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P Chavanet

Publications and source records attributed to P Chavanet.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients.

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.

Adult↗
PubMed2000

HIV-1 protease inhibitors induce an increase of triglyceride level in HIV-infected men without modification of insulin sensitivity: a longitudinal study.

We investigated longitudinally the effect of protease inhibitors (PI) on insulin sensitivity, glycemia, and serum lipids in HIV-infected patients. Ninety-one consecutive patients treated with PI for at least 12 months were included in this study. Fasting glycemia, lipid profile, insulinemia, CD4 T lymphocytes, and plasma HIV-1 RNA were performed at baseline and on PI therapy. Insulin sensitivity and insulin secretion were measured by the homeostasis model assessment (HOMA MODEL) using the fasting glucose and insulin concentrations. Triglycerides (+ 0.34 mmol/l, SD = 1.07, p = 0.001) and cholesterol (+ 1.07 mmol/l, SD = 1.21, p= 0.001) significantly increased on PI therapy. Fasting glycemia, insulin sensitivity, and insulin secretion were not modified after PI therapy. PI therapy significantly increased body mass index (0.35 kg/m2, p < 0.05). Serum lipid changes correlated with changes in the CD4+ cell count. Lipodystrophy was observed in 40.6% of patients treated with PI. Our longitudinal study found that PI therapy had no major impact on fasting glycemia, insulin sensitivity, and insulin secretion. These findings are not consistent with previous cross-sectional studies, which did not include baseline measurements before PI initiation. However, we observed a similar profile of lipid changes induced by PI therapy. These results suggest that PI could be responsible for the development of hypertriglyceridemia by a mechanism independent of insulin resistance which remains to be elucidated.

Adult↗
PubMed2000

Comparative genotyping of Candida albicans bloodstream and nonbloodstream isolates at a polymorphic microsatellite locus.

Molecular typing studies have shown that the predominant form of reproduction of Candida albicans is clonal and that, in a majority of situations, persistent or recurrent infections are due to a unique strain. Characterization of distinct subpopulations and correlation with clinical features may thus be important to understanding the pathogenesis of candidiasis. In a clonal model, a unique polymorphic marker may identify populations with different biological properties. We therefore compared 48 bloodstream isolates and 48 nonbloodstream matched strains of C. albicans at the elongation factor 3-encoding gene (CEF3) polymorphic microsatellite locus of C. albicans. Sizing of the alleles was performed by automated capillary electrophoresis. A new, 137-bp allele was characterized, and seven nondescribed combinations were observed, resulting in 15 and 11 distinct CEF3 profiles in bloodstream and control strains, respectively. Genotypes 126-135, 130-136, and 131-131 accounted for 60.4% of both bloodstream and control strains. Four bloodstream isolates but no control strains displayed the 135-135 combination. None of the other genotypes was present at an increased frequency in bloodstream isolates. Bloodstream and nonbloodstream strains of C. albicans thus have a heterogeneous structure at the CEF3 locus, with three major and multiple minor allelic combinations.

Alleles↗
PubMed1999

[Discontinuing protease inhibitor treatment of HIV-1 patients for intolerance. Longitudinal study of 309 patients].

OBJECTIVES: Determine the frequency and nature of interruptions in HIV-1 protease inhibitor treatment in HIV-infected patients. PATIENTS AND METHODS: A longitudinal study included patients treated with antiretroviral protocols including at least one antiprotease and followed from 1 March 1996 through 1 March 1998. RESULTS: Among the 309 patients followed for the duration of the study, 137 (44.3%) interrupted their antiprotease treatment at least once. Withdrawal was warranted by therapeutic failure in 49.6% of the cases and by drug intolerance in 45.4%. Drug intolerance concerned 37%, 36.7%, 5.7% and 2.9% of the patients taking ritonavir, indinavir, nelfinavir and saquinavir respectively (p < 106). Multivariate analysis demonstrated that saquinavir was significantly associated with better tolerance and with efficacy at least as good as ritonavir or indinavir. The most frequent cause for interrupting treatment were digestive disorders for ritonavir (20% of the treated patients) and lithiasic manifestations for indinavir (9.4%). The ritonavir-hepatitis C association appeared to predispose to drug-induced perturbed liver tests. CONCLUSION: Drug intolerance is a frequent cause of treatment interruption. Therapeutic success in HIV infection requires improved efficacy but also better tolerated antiretorviral drugs, particularly antiretroviral drugs.

Adult↗
PubMed1999

Development of a new experimental model of penicillin-resistant Streptococcus pneumoniae pneumonia and amoxicillin treatment by reproducing human pharmacokinetics.

The increase of penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia results in a greater risk of antibiotic treatment failure. In vitro data are not sufficient predictors of clinical efficacy, and animal models may be insufficiently contributive, since they often use immunocompromised animals and do not always respect the human pharmacokinetics of antibiotics. We developed an experimental PRSP pneumonia model in immunocompetent rabbits, by using intrabronchial instillation of PRSP (MIC = 4 mg/liter), without any adjuvant. This reproducible model was used to assess amoxicillin efficacy by reproducing human serum pharmacokinetics following 1-g oral or intravenous administrations of amoxicillin every 8 h. Evaluation was performed by using clinical, CT scan, macroscopic, histopathologic, and microbiological criteria. Experimental pneumonia in untreated rabbits was similar to untreated severe human bacteremic untreated pneumonia; in both rabbits and humans, (i) cumulative survival was close to 50%, (ii) red or gray lung congestion and pleuritis were observed, and (iii) lung and spleen concentrations reached 5 and 4 log(10) CFU/g. A 48-h treatment resulted in a significant bacterial clearance in the lungs (1.53 versus 5.07 log(10) CFU/ml, P < 0.001) and spleen (1.00 versus 4.40 log(10) CFU/ml, P < 10(-6)) and a significant decrease in mortality (0% versus 50%, P = 0.02) in treated versus untreated rabbits. No difference was observed on macroscopic and histopathologic lesions between treated and untreated rabbits (P = 0.36 and 0.78, respectively). Similar results were obtained by using a fully penicillin-susceptible S. pneumoniae strain (MIC = 0.01 mg/liter). Our findings suggest that (i) this new model can be contributive in the evaluation of antibacterial agents and (ii) 1 g of amoxicillin three times a day may be sufficient to treat PRSP pneumonia in immunocompetent humans.

Amoxicillin↗
PubMed1998

Does hepatitis C virus co-infection accelerate clinical and immunological evolution of HIV-infected patients?

OBJECTIVE: To study the influence of hepatitis C virus (HCV) co-infection on clinical and immunological evolution of HIV-infected patients. DESIGN: A longitudinal study of HIV-infected individuals with or without HCV infection, identified at the Infectious Diseases Department of Dijon University Hospital and enrolled in a historical cohort, was performed. METHODS: One hundred and nineteen HIV-infected people co-infected with HCV and 119 matched individuals infected with HIV alone were included in the cohort (median participation time 3 years; range, 2 months to 11.5 years). Clinical progression was defined as one or more of the following: a 30% decrease in the Karnofsky index; a 20% loss of body weight; an AIDS-defining illness (for non-AIDS patients); death (except by accident, suicide or overdose). Immunological progression was defined as a 50% decrease in the initial CD4 T-cell count (for patients with an initial count > 100 x 10(6) cells/l). Effects of HCV co-infection were evaluated using Kaplan-Meier survival analysis and significance was tested using univariate (log-rank and Peto's tests) and multivariate methods (Cox's model). RESULTS: In univariate analysis, immunological progression was not statistically different between the HCV-positive group and the HCV-negative group, whereas clinical progression was significantly faster in HCV-positive patients (P < 0.005, log-rank test). In a multivariate Cox model, clinical progression remained significantly associated with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI), 1.06-2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09-109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16-4.62; P < 0.02) for patients with an initial CD4 count above 600 x 10(6) cells/l. CONCLUSIONS: Clinical progression is more rapid in HIV-HCV co-infected patients than in HIV-seropositive patients are not infected by HCV. The prognostic value of HCV infection for both clinical and immunological progression is significant at early stages of HIV infection. These findings may argue for active management of hepatitis C infection in co-infected individuals, especially for asymptomatic patients whose CD4 count is above 600 x 10(6) cells/l, to predict and prevent accelerated progression of HCV and HIV diseases.

Adult↗
PubMed1998

Experimental efficacy of combined ceftriaxone and amoxycillin on penicillin-resistant and broad-spectrum cephalosporin-resistant Streptococcus pneumoniae infection.

The activity of amoxycillin and ceftriaxone, alone and in combination, was tested against four strains of penicillin-resistant pneumococci in vitro and in an animal model. Three of the strains were also resistant to third-generation cephalosporins. Fractional inhibitory concentration indexes for combined amoxycillin and ceftriaxone were measured by the Etest method and were considered additive (1.2; 1.1; 1.3 and 1.3 for the four strains). Twenty-four hour time-kill curves for two strains showed that the combination was additive or synergic for concentrations up to the MIC of the single drugs. The efficacy of these antibiotics alone and in various combinations against strains 16089 and 11724 were investigated in vivo using prolonged (48 h) experimental fibrin clot infection in rabbits. The bacterial reductions (delta log10 cfu/g) obtained for all the antibiotic combinations tested were significantly higher than those of the single drug regimens. The in-vivo efficacy of amoxycillin was significantly correlated with the time for which its concentration was above the MIC and that of ceftriaxone was correlated with its maximal concentration. From these findings, we concluded that, at concentrations easily achievable in humans, the combination of amoxycillin and ceftriaxone was strongly synergic against infection due to penicillin- and cephalosporin-resistant pneumococci.

Amoxicillin↗
PubMed1997

Non-Hodgkin's lymphoma of the heart in patients infected with human immunodeficiency virus.

A case of HIV-associated cardiac non-Hodgkin's lymphoma (NHL) is described, and the epidemiologic and clinicopathologic features of 21 cases previously reported in the literature are analyzed. All patients were homosexual males, and the cardiac NHL was the first acquired immune deficiency syndrome-defining condition in the majority. Patients were referred with nonspecific clinical findings including dyspnea and tachycardia, but rapid progression of cardiac dysfunction was frequent after symptoms appeared. Echocardiography constitutes the most useful noninvasive procedure in the diagnosis of cardiac NHL. Most of the patients had disseminated diseased at initial presentation; pathologically, the lymphomas were of B lymphocyte origin and of high-grade subtypes. Prognosis of HIV-associated cardiac NHL is generally poor, although clinical remission has been observed with combination chemotherapy. Cardiac lymphomas in HIV-associated patients are typically high-grade and often disseminate early. Although the prognosis is poor, patients in whom dissemination has not occurred could have longer survival under systemic chemotherapy.

Adult↗
PubMed1997

[Amphotericin B deoxycholate (Fungizone): old drug, new versions].

Amphotericin B-deoxycholate (Fungizone) remains the main treatment of systemic mycoses. However, its toxicity, especially renal impairment, limits its use. The chemical properties of this molecule led to its association with lipidic structures. Among the three so-called liposomal formulations of amphotericin B, only one (AmBisome) is a true liposome. Its tolerance is good, along with high blood concentrations. The two others formulations, either in disk or ribbon form, are not true liposomes and these formulations are not as well tolerated as the former. These three forms of amphotericin are very expensive, thus limiting their use. The association of amphotericin B with other lipidic structures is of great interest. The direct solubilization of Fungizone in an emulsion (Intralipid 20%) is inexpensive and easily prepared extemporaneously; this preparation of Fungizone leads to a strong reduction of side effects and its efficacy is at least equivalent to conventional Fungizone. In the future, the association with triglycerides or lecithins is probable: possibly providing promising formulations.

Amphotericin B↗
PubMed1997

In-vivo activity and tolerance of conventional formulation versus fat emulsion formulation of amphotericin B in experimental disseminated candidiasis in neutropenic rabbits.

Amphotericin B can cause significant toxicity but this can be reduced by direct dilution into a fat emulsion (Intralipid). To investigate the potential use of amphotericin B diluted in Intralipid, a study was made of its activity in the treatment of subacute disseminated candidiasis in persistently granulocytopenic rabbits, compared with the same dose of amphotericin B diluted in dextrose. Amphotericin-B-fat emulsion was at least as effective as amphotericin-B-dextrose. Amphotericin-B-fat emulsion was significantly more effective than amphotericin-B-dextrose therapy in reducing candida colony counts in both kidney and liver tissues (P < 0.05). Furthermore, amphotericin-B-fat emulsion was found less toxic on the renal function than conventional amphotericin B (P < 0.05). From these experimental results, we conclude that amphotericin-B-fat emulsion (Intralipid) was at least as effective and less toxic than conventional amphotericin B.

Amphotericin B↗
PubMed1996

Vertebral osteomyelitis due to Capnocytophaga species in immunocompetent patients: report of two cases and review.

Vertebral osteomyelitis caused by Capnocytophaga species was diagnosed in two adults. One of these infections was due to C. ochracea and the other was due to C. sputigena. Both patients were immunocompetent and presented with concomitant periodontitis and gingivitis. The infections were eradicated by means of prolonged antibiotic therapy, combined in one case with surgical treatment. Capnocytophaga species should be considered a potential cause of vertebral osteomyelitis in immunocompetent patients, especially in the presence of oral pathology.

Aged↗
PubMed1996

In-vivo activity and pharmacodynamics of cefotaxime in combination with vancomycin in fibrin clots infected with highly penicillin-resistant Streptococcus pneumoniae.

We studied the antipneumococcal efficacy of cefotaxime and vancomycin alone and a combination of cefotaxime with various dosages of vancomycin in the treatment of prolonged (48 h) experimental fibrin clot infections in rabbits. A clinical pneumococcal strain for which MICs were 2, 0.5 and 0.5 mg/L of penicillin, cefotaxime and vancomycin respectively, was used in this study. Cefotaxime was given iv at a fixed dose of 50 mg/kg and vancomycin iv at 1, 2.5, 5, 10 or 20 mg/kg. Maximal concentrations in clots were (mean +/- S.D.): 2.1 +/- 0.9, 1.1 +/- 0.4, 1.9 +/- 1, 2.3 +/- 1.5, 3.6 +/- 0.4 and 4 +/- 0.3 mg/g, respectively. The mean half-lives of elimination from clots were 2.2 h for cefotaxime and 7 h for vancomycin. We observed the highest bacterial reductions for the highest doses of vancomycin with or without cefotaxime. The combination of intermediate doses of vancomycin with cefotaxime led to higher antibacterial effects than either monotherapy. The low dose of vancomycin gave no significant additional effect compared with cefotaxime alone. The times of regrowth were similar for cefotaxime and cefotaxime-vancomycin 1, and also for vancomycin 10 and vancomycin 20 with or without cefotaxime but were significantly delayed for the combination cefotaxime-vancomycin 2.5 and cefotaxime-vancomycin 5 as compared with vancomycin 2.5 and vancomycin 5. By using a multivariate analysis, we demonstrated that the most important parameters were Cmax (r = 0.43) and AUC (r = 0.58) for cefotaxime alone and Cmax (r = 0.70) for vancomycin alone; none of the tested parameters was found to be significantly correlated with the efficacy of the combinations of cefotaxime and vancomycin. From these findings, and under the experimental conditions used (i.e., relatively low concentrations of cefotaxime), we demonstrated that the in-vivo antibacterial efficacy of the combination of cefotaxime and vancomycin was higher than each monotherapy when the local concentrations of vancomycin were at least 1.9 mg/L.

Analysis of Variance↗