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PubMed1998

Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care.

The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to be acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.

Antifungal Agents↗
PubMed1998

Surgical perspective on invasive Candida infections.

Invasive and disseminated Candida infections have become a major source of morbidity and mortality in the modern surgical intensive care unit. The most common risks for invasion and dissemination are the use of antibiotics, central venous lines, total parenteral nutrition, burns, immunosuppression, and other markers for severity of illness (APACHE > 10, ventilatory use for > 48 hours). Data suggest that colonization can be a late predictor of invasive disease in today's critically ill surgical patient and that prophylaxis or early treatment in high risk patients is warranted, particularly before invasive/disseminated disease becomes life-threatening. When advanced disease is present, the diagnosis of invasive or disseminated Candida infection is often prompted by clinical suspicion and supported by consistent clinical data; laboratory tests alone lack sufficient sensitivity and specificity to direct therapeutic decision-making. Once the diagnosis of invasive or disseminated Candida infection is ascertained, early systemic treatment, along with treatment of localized infection, is as fundamental as with any other serious infectious disease. Reported toxicity and efficacy supports the use of fluconazole for most patients with invasive/disseminated Candida infections. For the most critically ill surgical patient amphotericin B remains the treatment of choice. Prophylaxis and early treatment strategies with minimally toxic agents may diminish the need to use more toxic therapy in the most severely ill patients.

Anti-Bacterial Agents↗
PubMed1976

Candida myocarditis without valvulitis.

Thirty-one patients with systemic candidiasis at postmortem examination were found to have Candida involvement of the myocardium without valvulitis. Retrospective examination of their clinical course demonstrated that a new conduction disturbance was seen in 10, supraventricular arrhythmias in 5,QRS changes mimicking myocardial infarction in 3, and pronounced T wave changes in 13. Hypotension or shock was seen in 13 patients and could not be explained by coexistent bacteremia or blood loss in 8. One patient died suddenly. Of 19 patients with systemic candidiasis without myocardial invasion, 4 had minor T wave changes and one had a supraventricular arrhythmia. Candida invasion of the heart significantly complicates the clinical course in systemic candidiasis and should be suspected when a young person without preexistent heart disease has cultures positive for a Candida organism, a significant arrhythmia, conduction distrubance or other dramatic QRS change. The effect of therapy on Candida invasion of the heart is unknown.

Adult↗
PubMed1976

Candida peritonitis. Report of 22 cases and review of the English literature.

Thirty-one patients with Candida isolated from peritoneal fluid were examined. Twenty-two were considered to have Candida peritonitis. The data on these 22 patients, plus 12 additional patients described in the literature, were reviewed. This infection was observed as a complication of peritoneal dialysis, gastrointestinal surgery or perforation of an abdominal viscus. Recent antibiotic administration seemed to be an important predisposing factor. The disease usually remained localized intra-abdominally, although disseminated candidiasis was also noted in three cases. Clinically significant infection could be differentiated from peritoneal contamination with Candida by the presence and persistence of fever, peritoneal signs, peripheral leukocytosis, positive peritoneal cultures for Candida, abnormal films of the abdomen and purulent ascitic fluid. Surgical interventions and removal of infected peritoneal fluid were the cornerstones of therapy. Short-term, low-dose systemic and/or intraperitoneally administered amphotericin B appeared promising in the treatment of unremitting infection. Mortality in treated patients was low and was comparable to that in patients with bacterial peritonitis.

Adult↗
PubMed1994

Non-Candida fungal infections after bone marrow transplantation: risk factors and outcome.

PURPOSE: To determine the incidence, risk factors, and outcome of non-Candida fungal infections in a bone marrow transplant population. PATIENTS AND METHODS: A consecutive series of 1,186 patients who underwent bone marrow transplant at the University of Minnesota Hospital between 1974 and 1989 were analyzed for the occurrence of a post-transplant non-Candida fungal infection. The risk factors were analyzed with regard to clinical characteristics such as age, sex, primary disease process, type of transplant, recipient cytomegalovirus serostatus, time to engraftment, and the presence of graft-versus-host disease. RESULTS: In this population, 123 of 1,186 patients (10%) developed a non-Candida fungal infection within 180 days of transplant. The majority of infections (85%) occurred in allogeneic recipients, and 58% of infections were prior to white blood cell engraftment. The most common isolates were Aspergillus species (70%), Fusarium species (8%), and Alternaria species (5%). Although 47% of infections involved a single organ or site, 44% were disseminated and 9% were isolated fungemias. Only 17% of patients survived. Sixty-eight percent of deaths were related to the fungal infection. In univariate analysis, allogeneic transplant, positive recipient cytomegalovirus serostatus, delayed engraftment, and recipient age of greater than or equal to 18 years were identified as risk factors for non-Candida fungal infection. All of these factors except for recipient age were independently significant in multivariate analysis. In allogeneic recipients, positive cytomegalovirus serostatus, delayed engraftment, and age of greater than or equal to 18 years were each significantly associated with a greater risk of fungal infection; none of these factors were independently significant in the autologous recipients. CONCLUSION: Fungal infections remain a major cause of morbidity and mortality in patients undergoing bone marrow transplant. More effective antifungal prophylaxis and therapy, earlier diagnosis, and transplant regimens incurring a brief period of neutropenia may substantially reduce the incidence and clinical impact of these infections.

Adolescent↗
PubMed1995

Single oral dose fluconazole compared with conventional clotrimazole topical therapy of Candida vaginitis. Fluconazole Vaginitis Study Group.

OBJECTIVES: Candida vaginitis is currently treated with a wide range of intravaginal preparations usually prescribed over several days. Fluconazole with its marked activity against Candida species and favorable pharmacokinetics offered a safe, effective, and convenient alternative to topical therapy in a single-dose regimen. STUDY DESIGN: We conducted a multicenter, randomized, prospective, single-blinded study of 429 patients with acute Candida vaginitis, comparing the efficacy and safety of a single oral 150 mg dose of fluconazole with 7-day clotrimazole 100 mg vaginal treatment. Posttherapy evaluations and mycologic eradication rates were conducted. RESULTS: No statistically significant differences were seen between fluconazole and clotrimazole in the clinical, mycologic, or therapeutic responses. At the 14-day evaluation clinical cure or improvement was seen in 94% of fluconazole-treated patients and 97% of clotrimazole-treated patients. Mycologic and therapeutic cures were seen in 77% and 76% of the fluconazole and 72% of the clotrimazole groups, respectively. At the 35-day evaluation 75% of both groups remained clinically cured, and 56% of the fluconazole and 52% of the clotrimazole group were considered therapeutic cures. In both treatment groups patients with a history of recurrent vaginitis (33/84) compared with those without a history of recurrent vaginitis (177/266) were significantly less likely to respond clinically and mycologically (p < 0.001). Twenty-seven percent of the fluconazole-treated patients and 17% of the clotrimazole-treated patients reported mild side effects only. CONCLUSION: Fluconazole administered as a single 150 mg oral dose proved to be as safe and effective as 7 days of intravaginal clotrimazole therapy for Candida vaginitis. Therapy of vaginitis should be individualized, taking into consideration severity of disease, history of recurrent vaginitis, and patient preference.

Acute Disease↗
PubMed1990

Candida mediastinitis after a cardiac operation.

Candida mediastinitis is a rare condition characterized by a high mortality and chronic morbidity, Including the present review, only 39 cases have been described, 67% occurring after a cardiac operation. Candida mediastinitis has a 55% mortality in the postoperative setting and a mortality of 92% among patients without a prior cardiac procedure. Although no patient survived Candida mediastinitis without surgical drainage of the mediastinum, survival was 85% among 13 patients who underwent operative mediastinal drainage. Chronic wound infection developed in 6 survivors of operative drainage without muscle flap closure, but in all patients closed with vascularized flaps, healing ultimately occurred. Aggressive surgical management with mediastinal drainage, sternal debridement, and early wound closure with vascularized flaps are essential to minimize the otherwise high morbidity and mortality of Candida mediastinitis.

Adult↗
PubMed1982

Effects of specific antibodies on the interaction between the fungus Candida albicans and human oral mucosa.

Host-parasite interactions were studied in four groups: non-infected controls; infected carriers of Candida albicans without evidence of candidiasis; subjects with acute candidiasis; and subjects with chronic candidiasis. Specific anti-candida antibodies were demonstrated in saliva from subjects of all four groups; the titres reflected the degree of antigenic stimulation, being significantly higher in candidiasis than in controls or infected carriers. The adherence of C. albicans to buccal epithelial cells was not significantly different in a given saliva, regardless of whether the assay was carried out with autologous C. albicans and epithelial cells or with a stock strain in a standardized assay. Therefore, the standard assay was used to study the effects of specific salivary antibodies on adherence. A significant inverse correlation was found between salivary IgA anti-candida antibodies and the adherence of C. albicans to buccal epithelial cells, suggesting that IgA antibodies can inhibit adherence of candida to the oral mucosa. In some instances, removal of antibodies led to a significant increase in adherence; however, often this was not the case, indicating that some but not all of the antibodies present were capable of inhibiting the adherence of C. albicans to epithelial cells.

Adhesiveness↗
PubMed1991

Intra-uterine Candida infection: a report of four infected fetusses from two mothers.

Although Candida albicans is a frequent inhabitant of the female genital tract, chorioamnionitis is rarely caused by this fungal organism. In this report we present two cases with manifest Candida chorioamnionitis. The first case is a twin pregnancy with premature delivery and survival of both twins. The second case is a pregnancy with intra-uterine contraceptive device in situ ending in a midtrimester abortion, followed by the next pregnancy also ending in an abortion in the second trimester. Possible triggers responsible for the increased invasiveness of otherwise benign Candida vaginitis are discussed. Foreign intra-uterine bodies such as contraceptive devices and cerclage sutures necessitate repetitive search for Candida species infection, and prompt adequate antifungal treatment in cases of documented infection. Both cases of the present report add further substantial evidence to the hypothesis of amniotic infection by ascending transcervical infection. The frequent concomitant cervical infections with other infectious agents as well as antibiotherapy influencing the normal Lactobacillary defence mechanisms are both likely to increase the risk. Systemic debilitating diseases that promote invasiveness are briefly discussed.

Adult↗
PubMed1988

Evaluation of a Candida antigen detection test (Cand-Tec) in the diagnosis of deep candidiasis in neutropenic patients.

The diagnostic efficiency of a serum Candida antigen detection test Cand-Tec test) was prospectively investigated in 104 leukemic patients treated by intensive chemotherapy or allogeneic bone marrow transplantation. Candida antigen titers were determined on admission and then weekly as long as patients remained neutropenic. Nine patients had a proven disseminated yeast infection (diagnosed only at autopsy in five cases). The highest Candida antigen titers were 1:2 in two patients and 1:4 or more in seven patients (sensitivity: 76% for this last titer). This highest titer was observed 12 days before to 3 days after the diagnosis. Seven out of the 97 patients without proven deep candidiasis had a maximum titer of 1:4 (specificity: 93%). The positive predictive value was 50% for a titer of 1:4 and 24% for a titer of 1:2, whereas the negative predictive value was 100% for a titer of 1:4 and 97% for a titer of 1:2. Patients with elevated titers were mostly treated by chemotherapy, were older and had a worse prognosis than those with negative titers, although the duration of neutropenia was similar. It is concluded that Candida antigen detection is a reliable method of diagnosis of deep candidiasis in neutropenic patients. The clinical interest in this test, with special regard to empiric antifungal therapy, is discussed.

Agranulocytosis↗
PubMed1982

Pleural plaques in asbestosis: effect of Candida albicans.

Effect of chrysotile dust alone or together with Candida albicans administered intratracheally in guinea pigs was studied in the genesis of pleural plaques over a period of 12 months. A significant increase of mucopolysaccharides, phosphorus, calcium and -SH content was detected in pleural fluid of animals treated with chrysotile and Candida albicans together than in those treated with chrysotile or Candida albicans alone. The results suggest that an infection of Candida albicans accentuates the effect of chrysotile by altering the biochemical parameters preceding to the formation of pleural plaques.

Animals↗
PubMed2006

Medicinal plants used by Tanzanian traditional healers in the management of Candida infections.

An ethnomedical survey in Coast, Dar es Salaam, Morogoro and Tanga regions of Tanzania has resulted in the identification of 36 plant species belonging to 21 plant families that are used traditionally for the treatment of Candida infections. Twenty-one plants constituting 58.3% of all collected plants are used to treat of oral candidiasis (Utando) one of the important signs of HIV/AIDS. The knowledge of traditional healers for the treatment of Candida infections has been highly supported by the literature in that 13 (36.1%) out of the 36 plants identified have been proven to be active against Candida albicans and/or other species of Candida. Also, some of the plants were reported to be active against other species of fungi including Cryptococcus neoformans, one of the important pathogenic fungi in HIV/AIDS. It can be seen that ethnomedical information from traditional healers provides a solid lead towards development of new drugs than random screening. The task that remains is to screen extracts prepared from these plants and perform a bioassay-guided fractionation of the active extracts so as to isolate the active compounds from these plants.

Administration, Oral↗
PubMed1986

A macrophage defect in women with recurrent Candida vaginitis and its reversal in vitro by prostaglandin inhibitors.

The possible involvement of a defect in cellular immunity in the etiology of recurrent vaginal candidiasis was explored. The mean and range of in vitro lymphocyte proliferative responses induced by mitogens were comparable in 65 patients and 36 control subjects. In contrast, Candida-directed proliferation was reduced at least 70% below the mean control value in 73% of the patients. Further analyses on selected patients demonstrated that lymphocytes of the patients responded in the normal range to Candida if incubated in the presence of control macrophages. Conversely, macrophages of patients inhibited the responses of control lymphocytes to Candida. These effects were independent of mixed leukocyte reactions between allogeneic cells. Addition of the prostaglandin inhibitors ibuprofen and indomethacin prevented macrophages of patients from inhibiting patient or control lymphocyte proliferation. In response to Candida, macrophages from some women with recurrent vaginitis produce prostaglandin, which blocks the lymphocyte proliferation response to this organism.

Candidiasis, Vulvovaginal↗
PubMed2002

Bilateral presumed endogenous candida endophthalmitis and stage 3 retinopathy of prematurity.

PURPOSE: To report a case of presumed endogenous bilateral Candida endophthalmitis that developed in an infant with bilateral posterior stage 3 retinopathy of prematurity. DESIGN: Interventional case report. METHODS: In a very low birth weight and extremely premature infant, presumed endogenous bilateral Candida endophthalmitis was successfully eradicated from each eye and retinopathy of prematurity was managed. RESULTS: Candida endophthalmitis was successfully eradicated from each eye by vitrectomy with instillation of 5 microg amphotericin B. Stage 3 retinopathy of prematurity without "plus disease" in the right eye regressed without ablation of the avascular peripheral retina. Stage 3 retinopathy with "plus disease" in the left eye was successfully managed with endolaser photocoagulation. CONCLUSIONS: Concomitant Candida endophthalmitis and posterior stage 3 retinopathy of prematurity often portend a dismal prognosis. We describe an infant for whom prompt diagnosis and aggressive therapy of both conditions resulted in a favorable anatomic outcome in both eyes.

Amphotericin B↗
PubMed1991

Successful medical treatment of presumed Candida endocarditis in critically ill infants.

Few infants have been reported who survived fungal endocarditis; all have required both surgical and intensive antifungal therapy. We describe three infants, two weighing less than 1000 gm, who survived Candida endocarditis without surgery. Two had Candida parapsilosis, an agent not previously reported as a cause of neonatal endocarditis. All three infants were treated with amphotericin B and 5-flucytosine. Despite administration of 44, 38, and 48 mg/kg amphotericin B, respectively, no nephrotoxicity was noted; 5-flucytosine therapy was stopped in one infant because of thrombocytopenia. One infant died of an unrelated cause 6 months later; there was no evidence of Candida or endocarditis at autopsy. The other two infants are thriving 2 and 3 years after the completion of antifungal therapy; no remaining evidence of endocarditis is present on echocardiography. We conclude that antifungal therapy without surgery is an option for Candida endocarditis in critically ill infants.

Amphotericin B↗
PubMed1998

Longitudinal investigation of candida vaginitis in pregnancy: role of superimposed antibiotic use.

OBJECTIVE: To evaluate the purported association of antibiotic use and subsequent symptomatic Candida vaginitis among pregnant women. METHODS: Two hundred fifty obstetric patients were followed in a prospective, culture-based, longitudinal, and observational study from the first antepartum appointment through the postpartum visit at 6 weeks. All patients were cultured for yeast (Nickerson agar) initially. Patients with symptoms and microscopic evidence of vaginitis at the initial visit were followed through pregnancy but were not analyzed with asymptomatic individuals who had vaginal cultures for Candida at the first visit and at subsequent visits if they developed vulvovaginal symptoms. Patients were categorized as colonized or uncolonized on the basis of initial cultures and were evaluated at least monthly for antibiotic use and vaginal complaints. In addition, hospital records were reviewed after the final visit to document antibiotic use or vaginal infection. RESULTS: Asymptomatically colonized patients were at a threefold greater risk of developing symptoms than were uncolonized patients (P < .001). Among women receiving antibiotics during pregnancy, 6.1% developed symptoms of Candida vaginitis compared with 15.6% of women who did not receive antibiotics. For the entire study population, 46% of the patients received at least one course of antibiotic therapy and 21% had multiple courses. Only three of the seven who became symptomatic with yeast vaginitis did so within 4 weeks of treatment. Many of the antibiotic regimens were prescribed by providers other than the obstetrician. CONCLUSION: Antibiotic treatment during pregnancy was frequent in the study population, but was not associated with a significant risk of developing Candida vaginitis.

Antifungal Agents↗
PubMed1996

Treatment of Candida nail infection with terbinafine.

BACKGROUND: Terbinafine is a highly potent drug against dermatophytes. Data regarding its effectiveness against Candida species are few and variable. OBJECTIVE: Our purpose was to evaluate the efficacy and safety of oral terbinafine in patients with Candida nail infection. METHODS: In an open-label uncontrolled study, 20 patients completed 16 weeks of treatment with terbinafine, 250 mg/day, and an additional 8 weeks with placebo. Efficacy was assessed clinically and mycologically at weeks 0 (baseline), 4, 8, 16, 24, 36, and 48. Routine laboratory studies were performed at baseline and weeks 4, 8, and 16. RESULTS: At the end of the trial 60% of target nails were cured clinically and mycologically; in 10% there was mycologic cure with residual clinical signs, in 25% a moderate improvement (> 50%), and failure in only 5% (one patient). Most nails were infected by Candida parapsilosis. Two of 28 patients showed mild reversible elevation of liver enzymes 1 month after initiation of terbinafine treatment. CONCLUSION: The administration of terbinafine for 16 weeks is effective in the treatment of Candida nail infection. Liver enzyme values should be determined during the first month of treatment.

Administration, Oral↗
PubMed2003

[Vertebral osteomyelitis due to Candida spp].

INTRODUCTION: Vertebral osteomyelitis is rarely caused by Candida species; therefore, a high index of suspicion is required for its diagnosis. METHODS: We describe three cases of vertebral osteomyelitis due to Candida spp. diagnosed over a seventeen-year period. RESULTS: Among 110 episodes of vertebral osteomyelitis, three were caused by Candida spp. All three patients had risk factors for Candida infection: diabetes mellitus (2), immunosuppression (2), central venous catheters (3), antibiotic use (2) and parenteral nutrition (2). Radiographic studies and culture of vertebral specimens established the diagnosis in two patients. Blood cultures were positive in the third patient, who had aortic infectious endocarditis. Two of the three cases achieved clinical cure with medical treatment and the third relapsed after six months of therapy with fluconazole. CONCLUSION: Candidal vertebral osteomyelitis is an uncommon disease that should be suspected in patients with risk factors for candidemia.

Aged↗