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Biomedical subjects

C Perronne

Publications and source records attributed to C Perronne.

At least 19 recordsLinked to original sources

Should pulmonary tuberculosis be an AIDS-defining diagnosis in patients infected with HIV?

Between 1983 and 1989, we cared for 56 patients with tuberculosis and human immunodeficiency virus (HIV) infection. In 37 patients (66%), tuberculosis occurred before any other AIDS-defining disease (group 1); in 10 (18%) it occurred during the same month as another AIDS-defining disease (group 2); and in 9 (16%), after the diagnosis of AIDS (group 3). Tuberculosis was entirely pulmonary in 14 patients (25%), entirely extrapulmonary in 9 (16%), and both pulmonary and extrapulmonary in 33 (59%). The frequency of extrapulmonary involvement was similar in patients from group 1 and from groups 2 and 3 (combined): 76% versus 74%. Needle biopsy of the liver revealed hepatic involvement in 18 patients (32%). The mean CD4 lymphocyte count was 232/mm3 when tuberculosis was entirely pulmonary, and 243/mm3 when extrapulmonary disease was present (difference not significant). In group 1, the onset of both pulmonary and extrapulmonary tuberculosis occurred at the same stage of HIV infection, 12 and 10 months, respectively, before any other AIDS-defining disease. Treatment, planned to last 1 year, was highly effective, despite frequent side-effects. Among the 32 patients who completed treatment, relapse of tuberculosis occurred in 2 (6%) with a mean follow-up of 16 months (0-53 months) after completion. Our results suggest that pulmonary tuberculosis should be included in the criteria for diagnosis of AIDS.

Acquired Immunodeficiency Syndrome

Activities of WIN-57273, minocycline, clarithromycin, and 14-hydroxy-clarithromycin against Mycobacterium avium complex in human macrophages.

The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacterium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 micrograms of WIN-57273 per ml (MICs for the two strains, 1 microgram/ml), 4 microgram of 14-OH clarithromycin per ml (MICs, 8 and 2 micrograms/ml, respectively, at pH 7.4), 4 micrograms of minocycline per ml (MICs, 64 and 32 micrograms/ml, respectively), and 4 micrograms of clarithromycin per ml (MICs, 2 and 0.5 micrograms/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P less than 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P less than 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P less than 0.02), clarithromycin (P less than 0.02), 14-OH clarithromycin plus clarithromycin (P less than 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH clarithromycin (P less than 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P less than 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P less than 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.

Anti-Infective Agents

Sparfloxacin, ethambutol, and cortisol receptor inhibitor RU-40 555 treatment for disseminated Mycobacterium avium complex infection of normal C57BL/6 mice.

Sparfloxacin (50 mg/kg of body weight given subcutaneously each day), alone or in combination with ethambutol (50 mg/kg given subcutaneously each day), was examined for its therapeutic efficacy against experimental infection induced with the Mycobacterium avium complex in normal C57BL/6 mice. In addition, the potential anti-infective role of RU-40 555 (100 mg/kg given intraperitoneally each day), a drug that inhibits the cortisol receptors, was examined in the same model. Treatments were started 24 h after intravenous bacterial challenge and were continued for 21 days. Compared with controls, sparfloxacin or ethambutol decreased the CFU counts in spleens and lungs (P < 0.001). The sparfloxacin plus ethambutol combination was more effective than sparfloxacin alone in spleens (P < 0.001) but not in lungs. The sparfloxacin plus ethambutol plus RU-40 555 combination was more effective than the sparfloxacin plus ethambutol combination in spleens and lungs (P < 0.001). Thus, in this model, RU-40 555 enhanced the antibacterial activities of the antibiotics tested. Results of the study showed that normal C57BL/6 mice infected with the M. avium complex can be used for the evaluation of antimicrobial agents.

Animals

Bone manifestations associated with acquired immunodeficiency syndrome (AIDS).

To date, descriptions of bone manifestations associated with the acquired immunodeficiency syndrome (AIDS) have mostly been limited to case reports. Six such cases observed in our Departments of Rheumatology and Infectious Diseases, are reported. Three types of manifestations were observed: malignant lymphoma, infectious osteomyelitis, and reflex sympathetic dystrophy syndrome (algoneurodystrophy) secondary to central nervous system involvement.

Acquired Immunodeficiency Syndrome

Rifabutin in combination with clofazimine, isoniazid and ethambutol in the treatment of AIDS patients with infections due to opportunist mycobacteria. Groupe d'Etude et de Traitement des Infections à Mycobacteries Résistantes.

96 AIDS patients with fever and either acid-fast bacilli on microscopic examination of bacteriological samples or mycobacteria isolated by culture were treated with a daily 4-drug combination of 7-10 mg/kg rifabutin, 5 mg/kg isoniazid, 20 mg/kg ethambutol and 100 mg clofazimine. 46 patients were excluded from efficacy assessment: 13 died before or within the first days of treatment, 5 had negative initial cultures, 14 had initial cultures positive for M. tuberculosis, 4 for M. kansasii, 1 for M. flavescens, 1 for M. gordonae, 7 were lost to follow-up and 1 received no rifabutin. In the 50 remaining patients, 31 had disseminated disease due to M. avium intracellulare complex (MAIC) and 19 had apparently localised disease, due to MAIC in 15 cases and to M. xenopi in 4 cases. Side-effects led to withdrawal of isoniazid in 1 case (hepatic enzymes increased) and rifabutin in another (thrombocytopenia). After 1 month of treatment, fever decreased from 38.4 +/- 0.6 degrees C to 37.7 +/- 0.5 degrees C (p less than 0.01) and patients stopped losing weight. After 3 months treatment, only 37 patients were alive and still under treatment. Cultures became negative in 16 of 23 patients with available bacteriological data (9 of 14 patients with disseminated disease and 7 of 9 patients with localised disease), relapse occurred before death in 4 patients. 34 patients died before treatment was completed. Death was considered to be related to mycobacterial infection in 5 cases. We conclude that the 4-drug combination is safe and, in some cases, it appears to be effective.

Acquired Immunodeficiency Syndrome

Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages.

The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture. The intracellular CFU was counted 60 min after inoculation. The intracellular and supernatant CFU was counted on days 4 and 7 after inoculation. The concentrations used, which were equal to peak levels in serum, were 10 micrograms of rifapentine per ml (MICs for the two strains, 4 and 16 micrograms/ml), 4 micrograms of clarithromycin per ml (MICs, 8 and 4 micrograms/ml), 1 microgram of azithromycin per ml (MICs, 32 and 16 micrograms/ml), 4 micrograms of temafloxacin per ml (MICs, 2 and 16 micrograms/ml), and 1 microgram of sparfloxacin per ml (MICs, 0.5 and 2 micrograms/ml). Compared with controls on day 7 after inoculation, clarithromycin (P less than 0.001), sparfloxacin (P less than 0.001), and azithromycin (P less than 0.001 for the first strain, P less than 0.02 for the second) slowed intracellular replication. Rifapentine (P less than 0.001) and temafloxacin (P less than 0.001) slowed intracellular replication of the first strain but not of the second strain. Azithromycin plus sparfloxacin was as effective as sparfloxacin alone. In this macrophage model, sparfloxacin or clarithromycin (difference not significant) exhibited a better efficacy than rifapentine, azithromycin, or temafloxacin against intracellular M. avium complex infection.

4-Quinolones

[Neuromeningeal Listeria infections in adults. Clinical, biological and therapeutic aspects. Apropos of 36 cases].

In this retrospective study, 36 cases of Listeria monocytogenes meningitis were reviewed. A bacteriological confirmation was obtained for every patient either by lombar puncture or blood culture. The clinical picture and the composition of the cerebrospinal fluid were polymorphous. Most patients were previously in good health, while 10 of them (28%) had a predisposing factor: pregnancy, gastrectomy, diabetes mellitus, alcoholism or immunosuppression. The outcome was favorable in 23 patients (64%); 8 patients were cured with sequelae (22%); 5 patients died (14%). Death occurred in patients suffering from concomitant underlying disease, such as coronary insufficiency (n = 1) or immunosuppression (n = 2), or in the case of delayed diagnosis and treatment (n = 2).

Adult

[Zona in 50 patients infected by human immunodeficiency virus. Clinical manifestations and prognostic value].

Between January 1981 and April 1989, 50 patients infected with HIV were examined for herpes zoster. Herpes zoster enabled HIV infection to be detected in 23 patients (46 percent). It had only one localisation (involving contiguous dermatomes) in 37 patients, two localisations in 6 patients, three or four localisations in 1 patient each, and was disseminated in 5 patients. Localisations were mostly thoracic and cervicofacial. Herpes zoster was treated with acyclovir in 29 patients. All patients, treated or untreated, recovered from herpes zoster, but 9 of them (18 percent) had sequelae: pain in 8 and hypoacousia in 1. Herpes zoster recurred once in 8 patients and twice in 2. Among the patients with AIDS related complex 20 percent developed AIDS after herpes zoster at one year and 30 percent at two years. Among all the patients, the proportion of deaths after herpes zoster was 13 percent at one year and 34 percent at two years.

Acyclovir

Predictive value of cytomegalovirus viraemia for the occurrence of CMV organ involvement in AIDS.

In HIV-infected patients, the presence of cytomegalovirus (CMV) viraemia is predictive of the development of acquired immunodeficiency syndrome (AIDS), but it is not known whether it predicts further occurrence of CMV organ involvement. To assess the predictive value of CMV viraemia in the occurrence of CMV organ involvement, CMV blood cultures were performed at the onset of AIDS in 71 patients. They were prospectively followed up for at least 6 months, with a mean of 16.6 +/- 7 months (6-36 months). CMV viraemia was present in 28/71 patients (39.5%) at the onset of AIDS. CMV organ involvement occurred in 18/71 patients (25.4%) after 8.7 +/- 3.3 months. Fourteen of the 28 patients (50%) with early CMV viraemia developed CMV organ involvement after 7.7 +/- 6.3 months as compared with 4/43 patients (9.3%) who were not viraemic at the onset of AIDS with a mean follow-up of 11.8 +/- 3.8 months (P less than 0.001). At the time of CMV organ involvement, CMV viraemia, however, was present in 94.4% of the cases. No differences in survival was observed between initially viraemic and non-viraemic patients. No difference has found in mean CD4 cell count between viraemic and non-viraemic patients. This high predictive value of early CMV viraemia in AIDS for the occurrence of CMV organ involvement underlines the need for repeated search for CMV organ involvement when CMV viraemia is detected, and for less toxic antiviral drugs that might be used earlier.

Acquired Immunodeficiency Syndrome

Hypoglycaemia and diabetes mellitus following parenteral pentamidine mesylate treatment in AIDS patients.

Of 18 AIDS patients with Pneumocystis carinii pneumonia treated with pentamidine mesylate parenterally, four developed serious to severe hypoglycaemia, three hypoglycaemia followed by insulin-requiring diabetes, and two others diabetes alone. Hypoglycaemia (blood glucose 2.1 +/- 0.2 (+/- SE) mmol l-1) occurred 9 (2-22) days after starting treatment, and diabetes (initial blood glucose 30 +/- 6 mmol l-1) after 60 (20-90) days. The other patients remained euglycaemic. The dysglycaemic patients (hypo- and hyper-glycaemic) had a higher pentamidine dosage (p less than 0.01), and higher serum creatinine levels at end of treatment (p less than 0.001), consistent with drug accumulation and dose-dependent toxicity. Plasma C-peptide levels were low in the diabetic patients, in the basal state (0.25-0.28 nmol l-1) and following stimulation by IV glucagon (0.35-0.40 nmol l-1), vs 0.80 +/- 0.06 nmol l-1 (basal) and 1.83 +/- 0.16 nmol l-1 (stimulated) in 23 healthy control subjects (mean +/- SE). Islet cell or insulin antibodies were not detected. Serum amylase levels rose abnormally in the dysglycaemic group, and pancreatitis was proved in one, and suspected in another patient. None of 28 similar AIDS patients whose P. carinii pneumonia was treated with cotrimoxazole showed blood glucose disturbance.

Acquired Immunodeficiency Syndrome

Activities of clarithromycin, sulfisoxazole, and rifabutin against Mycobacterium avium complex multiplication within human macrophages.

The activities of clarithromycin, sulfisoxazole, and rifabutin against three virulent strains of Mycobacterium avium complex isolated from patients with acquired immunodeficiency syndrome were evaluated in a model of intracellular infection. Human monocyte-derived macrophages were infected at day 6 of culture with M. avium complex. Intracellular bacteria were counted 60 min after inoculation. Extra- and intracellular bacteria were counted at days 4 and 7 after inoculation. The concentrations used were 4 micrograms of clarithromycin per ml (MICs for the three strains, 4, 4, and 4 micrograms/ml), 50 micrograms of sulfisoxazole per ml (MICs, 50, 25, and 25 micrograms/ml), and 0.5 micrograms of rifabutin per ml (MICs, 2, 0.5, and 0.5 micrograms/ml). Compared with controls, clarithromycin and rifabutin slowed the intracellular replication of the three strains (at day 7 after inoculation, P was less than 0.01 for the first strain and less than 0.001 for the two others). Sulfisoxazole was ineffective against the three strains. Clarithromycin was as effective as rifabutin. Clarithromycin plus rifabutin was as effective as each single agent. Clarithromycin plus sulfisoxazole was as effective as clarithromycin alone.

Acquired Immunodeficiency Syndrome

Varicella in patients infected with the human immunodeficiency virus.

In a retrospective study of 421 patients infected with human immunodeficiency virus, 15 (3.5%) had varicella. Twelve patients had a typical varicella. Complications were as follows: profuse eruption, 6; hemorrhagic eruption, 1; hepatitis, 5; and pulmonary involvement, 1; 1 patient developed an intravascular disseminated coagulation and died of varicella. Three patients with acquired immunodeficiency syndrome, having a history of varicella, presented with an atypical form of varicella with a small number of disseminated cutaneous poxlike lesions; 1 of these patients experienced three relapses of atypical varicella. Assay of serum antibodies to varicella zoster virus showed that, while typical varicella was the primary varicella zoster virus infection, atypical varicella was a reactivation of varicella zoster virus infection. Acyclovir was given to 11 patients and vidarabine to 1 patient. The one patient who died and the one who suffered a relapse had received acyclovir. Thus, varicella in patients infected with human immunodeficiency virus may be complicated and even lethal. Atypical forms of varicella could be, as is the case with herpes zoster, a reactivation of endogenous varicella zoster virus.

Adolescent