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P Chavanet

Publications and source records attributed to P Chavanet.

At least 19 recordsLinked to original sources
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

[New macrolides].

The macrolides are still widely used in general practice and the new 14- or 15 membered-ring compounds-roxithromycin, clarithromycin, dirithromycin, azithromycin -may offer a new development. Their antibacterial activity is similar to erythromycin but azithromycin is more active against Gram negative strams. Roxythromycin exhibits high serum concentrations; azithromycin and dirithromycin present low serum concentrations but prolonged half-lives allowing a reduction of the duration of treatment particularly for pharyngitis (azithromycin). Macrolides are less useful for otitis and sinusitis treatment since their activity against H. influenzae and S. pneumoniae are weak. The activity against atypical bacteria justify their choice as first line treatment for benign atypical pneumonia of healthy young adults and for sexually transmitted diseases. In AIDS, these compounds are indicated in mycobacteriosis (clarithromycin), bacillary angiomatosis and excavated pneumonia due to Rhodococcus equi. Clinical tolerance is very good, particularly the gastro-intestinal one. The reported drug interactions are those of this class of antibiotics.

Anti-Bacterial Agents↗
PubMed1994

The penetration of amphotericin B from an Intralipid formulation into fibrin loci in a rabbit model of candidiasis.

The kinetics of amphotericin B (AMB) concentrations in plasma and interstitial fluid were studied in an experimental model of Candida albicans infection in rabbits. Rabbits were infected by subcutaneously implanted fibrin clots containing the yeast. Three groups of five rabbits received a 4 mg kg-1 AMB infusion. AMB (Fungizone) was dissolved in 5% glucose (group I) or in 20% Intralipid at a final concentration of 1.5 (group II) or 3 mg mL-1 (group III). AMB was measured by liquid chromatography in plasma and in trypsin-dissolved fibrin clots up to 72 h after the infusion. No significant differences in AMB plasma and interstitial-fluid concentration kinetics between the three modes of administration were found. AMB penetration into fibrin clots was slow, with no significant differences between treatments. Thus, formulation of AMB in Intralipid does not modify either the drug's interstitial or plasma kinetics at equivalent doses.

Amphotericin B↗
PubMed1994

A controlled trial of the tolerance of amphotericin B infused in dextrose or in Intralipid in patients with haematological malignancies.

Patients with haematological malignancies requiring an antifungal therapy were randomly assigned to receive amphotericin B diluted in either 5% dextrose or in fat emulsion (Intralipid). Twenty-one patients were included in each group. Mean duration of amphotericin B therapy was 8.4 days in the dextrose group and 12.8 days in the Intralipid group. Amphotericin B infusion induced chills in 16 of 21 patients in the dextrose group and in 5 of 21 in the Intralipid group (P = 0.0008). Serum creatinine increased > 75% from baseline in ten patients in the dextrose group compared with only two in the Intralipid group (P = 0.007). A > or = 50% decrease of creatinine clearance was observed in 14 of 21 patients in the dextrose group compared with seven of 21 patients in the Intralipid group (P = 0.025). No difference was found between the two groups with regard to potassium and sodium requirement. Among patients who did not receive magnesium before antifungal therapy, magnesium supplementation was required more frequently in the dextrose group (8/12 vs 2/11; P = 0.02). Concomitant amikacin dosage reduction was more frequent in the dextrose group due to nephrotoxicity (7/19 vs 2/20; P = 0.045). A similar difference in vancomycin dosage reduction was observed between the two groups (12/20 vs 5/19; P = 0.03).

Adult↗
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↗
PubMed1994

Influence of diet on experimental toxicity of amphotericin B deoxycholate.

The effects of pre- and postprandial levels of lipids in serum on the experimental in vivo and in vitro toxicities of amphotericin B deoxycholate (AmB-d) were studied. Normal OF1 mice were tested at baseline, after normal feeding, after 3 h of fasting, or after a sequence of feeding and fasting and vice versa. The 50% lethal dose (LD50) of AmB-d was significantly higher in fed mice than in mice which fasted or at baseline (2.38 +/- 0.12 versus 1.53 +/- 0.2 and 1.50 +/- 0.1 mg/kg of body weight, respectively; P < 0.05). When different nutritional regimens were alternated over a short period, the level of in vivo AmB-d toxicity was dictated by the last feeding regimen. Serum triglycerides, but not cholesterol in very-low-density and low-density lipoproteins, correlated significantly (P < 0.01) with the LD50 of AmB. In vitro experiments showed that the addition of human serum reduced AmB-d-induced toxicity against human erythrocytes, but serum drawn after fasting was less protective than postprandial serum. However, neither serum decreased the in vitro activity of AmB-d against Candida albicans. Circular dichroism, a method that enables the amount of free AmB to be measured, showed that both mouse and human total serum lipoproteins bound more AmB-d when serum was isolated postprandially than when it was obtained after fasting. Our results show that AmB-d toxicity is reduced by feeding-induced modifications in serum lipids. The influence of food intake on the clinical toxicity of the drug merits being investigated.

Amphotericin B↗
PubMed1994

Five versus ten days treatment of streptococcal pharyngotonsillitis: a randomized controlled trial comparing cefpodoxime proxetil and phenoxymethyl penicillin.

A total of 220 adults and children > 10 years old (mean 29.5 +/- 11.7 years) with pharyngitis/tonsillitis were randomized to receive either cefpodoxime proxetil 100 mg bid for 5 days (n = 113) or phenoxymethyl penicillin, 600 mg tid for 10 days (n = 107). At the end of treatment of the 166 evaluable patients, a satisfactory clinical response was obtained in 85/88 (96.6%) patients treated with cefpodoxime proxetil and in 75/78 (96.1%) treated with phenoxymethyl penicillin. Group A beta-hemolytic streptococci (GABHS) eradication was similar in both groups: 79/82 (96.3%) patients in the cefpodoxime proxetil group and 64/68 (94.1%) patients in the phenoxymethyl penicillin group. At follow-up (20-30 days after the end of treatment) the GABHS eradication persisted in 67/72 (93.1%) patients treated with cefpodoxime proxetil and in 56/61 (91.8%) patients treated with phenoxymethyl penicillin. Significantly better compliance (p < 0.01) was noticed with the cefpodoxime proxetil regimen compared with the phenoxymethyl penicillin regimen, with only 2/110 (2%) poorly compliant patients in the cefpodoxime proxetil group vs 17/104 (16%) in the phenoxymethyl penicillin group. Thus, the shorter duration of therapy, in conjunction with demonstrated clinical and bacteriological efficacy that is equivalent to standard therapy, makes cefpodoxime proxetil an acceptable alternative for the treatment of GABHS pharyngitis/tonsillitis.

Adolescent↗
PubMed1993

Three-week hepatitis B vaccination provides protective immunity.

To determine whether a 3-week hepatitis B (HB) vaccination could achieve protective immunity, 89 healthy non-immunized young adults received three doses of 20 micrograms each of HBs antigen (GenHevac B, Pasteur) and were randomly assigned to schedule A (n = 44): two doses at day 0, one dose at day 21; or schedule B (n = 45): one dose at days 0, 10 and 21. Seroprotection rates (anti-HBs > or = 10 mIU ml-1) for groups A and B respectively were: 23 and 40% at day 21; and 77 and 91% at day 82 (not significant). Anti-HBs geometric mean titres were higher in group B than in group A (p < 0.05) at days 21 (6.4 versus 3.8) and 82 (77.6 versus 33.5). One year after primary vaccination, the seroprotection rate remained as high as 90% in the vaccinees of group B; after boosting all vaccinees had protective levels of anti-HBs antibodies. Thus 3-week HB vaccination with GenHevac B allowed early and durable protective immunity.

Adolescent↗
PubMed1993

The in-vivo activity of co-amoxiclav with netilmicin against experimental methicillin and gentamicin resistant Staphylococcus epidermidis infection in rabbits.

This study compared co-amoxiclav, vancomycin and teicoplanin with and without netilmicin or amikacin for treating experimental subcutaneous fibrin-clot infection in rabbits due to a clinical beta-lactamase-positive methicillin- and gentamicin-resistant Staphylococcus epidermidis strain (MGRSE). MICs (mg/L) for this strain were: oxacillin 125, gentamicin 32, vancomycin 4, teicoplanin 8, netilmicin 1, amikacin 4, amoxycillin 64 with clavulanate at 2 mg/L. In rabbits treated with a single-dose i.v. regimen (netilmicin 8 mg/kg, amikacin 20 mg/kg, vancomycin 30 mg/kg, teicoplanin 15 mg/kg, co-amoxiclav 150-30 mg/kg), the bacterial count 24 h post-dose was reduced whatever the combination used (ANOVA, P < or = 0.001). Regimens were statistically classified in decreasing order of efficacy as follows: co-amoxiclav combined with netilmicin > vancomycin either alone or combined with either netilmicin or amikacin, teicoplanin with netilmicin > netilmicin and co-amoxiclav alone > teicoplanin or co-amoxiclav combined with amikacin, and teicoplanin alone > amikacin > no drug. From these findings, it is concluded that: co-amoxiclav could be useful for the treatment of beta-lactamase-positive and methicillin-resistant S. epidermidis infection; some enzyme-resistant aminoglycoside could be considered for treating gentamicin-resistant but netilmicin/amikacin-sensitive S. epidermidis infection; the combination of co-amoxiclav with netilmicin was synergistic and more rapidly bactericidal than vancomycin in this animal model.

Amoxicillin↗
PubMed1993

Efficacy and tolerance of an amphotericin B lipid (Intralipid) emulsion in the treatment of candidaemia in neutropenic patients.

The efficacy and tolerance of a new amphotericin B lipid emulsion (AmB-IL) in which amphotericin B was diluted in a lipid solution for parenteral nutrition (Intralipid) was assessed in fourteen episodes of candidaemia occurring in neutropenic patients. The strains isolated were Candida krusei (nine cases), Candida albicans (three cases), Candida parapsilosis (one case) and Candida lusitaniae (one case). An AmB-IL was administered at a mean dosage of 1.18 mg/kg/day (range 0.73-1.55) for 22 days (range 6-62). Flucytosine was added to AmB-IL in 12 patients (mean duration 10.6 days). Chills were noted in only 3/306 infusions of AmB-IL. A mild increase of serum creatinine level from 9.3 +/- 3 mg/L (baseline) to 10.9 +/- 3 mg/L (after completion of AmB-IL) and mild decrease of creatinine clearance from 83 +/- 28 mL/min to 56 +/- 21 mL/min were observed. These changes did not correlate with either daily or total dose of AmB-IL or length of therapy. Seven patients were cured and six improved (patients who subsequently died due to nonfungal cause) with AmB-IL. One patient died due to C. krusei pneumonia. In conclusion AmB-IL is a well-tolerated method of amphotericin B administration. It could facilitate the use of amphotericin B without impairing its efficacy for the treatment of candidaemia in neutropenic patients.

Adult↗
PubMed1992

[Treatment of acute pharyngitis].

The treatment of acute pharyngitis is mainly aimed at the prevention of complications, particularly rheumatic fever. To reach this objective group A beta-haemolytic streptococci must be eradicated. To be effective, antibiotics must penetrate into the pharyngeal and tonsillar tissues and be active against streptococci. Penicillin is effective if administered by intramuscular injection or administered orally for not less than 10 days. In practice, however, compliance with this treatment is insufficient, resulting in numerous bacteriological failures. A possible improvement in the effectiveness of treatment consists in the use of a first-generation cephalosporin with a prolonged half-life, taken daily for 10 days. Acute pharyngitis is an excellent indication for macrolides. In order to improve compliance, short treatments are being tested with promising results, but until studies on new therapeutic approaches have been completed, and in the present absence of rheumatic fever epidemics in France, acute pharyngitis must be treated systematically.

Humans↗
PubMed1992

Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma.

Interleukin-6 (IL-6) was demonstrated to be a strong autocrine or paracrine plasmocytoma cell growth factor in humans. Using a bioassay, high serum IL-6 (S-IL-6) levels were correlated with disease severity in plasma cell dyscrasias. Since other cytokines could interfere with the bioassays, we developed a specific radioimmunoassay to study S-IL-6 levels in 102 patients with monoclonal gammopathy (MG). S-IL-6 level was studied by a double antibody radioimmunoassay using a rabbit polyclonal anti-IL-6 antibody and a human recombinant IL-6 as the standard. The lowest value of the standard significantly different from zero was found to be 78 pg/ml. Within-run and between-run precisions were characterized by a mean coefficient of variation of 3.72 and 5.5%, respectively. The mean analytical recovery was found to be 113% and the immunochemical identity of IL-6 standard and S-IL-6 was shown by dilution tests. IL-6 was detected in all tested sera. Sera from 66 healthy volunteers and 43 patients with acute leukemia or malignant lymphoma were tested as controls. In healthy subjects, S-IL-6 values were 294 +/- 86 pg/ml. MG were classified as multiple myeloma (MM), macroglobulinemia, and MG of undetermined significance (MGUS). The distribution of S-IL-6 levels in patients with MG was significantly higher than in healthy subjects but lower than in patients with acute leukemia or Hodgkin's lymphoma. Results obtained in 55 patients with MM were related to other biological parameters. S-IL-6 levels correlated with bone-marrow plasmacytosis (P less than .0005), serum-lactate dehydrogenase (S-LDH; P less than .005), serum beta 2 microglobulin (S -beta 2m; P less than .01), and serum calcium (S-Ca; P less than .025) and inversely correlated with haemoglobin (P less than .025). Our results indicate that 1) radioimmunoassay is suitable for the measurement of human IL-6 in serum; 2) high S-IL-6 levels are observed in a small number of patients with MG; and 3) S-IL-6 level correlates with tumour cell mass in patients with overt MM.

Bone Marrow↗
PubMed1992

Clinical evaluation of a new lipid-based delivery system for intravenous administration of amphotericin B.

In a retrospective study a new lipid-based delivery system for administration of amphotericin B was evaluated in 26 treatment courses in 22 patients. Amphotericin B was given by infusion diluted in either the lipid solution (1 mg/kg/d; 13 courses) or dextrose (0.92 mg/kg/d; 13 courses). No differences were noted in the serum pharmacokinetics. Fever or rigors were observed in 6 of 13 courses in the conventional amphotericin B group versus none in the lipid amphotericin B group (p = 0.007). Four of 13 courses of treatment were discontinued due to adverse effects in the conventional amphotericin B group compared to none in the other group (p = 0.048). In the lipid amphotericin B group the decrease in creatinine clearance was significantly lower on the fourth day of treatment (p = 0.04) and significantly fewer patients had a decrease of more than 25% in creatinine clearance on the sixth day (4/12 vs 9/11 p = 0.02). These preliminary findings suggest that this lipid amphotericin B formulation is well tolerated with few nephrotoxic effects.

Adult↗
PubMed1992

High concentrations of intrathecal interleukin-6 in human bacterial and nonbacterial meningitis.

Interleukin-6 (IL-6) is multipotent cytokine that acts in a network of factors directing the inflammatory reaction of purulent bacterial meningitis (PBM). However, little is known about the role of IL-6 in aseptic or "viral" meningitis (AM). IL-6 was assayed by RIA in cerebrospinal fluid (CSF) and serum samples obtained from patients with AM (n = 65), PBM (n = 8), and lymphocytic bacterial meningitis (LBM, n = 11). Of patients with AM, 89% had detectable IL-6 in CSF, with high IL-6 titers (median, 2160 pg/mL; 95% confidence interval [CI], 1320-2540 pg/mL) compared with 100% in patients with PBM (median, 6575 pg/mL; 95% CI, 450-32,000 pg/mL) and 90.9% in patients with LBM (median, 875 pg/mL; 95% CI, 150-2180 pg/mL). There was a highly symmetrical correlation between IL-6 and the percentage of polymorphonuclear cells in CSF of patients with PBM (r = .97, P = .01) and AM (r = .49, P = .002). In conclusion, this study shows evidence that IL-6 is released into the meningeal space in aseptic meningitis and is correlated with the local acute inflammatory response.

Humans↗
PubMed1992

Diffusion of cefpirome into the cerebrospinal fluid of patients with purulent meningitis.

We evaluated the diffusion of cefpirome into the cerebrospinal fluid (CSF) of 25 patients with bacterial meningitis or ventriculitis who were receiving conventional antibiotic treatment. A single cefpirome dose of 2 g was infused at day 2-3 after the onset of therapy. Concentrations of cefpirome in serum and CSF obtained at 2, 4, 8 or 12 h after the infusion were determined by high-performance liquid chromatography. The mean (+/- S.E.M.) concentrations of cefpirome in CSF ranged from 2.26 +/- 1.16 to 4.17 +/- 0.83 mg/L. These concentrations were higher than the MBCs for the pathogens usually responsible for bacterial meningitis.

Adolescent↗