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Signs of chronic stress in women with recurrent candida vulvovaginitis.

OBJECTIVE: The purpose of this study was to determine whether there is an association between recurrent vulvovaginal candida and chronic stress. Chronic stress affects the hypothalamus-pituitary-adrenal axis, which influences the immune function. Recurrent candida vulvovaginitis is increasing. STUDY DESIGN: Women with recurrent vulvovaginal candida (n = 35) and age-matched healthy control subjects (n = 35) collected saliva for the analysis of cortisol. Hormone analyses of blood samples and vulvovaginal examinations were performed. A questionnaire was completed. RESULTS: Morning rise cortisol level was significantly blunted among patients compared with control subjects (P < .002). Mean levels of salivary cortisol were lower the first 45 minutes after awakening in women with recurrent vulvovaginal candida, compared with control subjects. More patients than control subjects reported a history of condyloma, bacterial vaginosis, and herpes genitalis. No differences were seen between patients and control subjects regarding sexual hormone binding globulin, dihydroepiandrosterone, testosterone or Hemoglobin A1c. CONCLUSION: Morning rise salivary cortisol level is blunted in women with recurrent vulvovaginal candida, which indicates signs of chronic stress. The higher incidence of vulvovaginal infections in these women compared with control subjects may reflect impaired immunity, which may be due to chronic stress.

Adult↗

Effects of insect growth regulators on the nontarget soil arthropod Folsomia candida (Collembola).

The aim of this study was to assess the effect of several insect growth regulators (IGRs) on the nontarget soil arthropod Folsomia candida (Collembola). The survival and reproduction rates of F. candida were evaluated after 28 days of exposure to six IGRs (methoprene, fenoxycarb, precocene II, tebufenozide, hexaflumuron and teflubenzuron) and to one herbicide (diuron) in artificial soil. The differences in the sensitivity of F. candida to these different substances are high. The chitin synthesis inhibitors teflubenzuron and hexaflumuron were the most toxic compounds with an EC50 of 0.05 mg/kg (dry weight) for teflubenzuron and an EC50 of 0.6mg/kg for hexaflumuron. Teflubenzuron is toxic for F. candida at concentrations that are probably close to environmental levels of this insecticide. Inhibition of reproduction is strongly related to adult survival for the juvenile hormone agonist methoprene and for the antijuvenile hormone precocene II, with an EC50 of 173 mg/kg and a LC50 of 178mg/kg for methoprene and an EC50 of 15 mg/kg and a LC50 of 26 mg/kg for precocene II. Fenoxycarb, another juvenile hormone analog, showed a dose-response curve for mortality different from that of methoprene; at concentrations such as 3052 mg/kg no effect on adult survival was observed. However, the EC50 value of 113mg/kg is of the same order of magnitude as that obtained for methoprene. A test with compressed soil contaminated with fenoxycarb was conducted to observe parameters such as numbers of eggs laid and juveniles hatched. No differences were observed between these two endpoints for fenoxycarb. An EC50 of 109 mg/kg was obtained for the ecdysone agonist tebufenozide. The herbicide diuron showed a relatively high toxicity for F. candida with an EC50 of 20 mg/kg. Our results show that some of the tested IGRs can have effects on Collembola at environmentally relevant concentrations (toxicity/exposure ratios < 5 for teflubenzuron, hexaflumuron, and diuron).

Animals↗

Risk factors for Candida infections in a neonatal intensive care unit in Costa Rica.

OBJECTIVE: To identify potential risk factors associated with Candida infections and compare these risk factors between patients who both died and survived. STUDY DESIGN: A group of patients with positive Candida spp. blood cultures admitted to a neonatal intensive care unit (NICU) in Costa Rica between January 1994 and December 1998. Cases were identified through a computerized search of the microbiology laboratory's database on blood cultures. RESULTS: One hundred and ten newborns were identified. Sixty-six patients (60%) were male; 46 (62%) were preterm infants. Thirty-seven (34%) patients died. Twenty (54%) of them died within three days of the candidemia diagnosis and 17 had disseminated Candida infection on autopsy. Candida albicans and Candida tropicalis were isolated in 90% and 10% of blood cultures, respectively. Mean +/- SD (range) number of days from admission to NICU to the initial positive blood culture were 13.5 +/- 8.5 (1-30) days. Most patients had at least two positive blood cultures (range 1-8). Median (range) days for the sterilization of blood culture were four (1-25) days. Significant differences in survival were identified in patients with axillary-inguinal lesions, apnea and seizures. CONCLUSIONS: Invasive fungal infections are frequent in NICU. Future case-control prospective studies should be carried out to confirm the findings from this report.

Amphotericin B↗

Postoperative Candida infections of the heart in children: clinicopathologic study of a continuing problem of diagnosis and therapy.

Fungal infections of the heart are infrequent postoperative complications in children, yet, when present are often fatal. Children autopsied at The Johns Hopkins Hospital from 1889 to the present were studied for cardiac fungal infection. Among the 14 children so identified, 8 developed cardiac fungal infection after surgery. All postoperative cardiac infections were caused by Candida species. All were autopsied since 1959. Gastrointestinal surgery was performed in 6 patients and cardiac surgery in 2. Candida infection was not confined to the endocardium; endocarditis developed in 2 patients, pericarditis in 1, and myocarditis in 5. None received cytotoxic agents or corticosteroids. Two patients died from direct cardiac involvement. Other deaths were related to Candida sepsis or bronchopneumonia. A clinical diagnosis of cardiac fungal infection was never made. Prolonged administration of multiple antibiotics, central venous catheterization, prematurity and immune deficiency predisposed to cardiac and systemic candidiasis. Clinical features facilitating early diagnosis are discussed. Removal of central venous catheters infected with Candida did not eliminate the source of continued sepsis, since Candida-laden vegetations related to the catheter adhered to the superior vena cava and endocardial surface. Postoperative cardiac candidiasis is a relatively new and persistent problem of early diagnosis and therapy. The post-surgical pediatric patient has major predisposing factors for cardiac candidiasis, which, if unrecognized, may be a source for continued dissemination or may in itself be the cause of death.

Adolescent↗

Atiprimod (SK&F 106615), a novel macrophage targeting agent, enhances alveolar macrophage candidacidal activity and is not immunosuppressive in Candida-infected mice.

Azaspiranes are novel macrophage-targeting agents with activity in preclinical animal models of autoimmune disease and transplantation. The purpose of this work was to determine the effects of atiprimod (SK&F 106615), an azaspirane being developed for the treatment of rheumatoid arthritis, on rat pulmonary alveolar macrophage (AM) function and immunocompetance in Candida-infected mice. AM from rats treated with 20 mg/kg/day of atiprimod for 15 days demonstrated enhanced killing of Candida albicans ex vivo. Concentration-dependent increases in candidacidal activity were also observed as early as one hour after exposure in vitro in AM from untreated normal rats. Treatment of AM with atiprimod in vitro did not increase particulate-stimulated superoxide production or phagocytosis of Candida but decreased their ability to concentrate acridine orange, indicating an increase in lysosomal pH. Increased candidacidal activity was inhibited by superoxide dismutase and catalase, suggesting a role for reactive oxygen intermediates (ROI). Atiprimod also increased free radical-mediated killing of Candida in the presence of H2O2, iron and iodide in a cell-free system. These findings indicated that treatment with atiprimod increased the candidacidal activity of rat AM in a free radical-dependent manner. The data also suggested that atiprimod did not increase ROI production by AM, but rather increased the efficiency of radical-mediated killing. This increase may be caused by cyclization of atiprimod, facilitating electron transfer and peroxidation of lipid membranes. In vivo studies in Candida-infected CBA mice showed that atiprimod (10 mg/kg/day), did not compromise immune function in the infected mice and could be differentiated from prototypical immunosuppressive compounds used for treatment of autoimmune diseases.

Acridine Orange↗

Criteria used when initiating antifungal therapy against Candida spp. in the intensive care unit.

Invasive candidiasis is a life threatening complication for intensive care unit (ICU) patients. The infection is difficult to recognise so that treatment may be delayed or even not given. Risk factors for candidiasis include the use of antimicrobial agents, central intravascular devices (mainly Hickmann catheters), recurrent gastrointestinal perforations, surgery for acute pancreatitis or splenectomy and renal dysfunction or haemodialysis. Therapy against Candida spp is recommended in ICU patients with endophthalmitis or chorioretinitis possibly caused by Candida spp., in symptomatic patients with risk factors for invasive candidiasis especially if two or more anatomical sites are colonised and for asymptomatic high-risk surgical patients (with recent abdominal surgery or recurrent gastrointestinal perforations or anastomotic leakages). The isolation of Candida from any site poses an increased risk but there are a few microbiological data that might help to establish the predictive value of a particular isolate. These include the site of isolation, the number of culture positive, noncontigous sites, the density of colonisation and the species isolated. Antifungals should be started when Candida spp. are recovered from blood cultures or from usually sterile body fluids, abscesses or wounds in burns patients. They should also be considered in patients with a colonisation index >0.5 or a corrected colonization index >0.4 or when the isolate is identified as Candida tropicalis.

Antifungal Agents↗

Rapid Speciation of the Five Most Medically Relevant Candida Species Using PCR Amplification and a Microtiter Plate-Based Detection System.

Background: Diagnosis of disseminated candidiasis can be difficult, as patient symptoms are often vague and blood cultures negative despite systemic involvement. Rapid detection of Candida would be advantageous, as delays in initiating antifungal therapy increase mortality. Conventional blood culturing methods require at least 3-7 days for detecting and speciating isolates, especially non-albicans species. In contrast, DNA amplification techniques make it possible to detect Candida DNA directly from clinical samples, thus eliminating the need to culture. Methods and Results: This study describes a polymerase chain reaction (PCR)-based assay, which permits amplification and speciation of the five most medically relevant Candida species, which cause over 95% of all Candida infections, namely, C. albicans, C. tropicalis, C. (Torulopsis) glabrata, C. parapsilosis, and C. krusei. Speciating these isolates has become more important recently with the introduction of fluconazole, and antifungal drug that has lower nephrotoxicity than fungizone but a narrower host range. Conclusions: By using this PCR-based assay in conjunction with a rapid microtiter plate-based detection system, samples can be analyzed for Candida DNA from five species in a single day. This represents a significant time saving as compared with the more lengthy but commonly used techniques of agarose gel electrophoresis and Southern blot hybridization for PCR product detection.

Journal Article↗

[Retrospective analysis of fluconazole efficacy in Candida-colonized, non-neutropenic, surgical patients in long-term intensive care].

BACKGROUND AND OBJECTIVE: The early clinical diagnosis of invasive candidiasis is difficult. Fluconazole, which has been available since the early 1990s, is a relatively atoxic intravenously applicable antimycotic agent. For this reason it has been widely used - possibly too much. The aim of this study was the retrospective critical evaluation of the efficacy of systemic antifungal chemotherapy in non-neutropenic, Candida-colonized, surgical patients in long-term intensive care. PATIENTS AND METHODS: 69 patients (54 men and 15 women, aged 55.8 [range 18-87] years) of 364 patients of the anaesthesiological intensive care unit (ICU) of the University Hospital of Heidelberg in 1991 and 1992 were selected for the study. None of the 69 patients was suffering from proven invasive candidiasis according to the gold-standard criteria of positive histology, blood culture, or isolation from a sterile compartment. However, 35 of the 69 patients were systemically treated with fluconazole (on average 295 mg per day for 10.2 days intravenously). 34 patients did not receive any antifungal therapy. Retrospectively we analysed the course of the disease in both groups of patients. Furthermore, 173 serum samples of these patients were available for investigations by Western blot for anti-Candida antibodies of the immune globulin classes M and G. RESULTS: Both groups, antimycotically treated and untreated patients, had similar characteristics at base-line: age, sex, underlying disease, severity of the disease (APACHE II Score), and also mortality (approximately 20 % in both groups). Only times in the ICU and on mechanical ventilation were significantly enhanced in fluconazole treated patients (p values 0.0004 each). Before therapy, the fluconazole patients had significantly more often yeasts in primarily non-sterile compartments (chi (2) test 0.05). The yeasts were partly eradicated by fluconazole (32/54, 59.3 %). Anti-Candida antibodies significantly correlated with higher age (anti 47 kDa antigen, p = 0.02), but not with other, clinically, diagnostically or prognostically relevant parameters. CONCLUSION: Fluconazole in non-neutropenic, Candida-colonized, surgical patients in long-term ICU care neither improved the clinical course nor the mortality rate among these patients. These observations indicate that there was a trend of overestimating the clinical significance of Candida in this group of patients. Fluconazole therapy may be significantly reduced in such patients.

APACHE↗

Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole.

BACKGROUND: In early 1990 fluconazole was introduced as a prophylactic antifungal agent after bone marrow transplantation. During the same year Candida krusei emerged as the chief candida pathogen among patients with bone marrow transplants. METHODS: To determine whether there was a correlation between the introduction of fluconazole and the increased incidence of C. krusei, we conducted a retrospective study based on the medical, mycologic, and autopsy records of all adult inpatients who had undergone bone marrow transplantation (n = 296) or who had leukemia (n = 167) at the study center during 1989 and 1990. RESULTS: The 84 patients who received antifungal prophylaxis with fluconazole had a sevenfold greater frequency of C. krusei infection than the 335 patients who did not receive fluconazole (8.3 percent vs. 1.2 percent, P = 0.002), despite having a lower frequency of disseminated C. albicans and C. tropicalis infections (0 vs. 6.0 percent, P = 0.02). Ten of the 11 C. krusei infections were controlled by a combination of amphotericin B and flucytosine. Colonization by C. krusei was found in 40.5 percent of the patients who received fluconazole but in only 16.7 percent of those who did not receive it (P less than 0.0001). Colonization was independently associated with the prophylactic use of both fluconazole (odds ratio, 3.50; P less than 0.001) and norfloxacin (odds ratio, 2.53; P = 0.04). C. krusei was not susceptible to fluconazole in vitro. CONCLUSIONS: In patients at high risk for disseminated candida infections, suppression of bacterial flora and the more common candida pathogens may permit some less pathogenic, but natively resistant candida species, such as C. krusei, to emerge as systemic pathogens.

Adult↗

Hematogenous candida endophthalmitis in patients receiving parenteral hyperalimentation fluids.

To determine the incidence of hematogenous candida endophthalmitis in seriously ill patients given parenteral hyperalimentation fluids, 131 hyperalimented postoperative patients were prospectively evaluated. All patients were screened weekly for the development of chorioretinal lesions, blood cultures positive for Candida albicans, and signs and symptoms of candida infection. Thirteen (9.9%) of 131 patients developed chorioretinal lesions compatible with hematogenous candida endophthalmitis. Seven of the 13 patients with eye lesions had blood cultures positive for yeast, whereas only two of 118 without eye lesions had blood cultures positive for yeast (P less than 0.0005). Thus, the occurrence of eye lesions consistent with hematogenous candida endophthalmitis correlated with positive blood cultures for yeast and strongly suggested invasive candidiasis.

Amphotericin B↗

The spectrum of non-Candida fungal infections following bone marrow transplantation.

We evaluated a consecutive series of patients who underwent bone marrow transplantation (BMT) at a single institution between 1974 and 1989 for the occurrence of a non-Candida fungal infection in the first 180 days after BMT. Of the 1186 patients, 129 (11%) patients developed a total of 138 significant non-Candida fungal infections in this period. Eight patients had multiple distinct infections. The most common isolate was Aspergillus spp. (n = 97), followed by Fusarium (n = 10), and Alternaria (n = 6). The 4 clinical subtypes of infections were minor skin or soft-tissue infections (n = 7), infections of a single organ or site (n = 61), disseminated fungal infection (n = 58), and isolated fungemia (n = 12). The respiratory tract was involved in 95% of single organ or site infections, and 84% of disseminated infections. Outcome was poor, with only 18% of patients surviving. The cause of death was directly related to the non-Candida fungal infection in 66% of patients who died. Mortality rates were significantly higher in patients with either single-organ or site infections (41%) or disseminated infections (83%). The cause-specific mortality rate was greatest following infections with Aspergillus, Chrysosporium, Fusarium, Mucor, or Scopulariopsis, in which there was a high potential for invasive disease and disseminated infection. In contrast, the cause-specific mortality rate was lowest in infections which were either isolated fungemia or were localized and amenable to surgical debridement, most often seen with those infections caused by Acremonium, Alternaria, Penicillium, and Saccharomyces. The spectrum of clinical infections caused by these uncommon non-Candida fungal isolates both in our series and in the literature is reviewed. These unusual opportunistic fungal isolates are now gaining recognition in immunosuppressed patients such as the BMT population, and have a significant impact on patient outcome. Effective therapy of non-Candida fungal infections remains difficult. Early aggressive surgical debridement appears to be important in control of localized invasive infections. Prolonged therapy with amphotericin B is the standard of care, although the role of the newer antifungal agents is not yet well-defined. Ancillary roles may also be provided by granulocyte transfusions and the colony-stimulating factors.

Adolescent↗

Candida glabrata Fungemia. Clinical features of 139 patients.

Candida species are now the fourth leading cause of nosocomial bloodstream infection in hospitalized patients, and non-Candida albicans species now surpass Candida albicans. The clinical features of the most common non-Candida albicans species, Candida (Torulopsis) glabrata, have not been well studied. We retrospectively reviewed the clinical features of 139 patients with C. glabrata blood-stream infection over a period of 7 years. The mean age of patients was 62 years, and the most common admitting diagnoses were malignancy (28%) and coronary artery disease (18%). The most common identified portals of entry were abdominal (22%) and intravascular catheters (16%). At the time of fungemia, 63% of patients had fever, 45% had change in mental status, and 30% were in septic shock. Three of 50 patients examined by an ophthalmologist had chorioretinitis. The overall hospital mortality was 49%. Factors associated with increased mortality in a regression model were prior abdominal surgery (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.2-6.3, p = 0.01), and an elevated creatinine (OR = 2.2; 95% CI = 1.0-4.7, p = 0.05). When early deaths (< or = 72 hours) were censored, amphotericin B treatment and total dose were associated with reduced mortality (OR = 0.2; 95% CI = 0.1-0.4, p < 0.001). Nosocomial C. glabrata fungemia is not just a disease of debilitated and neutropenic patients, but affects a wide variety of patients and is associated with a high mortality.

Aged↗

Candida infection of local necrosis in severe acute pancreatitis is associated with increased mortality.

The aim of this study was to evaluate the frequency of Candida infection of pancreatic necrosis in patients suffering from severe acute pancreatitis (SAP) and to analyze its impact on the outcome. Two-hundred and fifty consecutive patients with SAP from January 1986 to December 1998 were studied retrospectively. Their mean APACHE II score at the day of admission was in 16.1 (range 8-35). All patients were in need of operative therapy. Overall mortality was 38.8% (97 patients). One-hundred and eighty-two patients (72.8%) suffered from local infected necrosis. Among these patients, local Candida infection was observed in 31 patients, whereof 23 patients (74%) suffered from local fungal infection detected at first operation. During the course of disease, 12 patients (39%) also revealed fungemia. Local Candida infection as compared to no Candida infection was associated with an increased mortality rate (84% vs. 32%; P 0.0001). Multivariate logistic regression analysis identified APACHE II score (P < 0.0001), age of the patient (P < 0.003), extent of pancreatic necrosis (P < 0.002), and local bacterial (P < 0.04) and fungal infection (P < 0.004) as independent factors significantly contributing to mortality. SAP, requiring surgical treatment, is associated with high in-hospital mortality. Patients suffering from local Candida infection are at high risk of fatal outcome.

Adolescent↗

Candida oesophagitis with hepatitis C virus: an uncommon association.

Candida oesophagitis is an acquired immune deficiency syndrome (AIDS)-defining illness. We report a 28-year-old woman who presented with Candida oesophagitis with underlying chronic hepatitis C. The patient presented with anorexia and weakness and was noted to have raised serum transaminases. Upper-gastrointestinal endoscopy revealed Candida oesophagitis involving the whole oesophagus. Oesophageal biopsy demonstrated changes consistent with Candida oesophagitis. Serology was positive for hepatitis C antibodies, and polymerase chain reaction (PCR) genotyped hepatitis C virus (HCV) as genotype 3. Liver biopsy revealed chronic hepatitis with moderately active portal inflammation. A human immunodeficiency virus (HIV) test was non-reactive for types 1 and 2. The development of Candida oesophagitis in a patient with chronic HCV infection demands prompt consideration of general debility and immunosuppression as effects of HCV that led to an occurrence of opportunistic infection. Evaluation of this case provides insight into various mechanisms of immune suppression associated with HCV infection.

Adult↗

Candida as a risk factor for mortality in peritonitis.

OBJECTIVE: The clinical significance of Candida cultured from peritoneal fluid specimens remains a matter of debate. None of the studies that have addressed this issue have clearly distinguished between community-acquired peritonitis and nosocomial peritonitis. The current study tried to differentiate the pathogenic role of Candida in these two clinical settings and assess its importance on outcome. DESIGN: A multiple-center, retrospective, case-control study was conducted in intensive care unit patients. The interaction between mortality rates and type of patients was assessed. In the case of a significant interaction, a separate analysis of mortality and morbidity was planned. SETTING: Seventeen intensive care units in teaching and nonteaching hospitals. PATIENTS: Cases were patients operated on for peritonitis with Candida cultured from the peritoneal fluid, whereas controls were operated patients free from yeast. Cases and controls were matched for type of infection, Simplified Acute Physiology Score II, age, and time period of hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The following characteristics were collected: demographic variables, underlying disease, severity score, site of infection, microbiological features, and anti-infective treatments. Survival was defined as the main outcome criterion and morbidity variables as secondary criteria. Odds ratios of mortality were calculated. Matching was achieved in 91 cases and 168 controls. Matching criteria, clinical characteristics, and mortality rate were not statistically different between cases and controls. A significant interaction was demonstrated between mortality rates and type of infection, leading to separate analysis of patients with community-acquired peritonitis and nosocomial peritonitis. The subgroup analysis demonstrated an increased mortality rate only in nosocomial peritonitis with fungal isolates (48% vs. 28% in controls, p<.01). Upper gastrointestinal tract site (odds ratio, 4.9; 95% confidence interval, 1.6-14.8) and isolation of Candida species (odds ratio, 3.0; 95% confidence interval, 1.3-6.7, p<.001) were found to be independent risk factors of mortality in nosocomial peritonitis patients. CONCLUSIONS: Isolation of Candida species appears to be an independent risk factor of mortality in nosocomial peritonitis but not in community-acquired peritonitis.

Aged↗

Evaluation of the discriminatory power of pulsed-field gel electrophoresis and PCR fingerprinting for epidemiologic typing of Candida species.

OBJECTIVE: To evaluate the discriminatory power of genotyping methods (PCR fingerprinting and pulsed-field gel electrophoresis) validated for Candida albicans in other Candida species. METHODS: Molecular typing methods are increasingly being applied for studies where the interpretation of data essentially relies on the typing results rather than epidemiologic data. In this situation, the discriminatory power (ability to identify differences among epidemiologically unrelated strains) of the typing method is important in allowing one to draw valid conclusions. By applying PCR fingerprinting, electrophoretic karyotyping, and restriction fragment endonuclease analysis using standard restriction enzymes and primers proven to be useful in previous studies, we evaluated whether the use of multiple genotyping methods is sufficient to delineate known unrelated strains among seven Candida species. RESULTS: All three methods identified individual genotypes for each of the seven Candida species studied. However, optimal strain delineation required the combined use of all three typing methods and was observed only within the small number of C. albicans and C. tropicalis isolates tested in this study. CONCLUSION: Typing assays that are able to delineate a certain Candida species may not be used blindly for other species of that genus. Regarding the limited number of strains tested, further validation of the discriminative power of genotyping methods (including in C. tropicalis) should be done.

Journal Article↗

Studies of Candida serology in denture stomatitis patients.

The aim of the study was to determine the humoral antibody response to Candida by means of hemagglutinin and precipitin tests and to correlate these results to yeast colonization in the oral sites and feces and to the relapse tendency after treatment; and furthermore, to evaluate whether Candida serology can serve as a tool to predict a denture stomatitis risk group. The serologic tests were performed by means of passive hemagglutination (HA) and immunoelectroosmophoresis (counterimmunoelectrophoresis, CIE) tests in 51 denture stomatitis patients and compared with 25 individuals in the reference group. There were significantly more patients with increased hemagglutinin titers (pos. greater than or equal to 1:160) to Candida albicans polysaccharide (mannan) antigen and/or precipitin to crude C. albicans cytoplasmic antigen in serum (P less than 0.01) than in the reference group. In the denture stomatitis group there was no correlation between the presence of hemagglutinating and precipitating Candida antibody in serum and the parameters yeast colonization of the oral sites/feces, yeast score on the denture base and palatal erythema score. After local oral antimycotic treatment there was no significant change in the serum Candida hemagglutinin titers and serum precipitins. Serologic tests might be useful as a guidance in a selected group of patients for continued prosthetic treatment and as a prognostic instrument.

Adult↗

Antifungal activity of amphotericin B, fluconazole, and voriconazole in an in vitro model of Candida catheter-related bloodstream infection.

The activity of five simulated antifungal regimens for eradication of catheter-related bloodstream Candida infection was evaluated with an in vitro pharmacodynamic model. Single-lumen central venous catheters were colonized with Candida species by sequentially incubating central venous catheters in plasma and then in growth medium (RPMI plus morpholinepropanesulfonic acid) containing a standardized suspension (10(5) CFU/ml) of Candida albicans, Candida glabrata, or slime-producing Candida parapsilosis. Colonized central venous catheters were then placed in a one-compartment pharmacodynamic model where five antifungal regimens (plus control) were simulated: amphotericin B, 1.0 mg/kg every 24 h; amphotericin B, 0.5 mg/kg every 24 h; fluconazole, 400 mg every 24 h; fluconazole, 800 mg every 24 h; and voriconazole, 4 mg/kg every 12 h. During exposure to the simulated clinical regimens, samples were serially removed from the model over 48 h for quantitation of viable organisms. All antifungal regimens suppressed fungal counts by both peripheral and catheter sampling versus control (P = 0.001). Overall, antifungal activity ranked amphotericin B (1 mg/kg) > amphotericin B (0.5 mg/kg) > or = voriconazole > fluconazole (800 mg) > or = fluconazole (400 mg). No regimen, however, completely eradicated (by culture and electron microscopy) central venous catheter colonization. Regrowth was noted in the model during therapy against C. glabrata and C. parapsilosis but was not associated with an increase in the MICs for the isolates. Lack of in vitro antifungal activity against biofilm-encased organisms appeared to be the primary reason for mycological failure of antifungal regimens in the model.

Amphotericin B↗