Myelitis due to Toxoplasma gondii in a patient with AIDS.
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Biomedical subjects
Publications and source records attributed to C Perronne.
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OBJECTIVES: The aim of the study was to assess the incidence and aetiology of fever of unknown origin in human immunodeficiency virus (HIV)-infected patients, and to evaluate the usefulness of the main diagnostic procedures. DESIGN: A retrospective study. SETTING AND SUBJECTS: We reviewed the records of 270 HIV-infected patients who were hospitalized for the first time in a department of infectious and tropical diseases during the 27 month study period. MAIN OUTCOME MEASURES: Fifty-seven patients (21%) had a history of fever of unknown origin. RESULTS: The aetiology was found in 49 cases (86%). The major cause of the fever was mycobacteriosis: atypical mycobacteria in 10 cases, Mycobacterium tuberculosis in 10, mycobacteria of unspecified type in two, and BCG strain in one. A liver biopsy and a thoracic CT scan greatly contributed to the diagnosis of mycobacterial infection. Seventeen patients were given empiric antimycobacterial therapy as a therapeutic test, of whom seven had a favourable response. The other main causes of fever were cytomegalovirus infection in five patients, leishmaniasis in four, and lymphoma in four. CONCLUSIONS: Fever of unknown origin is a frequent occurrence in the course of HIV infection, and mycobacterial infection should be considered as a first-line diagnosis in such cases. The place of empiric antimycobacterial therapy in the diagnostic strategy requires further evaluation, but appears to be an alternative to multiple investigative procedures.
Relapse of brain toxoplasmosis in AIDS patients continue to occur despite maintenance therapy. The characteristics of 15 patients who experienced a relapse were reviewed. Mean delay of relapse was 7 months (2-20). Maintenance therapy for the 2 months prior to the relapse was pyrimethamine alone (n = 4), pyrimethamine plus dapsone (n = 3), pyrimethamine plus spiramycine (n = 1), pyrimethamine plus clindamycine (n = 4), pyrimethamine plus sulfadiazine (n = 1) and no treatment (n = 2). Strict compliance was ascertained for only 5 patients. Compared with the first episode of brain toxoplasmosis, all 15 patients had new neurological signs, and new lesions of the brain were detected by CT scan in 67% patients. This study showed that poor compliance to maintenance therapy is a major factor of relapse, and the less favourable response to acute therapy could be due to progression of immunodeficiency.
We report two cases of penicillin G-resistant pneumococcal meningitis in adults, with clinical and bacteriological failure of amoxicillin and negative or incomplete response to third generation cephalosporins. Meningitis occurred in a man treated for myeloma and in an elderly woman under prolonged intermittent amoxicillin therapy for chronic otitis. Such situations are known as exposing to pneumococcal meningitis and to resistance of the strain involved to penicillin G. Both patients were cured by vancomycin in continuous infusion associated with rifampicin or fosfomycin. Contrary to third generation cephalosporins, which have higher minimal inhibitory concentrations, vancomycin and rifampicin are still fully active against penicillin G-resistant pneumococcal strains. Thus, vancomycin administered in continuous infusion and associated with rifampicin and fosfomycin deserves to be tried as first-line treatment of pneumococcal meningitis in patients at risk of resistance to penicillin G.
To assess the clinical presentation and outcome of infectious sinusitis in HIV-infected patients, we analyzed in a retrospective study, the records of HIV-infected patients hospitalized from June 1986 to November 1989. Twenty-eight episodes of infectious sinusitis, defined by radiological signs, were recorded in 20 HIV-infected patients. Clinical presentation suggestive of acute sinusitis was inconstant and in 6 episodes a persistent fever was the only symptom. Concomitant pneumonia was detected in 8 episodes. Bacteria were isolated in 8 episodes, and in 4 of them, Haemophilus influenzae was identified. Clinical relapses occurred in 8/20 patients, requiring a surgical drainage in 3 cases. The frequency of relapses and the possibility of chronicity justify a more prolonged and aggressive therapy in infectious sinusitis occurring in HIV-infected patients.
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The case of an immunocompetent woman who died of disseminated cytomegalovirus infection with encephalitis and skin ulcerations is reported. The duration of the disease, from onset to death, was five months. Cytomegalovirus was found in the blood, urine, skin, muscle, liver and periventricular brain tissue, but not in frontal cortex tissue. This case underlines the fact that cytomegalovirus may exceptionally cause life-threatening illness in immunocompetent adults.
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OBJECTIVE: To evaluate alterations in lung function during the course of HIV infection. DESIGN: Total lung capacity (TLC), the ratio of forced expiratory volume in one second to vital capacity (FEV1/VC), the carbon monoxide transfer factor (TLCO) and the alveolar-arterial oxygen gradient [delta (A-a)O2] were determined in this retrospective study. PATIENTS: Pulmonary function tests (PFT) were performed on 331 patients at various stages of HIV infection. Patients with a history of intravenous drug use or Kaposi's sarcoma were excluded. RESULTS: No significant differences were observed between the results for asymptomatic patients and those with AIDS-related complex (ARC). TLC, delta (A-a)O2 and TLCO were greatly altered in patients with acute Pneumocystis carinii pneumonia (PCP). No significant differences were observed in the TLC, delta(A-a)O2 or TLCO results between AIDS patients with no history of PCP and those with a history of a single episode of PCP. TLCO was significantly lower (P < 0.001) in AIDS patients with one previous episode of PCP than in the patients with ARC. Interestingly, both TLC and TLCO were significantly lower in the AIDS patients with no history of PCP than in the patients with ARC. Follow-up of 28 patients at different stages of HIV infection confirmed the alteration of PFT results in the late stages. CONCLUSIONS: The reasons for alterations in PFT results in PCP-free AIDS patients remain to be determined. Our findings suggest that PFT can provide valuable information throughout the course of HIV infection, particularly with regard to the indication for bronchoalveolar lavage.
We compared the activities of two different biological-response modifiers with that of clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice. Mice were pretreated daily with clarithromycin (50 mg/kg of body weight subcutaneously [s.c.]), RU-40555 (100 mg/kg s.c.), or granulocyte colony-stimulating factor (G-CSF) at low dose (15 micrograms/kg intraperitoneally [i.p.]) or high dose (300 micrograms/kg i.p.) 3 days before intravenous challenge with 2.5 x 10(7) CFU of the MO-1 strain of M. avium complex. Mice were treated daily until sacrifice at day 1, 8, 15, or 21 after challenge, and the numbers of CFU were measured per gram of tissue in lung and spleen. Compared at day 21 with control treatment, clarithromycin significantly decreased the level of infection in spleen (P < 0.0001) and lungs (P < 0.0001). Compared with control treatment, G-CSF at low dose had no activity, but G-CSF in combination with clarithromycin was more effective than clarithromycin alone in spleen (P < 0.05) and lungs (P < 0.015). The high dose of G-CSF was as effective as the low dose. RU-40555 alone had no beneficial activity. The RU-40555-clarithromycin combination was more effective than control treatment in spleen (P = 0.0001) and lungs (P < 0.0005) and more effective than clarithromycin alone in spleen (P < 0.009) but not in lungs. Thus, our experiments suggest that clarithromycin alone or in combination with G-CSF should be further evaluated for the prophylaxis of M. avium complex infection.
C57BL/6 mice were pretreated with rifabutin or clarithromycin alone or combined with minocycline 3 days before intravenous challenge (day 0) with Mycobacterium avium. Treatment was continued until sacrifice at days 1, 8, 15, and 21. Rifabutin or clarithromycin decreased the level of infection in both the lungs and the spleen. Rifabutin was as effective as clarithromycin in the lungs but was less [corrected] effective in the spleen. The clarithromycin-minocycline combination was as effective as clarithromycin alone.
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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.
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.
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.