Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population

Abstract

Background: Sepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality.

Methodology/results: Three-hundred eighty-two patients fulfilled enrollment criteria for a severe sepsis syndrome. Vital signs, management and laboratory results were recorded. Outcomes measured included in-hospital and post-discharge mortality. Most patients were HIV-infected (320/377, 84.9%) with a median CD4+ T cell (CD4) count of 52 cells/mm(3) (IQR, 16-131 cells/mm(3)). Overall mortality was 43.0%, with 23.7% in-hospital mortality (90/380) and 22.3% post-discharge mortality (55/247). Significant predictors of in-hospital mortality included admission Glasgow Coma Scale and Karnofsky Performance Scale (KPS), tachypnea, leukocytosis and thrombocytopenia. Discharge KPS and early fluid resuscitation were significant predictors of post-discharge mortality. Among HIV-infected patients, CD4 count was a significant predictor of post-discharge mortality. Median volume of fluid resuscitation within the first 6 hours of presentation was 500 mLs (IQR 250-1000 mls). Fifty-two different empiric antibacterial regimens were used during the study. Bacteremic patients were more likely to die in hospital than non-bacteremic patients (OR 1.83, 95% CI = 1.01-3.33). Patients with Mycobacterium tuberculosis (MTB) bacteremia (25/249) had higher in-hospital mortality (OR 1.97, 95% CI = 1.19-327) and lower median CD4 counts (p = 0.001) than patients without MTB bacteremia.

Conclusion: Patients presenting with sepsis syndromes to two Ugandan hospitals had late stage HIV infection and high mortality. Bacteremia, especially from MTB, was associated with increased in-hospital mortality. Most clinical predictors of in-hospital mortality were easily measurable and can be used for triaging patients in resource-constrained settings. Procurement of low cost and high impact treatments like intravenous fluids and empiric antibiotics may help decrease sepsis-associated mortality in resource-constrained settings.

Figure 1. Flow diagram for study eligibility and follow-up to 30 days post-discharge.

Figure 2. In-hospital mortality and admission Karnofsky Performance Scale score.

[*Numbers in bars represent number of patients.]

Figure 3. Frequency of separate empiric antibiotic regimens used.

[*Represents 35 separate regimens used <1% of the time; Pen/Gent = Penicillin/Gentamicin; Pen/TMP-SMX = Penicillin/Trimethoprim-Sulfamethoxazole; Amp/Metro = Ampicillin/Metronidazole, Amp/Gent = Ampicllin/Gentamicin, Chlor/Pen = Chloramphenicol/Penicillin; Cipro/TMP-SMX = Ciprofloxacin/Trimethoprim-Sulfamethoxazole, Cipro/Metro = Ciprofloxacin/Metronidazole; TMP-SMX = Trimethoprim-Sulfamethoxazole]