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. 2019 Aug;11(8):3505-3514.
doi: 10.21037/jtd.2019.07.69.

Urine lipoarabinomannan (LAM) and antimicrobial usage in seriously-ill HIV-infected patients with sputum smear-negative pulmonary tuberculosis

Thuli Mthiyane  1 , Jonny Peter  2 , Jenny Allen  1   3 , Cathy Connolly  4 , Malika Davids  5 , Roxana Rustomjee  1   6 , Timothy H Holtz  7 , Lesibana Malinga  1 , Keertan Dheda  8   9
Affiliations

Urine lipoarabinomannan (LAM) and antimicrobial usage in seriously-ill HIV-infected patients with sputum smear-negative pulmonary tuberculosis

Thuli Mthiyane et al. J Thorac Dis. 2019 Aug.

Abstract

Background: Based on current WHO guidelines, hospitalized tuberculosis (TB) and HIV co-infected patients with CD4 count <100 cells/mm3 who are urine lipoarabinomannan (LAM) positive should be initiated on TB treatment. This recommendation is conditional, and data are limited in sputum smear-negative patients from TB endemic countries where the LAM test is largely inaccessible. Other potential benefits of LAM, including reduction in antibiotic usage have, hitherto, not been explored.

Methods: We consecutively enrolled newly-admitted seriously-ill HIV-infected patients (n=187) with suspected TB from three hospitals in KwaZulu-Natal, South Africa. All patients were empirically treated for TB as per the WHO 2007 smear-negative TB algorithm (patients untreated for TB were not recruited). Bio-banked urine, donated prior to anti-TB treatment, was tested for TB-infection using a commercially available LAM-ELISA test. TB sputum and blood cultures were performed.

Results: Data from 156 patients containing CD4 count, urine-LAM, sputum and blood culture results were analysed. Mean age was 37 years, median CD4-count was 75 cells/mm3 [interquartile range (IQR), 34-169 cells/mm3], 54/156 (34.6%) were sputum culture-positive, 12/54 (22.2%) blood-culture positive, and 53/156 (34.0%) LAM-positive. Thus, LAM sensitivity was 55.6% (30/54). The study design did not allow for calculation of specificity. Urine-LAM positivity was associated with low CD4 count (P=0.002). Ninety-point-six percent (48/53) of LAM-positive patients received antibiotics [15/48 (31.3%), 23/48 (47.9%) and 10/48 (20.8%) received one, two or three different antibiotics respectively], while the duration of antibiotic therapy was more than 5 days in 26 of 46 (56.5%) patients.

Conclusions: Urine LAM testing in sputum smear-negative severely-ill hospitalized patients with TB-HIV co-infection and advanced immunosuppression, offered an immediate rule-in diagnosis in one-third of empirically treated patients. Moreover, LAM, by providing a rapid alternative diagnosis, could potentially reduce antibiotic overusage in such patients thereby reducing health-care costs and facilitating antibiotic stewardship.

Keywords: HIV; Tuberculosis (TB); lipoarabinomannan (LAM); smear-negative; sputum.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Participant flow diagram of seriously-ill HIV-infected hospitalized patients with sputum smear-negative pulmonary tuberculosis. LAM, lipoarabinomannan.
Figure 2
Figure 2
LAM, sputum and blood culture, in seriously-ill, HIV-infected patients with sputum smear-negative pulmonary tuberculosis (n=156). LAM, lipoarabinomannan; Pos, positive; Neg, negative.
See this image and copyright information in PMC

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