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Biomedical subjects

F Meunier

Publications and source records attributed to F Meunier.

At least 19 recordsLinked to original sources

Fungal infections in cancer patients: an international autopsy survey.

In an attempt to estimate the frequency of fungal infections among cancer patients, a survey of autopsy examinations was conducted in multiple institutions in Europe, Japan and Canada. Fungal infections were identified most often in leukemic patients and transplant recipients (25% each). Fifty-eight percent of fungal infections were caused by Candida spp. and 30% by Aspergillus spp. There was considerable variability in the frequency of fungal infections in different countries. Nevertheless, this study clearly demonstrates that fungal infections represent a common complication in cancer patients, especially in patients with leukemia.

Aspergillosis

Bacteraemia caused by non-aeruginosa Pseudomonas species in a cancer centre.

Fifty-one episodes of bacteraemia due to Pseudomonas species other than Pseudomonas aeruginosa occurring between 1980 and 1990 in a Belgian cancer centre were reviewed. This corresponded to an incidence of 0.62/1000 admissions, or 1.5% of all bacteraemic episodes. Twenty-nine episodes, each with several positive blood culture sets were considered clinically significant, including six patients belonging to a well-documented outbreak of pseudobacteraemia with Xanthomonas maltophilia and associated with contaminated blood sampling tubes. The respiratory tract was the source in six (20.7%), an infected intravenous catheter in 10 (34.5%) and the source was unknown in seven (24.1%). Seven patients died from infection (24.1%). Twenty-three episodes with a single positive blood culture set were considered clinically not significant, although four of them were considered significant by the Centers for Disease Control (CDC) criteria because of the presence of symptoms and specific antibiotic treatment being administered. None of the patients with a single isolate died from infection despite the fact that 17 of 22 did not receive an effective antimicrobial agent. All isolates were susceptible to co-trimoxazole.

Adolescent

Invasive infections due to Candida krusei: report of ten cases of fungemia that include three cases of endophthalmitis.

Candida krusei has become an increasingly important invasive pathogen, particularly in immunocompromised patients. Previous experimental and clinical experience suggest that C. krusei has a low propensity for hematogenously infecting the eye. We report 10 cases of fungemia due to C. krusei at our institutions, including three cases of endophthalmitis due to C. krusei. Fungemia was associated with nodular skin lesions in all seven patients with neutropenia and occurred despite administration of antifungal prophylaxis or empirical therapy. None of the patients apparently died as a direct result of C. krusei fungemia. Treatment with amphotericin B resulted in resolution of endophthalmitis, although one patient required vitrectomy. Early institution of aggressive therapy with amphotericin B may alter the course and improve the prognosis of C. krusei infection, particularly in immunocompromised patients.

Aged

Candidemia in immunocompromised patients.

This study reviews data on patients with fungemia and confirms the high prevalence (50%) of infections caused by non-albicans species of Candida. Fungemia due to C. albicans or Torulopsis glabrata occurred significantly more often in patients with a solid tumor, while fungemia due to Candida tropicalis or Candida krusei was significantly more common in patients with hematologic malignancy (P = .001). For 31% of patients, only a single blood culture was positive for yeasts, and the prognosis for these patients was not significantly different than that for patients with three or more positive blood cultures (P = 1), including those who had C. albicans fungemia. The overall mortality rate was 41.8%, which is much lower than that previously reported in studies of patients with cancer. No significant difference was observed between patients treated with amphotericin B and those treated with fluconazole in this retrospective analysis. Although no significant difference was observed in the mortality rate among patients who had fungemia with or without neutropenia, the incidence of disseminated candidiasis was significantly higher among neutropenic patients (P = .03).

Adolescent

Streptococcal and enterococcal bacteremia in patients with cancer.

Eighty-two episodes of bacteremia due to streptococci (including the genus Enterococcus) in 78 patients hospitalized at Institut Jules Bordet between 1986 and 1988 were reviewed. The incidence ranged from 5.5 to 7.6 per 1,000 admissions (16% of all bacteremias). Enterococcus faecalis, Streptococcus sanguis, and Streptococcus mitis were the most prevalent isolates, followed by Streptococcus angionosus, Streptococcus salivarius, and large colony-forming beta-hemolytic species (A, B, C, and G). Twenty-one episodes were polymicrobial. One-half of the patients had solid tumors, and one-half had hematologic malignancies. Forty-two patients were neutropenic (less than 1,000 polymorphonuclear neutrophils/microL). Only 15 episodes were acquired outside the hospital, and 11 episodes were breakthrough bacteremias. Twenty patients died within 1 month of the onset of streptococcal bacteremia. Five patients, two of whom were neutropenic, had fatal adult respiratory distress syndrome. The source of bacteremia remained undetermined in 35.4% of the episodes; the oral mucous membrane and the gastrointestinal tract were the most frequently recognized associated sites of infection. No unexpected antimicrobial resistance was observed except in two penicillin-resistant strains, one S. mitis and one E. faecium. No relation between peak or trough serum bactericidal titers and outcome could be demonstrated.

Adult

Antimicrobial prophylaxis for major head and neck surgery in cancer patients: sulbactam-ampicillin versus clindamycin-amikacin.

A total of 99 patients with head and neck cancer who were to undergo surgery were randomized in a prospective comparative study of sulbactam-ampicillin (1:2 ratio; four doses of 3 g of ampicillin and 1.5 g of sulbactam intravenously [i.v.] every 6 h) versus clindamycin (four doses of 600 mg i.v. every 6 h)-amikacin (two doses of 500 mg i.v. every 12 h) as prophylaxis starting at the induction of anesthesia. The two groups of evaluable patients (43 in the clindamycin-amikacin treatment group and 42 in the sulbactam-ampicillin treatment group) were comparable as far as age (mean, 57 years; range, 21 to 84 years), sex ratio (71 males, 28 females), weight (mean, 66 kg; range, 40 to 69 kg), indication for surgery (first surgery, 48 patients; recurrence, 37 patients), previous anticancer treatment (surgery, radiation therapy, chemotherapy), type of surgery, and stage of cancer. The overall infection rate (wound, bacteremia, and bronchopneumonia) within 20 days after surgery was 20 patients in each group. Wound infections occurred in 14 (33%) sulbactam-ampicillin-treated patients and 9 (21%) clindamycin-amikacin-treated patients (P = 0.19; not significant). The rates of bacteremia were 2 and 4%, respectively. The rates of bronchopneumonia were 14.3 and 23.2%, respectively (P was not significant). Most infections were polymicrobial, but strict anaerobes were recovered only from patients who received sulbactam-ampicillin. Antimicrobial treatment was required within 20 days after surgery for 42% of the sulbactam-ampicillin-treated patients and 44% of the clindamycin-amikacin-treated patients. By comparison with previous studies, we observed a decreased efficacy of antimicrobial prophylaxis in patients with head and neck cancer undergoing surgery because of the increased proportion of patients who were at very high risk for infection (extensive excision and plastic reconstruction in patients with recurrent stage III and IV cancers) and because of the longer duration of surgery.

Adult

[European Organization for Research and Treatment of Cancer (EORTC): objectives, realizations and future perspectives].

The objectives and realizations of the EORTC are described. The activities of the treatment branch are centralized at the EORTC Data Center located in Brussels. Approximately 6000 patients are included every year within clinical trials run by EORTC, involving active participation of more than 2000 physicians distributed in 350 institutions in Europe. 80% of patients included in EORTC trials are located in EC countries. Recently, new cooperative groups have been created in order to study cancers in elderly, tumors related to AIDS as well as invasive fungal infections in cancer patients. New perspectives and further developments include cost evaluations of new therapeutic modalities in oncology as well as quality of life of cancer patients. Furthermore, EORTC promotes the creation of a meta-analysis unit. A fellowship program to allow training of medical doctors and statisticians at the EORTC Data Center including scientists coming from Eastern and Central Europe is also encouraging. Every year, EORTC activities lead to at least 40 publications and more than 80 scientific communications allowing rapid diffusion of the results of researches performed.

Clinical Trials as Topic

Tissue distribution and bioactivity of amphotericin B administered in liposomes to cancer patients.

Amphotericin B concentration was measured by high-pressure liquid chromatography (HPLC) and by bioassay in tissues of 11 cancer patients who died from infection and/or their underlying disease after having received amphotericin B entrapped into sonicated liposomes (ampholiposomes). These concentrations were compared to those measured in 28 patients who had only received the commercially available preparation of amphotericin B-Na deoxycholate complex (Fungizone). The fungistatic and fungicidal titres of the tissue homogenates were also evaluated using two strains of Candida spp. and one strain of Cryptococcus neoformans to determine the bioactivity of amphotericin B incorporated in our liposomes. Tissue concentrations varied with the tested tissues and were correlated with the total dose of amphotericin B administered whether given as amphotericin B-Na deoxycholate or ampholiposomes. Amphotericin B concentrations measured by bioassay in tissue methanolic extracts reached 58-81% of concentrations measured by HPLC, whereas only 15-41% was recovered from the unextracted homogenates. Fungicidal titres were seldom measured in tissues, but fungistatic titres were observed and were linearly correlated with amphotericin B concentration measured by HPLC. These results were similar for the patients who received only amphotericin B-Na deoxycholate and for those who received both preparations (amphotericin B-Na deoxycholate and ampholiposomes). Our results suggest that the tissue distribution of amphotericin B is not significantly modified by the type of preparation (deoxycholate complex or liposomes) and that most of the tissue-bound amphotericin B is not bioactive. However, higher daily doses of amphotericin B can be administered safely when incorporated in liposomes and therefore high tissue concentrations may be obtained more rapidly with ampholiposomes than with amphotericin B-Na deoxycholate.

Adult

Empirical antimicrobial therapy with a single daily dose of ceftriaxone plus amikacin in febrile granulocytopenic patients: a pilot study.

The optimal management of fever in granulocytopenic patients remains controversial. This pilot study investigated the potential value of single daily doses of amikacin administered empirically with ceftriaxone in febrile granulocytopenic patients. None of the patients died as a result of infection or toxicity from the prescribed regimen. Serum concentrations failed to show drug accumulation. Modifications of empirical antimicrobial therapy were made at a similar rate to other conventional regimens. Vancomycin seemed to increase the incidence of nephrotoxicity. Overall, this pilot study suggests that empirical therapy with single daily doses of amikacin plus ceftriaxone is safe and effective and should be further investigated in a larger number of patients.

Adolescent

Efficacy of amphotericin B encapsulated in liposomes (AmBisome) in the treatment of invasive fungal infections in immunocompromised patients.

One hundred and twenty-six patients were treated for 137 episodes of fungal infection with liposomal amphotericin B (AmBisome) at 43 investigational centres. Among the patients were 72 with malignancies, 17 organ transplant recipients, 20 patients with immunological disorders and 17 others. AmBisome treatment was instituted after toxicity from previous amphotericin B treatment in 49 cases, nephrotoxicity or renal insufficiency in 40 and failure of previous antifungal treatment in 41. One hundred and eight episodes were clinically evaluable; among these 52 were caused by Candida spp. and 34 by Aspergillus spp. Ninety-nine patients were treated for at least eight days with a maximum dose of 0.7-5 mg/kg/day. Among 64 cases with proven invasive fungal infection 58% were cured. Fungi were eradicated in 35 of 54 (65%) mycologically evaluable cases. The cumulative dose was 3.2 +/- 3.2 (mean +/- S.D.) in cases where fungi were eradicated in comparison with 3.3 +/- 2.3 g in cases where fungi persisted. The eradication rate was 83% for Candida spp. compared with 41% for Aspergillus spp. (P less than 0.01). Among 24 cases with presumptive invasive fungal infections 14 (58%) were cured. Candida spp. were eradicated in seven of ten of these cases. Among 11 cases with superficial fungal infections eight were cured and three improved. Candida spp. were eradicated in four of five patients. It is concluded that AmBisome is an effective antifungal agent in a majority of patients with invasive or superficial fungal infections.

Adolescent

Liposomal amphotericin B (AmBisome): safety data from a phase II/III clinical trial.

AmBisome is a commercially available preparation of amphotericin B incorporated in small unilamellar liposomes. The analysis of safety data provided in a multicentre compassionate phase II/III study evaluating 133 episodes of therapy with AmBisome in patients with severe underlying disease is very encouraging. Rapid (30-60 min) administration of a high daily dose of AmBisome is feasible without the well known side effects observed with the conventional formulation of amphotericin B (Fungizone). Although eleven of 71 patients with initially normal serum creatinine concentrations showed increased values after AmBisome therapy, 17 patients among 50 with initially high creatinine concentrations recovered normal renal function during AmBisome treatment. Hypokalaemia was observed in 24 episodes of treatment (18%). Increases in serum glutamyl oxaloacetic transaminase and alkaline phosphatase were also quite common in this selected population with severe underlying disease and the contribution of AmBisome to these changes is difficult to establish. AmBisome appears a safe alternative to conventional amphotericin B, and its efficacy should be further investigated.

Adolescent

Randomized study of vancomycin versus teicoplanin for the treatment of gram-positive bacterial infections in immunocompromised hosts.

Seventy-four immunocompromised patients with severe infection due to gram-positive organisms were randomized to receive either vancomycin or teicoplanin. Extensive cancer was present in 71 patients, of whom 47 died within a month. The types of infections were 46 bacteremias (39 associated with central catheters), 24 skin and soft tissue infections (3 with bacteremia), and 7 others (mainly bronchopneumonia). The most frequent pathogen was Staphylococcus epidermidis, followed by Staphylococcus aureus. Microbiological eradication was obtained in 23 of 35 evaluable patients treated with vancomycin (65.7%) and 28 of 36 patients treated with teicoplanin (77.8%) (P = 0.4). Clinical cure and improvement were obtained in 26 of 35 patients (74.3%) and 27 of 36 patients (75.0%), respectively. No significant side effects were observed with teicoplanin, in contrast to reversible increases in serum creatinine (three patients) and skin rashes (four patients) with vancomycin. Superinfection was observed in five patients treated with vancomycin and two patients treated with teicoplanin. No relation was found between peak concentration in serum (at steady state) or bactericidal titers and outcome.

Adult

Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection.

The pharmacologic parameters and toxicity of netilmicin (6 mg/kg/day) given once daily (qd) or thrice daily (tid) for the treatment of urinary tract infections were studied in a randomized prospective study of 60 cancer patients. The overall efficacy was 96%. Nephrotoxicity, assessed by the measure of urinary excretion of phospholipids, was lower for the patients receiving the qd regimen than for those receiving the tid regimen. Elevation of serum creatinine (20% over baseline) occurred in one patient receiving the qd regimen and in three receiving the tid regimen. Cochleotoxicity, assessed by pure-tone audiometry (250 to 18,000 Hz) occurred in one patient receiving the qd regimen and none receiving the tid regimen. Concentrations in sera were measured on days 1 and 5. No significant accumulation was observed in either group. Median serum bactericidal titers, expressed as reciprocal values (percentage of the sera with a titer greater than or equal to 8), were measured against 25 test organisms in samples collected 6 h after the administration of netilmicin and were, for the qd group, 16 (82%) against members of the family Enterobacteriaceae and less than 2 (8%) against Pseudomonas aeruginosa, and for the tid group, 4 (57%) against members of the Enterobacteriaceae and less than 2 (0%) against P. aeruginosa. The rate of killing in serum was rapid (2 to 3 log in 2 h against P. aeruginosa; 3 to 5 log in 2 h against members of the Enterobacteriaceae) and correlated with the sampling time and hence the concentration in serum of netilmicin. The duration of the postantibiotic effect in serum depended also on the strain and the sampling time of the serum.

Adult

Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperative Group.

Empiric therapy for febrile granulocytopenic patients is mandatory, but whether monotherapy is a safe alternative and whether fluoroquinolones are useful agents for this indication are still controversial issues. The use of monotherapy with intravenous ciprofloxacin (200 to 300 mg every 12 h) was evaluated against combined therapy with piperacillin plus amikacin in febrile granulocytopenic patients with solid tumor or lymphoma. The study was discontinued prematurely because patients treated with ciprofloxacin had a significantly lower overall success rate than patients treated with piperacillin plus amikacin (31 of 48 patients [65%] versus 48 of 53 patients [91%], P = 0.002). Patients with gram-positive coccal bacteremia had a particularly poor outcome: therapy failed for six of eight patients (75%) treated with ciprofloxacin, while therapy failed for none of four patients treated with piperacillin plus amikacin. Death from primary infection during initially randomized protocol therapy occurred in 7 of 48 patients (14.5%) treated with ciprofloxacin and in 3 of 53 (6%) treated with piperacillin plus amikacin. This study does not support the use of this dose of intravenous ciprofloxacin as empiric monotherapy for fever in granulocytopenic patients.

Adult