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Biomedical subjects

A C Cremieux

Publications and source records attributed to A C Cremieux.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers.

BACKGROUND: Serious adverse effects have been observed with some non-sedative H1-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this study was to evaluate the potential of pharmacokinetic interaction between cetirizine and ritonavir, the most potent cytochrome P450 (CYP) inhibitor. METHODS: An open-label, single-center, one-sequence crossover pharmacokinetic study was conducted in three running periods: cetirizine (CTZ) alone, ritonavir (RTV) alone and then CTZ plus RTV. For each period, steady-state pharmacokinetics were obtained. RTV and CTZ plasma concentrations were determined using validated liquid chromatography methods. The statistical method was based on a 90% confidence interval (CI) for the ratio of population geometric means (combination/drug alone) for each drug and for each parameter [area under the plasma concentration versus time curve (AUC(0-tau,ss)), value of maximum plasma concentration (C(max,ss))] and compared to bioequivalence ranges 80-125% and 70-143% for AUC(0-tau,ss) and C(max,ss), respectively. RESULTS: Among the 17 male subjects enrolled (26.4 +/- 8.6 years), 16 completed the study (1 withdrawal after the first period). The RTV pharmacokinetic parameter values were not affected by CTZ co-treatment. With RTV, a 42% increase in the CTZ AUC(0-tau,ss) (3406 versus 4840 microgh/l, 90% CI of 128-158%), a 53% increase in the CTZ elimination half-life (7.8 h versus 11.9 h, P = 0.001), a slight increase (15%) in the CTZ apparent volume of distribution (V(d,ss)/f) (34.7 l versus 39.8 l, P = 0.035), a 29% decrease in the CTZ apparent total body clearance (49.9 ml/min versus 35.3 ml/min, P < 0.001) and bioequivalent C(max,ss) (374 microg/l versus 408 microg/l) were observed. No serious drug related adverse effects were notified. CONCLUSIONS: CTZ does not significantly affect the pharmacokinetic parameters of RTV, and the association does not, thus, require a modification of the dosage of the protease inhibitor. The increased extent of exposure to CTZ in healthy subjects, in the presence of RTV administered at high doses, remained in the same range as previously observed in the elderly or in mildly renally impaired subjects.

Adolescent↗
PubMed2001

[Prosthetic valve endocarditis due to Coxiella burnetii: six cases].

PURPOSE: Prosthetic valve endocarditis is a dangerous complication of valvular surgery (3-6%). Among involved pathogens, Coxiella burnetii is an occasional agent, though isolated with increasing frequency. We report our experience with this peculiar endocarditis and lay stress on specific diagnostic and therapeutic difficulties. METHODS: Between 1990 and 1995, six patients retrospectively met the diagnosis criteria for definite endocarditis due to Coxiella burnetii. RESULTS: Five Algerian men and one French woman presented with prosthetic valve endocarditis with negative blood cultures (on bioprosthesis: four cases, on mechanical valve: two cases). The main clinical and biological feature was febrile congestive heart failure with hepatomegaly, splenomegaly, hepatic and renal abnormalities, inflammatory syndrome, hypergammaglobulinemia, anemia and lymphopenia. Serological testing for Coxiella burnetii provided diagnosis in all cases. Echocardiography displayed vegetations in all cases. Valvular replacement was performed in four patients. With antibiotic therapy including doxycycline or/and hydroxychloroquine, quinolones or rifampicine, all patients experienced complete clinical, biological and echographic remission. CONCLUSION: Q fever prosthetic valve endocarditis presents as a systemic disorder occurring in patients with valvular heart disease. From now on, early diagnosis and efficient medical treatment may provide permanent prosthetic sterilization.

Adult↗
PubMed2001

[Evaluation of three testing strategies for detection of hepatitis C in a hospital medical consultation and in an HIV testing center].

AIMS: Testing for hepatitis C virus (HCV) is recommended. The purpose of this study was to evaluate the efficacy of HCV testing in a medical consultation without an appointment and in an HIV testing center based on three testing strategies: 1997 French Consensus Conference, "Lettre de la Direction Générale de la Santé" (January 1996), and extension to other risk factors. PATIENTS AND METHODS: For 6 months a free blood test was offered to any patient with a risk factor according to the literature. RESULTS: There were 1 736 new patients at the medical consultation and 1 616 at the testing center. The patients were younger at the testing center than at the medical consultation (31.1 vs 43.3 years; P<0.001). Acceptance of screening was better at the testing center (97.8% vs 75.2%; P<0.001). There were more patients exposed to one of the risk factors at the testing center (31.2% vs 13.9%; P<0.001). Tests were more efficient at the testing center: 30 HCV positive patients/1 616 (1.86%) vs 11/1 736 (0.63%, P<0.01). Tests based on the 1997 French Consensus Conference provided detection in 27/30 (90%) of HCV positive patients at the testing center but only 4/11 (36.3%) at the medical consultation (P<0.01). CONCLUSION: Testing was effective in both places but was more efficient at the testing center. Efficacy of the testing strategies differs significantly according to the place of screening. At the testing center, screening can be restricted to patients with a history of intravenous drug use and blood transfusion. At the medical consultation, screening should be extended to other risk factors.

Adult↗
PubMed1995

[Pneumococcal septic arthritis in HIV infection].

Infections due to pneumococci are frequent in patients infected with the human immunodeficiency virus (HIV), but joint infections are rare. We observed two cases of septic arthritis due to pneumococci in two non-haemophilic HIV seropositive patients. In the first case, a 31-year old drug addict who had undergone splenectomy, developed hip joint infection during an episode of meningitis due to pneumococci. The germ was moderately sensitive to ampicillin. The second case involved the knee joint in a 29-year-old woman who developed pneumococcal pneumonia after a trip to Zaire. In both cases, joint infection developed after antibiotics had been initiated, and in the first case, after the infection appear to be under control. This would be similar to "post-infectious" arthritis described in gonococcal and meningococcal infections. In HIV positive patients, joint infections are rare compared with other types of immunodepression, but can be observed in all stages of the disease. A total of 75 cases have been reported in the literature, including 8 cases due to pneumococci. These joint infections could be another argument in favour of anti-pneumococcal vaccination in HIV positive patients.

AIDS-Related Opportunistic Infections↗
PubMed1994

Dextranase enhances antibiotic efficacy in experimental viridans streptococcal endocarditis.

In endocarditis, exopolysaccharide production by viridans streptococci has been associated with delayed antimicrobial efficacy in cardiac vegetations. We compared the efficacies of temafloxacin alone and in combination with dextranase, an enzyme capable of hydrolyzing 20 to 90% of the bacterial glycocalyx, in a rabbit model of endocarditis. In in vivo experiments, rabbits were infected intravenously with 10(8) Streptococcus sanguis organisms and were treated 6 days later with temafloxacin (50 mg/kg of body weight intramuscularly twice a day) alone or combined with dextranase (1,000 U per rabbit per day intravenously). After 4 days of treatment (day 11), the animals were sacrificed and vegetations were quantitatively cultured. For ex vivo experiments, rabbits were infected as stated above and, on day 11, vegetations were excised aseptically and incubated in vitro in rabbit serum alone (control) or with temafloxacin or temafloxacin plus dextranase at concentrations similar to peak levels in plasma. In vitro, dextranase alone had no antimicrobial effect. In vivo and ex vivo, temafloxacin combined with dextranase was more effective than temafloxacin alone (P < 0.05). Our results suggest that dextranase is able to increase the effects of temafloxacin by reducing the amount of bacterial glycocalyx in infected vegetations, as confirmed in vitro by electron microscopy showing a markedly reduced amount of glycocalyx and a more clearly visible fibrin matrix.

Animals↗
PubMed1992

Efficacy of temafloxacin in experimental Streptococcus adjacens endocarditis and autoradiographic diffusion pattern of [14C]temafloxacin in cardiac vegetations.

Temafloxacin, a new fluoroquinolone, alone or in combination with tobramycin, was compared with penicillin, tobramycin, and their combination in the therapy of rabbits with endocarditis caused by Streptococcus adjacens GaDT, a new species of nutritionally variant streptococci. Animals were injected intramuscularly for 4 days with temafloxacin (50 mg/kg of body weight twice daily [b.i.d.]) alone or combined with tobramycin (12 mg/kg once daily), with procaine penicillin (150,000 U/kg b.i.d.) alone or combined with tobramycin (12 mg/kg once daily), or with tobramycin (12 mg/kg once daily) alone. Another group of animals was treated with a higher dose of temafloxacin (100 mg/kg b.i.d.). Temafloxacin, penicillin, and tobramycin MICs and MBCs were 1 and 2, 0.015 and 1, and 8 and 16 micrograms/ml, respectively. Time-kill curves showed that the addition of tobramycin to penicillin or temafloxacin increased the killing rate. In vivo, treatment with temafloxacin (50 and 100 mg/kg b.i.d.) alone reduced the bacterial counts in vegetations (3.9 +/- 0.9 and 3.1 +/- 0.8 log10 CFU/g of vegetation) compared with those in the vegetations of control animals (7.5 +/- 0.9 log10 CFU/g of vegetation). This result was similar to that obtained with penicillin alone (4.5 +/- 0.8 log10 CFU/g of vegetation). The combination of temafloxacin (50 mg/kg) and tobramycin was as effective as penicillin plus tobramycin (2.5 +/- 0.3 versus 2.3 +/- 0.4 log10 CFU/g of vegetation, respectively). The autoradiographic pattern of [14C]temafloxacin diffusion into infected cardiac vegetations was studied. Thirty minutes after the end of infusion of 250 microCi of [14C]temafloxacin, the [14C]temafloxacin was homogeneously distributed throughout the vegetations. These data support further evaluation of quinolones in experimental endocarditis.

Animals↗
PubMed1992

Optimal aminoglycoside dosing regimen for penicillin-tobramycin synergism in experimental Streptococcus adjacens endocarditis.

The combination of penicillin and aminoglycoside is the recommended therapy for endocarditis caused by nutritionally variant streptococci (NVS). However, the optimal aminoglycoside dosing regimen remains controversial. We compared the efficacies of four regimens of tobramycin alone or combined with procaine penicillin in the therapy of rabbits with endocarditis caused by Streptococcus adjacens, a new species of NVS. Animals were injected intramuscularly for 4 days with procaine penicillin (150,000 U/kg of body weight twice daily) or tobramycin at a low dose (3 mg/kg every 24 h) or a high dose (12 mg/kg every 24 h) either once or three times daily (t.i.d.) alone or in combination with procaine penicillin. Additional groups of animals were treated with the combination regimens for a shorter period of time (2 days) in order to demonstrate a possible difference in the rapidity of efficacy between the regimens. The MICs and MBCs were 0.015 and 1 micrograms/ml and 8 and 16 micrograms/ml for penicillin and tobramycin, respectively. The mean peak tobramycin levels in plasma were 2.4 +/- 1.3 (1 mg/kg t.i.d.), 5.4 +/- 3.7 (4 mg/kg t.i.d.), and 25 +/- 9.3 (12 mg/kg once daily). The mean penicillin levels in serum were always above the MIC. In vitro kill curves plotted at the time that peak concentrations were reached in plasma showed a concentration-dependent killing effect of tobramycin alone but not in combination with penicillin. In vivo, low-dose tobramycin was significantly less effective than the high dose. Results for the combinations of the different dosing regimens of tobramycin with procaine penicillin were not significantly different. Our results suggest that (i) against susceptible strains of streptococci, aminoglycoside alone exhibits a concentration-dependent killing effect both in vitro and in vivo; (ii) against NVS strains, combinations of penicillin and high- or low-dose tobramycin are equally effective; and (iii) aminoglycoside given once daily or at a low dose t.i.d. with penicillin could be a cost-effective alternative with reduced toxic risk for patients with NVS endocarditis when the bacteria are susceptible to the killing activities of both compounds.

Animals↗
PubMed1992

Daptomycin or teicoplanin in combination with gentamicin for treatment of experimental endocarditis due to a highly glycopeptide-resistant isolate of Enterococcus faecium.

Using an experimental endocarditis model, we studied the activity of daptomycin used alone or in combination with gentamicin against an Enterococcus faecium strain that was highly resistant to glycopeptides and susceptible to gentamicin. In vitro, the MIC of daptomycin was 1 micrograms/ml. In vivo, daptomycin appeared to be effective only when it was used in a high-dose regimen, i.e., 12 mg/kg of body weight every 8 h (-2.5 log10 CFU/g versus controls; P < 0.05), particularly when it was combined with gentamicin (-5.0 log10 CFU/g versus controls; P < 0.01). Since the distribution of daptomycin into cardiac vegetations, as evaluated by autoradiography, appeared to be homogeneous, the poor in vivo activity of daptomycin was considered to be related to its high degree of protein binding, as suggested by killing curves studies. Since the MIC of teicoplanin for the vancomycin-resistant E. faecium strain used in the study was only 64 micrograms/ml and since an in vitro synergy between teicoplanin at high dose and gentamicin was observed, a high-dose regimen of teicoplanin, i.e., 40 mg/kg every 12 h, was also assessed in vivo. This treatment provided marginal activity only when it was combined with gentamicin (-2.3 log10 CFU/g versus controls; P < 0.05). These results suggest that the levels of daptomycin or teicoplanin in serum required to cure experimental endocarditis caused by a highly glycopeptide-resistant strain of E. faecium would not be achievable in humans.

Animals↗
PubMed1989

Evaluation of antibiotic diffusion into cardiac vegetations by quantitative autoradiography.

The reason bacterial endocarditis is difficult to cure has been controversial for many years. One explanation could be that antibiotic diffusion inside the vegetations is heterogeneous. This hypothesis was investigated by means of an autoradiographic study of diffusion of labeled antibiotics into large infected cardiac vegetations of nutritionally variant Streptococcus endocarditis in rabbits. Ten days after infection, 653 microCi of [3H]penicillin, 410 microCi of [3H]tobramycin, or 174 microCi of [14C]teicoplanin were injected iv over 30 min. Thirty minutes after the end of infusion (T30), vegetation/blood radioactivity ratios were 2.48 +/- 1.27, 2.49 +/- 0.67, and 3.94 +/- 1.19 for penicillin, tobramycin, and teicoplanin, respectively. Autoradiography clearly showed that distribution of the three drugs was different: Tobramycin was homogeneously distributed; penicillin was more concentrated at the periphery but still reached the center of vegetations; teicoplanin was concentrated only at the periphery. The same distribution pattern was observed with teicoplanin at T120 (i.e., one t1/2 beta later) and also after simultaneous infusion of a therapeutic dose (15 mg/kg) of cold teicoplanin. The diffusion gradient exhibited by some antibiotics could explain the difficulty in sterilizing vegetations despite high local concentrations, and the deleterious effect of the size of the vegetations on the therapeutic response.

Animals↗
PubMed1989

[Antibiotic prophylaxis in cardiac surgery in France].

Prophylactic administration of antibiotics in patients undergoing cardiac surgery is now an established procedure. The interest of a short prophylaxis (less then 48 h), directed mainly against Gram positive cocci has been demonstrated. However, there is no general agreement as to the agent to be used. We thus conducted a survey of the current practice of antibiotic prophylaxis (ABP) by sending a detailed questionnaire to each of the 51 centers performing cardiac surgery in France. 48 replies (94%) were received. Monotherapy was used in 42 centers, with cephalosporins in 41 (cefamandole: 22, cefazolin: 10, cefuroxime: 4, cephalothin: 3, cefotiam: 2) and with minocycline in one center. Six centers used a combination including aminoglycoside. Mean duration of ABP was 1.8 +/- 1.2 d. First dose of antibiotic was given before cardiopulmonary (C-P) bypass intravenously. In 29 centers, AB was injected into the C-P pump. Mean dosage of cephalosporin before surgery was 25 mg/kg and total dosage was 70 mg/kg/24 h. We conclude that cephalosporins are almost exclusively chosen in France contrasting with other european countries such as the United Kingdom where the most used regimen is a combination of penicillinase-resistant penicillin and an aminoglycoside.

Aminoglycosides↗
PubMed1988

Nutritionally variant streptococci develop ultrastructural abnormalities during experimental endocarditis.

Nutritionally variant streptococci (NVS) are fastidious micro-organisms responsible for most of the so-called negative blood culture endocarditis. In patients, the relative resistance of these bacteria to antibiotic treatment may be relevant to bacterial alterations in infected tissues. We used here a rabbit experimental model of endocarditis in order to examine, under scanning and transmission electron microscope, the NVS ultrastructure inside cardiac vegetations and to follow alterations at the different stages of the disease. In the early phase (day 7) of endocarditis, NVS were found dispersed inside vegetations and exhibited a typical streptococcal morphology similar to that observed during an in vitro balanced growth. In contrast, on day 11 and day 18, bacteria were found gathered as large and numerous clusters, in which they exhibited abnormal ultrasturctural features similar to those previously described during in vitro unbalanced growth. At this stage, ruthenium red staining revealed a large amount of exopolysaccharide surrounding the bacteria. None of these bacterial alterations were observed inside the vegetations of rabbits treated from day 7 to day 11 with penicillin or vancomycin. These abnormalities might be mainly related to nutrient limitation inside the clusters and could contribute to the pathogenicity of these micro-organisms.

Animals↗
PubMed1988

3H-spiramycin penetration into fibrin vegetations in an experimental model of streptococcal endocarditis.

In-vivo diffusion of labelled spiramycin into fibrin was investigated in a rabbit model of left sided subacute endocarditis caused by a nutritionally variant streptococcus that produces large fibrin vegetations. Animals received one 30 min infusion of different doses of 3H spiramycin alone (73.4 +/- 3.5 microCi and 846 microCi) or 57.5 +/- 3.5 microCi in combination with 50 mg/kg 'cold' spiramycin. Thirty minutes after the end of infusion (T30) these vegetation/blood and vegetation/muscle ratios were between 1 and 2 and the vegetation/plasma ratio was between 2 and 4 for the three doses tested. Autoradiography showed that 3H spiramycin was homogeneously distributed throughout the vegetation in comparison with some other drugs. On the other hand, there were considerable differences in antibiotic concentration among different vegetations in a single animal.

Animals↗
PubMed1988

Serum antibody response to the 70,000-molecular-weight neisserial common antigen in humans infected by Neisseria gonorrhoeae.

We evaluated the presence of antibodies directed against a 70,000-molecular-weight (70K) common neisserial antigen in sera from patients with first or repeated gonococcal infections and in sera from healthy controls. Sera were taken as soon as possible after the onset of disease, and anti-70K antibodies were detected by Western blot (immunoblot). Results show that significantly fewer patients with gonococcal infection possessed anti-70K antibodies than controls (P less than 0.001). This suggests a possible role of anti-70K antibodies in natural immunity against Neisseria gonorrhoeae.

Antibodies, Bacterial↗
PubMed1985

Clinical and echocardiographic observations in pulmonary valve endocarditis.

Clinical and echocardiographic data from 12 patients with pulmonary valve endocarditis are described. Seven patients had isolated pulmonary endocarditis and in 5 patients other valves were infected (aortic, tricuspid, mitral or all 3). Two patients were heroin addicts and 4 had underlying heart disease (congenital heart disease in 3 and aortic regurgitation in 1 patient). The organisms involved were alpha streptococci in 3 patients (all with underlying heart disease), Staphylococcus aureus in 4, Streptococcus D bovis in 1 patient and Candida guillermondii in 1. M-mode and 2-dimensional echocardiography was performed in 10 patients and revealed vegetations in 8. Pulsed Doppler echocardiography was performed in 6 patients and revealed pulmonary regurgitation in all 6. Seven patients had pulmonary emboli. Four patients underwent surgery. Four patients died, including 1 after cardiac surgery. Five patients, including the patient infected with Candida guillermondii, recovered with antibiotic treatment.

Adolescent↗
PubMed1985

Comparison of penicillin and vancomycin, individually and in combination with gentamicin and amikacin, in the treatment of experimental endocarditis induced by nutritionally variant streptococci.

Six different antibiotic treatment regimens were compared for efficacy in rabbits with endocarditis induced by inoculation with a nutritionally variant strain of streptococcus. Seven untreated animals, sacrificed at day 11, had vegetations containing 8.89 +/- 1.35 log10 CFU/g, none of which was sterile. The vegetations from the rabbits in all treated groups had bacterial titers significantly lower than those of the controls (P less than 0.001). Vegetations from penicillin-treated animals averaged 5.14 +/- 1.00 log CFU/g, and no vegetations were sterile. Treatment with penicillin plus gentamicin or amikacin was more effective than treatment with penicillin alone, resulting in 3.99 +/- 0.94 log CFU/g of vegetation and sterile lesions in 5 of 12 animals. Treatment with vancomycin alone was as least as efficient as that with penicillin plus an aminoglycoside, resulting in an average of 3.33 +/- 0.96 log CFU/g of vegetation and sterile lesions in five of eight animals. Treatment with vancomycin plus an aminoglycoside was not superior to treatment with vancomycin alone, resulting in an average of 3.68 +/- 1.37 log CFU/g of vegetation and sterile lesions in 8 of 13 animals. These in vivo results correlated poorly with the in vitro susceptibility of the strain to the various antibiotics, as measured by the time-kill method. These results support the current practice of using vancomycin as alternative therapy when a penicillin-aminoglycoside combination is ineffective or contraindicated in patients with endocarditis caused by nutritionally variant streptococci.

Amikacin↗