Effect of Empiric Anti–Mycobacterium tuberculosis Therapy on Survival Among Human Immunodeficiency Virus–Infected Adults Admitted With Sepsis to a Regional Referral Hospital in Uganda

Abstract

Background Mycobacterium tuberculosis is the leading cause of bloodstream infection among human immunodeficiency virus (HIV)–infected patients with sepsis in sub-Saharan Africa and is associated with high mortality rates. Methods We conducted a retrospective study of HIV-infected adults with sepsis at the Mbarara Regional Referral Hospital in Uganda to measure the proportion who received antituberculosis therapy and to determine the relationship between antituberculosis therapy and 28-day survival. Results Of the 149 patients evaluated, 74 (50%) had severe sepsis and 48 (32%) died. Of the 55 patients (37%) who received antituberculosis therapy, 19 (35%) died, compared with 29 of 94 (31%) who did not receive such therapy (odds ratio, 1.34; 95% confidence interval [CI], .56–3.18; P = .64). The 28-day survival rates did not differ significantly between these 2 groups (log-rank test, P = .21). Among the 74 patients with severe sepsis, 9 of 26 (35%) who received antituberculosis therapy died, versus 23 of 48 (48%) who did not receive such therapy (odds ratio, 0.58; 95% CI, .21–1.52; P = .27). In patients with severe sepsis, antituberculosis therapy was associated with an improved 28-day survival rate (log-rank test P = .01), and with a reduced mortality rate in a Cox proportional hazards model (hazard ratio, 0.32; 95% CI, .13–.80; P = .03). Conclusions Empiric antituberculosis therapy was associated with improved survival rates among patients with severe sepsis, but not among all patients with sepsis.

A Saudi Arabian Public Health Perspective of Tuberculosis

“…As a special case, a TB patient with severe sepsis can be administered with the empiric antituberculosis treatment. The WHO guidelines also support this strategy, calling for immediate instead of delayed empiric therapy in areas of high tuberculosis and HIV prevalence [ 109 ].…”

Population Pharmacokinetics and Significant Under-Dosing of Anti-Tuberculosis Medications in People with HIV and Critical Illness

“…An expected lower proportion of patients with confirmed TB died before the two-week PK visit compared to those without microbiological confirmation of TB. While the high and early case fatality rate is not dissimilar to other cohorts with HIV and critical illness in Uganda [ 19 ], we were unable to determine if there were PK differences among those with early mortality and those who survived to PK testing. Given that the pathophysiology of severe sepsis leads to altered plasma drug binding capabilities and decreased drug perfusion to tissues, and impaired metabolism and clearance due to liver and kidney injury [ 18 ], it is possible that those patients with early mortality may have had unexpectedly higher serum exposures than were measured in the cohort of survivors.…”

Performance of the Universal Vital Assessment (UVA) mortality risk score in hospitalized adults with infection in Rwanda: A retrospective external validation study

“…Similar to the findings of the Klinger study, we also found that the UVA score calculated at 72 hours after admission performed less well than when calculated at admission. This difference in performance may be because improvement in vital signs in the short term do not necessarily predict improved outcomes in the long term due in part to immunodeficiency, poor nutrition, and a lack of appropriate antimicrobial therapy [ 17 – 19 ]. For example, in a study of the resuscitation of patients with sepsis in Uganda, we found that vital signs and whole blood lactate improved over the first 6 hours but that these improvements were not associated with improved case fatality rates [ 18 ].…”