Use of a Rapid Test of Pneumococcal Colonization Density to Diagnose Pneumococcal Pneumonia

Background. There is major need for a more sensitive assay for the diagnosis of pneumococcal community-acquired pneumonia ( CAP). We hypothesized that pneumococcal nasopharyngeal (NP) proliferation may lead to microaspiration followed by pneumonia. We therefore tested a quantitative lytA real-time polymerase chain reaction (rtPCR) on NP swab samples from patients with pneumonia and controls. In a prospective study, human immunodeficiency virus (HIV)-infected patients with pneumococcal pneumonia had nasopharyngeal colonization densities 5 log(10) higher than those in concurrently identified HIV-infected asymptomatic controls, as measured by real-time polymerase chain reaction (rtPCR). A nasopharyngeal lytA density of >= 8000 copies/mL at rtPCR may be a useful diagnostic marker for pneumococcal pneumonia.Methods. In the absence of a sensitive reference standard, a composite diagnostic standard for pneumococcal pneumonia was considered positive in South African human immunodeficiency virus (HIV)-infected adults hospitalized with radiographically confirmed CAP, if blood culture, induced good-quality sputum culture, Gram stain, or urinary Binax demonstrated pneumococci. Results of quantitative lytA rtPCR in NP swab samples were compared with quantitative colony counts in patients with CAP and 300 HIV-infected asymptomatic controls. Results. Pneumococci were the leading pathogen identified in 76 of 280 patients with CAP (27.1%) using the composite diagnostic standard. NP colonization density measured by lytA rtPCR correlated with quantitative cultures (r = 0.67; P < .001). The mean lytA rtPCR copy number in patients with pneumococcal pneumonia was 6.0 log(10) copies/mL, compared with patients with CAP outside the composite standard (2.7 log(10) copies/mL; P < .001) and asymptomatic controls (0.8 log(10) copies/mL; P < .001). A lytA rtPCR density >= 8000 copies/mL had a sensitivity of 82.2% and a specificity of 92.0% for distinguishing pneumococcal CAP from asymptomatic colonization. The proportion of CAP cases attributable to pneumococcus increased from 27.1% to 52.5% using that cutoff. Conclusions. A rapid molecular assay of NP pneumococcal density performed on an easily available specimen may significantly increase pneumococcal pneumonia diagnoses in adults.