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

Thuli Mthiyane, Jonny Peter, Jenny Allen, Cathy Connolly, Malika Davids, Roxana Rustomjee, Timothy H. Holtz, Lesibana Malinga, Keertan Dheda


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.