Candidosis in children with onco-hematological diseases in Chennai, south India

Candida spp. are recognized as a leading contributor to mortality and morbidity in patients with onco-hematological malignancies. The rates and risk factors for mycotic infections in pediatric oncology patients are undetermined, particularly for those treated at centers in developing countries. The objective of the present study was to prospectively evaluate the species stratification and antifungal susceptibility profile of Candida spp. associated with superficial and systemic infection in children with onco-hematological diseases. Acute lymphoblastic leukemia was the most common underlying disease (71.4%) among the 91 children under study. Candida albicans was the predominant species, with 17/29 isolates (58.6%); followed by C. tropicalis, with 10/29 isolates (34.5%). The drug susceptibility data analysis for the clinical isolates of Candida revealed 17.2% (5/29) resistance to fluconazole. This study reinforces the need for the systematic surveillance of candidosis for the correct management of such life-threatening infections.     

Distribution and epidemiology of Candida species causing fungemia at a Saudi Arabian hospital, 1996-2004.

OBJECTIVES: The objective of this study was to evaluate the Candida species and the change over time in the organisms causing candidemia at Saudi Aramco Medical Services Organization in Saudi Arabia. We also describe the risk factors associated with mortality. METHODS: This was a retrospective study of candidemia over nine years (1996-2004). RESULTS: A total of 98 distinct episodes of candidemia were identified over the study period. The annual incidence of candidemia ranged between 0.2 and 0.76 cases/1000 hospital discharges with an incidence per 10 000 patient-days per year of 0.45 to 1.6. The most frequent Candida species were Candida albicans (53%), Candida tropicalis (19%), Candida parapsilosis (16%), and Candida glabrata (7%). In relation to predisposing factors, 83% of candidemia occurred in patients with central venous catheters and 96% had received broad-spectrum antibiotics. Other predisposing factors included complicated abdominal surgeries (22%), total parenteral nutrition (52%), neutropenia (9%), acute renal failure (24%), malignancy (26%) and burns (15%). However, prior fluconazole use was low (8%). The overall crude mortality rate was 43% for all candidemia. Logistic regression analysis identified two independent determinants of death, C. albicans (OR 5.91, 95% CI 1.50, 23.24, p=0.01) and acute renal failure (OR 5.15, 95% CI 1.18, 22.55, p=0.03). CONCLUSION: The study showed that the rate of candidemia was low in our hospital and that C. albicans was the major species followed by C. tropicalis and C. parapsilosis. Future studies are needed to evaluate the antifungal susceptibility pattern in our hospital.     

Species-specific prevalence of vaginal candidiasis among patients with diabetes mellitus and its relation to their glycaemic status

OBJECTIVES: Non- C. albicans Candida species are increasingly being recognized as the cause of vulvo-vaginal candidiasis. These species are often less susceptible to antifungal agents. Patients with diabetes mellitus are at risk for vulvo-vaginal candidasis. We assessed the species-specific prevalence rate and risk of candidiasis in patients with diabetes mellitus and healthy controls. METHODS: Genital tract examination, direct microscopy and fungal cultures of discharge collected by high vaginal swab were undertaken among 78 consecutive patients with diabetes mellitus (mean (+/-sd) age 32+/-12 years and body mass index (BMI) 22.3+/-5.5kg/m(2)) and 88 age- and BMI-matched healthy females. Glycaemic control in the diabetic cohort was assessed by measuring total glycosylated haemoglobin. RESULTS: Candida species were isolated in 36 of 78 (46%) subjects with diabetes mellitus and in 21 of 88 (23%) healthy subjects (Chi-squared 9.11, P=0.0025). The predominant Candida species isolated in diabetics with vulvo-vaginal candidiasis were Candida glabrata (39%), C. albicans (26%) and C. tropicalis (17%). In contrast, in the control group, C. albicans, C. glabrata and C. hemulonii comprised 30% each, with none having C. tropicalis infection (for C. tropicalis: diabetic vs. control; 17% vs. nil, P=0. 05). Among the diabetic group, subjects with vulvo-vaginal candidiasis had significantly higher mean HbA1 when compared to those who had no such infection (12.8+/-2.6% vs. 9.7+/-1.7% respectively, P=0.001). The overall accuracy of direct microscopy and clinical examination for predicting vulvo-vaginal candidiasis was only 77% and 51%, respectively, in the diabetic group, and 83% and 65% in the control group. CONCLUSIONS: Patients with diabetes mellitus had a high prevalence rate (46%) of vulvo-vaginal candidiasis with relative risk of 2.45. The non- C. albicans species such as C. glabrata and C. tropicalis were the predominant species isolated among them. There seems to be a significant link between hyperglycaemia and vulvo-vaginal candidiasis.     

Candida tropicalis: a major pathogen in immunocompromised patients.

Of 89 consecutive patients undergoing treatment for hematologic malignancies or undergoing allogeneic bone marrow transplantation, 60 were colonized with Candida albicans and 25 with C. tropicalis. However, of the 18 disseminated infections caused by Candida species, 15 infections in 14 patients were caused by C. tropicalis and only three infections in three patients by C. albicans. The setting in which the infection occurred, skin lesions, polyarthralgias, or polymyalgias, and the unexplained deterioration of renal function were features suggestive of the diagnosis. Defervescence occurred in 10 of the 14 treated patients with C. tropicalis infections in 1 to 6 d (mean, 2.5 d) after initiation of therapy, even though all continued to be granulocytopenic. Resolution occurred in eight of the 15 C. tropicalis infections. In one case outcome was indeterminate, four patients died due to the infection, and two died from other causes but with the infection unresolved.     

复发性外阴阴道念珠菌病患者的病原菌分析

目的了解复发性外阴阴道念珠菌病患者的念珠菌菌种分布。方法采集外阴阴道念珠菌病患者的标本,用CHROMagarCandida显色培养基及生物梅里埃API20CAUX酵母菌鉴定系统鉴定念珠菌的菌种。结果289例患者的阴道分泌物标本中,共检出念珠菌224株,检出率为77．51％。其中复发性外阴阴道念珠菌病患者的分泌物标本89例,检出72株。临床分离的念珠菌以白念珠菌居多共168株,占75．00％;其次为近平滑念珠菌19株（8．48％）,克柔念珠菌11株（4．91％）,其他为热带念珠菌、光滑念珠菌等。结论复发性外阴阴道念珠菌病患者以白念珠菌感染占明显优势,其他有近平滑念珠菌、克柔念珠菌感染等     

Oesophageal candidiasis: clinical and mycological analysis

Oesophageal candidiasis is an epithelial infection which requires an immune deficiency. C. albicans is commonly the cause, although other species may also be responsible. Resistance to fluconazole, drug of choice for treatment, is an emerging problem. The objectives of the current paper were: to determine the frequency of oesophageal candidiasis in patients submitted to upper gastrointestinal endoscopy, analyze risk factors, identify Candida species and determine in vitro susceptibility to fluconazole. During 12 months, 34 patients with oesophageal candidiasis were detected. Out of 1.230 HIV negative and 91 HIV positive patients submitted to upper endoscopy, 11 (0.9%) and 23 (25.3%), respectively, had candidiasis. Risk factors for HIV negative patients were systemic antibiotic therapy in 2, deficient dental cleaning in 2 aged patients, use of proton pump inhibitors in 3, inhaled steroids in 2, malignancy in 1 and oral steroids in 1. The histopathologic diagnosis was confirmed in 48.6% of cases. Cultures were positive in 91.2% C. albicans was prevalent (93.5%), and was associated to other species in 5 cases (16.1%), (3 C. glabrata, 1 C. tropicalis and 1 C. parapsilosis). One case cultured only C. glabrata and 1, only C tropicalis. Out of 31 cultures, 25 were susceptible to fluconazole, 4 dose dependent (1 C. albicans, 3 C. glabrata), and 2 resistant (1 C. albicans, 1 C. glabrata). Frequency of oesophageal candidiasis was low, except for HIV positive patients. The most common etiologic agent was C. albicans, though other Candida species were also found. C. albicans and C. glabrata showed dose dependency and resistance to fluconazole.     

Candida albicans stimulates endothelial cell eicosanoid production

The response of human umbilical vein endothelial cells to invasion by Candida species was examined in vitro. Live Candida albicans caused significant endothelial release of eicosanoids, mainly prostaglandins. Since prostaglandin I2 (PGI2) is an important prostaglandin produced by endothelial cells, factors influencing its release were studied. The ability of different strains and species of Candida to induce endothelial PGI2 release was closely related to their capacity to injure the endothelium (r = .99). C. albicans was the only species tested that either stimulated PGI2 release or damaged the endothelial cells; only this organism possessed detectable phospholipase activity. Candida glabrata and Candida tropicalis had no phospholipase activity and neither increased PGI2 release nor caused significant endothelial damage. Close proximity with germinated C. albicans was required for endothelial injury and PGI2 release. The ability of C. albicans to stimulate endothelial cells may have important implications in regulating neutrophil activities against organisms that interact with endothelial cells.     

National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units.

Candida species are the fourth most frequent cause of nosocomial bloodstream infections, and 25%-50% occur in critical care units. During an 18-month prospective study period, all patients admitted for > or = 72 hours to the surgical (SICUs) or neonatal intensive care units (NICUs) at each of the participant institutions were followed daily. Among 4,276 patients admitted to the seven SICUs in six centers, there were 42 nosocomial bloodstream infections due to Candida species (9.8/1,000 admissions; 0.99/1,000 patient-days). Of 2,847 babies admitted to the six NICUs, 35 acquired a nosocomial bloodstream infection due to Candida species (12.3/1,000 admissions; 0.64/1,000 patient-days). The following were the most commonly isolated Candida species causing bloodstream infections in the SICU: Candida albicans, 48%; Candida glabrata, 24%; Candida tropicalis, 19%; Candida parapsilosis, 7%; Candida species not otherwise specified, 2%. In the NICU the distribution was as follows: C. albicans, 63%; C. glabrata, 6%; C. parapsilosis, 29%; other, 3%. Of the patients, 30%-50% developed incidental stool colonization, 23% of SICU patients developed incidental urine colonization, and one-third of SICU health care workers' hands were positive for Candida species.     

Candidemia in a Brazilian tertiary care hospital: species distribution and antifungal susceptibility patterns

Recent studies have shown differences in the epidemiology of invasive infections caused by Candida species worldwide. In the period comprising August 2002 to August 2003, we performed a study in Santa Casa Complexo Hospitalar, Brazil, to determine Candida species distribution associated with candidemia and their antifungal susceptibility profiles to amphotericin B, fluconazole and itraconazole. Antifungal susceptibility was tested according to the broth microdilution method described in the NCCLS (M27A-2 method). Only one sample from each patient was analyzed (the first isolate). Most of the episodes had been caused by species other than C. albicans (51.6%), including C. parapsilosis (25.8%), C. tropicalis (13.3%), C. glabrata (3.3%), C. krusei (1.7%), and others (7.5%). Dose-dependent susceptibility to itraconazole was observed in 14.2% of strains, and dose-dependent susceptibility to fluconazole was found in 1.6%. Antifungal resistance was not found, probably related to low use of fluconazole. Further epidemiological surveillance is needed.     

Esophageal candidosis in progressive systemic sclerosis: occurrence, significance, and treatment with fluconazole

Esophageal mucosal brushings from 51 consecutive patients with progressive systemic sclerosis (PSS) (group I), 18 PSS patients continuously treated with high-dose ranitidine or omeprazole (group II), 34 controls referred to the outpatient clinic for endoscopy (group III), and 10 patients receiving long-term potent antireflux therapy for idiopathic gastroesophageal reflux (group IV) were cultured for Candida albicans. There were 44%, 89%, 9%, and 0% Candida albicans culture-positive patients in groups I through IV, respectively. Fifteen patients with candida esophagitis from group II were treated with fluconazole systemically. Eleven and 14 patients became culture-negative after 2 and 4 weeks' treatment, respectively. Three months after fluconazole withdrawal the recurrence rate was 100%. It is concluded that esophageal dysmotility predisposes for candidosis. Adding gastric acid inhibitory treatment to dysmotility enhances the risk significantly (p less than 0.01). The efficiency of fluconazole treatment was close to 100%, but so was the recurrence rate within a short period.     

The predictors of outcome in immunocompetent patients with hematogenous candidiasis.

OBJECTIVE: Clinical parameters that predict outcome in non-immunosuppressed candidemic patients are not fully understood. METHODS: Eighty-one consecutive episodes of candidemia were retrospectively evaluated in 75 patients during 1998-2000. RESULTS: Infection due to Candida albicans was common (n = 30; 37%) followed by Candida glabrata (n = 25; 31%), Candida parapsilosis (n = 14; 17%), Candida tropicalis (n = 6; 7%), Candida krusei (n = 5; 6%), and Candida lusitaniae (n = 1; 1%). Among 70 evaluable patients, 31 (44%) had fungemia-associated mortality; advanced age (P < 0.004), underlying malignancy (P < 0.025), coronary artery disease (P < 0.01), and concurrent non-Candida species fungal infection (P < 0.047) were significant prognosticators of compromised short-term survival by multivariate analysis. Mortality was higher in patients with Candida glabrata (60%) and C. tropicalis (75%) infection compared to 44% deaths in individuals with C. albicans infection (P > 0.1). 11/25 (44%) of non-immunocompromised individuals died and 20/45 (44%) immunosuppressed patients succumbed to fungemia: persistent vs. non-persistent (< 3 days) Candida bloodstream invasion, neutropenia, diabetes mellitus, renal insufficiency, prior antimicrobial therapy, cirrhosis of liver, abdomino-pelvis surgery, and critical-care-unit vs. non critical-care-unit admission did not significantly impact outcome in either group. All 11 infants, including nine with prematurity, survived Candida species bloodstream infection (P < 0.025). CONCLUSIONS: Short-term mortality in candidemic non-immunocompromised patients was comparable to fungemia-associated deaths in immunosuppressed patients. Ischemic heart disease has appeared as a new predictor of unfavorable outcome in patients with hematogenous candidiasis.     

Vertebral osteomyelitis due to Candida species: case report and literature review.

Candida species uncommonly cause vertebral osteomyelitis. We present a case of lumbar vertebral osteomyelitis caused by Candida albicans and review 59 cases of candidal vertebral osteomyelitis reported in the literature. The mean age was 50 years, and the lower thoracic or lumbar spine was involved in 95% of patients. Eighty-three percent of patients had back pain for >1 month, 32% presented with fever, and 19% had neurological deficits. The erythrocyte sedimentation rate was elevated in 87% of patients, and blood culture yielded Candida species for 51%. C. albicans was responsible for 62% of cases, Candida tropicalis for 19%, and Candida glabrata for 14%. Risk factors for candidal vertebral osteomyelitis were the presence of a central venous catheter, antibiotic use, immunosuppression, and injection drug use. Medical and surgical therapies were both used, and amphotericin B was the primary antifungal agent. Prognosis was good, with an overall clinical cure rate of 85%.     

Experimental hematogenous endophthalmitis due to Candida: species variation in ocular pathogenicity.

The ocular pathogenicity of species of Candida other than albicans was studied in the rabbit model of hematogenous candida endophthalmitis by injection of 10(5)-10(8) colony-forming units of Candida krusei, Candida parapsilosis, Candida guilliermondii, Candida tropicalis, Candida stellateoidea, and Candida albicans (control). At one and three weeks after infection, rabbits were examined by indirect ophthalmoscopy and were sacrificed for culture of eyes and kidneys. With an inoculum of 10(8) organisms, C. tropicalis and C. stellatoidea infected the kidneys but only occasionally infected the chorioretina and never infected the vitreous. Organisms were cultured only rarely from the kidneys of rabbits infected with C. krusei, C. guilliermondii, and C. parapsilosis; these species were never isolated from eyes. The C. albicans control consistently infected the kidney, chorioretina, and vitreous; approximately equal numbers of C. albicans were isolated from these organs. These data suggest a relative resistance of ocular tissues to hematogenous candida infections with species other than C. albicans.     

Speciation of fecal Candida isolates in antibiotic-associated diarrhea in non-HIV patients

Candida is the most frequently encountered fungal infection of the gastrointestinal tract after antibiotic exposure. The pathogenesis of Candida probably varies with each species. The speciation of fecal Candida after antibiotic use is not well investigated. One hundred and eleven fecal samples negative for Clostridium difficile toxin and for other enteric pathogens formed the basis of our investigation. The diarrheic samples came from patients receiving antibiotics in a hospital setting. In addition, samples from 30 age-matched healthy participants who did not receive antibiotics and did not have diarrhea were also studied. Initially, a Gram stain identification for yeasts was performed for each fecal sample, then each sample was cultured on Sabouraud's dextrose agar. Candida was isolated as pure growth (>10(5) cfu/ml) from the stools of 32 (28.8%) patients. The identification of the yeast was done based upon a combination of morphological, physiological and biochemical criteria. The predominant isolates were C. tropicalis (n=16), C. albicans (n=14) and C. krusei (n=2). Candida isolated from healthy participants (n=4) was sparse and therefore not speciated. Different Candida spp. may play an important role in precipitating antibiotic-associated diarrhea.     

Candida tropicalis fungemia in a tertiary care hospital

Candida tropicalis is a frequent cause of fungemia in hospitals in Latin America. Candida albicans (33%) was the most frequently isolated species, followed by Candida parapsilosis (27%), and Candida tropicalis (24%) in tertiary care hospital in Brazil. We identified and retrospectively reviewed 27 cases of C. tropicalis fungemia that occurred at Hospital de Clinicas de Porto Alegre from 1996 to 1999. The mean age of the patients was 32 years (range 6 months to 88 years). Eight patients (29.6%) had hematological malignancy, and four (14.8%) had solid tumors. All the patients were taking broad-spectrum antibiotics, including vancomycin for at least 7 days. Antibiotics were given through a central venous catheter for the majority of the patients (77.7%). Relevant risk factors for candidemia in our patients included neutropenia (59.2%), and use of corticosteroids (37.0%) or cytotoxic drugs (40.7%). The onset of fever was the most frequent clinical manifestation (92.5%) of fungemia. Most of the patients (81.4%) were treated with amphotericin B or fluconazole. Overall mortality was 48.1%, and 7 (53.4%) of 13 deaths occurred within 10 days of the detection of candidemia. Results of the in vitro susceptibility testing of nine isolates of C. tropicalis from seven patients did not show resistance to fluconazole and amphotericin B.C. tropicalis presents as an important cause of fungemia in oncological and nononcological patients with central venous catheters taking broad-spectrum antibiotics. Although there was no evidence of resistance of C. tropicalis to amphotericin B and fluconazole, patients treated with antifungal agents presented with a high mortality rate in the hospital setting.     

Oral candidal carriage and infection in insulin-treated diabetic patients.

AIM: To evaluate candidal load and carriage of candidal species in 414 insulin-treated diabetes mellitus patients with and without clinical signs of infection. Host factors that could influence candidal load in diabetic patients with oral candidosis were also investigated. METHODS: Candidal species were recovered from 414 insulin-treated diabetes mellitus patients attending two hospital diabetic clinics, using an oral rinse technique. RESULTS: Seventy-seven per cent of diabetic patients carried Candida species in their oral cavity, with C. albicans being the species most frequently isolated. C. dubliniensis was found for the first time in this patient group. Forty per cent of patients colonized with candidal species had no clinical signs of oral candidosis. Where oral candidosis was present, erythematous candidosis was the most common clinical presentation. Candidal load was not associated with age, sex or glycaemic control. However, it was significantly increased in those patients who were tobacco smokers, and non-significantly increased in those patients who wore dentures, or who had clinical signs of oral candidosis. CONCLUSION: The epidemiology of oral candidal carriage and infections in diabetic patients is complex and includes species which have not been previously reported in this group of patients. The development of oral candidosis in insulin-treated diabetes mellitus patients is not the result of a single entity, but rather, a combination of risk factors.     

Candidemia in a tertiary care cancer center: in vitro susceptibility and its association with outcome of initial antifungal therapy

Since the 1990s, changing trends have been documented in species distribution and susceptibility to bloodstream infections caused by Candida species in cancer patients. However, few data are available regarding the association between in vitro antifungal susceptibility and outcome of candidemia in this patient population. We therefore evaluated the association of in vitro antifungal susceptibility and other risk factors with failure of initial antifungal therapy in cancer patients with candidemia. Candidemia cases in cancer patients from 1998 to 2001 (n = 144) were analyzed retrospectively along with their in vitro susceptibility to amphotericin B, fluconazole, and itraconazole (National Committee for Clinical and Laboratory Standards M27-A method). Patients were evaluable for outcome analysis if they received continuous unchanged therapy with either fluconazole or amphotericin B for >/=5 days. We excluded cases of mixed candidemia. In vitro susceptibility testing data of the first Candida bloodstream isolate were analyzed. Appropriate therapy was defined as that using an active in vitro antifungal for >/=5 days. For fluconazole susceptible-dose dependent Candida species, we defined appropriate therapy as a fluconazole dose of >/=600 mg/day. The Candida species distribution was 30% Candida albicans, 24% Candida glabrata, 23% Candida parapsilosis, 10% Candida krusei, 9% Candida tropicalis, and 3% other. Overall, amphotericin B was the most active agent in vitro, with only 3% of the isolates exhibiting resistance to it (>1 mg/L). Dose-dependent susceptibility to fluconazole and itraconazole was seen in 13% and 21% of the isolates, respectively, while resistance to fluconazole and itraconazole was seen in 13% and 26%, respectively.Eighty patients were evaluable for outcome analysis. In multivariate analysis, the following factors emerged as independent predictors of failure of initial antifungal therapy: leukemia (p = 0.01), bone marrow transplantation (p = 0.006), and intensive care unit stay at onset of infection (p = 0.02). Inappropriate antifungal therapy, as defined by daily dose and in vitro susceptibility, was not shown consistently to be a significant factor (it was significant in multivariate analysis, p = 0.04, but not in univariate analysis), indicating the complexity of the variables that influence the response to antifungal treatment in cancer patients with candidemia.     

Fungemia in HIV-infected patients: a 12-year study in a tertiary care hospital

Opportunistic infections caused by fungi are common in human immunodeficiency virus (HIV)-infected patients. We focused on severe infections as indicated by detectable fungemia. Medical charts available for patients having positive blood cultures with fungi at the University of Geneva Hospital were retrospectively (1989 to 2000) reviewed. Of 328 patients with fungemia during the study period, 315 (96%) medical charts were accessible. Of these 315 patients, 37 (12.2%) were HIV-positive, and 13 (35.1%) died within 6 months from their episode of fungemia. This was a lower mortality rate than for the HIV seronegative patients (45.8%). The median and average age of the 34 HIV-positive patients was 37.2 years, and 24 (64.9%) were males. Cryptococcus neoformans (n = 14) and Candida albicans (n = 12) were the most frequently identified species, followed by Candida glabrata (n = 3), of which 3 were mixed C. albicans + C. glabrata, Histoplasma capsulatum (n = 2), and Penicillium marneffei (n = 2). The frequency decreased significantly (p < 0.007) from the time period 1993 to 1996 (n = 21) to the period 1997 to 2000 (n = 6). Fungemias in HIV-infected patients have declined significantly since 1996. This coincides with the introduction of highly active antiretroviral therapy (HAART).     

Antifungal susceptibility of Candida species causing candidemia in Kurume University Hospital and Shaiseikai Hutukaichi Hospital

Prevention of candidemia has been difficult and empirical therapy may eventually reduce morbidity and mortality. Successful empirical therapies depend on understanding of fungal features and antifungal agents. Susceptibility to amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), itraconazole (ITCZ), miconazole (MCZ), and micafungin (MCFG) of 41 Candida species isolated from blood were determined. Candida albicans was the most common species (23 species), followed by C. parapsilosis (5 species), C. tropicalis (4 species), C. glabrata (3 species), C. guilliermondii (2 species), C. krusei (1 specie), and Candida spp (3 species). The isolation rates of the drug-resistant (DR) fungi were 5% for 5-FC. The rates of DR and susceptible dose dependent (S-DD) fungi were 0% and 2% for FLCZ, respectively. The rates of DR and S-DD fungi were 0% and 17% for ITCZ, respectively. No shift to resistant species in C. albicans occurred in our hospitals. All C. albicans were susceptible for the antifungal agents examined.