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C Viscoli

Publications and source records attributed to C Viscoli.

At least 55 records · Page 3Linked to original sources
PubMed1996

Phase I study of simultaneous dose escalation and schedule acceleration of cyclophosphamide-doxorubicin-etoposide using granulocyte colony-stimulating factor with or without antimicrobial prophylaxis in patients with small-cell lung cancer.

A phase I study was designed to assess whether dose intensity of an 'accelerated' cyclophosphamide-doxorubicin-etoposide (CDE) regimen plus granulocyte colony-stimulating factor (G-CSF) could be increased further, in an outpatient setting, by escalating the dose of each single drug of the regimen. Patients with previously untreated small-cell lung cancer (SCLC) received escalating doses of cyclophosphamide (C) 1100-1300 mg m-2 intravenously (i.v.) on day 1, doxorubicin (D) 50-60 mg m-2 i.v. on day 1, etoposide (E) 110-130 mg m-2 i.v. on days 1, 2, 3 and every 14 days for at least three courses. Along with chemotherapy, G-CSF (filgastrim) 5 micrograms kg-1 from day 5 to day 11 was administered subcutaneously (s.c.) to all patients. Twenty-five patients were enrolled into the study. All patients at the first dose level (C 1100, D 50, E 110 x 3) completed three or more cycles at the dose and schedule planned by the protocol and no 'dose-limiting toxicity' (DLT) was seen. At the second dose level (C 1200, D 55, E 120 x 3) three out of five patients had a DLT consisting of 'granulocytopenic fever' (GCPF). Another six patients were treated at this dose level with the addition of ciprofloxacin 500 mg twice a day and only two patients had a DLT [one episode of documented oral candidiasis and one of 'fever of unknown origin' (FUO) with generalised mucositis]. Accrual of patients proceeded to the third dose level (C 1300, D 60, E 130 x 3) with the prophylactic use of ciprofloxacin. Four out of six patients experienced a DLT consisting of GCPF or documented non-bacterial infection. Accrual of patients at the third dose level was then resumed adding to ciprofloxacin anti-fungal prophylaxis (fluconazole 100 mg daily) and anti-viral prophylaxis (acyclovir 800 mg twice a day) from day 5 to 11. Out of five patients treated three experienced a DLT consisting of severe leucopenia and fever or infection. With a simultaneous dose escalation and schedule acceleration it is indeed possible to take maximum advantage of G-CSF activity and to increase CDE dose intensity by a factor 1.65-1.80 for a maximum of 3-4 courses. The role of antimicrobial prophylaxis in this setting deserves to be investigated further.

Antibiotic Prophylaxis↗
PubMed1996

Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program.

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

Adolescent↗
PubMed1996

Fungal infections in patients undergoing bone marrow transplantation: an approach to a rational management protocol.

Candida sp. and Aspergillus sp. are the most common fungal pathogens causing infection in bone marrow transplant recipients and represent an increasing cause of morbidity and mortality. At this time there is no generally accepted rule for the antifungal management of these complications. Antifungal drugs in immunocompromised patients are usually administered for prophylaxis, for therapy of specific infections or for empirical or preemptive therapy. The present article reports schedules of administrations and pediatric and adult dosages of the main antifungal drugs presently available, (fluconazole, itraconazole, amphotericin B deoxycholate, lipid formulations of amphotericin B and flucytosine), together with their spectrum of action and main toxicities. Thereafter, the available information about prevention and treatment of fungal infections in bone marrow transplant recipients is summarized. Briefly, fluconazole remains the drug of choice for prevention of Candida infections in bone marrow transplant recipients, while itraconazole has been seldomly used for this indication, due to erratic oral absorption. However, new itraconazole formulations are being studied, that might disclose new clinical perspectives, due to improved bioavailability. The duration of prophylaxis is still an open issue. Resistance to the new azoles may become a problem in the near future. For this reason, it is likely that the approach to the use of these new drugs should be similar to the one commonly used for antibacterial drugs, i.e. based on pathogen-related, drug-related and host-related factors. Mainly due to lack of diagnostic tools, very little studies have been performed for prevention of aspergillosis. Available data seem to show that there might be a role for low-dose intravenous amphotericin B, which has shown to be effective for secondary prophylaxis. Itraconazole and intranasal amphotericin B have been studied, as well. Although fluconazole and itraconazole (in the rare instances in which the oral route is reliable) can also have therapeutic indications, both for empirical and for specific therapy, amphotericin B (with or without flucytosine) remains the main therapeutic option. New antifungal drugs and new supportive strategies (i.e. role of hematopoietic growth factors) are in the research pipeline and will hopefully disclose new perspectives in the near future.

Adult↗
PubMed1995

Primary prevention of cryptococcal meningitis by fluconazole in HIV-infected patients.

To evaluate whether oral fluconazole reduces the risk of a first episode of cryptococcal meningitis in HIV-infected patients, we conducted a case-control study of patients cared for in a university teaching hospital and two urban HIV-outpatient clinics. Cases consisted of HIV-infected patients with CD4 cell counts less than 250/microL who developed a first episode of cryptococcal meningitis between July 1, 1990, and June 30, 1993. For each case (n = 18), 4 control subjects were chosen from HIV-infected patients (CD4 count < 250/microL) whose cerebrospinal fluid was negative for cryptococcal antigen and culture, and who were matched by age, sex, and time of lumbar puncture. There were no significant differences between cases and controls in age, sex, insurance status, mean CD4 count, history of oral candidosis, presence of a previous AIDS-defining illness, the number of visits to the HIV-outpatient clinic, or use of antiretroviral therapy. In the 6 months before lumbar puncture, 2 of 18 cases (11%) and 26 of 72 controls (36%) were exposed to fluconazole, a finding that gives a matched odds ratio (adjusted for race, route of HIV infection, and CD4 count) of 0.08 (95% CI 0.01-0.84; p = 0.035) and indicates a 92% protective efficacy. We conclude that fluconazole reduces the risk of a first episode of cryptococcal meningitis in HIV-infected patients with a CD4 count less than 250/microL. Although the optimum dose and duration of fluconazole could not be determined, our results suggest that less than daily use was effective in the prevention of cryptococcal meningitis.

Adult↗
PubMed1995

Prophylaxis of streptococcal bacteraemia with oral penicillin V in children undergoing bone marrow transplantation.

The work described aimed to evaluate the incidence of streptococcal bacteraemia in children undergoing bone marrow transplantation and receiving prophylaxis with penicillin V. From January 1991 to December 1993 oral penicillin V was administered as prophylaxis for streptococcal bacteraemia to patients undergoing bone marrow transplantation at G. Gaslini Children's Hospital, Genoa, Italy. The data were compared with those from a similar population receiving bone marrow transplantation from September 1984 to July 1990 and not receiving this kind of prophylaxis. Streptococcal bacteraemia was diagnosed in 7/17 (41%) episodes of bacteraemia observed in the period January 1991 to December 1993, while it accounted for 71% of all bacteraemias in the period from September 1984 to July 1990 and was especially frequent from January 1988 to July 1990, comprising 13/15 (87%) of observed bacteremias. The decrease of this complication observed after the beginning of the prophylaxis programme was statistically significant. Oral penicillin V is effective as prophylaxis of streptococcal bacteraemias in children receiving bone marrow transplantation in a centre with a high incidence of this complication.

Administration, Oral↗
PubMed1995

Changing pattern of pathogens causing broviac catheter-related bacteraemias in children with cancer.

The incidence of pathogens causing catheter-related bacteraemias in children undergoing antineoplastic chemotherapy with or without bone marrow transplantation at G. Gaslini Children's Hospital, Genoa, Italy, was analysed by comparing data from a retrospective study (1985-1988) with that obtained from a prospective one (1989-1992). In both periods catheter-related bacteraemias one (1989-1992). In both periods catheter-related bacteraemias were more frequent in non-neutropenic than in neutropenic patients. Among catheter-unrelated bacteraemias the pattern of infecting pathogens remained unchanged between the study periods, with Gram-positive bacteria remaining the predominant pathogens. Conversely, among catheter-related bacteraemias, the incidence of Gram-negative bacilli increased significantly from 3 to 38%, and that of Gram-positive bacteria fell from 63 to 32% (P = 0.001, chi 2 test for heterogeneity.

Antineoplastic Agents↗
PubMed1995

An approach to the design and implementation of clinical trials of empirical antibiotic therapy in febrile and neutropenic cancer patients.

The results of many clinical trials on empirical therapy in febrile, neutropenic cancer patients cannot be readily transferred to the clinical practice, because the methodology is often flawed and definitions, study endpoints and eligibility criteria differ from trial to trial. This article critically reviews some issues related to the design and implementation of randomised clinical trials of empirical antibiotic therapy in cancer patients. Within the definition of phase III clinical trials, two approaches co-exist, based on the trial's specific aims: the "explanatory" approach and the "pragmatic" approach. The usual "explicit" aim of clinical trials of empirical therapy in febrile, neutropenic patients has been that of comparing the "efficacy" of two regimens. However, this term has been more often used with reference to the antibacterial activity of the regimen under study (explanatory aim) than to indicate the practical benefits it draws to the overall patient population treated for fever and neutropenia (pragmatic aim). These two meanings are often taken as perfectly interchangeable, while, conversely, they are completely distinct (though not independent) treatment effects. Most trials conducted in this patient population in recent years are explanatory trials, though not explicitly so, but their results have been widely applied to clinical practice, as they were pragmatic trials. In an explanatory trial the appropriate endpoint is success or failure (defined by clinical and laboratory data) among those patients affected with the specific infection for which the study drug is being given, while in pragmatic trials survival is probably the more appropriate outcome variable, since they are designed to assess the practical benefits that the overall population of febrile and neutropenic patients can obtain from the new empirical treatment. Unfortunately, survival is not a practical study endpoint for the difficulty in assessing the cause of death in this patient population and, especially, for the need for very large sample sizes, which might render the implementation problematic even for large, multicentre groups. Both types of trials need an intention to treat analysis, but this is especially crucial for pragmatic trials, which should not differentiate those cases in which success was obtained through multiple treatment modifications from those who did not require any treatment change. Obviously, this implies that no conclusion should be drawn about the antibacterial activity of the study drugs and that the number of treatment modifications should be taken into account in the interpretation of the results, especially for quality of life and cost evaluations. Information related to fever and signs of infection, age, underlying disease, neutropenia and concomitant administration of other antibiotics are crucial entry criteria that need to be clearly discussed and defined. Finally, the evaluation of toxicity is problematic in this patient population, due to the existence of a number of toxigenic factors, including the underlying disease, the type of infectious complication, the administration of chemotherapy and radiotherapy and the use of parental nutrition. All these effects tend to overlap, thus impairing the investigator's ability to detect specific drug-related side-effects.

Anti-Bacterial Agents↗
PubMed1995

Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory. Thus, new antibiotics with better activity against gram-positive bacteria should be tested. The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients. A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy. The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group. A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05). A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02). This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients. Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.

Adolescent↗
PubMed1995

Sex differences in the management of patients hospitalized with ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: Previous studies suggest that the management of coronary artery disease differs for women compared with men. We examined this issue for ischemic cerebrovascular disease. METHODS: We reviewed the use of angiography and carotid endarterectomy among patients discharged from Connecticut hospitals during 6 years over the past decade. Crude and age-adjusted rates of angiography and endarterectomy were determined for each sex. RESULTS: Among 22,582 female and 19,729 male patients discharged, the rate of cerebral angiography was 11.8% for men and 7.2% for women; the age-adjusted odds ratio was 0.77 (95% confidence interval [CI], 0.72 to 0.82). The rate of endarterectomy was 10.6% for men and 5.7% for women; the age-adjusted odds ratio was 0.67 (95% CI, 0.62 to 0.72). The distribution of cerebrovascular disease type differed by sex, however, with carotid artery disease representing a larger proportion of men (12.2% [2415/19,729]) than women (6.9% [1554/22,582]) (chi 2 = 355.8, P < .0001). When restricted to this diagnosis, no sex differences exist (odds ratio for angiography, 1.00 [95% CI, 0.87 to 1.14] and for endarterectomy, 0.93 [95% CI, 0.81 to 1.07]). CONCLUSIONS: Overall, women hospitalized for ischemic cerebrovascular disease undergo fewer angiograms and are less likely to have carotid endarterectomy than men. These differences are not found when analysis is restricted to subjects with carotid disease and suggest that part of the difference in management may be due to biological differences between men and women.

Aged↗
PubMed1994

Factors associated with bacteraemia in febrile, granulocytopenic cancer patients. The International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC).

The objective of this investigation was to determine factors predictive of bacteraemia at presentation in febrile, granulocytopenic cancer patients in order to estimate the probability of bacteraemia in each patient, and to compare factors associated with a diagnosis of gram-positive or gram-negative bacteraemia. Retrospective analysis of two sets of data (derivation and validation sets) randomly obtained from a large prospective study was conducted in a multicentre study of febrile, granulocytopenic cancer patients admitted for empiric antibacterial therapy. Within the derivation set, prognostic factors (clinical and laboratory data) likely to be associated with a generic diagnosis of bacteraemia and with a specific diagnosis of gram-positive or gram-negative bacteraemia were analysed by means of three backward, stepwise, logistic regression analyses. The predictive probability of bacteraemia was calculated using the logistic equation. The discriminating ability of the model in predicting bacteraemia was evaluated in the derivation and validation sets using receiver-operating characteristic curves. The predictive probability of gram-positive or gram-negative bacteraemia was not calculated. In the derivation set, 157 of 558 episodes (28%) were microbiologically documented bacteraemias. Predicting factors were antifungal prophylaxis, duration of granulocytopenia before fever, platelet count, highest fever, shock and presence and location of initial signs of infection. The variables institution, antibacterial prophylaxis and underlying disease showed borderline associations with bacteraemia. Shock was associated with gram-negative bacteraemia, while signs of infection at catheter site were predictive of gram-positive bacteraemia. Quinolone prophylaxis was negatively associated with gram-negative bacteraemia. When tested in the validation set, the model was poorly predictive, although a small subgroup of episodes (representing only 16% of the total sample size) with low risk of bacteraemia was identified. Factors predictive of bacteraemia can be identified, with discrimination between gram-positive and gram-negative aetiology. Further studies are warranted in order to improve the discriminant ability of the model.

Adolescent↗
PubMed1993

CT of invasive pulmonary aspergillosis in children with cancer.

In treating cases of malignancy, the use of chemotherapy carries a high risk of lower respiratory tract infections, especially fungal pneumonopathy. This complication is a major cause of mortality and is often difficult to diagnose because of non-specific clinical or radiological changes, but the early recognition of invasive fungal disease is imperative. CT is an important non-invasive method for the detection and evaluation of opportunistic fungal infections. In these patients an improved survival rate can be achieved when early detection by CT leads to the prompt institution of high-dose antifungal therapy. We illustrate the spectrum of CT findings of invasive pulmonary aspergillosis encountered in children with cancer. These patients had previously been treated with high-dose chemotherapy with or without bone marrow rescue, and underwent radiological examinations because of clinical evidence of pneumonopathy. Representative cases demonstrate the clinical applications of CT in the evaluation and management of invasive fungal disease.

Aspergillosis↗
PubMed1991

Listeria monocytogenes brain abscesses in a girl with acute lymphoblastic leukaemia after late central nervous system relapse.

A case of Listeria monocytogenes bacteraemia and meningitis with intracerebral abscesses in a girl with acute lymphoblastic leukaemia in relapse is reported. The clinical features included subacute onset with fever and marked irritability followed by seizures, meningism and confusion. The pathogen was isolated from blood and cerebrospinal fluid. Computerised tomography of the brain showed two intracerebral parenchymal localisations, in the left frontal lobe and in the right occipital lobe, respectively. The patient survived this severe infection without neurological sequelae. 2 months later she underwent allogeneic bone marrow transplantation without major complications. This case report should alert pediatric oncologists about the possible occurrence of severe intracerebral listerial infections in the immunocompromised child and suggests that this infection can be treated successfully and should not necessarily preclude continuation of antineoplastic treatments.

Brain↗
PubMed1991

Infections in the compromised child.

Children receiving chemotherapy for malignant diseases show different patterns of infection depending on their underlying disease and its therapy. Granulocytopenia carries the risk of bacterial infection, and also, if prolonged, of fungal infection. Impairment of cell-mediated immunity predisposes to infections with Pneumocystis carinii and is thought to be responsible for severe primary infections with varicella and measles, as well as the severe cytomegalovirus infections seen after allogeneic bone marrow transplantation. Absence or impairment of splenic function predisposes to overwhelming septicaemia with encapsulated organisms, while defects in the normal mechanical barriers to infection provide routes for bacterial and fungal invasion. Despite the lack of physical signs of a normal inflammatory response, clinical evaluation may be critical to the localization of infection in the immunocompromised child. Blood culture and biopsy remain pivotal investigations in the achievement of a microbiological diagnosis. Empirical treatment with a combination of antibiotics has been shown in comparative studies to be effective in initial management of the febrile neutropenic patient: continuing studies are evaluating the role of monotherapy and of different antibiotic combinations, particularly in the light of changing patterns of bacterial infections. Empirical antifungal therapy has been shown to be necessary for persistent or recurrent fever, particularly as persistent fungal infection may compromise the outcome of continuing cytotoxic therapy. Continuing uncertainties over many aspects of management of the infected immunocompromised child provide scope for clinical trials in parallel with trials evaluating new anticancer regimens. The use of new diagnostic methods, the role of prophylaxis, the most appropriate empirical regimen, the evaluation of new antimicrobial agents, all require careful evaluation for efficacy and safety. Perhaps the greatest dilemma of all is how far results from trials in adults can be extrapolated to paediatric practice.

Agranulocytosis↗