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R Herbrecht

Publications and source records attributed to R Herbrecht.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prospective study of bacteraemia in cancer patients. Results of a French multicentre study.

We performed a prospective assessment of the current epidemiology of bacteraemia in cancer patients hospitalized in 70 different adult and paediatric haematology and oncology departments. Over a 1-month period, microbiologists from 54 hospitals collected clinical data relating to patients with at least one positive blood culture. In addition, all strains isolated were assessed for their in vitro susceptibility to three broad-spectrum cephalosporins suitable for empirical treatment in cancer patients: cefpirome, cefepime and ceftazidime. A total of 494 different strains were isolated from 1,038 blood cultures taken from 403 different patients. Seventeen strains were isolated from 13 patients with various nonmalignant diseases, and these cases were excluded from analysis. Overall, 330 (69.2%) of the strains were isolated in patients with haematological malignancy and 147 (30.8%), in patients with solid tumours. There was no difference in the distribution of the species involved in bacteraemia between patients with haematological malignancy and patients with solid tumours: coagulase-negative staphylococci were the leading pathogens (50.6% and 44.9%, respectively), followed by E. coli (11.2% and 12.2% respectively), S. aureus (6.3% vs 7.5%), streptococci (4.8% vs 5.4%) and P. aeruginosa (5.2% vs 4.8%). All other species accounted for less than 5% in both groups. There was no difference in the strain distribution with age (> or = 15 years vs < 15 years) or type of underlying disease. S. aureus and Enterobacteriaceae bacteraemia were more frequent in patients with end-stage disease, while oral streptococci, Enterobacteriaceae and P. aeruginosa infections were more frequent in patients who were severely neutropenic. Digestive tract decontamination was associated with increased frequency of oral streptococci and decreased frequency of Enterobacteriaceae infections. All three cephalosporins demonstrated similar activity against E. coli, while cefpirome and cefepime appeared to be more effective against other Enterobacteriaceae. Ceftazidime had better activity against P. aeruginosa. Cefpirome was the most effective against Gram-positive cocci, especially oral streptococci and methicillin-susceptible staphylococci.

Adolescent↗
PubMed1998

An EORTC multicentre prospective survey of invasive aspergillosis in haematological patients: diagnosis and therapeutic outcome. EORTC Invasive Fungal Infections Cooperative Group.

OBJECTIVES: The EORTC Invasive Fungal Infections Cooperative Group (IFICG) conducted a prospective survey by questionnaire of all cases of invasive aspergillosis (IA) in cancer patients to ascertain current diagnostic and therapeutic approaches. METHODS: All members of the IFICG were asked prospectively to complete a detailed questionnaire for each IA case identified in their institution over a 12-month period. RESULTS: One hundred and thirty questionnaires were returned. All cases were independently evaluated (DWD & JC) and 123 were eligible. Cases came from 20 hospitals in eight countries and the number of cases per institution varied from 1-21. Acute myeloid leukaemia (AML) (60, 49%), acute lymphoblastic leukaemia (ALL) (21, 17%) and lymphoma (11, 9%) were the most frequent underlying diseases, and 16 (12%) patients had received an allogeneic bone marrow transplant. Pulmonary involvement was present in 87%, infection of sinuses/nose in 16% and brain in 8%. The chest radiograph was initially normal in 9% of those with primary pulmonary disease. The diagnosis was confirmed in 50%, probable in 31% and possible in 19%. The evidence for IA was on the basis of clinical and radiological features alone in 28%, with culture or histology in another 31% and 9%, respectively, and with both culture and histology in 29%. In three (2%) patients with diagnosis was based on culture or histology alone. Treatment was given to 120 patients (98%)-amphotericin B 75%, lipid-associated amphotericin B 36%, itraconazole 40%, flucytosine 12%, growth factors 33%, lobectomy 5%. At 3 months after diagnosis or first suspicion of IA, 44 (36%) patients were alive and 79 (64%) dead. Outcome was best in those with AML (30% death and 46% with a complete antifungal response or cure). Growth factors (mostly granulocyte colony stimulating factor) appeared not to influence outcome (P = 0.99). CONCLUSION: IA remains a considerable diagnostic and therapeutic challenge. No single diagnostic procedure was universally successful and a multifaceted approach including surgery is necessary. There was no discernable difference in outcome between initial therapy with amphotericin B, itraconazole or lipid-associated amphotericin B, although numbers are limited and the study was retrospective.

Adolescent↗
PubMed1998

Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections.

It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n = 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n = 34) treated with AmB (P=0.09); P=0.03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P=0.05 and P=0.096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P=0.03). More patients on AmB had a >100% increase of their baseline serum creatinine (P<0.001). The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.

Adult↗
PubMed1997

Safety of amphotericin B colloidal dispersion.

The safety of amphotericin B colloidal dispersion (ABCD) was tested in five open-label Phase I/II clinical trials in 572 selected patients who had a fungal infection secondary to a severe underlying disease. In 442 cases ABCD was administered after therapy with amphotericin B, which had been withdrawn in 192 of them because of toxicity. One hundred and forty patients had pre-existing nephrotoxicity. ABCD doses of up to 6 mg/kg/day resulted in no differences in serum creatinine levels, even in patients with pre-existing renal failure. ABCD therapy resulted in no difference in liver function as measured by SGOT, alkaline phosphatase and total bilirubin levels in serum. Apart from thrombocytopenia, there was no significant alteration in hematological or other biochemical parameters in the blood. Adverse events attributable to ABCD requiring discontinuation of therapy occurred in 70 patients (12.2%). The most frequent of these were infusion-related adverse events, which occurred in 5.4% of patients. As a consequence, the maximum tolerated dose was set at 7.5 mg/kg/day. These studies show clearly that ABCD can be administered safely to patients without the risk of renal toxicity, even when renal impairment has already developed following therapy with conventional amphotericin B deoxycholate.

Amphotericin B↗
PubMed1997

A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients.

One hundred and thirty-four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c-AMB), liposomal amphotericin B 1 mg/kg/d(L-AMB1) or liposomal amphotericin B 3 mg/ kg/d (L-AMB3). Patients were entered if they had a pyrexia of unknown origin (PUO) defined as temperature of 38 degrees C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (< 0.5 x 10(9)/l). The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed, with success defined as resolution of fever for 3 consecutive days (< 38 degrees C) without the development of any new fungal infection. Clinical and laboratory parameters were collected for safety analysis. In both the paediatric and adult populations, L-AMB treated patients had a 2-6-fold decrease in the incidence (P < or = 0.01) of test-drug-related side-effects, compared to c-AMB. Severe trial-drug-related side-effects were seen in 1% of L-AMB treated patients, in contrast to 12% of patients on c-AMB (P < 0.01). Nephrotoxicity, in the patient subset not receiving concomitant nephrotoxic agents, defined as a doubling from the patients baseline serum creatinine level, was not observed in the L-AMB1 arm whereas the incidence was 3% in patients on L-AMB3 and 23% in those on c-AMB (P < 0.01). Moreover, time to develop nephrotoxicity was longer in both L-AMB arms than c-AMB (P < 0.01). Severe hypokalaemia was observed less frequently in both L-AMB arms (P < 0.01). Analysis was by intention-to-treat and included all patients randomized. Success was defined by a minimum of 3 consecutive days with fever (< 38 degrees C) continuing to study end indicated by recovery of neutrophils to 0.5 x 10(9)/l. Addition of systemic antifungal therapy or development of systemic fungal infection were failures as was persistent fever to study end. Efficacy assessments indicated success in 49% of the total group treated with c-AMB, 58% of patients responded to L-AMB1 and 64% to L-AMB3. A statistically significant difference was found between c-AMB and L-AMB3 (P = 0.03) but a Kaplan-Meier analysis of time to differvescence of fever showed there was no significant difference between the arms. It was concluded that liposomal amphotericin at either 1 or 3 mg/kg/d was significantly safer than conventional amphotericin B in children and adults. The main aim of this open-label study was to compare safety between the three trial arms. However, we provide evidence for an equivalent or possibly superior efficacy of liposomal amphotericin with regard to resolution of fever of unknown origin. Subsequent trials should compare amphotericin preparations in defined fungal infections.

Adult↗
PubMed1997

International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections.

Because of the rapidly increasing incidence of serious candidal infections, a consensus conference of 22 investigators from the United States, Europe, and Japan was held to discuss strategies for the prevention and treatment of deep-organ infections caused by Candida species. Commonly asked questions concerning the management of candidal infections were selected for discussion by the participating investigators. Possible answers to the questions were developed by the investigators, who then voted anonymously for their preferences. In certain instances, unanimity or a strong consensus was the result. In all cases, the full spectrum of responses was recorded and is presented in this report. The forms of candidal infection addressed included candidemia, candiduria, hepatosplenic candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and candidal peritonitis. Prevention and treatment strategies were considered for patients who have undergone surgery, for neutropenic and nonneutropenic patients, and for patients who have undergone bone marrow and solid organ transplantation. The therapeutic roles of amphotericin B (standard and lipid formulations) and the azoles were considered.

Animals↗
PubMed1997

Cefepime/amikacin versus ceftazidime/amikacin as empirical therapy for febrile episodes in neutropenic patients: a comparative study. The French Cefepime Study Group.

We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was < 100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.

Amikacin↗
PubMed1997

Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin's lymphoma: factors influencing chemotherapy administration. Groupe d'Etude des Lymphomes de l'Adulte.

The purpose of this study was to, assess the efficacy of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in the prevention of neutropenia and infection in patients receiving dose-intensive chemotherapy for non-Hodgkin's lymphoma (NHL). A second objective was to determine clinical predicators of delay to cytotoxic chemotherapy administration. One hundred-sixty two patients with intermediate- or high-grade NHL and at least one poor prognostic factor received a total of 4 cycles of the LNH-84-regimen every 2 weeks, with an open randomization to treatment with anthracyclines. Patients were randomized to receive subcutaneous lenograstim 5 micrograms/kg/day (n = 82) or placebo (n = 80) from day 6 to day 13 of each cycle. The incidence of severe neutropenia (absolute neutrophil count (ANC) < 0.5 x 10(9)/L) was reduced in the lenograstim group compared with placebo (52% vs 75%). A significant reduction (p < 0.001) in the median duration of ANC < 0.5 x 10(9)/L was also observed in patients treated with lenograstim during each cycle of chemotherapy (0-1 day vs 2-4 days in placebo recipients). Fever occurred in 66 patients in each treatment group. Thirty-four percent of placebo recipients had documented infections during ANC < 1.0 x 10(9)/L compared with 18.5% of lenograstim-treated patients (p < 0.05). Infections of > or = 2 severity were significantly less frequent (p = 0.001) among lenograstim recipients compared with placebo (25 vs 49). The most common adverse events among lenograstim recipients were headache, mild bone pain and injection site reactions. Although lenograstim significantly increased (p = 0.0001) relative dose intensity compared with placebo (93% vs 80%), no difference in CR rate (67% vs 71%) or 3-year survival (63% vs 55%) was observed. The results of this study suggest that patients treated with a chemotherapy regimen that induces severe neutropenia can benefit from treatment with lenograstim. Furthermore, lenograstim permits treatment to be delivered at full dose intensity at 2 week intervals, even in patients with bone marrow involvement, and may permit further dose escalation of the chemotherapeutic regimen used.

Adolescent↗
PubMed1997

Primary hepatic lymphoma associated with chronic hepatitis C.

Like other viruses (i.e Epstein'Barr virus), the role of hepatitis C virus is suspected in the pathogenesis of lymphoproliferative disorders. We report one case of primary hepatic malignant lymphoma associated with chronic hepatitis C viral infection. The diagnosis was obtained by percutaneous liver biopsy showing a non-Hodgkin's diffuse large cell lymphoma and micronodular cirrhosis. Serology for hepatitis C virus positivity was known three years before lymphoma diagnosis. Staging of the lymphoma confirmed multinodular primary hepatic lymphoma with no other detectable localisation. Complete remission has been obtained with aggressive chemotherapy. The role of hepatitis C virus in the pathogenesis of the lymphoma is unknown. An indirect mechanism is suspected. Chronic inflammation may evolve from polyclonal lymphocytic proliferation to true non-Hodgkin's lymphoma, as it has been suggested for non-Hodgkin's lymphoma in the emergence of cryoglobulinemia in hepatitis C positive patients.

Chronic Disease↗
PubMed1996

Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen. Groupe d'Etudes des Lymphomes de l'Adulte.

PURPOSE: Results of a multidrug chemotherapy regimen consisting of cyclophosphamide, pirarubicin, teniposide, and prednisolone (CTVP) plus subcutaneous granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS: Between January and December 1992, 46 previously untreated patients older than 69 years with intermediate- and high-grade NHL received cyclophosphamide 750 mg/m2, teniposide 75 mg/m2, pirarubicin 50 mg/m2 day 1, and prednisolone 40 mg/m2 days 1 to 3. G-CSF, 5 micrograms/kg/day, was administered from day 4 up to day 14 or when the absolute neutrophil count reached 5 x 10(9)/l. Six cycles were scheduled every 3 weeks. RESULTS: Grade 3 or grade 4 neutropenia complicated 22% and 26% of chemotherapy cycles, respectively. Fever or/and clinical infection were observed in 4% and 14% of cycles. One toxic death related to a septic shock occurred. Eight cycles (4%) were delayed with a median duration of 7 days. Administered median dose intensity was 93.5%. Objective response rate was 74% and 46% of the patients achieved a complete response. The 2-year overall survival and event-free survival rates were 47% and 28%. CONCLUSION: In comparison with a previous group of patients treated with CTVP, G-CSF allows delivery of chemotherapy with a reduced neutropenia-induced morbidity in an outpatient setting in elderly patients with aggressive NHL without modifying response rate or survival.

Aged↗
PubMed1996

The changing epidemiology of fungal infections: are the lipid-forms of amphotericin B an advance?

The incidence of invasive fungal infections is increasing and new fungal species are emerging as important pathogens. In cancer patients, the main risk factor for the development of systemic fungal disease is severe, prolonged neutropenia. Other factors, such as mucosal damage, presence of a central venous line, immunosuppressive therapy and treatment with broad spectrum antibiotics are contributory. Candida spp. are the fungi most commonly isolated in neutropenic patients. There has been a dramatic increase in non-C. albicans species, such as C. glabrata and C. krusei, largely as a result of extensive prophylactic and therapeutic use of fluconazole, to which these species are largely resistant. In neutropenic patients with candidaemia, amphotericin B is the drug of choice although the conventional formulation may be poorly tolerated. Lipid-based forms of amphotericin B, such as Abelcet, are better tolerated and can be given at a much higher dose and should therefore be considered in patients who fail on or are intolerant to the conventional agent. Aspergillosis is the second most frequent fungal infection in neutropenic patients. Primary invasive aspergillosis usually presents on chest X-ray with lung lesions and the brain is a frequent site of secondary infection. Fluconazole is inactive against Aspergillus spp. and amphotericin B is the standard treatment. Again, lipid-based forms are better tolerated than the conventional formulation in this setting, and have been shown to achieve response rates of 60% or more in a number of trials. Other potentially life-threatening fungal infections in which lipid-based amphotericin B may play an important therapeutic role in the future include cryptococcosis (increasingly problematic in AIDS patients), trichosporonosis, fusariosis and mucormycosis. Further randomized studies should be performed in a range of fungal infections to compare Abelcet with conventional amphotericin B and other lipid-based antifungal agents.

Amphotericin B↗
PubMed1996

Is the small non-cleaved-cell lymphoma histologic subtype a poor prognostic factor in adult patients? A case-controlled analysis. The Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To study the prognostic significance of the small non-cleaved-cell lymphoma (SNCCL) histologic subtype, we compared the outcome of adult patients with SNCCL with that of patients with aggressive lymphoma other than SNCCL by means of two case-controlled studies. PATIENTS AND METHODS: We analyzed the results of the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen used as a reference scheme in our cooperative study group (Groupe d'Etude des Lymphomes de l'Adult [GELA]) in 52 adult SNCCL patients with no bone marrow (BM) or CNS involvement. Forty-five SNCCL patients younger than 60 years could be compared with two separate case-matched groups of patients with aggressive lymphoma other than SNCCL undergoing the same therapeutic regimen. In the first case-controlled study, matching ensured identity of each risk factor of the age-adjusted International Index (ie, Ann Arbor stage, performance status, and lactate dehydrogenase [LDH] level); in the second study, matching was performed according to the number of presenting risk factors (zero, one, two, or three), regardless of their nature. RESULTS: The 5-year overall survival rates were not significantly different between SNCCL and control patients in both case-controlled studies: 48% versus 51% in the first study, and 48% versus 55% in the second study. CONCLUSION: These results support the thesis that in patients with no bone marrow or CNS involvement, the SNCCL histologic subtype does not confer a prognosis worse than that of other aggressive lymphoma.

Adolescent↗
PubMed1996

Idarubicin and high dose cytarabine: a new salvage treatment for refractory or relapsing non-Hodgkin's lymphoma.

Twenty three patients with relapsing (n = 11) or refractory (n = 12) non-Hodgkin's lymphoma (NHL) to one or two prior anthracycline based combination chemotherapy regimens were treated as second or third line regimen with 3 induction cycles of Idarubicin (IDA) (7 mg/m2/d i.v. d1-d3) and high dose cytarabine (HD Ara-C) (1 g/m2/12 h i.v. d1-d3), each cycle was repeated every 3 weeks. Responding patients received a maintenance therapy with monthly cycles of IDA: 15 mg/m2 d1-d3, Etoposide 100 mg/m2 d1-d3, both by oral route. Twenty two patients are evaluable and we observed 13 CR and 1 PR with an overall response rate of 61% (14/23: 95% Cl = 38.5% 80.3%). The median time to progression was 32 months (6.5 - 63 + m.). The response rate to IDA-HD Ara C was not different for patients with (n = 14) or without (n = 9) objective response to the last prior therapy. The main toxicity was hematological: all patients experienced grade 4 neutropenia and 22 patients had grade 4 thrombopenia, but there were no toxic deaths. IDA and HD-Ara-C combination is highly effective in refractory or relapsed. NHL. As hematological toxicity was the limiting factor for further escalation of dose-intensity, further studies might include hematopoietic growth factors support in the therapeutic scheme.

Adult↗
PubMed1996

Value of autologous bone marrow transplantation (ABMT) in 42 patients with follicular lymphomas responsive to conventional chemotherapy: a "France Autogreffe" study.

The value of high-dose chemotherapy with hematologic stem cell rescue has not yet been established in the treatment of low-grade non-Hodgkin's lymphoma. We report the results of a retrospective "France Autogreffe" study of 42 patients grafted during first partial remission (N = 13) or chemosensitive relapse (N = 29) for follicular lymphoma before January 1990. The median age was 38 years (range: 26 to 61 years). Preparative therapy was chemotherapy alone in 22 patients and total body irradiation (TBI)-containing regimens in 20 patients. Thirty-seven patients received hematopoietic marrow stem cells. Bone marrow purging was performed in 15 patients. Five patients received peripheral blood stem cells. With a median follow-up of 43 months, relapse-free survival is 66%, event-free survival 58%, and overall survival 83%. To date, no prognostic factors have been shown. Nine of these patients were tested for evaluation of minimal residual disease by polymerase chain reaction analysis of bc12 rearrangement in the blood. Six were positive.

Adult↗
PubMed1996

Cyclophosphamide/mitoxantrone/melphalan (CMA) regimen prior to autologous bone marrow transplantation (ABMT) in metastatic breast cancer.

Dose-intensive treatment followed by ABMT is currently used in different approaches to treat breast cancer patients. An active non cross-resistant regimen combining cyclophosphamide (C), mitoxantrone (M) and melphalan (A) (CMA), was developed as the conditioning regimen before ABMT. The purpose of this phase II study was to evaluate this protocol and the duration of its effect in metastatic patients, who responded to chemotherapy. Criteria for inclusion included histologically documented breast cancer, age < 55 years and the first detection of measurable metastatic lesions. Following first-line chemotherapy in responding patients, histologically negative bone marrow was collected and cryopreserved. Then, intensification with cyclophosphamide (120 mg/kg), mitoxantrone (60 mg/m2), and melphalan (140 mg/m2) was followed by ABMT. Sixty-one metastatic breast cancer patients with a mean age of 40 years were included. Sites of measurable metastases included: liver 24, lung 14, central nervous system four, pleura three, skin six, and chest wall six, nodes eight and bone marrow one. Nineteen patients had lesions in two or more sites, and 22 had bone involvement. The response of 60 patients could be evaluated: before ABMT 31 were in clinical complete response (CR), 22 in partial response > 50% (PR), and seven had new progression. After ABMT, 36 patients were in CR, 16 in PR, one progressed and one was stable. Seven (11.5%) toxic deaths occurred. Mean time for hematological recovery was 32.5 days, without hematopoietic growth factors. Median survival was 33 +/- 9.4 months from the start of therapy, and 25.7 +/- 4.6 months from the date of ABMT. Median event-free survival was 20 months from the start of therapy, and 13 +/- 2 months from ABMT. With a median follow-up of 51 months, probability of actuarial survival, measured from the beginning of initial chemotherapy, was 36%, and event-free survival was 18%. In metastatic breast cancer responding to chemotherapy, high-dose consolidation with CMA and ABMT resulted in a median survival of 33 months. These results lay the ground work for evaluation in a randomized trial in metastatic breast cancer.

Adult↗
PubMed1995

[Piperacilline/tazobactam combination+amikacin versus ceftazidime+amikacin in patients with neutropenia and fever. An open multicenter study. Groupe d'étude des Aplasies Fébriles].

OBJECTIVES: To evaluate the toxicity and effectiveness of piperacillin+tazobactam and amikacin compared with a reference treatment with ceftazidime and amikacin given as first line therapy in neutropenic patients with fever. METHODS: A multicentric randomized trial was conducted in 222 adults who had fever (38 degrees C for > 3 h) during a period of aplasia (white cell count < 0.5.10(9)/l for 22.9 +/- 10.4 days) induced by chemotherapy for acute leukaemia (68.1%) or by bone marrow autograft for lymphoma, myeloma or solid tumour (30.3%). 109 patients were assigned to the piperacillin (12 g/d)/tazobactam (1.5 g/d)+amikacin group and 113 to the ceftazidime (3 g/d)+amikacin group. Evaluation criteria were the frequency of apyrexia after a 72-hour antibiotic regimen and major infectious events defined as death due to infection and severe infections causing a delay in the chemotherapy protocol. RESULTS: Data obtained in 188 patients who fulfilled all the protocol criteria were evaluated. The episode of fever was controlled better with the piperacillin/tazobactam+amikacin combination (apyrexia achieved in 60.6% of the patients vs 44.7% in the ceftazidime+amikacin group, p = 0.028) and there were fewer superinfections (23% vs 41% respectively, p < 0.008). Tolerance was similar in the two groups. In vitro, 56% of the strains resistant to piperacillin and isolated prior to treatment were sensitive to the piperacillin/tazobactam combination. Among the strains isolated (41 Gram-, 61 Gram+), 72% were sensitive to ceftazidime and 84% were sensitive to the piperacillin/tazobactam combination. There were 16 deaths due to infection (8.5%) with no difference according to antibiotic regimen. There was no difference in toxicity. CONCLUSION: Tolerance was similar in the two groups. A combined regimen of piperacillin/tazobactam can be proposed as first line treatment for neutropenic patients with fever.

Adult↗
PubMed1995

The safety and efficacy of amphotericin B colloidal dispersion in the treatment of invasive mycoses.

Amphotericin B colloidal dispersion (ABCD), a novel formulation of amphotericin B and cholesteryl sulfate in a 1:1 ratio, was developed to reduce the toxicity of amphotericin B yet retain its antifungal efficacy. In an open-label trial, ABCD at dosages as high as 6 mg/(kg.d) was administered to 168 patients with documented or presumed systemic mycoses. All patients had responded incompletely to at least 7 days' treatment with conventional amphotericin B (CAB), had experienced CAB-induced nephrotoxic effects, had preexisting renal impairment, or had experienced other CAB-related, treatment-limiting toxic effects. The clinical response to ABCD could be evaluated in 97 patients. Complete clinical response or improvement was noted in 48 (49%) of them after a mean treatment duration of 18.5 days. All 168 enrolled patients were evaluated with regard to safety of the treatment. Even at daily doses as high as 6 mg/kg, and mean and median cumulative doses of 4.0 g and 2.4 g, respectively, ABCD had little renal toxicity: the mean change in serum level of creatinine from baseline to final value was -0.02 mg/dL. Hypokalemia developed in eight patients (5%). This study provides preliminary evidence that ABCD is effective in treating invasive mycoses and lacks the dose-limiting nephrotoxicity of CAB.

Adult↗