Esophageal candidiasis in patients from a specialty hospital
Méndez-Tovar Luis Javier,Rodríguez-Sánchez José Froylán,Manzano-Gayosso Patricia,Hernández-Hernández Francisca,Blancas-Valencia Juan Manuel,Silva-González Israel
Revista medica del Instituto Mexicano del Seguro Social
Background:Esophageal candidiasis (EC) is the most common cause of infectious esophagitis. So far, its main risk factor has been HIV infection; in recent years, EC has been favoured by the increasing of diabetes mellitus, wide-spread use of acid-lowering agents, broad-spectrum antibiotics, and inhaled steroids. In Mexico EC has been poorly studied. Objectives:To determine the clinical and epidemiological characteristics of EC, and to identify its etiological agents as well as its antifungal susceptibility. Methods:Patients who revealed the presence of scattered white spots through an upper gastrointestinal system endoscopy, in a period of one year, in a tertiary care hospital, were included. Samples from patches were collected for microscopic examination, culture, and susceptibility tests. Results:Out of 1763 patients studied, 23 had scattered white spots, and most of them presented Kodsi grade I; 13 were men; half of the patients were between the ages 20 to 40; main comorbidity was liver cirrhosis; use of omeprazole was significant. 22 isolates were obtained from 17 patients. The most frequent species were C. albicans (14) and C. parapsilosis (3). In five cases we found a two-species association v. g. Candida famata with Trichosporon mucoides. Half of the isolates showed resistance to one or several antifungal drugs. Conclusions:EC frequency in this study was similar to other studies’ results. Obtained isolates showed high resistance to azolic compounds and to caspofungin, which is relevant information to take a therapeutic decision.
The expression of the beta-defensins hBD-2 and hBD-3 is differentially regulated by NF-kappaB and MAPK/AP-1 pathways in an in vitro model of Candida esophagitis.
Steubesand Nadine,Kiehne Karlheinz,Brunke Gabriele,Pahl Rene,Reiss Karina,Herzig Karl-Heinz,Schubert Sabine,Schreiber Stefan,Fölsch Ulrich R,Rosenstiel Philip,Arlt Alexander
BMC immunology
BACKGROUND:Candida albicans resides on epithelial surfaces as part of the physiological microflora. However, under certain conditions it may cause life-threatening infections like Candida sepsis. Human beta-defensins (hBDs) are critical components of host defense at mucosal surfaces and we have recently shown that hBD-2 and hBD-3 are upregulated in Candida esophagitis. We therefore studied the role of Candidate signalling pathways in order to understand the mechanisms involved in regulation of hBD-expression by C. albicans. We used the esophageal cell line OE21 and analysed the role of paracrine signals from polymorphonuclear leukocytes (PMN) in an in vitro model of esophageal candidiasis. RESULTS:Supernatants of C. albicans or indirect coculture with C. albicans induces upregulation of hBD-2 and hBD-3 expression. PMNs strongly amplifies C. albicans-mediated induction of hBDs. By EMSA we demonstrate that C. albicans activates NF-kappaB and AP-1 in OE21 cells. Inhibition of these pathways revealed that hBD-2 expression is synergistically regulated by both NF-kappaB and AP-1. In contrast hBD-3 expression is independent of NF-kappaB and relies solely on an EGFR/MAPK/AP-1-dependent pathway. CONCLUSION:Our analysis of signal transduction events demonstrate a functional interaction of epithelial cells with PMNs in response to Candida infection involving divergent signalling events that differentially govern hBD-2 and hBD-3 expression.
10.1186/1471-2172-10-36
[Is endoscopic diagnosis of Candida albicans esophagitis reliable? Correlations with pathology and mycology].
Redah D,Konutse A Y,Agbo K,Dogbey E H,Napo-Koura G,Tchangai-Kao S T,Prince-David M,Amedegnato D M,Agbetra A
Gastroenterologie clinique et biologique
AIM OF STUDY:To assess the reliability of endoscopic diagnosis of Candida albicans esophagitis. PATIENTS AND METHODS:A case - control prospective study was carried out from November 1997 to July 1998 at the Campus Teaching Hospital of Lome, in patients with esophagitis macroscopically suggestive of Candida albicans origin at upper digestive endoscopy. Fifteen subjects with normal endoscopy served as controls. Esophageal biopsies for mycologic and pathological examination were performed, as well as HIV serology. RESULTS:During the study period, 26 of the 850 endoscopies performed in our Unit revealed an esophagitis suggestive of Candida albicans origin. Mycology confirmed the presence of filamentous form of Candida albicans in 23 patients and pathology showed non-specific lesions of esophagitis, 20 with intramucous hyphae. HIV serology was positive in 19/23 patients (82.6%) and in 1/15 controls (6.6%). Sensitivity and specificity of upper GI endoscopy for the diagnosis of Candida albicans were 100 and 83.3% respectively; positive and negative predictive values were 88.5 and 100%, respectively. CONCLUSION:Upper digestive endoscopy is a reliable method for the diagnosis of Candida albicans esophagitis. However, mycological confirmation is warranted.
Unique causes of esophageal inflammation: a histopathologic perspective.
Gopal Purva,Gibson Joanna A,Lisovsky Mikhail,Nalbantoglu ILKe
Annals of the New York Academy of Sciences
Gastroenterologists frequently perform endoscopic esophageal mucosal biopsies for pathologic diagnosis in patients experiencing symptoms of esophagitis. The more common causes of esophagitis diagnosed on esophageal mucosal biopsy include reflux esophagitis, eosinophilic esophagitis, and infectious esophagitis caused by Candida albicans, herpes simplex virus, and/or cytomegalovirus. However, there are several causes of esophagitis seen less frequently by pathologists that are very important to recognize. We discuss unique types of esophageal inflammation, including acute bacterial esophagitis, esophageal manifestations of dermatologic diseases, medication-induced esophageal injury, and sloughing esophagitis; and we review their clinical and histopathologic features.
10.1111/nyas.13732
Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans.
Antimicrobial agents and chemotherapy
PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P </= 0.05, P </= 0.01, P </= 0.001, respectively), while FLC had no significant activity. PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis.
10.1128/AAC.48.10.3959-3967.2004
Is empiric therapy with fluconazole appropriate for esophageal candidiasis?
Sajith Kattiparambil Gangadharan,Dutta Amit Kumar,Sahni Rani Diana,Esakimuthu Saritha,Chacko Ashok
Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology
We studied the prevalence of fluconazole resistance in esophageal candidiasis. Patients with suspected esophageal candidiasis during gastroscopy underwent culture of white plaques. Minimum inhibitory concentration (MIC) >64 μg/mL of fluconazole for Candida was indicative of resistance. Sensitivity of itraconazole was tested in a subset of resistant strains. Sixty-five patients were included. Mean (SD) age was 50.03 (13.5) years and 67.7 % were males. Predisposing factors for candidiasis were found in 42 (64.6 %) patients. C. albicans was identified in 64 (97.4 %) patients and C. glabrata in one patient. Fluconazole resistance was seen in 38 (59.4 %) patients with C. albicans and also in the one patient with C. glabrata. All the fluconazole resistant isolates of C. albicans had MIC >128 μg/mL suggesting very high resistance. Twelve patients with fluconazole resistance had itraconazole resistance as well. The study shows a high rate of fluconazole resistance in patients with esophageal candidiasis.
10.1007/s12664-013-0439-6
Adherence and invasion studies of Candida albicans strains, using in vitro models of esophageal candidiasis.
Bernhardt J,Herman D,Sheridan M,Calderone R
The Journal of infectious diseases
The adherence of clinical and commensal isolates and reference collection strains of Candida albicans to a human esophageal cell monolayer (HET1-A) and reconstituted human esophageal tissue was compared. Isolates from patients with a severe form of esophageal candidiasis or candidemia adhered to HET1-A cells to a significantly greater extent than did isolates from patients with mild esophageal candidiasis or commensal and reference collection strains. In addition, C. albicans strain SSK21, which lacks the ssk1 response regulator gene of a 2-component signal transduction pathway, adhered less readily to the HET1-A cells than did parental cells or a gene-reconstituted strain. In a reconstituted esophageal tissue model, all clinical strains but not commensal or reference collection strains penetrated the epithelium, albeit at different rates. Hyphal formation following yeast cell adherence to the esophageal tissue was a requirement for invasion. Scanning electron microscopy was also used to confirm the colonization of the esophageal tissues by various strains. These studies indicate that both the HET1-A and the reconstituted esophageal tissue models can be used as in vitro targets to evaluate the adherence phenotype and invasiveness of C. albicans strains.
10.1086/323807
PPARγ controls Dectin-1 expression required for host antifungal defense against Candida albicans.
Galès Amandine,Conduché Annabelle,Bernad José,Lefevre Lise,Olagnier David,Béraud Maryse,Martin-Blondel Guillaume,Linas Marie-Denise,Auwerx Johan,Coste Agnès,Pipy Bernard
PLoS pathogens
We recently showed that IL-13 or peroxisome proliferator activated receptor gamma (PPARgamma) ligands attenuate Candida albicans colonization of the gastrointestinal tract. Here, using a macrophage-specific Dectin-1 deficient mice model, we demonstrate that Dectin-1 is essential to control fungal gastrointestinal infection by PPARgamma ligands. We also show that the phagocytosis of yeast and the release of reactive oxygen intermediates in response to Candida albicans challenge are impaired in macrophages from Dectin-1 deficient mice treated with PPARgamma ligands or IL-13. Although the Mannose Receptor is not sufficient to trigger antifungal functions during the alternative activation of macrophages, our data establish the involvement of the Mannose Receptor in the initial recognition of non-opsonized Candida albicans by macrophages. We also demonstrate for the first time that the modulation of Dectin-1 expression by IL-13 involves the PPARgamma signaling pathway. These findings are consistent with a crucial role for PPARgamma in the alternative activation of macrophages by Th2 cytokines. Altogether these data suggest that PPARgamma ligands may be of therapeutic value in esophageal and gastrointestinal candidiasis in patients severely immunocompromised or with metabolic diseases in whom the prevalence of candidiasis is considerable.
10.1371/journal.ppat.1000714
A URA3 null mutant of Candida albicans (CAI-4) causes oro-oesophageal and gastric candidiasis and is lethal for gnotobiotic, transgenic mice (Tgepsilon26) that are deficient in both natural killer and T cells.
Balish Edward
Journal of medical microbiology
Current data suggest that functional URA3 genes are necessary for the full pathogenesis of Candida albicans. Herein it is shown that a putatively avirulent URA3/URA3 null mutant of C. albicans (CAI-4) can colonize the murine alimentary tract, invade oro-oesophageal and gastric tissues with yeasts and hyphae, evoke a granulocyte-dominated inflammatory response, and kill transgenic mice that are deficient for both natural killer cells and T cells. Because C. albicans-colonized (gnotobiotic) mice lack a viable prokaryotic microbiota, this study also demonstrates that the gut microbiome is not required to supply the mutant's nutritional needs. The gnotobiotic murine model described herein can be used to assess the capacity of C. albicans mutants to colonize and infect cutaneous, mucosal and systemic tissues and kill the susceptible host via a clinically common, natural route of infection; namely the alimentary tract.
10.1099/jmm.0.004846-0
The Relationship of Candida albicans with the Oral Bacterial Microbiome in Health and Disease.
Bertolini Martinna,Dongari-Bagtzoglou Anna
Advances in experimental medicine and biology
Candida albicans is an opportunistic pathogen colonizing the oropharyngeal, esophageal, and gastrointestinal mucosa in most healthy humans. In immunocompromised hosts, this fungal organism can cause mucosal candidiasis in these sites. C. albicans also causes fungemia, a serious consequence of cancer cytotoxic chemotherapy, which is thought to develop from fungal translocation through compromised mucosal barriers. Changes in endogenous bacterial population size or composition as well as changes in the host environment can transform fungal commensals into opportunistic pathogens in the upper and lower GI tract. Pioneering studies from our group have shown that a ubiquitous oral commensal of the mitis streptococcal group (Streptococcus oralis) has a mutualistic relationship with C. albicans, with C. albicans enabling streptococcal biofilm growth at mucosal sites, and S. oralis facilitating invasion of the oral and esophageal mucosa by C. albicans. In these studies, we used a cortisone-induced immunosuppression mouse model. More recently, the development of a novel mouse chemotherapy model has allowed us to examine the interactions of C. albicans with the endogenous bacterial microbiota in the oral and small intestinal mucosa, two sites adversely affected by cytotoxic chemotherapy. In this model, oral inoculation with C. albicans causes severe dysbiosis in the mucosal bacterial composition in both sites. We also found that antibiotic treatment ameliorates invasion of the oral mucosa but aggravates dissemination through the intestinal mucosa. In this chapter, we discuss work from our laboratory and others examining the relationships of C. albicans with oral bacteria and their role in mucosal homeostasis or disease.
10.1007/978-3-030-28524-1_6