Colonization density of the upper respiratory tract as a predictor of pneumonia - Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii

PERCH Study Group

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)S328-S336
JournalClinical Infectious Diseases
Volume64
DOIs
StatePublished - Jan 1 2017

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Moraxella (Branhamella) catarrhalis
Pneumocystis carinii
Haemophilus influenzae
Respiratory System
Staphylococcus aureus
Pneumonia
Nonparametric Statistics
Polymerase Chain Reaction
ROC Curve
Fluorescent Antibody Technique
Epidemiologic Studies
Thorax
Sensitivity and Specificity
Lung

Keywords

  • Colonization density
  • PERCH
  • Pneumonia

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

@article{60e770e03c4a44a386c7eb1212db41e2,
title = "Colonization density of the upper respiratory tract as a predictor of pneumonia - Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii",
abstract = "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.",
keywords = "Colonization density, PERCH, Pneumonia",
author = "{PERCH Study Group} and Park, {Daniel E.} and Baggett, {Henry C.} and Howie, {Stephen R.C.} and Qiyuan Shi and Watson, {Nora L.} and Brooks, {W Abdullah} and Knoll, {Maria Deloria} and Hammitt, {Laura L} and Kotloff, {Karen L.} and Levine, {Orin S.} and Madhi, {Shabir A.} and Murdoch, {David R.} and O'Brien, {Katherine L} and Scott, {J. Anthony G.} and Thea, {Donald M.} and Dilruba Ahmed and Martin Antonio and Baillie, {Vicky L.} and Andrea Deluca and Driscoll, {Amanda J.} and Wei Fu and Gitahi, {Caroline W.} and Emmanuel Olutunde and Melissa Higdon and Lokman Hossain and Karron, {Ruth A} and Maiga, {Abdoul Aziz} and Maloney, {Susan A.} and Moore, {David P.} and Morpeth, {Susan C.} and John Mwaba and Musaku Mwenechanya and Christine Prosperi and Mamadou Sylla and Somsak Thamthitiwat and Scott Zeger and Daniel Feikin and Nicholas Fancourt and Kagucia, {Eunice Wangeci} and Mengying Li and Zhenke Wu and Jane Crawley and Endtz, {Hubert P.} and Khalequ Zaman and Doli Goswami and Yasmin Jahan and Hasan Ashraf and Ebruke, {Bernard E.} and Jessica McLellan and Eunice Machuka",
year = "2017",
month = "1",
day = "1",
doi = "10.1093/cid/cix104",
language = "English (US)",
volume = "64",
pages = "S328--S336",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Colonization density of the upper respiratory tract as a predictor of pneumonia - Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii

AU - PERCH Study Group

AU - Park, Daniel E.

AU - Baggett, Henry C.

AU - Howie, Stephen R.C.

AU - Shi, Qiyuan

AU - Watson, Nora L.

AU - Brooks, W Abdullah

AU - Knoll, Maria Deloria

AU - Hammitt, Laura L

AU - Kotloff, Karen L.

AU - Levine, Orin S.

AU - Madhi, Shabir A.

AU - Murdoch, David R.

AU - O'Brien, Katherine L

AU - Scott, J. Anthony G.

AU - Thea, Donald M.

AU - Ahmed, Dilruba

AU - Antonio, Martin

AU - Baillie, Vicky L.

AU - Deluca, Andrea

AU - Driscoll, Amanda J.

AU - Fu, Wei

AU - Gitahi, Caroline W.

AU - Olutunde, Emmanuel

AU - Higdon, Melissa

AU - Hossain, Lokman

AU - Karron, Ruth A

AU - Maiga, Abdoul Aziz

AU - Maloney, Susan A.

AU - Moore, David P.

AU - Morpeth, Susan C.

AU - Mwaba, John

AU - Mwenechanya, Musaku

AU - Prosperi, Christine

AU - Sylla, Mamadou

AU - Thamthitiwat, Somsak

AU - Zeger, Scott

AU - Feikin, Daniel

AU - Fancourt, Nicholas

AU - Kagucia, Eunice Wangeci

AU - Li, Mengying

AU - Wu, Zhenke

AU - Crawley, Jane

AU - Endtz, Hubert P.

AU - Zaman, Khalequ

AU - Goswami, Doli

AU - Jahan, Yasmin

AU - Ashraf, Hasan

AU - Ebruke, Bernard E.

AU - McLellan, Jessica

AU - Machuka, Eunice

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Colonization density

KW - PERCH

KW - Pneumonia

UR - http://www.scopus.com/inward/record.url?scp=85038075179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038075179&partnerID=8YFLogxK

U2 - 10.1093/cid/cix104

DO - 10.1093/cid/cix104

M3 - Article

C2 - 28575367

AN - SCOPUS:85038075179

VL - 64

SP - S328-S336

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

ER -