Nosocomial bloodstream infections in Finnish hospitals during 1999-2000.

Prospective laboratory-based surveillance in 4 Finnish hospitals during 1999-2000 identified 1477 cases of nosocomial bloodstream infection (BSI), with an overall rate of 0.8 BSIs per 1000 patient-days. Of BSI cases, 33% were in patients with a hematological malignancy and 15% were in patients with a solid malignancy; 26% were in patients who had undergone surgery preceding infection. Twenty-six percent of BSIs were related to intensive care, and 61% occurred in patients with a central venous catheter. Sixty-five percent of the 1621 causative organisms were gram positive, 31% were gram negative, and 4% were fungi. The most common pathogens were coagulase-negative staphylococci (31%), Escherichia coli (11%), Staphylococcus aureus (11%), and enterococci (6%). Methicillin resistance was detected in 1% of S. aureus isolates and vancomycin resistance in 1% of enterococci. The 7-day case-fatality ratio was 9% and was highest for infections caused by Candida (21%) and enterococci (18%). The overall rate of nosocomial BSIs was similar to rates in England and the United States, but S. aureus, enterococci, and fungi were less common in our study, and the prevalence of antibiotic resistance was lower.

Bacteremia caused by Brevibacterium species in an immunocompromised patient.

A 46-year-old woman suffering from non-Hodgkin's lymphoma was admitted to the hospital because of high fever. Multiple blood cultures revealed an unusual finding, a Brevibacterium species, which was reisolated 16 days later from the tip of her long-term central venous catheter. This case indicates that Brevibacterium species isolated from normally sterile sites should be considered as a potential pathogen, especially in immunocompromised patients.

Neonatal Salmonella panama infection with meningitis.

Three full-term neonates contracted a hospital infection with Salmonella panama derived from the mother of one. Two had bacteraemia and meningitis; one developed a brain abscess and the other recurrent meningitis at two months. The third neonate had gastroenteritis only. Six months later they had developed normally and two were still excreting salmonellae in the stools.

Immunological and ultrastructural characterization of true histiocytic lymphoma in the northern pike, Esox lucius L.

An epidemic of a malignant neoplasm occurs in northern pike, Esox lucius L., from the Aland Islands of Finland. The neoplasm is morphologically similar to other pike hemic tumors reported in other areas of the world. Pike normal tissues showed evolutionary conservation with the mammalian intermediate filament proteins cytokeratin, desmin, vimentin, neurofilament protein, and glial fibrillary acidic protein; tumor cells are positive for vimentin, suggesting that the neoplasm is of mesenchymal origin. Hemic tissue mononuclear cells undergo polyclonal stimulation by the known mammalian T- and B-lymphocyte mitogens phytohemagglutinin P, concanavalin A, tuberculin-purified protein derivative, and lipopolysaccharide W; pike tumor cells are nonreactive. Pike normal hemic tissue mononuclear cells are variously positive for surface and cytoplasmic immunoglobulins, using rabbit anti-pike immunoglobulin M and cross-reactive mouse anti-carp immunoglobulin M antibodies; tumor cells, however, are not positive. The tumor cells were also diffusely stained with sodium fluoride-sensitive nonspecific esterase. The foregoing suggest that the neoplasm is not of B-lymphocytic or plasmacytic derivation, while the T-lymphocytic as opposed to monocytic derivation cannot be excluded on the basis of marker studies. The ultrastructural studies, however, suggest a neoplasm of histiomonocytic derivation, while the absence of sinusoidal infiltration of tumor cells to head kidney, spleen, liver, or peripheral blood suggests that it is a piscine analogue of human true histiocytic lymphoma. Population dynamics studies indicate that the neoplasm affects primarily sexually mature males 5 to 6 yr of age, but does not at present appear to be a major factor affecting Aland pike populations.

Serum levels of C-reactive protein in patients with pulmonary tuberculosis and malignant tumors of the chest.

Serum C-reactive protein (CRP) concentration was studied in patients with newly diagnosed post-primary pulmonary tuberculosis and in those with malignant intrathoracic tumors. In tuberculosis, there was a wide scatter in CRP values and the mean did not differ from that of the tumor patients. Tuberculous patients with cavitation in chest X-ray had significantly higher levels of CRP than those without as well as healthy controls. Normal CRP did not exclude tuberculosis and all the values were below 100 mg/l.

Cutaneous tumor of northern pike, Esox lucius L. II. Expression of surface and cytoplasmic immunoglobulins and alpha-naphthyl acetate esterase by mononuclear cells from lymphoid tissues and tumor.

Rabbit anti-pike IgM antibodies showed that up to 95% of mononuclear (MN) cells isolated on Ficoll-Isopaque gradients from peripheral blood, spleen, and head kidney of northern pikes carrying cutaneous tumors were surface (SIg) and cytoplasmic (CIg) immunoglobulin positive by indirect immunofluorescence. On the contrary, rabbit anti-winter flounder IgM antibodies gave totally negative results. Monoclonal anti-carp IgM antibodies stained approximately 40-56% of peripheral blood, splenic, and head kidney MN cells in assays for SIg and CIg. Monoclonal anti-rainbow trout IgM antibodies, however, did not cross-react with pike Ig. A maximum of 5% of MN cells from the tumor were SIg and CIg positive by anti-pike IgM as well as 6% by anti-carp IgM antibodies, and were negative by the other two antibodies even at low dilutions. A majority of cells in the tumor exhibited an intense diffuse staining pattern for alpha-naphthyl acetate esterase (ANAE) which was inhibited by sodium fluoride and was reminiscent of that noted in human monocytes. These findings show that the Aland pike neoplasm is not a B cell tumor or plasmacytoma, but more representative markers are needed to demonstrate whether it is of T lymphocytic or monocytic origin.

Arthritis caused by Haemophilus paraphrophilus and isolation of the organism by using an improved culture protocol.

A case of bacterial arthritis caused by Haemophilus paraphrophilus is presented. This is the first reported case of arthritis caused by this organism. Culturing joint fluid in blood culture bottles provides for bacteria that are slow growing or present in small numbers.

Serial study of C-reactive protein during fungal esophagitis and enterocolitis.

C-reactive protein (CRP) responses were followed in weekly serum samples in the course of eight episodes of esophagitis (37 sera) and ten episodes of enterocolitis (45 sera) caused by Candida albicans in an equal number of patients with hematologic malignancies under antibacterial medication. During fungal esophagitis CRP was elevated, with peak values ranging from 73 to 380 mg/l (mean +/- SD: 170 +/- 104 mg/l). The same was true for fungal enterocolitis, with the peak values ranging from 54 to 225 mg/l (mean +/- SD: 146 +/- 56 mg/l). In both these conditions, antimycotic treatment was followed by clinical improvement, reduced or eliminated fungal growth and falling levels of CRP, occasionally down to the normal value (less than 6 mg/l). Thus, follow-up of CRP level is useful as an aid in the diagnosis of gastrointestinal candidosis and in evaluating its treatment.

Cutaneous tumor of northern pike, Esox lucius L. I. In vitro mitogenic responses of mononuclear cells from lymphoid tissues and tumor.

To evaluate functional characteristics of lymphocytes from the northern pike, Esox lucius L., mononuclear cells were isolated by Ficoll-Isopaque gradients from lymphoid organs and cutaneous tumors of normal and tumor bearing pikes. The cells were tested in a lymphocyte proliferation assay in medium supplemented with fetal calf serum or autologous plasma using three concentrations of PHA, Con A, tuberculin PPD, and LPS. Lymphocytes of northern pike could be triggered to DNA synthesis in vitro. However, no clearcut anatomical partitioning of mitogen responses was found, since the mean optimal proliferation indices for each mitogen were similar in blood, head kidney, and spleen, while cells from head kidney, the equivalent of bone marrow, were stimulated as well with the murine T cell mitogens PHA and Con A as with the B cell mitogens PPD and LPS. Tumorous pikes seemed to have an apparently normal lymphocyte population since they responded by blastogenesis as well as normal pikes. Tumor cells exhibited a high basic metabolic rate and reactivity to mitogens was largely lacking.

Prospective study on humoral immune response induced by fungal infection in patients with hematologic malignancies.

To evaluate the immune response in an immunosuppressed population, antibodies against commercially available Candida albicans antigens were prospectively studied during 37 episodes of acute stomatitis caused by C. albicans and 36 episodes complicated by deep-seated mycoses in 62 adult patients with hematologic malignancies. During uncomplicated stomatitis in patients with acute leukemia, the mean peak IgM, IgG and IgA class enzyme-linked immunosorbent assay (ELISA) units differed significantly from the basic level preceding fungal infection. Mean time until peak values was 2.7-3.8 weeks after diagnosis of stomatitis. During systemic mycoses the antibody response was similar. Among patients with other hematologic malignancies, predominantly lymphomas, several were terminally ill and responded infrequently by antibody production. Similar results were given by Ouchterlony immunodiffusion and counterimmunoelectrophoresis. Thus, patients with acute leukemia showed an antibody response to fungal infection; the peak values, however, were somewhat delayed.

Immunological classification of a pike lymphoma.

Monoclonal and polyclonal antibodies against mammalian intermediate filament (IF) proteins were used to demonstrate IF expression in tissues and lymphoma tumors of northern pikes, Esox lucius L., from the Aland Islands of Finland by indirect immunofluorescence microscopy. Frozen sections of pike tissues demonstrated IFs in a manner confirming their evolutionary conservation and subclass specificity. Tumor cells showed morphological resemblance to head kidney cells and were positive for vimentin while negative for cytokeratin, desmin, neurofilament proteins, and glial fibrillary acidic protein. The results show that the neoplasm is a mesenchymal as opposed to an epithelial, muscle, neural, or glial tumor, and is probably hemic cell derived. A rabbit anti-pike IgM antiserum showed that up to 90% of mononuclear (MN) cells isolated on Ficoll-Isopaque gradients from peripheral blood, spleen and head kidney were surface- and cytoplasmic-immunoglobulin positive by indirect immunofluorescence, while a maximum of 5% of tumor cells were positive. A maximum of 5% of MN cells from hemic tissues exhibited rosettes when incubated with AET-treated sheep red blood cells; however, only 1% of cells in the tumor formed rosettes. Lymphocyte proliferation assays were performed on MN cells from hemic tissues and tumor using phytohemagglutinin P, concanavalin A, tuberculin purified protein derivative and lipopolysaccharide W in medium supplemented with fetal calf serum or autologous pike plasma. Proliferation indices in hemic tissues were similar in the groups. However, all proliferation indices in tissues were significantly higher than corresponding values in the tumor. These assays show that pike MN cells respond when stimulated by T and B cell mitogens, but that this reactivity is lacking in the tumor.

Follow-up of antibodies against single-stranded DNA in patients with haematological malignancies.

Antibodies against single-stranded DNA (ssDNA) were followed by enzyme-linked immunosorbent assay in weekly serum samples of 39 patients with acute myeloid leukaemia (AML), 11 with acute lymphatic leukaemia (ALL) and 26 with other haematological malignancies. Their frequency and mean level during the entire follow-up were higher than in sera of healthy blood donors. Patients with AML had the highest levels and prevalence of anti-ssDNA antibodies, i.e. overall frequencies of IgG class antibodies in patients with AML, ALL and other haematological malignancies were 97%, 82% and 58%, respectively. Antibodies of IgM class were less frequently found. Prevalence and levels of anti-ssDNA antibodies were already at least as high in newly diagnosed malignancies as later during the course of the disease. Following bacterial septicaemias, these antibodies were significantly low. No consistent correlations between levels of anti-Candida antibodies formed in response to fungal infections or concentrations of serum immunoglobulins and anti-ssDNA antibodies were found.

Levels of C-reactive protein in patients with hematologic malignancies.

The levels of C-reactive protein (CRP) were assayed in 282 serial sera of 70 patients with hematologic malignancies who were under antineoplastic medication, and surveyed with frequent blood cultures. The mean peak value of CRP in febrile patients with bacteriologically verified sepsis was 162 mg/l and differed significantly (p less than 0.001) from that (23 mg/l) of afebrile patients with negative blood cultures, but not from that (115 mg/l) of febrile patients without confirmed bacteremia. All the values in afebrile patients with negative blood cultures were less than 100 mg/l; 71% of their peak values were less than 40 mg/l. Thus the malignancy itself or its treatment did not considerably mount CRP response.

Susceptibility of fungi in mouthrinse specimens from patients with haematological malignancies.

Fungi isolated from mouthrinse specimens during episodes of acute pseudomembranous fungal stomatitis and deep-seated mycoses in patients with haematological malignancies were tested for susceptibility to seven antifungal agents. Topical treatment of stomatitis with clotrimazole or chlorhexidine did not induce any change in the susceptibility of oral Candida albicans. Treatment of deeper mycoses with 5-fluorocytosine, however, resulted in a significant increase in oral strains resistant to this agent. Of C. albicans strains isolated, 7% were resistant to 5-fluorocytosine greater than 32 micrograms/ml. One patient died of disseminated mycosis during treatment with this drug; the resistant C. albicans was isolated from the mouth, liver, spleen and kidneys. Strains of Torulopsis glabrata and C. krusei resistant to 5-fluorocytosine were also found in some patients. Organisms resistant to 5-fluorocytosine were generally sensitive to polyenes and imidazoles.

Broth dilution and disc diffusion methods in the susceptibility testing of pathogenic Candida albicans against four antimycotics.

Susceptibility of Candida albicans isolated from mouthrinse specimens during episodes of acute pseudomembranous candidiasis in patients with haematological malignancies was tested by the broth dilution and disc diffusion methods using 24 and 48 h of incubation. The time factor did not significantly affect the results with 5-fluorocytosine. With amphotericin B, prolonged incubation doubled the geometric mean MIC of C. albicans as well as the number of isolates with intermediate sensitivity. With the shorter incubation in the disc diffusion assay, few isolates showed lowered sensitivity to clotrimazole; at 48 h, however, this figure was as high as 54%. The yeasts were highly sensitive to ketoconazole at 24 h, whereas at 48 h the results were bizarre. At 24 h, correlations between disc diffusion and broth dilution methods were satisfactory, with clotrimazole and ketoconazole accounting for most of the discordancies. Accordingly, the disc diffusion results should be recorded at 24 h.