Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.

Publication Type
Journal Article
Year of Publication
Park, Daniel E; Baggett, Henry C; Howie, Stephen R C; Shi, Qiyuan; Watson, Nora L; Brooks, W Abdullah; Deloria Knoll, Maria; Hammitt, Laura L; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G; Thea, Donald M; Ahmed, Dilruba; Antonio, Martin; Baillie, Vicky L; DeLuca, Andrea N; Driscoll, Amanda J; Fu, Wei; Gitahi, Caroline W; Olutunde, Emmanuel; Higdon, Melissa M; Hossain, Lokman; Karron, Ruth A; Maiga, Abdoul Aziz; Maloney, Susan A; Moore, David P; Morpeth, Susan C; Mwaba, John; Mwenechanya, Musaku; Prosperi, Christine; Sylla, Mamadou; Thamthitiwat, Somsak; Zeger, Scott L; Feikin, Daniel R; PERCH Study Group
Clin Infect Dis
Date Published
2017 Jun 15
Child, Preschool; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Moraxella catarrhalis; Moraxellaceae Infections; Nasopharynx; Oropharynx; Pneumocystis carinii; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Pneumonia, Staphylococcal; Polymerase Chain Reaction; Respiratory Tract Infections; ROC Curve; Staphylococcus aureus

Background.: There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.

Methods.: In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens.

Results.: Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii.

Conclusions.: There is evidence for an association between H. influenzae colonization density and H. influenzae-confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings.