[Leukocytoclasic vasculitis and human immunodeficiency virus. 2 new cases].
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Biomedical subjects
Publications and source records attributed to E Bernard.
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In a model of bronchopulmonary aspergillosis terbinafine did not improve survival of experimental animals in doses up to 80 mg/kg/day despite adequate lung concentrations. Pretreatment and aerosolization of the compound were also ineffective. Terbinafine was markedly less active in vitro when serum was used instead of Yeast-Nitrogen-Glucose-broth. It is concluded that a lack of bioavailability in the presence of serum may explain the lack of activity of terbinafine in experimental aspergillosis.
Thirteen patients with bone infection caused by Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens or Escherichia coli in association with implanted foreign material were treated with pefloxacin 400 mg 12-hourly for up to six months. Satisfactory results, with fistula closure and eradication of the infecting bacteria, were achieved in nine patients, who have been followed up for four to seven years. Treatment failed in two patients, with re-isolation of the infecting bacteria (P. aeruginosa; Ser. marcescens) which showed reduced sensitivity to pefloxacin. Primary failure (failure to close of the fistula and re-isolation of bacteria sensitive to pefloxacin) occurred in one patient, who achieved a satisfactory result later after removal of foreign material. Relapse after treatment occurred in one patient. Eight patients suffered migrating arthralgia (without signs of arthritis) but this did not interfere with the treatment, which was generally well tolerated.
Sixty cases of septicaemia treated with pefloxacin, alone (30) or in combination with other antibiotics (30) were analysed retrospectively. A satisfactory outcome was achieved in 33 (87%) of 38 evaluable Gram-negative septicaemias (including success in 25 of 29 treated with pefloxacin alone) and in 15 of 21 staphylococcal septicaemias, mainly treated with combinations of antibiotics. Failures and relapses were associated with a variety of local or systemic underlying conditions.
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The pharmacokinetics and serum killing curves of amikacin, which was administered by a 30-minute intravenous infusion of single doses of 7.5 mg/kg and then 15 mg/kg, were investigated in six healthy volunteers who received the two doses in a crossover study with a washout period of 20 days. The serum killing curves were determined for four bacterial species: Escherichia coli, Serratia marcescens, Enterobacter cloacae, and Pseudomonas aeruginosa. All strains were serum resistant, and the bactericidal activity was analyzed by separating the early phase (first 5 h) and the late phase (24 h) of the killing curve. For the early phase, the bactericidal activity was evaluated by correlating an index of surviving bacteria with amikacin concentrations. This methodology allowed determination of two parameters: the maximal effective concentration and the lowest effective concentration. For the late phase, the threshold values separating bacteriostatic and bactericidal activities were lower than 10 mg/liter for each strain. The concentration dependence of amikacin bactericidal activity was confirmed for Escherichia coli and Enterobacter cloacae and, to a lesser extent, for Serratia marcescens and Pseudomonas aeruginosa. Correlation of these data with amikacin pharmacokinetic data in volunteers indicated that a daily dose of 15 mg/kg may be effective in the treatment of Escherichia coli and Enterobacter cloacae infections. For Pseudomonas aeruginosa and Serratia marcescens, the partially time-dependent activity probably necessitates two daily administrations and combination with another antibiotic.
A case of acquired immunodeficiency syndrome with a sudden death due to a toxoplasmic myocarditis is reported. The diagnosis was postmortem. At the autopsy, only the heart was affected by toxoplasmic lesions. The toxoplasmosis is a frequent disease in AIDS patients. So a toxoplasmic myocarditis must be suspected when a severe cardiac dysfunction is observed in these patients.
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For the HIV positive patient, salmonella raises numerous epidemiological and therapeutic problems. This microorganism, quite common before zidovudine therapy, seems to have diminished since this antiviral also has an antibiotic activity against salmonella. When bacterial contamination occurs, the decreased immunitary activity might play a role, but hypochloridria, frequently afflicting these patients, might also be involved. Therapeutically, antibiotics with high intramacrophagic diffusion yield excellent results and limit the incidence of recurrence. The effect of gamma interferon is well documented in vitro. However, the efficacy of these quinolones does not lead us to believe that it is the treatment of choice.
The pathologic study of the cardiac lesions in 25 persons who died of AIDS were studied from autopsies. Most of these patients were intravenous drug abusers (14 cases). Heart failure was symptomatic and lead to death in 4 cases. This study showed histological abnormalities in 76% of the cases. We observed 12 myocarditis. In 6 cases, pathogenes were found: Toxoplasma gondii (2), Cryptococcus neoformans (2), Candida (1), Aspergillus (1). A lymphocytic myocarditis was observed in 6 hearts. By immunohistochemical technique, we could distinguish 2 toxoplasmic myocarditis, and in 4 cases, solitary cysts in the myocardium without inflammation. The remaining lesions comprised respectively: 3 lymphocytic pericarditis, 2 marastic endocarditis and 1 dilated myocardiopathy.
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The anatomopathological study of the heart, carried out during the autopsy of a series of 38 subjects seropositive for the human immunodeficiency virus, has enabled the observation of histological lesions in 23 cases (60%). The heart affection is more often asymptomatic since it has been clinically suspected in only four cases. A myocarditis is present in 42 p. cent of the cases, and lesions specific to a pathogenic agent are visible in half of the myocarditis cases. These pathogenic agents are: toxoplasma (2 cases), cryptococcus (2 cases), candida (1 case), aspergillus (1 case) and cytomegalovirus (1 case). Lymphocytic myocarditis, with no isolated aetiological agent, and without viral inclusion, has been observed in 9 cases. The histological affection of the pericardium is observed in 4 cases and that of the endocardium in 3 cases. The lesions are not specific. The cardiotropism of the HIV is suspected, but not established. It could explain the frequency of lymphocytic myocarditis and dilated cardiomyopathies observed in HIV positive patients. The frequency of heart localizations in HIV positive subjects, even strictly asymptomatic as observed in this study, leads us to advise a systematic specialized cardiac examination.
Among the S. aureus 25/39 are non producing slime and non adherent isolates. These results did not allow a correlation between these properties and pathogenesis. Several different phenotyping systems (biotyping, phage typing, serotyping, antibiotic susceptibility profiling, and plasmid pattern analysis) have been used in an attempt to identify strains of CNS. There is still a need however, for a simple, rapid, and cost effective method of distinguishing true pathogens from simple contaminants. Our results suggest that testing isolates for slime positivity and for adherence property may fulfill this task.
From October 1983 to October 1986, 39 patients with chronic osteomyelitis (of at least two month's duration) were treated with either pefloxacin (n = 15), ofloxacin (n = 17), or ciprofloxacin (n = 7). The length of treatment ranged from 3 to 6 months; follow-up examinations were performed up until July 1988. The infecting bacterial strains (19 Staphylococcus aureus, 2 Staphylococcus epidermidis, 10 Escherichia coli, 8 Pseudomonas aeruginosa) were all sensitive to the quinolone prescribed. Twenty-nine of the 38 evaluable patients had a satisfactory outcome at follow-up examinations 14 to 48 months after the end of treatment. Fourteen of the 21 patients with gram-positive bacterial infections responded satisfactorily, as did 15 of the 17 patients infected by gram-negative bacteria. Nine cases of failure were observed (2 for pefloxacin, 4 for ofloxacin, 3 for ciprofloxacin). The infecting bacteria were Staphylococcus aureus in six cases (3 on ofloxacin, 3 on ciprofloxacin). The infecting bacteria were Staphylococcus aureus in six cases (3 on ofloxacin, 3 on ciprofloxacin), and Staphylococcus epidermidis (ofloxacin), Escherichia coli (pefloxacin), and Pseudomonas aeruginosa (pefloxacin) in one case each. In all these cases, local conditions (presence of a foreign body in 5 cases, sequestra in 3, and post-radiotherapy necrosis in 1) could have been responsible for treatment failure. Tolerance was good; adverse effects observed in the pefloxacin and ofloxacin groups disappeared after treatment was ended. Bone levels varied but were always superior to the MIC for the pathogen. In view of the satisfactory results, the possibility of oral administration, and the good tolerance, these quinolones should be considered as alternative agents for the treatment of chronic osteomyelitis.
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Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, was evaluated for the treatment of bacterial endocarditis in an open multicenter study from May 1985 to August 1987. A total of 20 patients with positive blood culture endocarditis received teicoplanin once daily as a mean intravenous injection of 7.3 mg/kg of body weight (range, 4.8 to 10.6 mg/kg); in 17 patients, teicoplanin was combined with another antibiotic, usually an aminoglycoside. The mean duration of therapy was 28 days (range, 7 to 66 days). The diagnosis of endocarditis was confirmed by echocardiography or anatomical findings in 15 patients and established on the basis of clinical manifestations plus positive blood cultures in 5 patients. The tricuspid valve was involved in 11 of the 20 patients. Isolates from blood were 12 Staphylococcus aureus, 1 Staphylococcus hominis, 1 Micrococcus sedentarius, 1 Enterococcus faecalis, 3 Streptococcus bovis, and 2 nongroupable Streptococcus sp. At the end of therapy, bacterial eradication was achieved in 17 of 20 patients (85%), and a favorable clinical outcome had occurred in 14 of 17 evaluable patients (82%). Of these 14 patients, one relapsed 4 months after the end of treatment. Thus, teicoplanin was effective in 13 of 17 patients (76%). Mean peak levels of teicoplanin in serum were lower, 23.1 +/- 2.9 micrograms/ml, in patients who failed than in those who were cured (45.8 +/- 8.4 micrograms/ml). Side effects occurred in 7 of 20 patients (35%), and required premature discontinuation of teicoplanin in 3 patients. These side effects were fever in three patients, rash in three patients, hearing loss in two patients, and increased serum transaminase levels in two patients. This study demonstrates the efficacy of teicoplanin in the treatment of endocarditis and the need for achieving peak levels in serum close to 40 micrograms/ml. Teicoplanin should now be further evaluated in endocarditis caused by gram-positive cocci means of controlled comparative study with standard therapy.
20 patients (18 men, 2 women), 10 of whom were HIV +, were given Fluconazole (F) for either systemic candidiasis (13 cases), histoplasmosis (1), or cryptococcosis (6). The localization of the Candida infections (12 C. albicans, 1 C. tropicalis), were: septicemic (2), urinary (7), bronchial (2), esophageal (5), uveal (1), soft tissue (2), and 1 undetermined localization but a positive serology (1). On day (d) 1, Candidiasis patients were given an initial dose of 400 mg (for septicemia) or 200 mg (other localizations) of FIV or PO, then 200 or 100 mg per d. The length of treatment lasted from 28 to 70 d. Evolution was favorable in all the patients. 4 relapses occurred after the end of treatment: at 10 d, a septicemic candidiasis (C. tropicalis) in 1 patient who had prosthetic endocarditis; and at 1 month, digestive candidiasis in 3 HIV + patients. For the patient, infected by Histoplasma capsulatum, despite a clinical improvement, urine were still positive at day 75. The patients with cryptococcosis (5 meningitidis in the AIDS patients) and renal (1) (kidney transplant) were given on the average 400 mg a d, IV or PO (mean length 8 weeks). Only 5 patients were evaluable. For 2 of the meningitis patients with other localizations, standard treatment was instituted due to the persistence of positive cultures. For the 2 other patients, the cerebrospinal fluid (1) and the urine (1) were sterilized by the 3d week. But they relapsed 1 month after the treatment stopped. For the 18 patients evaluable, clinical and biological tolerance was good except for 1 patient with transaminases rise for which fluconazole was probably the cause.