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Biomedical subjects

H Portier

Publications and source records attributed to H Portier.

At least 19 recordsLinked to original sources

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

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

[Efficacy and tolerance of cefotiam hexetil in the super-infected chronic sinusitis. A randomized, double-blind study in comparison with cefixime].

Efficacy and safety of a new oral third generation Cephalosporin, Cefotiam Hexetil (CTM) 200 mg bid were compared with those of Cefixime (CX) 200 mg bid over 10 day duration of treatment. One hundred and twenty two ambulatory adults suffering from chronic sinusitis were randomized by ENT specialists in this multicentre prospective double blind, doubled dummy study. Sinusitis diagnosis evocated in front of fascial pain, purulent nasal discharge and/or obstruction was confirmed with sinus X-ray. Use of antibiotics or corticosteroids concomitantly or 15 days prior inclusion represented one of the major exclusion criterion. One hundred and seventy one patients were evaluated for efficacy analysis (62 and 59 respectively in CTM and CX groups). Regarding demographic data, clinical and radiological signs, the two populations were comparable at inclusion excepted for sex and weight (female: 73% in CTM group versus 47% in CX group). The overall clinical success rate at the end of treatment (cure+improvement) was not significantly different between the two groups (CTM: 82% versus CX: 80%). The incidence of adverse events was less frequent in the CTM group (14.5% versus 19%). In conclusion, CTM 200 mg bid is as efficacious and as well tolerated as CX 200 mg bid in the treatment of chronic sinusitis in adults.

Anti-Infective Agents

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

Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis.

OBJECTIVES: To compare the tolerance, efficacy, and pharmacokinetics of amphotericin deoxycholate (Fungizone) prepared in a parenteral fat emulsion (Intralipid 20%) or glucose in HIV patients with candidiasis. DESIGN: Non-blind randomised controlled trial. SETTING: University hospital; tertiary clinical care. PATIENTS: 22 HIV positive patients with oral candidiasis. INTERVENTIONS: Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5% glucose (amphotericin-glucose) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion (amphotericin-fat emulsion). MAIN OUTCOME MEASURES: Clinical tolerance (fever, chills, sweats, nausea, arterial pressure, and pulse rate); biological tolerance (serum creatinine, electrolyte, and magnesium values); clinical score of candidiasis; and serum concentrations of amphotericin. RESULTS: 11 patients were enrolled in each group. All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment (n = 3) or severe chills (n = 2), or both. For patients completing the amphotericin-glucose treatment creatine concentration increased by 42 mumol/l; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion. Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion. Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion. Oral candidiasis score was reduced similarly in both groups. Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose. CONCLUSIONS: Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion. Preparation is simple and cost effective. Its efficacy is similar to that of conventional amphotericin.

AIDS-Related Opportunistic Infections

[Current status on the epidemiology of acute pharyngitis and post-streptococcal syndromes].

So far, no ideal study providing an exhaustive knowledge of acute pharyngitis epidemiology has been carried out. What is available now is a number of investigations, all with deficiencies, which concern the duration of the disease (there may be seasonal variations), its limits in space and, above all, the number of pathogens sought for. A well-organized investigation span over at least one year, involve a fairly wide range of age-groups and be repeated in several countries. Bacterial epidemiology is dominated by beta-haemolytic streptococci group A, but other streptococcal groups, notably group C, have been incriminated. Other responsible bacteria, such as Haemophilus spp., Staphylococcus spp. and Corynebacterium spp., are extremely rare but most probable. Mycoplasma pneumoniae and perhaps Chlamydia pneumoniae are probably found more frequently. Rheumatic fever--which had virtually disappeared in medically advanced countries due to a higher level of life and to the general use of penicillin therapy--has reappeared in recent years, as shown by a few North-American epidemics. Such epidemics have come on time to remind us that we should be vigilant and continue, as in the past, to treat all streptococcal foci systematically, in order to prevent the occurrence of rheumatic fever.

Acute Disease

[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

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

[Emulsion of amphotericin B in Intralipid 20%: in vitro and in vivo efficacy].

Toxic effects limit the use of amphotericin B (AmB) for the treatment of systemic Candida infections. In vitro and in vivo toxicity can be substantially reduced by mixing AmB with a lipid emulsion used for parenteral nutrition, intralipid 20% (IL). This study was designed to evaluate the potential effects of IL on the activity of Amphotericin B against Candida. A clinical strain of Candida albicans was used. AmB deoxycholate (Fungizone) was reconstituted in a 5% glucoce solution (AmB-G5), in 3 mg/ml IL (AmB-IL3) or in 1.5 mg/ml IL (AmB-IL 1.5). Minimum inhibitory concentrations and minimum lethal concentrations were 0.4 mg/l and 2.5 mg/l, respectively, with AmB-G5, 0.1 mg/l and 1 mg/l with AmB-IL3, and 0.24 mg/l and 1 mg/l with AmB-IL 1.5. In vitro killing curves with 0.1 mg/l, 0.25 mg/l, and 2.5 mg/l AmB were determined with the following results: 1) with 0.1 and 0.25 mg/l AmB, fungicidal activity was seen with AmB-IL3 and AmB-IL 1.5 but not with AmB-G5; 2) with 2.5 mg/l AmB, fungicidal activity was less marked with AmB-G5 (-1.7 log CFU/ml after 24 hours) than with AmB-IL3 and AmB-IL1.5 (-4.3 log CFU/ml and -4.2 log CFU/ml, respectively, after 24 hours; p less than 0.05). In rabbits given a single intravenous injection of 4 mg/kg AmB, analysis of infected subcutaneous fibrin clots detected measurable concentrations of AmB beyond the 24th-36th hour, with levels of 0.5 mg/l for AmB-G5 and 1 mg/l for the two AmB-IL preparations over a period of three days.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B