Invasive Candida Research Articles

The Gastrointestinal Tract Is Pinpointed as a Reservoir of Candida albicans, Candida parapsilosis, and Candida tropicalis Genotypes Found in Blood and Intra-Abdominal Samples.

Candida spp., as part of the microbiota, can colonise the gastrointestinal tract. We hypothesised that genotyping Candida spp. isolates from the gastrointestinal tract could help spot genotypes able to cause invasive infections. A total of 816 isolates of C. albicans (n = 595), C. parapsilosis (n = 118), and C. tropicalis (n = 103) from rectal swabs (n = 754 patients) were studied. Genotyping was conducted using species-specific microsatellite markers. Rectal swab genotypes were compared with previously studied blood (n = 814) and intra-abdominal (n = 202) genotypes. A total of 36/754 patients had the same Candida spp. isolated from blood cultures, intra-abdominal samples, or both; these patients had candidemia (n = 18), intra-abdominal candidiasis (n = 11), both clinical forms (n = 1), and non-significant isolation (n = 6). Genotypes matching the rectal swab and their blood cultures (84.2%) or their intra-abdominal samples (92.3%) were found in most of the significant patients. We detected 656 genotypes from rectal swabs, 88.4% of which were singletons and 11.6% were clusters. Of these 656 rectal swab genotypes, 94 (14.3%) were also detected in blood cultures and 34 (5.2%) in intra-abdominal samples. Of the rectal swab clusters, 62.7% were previously defined as a widespread genotype. Our study pinpoints the gastrointestinal tract as a potential reservoir of potentially invasive Candida spp. genotypes.

Roles of post-translational modifications of C-type lectin receptor-induced signaling cascades in innate immune responses against Candida albicans

Candida albicans (C. albicans), a conditional pathogenic fungus, is widespread in nature and can live in symbiosis with organisms in small quantities. When the normal microflora is imbalanced, the epithelial barrier is disrupted or the immune system becomes dysfunctional, C. albicans can change from commensal to pathogenic pathogen, causing both superficial and life-threatening systemic infections with no effective treatment. The morbidity and mortality of invasive Candida infections in perioperative patients are high due to underlying chronic diseases, immune deficiencies, and pathophysiological disorders. C-type lectin receptors (CLRs) are the main pattern-recognition receptors for fungal activation of innate immunity and host defense. Upon binding to ligands, CLRs induce multiple signal transduction cascades followed by activation of nuclear factor kappa B through spleen tyrosine kinase - and caspase recruitment domain containing protein 9-dependent pathways. Analyzing the effects of regulatory CLR-induced signaling cascades on host immune cells is critical for understanding the molecular mechanism in regulating antifungal immunity. As one of the core factors in host innate immune regulation, protein post-translational modifications regulate the strength of immune effects by modulating protein conformation, stability, affinity, subcellular localization, etc. This makes the post-translational modification sites promising as potential targets for modulating antifungal immunity. This review primarily described the study progress of post-translational modifications in controlling CLR-induced signaling cascades throughout the process of innate immunity against C. albicans. We aim to provide better understanding of these mechanisms and aid in the identification and development of biomarkers and drug targets for invasive candidiasis.

Risk factors and mortality of the newly emerging Candida auris in a university hospital in Saudi Arabia

ABSTRACT Candida auris presents a global health threat. We investigated risk factors and mortality of Candida auris infections in a retrospective study in Saudi Arabia. We included 27 patients ≥14 with invasive Candida auris from 2015–2022, with median age 58, and 66.7% males. All patients had indwelling devices. The most common infection sources were central line-associated bloodstream infection in 17 (63.0%), and urinary tract infections in four (12%). Fever and shock were observed in nine patients (33.3%) each, and 22 (81%) were admitted to the intensive care unit. Common comorbidities were diabetes and heart disease in 13 (48.1%) patients each. The median hospital stay was 78 days, and the median Charlson index was 4. The C. auris cultures were 100% susceptible to voriconazole, caspofungin, and amphotericin, while three were fully susceptible to fluconazole (11.1%). Despite treatment, 18 (66.7%) patients died. In conclusion, invasive C. auris infection had varied presentations. All patients had indwelling devices, and many had lengthy hospital stays. All isolates were susceptible to amphotericin and echinocandins, while few were fully susceptible to fluconazole.

Epidemiology of Invasive Candidiasis in Patients with Hematologic Malignancy on Antifungal Prophylaxis.

The landscape of invasive Candida infections in patients with hematologic malignancy has evolved due to the adoption of anti-fungal prophylaxis, advances in oncological therapies, and developments in antifungal therapies and diagnostics. Despite these scientific gains, the morbidity and mortality caused by these infections remain unchanged, highlighting the importance of an updated understanding of its epidemiology. Non-albicans Candida species are now the predominant cause of invasive candidiasis in patients with hematological malignancy. This epidemiological shift from Candida albicans to non-albicans Candida species is partially a consequence of selective pressure from extensive azole use. Further analysis of this trend suggests other contributing factors including immunocompromise caused by the underlying hematologic malignancy and the intensity of its associated treatments, oncological practices, and regional or institution specific variables. This review characterizes the changing distribution of Candida species in patients with hematologic malignancy, describes the causes driving this change, and discusses clinical considerations to optimize management in this high-risk patient population.

Invasive Candida hidden in plain sight.

Invasive Candida hidden in plain sight.

Retrospective analysis on distribution and antifungal susceptibility profile of Candida in clinical samples: a study from Southern India.

Candida is one of the rising primary causes of infections connected with health care. However, their distribution and susceptibility patterns vary widely amongst different regions. The study was carried out to retrospectively analyze the distribution of Candida in various clinical samples, their species types and susceptibility, in a tertiary care hospital, in India for 4 years using the Vitek-2 database. Candida infection was identified in 751 clinical samples, and the major source of infection was found to be urine samples accounting for about 58.32%. A total of 18 different Candida species were recorded. Non-albicans Candida (NAC) 73.64% (n = 553) predominated Candida albicans 26.36% (n = 198). Candida tropicalis was found to be identified at a higher frequency followed by C. albicans, Candida glabrata and Candida parapsilosis. Candida tropicalis was the only species which were recovered from bile; Candida pelliculosa was recorded merely from blood and Candida lipolytica from urine and blood and not in any other samples. In vaginal swabs, C. albicans accounted for 63.64% (n = 14) compared to NAC 36.36% (n = 8). The susceptibility test revealed that 75.44% (n = 559) isolates were susceptible and 24.56% (n = 182) were resistant to one or more drugs tested. Major resistance was exhibited to flucytosine by C. tropicalis 77.46% (n = 55) compared to C. albicans 11.27% (n = 8). Apart from C. albicans, NAC-C. tropicalis, C. glabrata and Candida krusei showed resistance to echinocandins, and Candida haemulonii to amphotericin-B. The knowledge of the incidence, resistance and emergence of different species might guide clinicians to select an appropriate antifungal therapy and plan effective strategies to control invasive and systemic Candida infections.

Abnormal Dihydrorhodamine Result in a Patient with Diabetes Mellitus, Recurrent Candida Liver Abscesses: Diagnostic Possibilities

A 17-year-old female with type I diabetes mellitus (DM) and a history of recurrent candidal vaginal infections and liver abscesses was assessed fora potential neutrophil oxidative burst defect by DHR flow cytometry. The DHR result was abnormal with significantly decreased MFI (MFI = 9; ref. cutoff: >/ = 60) after stimulation with PMA though all of her neutrophils (99%; ref. cutoff >/ = 95%) showed respiratory burst. This DHR pattern has been previously observed in patients with complete myeloperoxidase deficiency (cMPO), p40phox deficiency and hypomorphic X-linked chronic granulomatous disease (CGD). Genetic evaluation of the genes commonly associated with CGD (CYBB, CYBA, NCF1, NCF2 and NCF4) was negative. It must be noted that many genetic laboratories either do not sequence the NCF1 gene or have limited sequencing to the most commonly observed pathogenic variant in exon 2. Most targeted genetic panels currently do not include MPO (myeloperoxidase) or CYBC1 (Eros). The clinical phenotype of Candida infection in the context of diabetes has been previously reported in 5% of cMPO deficiency. The patient underwent a partial hepatectomy and was initiated on an 8-month course of fluconazole. Three months later, there was a recurrence of hepatic abscesses (Figure 1), requiring treatment with a 12-week course of IV micafungin. Complete MPO deficiency can cause a false-positive result on the DHR assay but the pattern is different from that observed in typical XL- and autosomal recessive CGD. There are two ways of confirming cMPO deficiency, besides genetic testing: 1) staining for MPO in neutrophils in a peripheral smear, or 2) repeating the DHR assay and gating on eosinophils as eosinophil peroxidase can overcome the lack of MPO deficiency and demonstrate a normal oxidative burst. These studies are currently under investigation. In summary, cMPO deficiency should be included in the differential diagnosis of patients with diabetes and invasive Candida infections. Communication with the clinical laboratory is essential to identify the DHR pattern and obtain additional confirmatory testing. From a clinical perspective, cMPO-deficient patients do not require prophylactic antibiotics but they have a high rate of recurrence of fungal infections and require aggressive management with antifungal therapies. [Display omitted]

Invasive Candida parapsilosis Bloodstream Infections in Children: The Antifungal Susceptibility, Clinical Characteristics and Impacts on Outcomes

Background: Candida parapsilosis is the most common non-albicans candida species that causes invasive candidiasis, but little is known about its impacts on the outcomes of pediatric patients. We aimed to characterize the clinical characteristics, risk factors and outcomes of C. parapsilosis bloodstream infections (BSIs) in children. Methods: All pediatric patients with Candida parapsilosis BSIs between 2005 and 2020 from a medical center in Taiwan were enrolled and analyzed. The antifungal susceptibility, clinical manifestations, management and outcomes were investigated. Cases of Candida parapsilosis BSIs were compared between patients with C. albicans BSIs and other Candida spp. BSIs. Results: During the study period, 95 episodes (26.0% of total cases) of Candida parapsilosis BSIs were identified and analyzed. No significant difference was found between pediatric patients with C. parapsilosis BSIs and those with C. albicans BSIs in terms of patients’ demographics, most chronic comorbidities or risk factors. Pediatric patients with C. parapsilosis BSIs were significantly more likely to have previous azole exposure and be on total parenteral nutrition than those with C. albicans BSIs (17.9 vs. 7.6% and 76.8 vs. 63.7%, p = 0.015 and 0.029, respectively). The duration of C. parapsilosis candidemia was relatively longer, and therefore patients often required a longer duration of antifungal treatment when compared with those of C. albicans candidemia, although the candidemia-attributable mortality rates were comparable. Of the C. parapsilosis isolates, 93.7% were susceptible to all antifungal agents, and delayed appropriate antifungal treatment was an independent factor in treatment failure. Conclusions: Pediatric patients with C. parapsilosis BSIs were more likely to have previous azole exposure and be on total parenteral nutrition, and the clinical significances included a longer duration of candidemia and patients often required a longer duration of antifungal treatment.

Miltefosine exhibits fungicidal activity through oxidative stress generation and Aif1 activation in Candida albicans

Invasive candidiasis is the most common and serious fungal disease worldwide, and the development of antifungal drug resistance in Candida spp. is an emerging problem. Miltefosine, approved as an orphan drug for the therapy of invasive candida infections by the US Food and Drug Administration, has broad-spectrum antifungal activity, but its mechanism of action is unclear. This study evaluated the antifungal drug susceptibility of azole-resistant Candida spp. isolates and found that miltefosine showed good activity, with a geometric mean value of 2 µg/mL. Miltefosine was found to increase production of intracellular reactive oxygen species (ROS) and induce apoptosis in Candida albicans. RNA sequencing (RNA-Seq) analysis and iTRAQ-labelling-based quantitative proteomic mass spectrometry analysis were undertaken. Aif1 and the oxidative stress pathway involved in miltefosine-mediated apoptosis were identified using global transcriptomic and proteomic combined screening. Miltefosine increased mRNA and protein expressions of Aif1. The localization of Aif1 was examined using confocal microscopy, and the GFP-Aif1 fusion protein was found to be translocated from the mitochondria to the nucleus when sensing miltefosine. Next, the pex8 Δ/Δ strain was constructed, and the minimum inhibitory concentration of miltefosine was found to decrease four-fold (from 2 to 0.5 µg/mL) and the intracellular ROS increased significantly after knocking out the PEX8 gene. Moreover, miltefosine was found to trigger Hog1 phosphorylation. These findings indicate that Aif1 activation and the Pex8-mediated oxidative stress pathway are the mechanisms of action of miltefosine on C. albicans. The results help to aid understanding of the mechanisms by which miltefosine acts on fungi.

Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis.

Candida parapsilosis is an emerging major human fungal pathogen. Echinocandins are first-line antifungal drugs for the treatment of invasive Candida infections. In clinical isolates, tolerance to echinocandins in Candida species is mostly due to point mutations of FKS genes, which encode the target protein of echinocandins. However, here, we found chromosome 5 trisomy was the major mechanism of adaptation to the echinocandin drug caspofungin, and FKS mutations were rare events. Chromosome 5 trisomy conferred tolerance to echinocandin drugs caspofungin and micafungin and cross-tolerance to 5-flucytosine, another class of antifungal drugs. The inherent instability of aneuploidy caused unstable drug tolerance. Tolerance to echinocandins might be due to increased copy number and expression of CHS7, which encodes chitin synthase. Although copy number of chitinase genes CHT3 and CHT4 was also increased to the trisomic level, the expression was buffered to the disomic level. Tolerance to 5-flucytosine might be due to the decreased expression of FUR1. Therefore, the pleiotropic effect of aneuploidy on antifungal tolerance was due to the simultaneous regulation of genes on the aneuploid chromosome and genes on euploid chromosomes. In summary, aneuploidy provides a rapid and reversible mechanism of drug tolerance and cross-tolerance in C. parapsilosis.

Annals for Hospitalists - April 2023

Annals for Hospitalists - April 2023

Worsening Spread of Candida auris in the United States, 2019 to 2021.

Candida auris is an emerging fungal threat that has been spreading in the United States since it was first reported in 2016. To describe recent changes in the U.S. epidemiology of C auris occurring from 2019 to 2021. Description of national surveillance data. United States. Persons with any specimen that was positive for C auris. Case counts reported to the Centers for Disease Control and Prevention by health departments, volume of colonization screening, and antifungal susceptibility results were aggregated and compared over time and by geographic region. A total of 3270 clinical cases and 7413 screening cases of C auris were reported in the United States through 31 December 2021. The percentage increase in clinical cases grew each year, from a 44% increase in 2019 to a 95% increase in 2021. Colonization screening volume and screening cases increased in 2021 by more than 80% and more than 200%, respectively. From 2019 to 2021, 17 states identified their first C auris case. The number of C auris cases that were resistant to echinocandins in 2021 was about 3 times that in each of the previous 2 years. Identification of screening cases depends on screening that is done on the basis of need and available resources. Screening is not conducted uniformly across the United States, so the true burden of C auris cases may be underestimated. C auris cases and transmission have risen in recent years, with a dramatic increase in 2021. The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive Candida infections, including C auris. These findings highlight the need for improved detection and infection control practices to prevent spread of C auris. None.

T2Candida assay: diagnostic performance and impact on antifungal prescribing.

To assess the performance of T2Candida for the diagnosis of invasive candidiasis (IC) against gold standards of candidaemia or consensus IC definitions, and to evaluate the impact of T2Candida on antifungal drug prescribing. A retrospective review was undertaken of all T2Candida (T2MR technology, T2 Biosystems) performed from October 2020 to February 2022. T2Candida performance was evaluated against confirmed candidaemia or against proven/probable IC within 48 hours of T2Candida, and its impact on antifungal drug prescriptions. T2Candida was performed in 61 patients, with 6 (9.8%) positive results. Diagnostic performance of T2Candida against candidaemia had a specificity of 85.7% and negative predictive value (NPV) of 96.8%. When comparing T2Candida results with consensus definitions of IC, the specificity and NPV of T2Candida was respectively 90% (54/60) and 98.2% (54/55) for proven IC, and 91.4% (53/58) and 96.4% (53/55) for proven/probable IC. Antifungals were initiated in three of six patients (50%) with a positive T2Candida result. Thirty-three patients were receiving empirical antifungals at the time of T2Candida testing, and a negative result prompted cessation of antifungals in 11 (33%) patients, compared with 6 (25%) antifungal prescriptions stopped following negative beta-d-glucan (BDG) testing in a control population (n = 24). T2Candida shows high specificity and NPV compared with evidence of Candida bloodstream infection or consensus definitions for invasive Candida infection, and may play an adjunctive role as a stewardship tool to limit unnecessary antifungal prescriptions.

RETROSPECTIVE RE- IDENTIFICATION OF CANDIDA STRAINS BY MALDI-TOF IN SEEK OF CANDIDA AURIS

The yeast C. auris was first described as a new species in 2009. Since then, this species was recognized as an emerging multi-drug-resistant (MDR) yeast that can cause a wide spectrum of infections, ranging from fungemia to deep-seated infections, especially in intensive care settings. It can be not- or misidentified by commercial identification systems. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has recently been considered as a convenient, rapid and accurate technology in the identification of yeast isolates to species level. A total of 132 clinical isolates, collected from 2015 to 2021 in the National Reference Laboratory of Mycology and Sexually Transmitted Infections were included in the study. The isolates were mainly from patients with candidemia and other specimens from invasive Candida infections. The isolates were identified by standard mycological procedures, the assimilation profile was done by commercially available strips and with the automated VITEK2 Compact system. All the strains were identified with MALDI-TOF MS. Antifungal susceptibility testing was conducted to some of the strains by agar disk-diffusion (according to CLSI M44-A2), E-test and VITEK2. Some of the strains which could not be identified or were misidentified by standard mycological procedures were correctly determined by MALDI-TOF MS. None of them was identified as C. auris. There were no large deviations in the antifungal susceptibility profiles of the tested strains. We assess MALDI-TOF MS as convenient, rapid, cost- effective and accurate technology in the identification of fungal strains which are difficult to determine with the traditional procedures. Up to now, isolation of C. auris has not been reported in Bulgaria.

Incidence of Invasive Fungal Infections in Liver Transplant Recipients under Targeted Echinocandin Prophylaxis

Invasive fungal infections (IFIs) are one of the most important infectious complications after liver transplantation, determining morbidity and mortality. Antimycotic prophylaxis may impede IFI, but a consensus on indication, agent, or duration is still missing. Therefore, this study aimed to investigate the incidence of IFIs under targeted echinocandin antimycotic prophylaxis in adult high-risk liver transplant recipients. We retrospectively reviewed all patients undergoing a deceased donor liver transplantation at the Medical University of Innsbruck in the period from 2017 to 2020. Of 299 patients, 224 met the inclusion criteria. We defined patients as being at high risk for IFI if they had two or more prespecified risk factors and these patients received prophylaxis. In total, 85% (190/224) of the patients were correctly classified according to the developed algorithm, being able to predict an IFI with a sensitivity of 89%. Although 83% (90/109) so defined high-risk recipients received echinocandin prophylaxis, 21% (23/109) still developed an IFI. The multivariate analysis identified the age of the recipient (hazard ratio-HR = 0.97, p = 0.027), split liver transplantation (HR = 5.18, p = 0.014), massive intraoperative blood transfusion (HR = 24.08, p = 0.004), donor-derived infection (HR = 9.70, p < 0.001), and relaparotomy (HR = 4.62, p = 0.003) as variables with increased hazard ratios for an IFI within 90 days. The fungal colonization at baseline, high-urgency transplantation, posttransplant dialysis, bile leak, and early transplantation showed significance only in a univariate model. Notably, 57% (12/21) of the invasive Candida infections were caused by a non-albicans species, entailing a markedly reduced one-year survival. The attributable 90-day mortality rate of an IFI after a liver transplant was 53% (9/17). None of the patients with invasive aspergillosis survived. Despite targeted echinocandin prophylaxis, there is still a notable risk for IFI. Consequently, the prophylactic use of echinocandins must be critically questioned regarding the high rate of breakthrough infections, the increased occurrence of fluconazole-resistant pathogens, and the higher mortality rate in non-albicans Candida species. Adherence to the internal prophylaxis algorithms is of immense importance, bearing in mind the high IFI rates in case algorithms are not followed.

Antifungal activity and potential mechanism of action of caspofungin in combination with ribavirin against Candida albicans

The number of invasive fungal infections has increased dramatically, resulting in high morbidity and mortality among immunocompromised patients. With increasing use of caspofungin (CAS), resistant strains have emerged frequently and led to limitations in the treatment of patients with severe invasive Candida albicans infections. Combination therapy is an important method to deal with this issue. As such, this study investigated the activity of CAS in combination with ribavirin (RBV) against C. albicans. The results of this in-vitro study showed that the minimum inhibitory concentrations (MICs) of CAS and RBV when they were used as monotherapy were 0.5-1 μg/mL and 2-8 μg/mL, respectively, while the MIC of CAS decreased from 0.5-1 μg/mL to 0.0625-0.25 μg/mL when used in combination with RBV, with a fractional inhibitory concentration index (FICI) ≤0.5. In addition, the RBV+CAS combination group displayed synergistic effects against C. albicans biofilm over 4 h; the sessile MIC (sMIC) of CAS decreased from 0.5-1 µg/mL to 0.0625-0.25µg/mL and the sMIC of RBV decreased from 4-16 µg/mL to 1-2 µg/mL, with FICI <0.5. The survival of C. albicans-infected Galleria mellonella was prolonged, the fungal burden was decreased, and the area of tissue damage was reduced after combination therapy. Further study showed that the mechanisms of action of the synergistic effect were related to the inhibition of biofilm formation, the inhibition of hyphal growth, and the activation of metacaspases, but were not related to the accumulation of reactive oxygen species. It is hoped that these findings will contribute to the understanding of drug resistance in C. albicans, and provide new insights for the application of RBV.

Race and ethnicity: Risk factors for fungal infections?

Racial and ethnic identities, largely understood as social rather than biologic constructs, may impact risk for acquiring infectious diseases, including fungal infections. Risk factors may include genetic and immunologic differences such as aberrations in host immune response, host polymorphisms, and epigenomic factors stemming from environmental exposures and underlying social determinants of health. In addition, certain racial and ethnic groups may be predisposed to diseases that increase risk for fungal infections, as well as disparities in healthcare access and health insurance. In this review, we analyzed racial and ethnic identities as risk factors for acquiring fungal infections, as well as race and ethnicity as they relate to risk for severe disease from fungal infections. Risk factors for invasive mold infections such as aspergillosis largely appear related to environmental differences and underlying social determinants of health, although immunologic aberrations and genetic polymorphisms may contribute in some circumstances. Although black and African American individuals appear to be at high risk for superficial and invasive Candida infections and cryptococcosis, the reasons for this are unclear and may be related to underling social determinants of health, disparities in access to healthcare, and other socioeconomic disparities. Risk factors for all the endemic fungi are likely largely related to underlying social determinants of health, socioeconomic, and health disparities, although immunologic mechanisms likely play a role as well, particularly in disseminated coccidioidomycosis.

Treatment of Invasive Candida Osteomyelitis of the Mandible: A Case Report

Treatment of Invasive Candida Osteomyelitis of the Mandible: A Case Report

352. Evaluation of Serial Serum (1-- &amp;gt;3)-b-D-glucan Assay in Patients with Invasive candidiasis, Pneumocystis Jiroveci Pneumonia and Aspergillosis

Abstract Background Serum (1-- &amp;gt;3)-b-D-glucan (BDG) assay is a noninvasive serological marker that can be used as an adjunct to the diagnosis of invasive candida infections, Pneumocystis jiroveci pneumonia (PJP) as well as aspergillosis. There is limited data in serial monitoring of serum BDG in those fungal infections after treatment was initiated. Figure 1:Serial serum BDG levels of each subject after treatment initiation Methods This is a cross-sectional study of subjects with proven fungal infection (invasive candidiasis, aspergillosis or PJP) and with increased serum BDG &amp;gt;500 pg/ml who were admitted to University of Kentucky (UK) hospitals or clinics from 01/2012 to 01/2021. It was approved by institutional IRB. We compared at least two measures of the serum β-D-glucan levels obtained within two to eight weeks after initial diagnosis to evaluate the levels of β-D-glucan during and post-treatment. A decrease in BDG level is defined as any value below 500 pg/ml; normal serum BDG level as &amp;lt; 80 pg/ml. Results Of 26 subjects included in this cohort, 14 (51.8%) subjects had invasive candidiasis, six (22.2%) subjects had PJP, and six (22.2%) subjects had invasive aspergillosis. Twelve patients did not have a repeat BDG level after at least two separate levels with &amp;gt;500 pg/ml. Ten (38.5%) subjects had a decline in BDG level 2-3 weeks after starting treatment. Serum BDG level did not return to within normal limits at week 4 of treatment except one patient. A repeat serum BDG level was seen decline at three weeks of treatment in four of six (66.6%) subjects with PJP, six weeks of treatment in three of six (50.0%) subjects with invasive aspergillosis and 8 weeks of treatment in six of 14 (42.8%) patients with invasive candidiasis. Two subjects had persistent elevation of BDG 8 weeks after treatment. (Figure 1) Conclusion Serial serum BDG level was not routinely done for monitoring the treatment response in this cohort. There was no linear decline in serum BDG level even after appropriate treatment in invasive fungal infections. A decline in serum BDG level was best observed among subjects with PJP pneumonia. It appears that the duration of a decline in serum BDG level was shorter in patients with PJP and longer in patients with invasive candidiasis. Disclosures All Authors: No reported disclosures.

Rezafungin and invasive candida infections: a new game changing antifungal?

Invasive candidiasis is a hospital-acquired infection with a high associated mortality.1 The antifungal drug armamentarium to manage patients with invasive candida infections is quite small and restricted to three drug families: the polyenes, the azoles, and the echinocandins. The Infectious Diseases Society of America and European Society for Clinical Microbiology Diseases international guidelines both support the use of echinocandins as first-line drugs for the treatment of invasive candida infections.