Outcomes of a clinical diagnostic algorithm for management of ambulatory smear and Xpert MTB/Rif negative HIV infected patients with presumptive pulmonary TB in Uganda: a prospective study.
BACKGROUND
Diagnostic guidelines for Tuberculosis (TB) in HIV infected patients previously relied on microscopy where the value of initial antibiotic treatment for exclusion of pulmonary TB (PTB) was limited. New guidelines rely on the Xpert MTB Rif test (Xpert). However, the value of the antibiotic treatment remains unclear particularly in individuals who are smear-negative and Xpert-negative-given Xpert has only moderate sensitivity for smear-negative PTB. We assessed an algorithm involving initial treatment with antibiotics prior empiric TB treatment in HIV patients with presumptive PTB who were both smear and Xpert negative.


METHODS
We performed a prospective study with six month follow-up to establish patient response to a course of broad spectrum antibiotics prior empiric TB treatment between March 2012 and June 2013. We calculated the proportion of patients who responded to the antibiotic treatment and those who did not. We computed the crude and adjusted odds ratios with their 95% confidence intervals, for response to the antibiotic treatment on various patient characteristics. We report treatment outcomes for patients who received broad spectrum antibiotics only or who were initiated empiric TB treatment.


RESULTS
Our cohort comprised 162 smear-negative and Xpert-negative patients, of whom 59% (96 of 162) were female, 81% (131 of 162) were on antiretroviral therapy (ART) for a median of 8.7 months. Overall, 88% (141 of 160) responded to the antibiotic treatment, 8% (12 of 160) got empiric TB treatment and 4% (7 out of 160) were treated for other respiratory disease. The odds of improvement on antibiotics were lower in patients with advanced HIV disease than in patients with early HIV disease. Adjusted odds ratios were significant for HIV clinical stage (AOR; 0.038,) and duration on ART (AOR; 1.038,).


CONCLUSIONS
The majority of HIV patients with presumptive PTB with smear-negative and Xpert negative results improved on the antibiotic treatment and did not require empiric TB treatment. Initial antibiotic treatment appeared more successful in patients with less advanced HIV disease. Findings from our study suggest it is useful to initiate HIV infected patients with presumptive PTB having smear and Xpert negative results on an initial course of antibiotic treatment prior empiric TB treatment.
Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda; Department of Public Health Sciences, Karolinska Institute, Solna, Sweden; Makerere University Joint AIDS Program, Kampala, Uganda.
Simon
S
Walusimbi
Makerere University Joint AIDS Program, Kampala, Uganda; Department of Internal Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Fred
F
Semitala
Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
Freddie
F
Bwanga
Department of Public Health Sciences, Karolinska Institute, Solna, Sweden; Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
Melles
M
Haile
Department of Public Health Sciences, Karolinska Institute, Solna, Sweden.
Ayesha
A
De Costa
University of California San Francisco, Pulmonary and Critical Care Medicine, San Francisco, United States.
Lucian
L
Davis
Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
Moses
M
Joloba
Department of Public Health Sciences, Karolinska Institute, Solna, Sweden; Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
Sven
S
Hoffner
Department of Internal Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Moses
M
Kamya
D000328:Adult; D000465:Algorithms; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy; D014454:Uganda
D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular
HIV; TB; Xpert-negative; algorithm; outcomes; smear-negative; strategy