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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.

Adult

Fungemia due to Torulopsis glabrata in the compromised host.

Ten episodes of Torulopsis glabrata fungemia occurring in nine patients with terminal illnesses are described. Eight patients had underlying malignancies and one patient had a plastic anemia. Two episodes of fungemia were considered transient since they were clearly related to the administration of intravenous hyperalimentation (IVH). Most patients were adult women and had solid tumors of the genitourinary tract. Contributory factors were: antibiotic therapy (100%), immunosuppressive drugs (75%), abdominal surgery (63%), IVH (50%), neutropenia (38%), and diabetes mellitus (13%). The clinical course was indistinguishable from a severe bacterial infection. However, endotoxic shock was not observed. The infection was rapidly fatal in four patients. In the remaining five patients, the infection was altered favorably by the discontinuation of infected intravenous hyperalimentation catheters. However, tissue invasion by T. glabrata was found in two of these patients who died shortly thereafter from tumor progression. At autopsy, T. glabrata was identified in tissue sections of the lungs, kidneys, and mucosas of the gastrointestinal and genitourinary tracts. In all cases there was tissue necrosis with a minor inflammatory response consisting of mononuclear cells. To our knowledge, this is the single largest series of T. glabrata fungemia ever reported.

Adult

Torulopsis glabrata fungemia secondary to stone colonization.

A case of Torulopsis glabrata fungemia with persistent funguria and pyelonephritis secondary to colonization of renal calculus is presented. The importance of secondary colonization of renal calculi in persistent infection and septicemia is discussed.

Aged

Metastatic lymphoma in the ureter complicated by bacteremia and fungemia.

A 64-year-old woman presented with retroperitoneal lymphoma metastatic to the left ureter. Lymphoma was not diagnosed and her clinical course was not fully explained until after surgery. The lack of superficial lymphoma delayed diagnosis and therefore prevented effective treatment. Her situation became unmanageable when it was complicated by bacteremia (E coli) and fungemia (Candida albicans).

Candidiasis

Nosocomial outbreak of Candida parapsilosis fungemia related to intravenous infusions.

Candida parapsilosis is rarely isolated from blood cultures. Our hospital surveillance detected an increased rate of isolation of C parapsilosis during a four month period. Fourteen postoperative patients receiving intravenous (IV) hyperalimentation and eight burn patients receiving IV albumin were involved. Hectic fever, the major clinical manifestation, was seen in 61% of cases. Therapy in the postoperative patients consisted merely of discontinuing IV catheters and hyperalimentation, while amphotericin B was needed in five of eight burn patients to control persistent fungemia. Epidemiologic analysis identified a source of the organism in the IV-additive preparation room where C parapsilosis was found contaminating a vacuum system. Organisms apparently refluxed into IV bottles when aliquots were removed to accommodate additives. Of 103 patients who received fluids prepared with the contaminated system, 21% became infected with C parapsilosis. Infection surveillance was instrumental in detection and control of the outbreak. Routine guideline should be established to insure the sterility of IV fluids containing additives.

Adult

Detection of experimental bacteremia and fungemia by examination of buffy coat prepared by a micromethod.

Rabbits received intravenous injections of bacteria or fungi, and a comparison was made of the abilities of broth cultures, plating after dilution either in saline solution or in distilled water containing Triton X-100, and buffy coat examinations to detect the organisms in heart blood. The most sensitive method was broth culture. By microscopy or subculture of buffy coat cells prepared by centrifugation of blood in microhematocrit tubes, organisms were rapidly and regularly detected when their viable counts increased to 300--1,000/ml as detected by plating. By micromodification, buffy coat examination is technically easy to perform, and the method is only slightly less sensitive than when a larger amount of blood is used. Thus, it would be ideal for rapid provisional diagnosis of sepsis in patients, e.g., neonates, when the use of only a small blood sample is preferred.

Animals

Fungal infections in renal transplant recipients.

Infection continues to be a major source of morbidity and the major source of mortality in renal transplant recipients who are susceptible to opportunistic infections. We recently reviewed all renal transplant recipients who had fungi cultured during a three year period. C. albicans and T. glabrata were cultured most frequently. Deep fungal infections occurred in many patients and were frequently observed late in the course of bacterial and viral infections. Ten patients had fungemia, and primary fungal pneumonia occurred in eight patients. Three patients had fungal infection of the central nervous system. Three of eight patients with fungal pneumonia and eight of ten patients with fungemia died as a result of their fungus infections. These patients frequently had poor renal function and were receiving high steroid doses or had recently been treated for kidney rejection. One patient with fungal pneumonia and six patients with fungemia had the fungus cultured from a superficial site. Several patients developed fungal infections late in the course of viral or bacterial infections. Amphotericin-B and 5-fluorocytosine remain the mainstays of antifungal therapy.

Adolescent

Successful medical therapy for endocarditis due to Candida parapsilosis. A clinical and epidemiologic study.

A heroin addict with asymmetric septal hypertrophy and persistent fungemia with Candida parapsilosis was treated with amphotericin B and flucytosine (5-fluorocytosine). The diagnosis of endocarditis was based on the subsequent development of a murmur of mitral regurgitation and echocardiographic evidence of prolapse of the posterior leaflet of the mitral valve. Cure was effected with antifungal therapy alone. Thus, when the diagnosis of fungal endocarditis is made early in its course, open-heart surgery may not be needed. To investigate the relative frequency of isolation of C parapsilosis from particular sites, a mycologic survey was conducted in our hospital. Among the isolates of yeasts, C parapsilosis represented 8.0, 17.1, and 26.7 percent of those from all cultured sites, from contaminated intravenous catheters, and from cultures of blood, respectively. Since this trend to cluster in cases of fungemia was not seen with other yeasts, C parapsilosis appears to be more invasive than other species of Candida.

Adult

Infections complicating orthotopic liver transplantation: a study emphasizing graft-related septicemia.

In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant.

Humans

Candida albicans infection of sternum and costal cartilages: combined operative treatment and drug therapy and 5-fluorocytosine.

Two patients with candidal sternal osteomyelitis have been successfully treated by operative debridement and adjuvant drug therapy with 5-fluorocytosine. One patient had developed postoperative candidal wound infection after sternotomy, and the other acquired candidal sternal osteomyelitis following Candida fungemia. The diagnosis, suggested by culture, was confirmed by identification of Candida pseudohyphae in debrided tissue. Histological confirmation of candidal sternal osteomyelitis indicates the need for operative debridement and specific systemic antifungal therapy. The drug 5-fluorocytosine appears to provide effective oral therapy in this situation.

Candidiasis

Overwhelming opportunistic histoplasmosis.

A patient with chronic granulocytic leukemia developed overwhelming histoplasmosis. During massive fungemia, 59% of peripheral blood neutrophils contained yeast forms. Disseminated intravascular coagulation occurred. Histoplasma capsulatum was isolated not only from the patient's tissues and urine, but also from a serum sample submitted to a reference laboratory for serological testing. The microorganism was demonstrated by specific immunofluorescent staining of peripheral blood films. We suggest that histoplasmosis deserves a definite place on the roster of "opportunistic fungi".

Antineoplastic Agents

Endocarditis caused by Torulopsis glabrata.

A case of Torulopsis glabrata endocarditis involving the mitral valve is reported. Endocarditis developed during convalescence from severe abdominal trauma and was associated with fungemia. Morphologically characteristic organisms were present in the mitral valve.

Adult

Venous catheter-associated candidemia.

Fifty-five patients with venous catheter-associated candidemia were seen over a 13-year period. Thirty-five patients recovered from the infection. Twenty-six of these patients became afebrile within 72 hours of catheter removal; none were treated with systemic antifungal agents. Endophthalmitis appeared in four patients, three of whom had significant loss of vision. Nine patients had persistent candidemia following catheter removal and required antifungal therapy; none developed metastatic infection. Twenty other critically ill patients died during fungemia. Two of these patients were found to have Candida endocarditis that arose from previous catheter infections not suspected of being caused by this organism. Prevention of candidemia by proper care of indwelling vascular catheters is the ultimate goal. Appropriate management of the episodes of candidemia that occur may avert serious metastatic complications.

Amphotericin B

Disseminated infection by Fusarium moniliforme during treatment for malignant lymphoma.

Disseminated infection caused by Fusarium moniliforme is described in a 32-year-old granulocytopenic man with malignant lymphoma being treated with cytotoxic drugs and corticosteroids. Infected skin denuded by antecedent severe varicella-zoster infection was the probable source of fungemia. F. moniliforme grows rapidly on common mycological media as a lavender- to violet-colored mold at 25 to 37 degrees C. Its aerial hyphae produce fusoid macroconidia and characteristic fusiform microconidia in chains. The morphology of hyphae in tissue closely resembles species of Aspergillus and is not diagnostically specific. Morphological characteristics which distinguish cultures of F. moniliforme from other medically important species of Fusarium are discussed.

Adult

The clinical significance and management of fever in acute myelocytic leukemia.

In order to optimize the clinical management of fever in acute myelocytic leukemia (AML), our experience with febrile patients during two therapy periods was reviewed. A structured approach to the management of fever was then devised and evaluated during a third period. Among a total of 104 patients with AML, 77 were febrile at presentation. Only agranulocytic patients (15%) had severe infection, while 43% had localized sites which responded to specific antibiotic therapy. The remainder (42%) had fever functionally attributed to leukemia. In contrast, life-threatening infection occurred in most patients (90%) after antileukemic treatment was begun. During the trial therapy period, the empiric use of carbenicillin-gentamicin for fever greater than or equal to 101 degree F during aplasia reduced the incidence of sepsis from 90 to 30% and of bacteremia from 50 to 23%. The fall in the incidence of blood and localized site cultures positive for Pseudomonas aeruginosa from 65 to 15% corresponded to a reduction in the number of distinct organisms per site from 1.6 to 1.0. These data suggest that hematogenously born invasion of infected sites by endogenous organisms has been prevented. Aplastic patients with fever responded to therapy by defervescing (54%) or improving clinically (34%). Stopping antibiotics once started while evaluating persistent fever was detrimental. Although the early empiric use of amphotericin B reduced the incidence of fungemia, its proper use in fever management is yet to be determined.

Anti-Bacterial Agents