Transient Fungemia Research Articles

First Report of Ventriculoperitoneal Shunt Infection due to Cyberlindnera fabianii.

Fungal infections in the central nervous system (CNS) are associated with significant morbidity and death. Transient fungemia in immunocompetent patients without any other risk factors for fungemia has been suggested as a possible mechanism that may lead to serious fungal ventriculoperitoneal (VP) shunt infections, but evidence is lacking. The clinical spectrum, diagnosis, and optimal therapy of Cyberlindnera fabianii infections remain to be determined. We describe the first case of CNS infection due to C. fabianii that occurred in an immunocompetent adult with a VP shunt. Spontaneous translocation with yeast that is not part of the normal gastrointestinal flora in the setting of ingestion of multiple servings of a fermentation product was the likely source from which Cyberlindnera fabianii gained entrance into the VP shunt system, causing meningitis in this patient. The authors conclude that, in view of the high morbidity associated with yeast infection of the CNS, long-term antifungal therapy should be strongly considered in cases where the VP shunt cannot be completely removed. Transient fungemia may lead to invasive disease in an immunocompetent host with VP shunt, even in the absence of any other risk factors for fungemia and even after remote placement of the VP shunt.

Fungal Endocarditis

Conclusion: This case illustrates the need for fungal prophylaxis during invasive gastrointestinal procedures in patients at high risk for endocarditis. A 53 year old man with two previous episodes of bacterial endocarditis resulting in aortic valve replacement and repair was admitted for evaluation of hematemesis. Several days after endoscopy, he developed shortness of breath and a progressive palpable purpuric rash. Studies revealed hypocomplementemia, anemia, thrombocytopenia, elevated creatinine and pleural effusions. Blood cultures revealed Candida parapsilosis. Echocardiography showed vegetations on the native mitral valve and prosthetic aortic valve. Due to the patient's previous valve replacement, he was a poor surgical candidate. Despite aggressive antifungal treatment, the patient's fungemia continued leading to valvular destruction and subsequent death. Fungal endocarditis is a rare, serious disease that often requires cardiac surgery and carries a poor prognosis. The updated American Heart Association guidelines do not address fungal prophylaxis and they no longer recommend routine bacterial prophylaxis for gastrointestinal procedures except in high risk patients. Recent reports show an association between Candida parapsilosis, nosocomial infections, invasive procedures and prosthetic devices. As Candida is normal flora in the upper gastrointestinal tract, endoscopy may lead to a transient fungemia which could seed the cardiac valves. In our high risk patients, prophylaxis for fungal infections during endoscopy may be beneficial. Animal models demonstrated that two doses of fluconazole prevented experimental endocarditis caused by Candida. Amphotericin B has also shown to be successful in preventing fungal endocarditis in animal models. Newer generation echinocandins may be able to achieve the same result with fewer side affects. Guidelines should be interpreted within a clinical context. Fungal prophylaxis of high risk individuals for invasive procedures may prevent unnecessary death.Figure

Autopsy findings in patients with repeated demonstration of Candida glabrata

In our mycological laboratory we saw an increase of Candida glabrata isolates from 0.5% in 1993 to 22.2% in 1996, mainly isolates of high risk patients of intensive care units and oncological wards. We were interested to know whether this increase of C. glabrata is also corresponding to the number of endomycoses. Eighteen patients have been autopsied and examined histologically. During the hospital course we found repeatedly in all patients C. glabrata with or without C. albicans. Serological and culture results of this intensive care/oncological patients were indicative of an invasive endomycosis. In 12 of 18 patients there was no evidence of an invasive mycosis in autopsy tissues. Three patients had a typical aspergillosis of the lungs, which was not diagnosed during hospital course. In 5 patients, two of them with aspergillosis of the lungs, we found in kidney or lung tissue sporadic yeast cells, typified by size and missing pseudomycelium as C. glabrata. In no case a tissue reaction as an intravital defense reaction against these yeast cells was observed. Therefore, we interpreted the findings of C. glabrata in tissues as representing a transient fungemia and not as an endomycosis due to C. glabrata.

Autoimmune arthritis caused by Candida septic arthritis

A 64-year-old woman with spina bifida, chronic paraplegia, chronic renal failure, hypertension, and a history of breast and bladder carcinoma was admitted in August 1991 with fever and chills after an episode in which her permanent catheter was irrigated with urokinase solution. Her initial blood culture grew out Candida tropicalis. Three subsequent blood cultures during the same hospital stay were negative for Candida, and as a result the patient was not treated. The diagnosis was a transient fungaemia. Throughout the next year the patient had intermittent pain in the left shoulder. The pain was not severe enough to require medical attention, and no aspirations of the shoulder were performed. In August 1992, approximately 1 year after the episode of transient fungaemia, the patient presented with progressive swelling, pain, and warmth of the left shoulder. No signs of systemic illness were seen, and no other joints were symptomatic. Routine radiographs were read as normal. Arthrocentesis yielded a large amount of cloudy fluid; Candida tropicalis was grown on culture. This condition was treated with serial aspirations, systemic

Candida tropicalis Vertebral Osteomyelitis: A Late Sequela of Fungemia

Two adult patients who had undergone bone marrow transplantation had transient fungemia due to Candida tropicalis during the posttransplantation neutropenic period and later (at 5 and 14 months post-transplantation) developed vertebral osteomyelitis due to the same organism. The courses of all adult patients who underwent bone marrow transplantation at our center during this time were reviewed for determining the frequency of this problem. Molecular typing techniques were used to establish the relationship between the organisms isolated during the initial fungemia and those causing the subsequent osteomyelitis. Only two of 532 adults who received transplants at our center from 1980 to 1993 developed candidal osteomyelitis. Moreover, they are part of a subset of 13 patients (2.4% of the total) whose cultures were positive for C. tropicalis; five of the 13 had fungemia. The study of fungal isolates from prior sites of colonization and from blood sampled during the original fungemia and of subsequently recovered vertebral bone isolates by means of DNA restriction fragment analysis (with use of standard agarose gel electrophoresis or pulsed-field gel electrophoresis) showed that the colonizing, bloodstream, and bone isolates were identical in each case. Transient C. tropicalis fungemia in severely immunocompromised patients may cause important late infectious complications, including osteomyelitis. Although these initial septic events may appear to resolve easily, the outcome in the two cases in this report suggests that special treatment considerations, such as immediate removal of the central venous catheter and intensive treatment with amphotericin B, may be required in selected cases for prevention of late sequelae.

Transient fungaemia due to Candida, pelliculosa in a patient with AIDS

Candida pelliculosa Redaelli (syn. Hansenula anomala) was isolated from blood cultures of a patient with acquired immunodeficiency syndrome. The transient candidaemia was apparently associated with intravenous drug addiction. The isolate was identified by standard methods such as API 20 C Aux and 16 discs carbon auxanogram. The isolate was sensitive to amphotericin B, 5-fluorocytosine and ketoconazole. This organism adds to the growing list of Candida species associated with acquired immunodeficiency syndrome.

Yeasts in blood cultures: impact of early therapy.

Patients with growth of yeast in blood cultures were analyzed during the 6-year-period 1981-1986, with special regard to predisposing factors, mortality, severity of the disease and therapy. There were 80 isolations of yeasts in blood cultures in 39 patients and Candida albicans was the most common. The majority of the patients in the material had multiple predisposing factors. The overall mortality was 58%. Patients with d disseminated disease had a mortality of 79% in contrast to 32% in patients with transient fungemia. Disseminated disease was more common in surgical patients. The prognosis of patients treated within 4 days from the onset of septic symptoms was significantly better than that of patients with a later start of therapy. On the basis of these results we emphasize the importance of early empiric therapy.

Transient Fungemia in Acute Pulmonary Histoplasmosis: Detection by New Blood-Culturing Techniques

Transient fungemia has been thought to occur with acute pulmonary histoplasmosis in humans, but this has never been confirmed. We report two cases of acute pulmonary histoplasmosis in which transient fungemia was detected by the lysis-centrifugation blood-culturing technique. Both patients had self-limited acute pulmonary histoplasmosis, and neither was treated with antifungal therapy. Follow-up evaluation at three years and at 17 months disclosed no evidence of active pulmonary or disseminated disease. Transient Histoplasma capsulatum var. capsulatum fungemia may occur with acute pulmonary histoplasmosis. Fungemia may be prevented or arrested by an intact immune system or by other factors not yet known.

Isolation of fungi in blood cultures. A review of fungal infections in the western part of Sweden 1970-1982.

Relevant data were analysed from 185 patients treated for various diseases in the Göteborg area, Sweden, between 1970 and 1982 and in whom fungi were isolated in blood cultures. The increase in isolations during the first part of the study seemed to coincide with extended use of central venous catheters. However, with greater awareness of factors contributing to yeast colonization, the annual incidence fell during the latter part of the period. A disseminated fungal infection was found in 45% of cases, with a mortality of 58%. 4/42 patients with transient fungemia died; 3 from concomitant bacterial septicemia. The mortality rate was 30% in patients with antimycotic treatment because of disseminated infection. Candida albicans, followed by C. glabrata, were the most commonly isolated strains (70% and 13%, respectively). C. albicans predominated in patients with fungal endophthalmitis (100%) and in neonatal infections (95%).

C-reactive protein response induced by fungal infections

Serial determinations of C-reactive protein (CRP) were performed by single radial immunodiffusion in four groups of patients with fungal disease in order to determine its use as an aid to diagnosis. Elevated values (17-284 mg/l) of CRP were seen in 13 patients with fungal septicaemia before and/or within a few days after the first positive blood culture. C-reactive protein was not elevated in two patients with transient fungaemia. In 76 per cent (25/33) of deep-seated fungal infections in patients with malignant disorders of the blood CRP increased to 104-380 mg/l. In the remainder values of 36-92 mg/l were seen. In 37 per cent (19/51) of episodes of acute uncomplicated fungal stomatitis in patients with malignant disorders of the blood CRP rose to 110-320 mg/l. C-reactive protein was not found to be raised from the normal value (less than or equal to 6 mg/l) in 6 per cent of the episodes; in the rest, values below 100 mg/l were seen. CRP in 23 patients with acute fungal stomatitis but who were not immunocompromised remained normal. Thus, with regard to its ability to induce high (greater than 100 mg/l) CRP values, deep-seated fungal disease would seem to resemble bacterial rather than viral infection.

Antibodies against antigens of Candida albicans in patients with fungaemia and bacteraemia, studied by ELISA, precipitation, passive haemagglutination and immunofluorescence techniques.

Antibodies against commercially available antigens of Candida albicans were assayed in 54 sera from 24 patients with fungaemia and in 66 sera from 33 patients with bacteraemia. In patients with persistent fungaemia, antibody was found during the week after the fungus was first cultured from the blood, but peak titres did not usually occur until the end of the second week. A significant rise in titre in C. albicans infection was observed in 50% of paired sera tested by passive haemagglutination (PHA), indirect immunofluorescence (IF) and Ouchterlony immunodiffusion (ID). The same percentage was obtained by counterimmunoelectrophoresis (CIE) against candida metabolic antigens, whereas it was increased to 88% when somatic antigens were used. Enzyme-linked immunosorbent assay (ELISA) demonstrated a rise of titre in 25, 75 and 50% of sera in IgM, IgG and IgA assays, respectively. Sera from patients with transient fungaemia demonstrated persistent antibody titres. In paired sera from patients with bacteraemia, ID and CIE titres were low (greater than or equal to 4). There was an increase of candida antibodies in 0-9% of patients by ELISA, ID or CIE and in 18-21% by PHA or IF. Clinically significant fungaemia was most reliably differentiated serologically from bacteraemia by CIE S-antigen and ELISA IgG assays.

Torulopsis glabrata fungemia--a clinical pathological study.

The clinical findings, pathologic features, and outcome were investigated in 46 patients in whom Torulopsis glabrata was isolated in 131 specimens of blood. Nineteen of the patients had only a single positive blood culture and no evidence of systemic yeast infection, while 27 patients had a clinically significant fungemia based upon the occurrence of 2 or more positive blood cultures, or the combination of a positive blood culture and isolation of the organism from a closed body cavity or demonstration of the yeast in tissue sections. The predisposing factors to the development of fungemia included the presence of intravenous lines, indwelling Foley catheters, antibiotics and surgery, especially when the gastrointestinal tract was involved. Only 22% of patients received either steroids or cytostatic agents. Possible portals of entry were suggested by the prior isolation of the organism from urine, sputum, wounds, and central venous catheter tips in most of the patients. Twelve of 27 patients with clinically significant fungemia were treated. The initial mode of therapy in nine patients was removal of intravenous lines because of the clinical suspicion of catheter related sepsis. Seven of the patients improved rapidly and one more after amphotericin B was subsequently administered. Amphotericin B was the initial therapy in three cases. One patient was cured while another died of an unrelated infection. Five patients were not treated although the isolation of T. glabrata had been reported; the fact that the presence of the organism was felt to be unimportant was considered to be a factor in the delay of treatment. In the remaining 10 patients the organism was isolated only after the patient had died. Division of the patients into four groups based upon whether the individuals survived, died of unrelated disease, died with potentially lethal infection, or died with T. glabrata infection significantly contributing to death, revealed a spectrum of disease, certain signs of which appeared to be of predictive value as prognostic indices of survival and severity of the infection. Seven patients with transient fungemia experienced an acute episode of high spiking fever (greater than 102.5 degrees F), rigors and/or hypotension, six of whom improved after the intravenous catheter was removed, suggesting a catheter-related sepsis. In contrast, persistent low grade fever (less than 102.5 degrees F) characterized eight of the nine patients in whom T. glabrata infection was considered either potentially lethal, or contributing significantly to death. A deteriorating clinical course with organ failure was also associated with this latter category of patients. Catheter-induced specticemia was considered in only two patients in this category. The autopsy and clinical findings in this investigation as well as reported experimental studies suggest that T. glabrata is an organism of low virulence. The patients' underlying disease (e.g., neoplasia) and coexisting bacterial infection are the most important factors responsible for death.

Fungal endocarditis: patients at risk and their treatment

SummaryFungal endocarditis is not rare. It usually develops in patients with abnormal or surgically traumatized hearts, to whose blood fungi have gained access, perhaps during temporary (often iatrogenic) impairment of host defences. Although the blood is cleared rapidly, the fungus can establish itself in the endocardium, where it grows slowly. Thus, clinical and laboratory procedures (including blood and urine cultures) that have permitted early diagnosis and treatment of bacterial endocarditis, are not reliable in early fungal endocarditis. Greater reliance must be placed on serological monitoring of patients who have had transient fungaemia and are at risk of endocarditis. The clinician must consider factors that enhance fungal proliferation and invasion and be cognizant of its dangers - even in the absence of clear signs of infection. Prophylactic measures should be employed to protect the patient at risk, including topical, oral and systemic use of appropriate antifungal agents. Early therapy, the extent and duration of which can be determined by (1) obtaining the MIC of transitory blood or urine isolates - which should not be ignored - and (2) monitoring serology, might eliminate early invaders of the endocardium. Sixty-four reported cures of fungal endocarditis caused by Candida, the most common fungal pathogen, are tabulated, 29 were of classic fungal endocarditis requiring surgery, 3 of whom were seen later by others as fatal recurrences. Those treated early (shortly after candidaemia was diagnosed - mostly in patients on treatment for bacterial endocarditis or after cardiac surgery) survived without need for surgical removal of vegetations or valve replacement. Despite strong suggestive evidence that the first 35 patients tabulated had fungal endocarditis, histological proof exists for only a few who had surgery.Cures of endocarditis caused by other fungi are noted. Improved surgical and medical therapy has improved the prognosis even of patients with the far-advanced disease. However, development of classic fungal endocarditis has been reported one or more years after cardiac surgery and late recurrences after intensive therapy of fungal endocarditis, that had led to clinical recovery of 2 years or more, have been reported. Serological monitoring of vulnerable patients might alert the physician to recurrence early enough for efficacy of drug therapy, averting fatal outcome or the need for further surgery.

Serologic tests in the diagnosis of systemic candidiasis: Enhanced diagnostic accuracy with crossed immunoelectrophoreses

In order to assess the diagnostic value of serologic methods in discriminating between colonization and disseminated infection with Candida species, serum samples from 201 consecutive patients receiving parenteral hyperallmentation were examined for the presence of agglutinating and precipitating antibodies to Candida albicans. In these patients, fungal colonization was detected in 50 per cent, transient fungemia in 6 per cent and disseminated candidlasis in 2.5 per cent. Agglutinating antibodies were of no diagnostic value in separating patients with Candida colonization from those with disseminated infection (sensitivity ⩽ 75 per cent, predictive value ⩽ 20 per cent). Serum Candida precipitins were detected by double immunodiffusion (DID) in all five patients with systemic candidiasis (100 per cent sensitivity); however, since only five of 53 patients with precipitins detected by DID demonstrated evidence of systemic candidiasis, the predictive value of the test was unacceptably low (9 per cent). When the serums which were positive by DID were submitted to crossed immunoelectrophoresis (XIE), precipitin bands to antigens other than mannan were obtained in only nine patients, including all five patients with disseminated candidiasis. Thus, detection by XIE of serum Candida precipitins directed against antigens other than mannan was associated with a predictive value of 56 per cent and a sensitivity of 100 per cent. The detection of serum Candida precipitins by DID is a sensitive screening test in patients at high risk for the development of systemic candidiasis; patients with persistently negative precipitins by DID are unlikely to harbor disseminated candidiasis. If precipitin bands are detected by XIE to antigens other than mannan, there is a high likelihood that the patient has disseminated or invasive Candida infection.

FUNGAL ENDOCARDITIS: ANALYSIS OF 24 CASES AND REVIEW OF THE LITERATURE

Fungal endocarditis occurs in heroin addicts, patients who have undergone cardiovascular surgery, and patients who are treated for prolonged periods with intravenous fluids and broad spectrum antibiotics. The organisms associated with endocardial infection differ in each of these groups. Candida parapsilosis is the fungal species most commonly isolated from narcotics addicts, Aspergillus species are most frequently found in patients after cardiovascular surgery, and Candida albicans occurs most frequently in patients who have received prolonged courses of intravenous fluids and antibiotics. Despite the availability of antifungal antibiotics and surgery, over 80% of patients with documented fungal endocarditis die of this infection. Thus, early diagnosis of fungal invasion and prevention of established endocardial infection are essential. Antifungal therapy and/or careful followup should be considered in patients in whom "transient fungemia" is documented by blood culture and serological and untrasonic techniques should be further evaluated as a means of early diagnosis.

Candida serology in open-heart surgery.

SUMMARY Sera from patients who had undergone open-heart surgery were examined for antibodies to Candida albicans by counter-immunoelectrophoresis, immuno-diffusion, immunofluorescence, and agglutination tests. No single test gave an absolute indication of systemic infection or endocarditis, although the immuno-diffusion procedure was the most specific test. A counter-immunoelectrophoresis test is recommended as a screening procedure, provided that positive results are confirmed by other techniques. Postive serological findings in the absence of clinical endocarditis is probably due to transient fungaemia but should alert the clinician to the possibility that endocarditis may develop later. Serological monitoring should be continued for at least 3 years after cardiac surgery.

Cerebral mucormycosis and renal aspergillosis in heroin addicts without endocarditis.

Abstract:The medical complications of narcotic addiction include fungal infections. Although Candida endocarditis is most commonly recognized, it is important to be aware of the occurence of focal infections resulting from transient fungemia with other ubiquitous organisms. A 23-year-old man is repo