Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques.

BACKGROUND: Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay. METHODS AND FINDINGS: We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults. CONCLUSIONS: Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

Management of nonsevere pneumonia in military trainees with the urinary antigen test for Streptococcus pneumoniae: an innovative approach to targeted therapy.

BACKGROUND: The drug of choice for treatment of Streptococcus pneumoniae infection is generally a penicillin (including amoxicillin). Targeted therapy is, however, rarely used, because results of definitive diagnostic tests for pneumonia are not available for several days. Thus, broad-spectrum antibiotics are used for empirical treatment of pneumonia to cover both typical and atypical pathogens. Our purpose was to assess the usefulness of a strategy of targeted antimicrobial therapy based on the results of a rapid urinary antigen test for S. pneumoniae. METHODS: Military trainees with pneumonia were prospectively assigned to 2 groups: patients with positive urinary antigen test results who were treated with amoxicillin (1000 mg 3 times per day), and patients with negative urinary antigen test results who were treated with clarithromycin (500 mg 2 times per day). The duration of therapy was 5-10 days for both groups. RESULTS: A total of 219 evaluable patients were enrolled in the study. The most common causes of pneumonia were S. pneumoniae, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Patients with positive urinary antigen test results had illness of greater severity at the time of study entry. Twenty-two percent of patients had positive urinary antigen test results (i.e., the amoxicillin group), and 78% had negative urinary antigen test results (i.e., the clarithromycin group). The clinical success rates were 94% for the clarithromycin group and 90% for the amoxicillin group (P = not significant). None of the patients who were classified as having treatment failure died. Resolution of clinical manifestations was slower for patients with pneumococcal pneumonia defined by a positive urinary antigen test result. CONCLUSIONS: The urine antigen test allowed targeted use of a penicillin (amoxicillin) for young immunocompetent individuals with nonsevere, community-acquired pneumonia. Clarithromycin was highly effective against both S. pneumoniae pneumonia and pneumonia due to atypical pathogens.

Two regimens of azithromycin prophylaxis against community-acquired respiratory and skin/soft-tissue infections among military trainees.

Epidemics of community-acquired pneumonia (CAP) are a frequent cause of morbidity among Russian military trainees. We evaluated azithromycin prophylaxis against CAP. In 2001-2002, incoming military trainees were randomized to 1 of 3 trial arms by training group: azithromycin, 500 mg per week for 8 weeks (R1); azithromycin, 1500 mg once at enrollment (R2); or no therapy (R3). During the 22 weeks of training, CAP was diagnosed in 20.2% of 678 subjects in the R3 group, 8.6% of 508 subjects in the R1 group, and 10.3% of 507 subjects in the R2 group. Throat carriage cultures revealed that the proportion of Streptococcus pneumoniae isolates with resistance to macrolides correspondingly increased during the study, from 0% (all) to 40% (R1) and 22.6% (R2) by week 20. Azithromycin prophylaxis is effective against CAP in a healthy population of young men at transient high risk of disease; however, azithromycin use must be tempered with the possible concomitant risk of selection for resistant endemic pathogens.