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Biomedical subjects

F Meunier

Publications and source records attributed to F Meunier.

At least 91 records · Page 5Linked to original sources

[Current progress in antifungal therapy: the value of fluconazole].

Invasive fungal infections are major problems in immunocompromised patients and optimal therapeutical modalities are still far from optimal. Recently, progresses of antifungal therapy have been achieved with the development of new antifungal agents. In particular, fluconazole seems very promising due to the availability of oral and intravenous formulations. Tolerance and compliance of patients are excellent and side effects as well as interaction with other drugs are less commonly observed than with other antifungal agents available so far. The major indications of fluconazole are candidiasis and cryptococcosis.

Acquired Immunodeficiency Syndrome↗

Polymicrobial septicemia with Clostridium difficile in acute diverticulitis.

A case is reported of a patient without previous gastrointestinal symptoms, who presented with polymicrobial septicemia caused by Escherichia coli, Enterococcus faecalis, Clostridium difficile and Bacteroides vulgatus. Septicemia occurred during acute diverticulitis. A strain of Clostridium difficile, which was of the same serogroup C as the blood culture isolate and also produced toxin, was recovered from the stools, but the pathogenic role of this organism in the gastrointestinal symptomatology was not clearly established. Other reported cases of Clostridium difficile septicemia are also reviewed.

Adult↗

Successful treatment with liposomal amphotericin B in two patients with persisting fungemia.

Two granulocytopenic patients in whom fungemia persisted despite therapy with deoxycholate amphotericin B were subsequently successfully treated by daily intravenous administration of amphotericin B entrapped in sonicated liposomes made of egg yolk lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. High serum concentrations of amphotericin B could be maintained in both patients during therapy with liposomal amphotericin B and were associated with high in vitro antifungal activity. Liposomal amphotericin B was tolerated much better than the deoxycholate preparation. These findings suggest that the liposomal amphotericin B preparation is superior in the treatment of fungemia in granulocytopenic patients, and that randomized trials are warranted.

Agranulocytosis↗

Candidiasis.

Candida spp. are the most common fungal pathogens isolated in immunocompromised hosts, particularly cancer patients. Numerous clinical manifestations of candidiasis have been recognized, including localized infection such as oropharyngeal candidiasis or focal hepatic candidiasis, and disseminated infection resulting from hematogenous spread, with or without documented fungemia. Granulocytopenic patients are particularly at risk. Candida albicans is isolated in approximately 40% of cases of fungemia, other Candida spp. now also commonly being isolated. The rate of morbidity and mortality secondary to candidiasis is still significant despite numerous attempts to develop better diagnostic techniques, and more effective means of chemoprophylaxis and therapy. Currently, new antifungal agents and galenic preparations of amphotericin B are being evaluated with the aim of improving the prognosis of candidiasis in immunocompromised hosts.

Candida↗

Septicemias in cancer patients during parenteral nutrition: contributing factors and detection by weekly blood cultures.

Infections constitute the main complication of parenteral nutrition, particularly in cancer patients, but prediction of catheter-related septicemias (CRS) has been little investigated. We have evaluated, in 200 consecutive episodes of parenteral nutrition (PN) in cancer patients, the factors contributing to infectious complications, and the predictive value of weekly blood cultures performed through the nutrition catheter. The median duration of PN was 22 days with a total of 5816 patient-days of PN, neutropenia (neutrophils < 1,000/microl) being present in 872 (15%). Catheters were placed either in a jugular vein (71% single-lumen silicone catheters, 18.5% double-lumen Hickman-Broviac catheters) or in a femoral vein (10.5%). We observed 62 episodes of septicemia of which 22 were CRS (11% incidence for the 200 cycles) and 40 were non-CRS (20% incidence); CRS were mostly due to Staphylococcus epidermidis (14/22). Neutropenic patients as a group did not suffer more CRS than non-neutropenic patients, but the risk of CRS was slightly increased when expressed per day of neutropenia (8 CRS/872 days vs 14 CRS/4942 days without neutropenia, P < 0.05). On the other hand, a femoral insertion site was associated with a much higher incidence of CRS (9 CRS/21 femoral catheters vs 13 CRS/179 jugular catheters, P < 0.0001). It was possible to evaluate 20 episodes of CRS for their predictability by weekly blood cultures: the sensitivity for detecting CRS due to Staphylococcus epidermidis was 67%, the specificity 92%, the negative predictive value 98% and the positive predictive value 36%. The simple and widely available procedure of routine surveillance blood cultures performed through the PN catheter should be further investigated, because it could help the clinician to determine the origin of recent fever, particularly to exclude CRS and avoid unnecessary removal of PN catheters.

Journal Article↗

In-vitro activity of cilofungin (LY121019) in comparison with amphotericin B.

The in-vitro activity of cilofungin, a derivative of echinocandin B, was compared with that of amphotericin B in Sabouraud dextrose and Antibiotic Medium No. 3 against 100 clinical isolates of yeasts. Cilofungin appeared to be as effective, as amphotericin B against Candida albicans and yet more effective against Can. tropicalis as far as growth inhibition was concerned. Cilofungin was less active than amphotericin B against Can. (Torulopsis) glabrata and other species of Candida. It was not active against Cryptococcus neoformans. Minimum fungicidal concentrations (MFCs) of cilofungin were highly dependent on the medium, especially with Can. albicans. Low MFCs were observed in Antibiotic Medium 3 and very high MFCs were measured in Sabouraud's medium. Using a killing curve method, the initial rate of killing of amphotericin B was proportional to concentration with Can. albicans, Can. tropicalis, and Can. glabrata. With cilofungin the rate of killing was proportional to concentration only for Can. tropicalis.

Amphotericin B↗

In-vitro effects of cilofungin (LY121019), amphotericin B and amphotericin B-deoxycholate on human polymorphonuclear leucocytes.

The in-vitro influence of cilofungin (LY121019) and amphotericin B on human polymorphonuclear leucocytes (PMNs) was studied by a multifunctional approach. Cilofungin at high concentration (greater than or equal to 20 mg/l) increased adherence to plastic and ingestion of Staphylococcus aureus by PMNs in suspension and Candida albicans by adherent PMNs, and slightly decreased MTT reduction and superoxide generation. Amphotericin B and amphotericin B-deoxycholate decreased adherence to plastic (IC50: 5.1 and 8.2 mg/l respectively) and superoxide generation induced by PMA and opsonized zymosan (IC50 1.1 mg/l for amphotericin B-deoxycholate). Variable results were observed for intra-cellular killing and ingestion. The functional assessment was made with four clinical isolates of yeasts (Can. albicans, Can. tropicalis, Can. Torulopsis) (glabrata, Cryptococcus neoformans). The inoculum was preincubated with the antifungals (PRE) or they were added during (PER) or after ingestion (POST) using PMNs in suspension (PRE and PER), or adhering to plastic (PRE, PER and POST). With the scheme PRE, killing was usually increased with amphotericin B-deoxycholate and cilofungin. With Crypt. neoformans, ingestion was also increased by the antifungals and sodium-deoxycholate, probably by altering the capsule. The results of the scheme POST showed that amphotericin B-deoxycholate, but not cilofungin, increased intracellular killing of Can. albicans, Can. tropicalis and Can. glabrata.

Amphotericin B↗

Tissue concentrations and bioactivity of amphotericin B in cancer patients treated with amphotericin B-deoxycholate.

We have studied amphotericin B concentrations in tissues of 13 cancer patients who died after having received 75 to 1,110 mg (total dose) of amphotericin B-deoxycholate for suspected or proven disseminated fungal infection. Amphotericin B concentrations were measured by high-pressure liquid chromatography (HPLC) and by bioassay, the latter being done on tissue homogenates as well as on tissue methanolic extracts. The fungistatic and fungicidal titers of the tissue homogenates were also tested against three strains of Candida albicans and one strain of Aspergillus fumigatus. Tissue concentrations of amphotericin B measured by HPLC varied with the tested tissues as well as with the total dose of amphotericin B-deoxycholate administered and ranged from 0.4 to 147.1 micrograms/g. A mean of 38.3% (range, 23.0 to 51.3%) of the total dose was recovered by HPLC from all of the tested organs. Bioassay of tissue methanolic extracts reached 58 to 81% of the concentration measured by HPLC, whereas only 15 to 41% was recovered from the homogenates. Overall, 27.5% of the total dose was recovered from the liver, 5.2% was recovered from the spleen, 3.2% was recovered from the lungs, and 1.5% was recovered from the kidneys. The median concentration in bile was 7.3 micrograms/ml, suggesting that biliary excretion could contribute to amphotericin B elimination to an estimated range of 0.8 to 14.6% of the daily dose. Fungicidal titers were seldom measured in tissues, but fungistatic titers were observed and were linearly correlated with amphotericin B concentration measured by HPLC. In conclusion, only a small proportion of the amphotericin B administered as amphotericin B-deoxycholate to patients seems diffusible and bioactive.

Adult↗

[Prevention of bacterial infections using ciprofloxacin in granulocytopenic patients with cancer].

The optimal approach to reduce bacterial infections in granulocytopenic patients is still controversial. Recently, fluoroquinolones have been developed and real progress has been achieved in the prevention of Gram negative bacilli septicemia. This study reports our experience with ciprofloxacin and shows the excellent tolerance of ciprofloxacin by our patients as well as promising data for the reduction of Gram negative bacilli infection. However, practical modalities to prevent infection caused by Gram positive cocci remain to be defined.

Adolescent↗

Hepatic candidosis in a patient with acute leukemia.

Isolated hepatic candidosis has been described more frequently in patients with leukemia and consists in a particular clinical entity which remains difficult to control. We report here the case of a patient treated for acute nonlymphoblastic who developed hepatic candidosis two months after the end of intensive consolidation therapy.

Candidiasis↗

Pneumococcal bacteremia in cancer patients.

Twenty-eight episodes of Streptococcus pneumoniae bacteremia occurring in 27 cancer patients hospitalized in the Institut Jules Bordet between July 1979 and April 1985 were reviewed. Ten patients had hematological malignancies and 17 had solid tumors (in 7 cases, of the lung). Forty-four per cent of the patients were neutropenic (less than 1000/microliters) and 36% of the patients were in septic shock. In 36% of the patients no clinical source of S. pneumoniae bacteremia could be found. Seventy-nine (21% patients) received empirical antibiotic treatment containing a beta-lactam. Two patients who did not receive any empirical treatment died within 12 hours. Overall, 11/27 patients died within the first week, and 8/27 died within the first three days. Mortality in neutropenic patients was not different from that in non-neutropenic patients. In comparison with a similar study performed previously in our institution, there was no difference in incidence, type of patient, source of bacteremia, or mortality.

Adult↗

Incidence and significance of Clostridium difficile in hospitalized cancer patients.

The aim of the study was to assess the incidence and clinical significance of Clostridium difficile in patients in our cancer center. Over a period of seven consecutive months, 557 stools samples obtained from 156 hospitalized cancer patients (37 leukemic patients receiving oral antimicrobial prophylaxis and 119 patients from whom a stool sample was sent to the laboratory) were analyzed for the presence of Clostridium difficile. Clostridium difficile and/or its toxin was recovered from 13 (35%) of the 37 patients receiving oral antimicrobial prophylaxis, and from 15 (12%) of the other 119 patients (p less than 0.05). Isolation of Clostridium difficile was associated with diarrhoea in 13 (46%) of 28 patients but specific treatment was initiated only in 7 (25%) of the 28 patients in whom Clostridium difficile was isolated. The wide distribution of the serotypes identified in our patients does not suggest an epidemic situation in our hospital.

Carrier State↗

Nosocomial bacteremia caused by Bacillus species.

During a six year period, 11 cases of bacteremia caused by Bacillus spp. were observed corresponding to 1% of all bacteremic episodes in our hospital. Most patients had cancer as underlying disease. All cases of positive blood cultures were associated with a clinical syndrome compatible with sepsis including high fever. None of the subsequent deaths could be related to the bacteremia caused by Bacillus spp. Four of eight cases of Bacillus subtilis bacteremia were associated with the absorption of an oral preparation containing Bacillus subtilis spores, which was administered empirically in some units of the hospital to reduce what was considered to be tube-feeding related diarrhea.

Adult↗

Pilot study of amphotericin B entrapped in sonicated liposomes in cancer patients with fungal infections.

A pilot study with amphotericin B incorporated in sonicated liposomes (ampholiposomes) made of egg phosphatidylcholine, cholesterol and stearylamine in a molar ratio 4:3:1 was performed in cancer patients with fungal infections. Fifteen patients received a total of 117 intravenous infusions of ampholiposomes. The total dose of amphotericin B administered per patient ranged from 20 to 1004 mg (mean 472 mg). The number of infusions per patient varied from 1 to 20 (mean 8) and the duration of treatment from 1 to 29 days (mean 10 days). Infusion of doses up to 1.8 mg/kg was well tolerated. None of the common side-effects of Fungizone, the colloidal suspension of amphotericin B, occurred; it was noteworthy that patients had no renal function impairment. Serum amphotericin B concentrations given as ampholiposomes were much higher than those obtained with Fungizone. With a daily treatment schedule, peak and trough serum amphotericin B concentrations, as measured by HPLC, were 10 to 20 micrograms/ml and 5 to 10 micrograms/ml respectively; while they did not exceed 2 micrograms/ml and 1 microgram/ml with Fungizone. Amphotericin B given as ampholiposomes had a prolonged serum beta half-life (25.3 +/- 16.0 h). Higher serum antifungal activity was observed with ampholiposomes as compared to Fungizone. We concluded that ampholiposomes have a better therapeutic index than Fungizone.

Adult↗