Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study).

Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.

Outbreak of Legionnaires' disease in immunosuppressed patients at a cancer centre: usefulness of universal urine antigen testing and early levofloxacin therapy.

This report describes an outbreak of Legionnaires' disease in severely immunosuppressed patients hospitalised at a cancer centre. Universal urine antigen testing and early levofloxacin therapy appeared to lower case fatality rates in comparison with previous reports concerning this high-risk population. This diagnostic and therapeutic strategy should be considered when facing a nosocomial outbreak of Legionnaires' disease in immunosuppressed hosts.

[Clinical utility of fused 67Ga SPECT/CT scan images in patients with lymphoma]. / Utilidad clínica de las imágenes de fusión 67Ga SPECT/TC en pacientes con linfoma.

AIM: The aim of this work is to show the clinical utility of the fused SPECT 67Ga/CT images in patients with lymphoma. MATERIAL AND METHOD: 44 patients (22 male) with lymphoma have been studied. 22 with Hodgkin's disease and 22 with non Hodgkin lymphoma. 59 studies were performed (33 thorax-cervical [T], 24 abdomen [A] and 2 skull-cervical area [SC]) with an hybrid gammacamera Millenium VG. We acquire consecutively a whole body scan, a SPECT and a CT, for its fusion with the SPECT, of the affects areas. The images were evaluated by two experts blinded, who classify the contribution of the fusion of images respect to the SPECT like: non changes, it improves the location or changes the extension of the injuries and it changes the staging. Final lesion location was confirmed by a high resolution CT performed within one month. RESULTS: 32/59 studies did not change the location or extension of the injuries (20T, 12A), 23/59 studies changed the location or extension of the injuries (12T, 9A and 2 SC) and on 4/59 the change of location induced a change of staging respect to showed by the SPECT. CONCLUSION: To make fused SPECT 67Ga/CT images in patients with lymphoma allows improving the diagnostic precision in a 46% of the cases, mainly in the abdominal, bone and of the diaphragmatic area studies.

Bacteremic pneumonia in neutropenic patients with cancer: causes, empirical antibiotic therapy, and outcome.

BACKGROUND: Bacteremic pneumonia is a major cause of death among neutropenic patients with cancer. METHODS: We analyzed the causes, empirical antibiotic therapy, and outcome of 40 consecutive cases of bacteremic pneumonia identified among 408 episodes of bacteremia in adult neutropenic patients with cancer, prospectively documented from 1986 to 1995. RESULTS: The most frequent causative organisms were Pseudomonas aeruginosa (17 cases), Streptococcus pneumoniae (12 cases), Escherichia coli (5 cases), and Streptococcus mitis (3 cases). Overall, P. aeruginosa and S. pneumoniae caused 72.5% of all episodes of bacteremic pneumonia, compared with 11.4% of bacteremic episodes from other sources (P< .001). Thirty patients received ceftazidime and 10 patients received imipenem as the beta-lactam component of the initial empirical treatment. All strains of P. aeruginosa were susceptible to both agents. Forty-seven percent of streptococcal strains were penicillin resistant and showed a decreased susceptibility to ceftazidime (minimum inhibitory concentration ranged from 1 to 64 microg/mL). Five patients (12.5%) were considered to have received inappropriate empirical antibiotic therapy. Attributable mortality in patients with bacteremic pneumonia was higher than in patients with bacteremia from other sources; 22 (55%) of the 40 patients with bacteremic pneumonia died, whereas 39 (10.6%) of the 368 patients with bacteremia from other sources died (P<.001). CONCLUSIONS: Our data suggest that bacteremic pneumonia in neutropenic cancer patients is associated with a poor outcome and that empirical antibiotic therapy for neutropenic patients with pneumonia should include agents active against both P. aeruginosa and cephalosporin-resistant streptococci.

Expression of adhesion molecules in 113 patients with B-cell chronic lymphocytic leukemia: relationship with clinico-prognostic features.

The B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease, its clinical and biological behavior possibly being influenced by surface molecules expressed in B-lymphocytes. These molecules mediate cell adhesion, mobility and homing. Expression of surface adhesion molecules of the integrin family (CD11a/CD18 or LFA-1, CD11c/CD18), of the immunoglobulin-related family (CD54), of the selectin family (CD62L or LAM-1) and the lymphocyte homing receptor (CD44) were analyzed in peripheral cells from 113 B-CLL patients. The association with three prognosis-related parameters (Rai stage, bone marrow pattern and doubling time) was determined. The study included only patients with B-CLL lymphocytes of typical morphology, which always expressed CD5 and CD23. Low expression of integrins, particularly CD18, was associated with advanced disease (Rai stages III-IV) and diffuse bone marrow pattern, even after adjusting for other prognosis-related variables. Expression of CD54 was associated independently with rapid doubling time (less than 12 months). The association persisted after adjusting for stage and bone marrow pattern; CD44 was expressed in all patients. No correlations were found between expression of CD62L and the prognostic variables analyzed. In conclusion, CD54 expression and low CD18 expression are both significantly associated with poor prognostic features.

Prognostic indexes in follicular lymphoma: a comparison of different prognostic systems.

BACKGROUND: The International Prognostic Index (IPI), initially designed for aggressive lymphomas, is also used in follicular lymphoma (FL) and other indolent lymphomas. Two new prognostic indexes have recently been proposed for FL [the Italian Lymphoma Intergroup (ILI) Index and the Follicular Lymphoma International Prognostic Index (FLIPI)]. PATIENTS AND METHODS: Three indexes, IPI [age >60 years, extranodal involvement two or more sites, elevated lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group performance status > or =2, stage > or =3], ILI (age >60 years, extranodal involvement two or more sites, elevated LDH, male sex, B symptoms, erythrocyte sedimentation rate > or =30 mm first hour) and FLIPI (age >60 years, stage > or =3, elevated LDH, nodal involvement five or more, haemoglobin level < or =12 g/dl) were calculated in 411 patients with FL. RESULTS: Overall concordance between the three indexes was 54%. A total of 126 (31%) patients were included in the high-risk group according to IPI, 131 (32%) according to ILI and 157 (38%) after FLIPI application. Ten-year overall survival rates after applying the prognostic indexes (IPI, ILI and FLIPI) were, respectively: 72%, 71% and 72%, in the low-risk group; 51%, 60% and 49% in the intermediate-risk group; and 24%, 16% and 31% in the high-risk group. CONCLUSIONS: In this series, all three indexes, IPI, ILI and FLIPI, were useful to classify FL patients into differentiated risk groups, although the FLIPI identified a larger proportion of high-risk patients than the IPI and ILI.

Serious complications of bacteremia caused by Viridans streptococci in neutropenic patients with cancer.

We prospectively studied 485 episodes of bacteremia in neutropenic patients with cancer. Viridans streptococci caused a total of 88 episodes (18%). Ten (11%) of these 88 cases were associated with serious complications: acute respiratory distress syndrome (ARDS) plus septic shock (5 cases), ARDS (3), and septic shock (2). Streptococcus mitis was the species most frequently isolated (7 of 10 episodes). Four viridans streptococci showed a diminished susceptibility to penicillin (MICs ranged from 0.25 to 4 microg/mL), and 5 strains were resistant to ceftazidime (MICs ranged from 2 to >32 microg/mL). Patients with viridans streptococcal bacteremia (VSB) who developed serious complications were compared with patients with VSB without complications. Severe oral mucositis (70% vs. 32.5%, respectively; P=.036), high-dose chemotherapy with cyclophosphamide (60% vs. 25%, respectively; P=.043), and allogeneic bone marrow transplantation (40% vs. 10%, respectively; P=.040) were the only variables found to be significantly associated with the development of complications. Neither a specific species of viridans streptococci nor resistance to penicillin was associated with the occurrence of complications. The mortality rate was higher in case patients than in control patients (80% vs. 17.5%, respectively; P<.001). Serious complications associated with VSB occur mainly in patients receiving high-dose chemotherapy with cyclophosphamide before allogeneic bone marrow transplantation who develop severe oral mucositis; these complications are associated with a high mortality rate.

Bacteremia due to viridans streptococci that are highly resistant to penicillin: increase among neutropenic patients with cancer.

We prospectively studied 260 episodes of bacteremia that occurred over a 6-year period in neutropenic patients with cancer. Twenty-three episodes were caused by viridans streptococci. Thirteen (57%) of these strains were penicillin-resistant (MICs of penicillin ranged from 0.25 micrograms/mL to 8 micrograms/mL). Ten of the 13 penicillin-resistant strains (77%) were highly resistant to penicillin (MIC, > or = 4 micrograms/mL). Rates of bacteremia due to highly penicillin-resistant viridans streptococci increased significantly from zero episodes per 1,000 admissions in 1987 to 17 episodes per 1,000 admissions in 1992 (P = .003). In a comparison between penicillin-resistant and penicillin-susceptible viridans streptococci bacteremia, the administration of beta-lactam antibiotics during the previous 2 weeks was the only factor significantly associated with penicillin-resistant cases: 9 (69%) of 13 patients with penicillin-resistant bacteremia had received beta-lactams vs. 2 (20%) of 10 patients with penicillin-susceptible bacteremia (P = .036). These findings may have significant clinical implications in the choice of both antimicrobial prophylaxis and empirical antibiotic regimens.

Emergence of quinolone-resistant Escherichia coli bacteremia in neutropenic patients with cancer who have received prophylactic norfloxacin.

Between January 1988 and December 1992, 35 episodes of Escherichia coli bacteremia were identified in a series of 230 cases of bacteremia in neutropenic patients with cancer. Thirteen episodes (37%) were due to quinolone-resistant strains. Minimal inhibitory concentrations of norfloxacin ranged from 16 micrograms/mL to 128 micrograms/mL, and those of ciprofloxacin from 8 micrograms/mL to 64 micrograms/mL. The incidence of bacteremia due to quinolone-resistant E. coli increased from zero episodes per 1,000 hospital admissions in 1988 to four episodes per 1,000 admissions in 1992 (P = .018). To identify risk factors for quinolone-resistant E. coli bacteremia, we compared episodes of quinolone-resistant and quinolone-susceptible E. coli bacteremia. Among the variables analyzed, prophylaxis with norfloxacin was the only factor significantly associated with the development of quinolone-resistant E. coli bacteremia; 13 of 13 patients with bacteremia due to resistant strains received norfloxacin, whereas only one (5%) of 22 patients with bacteremia due to susceptible strains did (P < .001). According to our data, neutropenic patients with cancer who receive fluoroquinolone prophylaxis may be at risk of developing E. coli bacteremia due to quinolone-resistant strains.

A papular eruption secondary to infection with Corynebacterium jeikeium, with histopathological features mimicking botryomycosis.

Corynebacterium jeikeium has been increasingly recognized as a pathogen, particularly in immunocompromised patients and in those with a prosthetic heart valve. Although cutaneous manifestations of C. jeikeium infection have been described, we have only found two case reports that give an histological description of the lesions. We present three patients with haematological malignancies who developed infection with C. jeikeium and a papular eruption. Skin biopsy disclosed similar histological features in all three patients, namely numerous Gram-positive bacteria enclosed in an eosinophilic matrix, with a minimal inflammatory response. C. jeikeium was cultured from cutaneous lesions in two cases.

Emergence of fluoroquinolone-resistant Escherichia coli in fecal flora of cancer patients receiving norfloxacin prophylaxis.

We studied 122 stool samples collected from 25 patients with hematologic malignancies who received prophylactic norfloxacin. Fecal samples were obtained at admission and twice weekly thereafter during prophylaxis. Fluoroquinolone-resistant Escherichia coli strains were isolated from the feces of 10 (40%) of the patients; two patients had fluoroquinolone-resistant E. coli strains prior to beginning norfloxacin treatment, and in the other eight patients, the strains appeared subsequently. One patient developed fluoroquinolone-resistant E. coli bacteremia after 10 days of norfloxacin administration.

Prospective study of 288 episodes of bacteremia in neutropenic cancer patients in a single institution.

Trends in causative organisms and sources of infection were studied in a series of 288 episodes of bacteremia in neutropenic cancer patients observed in a single institution from 1986 to 1993. The incidence of bacteremia increased significantly from 20 episodes per 1000 admissions in 1986 to 50 episodes per 1000 admissions in 1993 (p = 0.00001). Over the study period, a continuous increment in gram-positive bacteremia, which reached 81% of episodes in 1993 (p = 0.000001), was observed. Conversely, the incidence of gram-negative bacteremia remained stable. Coagulase-negative staphylococci and viridans group streptococci were the most commonly isolated pathogens. Bacteremia caused by coagulase-negative staphylococci increased from 3 episodes per 1000 admissions to 19 episodes per 1000 admissions (p = 0.0001), and viridans group streptococci bacteremia increased from 0 episodes per 1000 admissions to 19 episodes per 1000 admissions (p = 0.000001). The upward trend in gram-positive bacteremia appeared to be related to a significant increase in both intravascular catheters (p = 0.003) and oral mucositis (p = 0.003) as sources of infection. Specific strategies to prevent chemotherapy-induced mucositis and catheter-related bacteremia merit further investigations.

High rates of resistance to cephalosporins among viridans-group streptococci causing bacteraemia in neutropenic cancer patients.

The prevalence of resistance to cephalosporins among viridans-group streptococci causing 88 (18%) cases among 485 bacteraemias in neutropenic cancer patients was studied. Rates of resistance to ceftriaxone, ceftazidime, cefpirome and cefepime were 22, 53, 14 and 34%, respectively. Previous administration of beta-lactam therapy was the only factor significantly associated with bacteraemia due to cephalosporin-resistant strains; only 11 (16%) of 68 patients infected with cephalosporin-susceptible bacteria had received these antibiotics compared with 10 (50%) of 20 patients infected with cephalosporin-resistant bacteria (P = 0.0052).

Fatal myofascial necrosis due to imipenem-resistant Aeromonas hydrophila.

We report the case of a fatal myofascial necrosis caused by an imipenem-resistant Aeromonas hydrophila in a patient with a history of aplastic anemia. He presented with fever and left thigh tenderness. The CT scan was consistent with cellulitis and, after cultures were obtained, empirical treatment with imipenem and amikacin was started. Two days later, necrotic bullae appeared on his thigh, and cultures showed Aeromonas hydrophila which was imipenem-resistant. Although surgical debridement was performed and ciprofloxacin was initiated, the patient died.

Treatment of penicillin-resistant pneumococcal bacteremia in neutropenic patients with cancer.

We identified 17 cases of pneumococcal bacteremia among 340 neutropenic cancer patients with bacteremia. Pneumonia was more frequent in patients with pneumococcal bacteremia than in those with bacteremia due to other organisms: 12 (71%) of 17 patients with pneumococcal bacteremia had pneumonia, whereas only 23 (7%) of 323 patients with nonpneumococcal bacteremia had pneumonia (P < .001). Eight (47%) of the 17 episodes of pneumococcal bacteremia were caused by penicillin-resistant strains (MICs ranged from 0.12 microg/mL to 4 microg/mL); these penicillin-resistant pneumococci showed varying degrees of diminished susceptibility to all beta-lactams studied, especially ceftazidime (MICs of this drug ranged from 1 microg/mL to 64 microg/mL). Imipenem was the beta-lactam agent most active against these organisms (MICs ranged from 0.03 microg/mL to 0.25 microg/mL). Patients with penicillin-resistant pneumococcal bacteremia received inappropriate empirical antibiotic therapy more often than did patients with bacteremia due to susceptible strains (i.e., 4 (50%) of 8 patients vs. 0 of 9, respectively; P < .05). Eight (47%) of the 17 patients with pneumococcal bacteremia died. In areas where penicillin-resistant pneumococci are highly endemic, these findings should be considered in selecting empirical antibiotic therapy for neutropenic patients with cancer who are suspected of having pneumonia.

Predisposing factors and outcome of Staphylococcus aureus bacteremia in neutropenic patients with cancer.

Staphylococcus aureus caused 30 of 438 (7%) cases of bacteremia in neutropenic patients with cancer during a 10-year study period. Acute leukemia as an underlying disease and severe oral mucositis were more frequent among patients with Staphylococcus aureus bacteremia (57% vs. 33%, P = 0.01, and 32% vs. 12%, P = 0.006, respectively) than among the 151 patients who had gram-negative bacteremia during the same study period. The most frequent source of Staphylococcus aureus bacteremia was the venous catheter (35% vs. 1%; P = 0.00001). Septic metastases were more frequent in patients with Staphylococcus aureus bacteremia (14% vs. 4%, P = 0.03). Attributable mortality was 10% and overall mortality 23%. Staphylococcus aureus bacteremia remains a significant cause of morbidity and mortality in neutropenic patients with cancer.

Randomized, double-blind trial of an antibiotic-lock technique for prevention of gram-positive central venous catheter-related infection in neutropenic patients with cancer.

The aim of the present study was to determine the efficacy of an antibiotic-lock technique in preventing endoluminal catheter-related infection with gram-positive bacteria in neutropenic patients with hematologic malignancies. Patients with nontunneled, multilumen central venous catheters were assigned in a randomized, double-blinded manner to receive either 10 U of heparin per ml (57 patients) or 10 U of heparin per ml and 25 microg of vancomycin per ml (60 patients), which were instilled in the catheter lumen and which were allowed to dwell in the catheter lumen for 1 h every 2 days. Insertion-site and hub swabs were taken twice weekly. The primary and secondary end points of the trial were significant colonization of the catheter hub and catheter-related bacteremia, respectively. Significant colonization of the catheter hub occurred in nine (15.8%) patients receiving heparin (seven patients were colonized with Staphylococcus epidermidis, one patient was colonized with Staphylococcus capitis, and one patient was colonized with Corynebacterium sp.), whereas the catheter hubs of none of the patients receiving heparin and vancomycin were colonized (P = 0.001). Catheter-related bacteremia developed in four (7%) patients receiving heparin (three patients had S. epidermidis bacteremia and one patient had S. capitis bacteremia), whereas none of the patients in the heparin and vancomycin group had catheter-related bacteremia (P = 0.05). The times to catheter hub colonization and to catheter-related bacteremia by the Kaplan-Meier method were longer in patients receiving heparin and vancomycin than in patients receiving heparin alone (P = 0.004 and P = 0.06, respectively). Our study shows that a solution containing heparin and vancomycin administered by using an antibiotic-lock technique effectively prevents catheter hub colonization with gram-positive bacteria and subsequent bacteremia during chemotherapy-induced neutropenia in patients with hematologic malignancy.

Prognostic factors influencing mortality in cancer patients with neutropenia and bacteremia.

The purpose of this study was to identify risk factors for mortality in neutropenic patients with cancer and bacteremia. A consecutive sample of 438 neutropenic patients (granulocyte count <0.5 x 10(9)/l) with cancer and bacteremia was studied to identify the clinical characteristics associated with mortality at the onset of bacteremia. The mean age of the subjects was 48 years (range, 15-87 years). Most cases of bacteremia (77%) were hospital-acquired and occurred in patients with acute leukemia (48%). Gram-positive organisms caused 233 (53%) episodes of bacteremia, gram-negative organisms caused 151 (34%) episodes, and 48 (11%) episodes were polymicrobial. The overall mortality within 30 days of the onset of bacteremia was 24.4%. The variables found to be independently associated with increased mortality using logistic regression techniques were as follows: shock at the onset of bacteremia (OR, 10; 95% CI, 4.2-23.8), pneumonia (OR,4.4; 95% CI, 1.9-10), uncontrolled cancer (OR,4.3; 95% CI, 1.5-12.7), and absence of prophylaxis with norfloxacin (OR,2.4; 95% CI, 1.3-4.5). The prognostic factors ascertained in this study may help to identify those patients at higher risk of death. Medical intervention addressing some of these factors may improve the outcome of bacteremia in neutropenic patients with cancer.

Low-dose subcutaneous interleukin-2 in patients with minimal residual lymphoid neoplasm disease.

Interleukin-2 (IL-2) is a cytokine that became available for clinical use with the development of recombinant DNA technology. Patients with resistant or relapsed lymphoid neoplasm have been treated with high-dose IL-2 with some responses. The aim of the present study is to determine whether there may be a biological justification for the use of low dose subcutaneous (s.c.) IL-2 as maintenance therapy in patients with lymphoid neoplasm in complete remission with high risk of relapse. We treated 15 patients with sc IL-2, 4.5 Million International Units (MIU) daily, 5 days per week for 12 consecutive weeks, in the outpatient clinic. This therapy was well tolerated and could be administered in an outpatient regimen. It increased the eosinophil count (p = 0.009), but the number of granulocytes, monocytes, T-lymphocytes and B-lymphocytes did not change. The number of natural killer (NK) cells increased from 11% to 35% of all lymphocytes during IL-2 therapy (p = 0.0006). Effector lymphokine-activated killer activity (eLAK) also increased from 6x10(-3) Lytic Units (LU)/ml to 80x10(-3) LU/ml (p = 0.02). All these changes reached a "plateau" after the 4th week of therapy. The increase in the number of NK cells correlated strongly with the increase in eLAK activity (r = 0.96, p<0.0001). Disease-free survival was determined in 14 patients who completed the treatment and compared with historical controls. Patients treated with IL-2 had the same relapse risk (median time to relapse 11.1 months, 95% confidence interval 5.5-16.6) as did controls (median time to relapse 9.7 months, 95% confidence interval 1-27.7) (p = 0.9). Low dose s.c. IL-2 stimulated NK proliferation, which generated cytotoxic activity in vivo in patients with lymphoid neoplasms. However, these patients did not have a lower risk of disease relapse compared to historical controls.