Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data

被引：45

作者：

Barr, David A. ^{[1
,3
,6
]}

Lewis, Joseph M. ^{[6
,7
]}

Feasey, Nicholas ^{[6
,7
]}

Schutz, Charlotte ^{[2
,3
,5
]}

Kerkhoff, Andrew D. ^{[8
,9
]}

Jacob, Shevin T. ^{[6
]}

Andrews, Ben ^{[10
]}

Kelly, Paul ^{[11
]}

Lakhi, Shabir ^{[12
,13
]}

Muchemwa, Levy ^{[12
,13
,14
]}

Bacha, Helio A. ^{[15
]}

Hadad, David J. ^{[16
]}

Bedell, Richard ^{[17
,18
]}

van Lettow, Monique ^{[17
,19
]}

Zachariah, Rony ^{[20
]}

Crump, John A. ^{[21
,22
,23
]}

Alland, David ^{[24
]}

Corbett, Elizabeth L. ^{[7
,25
]}

Gopinath, Krishnamoorthy ^{[26
]}

Singh, Sarman ^{[27
]}

Griesel, Rulan ^{[5
]}

Maartens, Gary ^{[5
]}

Mendelson, Marc ^{[4
,5
]}

Ward, Amy M. ^{[3
]}

Parry, Christopher M. ^{[1
,6
,28
]}

Talbot, Elizabeth A. ^{[29
]}

Munseri, Patricia ^{[30
]}

Dorman, Susan E. ^{[31
]}

Martinson, Neil ^{[31
,32
]}

Shah, Maunank ^{[31
]}

Cain, Kevin ^{[35
]}

Heilig, Charles M. ^{[34
,35
]}

Varma, Jay K. ^{[35
]}

von Gottberg, Anne ^{[33
,36
]}

Sacks, Leonard ^{[37
]}

Wilson, Douglas ^{[38
]}

Squire, S. Bertel ^{[6
]}

Lalloo, David G. ^{[6
]}

Davies, Gerry ^{[1
]}

Meintjes, Graeme ^{[2
,3
,5
]}

机构：

[1] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L7 3EA, Merseyside, England

[2] Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Cape Town, South Africa

[3] Univ Cape Town, Inst Infect Dis & Mol Med, Cape Town, South Africa

[4] Univ Cape Town, Div Infect Dis & HIV Med, Cape Town, South Africa

[5] Univ Cape Town, Dept Med, Cape Town, South Africa

[6] Univ Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England

[7] Queen Elizabeth Cent Hosp, Coll Med, Malawi Liverpool Wellcome Clin Res Programme, Blantyre, Malawi

[8] Univ Calif San Francisco, Div HIV Infect Dis & Global Med, Zuckerberg San Francisco Gen Hosp, San Francisco, CA 94143 USA

[9] Univ Calif San Francisco, Dept Med, Trauma Ctr, San Francisco, CA 94143 USA

[10] Vanderbilt Univ, Sch Med, Inst Global Hlth, Nashville, TN 37212 USA

[11] Queen Mary Univ London, Barts & London Sch Med, Blizard Inst, London, England

[12] Univ Zambia, Sch Med, Dept Internal Med, Lusaka, Zambia

[13] Univ Teaching Hosp, Lusaka, Zambia

[14] Def Force Sch Hlth Sci, Lusaka, Zambia

[15] Inst Infectol Emilio Ribas, Sao Paulo, Brazil

[16] Univ Fed Espirito Santo, Ctr Ciencias Saude, Dept Clin Med, Vitoria, ES, Brazil

[17] Dignitas Int, Zomba, Malawi

[18] Univ British Columbia, Div Global Hlth, Vancouver, BC, Canada

[19] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada

[20] Med Sans Frontieres, Operat Ctr Brussels, Brussels, Belgium

[21] Univ Otago, Ctr Int Hlth, Dunedin, New Zealand

[22] Duke Univ, Med Ctr, Div Infect Dis & Int Hlth, Durham, NC USA

[23] Kilimanjaro Christian Med Ctr, Moshi, Tanzania

[24] Rutgers New Jersey Med Sch, Dept Med, Div Infect Dis, Newark, NJ USA

[25] London Sch Hyg & Trop Med, London, England

[26] Max Planck Inst Infect Biol, Berlin, Germany

[27] All India Inst Med Sci, Div Clin Microbiol & Mol Med, New Delhi, India

[28] Univ Nagasaki, Sch Trop Med & Global Hlth, Nagasaki, Japan

[29] Dartmouth Med Sch, Infect Dis & Int Hlth, Hanover, NH USA

[30] Muhimbili Univ Hlth & Allied Sci, Dept Internal Med, Dar Es Salaam, Tanzania

[31] Johns Hopkins Univ, Johns Hopkins Sch Med, Ctr TB Res, Baltimore, MD USA

[32] Univ Witwatersrand, Ctr Excellence Biomed TB Res, South African Med Res Council Soweto Matlosana Co, Perinatal HIV Res Unit, Johannesburg, South Africa

[33] Univ Witwatersrand, Fac Hlth Sci, Sch Pathol, Johannesburg, South Africa

[34] Ctr Surveillance Epidemiol & Lab Serv, Atlanta, GA USA

[35] US Ctr Dis Control & Prevent, Atlanta, GA USA

[36] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr Resp Dis & Meningitis, Johannesburg, South Africa

[37] US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD USA

[38] Univ KwaZulu Natal, Edendale Hosp, Dept Internal Med, Pietermaritzburg, South Africa

来源：

LANCET INFECTIOUS DISEASES | 2020年 / 20卷 / 06期

关键词：

HOSPITAL MORTALITY; SEVERE SEPSIS; BACTEREMIA; OUTCOMES; PREDICTORS; CHILDREN; AFRICA;

D O I：

10.1016/S1473-3099(19)30695-4

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. Methods We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. Findings We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96.2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per mu L (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio2.48, 95% CI 2.05-3.08) but not after 30 days (1.25, 0.84-2.49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3.15, 95% CI 1.16-8.84). Interpretation In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients.

引用

页码：742 / 752

页数：11

共 41 条

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