Deep, respiratory tract and ear infections caused by Pseudallescheria (Scedosporium) and Microascus (Scopulariopsis) in Finland. A 10-year retrospective multi-center study.

Deep, respiratory tract and ear infections due to Microascaceae (Pseudallescheria, Scedosporium, Microascus or Scopulariopsis) were studied nationwide in Finland during 1993-2002. The data were based on 52,000 fungal cultures that represented about 50% of all such specimens in Finland and included all Finnish cases of profound immunosuppression. There were 39 cases that were re-evaluated as clinically significant, i.e., three pneumonias, two deep pedal infections and five wound infections, 11 sinusitis and 18 ear infections. The pedal infections and most pneumonias occurred in immunocompromised patients. Most cases, except the ear infections, were due to Pseudallescheria boydii. Two patients had lethal P. boydii pneumonia and a deep P. boydii infection of the foot contributed to a third lethal case. Two of the patients with lethal outcomes had received an allogeneic haematopoietic stem cell transplantation (AHSCT). Two patients with haematological malignancies were cured of deep site infections by a prolonged course of itraconazole. Wound, sinus and ear infections were cured or improved by local surgery or topical therapy. There were 0.8-1.7 cases of any type of infection per million inhabitants per year (MY) and 3.4 cases/1000 AHSCT. Mortality associated with Microascaceae in any type of patient was 0.06-0.12 MY.

Roles of group IIA phospholipase A2 and complement in killing of bacteria by acute phase serum.

The complement system is regarded as an important component of the innate defence system against invading bacteria. However, synergistic actions between the complement and the other components of innate immunity are incompletely known. Human group IIA phospholipase A(2) (hGIIA PLA(2)) is an effective antibacterial enzyme in serum of patients with severe bacterial infections. Our aim was to investigate the significance of complement and hGIIA PLA(2) in acute phase serum. Serum samples were collected from patients with acute bacterial infections and from healthy control subjects. We prepared hGIIA PLA(2)-depleted serum by immunoadsorption and inhibited the activity of complement by a specific inhibitor, compstatin. The bactericidal effects of treated and untreated serum were compared by incubating Staphylococcus aureus and Listeria monocytogenes in the presence of serum. Acute phase serum effectively killed S. aureus and L. monocytogenes, and depletion of hGIIA PLA(2) significantly reduced the antibacterial effect. Complement had a weak bactericidal effect against L. monocytogenes. We conclude that hGIIA PLA(2) is the major antibacterial factor in human acute phase serum against the gram-positive bacteria S. aureus and L. monocytogenes, exceeding complement in efficiency.

Measurement of the D-arabinitol/L-arabinitol ratio in urine of neutropenic patients treated empirically with amphotericin B.

The aim of the present study was to evaluate the diagnostic significance of the D-arabinitol/L-arabinitol ratio in urine of neutropenic patients with suspected fungal infection. D-arabinitol/L-arabinitol ratios were determined in 373 serial urine samples of 104 patients with haematological malignancies receiving empirical amphotericin B treatment for suspected invasive fungal infection. Twenty-eight (8%) urine samples obtained from 17 (16%) patients were positive (ratio > or =4). Eight (47%) patients had positive urine samples at the initiation of empirical amphotericin B treatment and the rest from 7 to 30 days after empirical therapy was started. Several urine samples were positive in six patients. Only one of the five patients with candidemia had elevated D-arabinitol/L-arabinitol ratios (persistent Candida krusei fungaemia). Four patients with transient candidemia and seven patients with invasive mould infections were negative. Patients who died during the study period had significantly higher D-arabinitol/L-arabinitol ratios than patients who survived (P=0.0002). Pneumonia was the most common manifestation of infection (53% of patients with elevated D-arabinitol/L-arabinitol ratios) and was associated with an especially high mortality (67%). The present study shows that elevated urine D-arabinitol/L-arabinitol ratios are common in febrile, neutropenic patients. However, the urine arabinitol test did not detect transient candidemia at elevated levels during the course of infection. Furthermore, D-arabinitol/L-arabinitol ratios were often elevated in the late phase of infection only. This contests the use of this test in guiding the initiation of antifungal therapy. The detection of elevated arabinitol levels in neutropenic patients during empirical amphotericin B treatment is associated with poor prognosis.

Fungal colonization of haematological patients receiving cytotoxic chemotherapy: emergence of azole-resistant Saccharomyces cerevisiae.

Fungal colonization during cytotoxic chemotherapy was studied in 42 patients with a recent diagnosis of a haematological malignancy. In total, 2759 surveillance cultures were taken from the nostrils, throat, urine, stool and perineal region. Seven hundred and ninety-six positive surveillance cultures (28.9%) yielded 968 fungal isolates. The rate of fungal colonization did not differ between patients with acute leukaemia, patients with other haematological malignancies and control patients in the same ward at admission (71% vs. 67% vs. 80%). Patients with acute leukaemia were colonized at a significantly lower rate in samples from the throat (32%), urine (10%), stool (45%) and perineum (29%) taken during hospitalization when compared with other haematological patients (respective values 58%, 21%, 67% and 45%; P-values 0.001). This could be attributed to differences in the use of antifungal drugs. Although 21/42 (50%) of our patients had multiple-site fungal colonization at the end of follow-up, only one systemic Candida infection was diagnosed. Extensive use of antifungal treatment may have influenced the low incidence of systemic fungal infections during the follow-up. In addition to Candida species, Malassezia furfur, Geotrichum candidum and Saccharomyces cerevisiae were frequently isolated. The rate of S. cerevisiae isolation increased significantly over time after admission (1%, vs. 18% of isolates, P<0.001), suggesting hospital-acquired transmission. These isolates were highly resistant to azole antifungals (MIC90 128 microg/mL for fluconazole and 16 microg/ml, for itraconazole), and caused persistent multiple site colonization in 12 patients. Extensive use of antifungal agents in a haematological ward may keep the incidence of invasive fungal infections low in spite of heavy fungal colonization. However, there may be a risk of emergence of resistant fungal strains.

Clinical significance and outcome of anaerobic bacteremia.

We retrospectively studied the incidence of anaerobic bacteremia during 6 years (1991-1996) at Turku University Central Hospital (Turku, Finland). The clinical significance of a positive anaerobic blood culture, the effect of a positive culture on the choice of antimicrobial therapy, and the outcome for patients were evaluated. Cultures of blood from 81 patients yielded anaerobic bacteria (4% of all bacteremias). Anaerobic bacteremia was clinically significant in 57 patients (0.18 cases per 1,000 admissions). Only half (28) of these patients received appropriate and effective antimicrobial treatment before the results of blood cultures were reported; for 18 patients (32%), initially ineffective treatment was changed on the basis of the bacteriologic results, and for 11 patients (19%), the treatment was not changed. The mortality in these patient groups was 18%, 17%, and 55%, respectively. Empirical therapy may provide coverage for anaerobes in only half of the patients with anaerobic bacteremia, and failure to pay attention to the results of anaerobic blood cultures may have serious consequences for patients.