Clinical evaluation of cefozopran for infections associated with hematological malignancies

Cefozopran (CZOP) was used as an initial antibacterial therapy for infections in patients with hematological malignancies. CZOP was given at a daily dose of 4 g by drip intravenously to patients who were febrile over 38 degrees C and were suspected as having bacterial infections. As underlying diseases, 8 patients had acute lymphoblastic leukemia (ALL), 9 acute myeloblastic leukemia (AML), 2 aplastic anemia (AA), 2 adult T cell leukemia/lymphoma (ATLL), 28 non Hodgkin lymphoma (NHL), and 2 multiple myeloma (MM). Bacterial infections diagnosed were sepsis in 7 patients, suspected sepsis in 32, bronchitis in 6, pneumonia in 5 and acute peritonitis in 1. Clinical responses among 51 evaluable cases were excellent in 14, good in 15, fair in 3, poor in 19 and the overall response rate was 57%. The overall response rates for AML, ALL, AA, ATLL, NHL and MM were 56%, 63%, 100%, 50%, 50%, and 100%, respectively. Those for sepsis, suspected sepsis, bronchitis, pneumonia and acute peritonitis were 14%, 63%, 100%, 40%, and 0%, respectively. This therapy was effective in 53% (9/17) of patients whose granulocyte count remained below 500/microliter throughout the course of CZOP therapy. Six bacterial and one fungal strains were isolated from blood and sputum of six patients including five sepsis cases; two bacteria were eradicated and bacterial change was observed in one case. As side adverse effects, 10 patients had liver dysfunction, 1 anemia, 2 proteinemia, 1 indirect bilirubinemia, 2 thrombocytopenia, and 1 eosinophilia. We tried to establish a scoring system for the severities of patients with their infections, underlying diseases, treatments for the underlying disease, and granulocyte counts in order to evaluate the efficacy of CZOP more precisely. This scoring system was consisted of three grades; severe, moderate, and mild. CZOP was effective on mild and moderate grades. These results indicate that the initial antibacterial therapy by CZOP is useful for the treatment of mild and moderate grade infections complicated with hematological malignancies.     

MRI in acute transverse myelopathy

Cytokines have been widely tested in clinical trials during recent years and beneficial responses have been observed in a variety of malignant, infectious and autoimmune diseases. Interferon-alpha induces remissions in patients with certain hematological malignancies such as hairy cell leukemia and chronic myelogenous leukemia. A proportion of patients with chronic viral hepatitis is cured upon application of interferon-alpha. Treatment with interferon-gamma reduces the number of infections in patients with chronic granulomatous disease. In addition, several chronic infections with intracellular pathogens also respond to treatment with this cytokine. With the exception of some patients with renal cell carcinoma and malignant melanoma, solid tumors are largely resistant to administration of these cytokines. Cytokine treatment has changed the outlook for a small group of patients with selected chronic diseases. However, clinical experience with cytokines is still limited and only interferons have been tested for treatment of a variety of diseases. Thus, it seems reasonable to expect that more cytokine-responsive diseases might be identified by continued research efforts.     

Bacteremia due to Citrobacter species: significance of primary intraabdominal infection

From 1982 to 1994, 45 patients (1.22 episodes per 10,000 discharged patients) were treated for citrobacter bacteremia at National Taiwan University Hospital (Taipei). All patients had at least one underlying disease. Citrobacter bacteremia most commonly occurred in patients with malignancies (48.9%) or hepatobiliary stones (22.2%). Intraabdominal tumors comprised the majority (59.1%) of malignancies. Bacteremia commonly originated from sites such as the abdominal cavity (51.1%), urinary tract (20%), and lung (11.1%). Polymicrobial bacteremia was diagnosed in 15 patients (33.3%); for nine (60%) of these patients, the source of the infection was intraabdominal. Prior treatment with a third-generation cephalosporin was significantly associated (P < .01) with the development of multidrug resistance among the isolates. The mortality associated with citrobacter bacteremia was 17.8%. Poor prognostic factors included pneumonia, altered mental status on presentation, hypothermia, oliguria, septic shock, deterioration in mental status, hyperbilirubinemia, azotemia, and thrombocytopenia. Combination therapy, as compared with other regimens, improved the outcome of citrobacter bacteremia.     

Enterococcal bacteremia in a medical center

BACKGROUND: The enterococci have become important nosocomial pathogens. They can cause multiple site infections and enterococcal bacteremia becomes more frequently associated with a high mortality rate. Previous studies of enterococcal bacteremia showed a variety of results. To establish the significance and importance of enterococci as nosocomial pathogens in this hospital, to characterize their clinical pictures and to search for the risk factors for mortality, this retrospective study was performed. METHODS: There were 208 cases of enterococcal bacteremia which occurred from 1988 to 1992. Twenty-seven cases had no medical charts, dismissing possibility of evaluation. Finally, 181 cases of enterococcal bacteremia were analysed. RESULTS: One hundred and eighteen episodes were nosocomial infections. Polymicrobial bacteremia occurred in 68.5% of the patients and the most common co-isolate was Pseudomonas aeruginosa. Those patients (78.5%) with underlying diseases and malignancies were the most common underlying problems. The portal of entry could be found in 69.6 percent of patients, with the gastrointestinal tract the most common sources. Antimicrobial susceptibility testing showed high gentamicin resistance rate (89.5%), and ampicillin still had about 80 percent sensitivity rate. The group who received specific antibiotic therapy for enterococcus showed lower mortality (36.4% versus 47.6%). Only one case had infective endocarditis. Forty-nine patients suffered from septic shock, the cause of 30 deaths. Totally 75 patients died during hospitalization. Besides sepsis, another major cause of death was their underlying diseases itself. CONCLUSIONS: Enterococci have no doubt become important nosocomial pathogens and enterococcal bacteremia were associated with high mortality, especially in elderly patients with underlying diseases such as malignancy or diabetes. When clinically dealing with sepsis from the gastrointestinal or biliary tract, especially when previous cephalosporins therapy showed no response, the possibility of enterococcal bacteremia should always be considered.     

Bacteremia and fungemia in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan

To understand the etiology and clinical outcome of bacterial and fungal sepsis in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan, we conducted a prospective study of nonmycobacterial bacteremia and fungemia in HIV-infected patients with fever who were admitted to a university hospital in Taiwan during a 42-month period. Of 210 patients, 41 (19.5%) had a total of 52 episodes of sepsis due to nonmycobacterial bacteria or fungi, or both (15.5% of 336 episodes of fever). All but one patient had acquired immunodeficiency syndrome (AIDS), and the mean CD4 lymphocyte count was 29/microL (range, 0-321/microL). A total of 57 pathogens (39 bacteria and 18 fungi) were isolated from blood; polymicrobial sepsis due to both bacteria and fungi occurred in four episodes. Nontyphoid Salmonella (NTS) was the most common cause of community-acquired bacteremia (24/30, 80%). Staphylococcus aureus bacteremia was diagnosed in three episodes while Streptococcus pneumoniae bacteremia was found in only one. Cryptococcus neoformans was the most common cause of fungemia and was responsible for 12 episodes, while fungemia due to Penicillium marneffei and Histoplasma capsulatum, two emerging fungi in Taiwan, were diagnosed in four cases and one case, respectively. Nine episodes, eight of bacteremia and one of candidemia, were nosocomial. The overall in-hospital mortality was 29%, and nosocomial sepsis was associated with a higher mortality rate (56%, p = 0.02). The mean duration of survival after recovery from initial sepsis was 426 days. We conclude that NTS bacteremia was the most common cause of sepsis in patients with advanced HIV infection in Taiwan and clinicians caring for such patients should watch for emerging fungal infections. Nosocomial sepsis was associated with a high mortality rate. The mean survival duration after recovery from sepsis of our patients was short.     

Human vaginal mucosal immune system: characterization and function

The analysis of 49 fatal cases of venous thromboembolism--VTE (15% of total ambulatory patients number during long observation was performed. The advanced age of patients, multiple risk factors, underlying circulatory and respiratory tract diseases, malignancies, previous episodes of VTE especially with secondary pulmonary hypertension were the most important factors determining fatal prognoses in those patients.     

A spectroscopic study of the structures of latent, active and reactive-center-cleaved type-1 plasminogen-activator inhibitor

To our knowledge, Flavobacterium indologenes has never been reported as a cause of bacteremia in humans. F. indologenes bacteremia was diagnosed in 12 patients at a tertiary referral center in southern Taiwan between 1 January 1992 and 31 December 1994. Six of these patients had ventilator-associated pneumonia, two had primary bacteremia, and one patient each had pyonephrosis, peritonitis, biliary tract infection, and surgical wound infection. Five patients (42%) had malignancies, and three (25%) had multiple burns. Polymicrobial bacteremia was diagnosed in eight patients (67%). Two (17%) of the patients in this study died; both had polymicrobial bacteremia. Antimicrobial susceptibility testing of the blood isolates from the 12 patients showed that > 90% of the isolates were susceptible to piperacillin, cefoperazone, ceftazidime, and minocycline. The chromatograms of esterified fatty acids for the isolates were identical. F. indologenes should be considered an etiologic agent of bloodstream infection, especially in hospitalized patients with severe underlying diseases.     

Background and prognostic factors of fungemia in patients with hematological disease

Sixty-two episodes of fungemia which occurred in patients with hematological disorders between 1976 and 1996 in our hospital were analyzed with respect to background and prognostic factors. Forty-four of the patients were male and 18 were female. The underlying diseases were acute leukemia in 36 cases, chronic myelogenous leukemia in 9, malignant lymphoma in 9 and others in 8 cases. Trichosporon beigelii and Candida tropicalis were the most frequently isolated fungal pathogens. The prevalence of C. crusei increased while that of C. albicans decreased after 1988. Fuungemia frequently occurred in patients with following factors: 1) advanced disease, such as relapse of acute leukemia or malignant lymphoma or blast crisis of chronic myelogenous leukemia; 2) neutrophil count less than 100/microliter; 3) administration of antibiotics; 4) focal infection, gastrointestinal hemorrhage or urinary catheterization; and 5) isolation of causative organisms from surveillance cultures obtained just before the onset of fungemia. The mortality rate of patients with fungemia was 74%. Absence of hypotension, increased neutrophil count for a week after the onset of fungemia, and the intravenous administration of Amphotericin B (AMPH) were good prognostic factors. Fungemia frequently occurred in patients with advanced disease and had a very poor prognosis. These results emphasized the importance of isolation of fungus from surveillance cultures, early initiation of AMPH administration, and attempts to increase neutrophil counts with G-CSF and other measures for improving the prognosis of fungemia in patients with hematological disorders.     

Comparison of reticuloendothelial scans with bone scans in malignant disease

Thirty patients with histologically proven malignant disease were selected for reticuloendothelial scans and bone scans because of suspected bone or bone marrow involvement. Reticuloendothelial scans were abnormal in 83% of the patients and bone scans were abnormal in 47%. Focal defects on the reticuloendothelial marrow scan correlated better with tumor infiltration of the marrow than did diffusely abnormal scans. Focal defects were found in nine patients (30% of total), four of whom had negative or equivocal bone scans. In multiple myeloma, reticuloendothelial marrow scans were more sensitive than bone scans, but were not clearly better than bone scans in patients with solid tumors. In the interpretation of reticuloendothelial scans, consideration must be given to the effects of radiation, chemotherapy, and uremia, all of which may cause decreased reticuloendothelial uptake and falsely positive reticuloendothelial scans. Reticuloendothelial scans seem most useful for hematologic malignancies that have not been previously treated. The advantages and disadvantages of reticuloendothelial scans are discussed.     

Expression of CD44 variant isoforms in peripheral blood leukocytes in malignant lymphoma and leukemia: inverse correlation between expression and tumor progression

In a variety of human tumors, including high grade Non-Hodgkin's lymphoma (hgNHL), a linkage between expression of CD44 variant isoforms (CD44v) and tumor progression has been described. In search of an easily accessible diagnostic parameter, expression of CD44 standard (CD44s) and CD44 variant isoforms (exons v5, v6, v7 and v10) in peripheral blood lymphocytes (PBLs) of patients with hematological malignancies was evaluated by fluorescence activated cell scanning. The analysis of 30 blood samples of healthy donors and patients with non-malignant diseases and of 183 blood samples of patients with malignant hematological disorders revealed that only in patients with malignant disorders did a measurable proportion of PBLs express CD44 variant isoforms, mostly exons v5, v6, v7 and, less frequently, exon v10. Elevated levels of CD44v expression were noted in PBLs of patients with acute and chronic myeloid leukemia (AML: 16%, CML: 25%), Hodgkin's disease (HD: 17%), multiple myeloma (MM: 22%), polycythemia vera (PV: 33%), acute lymphoid leukemia (ALL: 23%) and, most frequently, in PBLs of patients with non-Hodgkin's lymphoma (NHL:54%). CD44v expression was not restricted to the malignant phenotype, but instead was also noted in T cells, B cells and monocytes, preferentially in a subpopulation of large cells. Furthermore, expression of CD44v in PBLs was not linked to the histological grading or clinical staging. There was, however, an inverse correlation with tumor progression, whereas response to therapy was frequently accompanied by upregulation of CD44v. Thus, expression of CD44v in the PBLs of patients with NHL mainly reflected immune responsiveness. Since NHL manifests itself primarily in lymphoid organs, its progression is difficult to follow. Monitoring of CD44v in PBLs could be used as an additional and convenient parameter for surveying the course of disease.     

Diagnostic value of Doppler ultrasound in evaluation of breast tumors

Angiogenesis is an essential condition for tumor growth. Therefore, it seems to be of interest to prove if blood flow and vascularization of breast tumors give information concerning their dignity. Consequently, 205 patients with palpable and/or mammographically detected breast tumors were examined prior to surgery by doppler sonography for blood flow in the area of the tumor. In 174 patients of this group the corresponding area of the contralateral breast was also screened by doppler ultrasound. With third doppler generation angiodynography tumors can be visualized as B-images with simultaneous information on vascularization. An integrated doppler system shows the detected blood flow in form of a doppler curve, also allowing quantification according to doppler criteria (Resistance Index RI). Blood flow detection in the tumor itself was successful in 71% of all malignancies, whereas in only 6.6% of the 76 benign lesions (n = 5) blood flow was found in the central tumor area. In the area surrounding the tumor blood flow was detected in 83% of all carcinomas, but only in 29% of benign findings. Blood flow could be detected significantly higher in malignancies than in benign lesions (p = 0.003). Blood flow detection in the tumor itself was a highly specific (93%) method of discrimination between malignant and benign breast tumors. Further quantification by means of doppler parameters only increases insignificantly specificity, quantification of blood flow in the area surrounding the tumor using the RI and the comparison with the contralateral breast could improve the diagnostic value as our findings RI < 8 for benign vs. > or = 8 for malignant lesions demonstrated. Detection of malignant tumors showed a sensitivity of 80%, a specificity of 90%, and a positive predictive value of 93%. In patients with breast cancer (histologically confirmed) the detection rate of blood flow in tumors and surrounding areas was independent of tumor size or nodal status.     

Enterococcal bacteremia in children: a review of seventy-five episodes in a pediatric hospital

BACKGROUND: Enterococcal bacteremia is being increasingly reported. Although there have been a number of recent studies of enterococcal bacteremia in adults, there are few studies involving children. We carried out a prospective study to determine the epidemiologic, clinical and laboratory characteristics of such bacteremia in children. METHODS: Clinical and microbiologic data were recorded prospectively for all episodes of enterococcal bacteremia occurring during a 3-year period between January 1, 1995, and December 31, 1997. RESULTS: Seventy-five episodes of enterococcal bacteremia occurring in children at our institution during a 3-year period were prospectively analyzed. Serious underlying disease was present in 67 (89.3%) episodes, and in 48 (64.%) episodes patients had received antibiotics during the 2 weeks preceding enterococcal bacteremia. Forty-seven (62.7%) episodes were nosocomial in origin and 26 (34.7%) were polymicrobial. Fifty (66.7%) episodes occurred in children 1 year old or less. A source of bacteremia was identified in 33 (44%) episodes, intravascular device being the most common identifiable source. Of the 73 isolates identified to species level, there were 36 Enterococcus faecium, 36 Enterococcus faecalis and one Enterococcus avium. In 60 (80%) episodes appropriate anti-enterococcal therapy was given. The overall mortality rate was 7.5%. Four clinical patterns of infection were identified: self-limited bacteremia, 16.0%; low grade sepsis with a favorable outcome after specific therapy, 65.3%; severe and prolonged infection associated with a high mortality rate, 14.7%; and fulminant neonatal sepsis in previously healthy babies, 4.0%. CONCLUSION: Enterococcal bacteremia in children comprises a heterogeneous group. Bacteremias that are mild and self-limited and respond promptly to antibiotic therapy appear to be more common in children.     

Citrate values in the whole blood of patients with malignant tumors of various locations

Based on reports on elevated concentrations of 2-oxoglutarate in the blood of human subjects with tumors of various locations, data are presented on the concentration of citrate and pyruvate in the whole blood of 41 patients with malignant tumors (mainly of the female breast and of the digestive tract), 30 patients with benign surgical diseases and 12 healthy subjects. Adopting a level of significance of 2P=0.10 differences of concentration were found between the following collectives: (1) The mean value of citrate for the patients in tumor stage T4 was decreased by 23%, compared with healthy persons, and by 19%, compared with patients with benign surgical diseases. (2) The mean value of pyruvate for the patients with malignant tumors was increased by 40%, compared with healthy subjects and by 17%, compared with patients with benign surgical diseases. (3) The maximum of the pyruvate concentration was reached in tumor stage T3, where an increase of 52% was noted, compared with healthy subjects. (4) The pyruvate value of the patients with tumors of the digestive tract was increased by 34%, compared with healthy subjects. With regard to the total group of patients with malignant tumors, even with a low level of significance, no differences in citrate values were found as compared with the control groups. Thus the results do not indicate a disturbance of the citric acid cycle in the organism of tumor bearing hosts in general.     

Interleukin 6, but not tumour necrosis factor-alpha, is a good predictor of severe infection in febrile neutropenic and non-neutropenic children with malignancy

OBJECTIVE: Interleukin-6 (IL6), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the inflammatory response in human infection. The aim of this study was to determine the relationship between serum levels of IL6, TNF-alpha, IFN-gamma and CRP in febrile children with malignant disease, and relate these levels to aetiology of fever, presence of neutropenia and the effect of untreated malignancy. METHODS: 110 febrile episodes in 70 children with malignant disease were included. Cytokine analyses were performed with sensitive immunoradiometric methods using double monoclonal antibodies. RESULTS: IL6 had a sensitivity of 74% in detecting sepsis in children with fever and malignant disease. This sensitivity was not influenced by the presence of neutropenia or newly diagnosed malignancy. A positive correlation between IL6 and the CRP levels on the following day was observed (r = .53). TNF-alpha was elevated in 22% of the episodes and mean levels were significantly higher in untreated malignancy but lower in neutropenic patients. IFN-gamma was elevated in 18% of cases and correlated strongly with mean TNF-alpha levels. CONCLUSIONS: IL6 is a sensitive and early predictor of bacterial infection in both neutropenic and non-neutropenic febrile children with malignancy. It is more sensitive than CRP in detecting sepsis, but the predictive value is too low to allow IL6 levels to influence initial treatment decisions in patients with granulocytopenia. TNF-alpha production seems to be impaired in neutropenic children and serum TNF-alpha cannot be employed as an indicator of bacterial infection.     

Coal miners'' respiratory disease litigation

Between 1985 and 1995, 1037 bacteremic episodes were recorded in a pediatric tertiary care center and analyzed retrospectively. Gram-positive bacteria accounted for 719 episodes (68%), gram-negative bacteria for 303 (29%), fungi for 16 (2%), and anaerobes for 12 (1%). In 526 (51%) patients, primarily neonates and oncology patients, a predisposing condition was present. In 390 (38%) episodes a clinical source of infection was documented. Mortality was highest in Pseudomonas bacteremia (45%). Since the bacterial spectrum differed widely between patient groups, the choice of empirical antimicrobial therapy should be based on any underlying condition present in the patient and the clinical source of infection. As anaerobes were rarely isolated. the routine use of anaerobic blood cultures in patients without predisposing conditions does not seem warranted.     

Outbreak of Pseudomonas fluorescens bacteremia among oncology patients

From 7 to 24 March 1997, four patients developed Pseudomonas fluorescens bacteremia at the hospital; one on the oncology ward and the other three in the chemotherapy room. These patients all had underlying malignancies and had the Port-A-Cath (Smiths Industries Medical Systems, Deltec, Inc., St. Paul, Minn.) implants. Three patients had primary bacteremia, and one had Port-A-Cath-related infection. None of these patients had received a blood transfusion before the episodes of bacteremia. All patients recovered: two received antimicrobial agents with in vitro activity against the isolates, and the other two did not have any antibiotic treatment. A total of eight blood isolates were recovered from these patients during the febrile episodes that occurred several minutes after the infusion of chemotherapeutic agents via the Port-A-Cath. These isolates were initially identified as P. fluorescens or Pseudomonas putida (four), Burkholderia (Ralstonia) pickettii (three), and a non-glucose-fermenting gram-negative bacillus (one) by routine biochemical methods and the Vitek GNI card. These isolates were later identified as P. fluorescens on the basis of the characteristic cellular fatty acid chromatogram and the results of supplemental biochemical tests. The identification of identical antibiotypes by the E test and the random amplified polymorphic DNA patterns generated by arbitrarily primed PCR of the isolates showed that the outbreak was caused by a single clone of P. fluorescens. Surveillance cultures of the possibly contaminated infusion fluids and disinfectants, which were performed 7 days after recognition of the last infected patient, failed to isolate P. fluorescens. This report of a small outbreak caused by P. fluorescens suggests that timely, accurate identification of unusual nosocomial pathogens is crucial for early initiation of an epidemiological investigation and timely control of an outbreak.     

2-Chlorodeoxyadenosine dose escalation in nonhematologic malignancies

PURPOSE: We performed a dose-escalation study of 2-chlorodeoxyadenosine (2-CdA) in solid tumors to determine the maximum-tolerated dose (MTD) and define its toxicity profile at higher doses. PATIENTS AND METHODS: Twenty-one patients, seven with malignant astrocytoma, twelve with metastatic melanoma, and two with metastatic hypernephroma, were enrolled onto the study. Patients were entered onto cohorts that received 0.10, 0.15, or 0.20 mg/kg/d of 2-CdA by continuous intravenous infusion for 7 days every 28 days. 2-CdA levels were determined by radioimmunoassay. In tumor tissue samples, deoxycytidine kinase (dCK) levels were measured by both enzyme activity and immunoreactive protein analysis. RESULTS: Of seven patients treated with 2-CdA at 0.1 mg/kg/d, one experienced grade 3 or 4 myelotoxicity. Of 11 patients treated at 0.15 mg/kg/d, four experienced myelotoxicity, two after a single course of 2-CdA. All three patients who received 2-CdA at 0.2 mg/kg/d experienced myelosuppression. Neurologic events occurred in two patients, both with malignant melanoma. Two of seven patients (28.6%) with astrocytomas obtained partial responses with a median duration of 8 months. 2-CdA penetrated the blood-brain barrier. An association was found between dCK levels as measured by enzymatic activity and immunoreactive proteins, but this did not correlate with 2-CdA tumor responsiveness. CONCLUSION: The MTD for 2-CdA delivered as a 7-day intravenous infusion in patients with nonhematologic malignancies was determined to be 0.1 mg/kg/d, the same as the MTD for patients with hematologic malignancies. There was no clinical correlation with dCK expression and response to 2-CdA. The responses noted in patients with malignant astrocytoma warrant further phase II study.     

Randomised comparison of ceftazidime and imipenem as initial monotherapy for febrile episodes in neutropenic cancer patients

With the availability of new, broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations in the management of febrile, neutropenic cancer patients. The aims of this study were to compare the efficacy of ceftazidime and imipenem as empirical monotherapy of febrile episodes in neutropenic patients, and to examine the frequency with which second-line antibiotics (amikacin, vancomycin, or both) were required. A prospective clinical trial was carried out in a single centre. Eligible patients with solid tumours or lymphoma were randomised to receive monotherapy with ceftazidime or imipenem. In the event of no response, amikacin and/or vancomycin were added in 48-72 h intervals (sequentially, or according to clinical or microbiological data). Efficacy was evaluable for 111 assessable episodes. Median neutrophil count at entry was 100 cells/microliters and median duration of neutropenia was 4 days. Febrile episodes were classified as microbiologically (34%) or clinically documented (42%), and fever of unknown origin (24%). Gram-negative infections (57%) predominated over gram-positive isolates (30%). The overall success rate with monotherapy (69% versus 70%), or with modification (20% versus 23%) were equivalent for ceftazidime and imipenem (P = 0.75). The mortality in this series was 5%. Single-agent therapy with either ceftazidime or imipenem is effective for the empirical treatment of febrile episodes in neutropenic patients with solid tumours. Early addition of amikacin and/or vancomycin resolves most failures of the first step.     

Survey bacterial isolates from blood samples during 1987-1993 in our department

We analyzed the changes in frequency of bacterial isolates from the blood samples in our department from May 1987 to December 1993. 565 isolates from 4887 samples (11.6%) were detected. Among the detected microorganisms, the rate of gram-positivecocci (GPC) was much higher than the other kinds of the isolates each year. Especially, 80-90% of GPC were occupied by only 2 kinds of microorganisms, coagulase negative Staphylococci (CNS) and S. aureus. Among gram-negative-rods (GNR), constant increase of S. marcescens and transient increase of Enterobacter and P. aeruginosa were recognized. In 30 cases (5.3%), 2-3 kinds of microorganisms were isolated concomitantly, and in 55 cases (9.7%), the microorganisms, which was mainly caused by CNS, S. aureus and Candida, was isolated from both blood samples and the tip of the IVH catheter concomitantly. 42.5% of the bacterial positive cases in 1933 underwent 2 more kinds of the indwelling catheters and 48.3% were administrated antibiotics. Most of the cases had underlying diseases including mainly malignant tumor (leukemia, solid tumor), cerebrovascular diseases, and multiple injuries.     

In vitro resistance to thrombin-induced platelet microbicidal protein among clinical bacteremic isolates of Staphylococcus aureus correlates with an endovascular infectious source

Platelet microbicidal proteins (PMPs), small cationic peptides released at sites of endovascular damage, kill common bloodstream pathogens in vitro. Our group previously showed that in vitro resistance of clinical staphylococcal and viridans group streptococcal bacteremic strains to PMPs correlated with the diagnosis of infective endocarditis (IE) (Wu et al., Antimicrob. Agents Chemother. 38:729-732, 1994). However, that study was limited by (i) the small number of Staphylococcus aureus isolates from IE patients, (ii) the retrospective nature of the case definitions, and (iii) the diverse geographic sources of strains. The present study evaluated the in vitro PMP susceptibility phenotype of a large number of staphylococcemic isolates (n = 60), collected at a single medical center and categorized by defined and validated clinical criteria. A significantly higher proportion of staphylococcemic strains from patients with IE was PMP resistant in vitro than the proportion of strains from patients with soft tissue sepsis (83% and 33%, respectively; P < 0.01). Moreover, the levels of PMP resistance (mean percent survival of strains after 2-h exposure to PMP in vitro) were significantly higher for isolates from patients with IE and with vascular catheter sepsis than for strains from patients with abscess sepsis (P < 0.005 and P < 0.01, respectively). These data further support the concept that bloodstream pathogens that exhibit innate or acquired PMP resistance have a survival advantage with respect to either the induction or progression of endovascular infections.