriconazole‐resistant, but echinocandin‐ and amphotericin B‐susceptible. Thirty‐day mortality rate was 41.4%, and severe septic metastasis as spondylodiscitis and endocarditis were observed in 5 patients (12%). C. auris was also recovered from inanimate patient surroundings and medical equipment. Despite antifungal treatment, high mortality and late complication rates were recorded. Molecular typing suggested a clonal outbreak different from those previously published.     

Echinocandin to fluconazole step‐down therapy in critically ill patients with invasive,susceptible Candida albicans infections

Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step‐down to fluconazole when the patients’ condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step‐down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step‐down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28‐day or 90‐day mortality between the groups. Step‐down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin.     

In vitro combination between antifungals and diphenyl diselenide against Cryptococcus species

Cryptococcus species are an encapsulated fungal pathogen that cause cryptococcal meningitis. There are limited therapeutic options for this infection. The management includes the use of different antifungals such as amphotericin B, flucytosine, or fluconazole, either alone or in combination. However, numerous therapeutic failures, as well as the limited effectiveness of such therapeutics, have been described. Diphenyl diselenide is a chemically synthesised molecule with was found to have antimicrobial activity. In this study, we evaluated the antifungal activities of fluconazole, amphotericin B and flucytosine, in combination with diphenyl diselenide against 30 clinical isolates of Cryptococcus spp. using CLSI M27‐A3 method and the checkerboard microdilution technique. Our results show that the combination of flucytosine and diphenyl diselenide displayed 100% of synergism. However, when we analysed (PhSe)₂ plus AMB or FLZ we observed around 70% of indifference. Our results suggest that the combination of diphenyl diselenide with other antifungal agents deserves attention as a new option for the development of alternative therapies for cryptococcosis.     

Central nervous system infection due to Cryptococcus gattii sensu lato in India: Analysis of clinical features,molecular profile and antifungal susceptibility

Cryptococcus gattii species complex has evolved as a pathogen in the last two decades causing infection among both immunocompetent and immunocompromised hosts. We aimed to analyse the clinical features of CNS infection caused by C. gattii sensu lato, molecular and antifungal susceptibility profile of this pathogen. Cases diagnosed to have CNS cryptococcosis were included in the study. Cryptococcus recovered from patient's specimen was identified by standard protocol. Species confirmation, mating type and molecular type determination were performed by PCR based methods. Antifungal susceptibility was tested in VITEK2C to amphotericin B, 5‐flucytosine, fluconazole and voriconazole. Among 199 cases, 20 (10%) were due to C. gattii, comprising of 75% cryptococcal meningitis and 25% cryptococcoma cases. Young adult males were commonly affected. Headache and vomiting were prominent symptoms and 50% were immunocompromised. Among the isolates, 75%, 20% and 5% were C. tetragattii, C. gattii sensu stricto and C. bacillisporus respectively and all had mating type α. Four (20%) isolates of C. tetragattii and the only isolate of C. bacillisporus were resistant to fluconazole. The most common species isolated from south India is C. tetragattii. The study contributes to the epidemiology of C. gattii and reiterates the need for genotyping and antifungal susceptibility testing.     

Efficacy of micafungin in invasive candidiasis caused by common Candida species with special emphasis on non‐albicans Candida species

The incidence of invasive candidiasis caused by non‐albicans Candida (NAC) spp. is increasing. The aim of this analysis was to evaluate the efficacy of micafungin, caspofungin and liposomal amphotericin B in patients with invasive candidiasis and candidaemia caused by different Candida spp. This post hoc analysis used data obtained from two randomised phase III trials was conducted to evaluate the efficacy and safety of micafungin vs. caspofungin and micafungin vs. liposomal amphotericin B. Treatment success, clinical response, mycological response and mortality were evaluated in patients infected with C. albicans and NAC spp. Treatment success rates in patients with either C. albicans or NAC infections were similar. Outcomes were similar for micafungin, caspofungin and liposomal amphotericin B. Candida albicans was the most prevalent pathogen recovered (41.0%), followed by C. tropicalis (17.9%), C. parapsilosis (14.4%), C. glabrata (10.4%), multiple Candida spp. (7.3%) and C. krusei (3.2%). Age, primary diagnosis (i.e. candidaemia or invasive candidiasis), previous corticosteroid therapy and Acute Physiology and Chronic Health Evaluation II score were identified as potential predictors of treatment success and mortality. Micafungin, caspofungin and liposomal amphotericin B exhibit favourable treatment response rates that are comparable for patients infected with different Candida spp.     

First isolation of Candida wangnamkhiaoensis from the blood of immunocompromised paediatric patient

Candida wangnamkhiaoensis is a species clustered under the Hyphopichia clade has not ever been isolated from any clinical specimens. To the best of our knowledge, this is the first report of C. wangnamkhiaoensis associated with fungaemia in immunocompromised paediatric patient. The isolate was assigned a strain name as UZ1679/14, in which the identification was confirmed by a polymerase chain reaction‐sequencing of the internal transcribed spacer (ITS) and large subunit (LSU) regions of the rRNA gene. Antifungal susceptibility pattern showed that the isolate was sensitive to anidulafungin, caspofungin, fluconazole and voriconazole. The patient clinically improved after the antifungal treatment with caspofungin.     

Susceptibility profile and epidemiological cut‐off values of Cryptococcus neoformans species complex from Argentina

Epidemiological cut‐off values (ECVs) based on minimal inhibitory concentration (MIC) distribution have been recently proposed for some antifungal drug/Cryptococcus neoformans combinations. However, these ECVs vary according to the species studied, being serotypes and the geographical origin of strains, variables to be considered. The aims were to define the wild‐type (WT) population of the C. neoformans species complex (C. neoformans) isolated from patients living in Argentina, and to propose ECVs for six antifungal drugs. A total of 707 unique C. neoformans isolates obtained from HIV patients suffering cryptococcal meningitis were studied. The MIC of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole was determined according to the EDef 7.2 (EUCAST) reference document. The MIC distribution, MIC₅₀, MIC₉₀ and ECV for each of these drugs were calculated. The highest ECV, which included ≥95% of the WT population modelled, was observed for flucytosine and fluconazole (32 μg ml^?1 each). For amphotericin B, itraconazole, voriconazole and posaconazole, the ECVs were: 0.5, 0.5, 0.5 and 0.06 μg ml^?1 respectively. The ECVs determined in this study may aid in identifying the C. neoformans strains circulating in Argentina with decreased susceptibility to the antifungal drugs tested.     

Trichosporon asahii infection presenting as chronic meningo‐ventriculitis and intra ventricular fungal ball: a case report and literature review

Central nervous system trichosporonosis is a rare clinical entity and so far only six cases including three each of brain abscess and meningitis has been on record. We report a rare case of chronic meningo‐ventriculitis and intraventricular fungal ball due to Trichosporon asahii in an 18‐year‐old immunocompetent male from Burundi, east Africa. Neuroendoscopy showed multiple nodules and a fungal ball within the ventricle, which on culture grew T. asahii. He was initially empirically treated with liposomal amphotericin B. However, the antifungal susceptibility testing of T. asahii isolate revealed high minimum inhibitory concentration for amphotericin B (2 μg ml^?1), flucytosine (16 μg ml^?1) and caspofungin (2 μg ml^?1) but exhibited potent activity for voriconazole, posaconazole, itraconazole and fluconazole. The patient rapidly succumbed to cardiac arrest before antifungal therapy could be changed. Although disseminated trichosporonosis has been increasingly reported the diagnosis represents a challenge especially in rare clinical settings such as intraventricular fungal ball in the present case, which has not been described previously.     

Kodamaea ohmeri isolate from two immunocompromised patients: first report in Italy

Kodamaea ohmeri is an unusual yeast‐form fungus that has recently been identified as an important aetiological agent of fungaemia, endocarditis, cellulitis, funguria and peritonitis in immunocompromised patients. We present two new isolated of K. ohmeri. The microorganisms were identified by CHROMagar Candida medium, VitekII system and API ID32C. Biochemical identification of the two yeast isolates was confirmed by sequence analysis of the 26S ribosomal DNA. Antifungal susceptibility testing done by Sensititre YeastOne showed that the isolates were susceptible to amphotericin B, voriconazole and itraconazole. This work is the first report of isolation of K. ohmeri in immunocompromised patients in Italy.     

Fluconazole plus flucytosine is a good alternative therapy for non‐HIV and non‐transplant‐associated cryptococcal meningitis: A retrospective cohort study

Cryptococcal meningitis (CM) carries a high risk of mortality with increasing incidences in immune competent hosts. Current treatments are not well tolerated, and evaluation of other treatments is needed. Fluconazole and 5‐flucytosine in treating immune competent hosts have not been characterised. To evaluate the efficacy of fluconazole and 5‐flucytosine in treating non‐HIV‐ and non‐transplant‐associated CM. We performed a retrospective cohort study of the outcomes in immune competent patients with CM treated with fluconazole and 5‐flucytosine or deoxycholate‐amphotericin B and 5‐flucytosine. The primary outcome was treatment response evaluated at the 12th week after initiation of antifungal therapy. A total of 43 and 47 patients received amphotericin B deoxycholate and 5‐flucytosine or fluconazole and 5‐flucytosine, respectively. A total of 38 (88.4%) patients cannot tolerate recommended doses of amphotericin B deoxycholate and 5‐flucytosine (patients needed dose reduction during the treatment). Patients given fluconazole and 5‐flucytosine had higher baseline cryptococcal burdens (median 3632 versus 900 cryptococci/mL, P = 0.008). No significant differences were seen in cryptococcus clearance (74.4% vs 70.2%, P = 0.814), treatment time (39 days, 20‐69 days vs 21 days, 7‐63 days, P = 0.107) and successful response (including complete and partial responses) rates (69.7% vs 72.3%, P = 0.820). Fluconazole and 5‐flucytosine treatment had lower total adverse events (19.1% vs 90.7%, P < 0.001). Fluconazole and 5‐flucytosine had relatively high efficacy with few adverse events in treating CM. Fluconazole and 5‐flucytosine therapy is promising in patients that do not tolerate or are not suited for amphotericin B deoxycholate treatment.     

Hampered by historical paradigms – echinocandins and the treatment of Candida endocarditis

Infective endocarditis due to Candida sp. has a high mortality rate. Traditionally, management involves early surgery and prolonged amphotericin ± flucytosine. We report a case of Candida parapsilosis bileaflet mitral valve endocarditis cured with anidulafungin and fluconazole, and review the role of echinocandins in the management of Candida endocarditis.