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
Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Milken Institute School of Public Health, Department of Epidemiology and Biostatistics, George Washington University, Washington, District of Columbia.
Clin Infect Dis. 2017 Jun 15;64(suppl_3):S328-S336. doi: 10.1093/cid/cix104.
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.
关于上呼吸道定植菌的定植密度与病原体特异性肺炎之间的关联，目前信息有限。我们评估了流感嗜血杆菌、卡他莫拉菌、金黄色葡萄球菌和耶氏肺孢子菌的这种关联。
在7个低收入和中等收入国家，使用定量聚合酶链反应（PCR）对患有重症肺炎的儿童以及年龄频率匹配的社区对照的鼻咽/口咽拭子进行检测。使用Wilcoxon秩和检验评估定植密度中位数的差异。使用受试者工作特征曲线确定密度临界值。从肺穿刺培养或PCR、胸腔积液培养或PCR、血培养以及耶氏肺孢子菌免疫荧光检测中鉴定出病原体的病例定义为给定病原体的微生物学确诊病例。
与对照组相比，在微生物学确诊病例和胸部X线片（CXR）阳性病例中均观察到流感嗜血杆菌的密度更高。金黄色葡萄球菌和耶氏肺孢子菌在CXR阳性病例中的密度高于对照组。流感嗜血杆菌密度临界值为5.9 log10拷贝/毫升时，检测微生物学确诊病例的灵敏度为86%，特异性为77%；然而，病例组和对照组之间的密度有重叠，阳性预测值较低（<3%）。未找到金黄色葡萄球菌和卡他莫拉菌的有效密度临界值，且缺乏确诊病例数据限制了耶氏肺孢子菌临界值的确定。
有证据表明儿童流感嗜血杆菌定植密度与流感嗜血杆菌确诊肺炎之间存在关联；这种关联在流行病学研究中可能特别有意义。卡他莫拉菌、金黄色葡萄球菌和耶氏肺孢子菌的定植密度在临床环境中不太可能具有诊断价值。
