Bacterial spondylodiskitis--i.e., adjacent vertebral osteomyelitis and diskitis--was studied in 80 adult patients. The infection was due to Mycobacterium tuberculosis in 31 cases (39%) and to pyogenic bacteria in 49 cases (61%). The latter pathogens included gram-negative bacilli in 16 cases (20%), Staphylococcus species in 15 (19%), Streptococcus species in 9 (11%), and Corynebacterium species in 1 (1%); the pathogens in the 8 remaining cases (10%) were not identified. Of the patients with tuberculous spondylodiskitis, 55% came from countries where tuberculosis is endemic (P < .001). Cases due to staphylococci and those due to M. tuberculosis were associated with a high frequency of previous active infection with those respective organisms at any site (47% and 42%, respectively; P < .001) and with a high rate of neurological complications (33% and 32%, respectively; P < .001). Nine patients with pyogenic spondylodiskitis (18%) but only one patient with tuberculous spondylodiskitis (3%) had diabetes mellitus (P < .05). Blood cultures were positive in 23 (56%) of the 41 cases of pyogenic spondylodiskitis due to an identified bacterium. Discovertebral needle biopsy contributed to the bacteriologic diagnosis in 29 (74%) of 39 cases.

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 ,ug of rifapentine per ml (MICs for the two strains, 4 and 16 ,ug/ml), 4 ,ug of clarithromycin per ml (MICs, 8 and 4 ,ug/ml), 1 ,ug of azithromycin per ml (MICs, 32 and 16 ,ug/ml), 4 ,ug of temafloxacin per ml (MICs, 2 and 16 ,ug/ml), and 1 ,ug of sparfloxacin per ml (MICs, 0.5 and 2 ,ug/ml). Compared with controls on day 7 after inoculation, clarithromycin (P < 0.001), sparfloxacin (P < 0.001), and azithromycin (P < 0.001 for the first strain, P < 0.02 for the second) slowed intracellular replication. Rifapentine (P < 0.001) and temafloxacin (P < 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.Mycobacterium avium complex infection remains a frequent opportunistic infection in patients with AIDS (25, 26). New drugs with potent intracellular activity against the M. avium complex inside phagocytes are needed to improve the treatment of this persistent infection. Cell models permit assessment of the activity of antimicrobial agents against the M. avium complex when it is multiplying within human macrophages (1,2,3,20). We have previously shown in a human macrophage model that clarithromycin could be a promising drug in the treatment of M. avium complex infections (20). In a pilot randomized trial, clarithromycin decreased the bacterial counts in the blood of patients with AIDS who presented with a disseminated M. avium complex infection (7). The aim of the present study was to evaluate, in the same model, the activities of new drugs active in vitro against the M. avium complex. The new drugs tested were a macrolide, azithromycin, two fluoroquinolones, temafloxacin and sparfloxacin, and a rifamycin, rifapentine (1, 2, 14-17). Their activities were compared with that of clarithromycin, which was studied in the same model (20 (Becton Dickinson Labware, Oxnard, Calif.). After 21 days of culturing, the bacterial suspension was adjusted to a density of 1 mg/ml with a turbidimeter (Institut Pasteur Production, Paris, France). For each strain, counts of CFU on 7H11 agar correlated this density to a bacterial concentration of 1.5 x 108 and 5 x 108 CFU/ml, respectively. Aliquots of the bacterial suspensions were frozen at -80°...

The eosinophil count appears to normalize faster than C-reactive protein (CRP) and polymorphonuclear neutrophils in eosinopenic patients on appropriate antimicrobial therapy. This simple test is easy to perform as part of a regular complete blood count, with no additional costs as required for CRP or procalcitonin.

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.

Sparfloxacin (50 mg/kg of body weight given subcutaneously each day), alone or in combination with ethambutol (50 mgtkg 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 sparfioxacin 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 C57BV6 mice infected with the M. avium complex can be used for the evaluation of antimicrobial agents. fluoroquinolones (4, 6, 11, 20, 21, 30, 31). Sparfloxacin is a fluoroquinolone that exhibits a good efficacy against the M. avium complex in vitro and in a model of intracellular infection within human macrophages (26,31,36). Ethambutol, which inhibits bacterial cell envelope synthesis, has been shown to be synergistic with fluoroquinolones against the M. avium complex (32). Mifepristone (RU-38 486; Roussel-UCLAF, Romainville, Seine-Saint Denis, France), an inhibitor of the progesterone receptors, is used in humans as a short course of treatment for early pregnancy interruption and for prolonged periods, with good tolerance, for the treatment of some cases of breast cancer, meningioma, and Cushing's syndrome (2,27,33,34). It has been shown in animals that mifepristone is also an inhibitor of the cortisol receptors and could enhance the inflammatory reaction (5, 7, 8, 10, 12, 17, 18, 23-25, 28, 35 In a preliminary study, mice were kept untreated after the

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