Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans

BACKGROUND Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections. OBJECTIVE To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis. METHODS Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis. FINDINGS Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B. CONCLUSIONS The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

Uncommon Candida Species Fungemia among Cancer Patients, Houston, Texas, USA.

Many uncommon Candida species that cause bloodstream infections (BSIs) are not well-characterized. We investigated the epidemiology, antifungal use, susceptibility patterns, and factors associated with all-cause death among cancer patients in whom uncommon Candida spp. BSIs were diagnosed at a cancer treatment center during January 1998­September 2013. Of 1,395 Candida bloodstream isolates, 79 from 68 patients were uncommon Candida spp. The incidence density of uncommon Candida spp. BSIs and their proportion to all candidemia episodes substantively increased during the study period, and the rise was associated with increasing use of echinocandin antifungal drugs. Thirty-seven patients had breakthrough infections during therapy or prophylaxis with various systemic antifungal drugs for >7 consecutive days; 21 were receiving an echinocandin. C. kefyr (82%), and C. lusitaniae (21%) isolates frequently showed caspofungin MICs above the epidemiologic cutoff values. These findings support the need for institutional surveillance for uncommon Candida spp. among cancer patients.

Relationship between clinical factors and severity of esophageal candidiasis according to Kodsi's classification.

Severe Candida esophagitis (CE) may lead to development of strictures, hemorrhage, esophagotracheal fistula, and a consequent decrease in quality of life. Although the severity of CE has been classified based on macroscopic findings on endoscopy, the clinical significance remains unknown. The aim of the study was to elucidate the predictive clinical factors for endoscopic severity of CE. Patients who underwent upper endoscopy and answered questionnaires were prospectively enrolled. Smoking, alcohol, human immunodeficiency virus (HIV) infection, diabetes mellitus, chronic renal failure, liver cirrhosis, systemic steroids use, proton pump inhibitor use, H2 blocker use, and gastrointestinal (GI) symptoms were assessed on the same day of endoscopy. GI symptoms including epigastric pain, heartburn, reflux, hunger cramps, nausea, dysphagia, and odynophagia were assessed on a 7-point Likert scale. Endoscopic severity was classified as mild (Kodsi's grade I/II) or severe (grade III/IV). Of 1855 patients, 71 (3.8%) were diagnosed with CE (mild, n = 48; severe, n = 23). In the CE patients, 50.0% (24/48) in the mild group and 23.1% (6/23) in the severe group did not have any GI symptoms. In HIV-infected patients (n = 17), a significant correlation was found between endoscopic severity and declining CD4 cell count (Spearman's rho = -0.90; P < 0.01). Multivariate analysis revealed that GI symptoms (odds ratio [OR], 3.32) and HIV infection (OR, 3.81) were independently associated with severe CE. Patients in the severe group experienced more epigastric pain (P = 0.02), reflux symptoms (P = 0.04), dysphagia (P = 0.05), and odynophagia (P < 0.01) than those in the mild group. Of the GI symptoms, odynophagia was independently associated with severe CE (OR 9.62, P = 0.02). In conclusion, the prevalence of CE in adults who underwent endoscopy was 3.8%. Silent CE was found in both mild and severe cases. Endoscopic severity was associated with characteristic GI symptoms and comorbidity of HIV infection. A decline in immune function correlated with CE disease progression.

Candidiasis esofágica / Esophageal candidiasis

La Candidiasis esofágica es una entidad frecuente en pacientes con VIH, cáncer, usuarios de corticoides, algorra orofaringea. La Candida es un organismo comensal y puede infectar al ser humano. Existe una serie de factores locales y sistémicos del huésped que favorecen la infección por Candida. El cuadro clínico se presenta frecuentemente con odinofagia, disfagia y dolor retroesternal. El diagnóstico de certeza es histológico. El estudio endoscópico entrega un estudio de alta calidad, altamente sensible y permite diferenciar distintas causas de esofagitis. La candidiasis esofágica debe ser tratada con terapia sistémica. El fármaco más recomendado es el fluconazol.

Esophageal candidiasis is a frequently occurring entity in corticoid users, patients with HIV and oropharyngeal involvement. Candida is a commensal organism, and it can infect humans. There are many local and systemic factors of the host that favor Candida infection. Frequently clinical manifestations are odynophagia, dysphagia and retrosternal pain. Diagnostic certainty reached by histological assays. Endoscopic studies provide high-quality and highly-sensitive results that allow to differentiate esophagitis causes. Esophageal Candidiasis must receive systemic treatment. The most recommended drug is Fluconazol.

Candidosis en pacientes HIV o con otras inmunodeficiencias secundarias en hospitales de la ciudad de Tucumán (Argentina) / Candidosis in HIV patients or with other secondary immunodeficiencies detected in hospitals of the city of Tucumán (Argentina)

Con el objeto de conocer las especies causantes de candidosis humanas en pacientes HIV positivos o con otras inmunodeficiencias secundarias y la incidencia de especies con capacidad de resistencia a antifúngicos, se estudiaron 76 aislamientos de Candida procedentes de 61 casos de candidosis superficiales y profundas de niños y adultos. Obtenidas desde piel, anexos, mucosas, abscesos, catéteres y secreciones diversas, entre otras. La identificación de las especies fue realizada por estudios de características morfológicas, cromogénicas y bioquímicas (CHROMagar , Candifast, API 20 y API 32). Los resultados revelan predominio de especies noalbicans (52.7 por ciento), obteniéndose las siguientes frecuencias de aislamientos: C.albicans (47,3 por ciento), C. parapsilosis: 15,8 por ciento, C. glabrata: 13,2 por ciento, C. krusei: 11,8 por ciento, C. tropicalis: 10,6 por ciento y C. dubliniensis: 1,3 por ciento. Algunas de ellas pueden presentar resistencia primaria o secundaria a algunos antifúngicos de uso habitual, por lo cual es necesario incluir estudios de sensibilidad a estos, para una mejor conducta terapéutica.

In order to find out species causing human candidosis in positive HIV patients or in individuals suffering from other secondary immunodeficiencies and the incidence of species bearing a resistance ability to antifungal agents, 76 Candida isolations obtained from 61 cases of superficial and deep candidosis in children and adults were studied. Samples were collected from skin, annexa, mucosities, abscesses, catheters and diverse secretions, among others. The identification of species was carried out through studies on morphological, chromogenic and biochemical characteristics (CHROMagar, Candifast, API 20 and API 32). Results reveal a predominance of non-albican species (52,7 percent), and the following frequencies of isolation: C.albicans (47.3 percent), C. parapsilosis: 15.8 percent, C.glabrata: 13.2 percent, C. krusei: 11.8 percent, C. tropicalis: 10.6 percent and C. dubliniensis: 1.3 percent. Some of them may exhibit some primary or secondary resistance to certain antifungal agents of common use, this is why it is necessary to include studies on sensitivity of them so as to attain a better therapeutical behaviour.

Mixed fungemia: incidence, risk factors, and mortality in a general hospital.

BACKGROUND: Fungemia has been historically considered to be a disease caused by a single Candida species; the detection of >1 species of yeast in circulating blood was distinctly uncommon using traditional microbiological procedures. We describe episodes of mixed fungemia (MF), detected between 1985 and 2006, in a large teaching hospital. METHODS: The study was divided into 2 periods that were separated by the introduction, in January 2005, of the CHROmagar Candida medium (CHROMagar) for the routine subculturing of blood cultures in which yeast has been identified. Overall, we documented 747 cases of fungemia. During the first period (1985-1994), we identified 217 episodes of fungemia and no single episode of MF; during the second period (1995-2006), 15 episodes of MF were detected among 530 episodes of fungemia (2.8%). Candida albicans was isolated in 13 patients, non-albicans species of Candida in 16 patients, and Saccharomyces cerevisiae in 1 patient. Each episode of MF was compared with 2 control episodes of monomicrobial fungemia. RESULTS: Patients with MF had more frequently experienced organ transplantation (13% vs. 0%) and surgery (60% vs. 27%), had less frequently received parenteral nutrition (40% vs. 70%) or had intravenous lines (80% vs. 100%), and had a lower incidence of shock (6% vs. 37%) and a lower mortality (20% vs. 53%). CONCLUSIONS: Despite the introduction of chromogenic agar, MF is still an uncommon disease and has a less severe outcome than does monomicrobial candidemia.

Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients.

STUDY OBJECTIVES: To develop and prospectively validate models of independent predictors of candidemia and candidemia-related death in cardiothoracic ICU (CICU) patients. DESIGN: (1) An initial, prospective, one-center, case-control, independent predictor-model determining study; and (2) a prospective, two-center, model-validation study. SETTING: The initial study was performed at the 14-bed CICU of the Onassis Cardiac Surgery Center, Athens, Greece; the model-validation study was performed at the Onassis Cardiac Surgery Center CICU and the 12-bed CICU of Henry Dunant General Hospital, Athens, Greece. PATIENTS: In the initial study, 4,312 patients admitted to the Onassis Center CICU between March 1997 and October 1999 were considered for enrollment; 30 candidemic and 120 control patients (case/control ratio, 1/4) matched according to potential confounders were ultimately enrolled. In the model-validation study, 2,087 patients admitted to the Onassis and Henry Dunant CICUs between November 1999 and May 2002 were prospectively enrolled. MEASUREMENTS AND RESULTS: Models of predictors of candidemia and associated death were constructed with stepwise logistic regression and subsequently validated. Independent candidemia predictors were ongoing invasive mechanical ventilation (IMV) > OR =10 days, hospital-acquired bacterial infection and/or bacteremia, cardiopulmonary bypass duration > 120 min, and diabetes mellitus. Model performance was as follows: sensitivity, 53.3%/57.9%; specificity, 100%/100%; positive predictive value (PPV), 100%/100%; negative predictive value (NPV), 88.9%/99.6%; and accuracy, 90.1%/99.6% (initial/model-validation study values, respectively). IMV > or =10 days and hospital-acquired bacterial infection/bacteremia were the two strongest candidemia predictors. APACHE (acute physiology and chronic health evaluation) II score > or =30 at candidemia onset independently predicted candidemia-related death with 80.0%/85.7% sensitivity, 80%/75% specificity, 66.7%/66.7% PPV, 88.9%/88.9% NPV, and 80.0%/78.9% accuracy (initial/model-validation study values, respectively). CONCLUSIONS: We provided a set of easily determinable independent predictors of the occurrence of candidemia in CICU patients. Our results provide a rationale for implementing preventive measures in the form of independent predictor control, and initiating antifungal prophylaxis in high-risk CICU patients.

Epidemiologia de candidíase hospitalar: importância da identificação específica / Epidemiology of nosocomial candidiasis: the importance of specific identification

Infecções fúngicas sistêmicas são hoje importante causa de morbidade e mortalidade em pacientes imunossuprimidos ou com outras condições predisponentes. Candida albicans e as não-albicans são importante causa de infecções nosocomiais e vários destes agentes são menos suscetíveis às drogas antifúngicas, principalmente os azólicos, um fato que tem significado no tratamento destes pacientes. O moderno laboratório de micologia tem importante papel no esclarecimento destas infecções, incluindo sua detecção , identificação e a sensibilidade a drogas antifúngicas, bem como a análise epidemiológica. Neste estudo, foi comparada a distribuição de espécies de Candida relacionadas a fungemias e outras fontes, em quatro hospitais do Estado de São Paulo. Das 40 leveduras identificadas, C. albicans, C. parapsilosis e C. tropicalis foram isoladas, respectivamente, em 35 por cento, 50 por cento e 15 por cento, revelando uma tendência de ser maior a freqüência de espécies não-albicans. As fungemias foram causadas por C. parapsilosis (45,4 por cento). C. albicans (36,4 por cento) e C. tropicalis (18,2 por cento), o que revela um aumento de espécies não-albicans em relação a séries históricas. As três diferentes espécies foram incluídas em 6,3 e 4 biótipos diferentes, respectivamente para C.albicans, C.parapsilosis e C.tropicalis. Este estudo enfatiza a importância da avaliação de espécies de Candida especialmente em centros hospitalares com pacientes de risco.

Comparison of caspofungin and amphotericin B for invasive candidiasis.

BACKGROUND: Caspofungin is an echinocandin agent with fungicidal activity against candida species. We performed a double-blind trial to compare caspofungin with amphotericin B deoxycholate for the primary treatment of invasive candidiasis. METHODS: We enrolled patients who had clinical evidence of infection and a positive culture for candida species from blood or another site. Patients were stratified according to the severity of disease, as indicated by the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the presence or absence of neutropenia and were randomly assigned to receive either caspofungin or amphotericin B. The study was designed to compare the efficacy of caspofungin with that of amphotericin B in patients with invasive candidiasis and in a subgroup with candidemia. RESULTS: Of the 239 patients enrolled, 224 were included in the modified intention-to-treat analysis. Base-line characteristics, including the percentage of patients with neutropenia and the mean APACHE II score, were similar in the two treatment groups. A modified intention-to-treat analysis showed that the efficacy of caspofungin was similar to that of amphotericin B, with successful outcomes in 73.4 percent of the patients treated with caspofungin and in 61.7 percent of those treated with amphotericin B (difference after adjustment for APACHE II score and neutropenic status, 12.7 percentage points; 95.6 percent confidence interval, -0.7 to 26.0). An analysis of patients who met prespecified criteria for evaluation showed that caspofungin was superior, with a favorable response in 80.7 percent of patients, as compared with 64.9 percent of those who received amphotericin B (difference, 15.4 percentage points; 95.6 percent confidence interval, 1.1 to 29.7). Caspofungin was as effective as amphotericin B in patients who had candidemia, with a favorable response in 71.7 percent and 62.8 percent of patients, respectively (difference, 10.0 percentage points; 95.0 percent confidence interval, -4.5 to 24.5). There were significantly fewer drug-related adverse events in the caspofungin group than in the amphotericin B group. CONCLUSIONS: Caspofungin is at least as effective as amphotericin B for the treatment of invasive candidiasis and, more specifically, candidemia.

The epidemiology of Candida glabrata and Candida albicans fungemia in immunocompromised patients with cancer.

PURPOSE: Candida glabrata is an increasing cause of candidemia, especially at cancer and bone marrow transplant centers where fluconazole is used for antifungal prophylaxis. This yeast is less susceptible to fluconazole in vitro than is Candida albicans. We compared the characteristics of patients who had C. glabrata and C. albicans candidemia at a large cancer center. SUBJECTS AND METHODS: We searched the microbiological laboratory reports and identified 116 cases of C. glabrata candidemia between 1993 and 1999. The 116 cases of C. albicans candidemia that occurred most closely in time (before or after each case of C. glabrata candidemia) served as the control group. Data were collected from patients' medical records. RESULTS: When compared with patients who had C. albicans infection, patients with C. glabrata candidemia more often had an underlying hematologic malignancy (68 [59%] vs. 26 [22%], P = 0.0001), had an Acute Physiology and Chronic Health Evaluation (APACHE) II score > or =16 (55 [48%] vs. 28 [25%], P = 0.0002), and received fluconazole prophylaxis (57 [49%] vs. 8 [7%], P = 0.0001). Patients with C. albicans candidemia more often had concomitant infections (101 [87%] vs. 78 [67%], P = 0.0003) and septic thrombophlebitis (11 [10%] vs. 2 [2%], P = 0.01). Among patients treated with antifungal therapy, those with C. albicans candidemia had a significantly greater overall response to therapy (83/104 [80%] vs. 60/97 [62%], P = 0.005) and to primary therapy (74/104 [71%] vs. 45/97 [46%], P = 0.0003). Amphotericin B preparations were not more effective than fluconazole (19/45 [42%] vs. 20/38 [53%], P = 0.5) in patients with C. glabrata candidemia. Fluconazole was less effective against C. glabrata than against C. albicans (20/38 [53%] vs. 57/74 [77%], P = 0.008). CONCLUSION: C. glabrata has emerged as an important cause of candidemia, especially among neutropenic patients who receive fluconazole prophylaxis.

[Is endoscopic diagnosis of Candida albicans esophagitis reliable? Correlations with pathology and mycology]. / Le diagnostic endoscopique d'oesophagite à Candida albicans est-il fiable?

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.

Candidiasis gastrointestinal

Se presenta la historia de un paciente de 19 años con úlcera péptica perforada, quien después de resección y reconstrucción quirúrgica de la lesión de base, desarrolló candidiasis del tracto gastrointestinal intervenido. El curso postoperatorio estuvo lleno de complicaciones (dehiscencia de tejidos suturados, formación de fístula, eviseración) y llevó al uso permanente de antibióticos, con la consecuente proliferación de levaduras normales del tracto gastrointestinal. Los exámenes de laboratorio de muestras representativas de las áreas afectadas, permitieron establecer el diagnóstico de candidiasis sobreagregada; a pesar de la severidad del cuadro, el paciente respondió prontamente al tratamiento con fluconazol. Este caso revela la necesidad de recurrir al laboratorio y de prestar atención a la presencia de levaduras del género Candida en nuestras clínicas adecuadamente colectadas del tracto gastrointestinal, ya que estos hongos pueden causar daños severos en pacientes con antecedentes quirúrgicos y terapias antimicrobianas prolongadas

[Internal mycoses of exogenous origin (author's transl)]. / Exogene Mykosen der inneren Organe (Systemmykosen).

The increase of both visceral mycoses and designations used for them requires, among other matters an accord on a better non-ambiguous terminology. The disease designation "blastomycosis" is quite obsolete and should be replaced by proper terms such as candida mycosis, cryptococcus mycosis, histoplasma mycosis etc. The frequently used term "systemic mycosis" should be restricted to exogenous mycotic infections of internal organs caused by obligatory pathogenic fungi such as Coccidioides immitis, Histoplasma capsulatum and others. The common term "endomycosis" is considered appropriate for fungal infections provoked by secondary disease provoking fungi of opportunistic pathogenicity especially by species of the form genus Candida. Other mycotic infections of visceral organs, mainly of the respiratory tract f.i. by species of Aspergillus and other molds, are likewise mostly of secondary nature and should not be considered as systemic mycosis in the restricted meaning of the word because of their lacking tendency to dissemination.