Статті в журналах: "Intra-Abdominal candidiasis"

1

Montravers, Philippe, Herve Dupont, and Philippe Eggimann. "Intra-abdominal candidiasis: the guidelines—forgotten non-candidemic invasive candidiasis." Intensive Care Medicine 39, no. 12 (October 24, 2013): 2226–30. http://dx.doi.org/10.1007/s00134-013-3134-2.

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Rex, John H., and Jack D. Sobel. "Preventing intra-abdominal candidiasis in surgical patients." Critical Care Medicine 27, no. 6 (June 1999): 1033–34. http://dx.doi.org/10.1097/00003246-199906000-00001.

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3

Derek Oh, Kenneth Rodrigues, Blerina Asllanaj, Alexander Urzua, Andy He, and Rosaly Diaz. "Intra-abdominal abscess with Candida in a post-operative setting." World Journal of Advanced Research and Reviews 18, no. 1 (April 30, 2023): 783–86. http://dx.doi.org/10.30574/wjarr.2023.18.1.0211.

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The goal in this case report is to discuss one presentation of the microbiology of the Candida species in an intra-abdominal abscess which is under reported. In general, the Candida species fungi is a common yeast found human beings as part of the microbiology. Common sites of candidiasis are often the oral cavity or the genitalia. Candida species have been found to have a mutualistic relationship with different species with the body [5]. When overproduction of Candida species occurs, it can cause pathological infections in patients. While it is common to see patients with Candida species in their gut micro biome, it is not well documented to have intra-abdominal abscesses that grow Candida species. Typically, bacterial causes are first on the differential for clinicians. This case presentation looks to discuss some of presenting factors seen in intra-abdominal candidiasis (IAC) and what leads to it being under diagnosed.

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4

Wan, Kaijing, Chong Kiat Khoo, and Rajeswari Kathirvel. "Unusual case of intra-abdominal candidiasis following laparoscopic hysterectomy." BMJ Case Reports 12, no. 4 (April 2019): e227897. http://dx.doi.org/10.1136/bcr-2018-227897.

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A 41-year-old woman with menorrhagia secondary to adenomyosis underwent an elective uncomplicated total laparoscopic hysterectomy after failed medical therapy. She developed fever, epigastric pain, nausea and diarrhoea on postoperative day (POD) 2. CT of abdomen and pelvis performed on POD 3 revealed an 8×3×3 cm fluid collection superior to the bladder. She did not respond to conservative treatment with intravenous antibiotics and therefore underwent an ultrasound-guided drainage on POD 7. The green-debris-laden fluid that was drained grewCandida. Investigations to screen for an immunocompromised state were negative. Her symptoms resolved after commencement of fluconazole and she was discharged home on POD 12. Repeat scans in 4 weeks’ time showed a marked reduction in collection. In a well patient, the presence of green intra-abdominal fluid should raise a suspicion for intra-abdominal candidiasis after ruling out bowel injury.

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Eggimann, Philippe, Patrick Francioli, Jacques Bille, Remy Schneider, Mei-Miau Wu, Germain Chapuis, Rene Chiolero, et al. "Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients." Critical Care Medicine 27, no. 6 (June 1999): 1066–72. http://dx.doi.org/10.1097/00003246-199906000-00019.

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6

Hargarten, Jessica C., Audrey L. Atkin, and Deborah M. Brown. "The Candida albicans quorum-sensing molecule, farnesol, remodels the peritoneal cavity microenvironment to promote innate inflammatory responses in mice." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 205.8. http://dx.doi.org/10.4049/jimmunol.196.supp.205.8.

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Abstract Candida albicans is a polymorphic fungus that causes mucosal candidiasis and life threatening, systemic and intra-abdominal disease in immunocompromised and transplant patients. In normal healthy adults, C albicans is maintained as a commensal mainly through the actions of innate cells. Secretion of the quorum-sensing molecule, farnesol, acts as a virulence factor for C. albicans during systemic infection, but is protective in oral models of infection. Despite the clinical importance of intra-abdominal candidiasis with a mortality rate as high as 65%, the role of farnesol in its pathogenesis has not been studied. In ongoing experiments, we found that introduction of farnesol into the peritoneal cavity (PC) of mice remodels the peritoneal microenvironment to promote innate inflammatory responses. Early following intraperitoneal injection, farnesol stimulates the rapid depletion of B cells followed by recruitment of inflammatory macrophages and neutrophils into the PC compared to thioglycollate and control mice. Kinetic analyses of the transcriptional profile of farnesol-elicited cells reveal an early increase in chemokines followed by increased proinflammatory cytokines consistent with macrophage recruitment and activation. In addition, farnesol-elicited macrophages and dendritic cells demonstrate hallmarks of innate immune activation through high surface expression of class II and co-stimulatory molecules. Current experiments aim to determine the impact of this innate immune recruitment on antifungal defenses and clearance in the PC. Defining the immunostimulatory properties of farnesol will inform development of more appropriate therapeutic strategies for treatment of intra-abdominal Candida infection.

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Vergidis, Pascalis, Cornelius J. Clancy, Ryan K. Shields, Seo Young Park, Brett N. Wildfeuer, Richard L. Simmons, and M. Hong Nguyen. "Intra-Abdominal Candidiasis: The Importance of Early Source Control and Antifungal Treatment." PLOS ONE 11, no. 4 (April 28, 2016): e0153247. http://dx.doi.org/10.1371/journal.pone.0153247.

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8

Montravers, Philippe, Olivier Leroy, and Christian Eckmann. "Intra-abdominal candidiasis: it’s still a long way to get unquestionable data." Intensive Care Medicine 41, no. 9 (June 19, 2015): 1682–84. http://dx.doi.org/10.1007/s00134-015-3894-y.

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9

Behrns, K. E. "Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients." Yearbook of Surgery 2010 (January 2010): 237–38. http://dx.doi.org/10.1016/s0090-3671(09)79604-1.

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10

Senn, Laurence, Philippe Eggimann, Riadh Ksontini, Andres Pascual, Nicolas Demartines, Jacques Bille, Thierry Calandra, and Oscar Marchetti. "Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients." Intensive Care Medicine 35, no. 5 (January 27, 2009): 903–8. http://dx.doi.org/10.1007/s00134-009-1405-8.

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11

Novy, Emmanuel, François-Xavier Laithier, Jeremie Riviere, Thomas Remen, Marie-Reine Losser, Philippe Guerci та Marie Machouart. "Protocol for the pBDG2 Study: Prospective Evaluation of 1.3-β-D-Glucan in the Peritoneal Fluid for the Diagnosis of Intra-Abdominal Candidiasis in Critically Ill Patients". Microbiology Research 12, № 1 (17 березня 2021): 196–203. http://dx.doi.org/10.3390/microbiolres12010015.

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Background: The delayed diagnosis of the presence of Candida in severe intra-abdominal infections exposes patients to an increased risk of mortality. The prevalence of intra-abdominal candidiasis (IAC) varies with the type of intra-abdominal infection, the underlying conditions and the presence of risk factors for Candida infection. This study aims to evaluate the interest of the measure of 1.3-β-D-glucan (BDG) in the peritoneal fluid for the early diagnosis of IAC. Methods and analysis: This is a prospective multicenter (n = 5) non-interventional study, focusing on all critically ill patients with an intra-abdominal infection requiring intra-abdominal surgery. The primary objective is to assess the diagnostic performance of the BDG measured in the peritoneal fluid for the early detection of IAC using the Candida culture as the gold standard. The secondary objective is to report the prevalence of IAC in the selected population. This study aims to enroll 200 patients within 48 months. By estimating the prevalence of IAC in the selected population at 30%, 50 patients with IAC (cases) are expected. These 50 IAC cases will be matched with 50 non-IAC patients (as a control group). The peritoneal BDG will be measured a posteriori in all of these 100 selected patients. This article presents the protocol and the current status of the study. Only the prevalence of IAC is reported as preliminary result.

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12

Mesquida, Aina, Marina Machado, Lorena Dávila-Cherres, Teresa Vicente, Carlos Sánchez-Carrillo, Luis Alcalá, Elena Reigadas, Patricia Muñoz, Jesús Guinea, and Pilar Escribano. "The Gastrointestinal Tract Is Pinpointed as a Reservoir of Candida albicans, Candida parapsilosis, and Candida tropicalis Genotypes Found in Blood and Intra-Abdominal Samples." Journal of Fungi 9, no. 7 (July 6, 2023): 732. http://dx.doi.org/10.3390/jof9070732.

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Background: 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. Materials/methods: 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. Results: 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. Conclusions: Our study pinpoints the gastrointestinal tract as a potential reservoir of potentially invasive Candida spp. genotypes.

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13

Cheng, Shaoji, Cornelius J. Clancy, Douglas J. Hartman, Binghua Hao, and M. Hong Nguyen. "Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses." Infection and Immunity 82, no. 7 (May 5, 2014): 3015–22. http://dx.doi.org/10.1128/iai.00062-14.

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ABSTRACTThe pathogenesis ofCandida glabratainfections is poorly understood. We studied the pathogenesis of intra-abdominal candidiasis (IAC) in mice that were infected intraperitoneally withC. glabrataand sterile feces.C. glabrataBG2 (5 × 108CFU) caused a 100% mortality rate. Sublethal inocula of BG2 (1 × 108or 1 × 107CFU) caused peritonitis that progressed to abscesses. Three clinicalC. glabratastrains (5 × 108CFU) caused 80 to 100% mortality rates, while a fourth (strain 346) caused a 29% mortality rate. Following sublethal inocula (1 × 107CFU), the intra-abscess burdens of virulent strain 356 were ∼1 log greater than those of strain 346. AC. glabrataΔplb1-2mutant (phospholipase B genes disrupted) killed mice as well as BG2 did. When sublethal inocula were used, however, the Δplb1-2mutant was associated with more rapid abscess resolution and lower intra-abscess burdens; these findings were reversed byPLB1andPLB2reinsertion. The Δplb1-2mutant was also more susceptible than BG2 to killing by human neutrophilsin vitro. BG2 and the Δplb1-2mutant were indistinguishable during hematogenously disseminated candidiasis.C. albicansSC5314 was more virulent thanC. glabrataBG2 during IAC, causing a 100% mortality rate following a challenge with 5 × 107CFU. In contrast, a sublethal inoculum (1 × 107CFU) of BG2 caused less neutrophil infiltration and greater burdens in peritoneal fluid than SC5314 did and abscesses that persisted longer and contained greater burdens. In conclusion, a mouse model ofC. glabrataIAC mimics disease in humans and distinguishes the relative virulence of clinical and gene disruption strains.C. glabratadiffered fromC. albicansduring IAC by being less lethal and eliciting dampened neutrophil responses but resulting in more persistent peritonitis and abscesses.

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14

Šašala, Martin, Emeše Majorová, Andrej Vrzgula, and Iveta Fandáková. "Evaluation of Invasive Intra-abdominal Candidiasis in Crohn Disease at the Time of Surgery." Annals of Coloproctology 36, no. 1 (February 29, 2020): 12–16. http://dx.doi.org/10.3393/ac.2018.10.15.2.

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Purpose: The aim of this study was to determine whether a connection exists between Crohn disease and fungi, specifically Candida albicans, because one possible cause of disease is thought to be the presence of fungi in the intra-abdominal cavity. The diagnosis of invasive candidiasis is difficult due to the lack of specific clinical manifestations of the disease. A retrospective evaluation of the presence of invasive candidiasis was done in a group of 54 patients with Crohn disease and in a group of 31 patients who received surgery primarily for right-sided cancer of the colon.Methods: Culture samples were obtained from the wall of the extraluminal portion of the terminal ileum and the adjacent mesenterium, and then sent to the microbiology laboratory for further investigation. Sabouraud agar (SGC2) and chromID Candida agar (CAN2) were used for both short-term (48 hours) and long-term (10 days) cultivation.Results: Pearson chi-square test revealed a statistically significant difference in the prevalence of fungi and yeast between the 2 groups of patients (χ2 = 4.3873, P < 0.05).Conclusion: Patients with Crohn disease had a significantly higher prevalence of fungi and yeasts in the intra-abdominal cavity compared with cancer patients.

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15

Colombo, Jacopo, Angela Arena, Daniela Codazzi, and Martin Langer. "Intra-abdominal candidiasis and probiotics: we know little but it’s time to try." Intensive Care Medicine 40, no. 2 (December 11, 2013): 297–98. http://dx.doi.org/10.1007/s00134-013-3172-9.

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16

Díaz-García, Judith, Ana Gómez, Marina Machado, Luis Alcalá, Elena Reigadas, Carlos Sánchez-Carrillo, Ana Pérez-Ayala, et al. "Candida Genotyping of Blood Culture Isolates from Patients Admitted to 16 Hospitals in Madrid: Genotype Spreading during the COVID-19 Pandemic Driven by Fluconazole-Resistant C. parapsilosis." Journal of Fungi 8, no. 11 (November 21, 2022): 1228. http://dx.doi.org/10.3390/jof8111228.

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Background: Candidaemia and invasive candidiasis are typically hospital-acquired. Genotyping isolates from patients admitted to different hospitals may be helpful in tracking clones spreading across hospitals, especially those showing antifungal resistance. Methods: We characterized Candida clusters by studying Candida isolates (C. albicans, n = 1041; C. parapsilosis, n = 354, and C. tropicalis, n = 125) from blood cultures (53.8%) and intra-abdominal samples (46.2%) collected as part of the CANDIMAD (Candida in Madrid) study in Madrid (2019–2021). Species-specific microsatellite markers were used to define the genotypes of Candida spp. found in a single patient (singleton) or several patients (cluster) from a single hospital (intra-hospital cluster) or different hospitals (widespread cluster). Results: We found 83 clusters, of which 20 were intra-hospital, 49 were widespread, and 14 were intra-hospital and widespread. Some intra-hospital clusters were first detected before the onset of the COVID-19 pandemic, but the number of clusters increased during the pandemic, especially for C. parapsilosis. The proportion of widespread clusters was significantly higher for genotypes found in both compartments than those exclusively found in either the blood cultures or intra-abdominal samples. Most C. albicans- and C. tropicalis-resistant genotypes were singleton and presented exclusively in either blood cultures or intra-abdominal samples. Fluconazole-resistant C. parapsilosis isolates belonged to intra-hospital clusters harboring either the Y132F or G458S ERG11p substitutions; the dominant genotype was also widespread. Conclusions: the number of clusters—and patients involved—increased during the COVID-19 pandemic mainly due to the emergence of fluconazole-resistant C. parapsilosis genotypes.

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Bassetti, Matteo, Antonio Vena, Daniele R. Giacobbe, Cecilia Trucchi, Filippo Ansaldi, Massimo Antonelli, Vaclava Adamkova, et al. "Risk Factors for Intra-Abdominal Candidiasis in Intensive Care Units: Results from EUCANDICU Study." Infectious Diseases and Therapy 11, no. 2 (February 19, 2022): 827–40. http://dx.doi.org/10.1007/s40121-021-00585-6.

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Krifors, Anders, Måns Ullberg, Markus Castegren, Johan Petersson, Ernesto Sparrelid, Volkan Özenci, and Ola Blennow. "Combining T2Bacteria and T2Candida Panels for Diagnosing Intra-Abdominal Infections: A Prospective Multicenter Study." Journal of Fungi 8, no. 8 (August 9, 2022): 832. http://dx.doi.org/10.3390/jof8080832.

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The T2Bacteria panel is a direct-from-blood assay that delivers rapid results, targeting E. coli, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa, and E. faecium (ESKAPE pathogens). In this study, T2Bacteria and T2Candida (targeting C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis) were evaluated in parallel with blood cultures in 101 consecutive surgical patients with suspected intra-abdominal infection admitted to the intensive care unit or high dependency unit. Fifteen patients had bacteremia, with T2Bacteria correctly identifying all on-panel (n = 8) pathogens. T2Bacteria was positive in 19 additional patients, 11 of whom had supportive cultures from other normally sterile sites (newly inserted drains, perioperative cultures or blood cultures) within seven days. Six of these eleven patients (55%) received broad-spectrum antibiotics at the sampling time. T2Candida identified the two cases of blood-culture-positive candidemia and was positive in seven additional patients, three of whom were confirmed to have intra-abdominal candidiasis. Of four patients with concurrent T2Bacteria and T2Candida positivity, only one patient had positive blood cultures (candidemia), while three out of four patients had supporting microbiological evidence of a mixed infection. T2Bacteria and T2Candida were fast and accurate in diagnosing on-panel bloodstream infections, and T2Bacteria was able to detect culture-negative intra-abdominal infections.

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19

de la Torre, Pola, and Annette C. Reboli. "Anidulafungin: Review of its Role in the Treatment of Invasive Candidiasis." Clinical Medicine Insights: Therapeutics 3 (January 2011): CMT.S3153. http://dx.doi.org/10.4137/cmt.s3153.

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In 2006 a third echinocandin, anidulafungin, was approved in the USA for the treatment of candida esophagitis, candidemia, and invasive candida infections such as intra-abdominal abscesses and peritonitis in the non-neutropenic patient. Two years later it was approved in the EU for invasive candidiasis in non-neutropenic patients. Like other echinocandins, it is fungicidal against Candida species and fungistatic against Aspergillus species. It does not need adjustment for renal or hepatic insufficiency, and has no known drug interactions. Its administration is by the intravenous route only, and it is well tolerated. A steady state concentration can be achieved on day two by giving twice the maintenance dose on day one.

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De Oliveira, Michael Éder, William Gustavo De Lima, Carla Ferreira Bruno Alves, Karina Marjorie Silva Herrera, Patrícia Campi Santos, Daniele da Glória De Souza, Maria Emilia Soares Martins Dos Santos, et al. "Synergetic action of atorvastatin and fluconazole against fluconazole-resistant Candida albicans in vitro and in a murine model for intra-abdominal Candidiasis / Ação sinérgica da atorvastatina e fluconazol contra Candida albicans resistente ao fluconazol in vitro e em um modelo murino contra Candidíase intra-abdominal." Brazilian Journal of Development 8, no. 5 (May 26, 2022): 41115–37. http://dx.doi.org/10.34117/bjdv8n5-543.

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Introduction: Candida albicans is the most common causative agent of Intra-abdominal Candidiasis (IAC) and it is resistant to most antifungal drugs currently available. Here we investigated atorvastatin in vitro and in vivo antifungal activities against a fluconazole-resistant C. albicans strain as a potential repurposed drug. The following tests were carried out: antifungal susceptibility tests to determine minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), determination of time-kill curve, biofilm assays, Candida albicans yeast-hyphae transition inhibition assay, murine model of Intra-abdominal candidiasis, survival curve, fungal load quantification, histopathology analysis, quantification of TNF-α and IL-17 cytokines, quantification of N-acetyl-β-D-glucosaminidase. In vitro assays showed the synergetic action of atorvastatin and fluconazole against C. albicans growth and biofilm maturation while the time-kill curve assay revealed their fungicidal effect after 24 h of treatment. When yeast-to-hyphae transition was assessed, the synergetic effect of atorvastatin and fluconazole reduced C. albicans filamentation significantly. In vivo tests showed that one of the most noticeable signs of IAC is the intense systemic inflammation. However, our survival curve test showed that despite being ill, animals exhibited little to no clinical signs of systemic inflammation when treatment included a combination of atorvastatin and fluconazole. Altogether, these findings suggest that atorvastatin could be feasibly used in the treatment fluconazole-resistant C. albicans strains, showing that drug repurposing is an important strategy when considering the limited number of antifungal drugs available for treatment in addition to financial hardship experienced in research and development of new antifungal drugs.

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Meena, Durga Shankar, and Deepak Kumar. "Candida Pneumonia: An Innocent Bystander or a Silent Killer?" Medical Principles and Practice 31, no. 1 (October 12, 2021): 98–102. http://dx.doi.org/10.1159/000520111.

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Invasive candidiasis is predominantly seen in immunosuppressed patients and carries a significant mortality. The clinical spectrum of invasive candidiasis encompasses candidemia and disseminated infection (intra-abdominal abscess, osteomyelitis, endophthalmitis, and Candida meningitis). The existence of Candida pneumonia has been largely debated over the years due to its rarity and presence of frequent colonization. Demonstration of Candida species by lung biopsy along with evidence of inflammation is the only way to confirm this entity. The interpretation of Candida in respiratory specimens and the decision to initiate antifungal therapy is controversial due to the lack of clinical evidence. In this mini-review, we discuss the currently available clinical data from the literature on Candida pneumonia and future perspectives regarding the need for antifungal therapy in such patients.

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Cheng, Shaoji, Cornelius J. Clancy, Wenjie Xu, Frank Schneider, Binghua Hao, Aaron P. Mitchell, and M. Hong Nguyen. "Profiling of Candida albicans Gene Expression During Intra-abdominal Candidiasis Identifies Biologic Processes Involved in Pathogenesis." Journal of Infectious Diseases 208, no. 9 (September 4, 2013): 1529–37. http://dx.doi.org/10.1093/infdis/jit335.

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Pea, F., E. Righi, P. Cojutti, A. Carnelutti, U. Baccarani, G. Soardo, and M. Bassetti. "Intra-abdominal penetration and pharmacodynamic exposure to fluconazole in three liver transplant patients with deep-seated candidiasis." Journal of Antimicrobial Chemotherapy 69, no. 9 (May 15, 2014): 2585–86. http://dx.doi.org/10.1093/jac/dku169.

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Bassetti, Matteo, Monia Marchetti, Arunaloke Chakrabarti, Sergio Colizza, Jose Garnacho-Montero, Daniel H. Kett, Patricia Munoz, et al. "A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts." Intensive Care Medicine 39, no. 12 (October 9, 2013): 2092–106. http://dx.doi.org/10.1007/s00134-013-3109-3.

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KAYANO, Masashi, Kenya YAMANAKA, Yumiko FUJIWARA, Misaki TASHIMA, Kaichiro HARADA, and Jun TAMURA. "A Case of Surgical Drainage for Intra-abdominal Candidiasis after Peritonitis due to a Perforated Duodenal Ulcer." Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 83, no. 8 (2022): 1544–49. http://dx.doi.org/10.3919/jjsa.83.1544.

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Huseynov, Ravil M., Samir S. Javadov, Ali Osmanov, Shahin Khasiyev, Samira R. Valiyeva, Esmira Almammadova, and David W. Denning. "The burden of serious fungal infections in Azerbaijan." Therapeutic Advances in Infectious Disease 8 (January 2021): 204993612110439. http://dx.doi.org/10.1177/20499361211043969.

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Background: Azerbaijan is an upper middle-income country in South Caucasus with an area of 86,600 km2 and a total population of 10 million people and gross domestic product of US $4480 per capita. The aim of this research is to estimate fungal infection burden and highlight the problem at national and international levels. Methods: Fungal infection burden was estimated using data from epidemiological papers and population at risk and LIFE (Leading International Fungal Education) modelling. Results: The number of people living with human immunodeficiency virus (PLHIV) in 2018 was 6193, 29% of them not receiving antiretroviral therapy. Based on 90% and 20% rates of oral and oesophageal candidiasis in patients with CD4 cell count <200 µl–1 we estimate 808 and 579 patients with oral and oesophageal candidiasis, respectively. The annual incidences of cryptococcal meningitis and Pneumocystis pneumonia are 5 and 55 cases, respectively. We estimated 2307 cases of chronic pulmonary aspergillosis (CPA), 4927 patients with allergic bronchopulmonary aspergillosis (ABPA), and 6504 with severe asthma with fungal sensitization (SAFS). Using data on chronic obstructive pulmonary diseases (COPD), lung cancer, acute myeloid leukaemia rates, and number of transplantations, we estimated 693 cases of invasive aspergillosis following these conditions. Using a low-European rate for invasive candidiasis, we estimated 499 and 75 patients with candidemia and intra-abdominal candidiasis respectively. The number of adult women (15–55 years) in Azerbaijan is ~2,658,000, so it was estimated that 159,490 women suffer from recurrent vulvovaginal candidiasis (rVVC). Discussion: In total, the estimated number of people suffering from fungal diseases in Azerbaijan is 225,974 (2.3% of the population). However, the fungal rate is underestimated due to lack of epidemiological data. The most imminent need is improvement in diagnostic capabilities. This aim should be achieved via establishing a reference laboratory and equipping major clinical centers with essential diagnostics assays.

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Bassetti, Matteo, Maddalena Peghin, Alessia Carnelutti, Elda Righi, Maria Merelli, Filippo Ansaldi, Cecilia Trucchi, et al. "Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study." Intensive Care Medicine 43, no. 4 (March 7, 2017): 509–18. http://dx.doi.org/10.1007/s00134-017-4717-0.

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Dupont, Hervé, Stéphanie Malaquin, Léonie Villeret, Pierre-Yves Macq, Nacim Ammenouche, François Tinturier, Momar Diouf, Matthieu Rumbach, and Taieb Chouaki. "Is ß-d-glucan Relevant for the Diagnosis and Follow-up of Intensive Care Patients with Yeast-Complicated Intra-Abdominal Infection?" Journal of Fungi 8, no. 5 (May 6, 2022): 487. http://dx.doi.org/10.3390/jof8050487.

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The usefulness of (1,3)-ß-d-glucan (BDG) detection for the diagnosis of intra-abdominal candidiasis and treatment monitoring is unknown. A prospective, single-center study of consecutive patients admitted to an ICU with complicated intra-abdominal infection (IAI) over a 2-year period was conducted. BDG was measured in the peritoneal fluid and serum between day 1 (D1) and D10. Patients with a positive peritoneal fluid yeast culture (YP) were compared to those with a negative yeast culture (YN). The evolution of serum BDG was compared in the two groups. Seventy patients were included (sixty-five analyzed): YP group (n = 19) and YN group (n = 46). Median peritoneal BDG concentration during surgery was 2890 pg.mL−1 [IQR: 942‒12,326] in the YP group vs. 1202 pg.mL−1 [IQR: 317‒4223] in the YN group (p = 0.13). Initial serum BDG concentration was 130 pg.mL−1 [IQR: 55‒259] in the YP group vs. 88 pg.mL−1 [IQR: 44‒296] in the YN group (p = 0.78). No difference in evolution of serum BDG concentrations was observed between the groups (p = 0.18). In conclusion, neither peritoneal BDG nor serum BDG appear to be good discriminating markers for the diagnosis of yeast IAI. In addition, monitoring the evolution of serum BDG in yeast IAI did not appear to be of any diagnostic value.

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Fidel, Paul L., Junko Yano, Shannon K. Esher, and Mairi C. Noverr. "Applying the Host-Microbe Damage Response Framework to Candida Pathogenesis: Current and Prospective Strategies to Reduce Damage." Journal of Fungi 6, no. 1 (March 11, 2020): 35. http://dx.doi.org/10.3390/jof6010035.

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Disease is a complex outcome that can occur as a result of pathogen-mediated damage, host-mediated damage or both. This has led to the revolutionary concept of the damage response framework (DRF) that defines microbial virulence as a function of host immunity. The DRF outlines six scenarios (classes) of host damage or beneficial outcomes, depending on the microbe and the strength of the immune response. Candida albicans is uniquely adapted to its human host and can exist as either a commensal, colonizing various anatomical sites without causing notable damage, or as a pathogen, with the ability to cause a diverse array of diseases, ranging from mucosal to invasive systemic infections that result in varying levels of microbe-mediated and/or host-mediated damage. We recently categorized six different forms of candidiasis (oropharyngeal, hematogenous, intra-abdominal, gastrointestinal, denture stomatitis, and vulvovaginitis) into independent DRF classes, supporting a contemporary view of unique mechanisms of pathogenesis for these Candida infections. In this review, we summarize the evidence for the pathogenesis of these various forms of candidiasis in the context of the DRF with the further intent to provide insights into strategies to achieve a level of host response or outcome otherwise, that limits host damage.

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Maseda, Emilio, Alejandro H. Rodríguez, Gerardo Aguilar, Javier Pemán, Rafael Zaragoza, Ricard Ferrer, Pedro Llinares, and Santiago Grau. "EPICO 3.0. Recommendations on invasive candidiasis in patients with complicated intra-abdominal infection and surgical patients with ICU extended stay." Revista Iberoamericana de Micología 33, no. 4 (October 2016): 196–205. http://dx.doi.org/10.1016/j.riam.2016.02.003.

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Yan, Ting, Shuang-Ling Li, Hai-Li Ou, Sai-Nan Zhu, Lei Huang, and Dong-Xin Wang. "Appropriate Source Control and Antifungal Therapy are Associated with Improved Survival in Critically Ill Surgical Patients with Intra-abdominal Candidiasis." World Journal of Surgery 44, no. 5 (January 21, 2020): 1459–69. http://dx.doi.org/10.1007/s00268-020-05380-x.

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Clancy, Cornelius J., Palash Samanta, Shaoji Cheng, Kevin Squires, and Minh-Hong Nguyen. "1726. Candida albicans Virulence Genes Induced During Intra-abdominal Candidiasis (IAC) in the Absence of Antifungal Exposure Mediate Echinocandin Resistance." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S633. http://dx.doi.org/10.1093/ofid/ofz360.1589.

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Abstract Background We developed and validated a mouse model of C. albicans IAC that mimics peritonitis and abscesses (IAA) in humans, and that is amenable to temporal–spatial transcriptional profiling and virulence studies. Methods We measured C. albicans SC5314 gene expression by RNA-Seq (RiboPure extraction; Illumina MiSeq) in triplicate during early peritonitis (within 30 minutes of infection), late peritonitis (24 hours) and IAA (48 hours). Differential expression was defined by ≥2-fold differences at false discovery rate ≤0.01. Results ≥7 million C. albicans reads were detected in each experiment. 67% of C. albicans reads mapped to coding sequences, covering 93% of open reading frames. The 50 C. albicans genes most highly expressed during early peritonitis were associated with pH (including RIM101 and PHR1) and oxidative stress responses, and adhesion/hyphal growth (e.g., ALS3, HWP1, ECM331, SAP6). The corresponding 50 C. albicans late peritonitis genes were associated with neutrophil/macrophage responses and nutrient acquisition (glyoxylate cycle, fatty acid β-oxidation, iron homeostasis). Responses within IAA included DNA damage and iron metabolism, reflecting stress response and nutrient/metal limitation. The top 50 core gene responses for all stages were associated with adhesion, stress response, and glucose transport. Among the most up-regulated genes in late peritonitis and IAA compared with early peritonitis were those involved antifungal drug resistance (CDR family, MDR1, FLU1, and ERG family), although mice were not exposed to antifungals. Null and reconstitution mutants for genes involved in adhesion (ALS3), copper transport (CCC2), DNA (DDI1) and cell wall damage responses (DAP1 homologs), and glycerol biosynthesis (RHR2) were attenuated for virulence in temporal-spatial fashion during peritonitis and IAA, and/or hyper-susceptible to phagocytosis and echinocandins (table). Conclusion C. albicans relies upon diverse biologic processes to cause peritonitis and IAA. Multiple genes induced in response to stress during IAC mediate virulence, phagocyte, and echinocandin resistance. Therefore, pathogenic strategies used by C. albicans during IAC may lessen responses to echinocandin treatment, even in the absence of drug exposure or FKS mutations. Disclosures All authors: No reported disclosures.

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Clancy, Cornelius J., Shaoji Cheng, Kevin Squires, and Minh-Hong Nguyen. "2887. Identifying Candida albicans Transcription Factors (TFs) That Regulate Pathogenesis of Intra-abdominal Candidiasis (IAC) by Screening a Deletion Mutant Library." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S77. http://dx.doi.org/10.1093/ofid/ofz359.165.

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Abstract Background IAC is a common manifestation of invasive candidiasis, but its pathogenesis is poorly understood. We developed a mouse model of C. albicans IAC, in which disease progresses from peritonitis to abscesses (IAA) in a manner that recapitulates human infection. Our goal was to use the model to identify C. albicans TFs that regulate virulence during IAC. Methods We screened a signature-tagged library (48 unique oligonucleotide markers) of homozygous deletion mutants for 165 C. albicans TF genes, created in duplicate in strain SC5314 (S. Noble). Mice were infected intra-peritoneally in triplicate with pools of 24 mutants and wild-type, and strains harvested at 72 hours in IAA. Results Twenty-one TF mutants were significantly attenuated for virulence in both libraries, and 2 TF mutants were significantly more virulent in both libraries, as measured by tissue burdens (figure). Biologic processes over-represented among attenuated mutants were regulation of pH responses, biofilm, hyphal formation, echinocandin responses, and copper metabolism. pH responses are likely to be crucial to pathogenesis of IAC, as C. albicans transitions from pH 8 during peritonitis to pH 6.8 within IAA. 9 pH response regulators contributing to virulence included RIM101, STP2 (alkaline), ASH1, SFL1, SFL2 (neutral), MNL1, SKO1, PHO4 (weak acid), and CSR1 (acid). We created rim101 null mutant and reconstitution strains, and demonstrated that the gene was essential for complete virulence during peritonitis and IAA. Transcriptional profiling of strains by RT-PCR during peritonitis and in vitro showed both conserved and rewired Rim101 targets. SAP5, which encodes an aspartyl protease, is a major Rim101 target in vivo and in vitro; over-expression of SAP5 in rim101 restored virulence during IAA at 3, 7, and 10 days, but not during peritonitis. Other pH regulatory TF genes are currently being validated as virulence determinants, and pathway relationships between MNL1, SKO1, and PHO4 during IAA formation are being explored through epistasis approaches. Conclusion Screening of a C. albicans TF mutant library identified pH responses and other biologic processes as important during pathogenesis of IAC. Rim101, an alkaline pH response regulator, contributes to both peritonitis and IAA, the latter at least in part through its effects on Sap5. Disclosures All Authors: No reported Disclosures.

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Sganga, Gabriele, Minggui Wang, M. Rita Capparella, Margaret Tawadrous, Jean L. Yan, Jalal A. Aram, and Philippe Montravers. "Evaluation of anidulafungin in the treatment of intra-abdominal candidiasis: a pooled analysis of patient-level data from 5 prospective studies." European Journal of Clinical Microbiology & Infectious Diseases 38, no. 10 (July 6, 2019): 1849–56. http://dx.doi.org/10.1007/s10096-019-03617-9.

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Fortún, J., M. J. Buitrago, F. Gioia, E. Gómez-Gª de la Pedrosa, M. E. Alvarez, P. Martín-Dávila, V. Pintado та ін. "Roles of the multiplex real-time PCR assay and β-D-glucan in a high-risk population for intra-abdominal candidiasis (IAC)". Medical Mycology 58, № 6 (7 грудня 2019): 789–96. http://dx.doi.org/10.1093/mmy/myz123.

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Abstract Multiplex quantitative real-time PCR (MRT-PCR) using blood can improve the diagnosis of intra-abdominal candidiasis (IAC). We prospectively studied 39 patients with suspected IAC in the absence of previous antifungal therapy. Blood cultures, MRT-PCR, and β-D-glucan (BDG) in serum were performed in all patients. IAC was defined according to the 2013 European Consensus criteria. For MRT-PCR, the probes targeted the ITS1 or ITS2 regions of ribosomal DNA. Candidaemia was confirmed only in four patients (10%), and IAC criteria were present in 17 patients (43.6%). The sensitivity of MRT-PCR was 25% but increased to 63.6% (P = .06) in plasma obtained prior to volume overload and transfusion; specificity was above 85% in all cases. BDG performance was improved using a cutoff > 260 pg/ml, and improvement was not observed in samples obtained before transfusion. In this cohort of high risk of IAC and low rate of bloodstream infection, the performance of non-culture-based methods (MRT-PCR or BDG) was moderate but may be a complementary tool given the limitations of diagnostic methods available in clinical practice. Volume overload requirements, in combination with other factors, decrease the accuracy of MRT-PCR in patients with IAC.

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Lagunes, L., A. Rey-Pérez, M. T. Martín-Gómez, A. Vena, V. de Egea, P. Muñoz, E. Bouza, et al. "Association between source control and mortality in 258 patients with intra-abdominal candidiasis: a retrospective multi-centric analysis comparing intensive care versus surgical wards in Spain." European Journal of Clinical Microbiology & Infectious Diseases 36, no. 1 (September 21, 2016): 95–104. http://dx.doi.org/10.1007/s10096-016-2775-9.

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Breitkopf, Robert, Benedikt Treml, Thomas Senoner, Zoran Bukumirić, and Sasa Rajsic. "Invasive Fungal Breakthrough Infections under Targeted Echinocandin Prophylaxis in High-Risk Liver Transplant Recipients." Journal of Fungi 9, no. 2 (February 18, 2023): 272. http://dx.doi.org/10.3390/jof9020272.

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Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of discussion. Echinocandins are increasingly being used due to their advantageous safety profile and the increasing number of non-albicans Candida infections. However, the evidence justifying their use remains rather sparse. Recently published data on breakthrough IFI (b-IFI) raise concerns about echinocandin efficacy, especially in the case of intra-abdominal candidiasis (IAC), which is the most common infection site after OLT. In this retrospective study, we analyzed 100 adult HR-LTRs undergoing first-time OLT and receiving echinocandin prophylaxis between 2017 and 2020 in a tertiary university hospital. We found a breakthrough incidence of 16%, having a significant impact on postoperative complications, graft survival, and mortality. The reasons for this may be multifactorial. Among the pathogen-related factors, we identified the breakthrough of Candida parapsilosis in 11% of patients and one case of persistent IFI due to the development of a secondary echinocandin resistance of an IAC caused by Candida glabrata. Consequently, the efficacy of echinocandin prophylaxis in liver transplantation should be questioned. Further studies are necessary to clarify the matter of breakthrough infections under echinocandin prophylaxis.

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Shields, Ryan K., M. Hong Nguyen, Ellen G. Press, Andrea L. Kwa, Shaoji Cheng, Chen Du, and Cornelius J. Clancy. "The Presence of anFKSMutation Rather than MIC Is an Independent Risk Factor for Failure of Echinocandin Therapy among Patients with Invasive Candidiasis Due to Candida glabrata." Antimicrobial Agents and Chemotherapy 56, no. 9 (July 2, 2012): 4862–69. http://dx.doi.org/10.1128/aac.00027-12.

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ABSTRACTEchinocandins are frontline agents against invasive candidiasis (IC), but predictors for echinocandin therapeutic failure have not been well defined. Mutations inCandida FKSgenes, which encode the enzyme targeted by echinocandins, result in elevated MICs and have been linked to therapeutic failures. In this study, echinocandin MICs by broth microdilution andFKS1andFKS2mutations amongC. glabrataisolates recovered from patients with IC at our center were correlated retrospectively with echinocandin therapeutic responses. Thirty-five patients with candidemia and 4 with intra-abdominal abscesses were included, 92% (36/39) of whom received caspofungin. Twenty-six percent (10) and 74% (29) failed and responded to echinocandin therapy, respectively. Caspofungin, anidulafungin, and micafungin MICs ranged from 0.5 to 8, 0.03 to 1, and 0.015 to 0.5 μg/ml, respectively.FKSmutations were detected in 18% (7/39) ofC. glabrataisolates (FKS1,n= 2;FKS2,n= 5). Median caspofungin and anidulafungin MICs were higher for patients who failed therapy (P= 0.04 and 0.006, respectively). By receiver operating characteristic (ROC) analyses, MIC cutoffs that best predicted failure were >0.5 (caspofungin), >0.06 (anidulafungin), and >0.03 μg/ml (micafungin), for which sensitivity/specificity were 60%/86%, 50%/97%, and 40%/90%, respectively. Sensitivity/specificity of anFKSmutation in predicting failure were 60%/97%. By univariate analysis, recent gastrointestinal surgery, prior echinocandin exposure, anidulafungin MIC of >0.06 μg/ml, caspofungin MIC of >0.5 μg/ml, and anFKSmutation were significantly associated with failure. The presence of anFKSmutation was the only independent risk factor by multivariate analysis (P= 0.002). In conclusion, detection ofC. glabrata FKSmutations was superior to MICs in predicting echinocandin therapeutic responses among patients with IC.

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Dunaiski and Denning. "Estimated Burden of Fungal Infections in Namibia." Journal of Fungi 5, no. 3 (August 16, 2019): 75. http://dx.doi.org/10.3390/jof5030075.

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Namibia is a sub-Saharan country with one of the highest HIV infection rates in the world. Although care and support services are available that cater for opportunistic infections related to HIV, the main focus is narrow and predominantly aimed at tuberculosis. We aimed to estimate the burden of serious fungal infections in Namibia, currently unknown, based on the size of the population at risk and available epidemiological data. Data were obtained from the World Health Organization (WHO), Joint United Nations Programme on HIV/AIDS (UNAIDS), and published reports. When no data existed, risk populations were used to estimate the frequencies of fungal infections, using the previously described methodology. The population of Namibia in 2011 was estimated at 2,459,000 and 37% were children. Among approximately 516,390 adult women, recurrent vulvovaginal candidiasis (≥4 episodes /year) is estimated to occur in 37,390 (3003/100,000 females). Using a low international average rate of 5/100,000, we estimated 125 cases of candidemia, and 19 patients with intra-abdominal candidiasis. Among survivors of pulmonary tuberculosis (TB) in Namibia 2017, 112 new cases of chronic pulmonary aspergillosis (CPA) are likely, a prevalence of 354 post-TB and a total prevalence estimate of 453 CPA patients in all. Asthma affects 11.2% of adults, 178,483 people, and so allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) were estimated in approximately 179/100,000 and 237/100,000 people, respectively. Invasive aspergillosis (IA) is estimated to affect 15 patients following leukaemia therapy, and an estimated 0.13% patients admitted to hospital with chronic obstructive pulmonary disease (COPD) (259) and 4% of HIV-related deaths (108) — a total of 383 people. The total HIV-infected population is estimated at 200,000, with 32,371 not on antiretroviral therapy (ART). Among HIV-infected patients, 543 cases of cryptococcal meningitis and 836 cases of Pneumocystis pneumonia are estimated each year. Tinea capitis infections were estimated at 53,784 cases, and mucormycosis at five cases. Data were missing for fungal keratitis and skin neglected fungal tropical diseases such as mycetoma. The present study indicates that approximately 5% of the Namibian population is affected by fungal infections. This study is not an epidemiological study—it illustrates estimates based on assumptions derived from similar studies. The estimates are incomplete and need further epidemiological and diagnostic studies to corroborate, amend them, and improve the diagnosis and management of these diseases.

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Maseda, Emilio, Alejandro H. Rodríguez, Gerardo Aguilar, Javier Pemán, Rafael Zaragoza, Ricard Ferrer, Pedro Llinares, and Santiago Grau. "Erratum to: “EPICO 3.0. Recommendations on invasive candidiasis in patients with complicated intra-abdominal infection and surgical patients with ICU extended stay” [Rev Iberoam Micol. 33 (4) (2016) 196–205]." Revista Iberoamericana de Micología 34, no. 1 (January 2017): 61. http://dx.doi.org/10.1016/j.riam.2017.02.002.

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Cheng, Shaoji, Badrane Hassan, Guojun Liu, Cornelius J. Clancy, and Minh-Hong Nguyen. "116. Characterization of small colony variants from a patient with bloodstream infection of Candida glabrata." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S70—S71. http://dx.doi.org/10.1093/ofid/ofab466.116.

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Abstract Background Bacterial small colony variants (SCVs) that are tolerant to commonly used antibiotics are well recognized. Clinical SCV Candida have been rarely reported. We describe SCV C. glabrata (CG) strains recovered from within a population causing bloodstream infection (BSI) in a patient (pt), which were not recognized by the micro lab. Pt J developed CG BSI shortly after liver transplant (OLTX), which was treated with voriconazole (VOR). VOR was also used for post-OLTX mold prophylaxis. 67 d after BSI, he developed intra-abdominal infection due to VOR-resistant CG. We hypothesized that BSI might be caused by an unrecognized mixed population of azole-susceptible and –resistant strains. Methods Ten colonies from small (SCV) and large colonies (LC) from blood culture (BC) agar plates underwent Illumina NextSeq WGS and phenotype testing. Results BCs from pt J harbored a diverse population of genetically distinct CG strains, differing by unique SNPs and indels [Fig. 1]. Gene variants identified were enriched for biological processes involved in mitochondrial processes (2.5e-9), cell adhesion (3.3e-5), and respiration (3.5e-4). Unlike LC, SCVs were fluconazole (FLU) resistant (MIC: 128 µg/mL), and exhibited enhanced CDR1 and PDR1 expression (257 ± 11, 15 ± 4, respectively). Compared to LCs, SCVs grew slowly in YPD, did not grow on media containing glycerol as sole carbon source, and were less adherent to agar. SCVs stained poorly with rhodamine 123 by fluorescence flow cytometry and had fewer mitochrondria by transmission electron microscopy, consistent with WGS findings and respiratory deficiency. SCVs were less susceptible to macrophage (J774) phagocytosis, and they were significantly outgrown by other strains in competitive infections in vitro and during disseminated candidiasis in mice. LCs incubated with FLU in vitro yielded SCVs in concentration-dependent manner. Likewise, LCVs passed through spleens of mice following IV inoculation yielded SCVs in both presence and absence of FLU. Venn diagram for 5 representative stranis of C.glabrata Conclusion Mitochondrial dysfunction and SCVs may be under-recognized determinants of azole resistance in CG, if micro labs select single colonies from BCs for antifungal susceptibility testing, or in absence of prolonged incubation. Disclosures Cornelius J. Clancy, MD, Merck (Grant/Research Support) Minh-Hong Nguyen, MD, Merck (Grant/Research Support)

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Alexander, Barbara D., Oliver Cornely, Peter Pappas, Rachel Miller, Jose A. Vazquez, Luis Ostrosky-Zeichner, Andrej Spec, et al. "1248. Efficacy and Safety of Oral Ibrexafungerp in 41 Patients with Refractory Fungal Diseases, Interim Analysis of a Phase 3 Open-label Study (FURI)." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S642. http://dx.doi.org/10.1093/ofid/ofaa439.1432.

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Abstract Background Candida infections resistant to currently available antifungals are an emerging global threat. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of oral ibrexafungerp (FURI) (Clinicaltrials.gov NCT03059992) is ongoing for the treatment of patients (≥18 years) with fungal diseases who are intolerant of or refractory to standard antifungal therapies. Methods An independent Data Review Committee (DRC) provided an assessment of treatment response for 41 patients. Patients were enrolled in 22 centers from 6 countries. Patients were eligible for enrollment if they had proven or probable, invasive or severe mucocutaneous candidiasis and documented evidence of failure of, intolerance to, or toxicity related to a currently approved standard-of-care antifungal treatment or could not receive approved oral antifungal options (e.g., susceptibility of the organism) and a continued IV antifungal therapy was undesirable or unfeasible. Results The 41 patients assessed had the following infection types: intra-abdominal abscesses, oropharyngeal candidiasis, esophageal candidiasis, candidemia, and others. The DRC adjudicated 23 patients (56%) as achieving complete or partial response, 11 patients (27%) maintaining stable disease, 6 patients (15%) with progression of disease and one case was considered as indeterminate. The efficacy of oral ibrexafungerp by pathogen is shown in Table 1. Ibrexafungerp was well-tolerated with the most common treatment-related adverse events being of gastrointestinal origin. No deaths due to progression of fungal disease were reported. Table 1: Ibrexafungerp Outcomes by Pathogen Conclusion Preliminary analysis of these 41 cases indicate that oral ibrexafungerp provides a favorable therapeutic response in the majority of patients with difficult to treat Candida spp. infections, including those caused by non-albicans Candida species. Disclosures Barbara D. Alexander, MD, MHS, SCYNEXIS, Inc. (Employee, Scientific Research Study Investigator, Research Grant or Support) Oliver Cornely, Prof., Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Rachel Miller, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Luis Ostrosky-Zeichner, MD, Amplyx (Scientific Research Study Investigator)Astellas (Consultant, Scientific Research Study Investigator, Other Financial or Material Support, Non-branded educational speaking)Biotoscana (Consultant, Other Financial or Material Support, Non-branded educational speaking)Cidara (Consultant, Scientific Research Study Investigator)F2G (Consultant)Gilead (Consultant)Mayne (Consultant)Octapharma (Consultant)Pfizer (Other Financial or Material Support, Non-branded educational speaking)Scynexis (Consultant, Grant/Research Support, Scientific Research Study Investigator)Stendhal (Consultant)Viracor (Consultant) Andrej Spec, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator, Advisor or Review Panel member) Riina Rautemaa-Richardson, DDS, PhD, FRCPath, SCYNEXIS, Inc. (Scientific Research Study Investigator) Robert Krause, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Caryn Morse, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) John W. Sanders, III, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) David Andes, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator, Advisor or Review Panel member) George Lyon, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Francisco M. Marty, MD, Allovir (Consultant)Amplyx (Consultant)Ansun (Scientific Research Study Investigator)Avir (Consultant)Cidara (Scientific Research Study Investigator)F2G (Consultant, Scientific Research Study Investigator)Kyorin (Consultant)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)New England Journal of Medicine (Other Financial or Material Support, Honorarium for Video)Regeneron (Consultant, Scientific Research Study Investigator)ReViral (Consultant)Scynexis (Scientific Research Study Investigator)Symbio (Consultant)Takeda (Scientific Research Study Investigator)United Medical (Consultant)WHISCON (Scientific Research Study Investigator) Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member) Thomas F. Patterson, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, SCYNEXIS, Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder)

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Azim, Afzal, Armin Ahmed, Arvind Kumar Baronia, Rungmei S. K. Marak, and Nabeel Muzzafar. "Intra-Abdominal Candidiasis." EMJ Nephrology, July 18, 2017, 82–93. http://dx.doi.org/10.33590/emjnephrol/10310735.

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Intra-abdominal candidiasis (IAC) is the second most common form of invasive candidiasis after candidaemia. IAC is a broad term and can be classified on the basis of anatomical site (Candida peritonitis, pancreatic candidiasis, biliary tract candidiasis, gastrointestinal candidiasis, and hepatosplenic candidiasis) as well as clinical setting (community acquired versus nosocomial). The risk factors linked with IAC are candida colonisation, anastomotic leak, multiple instrumentation, long-term broad spectrum antibiotic use, total parenteral nutrition, and immunocompromised state. Clinically, IAC is not different from intraabdominal bacterial infection. Patients generally present with signs and symptoms of intra-abdominal sepsis after not responding to antibiotic therapy and with a background history of multiple surgical interventions or history of delayed source control. Radiological investigations, like ultrasonography and computed tomography scan, not only aid in diagnosis but also assist in differentiating medical from surgical cases. Microbiological diagnosis requires isolation of candida from an intra-abdominal specimen. Differentiation between colonisation and infection is difficult. Generally, progressive and persistent colonisation is associated with high risk of infection. Blood cultures have poor sensitivity for IAC. Non-culture based techniques used for diagnosis are mannan/anti-mannan assay, beta-D glucan assay, and validated polymerase chain reaction. Four types of antifungal strategies described in the literature are prophylaxis (risk factor driven), pre-emptive (colonisation or biomarker driven), empirical (fever driven), and targeted therapy (microbiology driven). Over recent years, global epidemiology has shown a shift from Candida albicans to non-albicans. Local epidemiology plays an important role in selection of the appropriate empirical therapy. The purpose of this review is to discuss different types of IAC based on their classification, risk factors, and management.

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Habighorst, Kelsey, James M. Sanders, Sara A. Hennessy, Kristina Goff, Bingchun Wan, and Meagan Johns. "Identification of Risk Factors for Intra-Abdominal Candidiasis." Surgical Infections, November 23, 2023. http://dx.doi.org/10.1089/sur.2023.149.

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Liao, Min, Xuekui Xia, Qingzhou Meng, Chengguang Zhu, Binyou Liao, Jiannan Wang, Lichen Gou, et al. "Holotoxin A₁ from Apostichopus japonicus inhibited oropharyngeal and intra‐abdominal candidiasis by inducing oxidative damage in Candida albicans." British Journal of Pharmacology, February 21, 2024. http://dx.doi.org/10.1111/bph.16333.

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AbstractBackground and PurposeThe holotoxin A1, isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A1 against Candida albicans and in murine oropharyngeal and intra‐abdominal candidiasis.Experimental ApproachThe antifungal effect of holotoxin A1 against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A1, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. Effectiveness and systematic toxicity of holotoxin A1 in vivo was assessed in the oropharyngeal and intra‐abdominal candidiasis models in mice.Key ResultsHolotoxin A1 was a potent fungicide against C. albicans SC5314, clinical strains and drug‐resistant strains. Holotoxin A1 inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A1 induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A1 directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of complex I, against C. albicans. Meanwhile, the complex I subunit NDH51 null mutants showed a decreased susceptibility to holotoxin A1. Furthermore, holotoxin A1 significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra‐abdominal candidiasis in murine models.Conclusion and ImplicationsHolotoxin A1 is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra‐abdominal candidiasis, especially when caused by drug‐resistant strains.

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Lee, Annie, Ning Wang, Claire L. Carter, Matthew Zimmerman, Véronique Dartois, Karen Joy Shaw, David S. Perlin, and Yanan Zhao. "Therapeutic Potential of Fosmanogepix (APX001) for Intra-abdominal Candidiasis: from Lesion Penetration to Efficacy in a Mouse Model." Antimicrobial Agents and Chemotherapy 65, no. 4 (March 18, 2021). http://dx.doi.org/10.1128/aac.02476-20.

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Intra-abdominal candidiasis (IAC) is one of the most common yet underappreciated forms of invasive candidiasis. IAC is difficult to treat, and therapeutic failure and drug-resistant breakthrough infections are common in some institutions despite the use of echinocandins as first-line agents.

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Hargarten, Jessica C., Malcolm J. Vaughan, Anna T. Lampe, Riley M. Jones, Kenneth Ssebambulidde, Kenneth W. Nickerson, Peter R. Williamson, Audrey L. Atkin, and Deborah M. Brown. "Farnesol remodels the peritoneal cavity immune environment influencing Candida albicans pathogenesis during intra-abdominal infection." Infection and Immunity, November 17, 2023. http://dx.doi.org/10.1128/iai.00384-23.

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ABSTRACT Candida albi c ans is a lifelong member of the mycobiome causing mucosal candidiasis and life-threatening, systemic, and intra-abdominal disease in immunocompromised and transplant patients. Despite the clinical importance of intra-abdominal candidiasis with mortality rates between 40% and 70%, the contribution of fungal virulence factors and host immune responses to disease has not been extensively studied. Secretion of the quorum-sensing molecule, farnesol, acts as a virulence factor for C. albicans during systemic infection, while inducing local, protective innate immune responses in oral models of infection. Previously, we reported that farnesol recruits macrophages to the peritoneal cavity in mice, suggesting a role for farnesol in innate immune responses. Here, we expand on our initial findings, showing that farnesol profoundly alters the peritoneal cavity microenvironment promoting innate inflammation. Intra-peritoneal injection of farnesol stimulates rapid local death of resident peritoneal cells followed by recruitment of neutrophils and inflammatory macrophages into the peritoneal cavity and peritoneal mesothelium associated with an early increase in chemokines followed by proinflammatory cytokines. These rapid inflammatory responses to farnesol significantly increase morbidity and mortality of mice with intra-abdominal candidiasis associated with increased formation of peritoneal adhesions, despite similar rates of fungal clearance from the peritoneal cavity and retro-peritoneal organs. C. albicans ddp3Δ/ddp3Δ knockout and reconstituted strains recapitulate these findings. This indicates that farnesol may be detrimental to the host during intra-abdominal infections. Importantly, our results highlight a need to understand how C. albicans virulence factors modulate the host immune response within the peritoneum, an exceedingly common site of Candida infection.

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Novy, Emmanuel, Mathieu Esposito, Julien Birckener, Adeline Germain, Marie-Reine Losser, Marie-Claire Machouart, and Philippe Guerci. "Reappraisal of intra-abdominal candidiasis: insights from peritoneal fluid analysis." Intensive Care Medicine Experimental 11, no. 1 (September 30, 2023). http://dx.doi.org/10.1186/s40635-023-00552-0.

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Abstract Background The understanding of high mortality associated with intra-abdominal candidiasis (IAC) remains limited. While Candida is considered a harmless colonizer in the digestive tract, its role as a true pathogen in IAC is still debated. Evidence regarding Candida virulence in the human peritoneal fluid are lacking. We hypothesized that during IAC, Candida albicans develops virulence factors to survive to new environmental conditions. The objective of this observational exploratory monocentric study is to investigate the influence of peritoneal fluid (PF) on the expression of C. albicans virulence using a multimodal approach. Materials and methods A standardized inoculum of a C. albicans (3.106 UFC/mL) reference strain (SC5314) was introduced in vitro into various PF samples obtained from critically ill patients with intra-abdominal infection. Ascitic fluids (AFs) and Sabouraud medium (SBD) were used as control groups. Optical microscopy and conventional culture techniques were employed to assess the morphological changes and growth of C. albicans. Reverse transcriptase qPCR was utilized to quantify the expression levels of five virulence genes. The metabolic production of C. albicans was measured using the calScreener™ technology. Results A total of 26 PF samples from patients with secondary peritonitis were included in the study. Critically ill patients were mostly male (73%) with a median age of 58 years admitted for urgent surgery (78%). Peritonitis was mostly hospital-acquired (81%), including 13 post-operative peritonitis (50%). The infected PF samples predominantly exhibited polymicrobial composition. The findings revealed substantial variability in C. albicans growth and morphological changes in the PF compared to ascitic fluid. Virulence gene expression and metabolic production were dependent on the specific PF sample and the presence of bacterial coinfection. Conclusions This study provides evidence of C. albicans virulence expression in the peritoneal fluid. The observed variability in virulence expression suggests that it is influenced by the composition of PF and the presence of bacterial coinfection. These findings contribute to a better understanding of the complex dynamics of intra-abdominal candidiasis and advocate for personalized approach for IAC patients. Trial registrationhttps://clinicaltrials.gov/ (NCT05264571; February 22, 2022) Graphical Abstract

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Melnikoff, Brett A., and René P. Myers. "Candidiasis." DeckerMed Surgery, March 29, 2018. http://dx.doi.org/10.2310/surg.2364.

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Fungal infections remain an important cause of morbidity and mortality in surgical settings, with critically ill patients, transplant recipients, and sick neonates all especially vulnerable. Over the past few decades, technological and scientific advancements have improved physicians’ ability to sustain life in critically ill patients; developments in chemotherapeutics and immune-based therapies have yielded increased survival for many cancer patients; organ transplantation has evolved dramatically; and the use of invasive therapies (eg, ventricular assist devices) has increased markedly. With these changes has come an increase in the incidence of serious Candida infections. This review covers the definition and classification, epidemiology and risk factors, and clinical evaluation of candidiasis, as well as management of candidemia, acute disseminated candidiasis, nonhematogenous candidiasis, and peritonitis and intra-abdominal abscess. Figures show Candida endophthalmitis in patients with persistent fungemia and superficial candidiasis in the gastrointestinal tract. Tables list clinical presentation and diagnostic methods for common fungal infections, antimicrobial agents of choice for candidal infections, and the latest guidelines for candidiasis. This review contains 2 figures, 3 tables and 131 references Key words: acute disseminated candidiasis, candidemia, candidiasis, candiduria, nonhematogenous candidiasis

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Melnikoff, Brett A., and René P. Myers. "Candidiasis." DeckerMed Anesthesiology, March 29, 2018. http://dx.doi.org/10.2310/anes.2364.

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Fungal infections remain an important cause of morbidity and mortality in surgical settings, with critically ill patients, transplant recipients, and sick neonates all especially vulnerable. Over the past few decades, technological and scientific advancements have improved physicians’ ability to sustain life in critically ill patients; developments in chemotherapeutics and immune-based therapies have yielded increased survival for many cancer patients; organ transplantation has evolved dramatically; and the use of invasive therapies (eg, ventricular assist devices) has increased markedly. With these changes has come an increase in the incidence of serious Candida infections. This review covers the definition and classification, epidemiology and risk factors, and clinical evaluation of candidiasis, as well as management of candidemia, acute disseminated candidiasis, nonhematogenous candidiasis, and peritonitis and intra-abdominal abscess. Figures show Candida endophthalmitis in patients with persistent fungemia and superficial candidiasis in the gastrointestinal tract. Tables list clinical presentation and diagnostic methods for common fungal infections, antimicrobial agents of choice for candidal infections, and the latest guidelines for candidiasis. This review contains 2 figures, 3 tables and 131 references Key words: acute disseminated candidiasis, candidemia, candidiasis, candiduria, nonhematogenous candidiasis

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