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H Portier

Publications and source records attributed to H Portier.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

Papillary necrosis: a late complication of nephropathia epidemica?

In the following we describe a case of nephropathia epidemica, which exhibited, a few years after acute infection, arterial hypertension and multiple papillary necrosis. Papillary necrosis was diagnosed by i.v. pyelography and CT Scan. A complete evaluation of the patient failed to show any other etiology for medullary necrosis. If arterial hypertension has already been reported as a complication of nephropathia epidemica, papillary necrosis is exceptional, but may be explained by the severe vascular troubles engendered by Hantavirus infection in kidney medulla.

Adult↗

Nasopharyngeal lymphomas: further evidence for a natural killer cell origin.

The authors report four cases of sinonasal lymphomas with immunophenotypic (four cases) and genotypic (three cases) studies. These lymphomas are frequent in Oriental countries, but unusual in Western populations, particularly in France. Although they have been originally considered as T-cell lymphomas, their origin remains unclear, and several authors have recently suggested that they are a natural killer (NK)-cell proliferation. The tumor cells of the four cases reported here showed characteristics of NK cells. On cryostat sections, they were CD3 negative, but CD2 and CD56 positive. The cytoplasm of the tumor cells exhibited azurophilic granulations. Using polymerase chain reaction (PCR), no clonal rearrangement of the T-cell receptor gamma gene was present. Furthermore, clinically, two presented a pharyngeal involvement, and two were also characterized by hepatosplenic involvement at the time of the diagnosis. Thus, the present cases provide additional evidence toward the NK-cell origin of these rare lymphomas. Many sinonasal lymphomas, including the present cases, are positive for Epstein-Barr virus (EBV) (LMP-1 antibody and EBER-messenger RNA probes). This may suggest an important role of EBV as a local factor in their pathogenesis.

Adult↗

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↗

Comparative efficacy of sparfloxacin in comparison with amoxycillin plus ofloxacin in the treatment of community-acquired pneumonia. French Study Group.

A prospective, placebo controlled double-blind, randomised study comparing oral sparfloxacin 200 mg once daily following a 400 mg loading dose on day 1 with an oral combination of amoxycillin 1 g tid plus ofloxacin 200 mg bid was conducted in 211 hospitalised patients with community-acquired pneumonia. Patients were included in the study if they were aged > 65 years or had failed a previous course of antibacterial therapy. The duration of treatment was 10 days. The overall efficacy rates for the sparfloxacin and amoxycillin plus ofloxacin treatment groups were 91.9% and 81.5%, respectively, in evaluable patients at the end of treatment. Age or prior failure of antibacterial therapy did not affect the overall success rate of sparfloxacin. The safety profile of sparfloxacin was similar to that of the antibacterial combination. This study demonstrated that sparfloxacin given once daily is a suitable therapy for the treatment of community-acquired pneumonia in the elderly or in patients with failure of previous antibiotic therapy.

Administration, Oral↗

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↗

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↗

Cost saving of 5-day therapy with cefpodoxime proxetil versus standard 10-day beta-lactam therapy for recurrent pharyngotonsillitis in adults. A prospective general practice study.

A prospective economic evaluation was undertaken as part of a randomised clinical trial conducted in French general practice. Its aim was to compare the costs and therapeutic outcomes of a 5-day course of cefpodoxime proxetil 100 mg twice daily with 10-day courses of phenoxymethylpenicillin (penicillin V) 1 MIU 3 times daily and amoxicillin-clavulanic acid 500/125 mg 3 times daily for the treatment of recurrent pharyngotonsillitis in 575 adults. Over the 6-month study period, the total cost to society per patient treated with cefpodoxime proxetil was 123 French francs (FF; 1993 values) lower than that for patients treated with phenoxymethylpenicillin and FF227 lower than that for patients treated with amoxicillin-clavulanic acid. This cost saving was primarily attributable to a lower initial drug acquisition cost, and a reduction in the cost associated with lost productivity and general practitioner consultations. Furthermore, as a consequence of a lower relapse rate, the cost-saving ratio for cefpodoxime proxetil, expressed as FF per month free of recurrence, was FF50 less than for phenoxymethylpenicillin and FF60 less than for amoxicillin-clavulanic acid. Thus, a 5-day course of cefpodoxime proxetil is likely to be less costly for treatment of pharyngotonsillitis in the general practice setting than standard 10-day courses of phenoxymethylpenicillin and amoxicillin-clavulanic acid.

Adult↗

6-day amoxicillin versus 10-day penicillin V for group A beta-haemolytic streptococcal acute tonsillitis in adults: a French multicentre, open-label, randomized study. The French Study Group Clamorange.

We compared the efficacy and safety of amoxicillin 1 g b.i.d. for 6 days and penicillin V 1 MU t.i.d. for 10 days in the treatment of group A beta-haemolytic streptococcal (GABHS) tonsillitis in adults. 342 patients with acute tonsillitis and a positive test for streptococcal antigen were included in a multicentre, randomized, open-label study; 338 patients were evaluable in an intention-to-treat analysis, and 234 with a positive throat swab culture in a per-protocol analysis. In the per-protocol analysis, the GABHS eradication rate at the end of treatment was comparable in the two groups: 92% (115/125) on amoxicillin and 92.7% (101/109) on penicillin (p = 0.95), as were the clinical success rates of 96% and 95.4%, respectively (p = 0.92). At the follow-up visit (day 28-32), 90.8% of patients treated with amoxicillin and 92.6% of those treated with penicillin V were free of GABHS (p = 0.85). Sore throat disappeared significantly faster on day 2 (p = 0.039) in the amoxicillin group. The intention-to-treat analysis gave similar clinical results. Tolerability was good in both groups. The efficacy and safety of amoxicillin 1 g b.i.d. for 6 days were not statistically different from those of penicillin V 1 MU t.i.d. for 10 days in the treatment of streptococcal tonsillitis in adults.

Acute Disease↗

[Treatment of bacterial pneumonias with cefuroxime-axetil. Predictive value of measurement of the in vitro susceptibility].

Cefuroxime axetil is an oral cephalosporin with proven efficacy in adult lower respiratory tract infections. Indeed, it has a broad spectrum of activity in vitro, covering most pathogens isolated in this setting and showing good stability in the presence of betalactamases. In vitro susceptibility data are a major element in the choice of antimicrobial agent. The aim of this study was to determine the predictive value of the cefuroxime minimal inhibitory concentration (MIC) on the clinical outcome of infections treated with cefuroxime axetil. One hundred-and-seventeen (117) patients with radiologically confirmed community-acquired pneumonia of presumed bacterial origin were enrolled in a prospective multicenter trial of cefuroxime axetil therapy (500 mg twice daily). The pathogen was identified in 44 patients who were treated for a mean of 8.8 days. Most isolates were S. pneumoniae (65.9%) and H. influenzae (15.9%). The MIC was known for 35 isolates and was < or = 4 micrograms/ml in 30 cases (85.7%). The MIC value was a good predictor of clinical efficacy with a sensitivity of 100%, a specificity of 83% and a positive predictive value of 97%; the latter value indicates that therapeutic success is virtually certain when the bacterium causing pneumonia is susceptible to cefuroxime.

Adolescent↗

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↗

[Purulent pericarditis in dermatopolymyositis].

The authors report the case of a 33-year-old patient with dermatopolymyositis, admitted to hospital for acute cystic pericarditis with fever and deterioration of the general state. The aetiological diagnosis was obtained by analysis of the pericardial fluid after surgical drainage, revealing purulent Staphylococcus aureus pericarditis. This case emphasises that, despite the marked rarity of pericardial effusion in the course of dermatopolymyositis, due to the steroid sensitivity of this disease, the possibility of septic contamination should be considered in the presence of persistent pericarditis in the context of this disease.

Adult↗

[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↗

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↗