Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
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Clinical features such as cough, sputum production, fever, and the presence of a new lung infiltrate seen on radiograph are not specific to respiratory tract infection, nor do they define the need for antibiotic therapy. Therefore, investigators have looked for biological markers that can supplement clinical information to determine whether the etiology of the infection is more likely bacterial, needing antibiotic therapy, or viral. There are studies of a number of biological markers in serum and bronchoalveolar lavage fluid, including cytokines, acute-phase reactants, and immunoglobulins. ⋯ In addition, serial measurements of PCT have been reported to correlate with clinical response to therapy and may be able to guide short durations of therapy. In the future design of trials for community-acquired pneumonia, we may want to exclude patients with low PCT levels, because they are unlikely to benefit from antibiotic therapy. On the other hand, inclusion of patients with low PCT values creates heterogeneity in the study population and confounds the interpretation of clinical trial end points.
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Initial antibiotic selection and patient outcomes: observations from the National Pneumonia Project.
Guidelines for empirical treatment of hospitalized patients with pneumonia provide specific recommendations for antibiotic selection that are primarily based on findings from observational studies. ⋯ Initial antimicrobial treatment with the combination of a second- or third-generation cephalosporin and a macrolide or initial treatment with a fluoroquinolone was associated with a reduced 30-day mortality rate, compared with treatment with third-generation cephalosporin monotherapy, among non-intensive care unit patients. Although our results are consistent with other observational studies, controversy continues to exist about the use of nonexperimental cohort studies to demonstrate associations between processes of care, such as antibiotic selection, and patient outcomes.
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Review
Clinical trial design for mild-to-moderate community-acquired pneumonia--an industry perspective.
The use of noninferiority clinical trials is problematic unless one can establish the benefit of the active control versus no treatment. In community-acquired pneumonia, there are no placebo-controlled clinical trials establishing the benefit of antibiotic treatment, because the observed benefit of sulfapyridine and, subsequently, penicillin was established before the advent of randomized clinical studies. ⋯ In addition, there is one contemporary clinical trial that demonstrated superiority in clinical response of levofloxacin versus a cephalosporin regimen of ceftriaxone and/or cefuroxime for treatment of mild-to-moderate community-acquired pneumonia. Using either the historical data or the superiority study of levofloxacin, one can justify a noninferiority margin of 10% for the per-protocol population and 15% for the microbiologically evaluable population for future noninferiority clinical trials for mild-to-moderate community-acquired pneumonia.