Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected Patients Hospitalized with Severe Sepsis in Uganda–High Frequency, Low Clinical Sand Derivation of a Clinical Prediction Score

Abstract

BackgroundWhen manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.MethodsWe prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.ResultsAmong 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm3, p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89].ConclusionsNearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection.

Bloodstream infections in HIV-infected patients

“…34 Other studies report lower rates of BSI due to coagulase-negative staphylococci, ranging from 0%-6%. 11,32,33,42 Gram-negative bacteria Among the Gram-negative bacteria, nontyphoidal Salmonella (NTS) is correlated to HIV infection. NTS refers to infections caused by all serotypes of Salmonella except typhi and paratyphi A, B and C. NTS transmission can occur via the consumption of food or water contaminated with animal feces and, less frequently, through direct contact with infected animals and/or directly between humans.…”

“…The mycobacteria account for a number of BSI ranging from 17% to 54% of all etiologies in studies performed in endemic areas (Table 1). 42,50,53,[56][57][58] This high prevalence may depend on the high frequency of tubercular disease in these geographic areas, as nearly one quarter of the new MTB cases worldwide are estimated to occur in sub-Saharan Africa. 59 In addition, advanced HIV disease may play a role.…”

Policy to practice: impact of GeneXpert MTB/RIF implementation on the TB spectrum of care in Lilongwe, Malawi

“…20,21 Physicians working in such environments may start patients on empiric therapy based on factors such as failure of antibiotic treatment, clinical danger signs, low healthcare access environment, delay in GeneXpert results, positive results using other radiologic modalities, or high patient mortality rate. [22][23][24] Overall, these findings suggest that empiric TB therapy is prevalent although the impact on patient outcomes is currently the subject of clinical trials.…”

“…25 In high HIV-TB burden environments, empiric treatment is often used to offset the diagnostic limitations and provide, possibly, same day treatment to decompensating patients. [21][22][23][24][25] The few studies presenting diagnostic information on GeneXpert negative individuals suggest that smear microscopy and chest x-ray have limited utility in detecting culture positive, Xpert negative, extrapulmonary or disseminated TB. 6,11 For sputum scarce patients, rapid diagnostics using other samples such as urine (urine LAM or urine GeneXpert) or blood may prove more feasible for testing.…”

Detection of Mycobacterium Tuberculosis in Blood for Diagnosis of Generalised Tuberculosis in Hiv-Positive Patients

“…Вероятность выявления мико-бактерии в крови у ВИЧ-инфицированных паци-ентов варьирует от 5 до 30% от числа исследован-ных образцов [4,5].…”