scholarly journals Diagnosing Invasive Candidiasis

2018 ◽  
Vol 56 (5) ◽  
pp. e01909-17 ◽  
Author(s):  
Cornelius J. Clancy ◽  
M. Hong Nguyen

ABSTRACTCultures are negative in ∼50% of invasive candidiasis. Data are emerging for the performance of nonculture tests such as mannan/antimannan,Candida albicansgerm tube antibody, 1,3-β-d-glucan, PCR, and the T2Candida panel in diagnosing both candidemia and deep-seated candidiasis. In most settings, positive predictive values of nonculture test are low, and negative predictive values are high. For tests to be useful, clinicians must understand the pretest likelihood of invasive candidiasis and test performance for the most common disease manifestation in a given patient. This paper reviews noncultureCandidadiagnostics and discusses how they might be used effectively in patient care.

2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Rosie Bocanegra ◽  
Marcos Olivo ◽  
...  

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.


2015 ◽  
Vol 41 (8) ◽  
pp. 1424-1432 ◽  
Author(s):  
Estrella Martín-Mazuelos ◽  
Ana Loza ◽  
Carmen Castro ◽  
Desirée Macías ◽  
Ismail Zakariya ◽  
...  

2011 ◽  
Vol 55 (7) ◽  
pp. 3254-3260 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Rosie A. Bocanegra ◽  
William R. Kirkpatrick ◽  
Thomas F. Patterson

ABSTRACTPreviousin vivostudies have reported caspofungin dose escalation to be effective againstCandida glabratawith reduced susceptibility. We hypothesized that higher doses of caspofungin would be effective against invasive candidiasis caused by the more virulent speciesCandida albicans, including isolates resistant to this echinocandin. Immunocompetent mice were inoculated with one of threeC. albicansisolates, including one susceptible and two resistant isolates with differentFKS1hot spot 1 point mutations. Mice received daily caspofungin treatment for 7 days and were then followed off therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1→3)-β-d-glucan were measured. Significant differences in virulence were observed among the threeC. albicansisolates, which translated into differences in responses to caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to caspofungin doses of up to 10 mg/kg of body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1→3)-β-d-glucan concentration compared to those for untreated controls. Higher doses of caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg/kg; 80% survival). In contrast, caspofungin doses as low as 1 mg/kg improved survival (85 to 95%) and reduced tissue burden and (1→3)-β-d-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that caspofungin dose escalation for invasive candidiasis may not be consistently effective against resistantC. albicansisolates, and this may be associated with the virulence of the strain.


2007 ◽  
Vol 14 (3) ◽  
pp. 318-319 ◽  
Author(s):  
Ana Laín ◽  
María D. Moragues ◽  
Juan Carlos García Ruiz ◽  
Joaquín Mendoza ◽  
Ana Camacho ◽  
...  

ABSTRACT The performance of a new test to detect antibodies to Candida albicans recombinant enolase was investigated in 47 immunocompromised and 51 immunocompetent patients. The sensitivity, specificity, and positive and negative predictive values of the test for the diagnosis of invasive candidiasis were 81.0, 83.9, 79.1, and 85.5%, respectively.


2012 ◽  
Vol 11 (10) ◽  
pp. 1210-1218 ◽  
Author(s):  
Lifang Li ◽  
Chengda Zhang ◽  
James B. Konopka

ABSTRACTSeptins were identified for their role in septation inSaccharomyces cerevisiaeand were subsequently implicated in other morphogenic processes. To study septins inCandida albicanshyphal morphogenesis, a temperature-sensitive mutation was created that altered the C terminus of the essential Cdc12 septin. Thecdc12-6cells grew well at room temperature, but at 37°C they displayed expected defects in septation, nuclear localization, and bud morphogenesis. Although serum stimulated thecdc12-6cells at 37°C to form germ tube outgrowths, the mutant could not maintain polarized hyphal growth and instead formed chains of elongated cell compartments. Serum also stimulated thecdc12-6mutant to induce a hyphal reporter gene (HWP1-GFP) and a characteristic zone of filipin staining at the leading edge of growth. Interestingly,cdc12-6cells shifted to 37°C in the absence of serum gradually displayed enriched filipin staining at the tip, which may be due to the altered cell cycle regulation. A striking difference from the wild type was that thecdc12-6cells frequently formed a second germ tube in close proximity to the first. The mutant cells also failed to form the diffuse band of septins at the base of germ tubes and hyphae, indicating that this septin band plays a role in preventing proximal formation of germ tubes in a manner analogous to bud site selection. These studies demonstrate that not only are septins important for cytokinesis, but they also promote polarized morphogenesis and selection of germ tube sites that may help disseminate an infection in host tissues.


2014 ◽  
Vol 59 (1) ◽  
pp. 690-692 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Dora I. McCarthy ◽  
Rosie Bocanegra ◽  
...  

ABSTRACTThein vitroandin vivoactivity of the inositol acyltransferase inhibitor E1210 was evaluated against echinocandin-resistantCandida albicans. E1210 demonstrated potentin vitroactivity, and in mice with invasive candidiasis caused by echinocandin-resistantC. albicans, oral doses of 10 and 40 mg E1210/kg of body weight twice daily significantly improved survival and reduced fungal burden compared to those of controls and mice treated with caspofungin (10 mg/kg/day). These results demonstrate the potential use of E1210 against resistantC. albicansinfections.


mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Eva Pericolini ◽  
Elena Gabrielli ◽  
Mario Amacker ◽  
Lydia Kasper ◽  
Elena Roselletti ◽  
...  

ABSTRACTVaginal inflammation (vaginitis) is the most common disease caused by the human-pathogenic fungusCandida albicans. Secretory aspartyl proteinases (Sap) are major virulence traits ofC. albicansthat have been suggested to play a role in vaginitis. To dissect the mechanisms by which Sap play this role, Sap2, a dominantly expressed member of the Sap family and a putative constituent of an anti-Candidavaccine, was used. Injection of full-length Sap2 into the mouse vagina caused local neutrophil influx and accumulation of the inflammasome-dependent interleukin-1β (IL-1β) but not of inflammasome-independent tumor necrosis factor alpha. Sap2 could be replaced by other Sap, while no inflammation was induced by the vaccine antigen, the N-terminal-truncated, enzymatically inactive tSap2. Anti-Sap2 antibodies, in particular Fab from a human combinatorial antibody library, inhibited or abolished the inflammatory response, provided the antibodies were able, like the Sap inhibitor Pepstatin A, to inhibit Sap enzyme activity. The same antibodies and Pepstatin A also inhibited neutrophil influx and cytokine production stimulated byC. albicansintravaginal injection, and a mutant strain lackingSAP1,SAP2, andSAP3was unable to cause vaginal inflammation. Sap2 induced expression of activated caspase-1 in murine and human vaginal epithelial cells. Caspase-1 inhibition downregulated IL-1β and IL-18 production by vaginal epithelial cells, and blockade of the IL-1β receptor strongly reduced neutrophil influx. Overall, the data suggest that some Sap, particularly Sap2, are proinflammatory proteinsin vivoand can mediate the inflammasome-dependent, acute inflammatory response of vaginal epithelial cells toC. albicans. These findings support the notion that vaccine-induced or passively administered anti-Sap antibodies could contribute to control vaginitis.IMPORTANCECandidal vaginitis is an acute inflammatory disease that affects many women of fertile age, with no definitive cure and, in its recurrent forms, causing true devastation of quality of life. Unraveling the fungal factors causing inflammation is important to be able to devise novel tools to fight the disease. In an experimental murine model, we have discovered that aspartyl proteinases, particularly Sap2, may cause the same inflammatory signs of vaginitis caused by the fungus and that anti-Sap antibodies and the protease inhibitor Pepstatin A almost equally inhibit Sap- andC. albicans-induced inflammation. Sap-induced vaginitis is an early event during vaginal infection, is uncoupled from fungal growth, and requires Sap and caspase-1 enzymatic activities to occur, suggesting that Sap or products of Sap activity activate an inflammasome sensor of epithelial cells. Our data support the notion that anti-Sap antibodies could help control the essence of candidal vaginitis, i.e., the inflammatory response.


mSystems ◽  
2021 ◽  
Author(s):  
Ahinara Amador-García ◽  
Inés Zapico ◽  
Ana Borrajo ◽  
Johan Malmström ◽  
Lucía Monteoliva ◽  
...  

Fungal infections are a worldwide health problem, especially in immunocompromised patients and patients with chronic disorders. Invasive candidiasis, caused mainly by C. albicans , is among the most common fungal diseases.


2012 ◽  
Vol 38 (8) ◽  
pp. 1315-1325 ◽  
Author(s):  
Cristóbal León ◽  
Sergio Ruiz-Santana ◽  
Pedro Saavedra ◽  
Carmen Castro ◽  
Alejandro Úbeda ◽  
...  

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