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Biomedical subjects

S de Marie

Publications and source records attributed to S de Marie.

At least 37 records · Page 2Linked to original sources
PubMed1996

Liposomal amphotericin B (AmBisome) reduces dissemination of infection as compared with amphotericin B deoxycholate (Fungizone) in a rate model of pulmonary aspergillosis.

The efficacy of AmBisome, a liposomal formulation of amphotericin B, was compared with that of Fungizone (amphotericin B desoxycholate), in a rat model of unilateral, pulmonary aspergillosis. Repeated administration of cyclophosphamide resulted in persistent, severe granulocytopenia. The left lung was inoculated with a conidial suspension of Aspergillus fumigatus, thus establishing an unilateral infection. Antifungal treatment was started 40 h after fungal inoculation, at which time mycelial disease was confirmed by histological examination. Both Fungizone 1 mg/kg and AmBisome 10 mg/kg resulted in increased survival in terms of delayed as well as reduced mortality. Quantitative cultures of lung tissue showed that only AmBisome 10 mg/kg resulted in reduction of the number of fungal cfus in the inoculated left lung. Compared with Fungizone, both AmBisome 1 mg/kg/day and AmBisome 10 mg/kg/day significantly prevented dissemination from the infected left lung to the right lung. In addition, both AmBisome regimens reduced hepatosplenic dissemination, and the 10 m/kg dosage fully prevented this complication. In conclusion, when compared with Fungizone, in this model AmBisome is more effective in reducing dissemination of unilateral, pulmonary aspergillosis, even when given in relatively low dosage. Such low dosages may have a place in prophylactic settings.

Agranulocytosis↗
PubMed1996

Molecular epidemiology of apparent outbreak of invasive aspergillosis in a hematology ward.

During a 2-month period, five patients suffering from invasive infections caused by Aspergillus flavus or Aspergillus fumigatus were identified in the Hematology Department of the University Hospital Dijkzigt (Rotterdam, The Netherlands). To study the epidemiological aspects of invasive aspergillosis, strains from these patients and from the hospital environment, isolated during extensive microbiological screening, were subjected to genotyping. A novel DNA extraction technique, involving freezing, grinding, and direct lysis in guanidium isothiocyanate-containing buffers of mycelial material, was applied. DNA isolation was followed by typing by random amplification of polymorphic DNA (RAPD) analysis. This showed that strains isolated from all patients infected with the same fungal species were genotypically distinct, thus providing evidence against the possibility of an ongoing, single-source nosocomial outbreak. Strains could also be differentiated from strains of geographically diverse origins. However, an A. flavus strain from one of the patients was also frequently encountered in the hospital environment. As all environmental strains were collected after this patient had been diagnosed with invasive disease, the epidemiological value of this observation could not be ascertained. Intensive investigations showed no single source of A. flavus or other aspergilli. RAPD genotyping proved that the outbreak of invasive aspergillosis in the hematology ward consisted of a series of unrelated events and was not due to a common source within the hospital. RAPD fingerprinting of aspergilli may greatly facilitate future investigations of the epidemiology of invasive disease caused by these pathogens.

Adult↗
PubMed1996

Liposomal and lipid-based formulations of amphotericin B.

Encapsulating amphotericin B (AmB) into liposomes or binding of AmB to other lipid carriers results in a significant reduction of toxicity of AmB and possibly an increased therapeutic index. Following promising clinical results with investigational formulations, three industrial compounds have been developed: AmBisome, Amphocil (Amphotericin B Colloidal Dispersion) and Amphotericin B Lipid Complex (ABLC, Abelcet). These three formulations differ significantly in composition and pharmacokinetics. AmB serum levels after ABLC and Amphocil administration are low, but after AmBisome much higher. However, the interpretation of the pharmacokinetic data is hampered by the inability to separate free AmB fractions from tissue-, protein- and lipid carrier bound fractions. All three compounds share a considerable reduction of nephrotoxicity. However, the acute reaction rates differ among these compounds. Amphocil showing the highest and AmBisome the lowest rate. Unfortunately, efficacy data of ongoing trials comparing these formulations with conventional AmB are scarce. Therefore, for the moment we can recommend these compounds only in cases of intolerance to or failure on AmB therapy. The optimal therapeutic dosages have not been established, but dosages as low as 1 mg/kg should be avoided in the initial treatment of fulminant fungal infections, since efficacy may be inferior to equal doses of conventional AmB.

Amphotericin B↗
PubMed1996

The use of lipid formulations of amphotericin B for systemic fungal infections.

Despite its considerable toxicity, amphotericin B (AmB) remains the 'golden standard' in the treatment of many systemic fungal infections. To reduce this toxicity, with the aim of increasing its therapeutic index, AmB can be encapsulated into liposomes or bound to lipid carriers. Following promising clinical results with investigational formulations, three industrial compounds are available at this moment: Abelcet (Amphotericin B Lipid Complex, ABLC), Amphocil (Amphotericin B Colloidal Dispersion) and AmBisome. These three formulations differ significantly in composition and pharmacokinetics. All three compounds share a considerable reduction of nephrotoxicity, but the number of acute reactions differ among these compounds, Amphocil showing the highest and AmBisome the lowest rate. Increased therapeutic indexes for all three formulations were shown only in some of the animal models for several fungal infections. Four recent clinical trials comparing these formulations with AmB demonstrated their clinical efficacy but failed to clearly show an increased therapeutic index. Therefore these compounds can be recommended in cases of intolerance to or failure on AmB therapy. The optimal therapeutic dosages have not been established, but dosages as low as 1 mg/kg should probably be avoided in the initial treatment of fulminant fungal infections, since efficacy may be inferior to equal dosages of conventional AmB.

Amphotericin B↗
PubMed1995

[HIV infection in the Rijnmond area, 1985-1993: more transmission via heterosexual contact and drug use, and more female patients].

OBJECTIVE: To evaluate the characteristics of HIV infected patients in the Rijnmond region during 1985-1993. DESIGN: Descriptive. SETTING: University Hospital Rotterdam-Dijkzigt (AZR). METHOD: Data of medical records of all HIV infected patients in AZR were prospectively collected from 1988 on and retrospectively for 1985-1987. RESULTS: During the period 1985-1993 510 HIV positive patients consulted an internist at AZR (eight were infected with HIV-2). During the study 255 patients developed AIDS. Since 1991 fewer than 50% of the new HIV infected individuals belonged to the risk group of homosexual and bisexual men. The majority was infected by intravenous drug abuse or by heterosexual intercourse. Half the population infected by heterosexual transmission came from HIV endemic areas. The increasing number of HIV infection among heterosexuals was associated with an increasing number of HIV infected women. CONCLUSION: The Rijnmond region showed a noticeable shift of risk groups with HIV infection: heterosexual transmission and intravenous drug abuse were the cause of HIV infection in more than half of the HIV infections at AZR in 1992 and 1993. Counselling, health care and treatment should take account of the diversity of cultural backgrounds of the patient groups.

Adult↗
PubMed1994

Clinical use of liposomal and lipid-complexed amphotericin B.

Encapsulation of amphotericin B in liposomes or complexing of the compound with other lipid carriers brings about a major reduction in toxicity. Although animal experimental studies have shown an increased therapeutic index for a variety of such lipid formulations resulting in higher dose-dependent efficacy rates, clinical data on pharmacokinetics and efficacy are still scanty. AmBisomeR, Amphotericin B Lipid Complex (ABLC) and AmphocilR (Amphotericin B Colloidal Dispersion, ABCD) have quite different structural and pharmacokinetic characteristics; however, it is not clear whether these differences are important with respect to tolerance and efficacy. At this moment, most published clinical data are available for AmBisomeR, which shows encouraging results in a variety of invasive fungal infections. AmBisomeR has been safely administered in high dosages up to 5 mg/kg/day. Randomized comparative trials with liposomal and other lipid-complexed amphotericin B formulations versus conventional amphotericin B are urgently needed to assess their respective clinical values.

Amphotericin B↗
PubMed1994

Post-sclerotherapy bacterial peritonitis: a complication of sclerotherapy or of variceal bleeding?

To assess the risk of bacterial peritonitis following endoscopic variceal sclerotherapy (EVS), we recorded the incidence of this complication within 2 wk of the procedure in all patients (n = 216) undergoing 1092 sclerotherapy sessions in our hospital during a 5-yr period (1987-1992). The sclerotherapy sessions were separated in prophylactic EVS (without a previous bleeding, n = 172 sessions), elective EVS (following a previous variceal bleeding, n = 720), and emergency EVS (within 24 h of a variceal bleeding, n = 200). During the study period, 60 patients with spontaneous bacterial peritonitis were recorded. In 10 patients, peritonitis was diagnosed within 14 days after EVS. Six patients received emergency EVS and four elective EVS. In seven patients, Gram-negative aerobic and anaerobic microorganisms were cultured from the ascitic fluid, and in three patients cultures were negative; however, an elevated ascitic fluid polymorphonuclear cell count of > 0.5 x 10(9) cells/L was present. The mean period between EVS and the diagnosis of peritonitis was 3.5 days. On average, the patients had been febrile during 2.1 days before the diagnosis was established. None of the patients who had received prophylactic EVS developed peritonitis. The calculated risk to develop peritonitis following elective EVS was 0.5% (4/742 sessions) and following emergency EVS 3% (6/200 sessions) (p = 0.019, Fisher's exact test). Gram-negative gut-derived microorganisms were the most common pathogenic bacteria cultured from the ascites, which is different from the microbial flora causing bacteremia after EVS. This suggests that the risk for bacterial peritonitis is determined primarily by factors associated with bleeding, such as shock with increased bowel wall translocation of bacteria. These results indicate that standard antibiotic prophylaxis before EVS is not indicated, but could be considered in patients with liver cirrhosis and ascites receiving emergency EVS.

Adult↗
PubMed1993

Strategy for antibiotic therapy in febrile neutropenic patients on selective antibiotic decontamination.

In a non-randomized prospective study the need for broad-spectrum antibiotic therapy was evaluated in selectively decontaminated neutropenic patients with fever. Fifty-two adult patients with a neutrophil count < 0.5 x 10(9)/l suffered 77 febrile episodes while receiving oral antibiotics for selective decontamination. Antibiotic treatment was only initiated if additional clinical signs or the microbiological culture results pointed to the likelihood of an infection. Treatment was either empirically based (broad-spectrum) or specific (narrow-spectrum). If a causative agent was identified, therapy was adjusted accordingly. If evidence of infection was lacking after 72-96 hours, the antibiotics were discontinued, and these patients were reexamined meticulously and repeatedly. For the 40 episodes without confirmed infection, the median duration of therapy was three days (range 0-13 days) and the survival rate 100%; for the 37 episodes with confirmed infection, the median duration of therapy was 12 days (range 1-49 days, p < 0.0001) and the survival rate 85%. After adjustment of therapy the final regimen was broad-spectrum in only 18% of treated episodes. None of the six deaths could be attributed to the withholding or stopping of broad-spectrum therapy. It is concluded that in febrile neutropenic patients on selective decontamination a standard therapy regimen with prolonged administration of broad-spectrum antibiotics is not necessary. After initial intervention antibiotic therapy can safely be tailored to the needs of the individual patient.

Adult↗
PubMed1993

Diseases and drug-related interventions affecting host defence.

Recognition of an impaired immune system has implications for the diagnosis, treatment and outcome of infections. Not only the type of immunological dysfunction but also the degree of the dysfunction is important. A review is presented of the systemic diseases and immunosuppressive agents which may result in defects in host defence and associated infections. Especially in transplant patients and patients with HIV infection, knowledge of the stage of the host defense defect is important for the success of prophylactic regimens and for the clinical approach in the event of infection.

Alcoholism↗
PubMed1992

Blood culture bottles are superior to lysis-centrifugation tubes for bacteriological diagnosis of spontaneous bacterial peritonitis.

The conventional method of ascitic fluid culturing was compared with the bedside inoculation of ascites into blood culture bottles and into lysis-centrifugation tubes. The conventional culture method was compared with the blood culture bottle method in 31 episodes of spontaneous bacterial peritonitis (SBP). Cultures were positive with the conventional culture method in 11 (35%) episodes and with the blood culture bottle method in 26 (84%) episodes (P less than 0.001). The lysis-centrifugation tube method was compared with the blood culture bottle method in 24 episodes of SBP. Cultures were positive with the lysis-centrifugation tube method in 11 (46%) episodes and with the blood culture bottle method in 19 (79%) episodes (P less than 0.05). Moreover, the blood culture bottle method also shortened the time needed for the detection of bacterial growth. In conclusion, bedside inoculation of ascites into blood culture bottles should be used routinely for patients with suspected SBP. Culturing of ascites in lysis-centrifugation tubes is more laborious than and inferior to that in blood culture bottles.

Ascites↗
PubMed1992

Liposomal and lipid formulations of amphotericin B. Clinical pharmacokinetics.

Amphotericin B remains a very important drug for the treatment of fungal infections despite its toxicity. Encapsulation of amphotericin B into liposomes appears to reduce the toxic effects and to improve the clinical efficacy, allowing higher dosages to be given. The exact mechanism behind the reduced toxicity is not yet known. Amphotericin B is widely distributed after intravenous administration as the deoxycholate solubilisate. The highest concentrations are found in the liver, spleen and kidney. Protein binding and binding to the tissues is very high. The fate of the drug in the body is not known in detail. Renal and biliary excretion are both low and no metabolites have been identified. The drug is still detectable in the liver, spleen and kidney for as long as 1 year after stopping therapy. The pharmacokinetics of the different liposomal amphotericin B or lipid complexes of amphotericin B, which were recently developed, are quite diverse. A number of these preparations, such as amphotericin B lipid complex (ABLC), 'AmBisome' and amphotericin B colloidal dispersion (ABCD) are in clinical development. Their pharmacokinetics depend to a large extent on the composition and particle size of the liposomes or lipid complexes. Relatively large structures such as ABLC are rapidly taken up by the mononuclear phagocyte system, whereas smaller liposomes remain in the circulation for prolonged periods. In all studies only the total amphotericin B (both free and liposome- or lipid-associated) concentrations were determined. There is a need for studies correlating clinical efficacy and tolerability of liposomal amphotericin B with the pharmacokinetic properties of these formulations.

Amphotericin B↗
PubMed1990

Difficult-to-treat infections.

The most common problems in the management of serious bacterial infections were reviewed. As illustrations, the diagnostic and therapeutic strategies in two types of deep-seated infections--both associated with a poor penetration of antibiotics--were discussed: (1) In suppurative central venous thrombophlebitis, conservative therapy frequently fails; if so, one should promptly switch to a surgical approach; (2) in most patients with a parapharyngeal space infection, a non-surgical approach can be recommended including early diagnosis by computed tomography (CT), CT-guided needle aspiration, prompt administration of benzylpenicillin in high and frequent dosages or continuously, and follow-up by CT. This regimen may prevent radical surgery even in the presence of deep neck or mediastinal abscesses.

Anti-Bacterial Agents↗