Treatment of tularemia with fluoroquinolones: two cases and review.

Streptomycin, gentamicin, and tetracycline are currently considered the antimicrobials of choice for the treatment of tularemia. Preliminary data suggest that quinolones may be effective alternative agents; however, clinical experience is limited, and their role in treating severe disease is uncertain. We recently treated two acutely ill immunocompromised patients who had presumed "atypical" pneumonia with levofloxacin. Both patients had an excellent clinical response and were diagnosed with tularemia only when blood cultures subsequently yielded Francisella tularensis. Neither patient relapsed during 12 months of follow-up. Including our two cases, a total of 10 cases of tularemia treated with quinolones have been reported. In all 10 cases, a favorable clinical response was documented, and no relapses occurred. We conclude that the quinolones appear promising for the treatment of even severe tularemia, and they should be considered efficacious alternative agents for patients who do not require parenteral therapy or are intolerant of more standard treatment regimens.

Multicenter evaluation of quantification methods for plasma human immunodeficiency virus type 1 RNA.

Six procedures for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated by nine laboratories. The procedures differed in their sample volume and preparation of samples and methods of amplification and detection. Coded samples in a 10-fold dilution series of HIV-1-spiked plasma were correctly ranked by all six procedures. Subsequently, coded duplicate plasma samples from 16 HIV-1-infected patients were tested using a common set of standards. Several HIV-1 RNA procedures were sufficiently reproducible so that an empiric 4-fold change could be viewed as significant. HIV-1 RNA levels in the patients (up to 370,000 RNA copies/mL) correlated with proviral HIV-1 DNA and were inversely correlated with CD4 cell counts; HIV-1 RNA assays were more sensitive than plasma viremia, standard p24 antigen, or immune complex-dissociated p24 antigen assays. This study demonstrated that several HIV-1 RNA quantitative assays are ready for use in clinical trials.

Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection.

OBJECTIVE: To assess safety, pharmacokinetics, and in-vivo virologic activity of five different combination regimens of zidovudine and didanosine compared with zidovudine alone in patients with human immunodeficiency virus type 1 (HIV-1) infection. DESIGN: Open-label, partially randomized, dose-ranging study. SETTING: University-affiliated, medical center clinics. PATIENTS: A total of 69 patients with HIV-1 infection, CD4+ cell counts fewer than 400 cells/mm3, and fewer than 121 days of previous zidovudine treatment. INTERVENTIONS: Fifty-five patients received combination therapy with zidovudine and didanosine, and 14 received zidovudine therapy alone (600 mg/d). Daily dosages in milligrams of zidovudine and didanosine, respectively, in the five combination groups were 150 and 90 mg, 300 and 334 mg, 600 and 334 mg, 300 and 500 mg, and 600 and 500 mg. MEASUREMENTS: CD4+ cell counts, HIV-1 RNA titers in plasma, and toxic effects. RESULTS: The combination regimens were associated with higher and more sustained increases in CD4+ cells than zidovudine alone, even after adjustment for initial CD4+ counts and previous zidovudine therapy (P < 0.001). The median increase in CD4+ cell counts was 166 cells/mm3 with combination therapy and 77 cells/mm3 with zidovudine alone (P = 0.001) and did not differ statistically among the five combination regimens. Human immunodeficiency virus type 1 RNA titers in plasma decreased in 15 (83%) of 18 combination-therapy recipients compared with 2 of 7 zidovudine-alone recipients (P = 0.017). No pharmacokinetic interactions were seen between zidovudine and didanosine. Toxicity rates were low among all treatment groups. A greater decrease in hemoglobin levels was seen with the regimen using zidovudine alone (-8 g/L) compared with combination regimens using the same zidovudine dose (-1.5 g/L, P = 0.03). CONCLUSIONS: Combination therapy with zidovudine and didanosine produced larger and more sustained increases in CD4+ cell counts, more frequent decreases in plasma HIV-1 RNA titers, and more stable hematologic status than zidovudine therapy alone. The effects of this combination on the progression of HIV disease merit further study, to provide information about clinical outcome, because this was a relatively small study based on surrogate markers of HIV-1 infection.

Serial immunological studies in multiple sclerosis patients treated systemically with human alpha interferon.

A battery of immunological functions was studied over a 2-year period in conjunction with a placebo-controlled trial of natural human alpha interferon in patients with multiple sclerosis. IgG synthesis was increased both systemically and intrathecally by administration of interferon; however, there were only minor changes in cerebrospinal fluid oligoclonal bands. Levels of helper and suppressor T lymphocytes fluctuated independently of clinical exacerbations, although mean helper/suppressor ratios were higher in multiple sclerosis patients than in controls and increased further during interferon treatment. Cerebrospinal fluid myelin basic protein and antibodies to basic protein were not affected by exacerbations or by interferon administration. Circulating IgG antibodies induced by interferon treatment appeared to be directed at a non-interferon contaminant of the preparation. None of the assays was a consistent indicator of disease activity or of clinical response to interferon.

CSF antibody to myelin basic protein. Measurement in patients with multiple sclerosis and subacute sclerosing panencephalitis.

A solid phase radioimmunoassay was used to detect antibodies to myelin basic protein (MBP) in the CSF of patients with multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE). F(ab')2 fragments prepared from SSPE IgG retained their activity, which showed that the assay measures a true antigen-antibody reaction rather than nonspecific adherence to IgG to MBP. Samples of CSF from 48 patients with MS and 30 patients with SSPE were tested and, in both conditions, antibody activity was significantly greater than in controls, when tested at identical IgG concentrations. In MS, levels of antibody were highest in patients with acute exacerbations and lower in patients in remission, which supported the hypothesis that autoimmunity to a myelin antigen may play a role in the pathogenesis of the disease. The reaction with MBP was consistently more pronounced in SSPE than in MS. In view of the association of SSPE with measles virus and the presence of high titers of measles antibody in the CSF, antibodies to measles and to MBP may be directed against similar antigenic determinants.