Spectrum and management of rare Candida/yeast infections in Kuwait in the Middle East.

Invasive fungal infections (IFIs) are associated with high mortality rates and mostly affect patients with compromised immunity. The incidence of IFIs is increasing worldwide with the expanding population of susceptible patients. Candida and other yeast infections represent a major component of IFIs. Rare Candida/yeast infections have also increased in recent years and pose considerable diagnostic and management challenges as they are not easily recognized by routine phenotypic characteristic-based diagnostic methods and/or by the automated yeast identification systems. Rare Candida/yeasts also exhibit reduced susceptibility to antifungal drugs making proper management of invasive infections challenging. Here, we review the diagnosis and management of 60 cases of rare Candida/yeast IFIs described so far in Kuwait, an Arabian Gulf country in the Middle East. Interestingly, majority (34 of 60, 56.7%) of these rare Candida/yeast invasive infections occurred among neonates or premature, very-low-birth-weight neonates, usually following prior bacteremia episodes. The clinical details, treatment given, and outcome were available for 28 of 34 neonates. The crude mortality rate among these neonates was 32.2% as 19 of 28 (67.8%) survived the infection and were discharged in healthy condition, likely due to accurate diagnosis and frequent use of combination therapy. Physicians treating patients with extended stay under intensive care, on mechanical ventilation, receiving broad spectrum antibiotics and with gastrointestinal surgery/complications should proactively investigate IFIs. Timely diagnosis and early antifungal treatment are essential to decrease mortality. Understanding the epidemiology and spectrum of rare Candida/yeast invasive infections in different geographical regions, their susceptibility profiles and management will help to devise novel diagnostic and treatment approaches and formulate guidelines for improved patient outcome.

High Prevalence of Novel Sequence Types in Streptococcus pneumoniae That Caused Invasive Diseases in Kuwait in 2018.

BACKGROUND: Multilocus sequence typing (MLST) is used to gain insight into the population genetics of bacteria in the form of sequence type (ST). MLST has been used to study the evolution and spread of virulent clones of Streptococcus pneumoniae in many parts of the world. Such data for S. pneumoniae are lacking for the countries of the Arabian Peninsula, including Kuwait. METHODS: We determined the STs of all 31 strains of S. pneumoniae from invasive diseases received at a reference laboratory from various health centers in Kuwait during 2018 by MLST. The relationship among the isolates was determined by phylogenetic analysis. We also determined the serotypes by Quellung reaction, and antimicrobial susceptibility by Etest, against 15 antibiotics belonging to 10 classes. RESULTS: There were 28 STs among the 31 isolates, of which 14 were new STs (45.2%) and 5 were rare STs (16.1%). Phylogenetic analysis revealed that 26 isolates (83.9%) were unrelated singletons, and the Kuwaiti isolates were related to those from neighboring countries whose information was gleaned from unpublished data available at the PubMLST website. Many of our isolates were resistant to penicillin, erythromycin, and azithromycin, and some were multidrug-resistant. Virulent serotype 8-ST53, and serotype 19A with new STs, were detected. CONCLUSIONS: Our study detected an unusually large number of novel STs, which may indicate that Kuwait provides a milieu for the evolution of novel STs. Novel STs may arise due to recombination and can result in capsular switching. This can impact the effect of vaccination programs on the burden of invasive pneumococcal disease. This first report from the Arabian Peninsula justifies the continuous monitoring of S. pneumoniae STs for the possible evolution of new virulent clones and capsular switching.

Whole genome sequencing analysis demonstrates therapy-induced echinocandin resistance in Candida auris isolates.

Candida auris is an emerging, multidrug-resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra-patient resistance development, whole genome sequencing (WGS) single-nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin-resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17-127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1-10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin-resistant strains are capable of long-term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross-infect other patients, or remain viable for longer time periods in the hospital environment.

Molecular fingerprinting by multi-locus sequence typing identifies microevolution and nosocomial transmission of Candida glabrata in Kuwait.

Backgrounds: Candida glabrata is a frequently isolated non-albicans Candida species and invasive C. glabrata infections in older patients are associated with high mortality rates. Opportunistic Candida infections in critically ill patients may be either endogenous or nosocomial in origin and this distinction is critical for effective intervention strategies. This study performed multi-locus sequence typing (MLST) to study genotypic relatedness among clinical C. glabrata isolates in Kuwait. Methods: Candida glabrata isolates (n = 91) cultured from 91 patients were analyzed by MLST. Repeat isolates (n = 16) from 9 patients were also used. Antifungal susceptibility testing for fluconazole, voriconazole, caspofungin and amphotericin B (AMB) was determined by Etest. Genetic relatedness was determined by constructing phylogenetic tree and minimum spanning tree by using BioNumerics software. Results: Resistance to fluconazole, voriconazole and AMB was detected in 7, 2 and 10 C. glabrata isolates, respectively. MLST identified 28 sequence types (STs), including 12 new STs. ST46 (n = 33), ST3 (n = 8), ST7 (n = 6) and ST55 (n = 6) were prevalent in ≥4 hospitals. Repeat isolates obtained from same or different site yielded identical ST. No association of ST46 with source of isolation or resistance to antifungals was apparent. Microevolution and cross-transmission of infection was indicated in two hospitals that yielded majority (57 of 91, 67%) of C. glabrata. Conclusion: Our data suggest that C. glabrata undergoes microevolution in hospital environment and can be nosocomially transmitted to other susceptible patients. Thus, proper infection control practices during routine procedures on C. glabrata-infected patients may prevent transmission of this pathogen to other hospitalized patients.

First Report of Azole-Resistant Aspergillus fumigatus with TR46/Y121F/T289A Mutations in Kuwait and an Update on Their Occurrence in the Middle East.

Pulmonary aspergillosis is a common fungal infection with several clinical manifestations including invasive, allergic and chronic chest diseases. Invasive pulmonary aspergillosis (IPA) is a leading cause of death in immunocompromised patients, particularly those receiving chemotherapy and among bone marrow transplant recipients. Aspergillus fumigatus is the most prevalent causative agent and voriconazole is the first-line therapy for IPA. In this study, we report the first isolation of voriconazole-resistant A. fumigatus carrying TR46/Y121F/T289A mutations from an immunocompromised pregnant lady in Kuwait. The patient was successfully treated for a probable respiratory infection with caspofungin and voriconazole. The literature review from PubMed has identified itraconazole-resistant clinical and environmental A. fumigatus isolates with TR34/L98H mutations in the cyp51A from several Middle Eastern countries including Kuwait. However, clinical A. fumigatus isolates with cyp51A TR46/Y121F/T289A mutations have not been reported previously from any country in the region while environmental isolates have been reported only from Iran. The source of voriconazole-resistant A. fumigatus CYP51A TR46/Y121F/T289A mutant in our patient remained unknown. Surveillance for azole resistance among clinical and environmental isolates of A. fumigatus is warranted in Kuwait.

Material Data Identification in an Induction Hardening Test Rig with Physics-Informed Neural Networks.

Physics-Informed neural networks (PINNs) have demonstrated remarkable performance in solving partial differential equations (PDEs) by incorporating the governing PDEs into the network's loss function during optimization. PINNs have been successfully applied to diverse inverse and forward problems. This study investigates the feasibility of using PINNs for material data identification in an induction hardening test rig. By utilizing temperature sensor data and imposing the heat equation with initial and boundary conditions, thermo-physical material properties, such as specific heat, thermal conductivity, and the heat convection coefficient, were estimated. To validate the effectiveness of the PINNs in material data estimation, benchmark data generated by a finite element model (FEM) of an air-cooled cylindrical sample were used. The accurate identification of the material data using only a limited number of virtual temperature sensor data points was demonstrated. The influence of the sensor positions and measurement noise on the uncertainty of the estimated parameters was examined. The study confirms the robustness and accuracy of this approach in the presence of measurement noise, albeit with lower efficiency, thereby requiring more time to converge. Lastly, the applicability of the presented approach to real measurement data obtained from an air-cooled cylindrical sample heated in an induction heating test rig was discussed. This research contributes to the accurate offline estimation of material data and has implications for optimizing induction heat treatments.

Molecular Characterization and Sterol Profiles Identify Nonsynonymous Mutations in ERG2 as a Major Mechanism Conferring Reduced Susceptibility to Amphotericin B in Candida kefyr.

The molecular basis of reduced susceptibility to amphotericin B (rs-AMB) among any yeasts is poorly defined. Genetic alterations in genes involved in ergosterol biosynthesis and total cell sterols were investigated among clinical Candida kefyr isolates. C. kefyr isolates (n = 81) obtained from 74 patients in Kuwait and identified by phenotypic and molecular methods were analyzed. An Etest was initially used to identify isolates with rs-AMB. Specific mutations in ERG2 and ERG6 involved in ergosterol biosynthesis were detected by PCR sequencing. Twelve selected isolates were also tested by the SensiTitre Yeast One (SYO), and total cell sterols were evaluated by gas chromatography-mass spectrometry and ERG3 and ERG11 sequencing. Eight isolates from 8 patients showed rs-AMB by Etest, including 2 isolates with additional resistance to fluconazole or to all three antifungals. SYO correctly identified 8 of 8 rs-AMB isolates. A nonsynonymous mutation in ERG2 was detected in 6 of 8 rs-AMB isolates but also in 3 of 73 isolates with a wild-type AMB pattern. One rs-AMB isolate contained a deletion (frameshift) mutation in ERG2. One or more nonsynonymous mutations was detected in ERG6 in 11 of 81 isolates with the rs-AMB or wild-type AMB pattern. Among 12 selected isolates, 2 and 2 isolates contained a nonsynonymous mutation(s) in ERG3 and ERG11, respectively. Ergosterol was undetectable in 7 of 8 rs-AMB isolates, and the total cell sterol profiles were consistent with loss of ERG2 function in 6 rs-AMB isolates and loss of ERG3 activity in another rs-AMB isolate. Our data showed that ERG2 is a major target conferring rs-AMB in clinical C. kefyr isolates. IMPORTANCE Some yeast species exhibit intrinsic resistance or rapidly acquire resistance to azole antifungals. Despite >50 years of clinical use, resistance to amphotericin B (AMB) among yeast species has been extremely rarely reported until recently. Reduced susceptibility to AMB (rs-AMB) among yeast species is, therefore, a matter of serious concern due to the availability of only four classes of antifungal drugs. Recent studies in Candida glabrata, Candida lusitaniae, and Candida auris have identified ERG genes involved in ergosterol biosynthesis as the major targets conferring rs-AMB. The results of this study also show that nonsynonymous mutations in ERG2 impair its function, abolish ergosterol from C. kefyr, and confer rs-AMB. Thus, rapid detection of rs-AMB among clinical isolates will help in proper management of invasive C. kefyr infections.

Strategies to Prevent Transmission of Candida auris in Healthcare Settings.

Purpose of Review: Candida auris, a recently recognized yeast pathogen, has become a major public health threat due to the problems associated with its accurate identification, intrinsic and acquired resistance to antifungal drugs, and its potential to easily contaminate the environment causing clonal outbreaks in healthcare facilities. These outbreaks are associated with high mortality rates particularly among older patients with multiple comorbidities under intensive care settings. The purpose of this review is to highlight strategies that are being adapted to prevent transmission of C. auris in healthcare settings. Recent Findings: Colonized patients shed C. auris into their environment which contaminates surrounding equipment. It resists elimination even by robust decontamination procedures and is easily transmitted to new patients during close contact resulting in outbreaks. Efforts are being made to rapidly identify C. auris-infected/C. auris-colonized patients, to determine its susceptibility to antifungals, and to perform effective cleaning and decontamination of the environment and isolation of colonized patients to prevent further transmission. Summary: Rapid and accurate identification of hospitalized patients infected/colonized with C. auris, rapid detection of its susceptibility patterns, and appropriate use of infection control measures can help to contain the spread of this highly pathogenic yeast in healthcare settings and prevent/control outbreaks.

Molecular epidemiology and genetic characterization of SARS-CoV-2 in Kuwait: A descriptive study.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been fatal to human health, affecting almost the entire world. Here we reported, for the first time, characterization of the genetic variants of SARS-CoV-2 circulating in Kuwait to understand their genetic diversity and monitor the accumulation of mutations over time. This study randomly enrolled 209 COVID-19 patients whose nasopharyngeal swabs were positive for SARS-CoV-2 between February 2020 and June 2021 using RT-PCR. The whole genomes of SARS-CoV-2 from the nasopharyngeal swabs were sequenced using the Oxford Nanopore sequencing technology following the ARTIC network protocol. Whole-genome sequencing has identified different clades/sub-clades circulating in Kuwait, mimicking the virus's global spread. Clade 20A was dominant from February 2020 until January 2021, and then clade 20I (Alpha, V1) emerged and dominated. In June 2021, the number of cases infected with clades 21I, 21A, and 21 J (Delta) increased and dominated. We detected several known clade-defining missense and synonymous mutations and other missense mutations in the genes encoding important viral proteins, including ORF1a, S, ORF3a, ORF8 regions and a novel mutation in the N region. ORF1ab region harbored more mutations and deletions (n = 62, 49.2%) compared to the other 12 gene regions, and the most prevalent missense mutations were P314L (97%) in ORF1b and D614G (97%) in the S glycoprotein regions. Detecting and analyzing mutations and monitoring the evolution of SARS-CoV-2 over time is essential to help better understand the spread of various clades/strains of SARS-CoV-2 and their implications for pathogenesis. In addition, knowledge of the circulating variants and genome sequence variability of SARS-CoV-2 may potentially influence the development of vaccines and antiviral drugs to control the COVID-19 pandemic.

Fatal Lodderomyces elongisporus Fungemia in a Premature, Extremely Low-Birth-Weight Neonate.

Many rare yeasts are emerging as pathogens, causing invasive infections in susceptible hosts that are associated with poor clinical outcome. Here, we describe the first and fatal case of Lodderomyces elongisporus fungemia in a premature, extremely low-birth-weight neonate after spontaneous vaginal delivery. The bloodstream isolate was identified as C. parapsilosis by the VITEK 2 yeast identification system and as L. elongisporus by PCR-sequencing of the internal transcribed spacer (ITS) region of ribosomal DNA. Antifungal susceptibility testing data for the isolate, performed by the broth microdilution-based MICRONAUT-AM assay, showed susceptibility to all nine antifungal drugs tested. Despite the initiation of treatment with liposomal amphotericin B, the patient died on the same day that the blood culture yielded yeast growth. This is the first report of L. elongisporus bloodstream infection in a neonate as the previous nine cases reported in the literature occurred in adult patients. The crude mortality rate for invasive L. elongisporus infection is 50%, as only 5 of 10 patients survived.

A review study of the providing elderly care services in different countries.

Background: Population aging leads to change of population structure and increase care needs. Lack of proper planning in this field will lead to occur increasing problems. In this paper, the review of the elderly care plans at various levels in some European and Asian countries, comparing these countries with Iran with the goal of using their experiences to enhance elderly plans have been done. Methods: This research was a review study of library documents and resources and systematic search. Data were collected using the resources, databases, scientific databases and websites of the Ministry of Health and Welfare of the studied countries. Results: Based on this research in the studied countries, the care services of the elderly is based on the important principle of coordination between different organs of the country, followed by the creation of LTC insurance and provision of health and social services for the elderly and mainly the type of home care. In Iran country, providing appropriate services and cares for the elderly with existing plans and policies is not possible and the need to provide appropriate service packages based on the different systems of successful countries and applying the experiences of these countries is essential. Conclusion: Given the current status of the Iranian elderly population in terms of policies and plans and the types and methods of providing services, quality, access and financial resources allocated to this age group, compared to the studied countries, there is a well and integrated plan is essential.

Fatal Breakthrough Candidemia in an Immunocompromised Patient in Kuwait Due to Candida auris Exhibiting Reduced Susceptibility to Echinocandins and Carrying a Novel Mutation in Hotspot-1 of FKS1.

Candida auris is an emerging yeast pathogen that has recently caused major outbreaks in healthcare facilities worldwide. Clinical C. auris isolates are usually resistant to fluconazole and readily develop resistance to echinocandins and amphotericin B (AMB) during treatment. We describe here an interesting case of C. auris infection in an immunocompromised patient who had previously received AMB and caspofungin treatment. Subsequently, C. auris was isolated from tracheal (tracheostomy) secretions and twice from urine and all three isolates were susceptible to AMB and micafungin. The patient received a combination therapy with AMB and caspofungin. Although the C. auris was cleared from the urine, the patient subsequently developed breakthrough candidemia and the bloodstream isolate exhibited a reduced susceptibility to micafungin and also showed the presence of a novel (S639T) mutation in hotspot-1 of FKS1. Interestingly, C. auris from the tracheal (tracheostomy) secretions recovered one and four days later exhibited a reduced susceptibility to micafungin and S639Y and S639T mutations in hotspot-1 of FKS1, respectively. Although the treatment was changed to voriconazole, the patient expired. Our case highlights a novel FKS1 mutation and the problems clinicians are facing to treat invasive C. auris infections due to inherent or developing resistance to multiple antifungal drugs and limited antifungal armamentarium.

Molecular characterisation of Candida auris isolates from immunocompromised patients in a tertiary-care hospital in Kuwait reveals a novel mutation in FKS1 conferring reduced susceptibility to echinocandins.

BACKGROUND: Candida auris is an emerging, potentially multidrug-resistant pathogen that exhibits clade-specific resistance to fluconazole and also develops resistance to echinocandins and amphotericin B easily. This study analysed 49 C auris isolates for alterations in hotspot-1 and hotspot-2 of FKS1 for the detection of mutations conferring reduced susceptibility to echinocandins. METHODS: C auris isolates (n = 49) obtained from 18 immunocompromised patients during June 2016-December 2018 were analysed. Antifungal susceptibility testing was performed by Etest and broth microdilution-based MICRONAUT-AM assay. Mutations in hotspot-1 and hotspot-2 regions of FKS1 were detected by PCR sequencing and fingerprinting of the isolates was done by short tandem repeat typing. RESULTS: The patients had multiple comorbidities/risk factors for Candida spp. infection including cancer/leukaemia/lymphoma/myeloma (n = 16), arterial/central line (n = 17), urinary catheter (n = 17), mechanical ventilation (n = 14) and major surgery (n = 9) and received antifungal drugs as prophylaxis and/or empiric treatment. Seven patients developed C auris candidemia/breakthrough candidemia, nine patients had candiduria with/without candidemia and four patients developed surgical site/respiratory infection. Resistance to fluconazole and amphotericin B was detected in 44 and four isolates, respectively. Twelve C auris isolates from eight patients showed reduced susceptibility to echinocandins. Seven isolates contained hostspot-1 mutations and three isolates from a candidemia patient contained R1354H mutation in hotspot-2 of FKS1. Ten patients died, five were cured, two were lost to follow-up and treatment details for one patient were not available. CONCLUSIONS: Our findings describe development of a novel mutation in FKS1 conferring reduced susceptibility to echinocandins in one patient during treatment and unfavourable clinical outcome for many C auris-infected patients.

First report of invasive Aspergillus rhinosinusitis in a critically ill COVID-19 patient affected by acute myeloid leukemia, northeastern Iran.

This is a report of established invasive Aspergillus rhinosinusitis in a patient diagnosed with COVID-19 and afflicted by AML, which was initially considered to be rhinocerebral mucormycosis.

Liquid Metal Embrittlement of Advanced High Strength Steel: Experiments and Damage Modeling.

In the automotive industry, corrosion protected galvanized advanced high strength steels with high ductility (AHSS-HD) gain importance due to their good formability and their lightweight potential. Unfortunately, under specific thermomechanical loading conditions such as during resistance spot welding galvanized, AHSS-HD sheets tend to show liquid metal embrittlement (LME). LME is an intergranular decohesion phenomenon leading to a drastic loss of ductility of up to 95%. The occurrence of LME for a given galvanized material mainly depends on thermal and mechanical loading. These influences are investigated for a dual phase steel with an ultimate tensile strength of 1200 MPa, a fracture strain of 14% and high ductility (DP1200HD) by means of systematic isothermal hot tensile testing on a Gleeble® 3800 thermomechanical simulator. Based on the experimental findings, a machine learning procedure using symbolic regression is applied to calibrate an LME damage model that accounts for the governing quantities of temperature, plastic strain and strain rate. The finite element (FE) implementation of the damage model is validated based on the local damage distribution in the hot tensile tested samples and in an exemplary 2-sheet resistance spot weld. The developed LME damage model predicts the local position and the local intensity of liquid metal induced cracking in both cases very well.

Epidemiology of Candidemia in Kuwait: A Nationwide, Population-Based Study.

The Candida species cause a majority of invasive fungal infections. In this article, we describe the nationwide epidemiology of candidemia in Kuwait in 2018. Yeast bloodstream isolates submitted from all major hospitals and identified by phenotypic MALDI-TOF MS and/or by molecular methods were studied. Susceptibility testing was performed by Etest. Out of 313 bloodstream yeasts, 239 Candida spp. isolates (excluding duplicate isolates) were obtained during 234 candidemic episodes among 223 patients. Mixed-species candidemia and re-infection occurred in 5 and 11 patients, respectively. C. albicans (n = 74), C. parapsilosis (n = 54), C. tropicalis (n = 35), C. auris (n = 33), C. glabrata (n = 32), other Candida spp. (n = 11), and other yeasts (n = 9) caused fungemia. Nearly 50% of patients were in intensive care units. Candida spp. isolates (except C. glabrata) were susceptible to caspofungin and 27% of C. auris were amphotericin B-resistant. Resistance to fluconazole was 100% in C. auris, 17% in C. parapsilosis, 12% in C. glabrata, and 1% in C. albicans. Mortality was 47% for other Candida/yeast infections. Nationwide candidemia incidence in 2018 was 5.29 cases/100,000 inhabitants. Changes in species spectrum, increasing fluconazole resistance in C. parapsilosis, and the emergence of C. auris as a major pathogen in Kuwait are noteworthy findings. The data could be of help in informing decisions regarding planning, in the allocation of resources, and in antimicrobial stewardship.

Neurological manifestations of COVID-19: with emphasis on Iranian patients.

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has instigated a global pandemic as a formidable and highly contagious infectious disease. Although the respiratory system remains the most frequently affected organ, several case reports have revealed that the complications are not merely limited to the respiratory system, and neurotropic and neuroinvasive properties have also been observed, leading to neurological diseases. In the present paper, it was intended to review the possible neuroinvasive routes of SARS-CoV-2 and its mechanisms that may cause neurological damage. Additionally, the neurological manifestations of COVID-19 across the globe were discussed with emphasis on Iran, while highlighting the impact of SARS-CoV-2 on the central and peripheral nervous systems.

Papiliotrema laurentii fungemia in a premature, very low-birth-weight neonate in Kuwait successfully treated with liposomal amphotericin B.

Papiliotrema laurentii (formerly Cryptococcus laurentii) and Papiliotrema albidus (formerly Cryptococcus albidus) are yeast-like environmental fungi which are largely considered as non-pathogenic to humans. However, invasive infections caused by P. laurentii have recently been reported in some patients with an impaired immune system. Here, we describe the first case of P. laurentii fungemia in a premature, very low-birth-weight neonate in Kuwait and the Middle East. Repeated bloodstream isolates were obtained and were tentatively identified as P. laurentii by Vitek 2 yeast identification system. The identification of the yeast isolates as P. laurentii was confirmed by PCR-sequencing of ribosomal DNA (rDNA). Antifungal susceptibility testing data showed that the isolates were susceptible to amphotericin B, fluconazole and voriconazole but appeared resistant to caspofungin. The baby was successfully treated with liposomal amphotericin B.

First Isolation of Candida nivariensis, an Emerging Fungal Pathogen, in Kuwait.

OBJECTIVE: C. nivariensis is a rare Candida species which is phenotypically closely related to Candida glabrata and Candida bracarensis. The 3 species form the C. glabrata sensu lato complex. Here, we describe the first isolation and characterization of a C. nivariensis isolate cultured from the tracheal aspirate obtained from a young man in Kuwait. MATERIALS AND METHODS: The yeast isolate was initially tested by VITEK 2 followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and multiplex PCR. The identification was confirmed by sequencing of internal transcribed spacer (ITS) region of rDNA. Antifungal susceptibility testing was performed by Etest, and phylogenetic comparison with other international strains was carried out by using MEGA version 7 software. RESULTS: The C. nivariensis isolate was misidentified by VITEK 2, but correctly identified by MALDI-TOF MS with updated software and multiplex PCR. The identity was confirmed by sequence comparisons of ITS region of rDNA. Antifungal susceptibility testing revealed high minimum inhibitory concentration (MIC) against fluconazole, but low MICs against amphotericin B and echinocandins. Phylogenetically, our isolate was closely related to Indian isolates. CONCLUSIONS: This report extends the geographic distribution of C. nivariensis to the Arabian Peninsula. MALDI-TOF MS with updated software and molecular tests are needed to correctly identify C. nivariensis. Since C. nivariensis may exhibit reduced susceptibility to antifungal agents, accurate identification and antifungal susceptibility testing are essential, particularly for isolates from sterile sites, for optimal patient management.