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M Duong

Publications and source records attributed to M Duong.

52 records · Page 3Linked to original sources
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↗
PubMed1996

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

Using a clinical pneumococcal strain for which MICs were 4, 2, and 32 mg/liter for penicillin, amoxicillin, and fosfomycin, respectively, we studied the efficacies of these antibiotics alone and their combinations in the treatment of prolonged (48-h) experimental fibrin clot infection in rabbits. Treatments were as follows: amoxicillin IV at 20 mg/kg of body weight in one dose (Amo20), 50 mg/kg in one dose (Amo50), or two doses 6 h apart (Amo20 x 2 and Amo50 x 2); fosfomycin IV at a fixed dose of 50 mg/kg in one dose (Fos50) or two divided doses 6 h apart (Fos50 x 2); or the combinations of amoxicillin and fosfomycin with the same schedules. Maximum concentrations in clots were 2.03 +/- 1.02 and 2.13 +/- 0.33 mg/liter for Amo20 regimens, 3.7 +/- 1.9 and 4 +/- 1.3 mg/liter for Amo50 regimens, and 24 +/- 7 and 40 +/- 8 mg/liter for fosfomycin regimens, respectively. The mean half-lives of elimination from clots were between 2 and 3 h for amoxicillin regimens and between 5 and 7 h for fosfomycin. We observed the highest bacterial reductions (log10 CFU/gram) for Amo50 in two divided doses with or without fosfomycin. A significantly higher bacterial reduction than that with each monotherapy was observed when Amo20 was combined with fosfomycin in either one dose or two doses 6 h apart (0.16 +/- 0.8 and 1.64 +/- 1.6 log10 CFU/g for Amo20 in one and two doses, respectively, and 0.93 +/- 0.81 and 0.61 +/- 0.56 log10 CFU/g for fosfomycin in one and two doses, respectively, versus 3.46 +/- 1.26 and 3.16 +/- 1.31 log10 CFU/g for Amo20 plus fosfomycin in one and two doses, respectively [P < 0.001]). A time-dependent effect was observed with amoxicillin regimens. The time of regrowth was significantly delayed when amoxicillin was combined with fosfomycin. By using a multivariate analysis, we demonstrated that the most important parameter correlated to efficacy of the combination amoxicillin-fosfomycin was the length of the period during which the concentration of amoxicillin remained above the MIC. We demonstrated that the in vivo efficacy of the combination of amoxicillin and fosfomycin gave higher antibacterial effect than each monotherapy.

Amoxicillin↗
PubMed1995

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

Using a clinical pneumococcal strain for which MICs were 2, 0.5, 0.5, and 16 mg/liter for penicillin, cefotaxime, ceftriaxone, and fosfomycin, respectively, we studied the efficacies of these antibiotics alone and in combination in one or two doses or in continuous infusion over 6 h in the treatment of the prolonged (48-h) experimental fibrin clot infections in rabbits. Doses were chosen to obtain low antibiotic concentrations. We observed the highest bacterial reductions (change in log10 CFU per gram) with the following five regimens: combination of cefotaxime plus fosfomycin given in two divided doses 6 h apart (each at 50 mg/kg of body weight given intravenously (4.2 +/- 0.7 CFU/g), ceftriaxone (8 mg/kg given once intravenously) along with one or two doses of fosfomycin (3.79 +/- 0.6 and 3.95 +/- 0.5 CFU/g), cefotaxime alone administered in two divided doses (3.6 +/- 0.4 CFU/g), and a 6-h continuous infusion of cefotaxime (100 mg/kg) with fosfomycin (100 mg/kg) (3.5 +/- 0.4 CFU/g). The bacterial reductions obtained with these five regimens were all higher than those obtained with the other regimens tested (P < 0.05). The time of bacterial regrowth was significantly delayed with the two doses of the cefotaxime-fosfomycin regimens (23.2 +/- 11 h) compared with those with the other combinations (P < 0.05). The rate of bacterial regrowth with this regimen was even lower than that observed with cefotaxime alone given in two doses (P < 0.05). By a multivariate analysis, the most important independent parameters for efficacy were the maximal concentrations of beta-lactam antibiotics and the residual concentration of fosfomycin and, for the combinations, the log of the area under the concentration-time curve/MIC ratio for beta-lactam antibiotics. From these findings, the combinations cefotaxime or ceftriaxone plus fosfomycin could be proposed for the treatment of infections caused by highly penicillin-resistant pneumococci.

Animals↗
PubMed1994

Cross-sectional study of the susceptibility of Candida isolates to antifungal drugs and in vitro-in vivo correlation in HIV-infected patients.

OBJECTIVES: To investigate (1) the frequency of clinical resistance to oral polyenes or azole treatment for oral candidiasis, (2) the frequency of resistant in vitro Candida strains, (3) the relationship between the susceptibilities of in vitro Candida species and in vivo status in HIV patients. DESIGN: Prospective cross-sectional study. SETTING: Tertiary care clinic at Bocage Hospital, Dijon, France. PATIENTS: HIV-infected patients with and without oral candidiasis. INTERVENTIONS: Clinical examination, oral swab for mycologic investigations. MAIN OUTCOME MEASURES: Clinical diagnosis of oral candidiasis, identification of the antifungal treatment given within the previous month, identification of Candida species, antimycogramm and determination of the minimal inhibitory concentration (MIC) for fluconazole, and measurement of T-helper cell count. RESULTS: Within a 2-month period, 154 HIV-infected patients were studied: 46 heterosexuals, 51 intravenous drug users (IVDU), 52 homosexuals and five blood transfusion recipients. The percentages of patients with oral candidiasis were: 41, 80, 44 and 20%, respectively (P < 0.05); the mean T-helper cell counts were 200, 135, 210 and 238 x 10(6)/l cells, respectively (P < 0.05). Twenty-two patients (14.3%) had received recent azole treatment and 29 (18.8%) recent oral polyene treatment. Among the 84 patients with and the 70 patients without oral candidiasis, 78 and 28 Candida strains were isolated, respectively. Although Candida albicans represented the majority of Candida species (88 strains, 83%), the non-albicans strains were isolated more frequently in patients who had received recent antifungal treatment. No strains were resistant to ketoconazole, miconazole or econazole; however, six (5.6%), 16 (15%) and 10 (9.5%) were intermediately susceptible to the three drugs, respectively. Twelve (13.6%) of the 88 C. albicans, five of the six C. (Torulopsis) glabrata, one of the five C. tropicalis and all three C. krusei strains were resistant to fluconazole. These resistant strains were separated as follows: 41.1% of C. albicans strains resistant to fluconazole were isolated from patients who had received recent azole therapy, 17.6% from patients who received recent oral polyene, and 3.7% from patients who had not received any recent antifungal treatment (P = 0.004). The mean MIC of these three categories of isolates were 3.6, 1.6 and 0.6 mg/l, respectively (P = 0.06). CONCLUSIONS: Oral candidiasis and fluconazole-resistant Candida isolates are more frequently found in IVDU. Treatments using azoles select non-albicans strains and are associated with decreased susceptibilities of C. albicans strains to fluconazole in particular. These findings show that prolonged azole treatment in severely immunocompromised patients should be avoided.

AIDS-Related Opportunistic Infections↗
PubMed1991

In vivo and in vitro mechanisms of drug resistance in a rat mammary carcinoma model.

Many in vitro tumor models have been examined to help understand the precise mechanisms responsible for drug resistance. The importance of these results in vivo remains uncertain. MatB 13762 is a rat mammary adenocarcinoma cell line that can be grown both in vitro and as a solid tumor in Fischer 344 rats, thus permitting the examination of tumor cell drug resistance under both conditions. Two cell lines have been selected in vitro for resistance to Adriamycin (AdrR) and melphalan (MlnR), respectively. Each subline has the following features: AdrR, increased mdr-1 messenger RNA, a high level of cross-resistance to vincristine and atypical low level resistance to melphalan and 1,3-bis(2-chloroethyl)-1-nitrosourea, decreased cellular glutathione content, and increased expression of Yc and Yp glutathione S-transferase isozymes; MlnR, low level drug resistance to melphalan and cross-resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea, Adriamycin, and vincristine; increased cellular concentration of glutathione; elevated glutathione S-transferase activity; and greatly increased messenger RNA specific to the Yc and Yp glutathione-S-transferase subunits. Most of the biochemical and molecular features described above are present but significantly less prominent in tumors grown in vivo. This model provides the opportunity to examine the magnitude of expression and the clinical significance of in vitro resistance in an in vivo model.

Animals↗
PubMed1989

Glutathione and glutathione S-transferases in clones of cultured rat liver epithelial cells that express varying activity of gamma-glutamyl transpeptidase.

In rat chemical hepatocarcinogenesis models, the hepatocytes in the preneoplastic/neoplastic nodules characteristically demonstrate common biochemical changes including significant and often marked elevation in the cellular glutathione (GSH) content and in the activities of the enzymes gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST). Such consistent and concomitant biochemical changes may signify a common regulatory mechanism in the expression of these enzymes. We have utilized a panel of clonally derived rat liver epithelial cell lines that express varying activities of GGT to study the quantitative correlation between these three cellular components of the phase II drug metabolizing enzyme system. The results indicate that in confluent cultures, cells with high GGT activities have significantly higher cellular GSH content, and a linear correlation exists between the glutathione content and the logarithm of the GGT activity. In contrast, the basal activities of GST and GGT were not coordinately regulated. However, most of the chemical carcinogen-treated cell lines, regardless of their GGT activity, expressed higher GST activity than the normal parental rat liver epithelial cells. The basal expressions of both the Yb and Yp subunits of GST were also not correlated with the relative expression of GGT. Since GGT may play an important role in supplying the cells with the basic constituents for the synthesis of GSH and since GSH is an important cellular molecule in the protection of cells from toxic electrophiles, enhancement of GGT activity in preneoplastic/neoplastic nodules of chemical carcinogen-treated rats may represent a necessary biochemical adaptation for the induction of the "resistant" phenotype of these hepatocytes.

Animals↗
PubMedDate not supplied

Therapeutic trials in HIV infection: which benefits for which patients?

PURPOSE: The purpose of our study was to make an assessment of the HIV patients' overall opinion of therapeutic trials, to analyze the motivations and the reasons linked to this perception, and to determine if their involvement in a therapeutic trial is a help or a hindrance to their treatment. METHOD: All the inpatients and outpatients attending the Dijon University Hospital AIDS day care unit during the first 4 months of 1999 were given an anonymous questionnaire designed to record the patients' attitudes toward therapeutic trials, their motivations, and the perceived risks. The questionnaire was often completed in consultation with a psychoanalyst. RESULTS: Two hundred and seven (207) patients were surveyed; 194 of them had a favorable opinion of therapeutic trials. The main motivations to take part in a therapeutic trial were altruistic. In contrast, individualistic considerations and relational motivations (such as to modify the relationship between the caregiver and the patient) were more closely associated with a negative perception. CONCLUSION: Most of the patients will benefit or at least will not be harmed by being involved in a trial. However, the patients' attitudes toward the principle of therapeutic trials have to be determined before these patients are included in a given therapeutic trial. This is necessary to avoid the risk of subsequent medical care being altered because participation was either induced or compelled.

Adult↗
PubMedDate not supplied

Randomized salvage therapy with saquinavir-ritonavir versus saquinavir-nelfinavir for highly protease inhibitor-experienced HIV-infected patients.

PURPOSE: To compare saquinavir + ritonavir and saquinavir + nelfinavir with nucleoside recycling in patients with multiple failures of highly active antiretroviral therapy (HAART). METHOD: This was a prospective, multicenter, randomized open trial. Inclusion criteria were the following: consent, age > 18, previous protease inhibitor (PI) exposure > 6 months, unchanged HAART > 3 months, and viral load > 3 log. The treatments compared were ritonavir 200 mg bid + saquinavir 600 mg bid (Rito-Saq), and nelfinavir 1,000 mg bid + saquinavir 600 mg bid (Nelf-Saq). Nucleoside analogues were recycled, and nonnucleoside inhibitors were not permitted. Trough levels of the three drugs were measured by high-performance liquid chromatography at the month 3 visit. After the study had been completed, genotyping analysis was done on the first serum at entry. RESULTS: The study was interrupted due to the availability of new anti-HIV drugs. A random sample of 31 (16 Rito-Saq and 15 Nelf-Saq) patients was divided into two groups, which were comparable in terms of demographic data and previous history of HIV infection. Mean CD4 cell count and plasma viral load (pVL) were 316 +/- 169 and 3.89 +/- 0.87 for Rito-Saq and 448 +/- 238 and 3.85 +/- 0.32 for Nelf-Saq. Previous duration of PI exposure was 31 months for both groups. The mean number of protease gene mutations was 3.8 (range, 2-7) and 4.4 (range, 2-9), respectively. On intention-to-treat (ITT) analysis at month 6, pVL stabilization or decrease >/= 0.5 log was observed in 18 patients (58%): 10 for Rito-Saq and 8 for Nelf-Saq. In a multivariate logistic regression analysis, virological success at month 3 was inversely correlated to baseline viral load (R = 0.14; 95% CI 0.03-2.9; p =.01); and at month 6, virological success was inversely associated to the number of mutations in the protease gene (R = 2.2; 95% CI 0.73-6.53; p =.06). CONCLUSION: Nelf-Saq and Rito-Saq combinations can be proposed in case of multiple HAART failures. The fact that the virological response was inversely correlated to baseline viral load makes the case for an early switch after a HAART failure.

Adult↗
PubMedDate not supplied

Evaluation of the Patient Medication Adherence Questionnaire as a tool for self-reported adherence assessment in HIV-infected patients on antiretroviral regimens.

PURPOSE: Adherence to antiretroviral medications is critically important for the success of therapy in patients treated for HIV infection. Patient self-report is a simple method to measure and explore adherence. Even though a variety of surveys have been developed to monitor self-reported adherence, there is no standardized instrument that may be used in routine clinical practice. The usefulness of the Patient Medication Adherence Questionnaire (PMAQ) was evaluated in HIV-infected patients on protease inhibitor (PI)-containing regimens. METHOD: Data from 149 patients were collected. Study participants completed the PMAQ and provided blood samples to measure plasma HIV-1 RNA concentrations and trough plasma levels of PI. Patients were considered adherent if they had a virologic response and/or had an adequate trough plasma level of PI. RESULTS: A close relationship was found between patient reports of adherence during the previous 4 days and objective measures such as HIV RNA level and plasma levels of PI. Motivation with regard to antiretroviral treatment, confidence in personal skills, and an optimistic attitude to life were identified as important determinants of adherence. On the other hand, sociodemographic background, social support, alcohol and illicit drug use, bothersome symptoms, and depression were not associated with a lower medication adherence. CONCLUSION: Patients' psychological and behavioral factors are central in the acceptance and adherence to antiretroviral therapy. To improve the feasibility and the reproducibility of the PMAQ, we propose a revised form of the PMAQ, focusing on the variables identified as strong predictors of adherence.

Adult↗