Candida Meningitis/Course, Prognosis and Mortality before and after Introduction of the New Antimycotics. Die Candida Meningitis: Verlauf, Prognose und Letalität vor und nach Einführung der neuen Antimycotica

Summary: Screening of all the cases of Candida meningitis accessible to the authors from the literature of the last 40 years has shown that amphotericin B and 5-fluorocytosin have lowered the mortality rate by 7 1/2 times compared with the period before 1958. The combination of amphotericin B and 5-fluorocytosin is significantly more effective than amphotericin B alone and seems to bring the mortality rate down to almost nil. The number of cures without residual mental handicap has however only doubled. Of the survivors, almost one-third still suffer long-term damage as a result of this disease, a proportion similar to that recorded in the pre-antimycotic era.
Zusammenfassung: Die Sichtung sämtlicher den Verfassern zugänglichen Candida-Meningitiden der Literatur der letzten 40 Jahre hat gezeigt, daß Amphotericin B und 5-Fluorocytosin die Sterblichkeit, verglichen mit der Zeit vor 1958, um das 7 1/2-fache gesenkt haben. Die Kombination von Amphotericin B und 5-Fluoro-cytosin ist bedeutend wirksamer als die Applikation von Amphotericin B allein und scheint die Letalität sogar gegen Null zu verschieben. Die Heilungen ohne Defekt sind aber nur um das Doppelte angestiegen. Von den überlebenden trägt auch weiterhin fast ein Drittel Spätschäden davon, ähnlich wie in der vor-antimycotischen Aera.     

Candida guilliermondii var. guilliermondii Infection in Infertile Women: Candida guillievmondii var. guilliermondii-Infektionen bei unfruchtbaren Frauen

The sera of 263 women--217 infertile and 46 pregnant--were examined by various serological methods (precipitation test, agglutination, indirect immunofluorescence) to detect Candida guilliermondii var. guilliermondii (C.g.) infection. The precipitation reaction was performed with extracellular C. guilliermondii antigen, the agglutination reaction was employed parallel with C. albicans. In the infertile group 122 (56.2%) proved to be C.g. positive, while in the fertile 11 women (23.9%) proved to be so, the level of significance being p less than 0.0001 between the two groups. A one-month ketoconazole treatment (one tablet, 200 mg/day) was adequate for eliminating the C.g. infection. In a few cases hystological examinations were also performed according to Gomori-Grocott and yeast cells could be detected in the stroma of the ovary. IgA, IgG, IgM, Gc-globulin, transferrin and ferritin determinations were carried out before and after the ketoconazole treatment, and there were significant differences in the IgM and transferrin levels between the infected and non-infected groups. The authors achieved 5 pregnancies of 56 treated women in 6 months.     

Prevalence and Role of Candida in Acute Gastroenteritis (Choleraic and non-choleraic)

Candida species were isolated and identified from the stool samples of cholera and non-dioleraic acute gastroenteritis (GE) cases. From 500 samples (398 from GE and 102 from cholera cases) 129 strains of Candida were isolated. The total rate percentage of Candida in both the groups varied from 25–26 %.
The incidence of Candida in GE was higher in children from 1–4 years whereas in cholera cases the incidence was higher in the group from 5–9 years.
On statistical analysis it was found that the association of C. albicans and C. tropicalis with gastroenteritis, either choleraic or non-choleraic, bears no significance to the disorder. Complete dissociation of the species of C. albicans and C. tropicalis was found in the stool samples of the two groups of gastroenteritis cases.

Zusammenfassung

Candida -Arten — 129 Stämme — wurden aus Stuhlproben von Patienten, die an Cholera (102 Fälle) oder an einer akuten Gastroenteritis (398 Fälle) erkrankt waren, isoliert und identifiziert. Bei beiden Patientengruppen lag der Prozentsatz des Candida -Nachweises zwischen 25 bis 26 %. Das Sproßpilzvorkommen lag bei 1–4 Jahre alten Kindern nit einer Gastroenteritis höher. Bei der Vergleichsgruppe der Cholera-Kranken waren vermehrt Sproßpilze bei 5–9 Jahre alten Kindern nachzuweisen.
Statistische Berechnungen zeigten keine Verbindung zwischen Candida albicans - und Candida tropicalis -Nachweis zu den Cholera- oder nicht Cholera-bedingten Gastro-enteritiden. Die beiden Candida -Arten wurden in keinem Fall gemeinsam aus einer der Stuhlproben gezüchtet.     

Nicht übliche opportunistische Mykosen bei Immundefekt/Uncommon Mycoses with Immunodeficiencies

Zusammenfassung: Die Autoren beschreiben die Entwicklung der durch saprophytische und bedingt pathogene Pilze verursachten Mykosen sowohl bei einem primären und sekundären Defekt im Bereich der humoralen und Zellimmunität als auch bei einer vorübergehenden Stöning der Immunmechanismen.
Es handelte sich um rekurrente chronische, gegen die Therapie resistente vaginale Mykosen, urn Magencandidosen und um eine Aspergillose der Haut. Die Labordiagnostik besteht in mykologischen (Direktpräparat, Kultur), serologischen und allergologischen Untersuchungen.
Die Möglichkeit der Entstehung weiterer opportunistischer Mykosen, der mucocutanen Candidose, der Cryptococcose sowie mykotischer Erkrankung bei Transplantationen und Geschwulstkrankheiten wird diskutiert.
Summary: The authors studied the development of mycoses caused by saprophytic and opportunistic fungi. These infections were promoted by primary or secondary deficiencies of the humoral or the cell mediated immunity. Transient disturbance of immune defense mechanisms may also predispose to fungal infections.
The mycoses studied were therapy-resistent chronic, recurrent vaginal candidoses, candidoses of the stomac and an aspergillosis of the skin. Laboratory diagnosis in these cases was based on mycological (direkt microscopy and culture), serological and allergological investigations.
The possibility of development of other opportunistic mycoses — mucocutaneous candidosis, cryptococcosis, mycoses in patients with organ transplantation or with malignant tumours — is discussed.     

Four cases of Candida albicans infections with isolates developing pink colonies on CHROMagar Candida plates

Candida albicans, the most commonly isolated yeast species, is typically identified by its green colony-colour on CHROMagar Candida plates. We here report four cases of Candida albicans infections, in which the initial identification was non-albicans isolates due to a clear pink colour of the colonies on CHROMagar Candida plates. However, classical phenotypic criteria, biochemical assimilation pattern and molecular characterisation identified all four isolates as C. albicans isolates.     

Zum Vorkommen von Hefen in der tiefen kariösen Kavitation*

Zusammenfassung: Nach einzeitiger und schrittweiser Caries profunda-Therapie an Milchmolaren 6 bis 7 Jahre alter Kinder wurde die Mikroflora des Kavitätenbodens bestimmt. Von 47 Patientenpaaren mit röntgen-topographisch vergleichbaren kariösen Kavitationen unterer zweiter Milchmolaren wurde unter aseptischen Kautelen erweichtes und hartes Dentin entnommen. Hefen wurden in 5, 6% der Dentinproben isoliert. Sie bestimmen das ätiopathogenetische Geschehen nur im Einzelfall. Summary: The presence of microorganisms of the cavity floor in primary molars in children aged six to seven was investigated after one-step or stepwise excavation of deep carious lesions. Softened and hard dentine was excavated under aseptic operating technique from 47 pairs of outpatients with radiographically comparable cavitations. Yeasts were isolated in 5, 6 % of the dentinal samples. They determine the etiopathogenic process only in single cases.     

The Significance of Candida pulcherrima Findings in Human Clinical Specimens: Die Bedeutung von Candida pulcherrima-Befunden in klinischem Untersuchungsmaterial vom Menschen

From 1971 to 1976 the author examined by cultivation on Sabouraud glucose agar, 1720 specimens of the most varied materials--skin scales, nails, hair, beard, sputum--obtained from patients suffering from skin problems. In no one single case did he find Candida pulcherrima. However, since 1977 he has found C. pulcherrima to be on an increase. From 1977 to 1984 in 4644 specimens C. pulcherrima was found in 44 cases. 38 strains, i.e. 86%, were isolated from patients with clinical diagnosis of mycotic infection. The most frequent diagnosis was onychomycosis, 36%. Cultivation findings were mostly profuse and massive relative to the number of germs, in some patients even occurring repeatedly. In view of these findings it may be necessary to revise the views purporting the finding of C. pulcherrima from human material to be insignificant.     

A case of Candida parapsilosis endocarditis

The authors report a case of Candida parapsilosis endocarditis in a non-drug-addicted young patient who, 6 months before the manifestation of endocarditis, was submitted to cardiac surgery. This is the first report from Greece and the second found in the accessible literature.     

Candida endocarditis in neonates: report of five cases and review of the literature

Candidal endocarditis is an uncommon and serious complication of invasive Candida infection in neonates. The aim of this study was to further characterise candidal endocarditis in neonates. Between 1995 and 2000, 56 patients were diagnosed with Candida bloodstream infections (CBSI) in the Neonatal Intensive Care Unit of Schneider Children's Medical Center of Israel. Five of them (9%) developed mycetoma of the right atrium. None of the patients had congenital heart disease or a central venous catheter in the right heart at the time of diagnosis. All were treated with amphotericin B alone or in combination with other antifungals, without surgical intervention. One patient died of the disease and one died later of polymicrobial sepsis and necrotizing enterocolitis. A review of the literature since 1980 yielded an additional 25 cases of candidal endocarditis. For the whole sample (n = 30) survival rate was 73.1%. Six of the 10 patients treated with antifungal agents and surgery survived (60%), compared with 13 of the 20 patients treated only medically (65%) (P = 1.0). Candida endocarditis in neonates differs from fungal endocarditis in adults in risk factors, clinical presentation and outcome. As the outcome of surgical and medical treatment are comparable, antifungal therapy alone may be a valid therapeutic option in high-risk cases.     

Candida africana and its closest relatives

Candida africana is a recently described opportunistic yeast pathogen that has been linked to vaginal candidiasis. This yeast was first described, in 1995, as atypical chlamydospore‐negative Candida albicans strain, and subsequently proposed as a new Candida species on the basis of morphological, biochemical and physiological characteristics clearly different from those of typical C. albicans isolates. Phylogenetic studies based on the comparison of ribosomal DNA sequences demonstrated that C. africana and C. albicans isolates are too closely related to draw any conclusions regarding the status of a new species. Therefore, on the basis of these studies, some authors considered C. africana as a biovar of C. albicans even if genetic differences may be found if additional regions of genomic DNA are sequenced. The taxonomic situation of C. africana and its phylogenetic relationship with other Candida species is still controversial and remains, at present, a matter of debate. Our goal is to review the current knowledge about C. africana and highlight the development of rapid and accurate tests for its discrimination from C. albicans, Candida dubliniensis and Candida stellatoidea. Furthermore, through the analysis of literature data, we have found that C. africana has a worldwide distribution and a considerable number of features making its study particularly interesting.     

The Chlamydospore of Candida albicans.

Summary:  The chlamydospore of Candida albicans is a disputable growth from the point of view of its development and function. On the basis of light microscopic as well as scanning electron microscopic (SEM) investigations difficulties of distinguishing chlamydospores and their holding structure are discussed by the authors. Attempts are made to draw conclusions from some morphological properties on the ancient, reproductive organ function of the chlamydospores.
Zusammenfassung:  Die Chlamydospore von Candida albicans ist ein Formelement, dessen Entwicklung und Funktion umstritten ist. Auf der Grundlage von licht- und rasterelektronenmikroskopischen Untersuchungen werden die Schwierigkeiten der Unterscheidung der Chlamydosporen und ihrer Trägerapparate von den Autoren diskutiert. Es wird versucht, aus einigen morphologischen und physiologischen Eigenschaften auf die ursprüngliche, reproduktive Organfunktion der Chlamydosporen zu schließen.     

Das Vorkommen hefeartiger Pilze in menschlicher Galle

Summary:  The influence of the drinking cure on yeast-like species and their number in the bile of patients suffering gall-bladder diseases was followed up. The majority of identified species was Candida albicans in 76%, and C. parapsilosis in 13%; some individual strains of C. langeronii, C. viswanathii, C. iberica, C. pseudotropicalis, C. lusitaniae and Geotrichum candidum were found. Only one species of the genus Candida occurred in the majority of bile samples, but in five cases two different species appeared and in one case also three species of yeasts. The number of colonies did not surpass 10 in 1 ml of the bile, only in 5 cases was the number of colonies in 1 ml of the bile higher then 100.
Zusammenfassung:  Es wurde der Einfluß von Trinkkuren auf das Vorkommen und die Konzentration hefeähnlicher Pilze in Gallenproben von Patienten untersucht, die an Gallenkrankheiten litten. In den meisten Proben wurde Candida albicans (76%) und Candida parapsilosis (13%) gefunden, verein-zelt auch andere Candida -Arten wie C. langeronii, C. lusitaniae, C. iberica, C. viswanathii, C. pseudotropicalis , in einem Fall auch Geotrichum candidum. Die Gallenproben enthielten meist nur eine Pilzart, in 5 Fällen jedoch zwei Arten, in einem Fall sogar drei. Die Konzentration überschritt nicht 10 Hefezellen pro ml, nur in 5 Fällen war die Konzentration größer als 100 Hefen pro ml Galle.     

Penetrating gastric ulcer as a cause of mixed bacterial and fungal pericarditis

We describe a case of pneumopyopericarditis caused by a mixture of fungal and bacterial pathogens. This originated from a gastric ulcer (within a hiatus hernia) which had eroded into the pericardial sac. Further complications included the late discovery of the ulcer and asplenism. Similar cases have been reported, but to the best of the authors' knowledge, none with an actual mixture of the two pathogens.     

Incidence and outcome of early Candida peritonitis after liver and pancreas transplantation

Candida peritonitis is a potentially life‐threatening infection after abdominal transplantation, although there is scant information regarding its incidence and outcome. We analysed the incidence rate and outcome of Candida peritonitis in 717 liver or pancreas transplant recipients. Five cases of Candida peritonitis were diagnosed, representing the second most frequent cause of invasive fungal infection in the cohort. The incidence rate of Candida peritonitis during the first 30 days after transplantation was 6.5 cases/10 000 transplant days in pancreas recipients and 1.2 cases/10 000 transplant days in liver recipients (P = 0.035). Four of the five patients received an echinocandin in combination with other antifungal. All patients were alive and with good graft function at 1‐year follow‐up. In our series, Candida peritonitis in liver and pancreas transplant recipients was not uncommon and had a good prognosis.     

Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001‐2007)

BACKGROUND:

The incidence, epidemiology, Candida species distribution, resistance patterns, and outcome of candidemia in high‐risk hematologic malignancy and/or stem cell transplantation patients have not been extensively described since the introduction of new antifungal agents.

METHODS:

In this retrospective study, the authors reviewed the medical records and microbiologic data of hematologic malignancy patients with candidemia at The University of Texas M. D. Anderson Cancer Center from March 2001 to February 2007.

RESULTS:

The authors analyzed 173 episodes of candidemia (170 patients), 125 (72%) of which were breakthrough cases after prior antifungal agents, mainly fluconazole (28 [22%]), caspofungin (25 [20%]), and voriconazole (18 [14%]). The incidence of candidemia (per 100,000 inpatient days) remained relatively stable, from 13.9 in 2001 to 19.2 in 2006. However, compared with the findings of previous studies at the authors' institution, the frequency of Candida glabrata and C. krusei infection decreased (to 5% and 17%, respectively) and C. parapsilosis (24%) and C. tropicalis (21%) increased. C. parapsilosis fungemia was associated with prior caspofungin use (P < .001). The overall 30‐day crude mortality rate was 38%, and the attributable mortality rate was 19%, similar to previous findings at the authors' institution. The Candida species associated with the highest mortality rate was C. glabrata.

CONCLUSIONS:

Despite the widespread use of antifungal prophylaxis and the introduction of new antifungal agents, the incidence and associated mortality rates of candidemia remained stable in high‐risk hematologic malignancy patients. However, its epidemiological characteristics have shifted, with C. parapsilosis and C. tropicalis becoming more common. Cancer 2009. © 2009 American Cancer Society.     

Effects of Two Stains on Blastoconidia of Candida albicans: Scanning Electron Microscope Studies. Wirkungen von zwei Farbstoffen auf die Blastosporen von Candida albicans: Untersuchungen mit dem Rasterelektronenmikroskop

Summary:  The authors report observations using scanning electron microscopy (S.E.M.) of cell morphological alterations induced by two stains (crystal violet and malachite green) in cultures of Candida albicans. A marked ultrastructural polymorphism was found. Thus it is suggested that the two stains induced a cellular suffering of the mycete whose functions are then inhibited.
Zusammenfassung:  Die Verfasser berichten über die morphologischen Veränderungen, die von den Farbstoffen Kristallviolett und Malachitgrün bei pathogenen Candida albicans-Stämmen verursacht werden. Auffälliger ultrastruktureller Polymorphismus wurde bei den Sproßzellen festgestellt. Es wird angenommen, daß durch den Farbstoffkontakt die Sproßzellen biologisch inaktiviert werden.     

On the Incidence of Yeast Species from Human Sources in Finland: V. Yeasts Occurring in Mixed Cultures with Dermatophytes, or with Other Yeast Species

Summary: This report is an addendum to part IV (see Mykosen 23) of a survey on yeasts isolated from 16 460 out of 54 635 specimens examined in the years 1960–1976 at the Mycological Laboratory of the Department of Dermatology, University of Turku. A combination of yeasts and dermatophytes, growing simultaneously, was demonstrated in 98 cultures from the inguinal and genitofemoral area in subjects suffering from tinea cruris. The dermatophytes were chiefly Trichophyton rubrum (53 cases) or Epidermophyton floccosum (35 cases), other species were uncommon. The most frequent species among the yeasts involved was Pityrosporum ovale, found in about 50% of the mixed cultures. Candida albicans occurred together with dermatophytes only in 18% of the cases, although it was demonstrated from the same area in 52% in intertriginous conditions without tinea infection. In cases of tinea pedis dermatophytes were somewhat more commonly found together with yeasts. A survey of 545 mixed cultures isolated from toe webs and nails is shown in table 2. The yeast species most frequently involved were C. parapsilosis (141), Tr. cutaneum (66), C. guilliermondii (59), T. famata (58), and C. albicans (57). Simultaneous occurrence of two yeast species was found in the webs of 168 females and 219 males, and in the nails of 227 females and 79 males. Mixed growth of 3 or 4 yeast species was found from toe webs in 32 cases, and from nail scrapings in 18 cases. No less than 180 different combinations between the yeasts were encountered. Zusammenfassung: Die bereits in Mykosen 21–23 (als Teile I–IV) erschienene Übersicht über das Vorkommen von Hefearten beim Menschen in Finnland wird hier abschließend mit einem Verzeichnis der verschiedenen Mischkulturen ergänzt. Bei inguinalen bzw. genitofemoralen Epidermophytien (Tinea cruris) wurde ein gleichzeitiges Wachstum von Faden- und Sproßpilzen 98mal demonstriert. Die häufigsten Fadenpilze waren Trichophyton rubrum und Epidermophyton floccosum. Unter den Hefen war Pityrosporum ovale die vorherrschende Art. Candida albicans, die sonst in diesen Regionen bei intertriginösen Zuständen ohne Fadenpilze am häufigsten (d. h. in 52% der Fälle) vorkommende Hefe, wurde dagegen in den gemischten Kulturen nur in 18,4% der Fälle gefunden. Bei Fuß- und Nagelmykosen kam eine Kombination von Faden- und Sproßpilzen 545mal zur Beobachtung (Tabelle 2). Am häufigsten beteiligt unter den Hefen waren dabei C. parapsilosis (141mal), Tr. cutaneum (66), C. guilliermondii (59), T. famata (58), und C. albicans (57mal). Eine Mischkultur von zwei nebeneinander wachsenden Hefearten wurde aus den Zehenzwischenräumen von 168 Frauen und 219 Männern, sowie aus den Nägeln von 227 Frauen und 79 Männern gezüchtet (Tabelle 3). Ein Gemisch von 3 oder 4 Hefearten wurde in den Kulturen 18mal aus Nägeln und 32mal aus der Interdigitalhaut demonstriert. Insgesamt wurden wenigstens 180 verschiedene Kombinationen von gleichzeitig vorkommenden Hefearten festgestellt. (Eine genaue Zahl kann nicht ermittelt werden, weil einige Kryptokokken und Rhodotorula Sp. nicht näher bestimmt wurden.)     

Performance of the Candida mannan antigen detection in patients with fungemia

For several years, the Platelia Candida mannan antigen enzyme immunoassay (Candida EIA) has been commercially available as a diagnostic test for invasive candidosis. We evaluated the Candida EIA with patients with proven fungemia caused by yeasts from which at least one serum sample was available. Fifty-nine patients with 121 serum samples were included in the study. Sixty-one different yeast strains were isolated from positive blood-cultures. The Candida EIA was positive (n = 35) or borderline positive (n = 8) in 43 of 59 patients with fungemia, resulting in an overall sensitivity of 73%. For the different yeast species, the following sensitivities were calculated: Candida albicans 30 of 39 (77%), Candida glabrata 7 of 11 (64%), Candida parapsilosis 1 of 3, Candida tropicalis 2 of 2, Candida kefyr 2 of 2, Candida lipolytica 0 of 1, Candida lusitaniae 1 of 1, Candida krusei 1 borderline positive of 1, Saccharomyces cerevisiae 1 of 1. In six patients the antigen levels over time were evaluable. In three cases the antigen was positive 3-4 days before the day the blood culture was drawn, in one case on the same day, and in two cases 2 and 5 days afterwards. In conclusion, the Candida EIA was suitable for the detection of fungemia due to the major facultatively pathogenic yeast species. The test was positive in about half of the patients before blood cultures became positive. In these cases, it contributed to an early diagnosis of invasive candidiasis.     

Diagnostische Bedeutung des Candida albicans abtotenden Faktors*

Zusammenfassung: In der vorliegenden Arbeit wird die Methodik des Nachweises des Candida albicans abtötenden Faktors und dessen Bewertung beschrieben. Die Untersuchung wurde an Seren von Patienten, die durch eine invasive Kandidose gefährdet sind und von gesunden Menschen durchgeführt. Der candidocide Faktor wurde bei gesunden Menschen, aber auch bei Asthmatikern, die mit Kortikosteroiden behandelt wurden, weiter bei Kranken mit Niereninsuffizienz und bei Leukämikera festgestellt Zur wesentlichen Reduktion dieses Faktors kam es bei Kranken mit Tumoren, Leberzirrhose und besonders bei Diabetikern. Diese Patienten sind deshalb gegen die invasive Form der Kandidose anfällig, denn Candida-Zellen können sich in ihrem Blut ungestört vermehren. Bei den untersuchten Kranken wurden auch komplementfixierende und präzipitierende Anti-körper vorgefunden, die nut dem erhöhten Vorkonunen von Candida im Infektionsmaterial korrelierten. Diese immunologische Reaktion spricht auch für die parasitische Wirkung der Candida-Pilze. Summary: Proof and evaluation of the candidacidal factor ist described in the sera of patients compromised of invasive candidiasis as well as in the sera of healthy persons. The candidacidal factor was found in the sera of healthy persons, of patients treated with corticosteroids, of patients with leukaemia and kidney insufficiency. The factor was substantially reduced in the sera of patients with cancer, cirrhosis and especially with diabetes mellitus. These patients are therefore sensitive to invasive candidiasis as the Candida cells can multiply uninhibited in the serum. Complement fixing antibodies as well as precipitins were found in the investigated patients. The antibodies were in correlation with the high Candida colonisation of these persons. This immunological reaction agrees with the parasitic effect of Candida in these cases.     

Candida endocarditis: role of new antifungal agents

Despite the relative high frequency of Candida bloodstream infection, Candida endocarditis is a rare entity. We report seven cases, which occurred during a period of 1 year in western France. Six cases were because of Candida albicans , and one pacemaker endocarditis was because of Candida parapsilosis . All patients were men and presented risk factors for candidaemia. Of the six patients with valvular involvement, five received caspofungin and two had surgical valve replacement. Three patients treated with caspofungin antifungal therapy without valve replacement were cured from endocarditis. Antifungal and surgical strategies are discussed, in particular, the possible role of new antifungal therapies and long-term suppression therapy without surgery. One patient died in the acute phase of endocarditis, three patients died of causes unrelated to infective endocarditis and three patients had a favourable outcome.