Presentation and outcome of suspected sepsis in a high-HIV burden, high antiretroviral coverage setting.

Objective: To define sepsis syndromes in high-HIV burden settings in the antiretroviral therapy (ART) era.

Methods: We characterized a prospective cohort of adults presenting to a tertiary emergency department in Harare, Zimbabwe with suspected community-acquired sepsis using blood and urine cultures, urine tuberculosis lipoarabinomannan (TB LAM), and serum cryptococcal antigen (CrAg) testing. The primary outcome was 30-day all-cause mortality.

Results: Of 142 patients enrolled 68% (n=96/142, 95% confidence interval (CI) [60-75%]) were HIV-positive, 41% (n=39/96, 95% CI [31-50%]) of whom were ART-naïve. Among HIV-positive patients, both opportunistic pathogens (TB LAM-positivity, 36%, 95% CI [24-48%]; CrAg-positivity, 15%, 95% CI [7-23%]) and severe non-AIDS infections (S. pneumoniae urine antigen-positivity 12%, 95% CI [4-20%]; bacteraemia 17% (n=16/96, 95% CI [9-24%]), of which 56% (n=9/16, 95% CI [30-80%]) were gram-negative organisms) were common. Klebsiella pneumoniae recovered from blood and urine was uniformly resistant to ceftriaxone, as were most Escherichia coli isolates. Acknowledging the power limitations of our study, we conclude that relative to HIV-negative patients, HIV-positive patients had modestly higher 30-day mortality (adjusted hazard ratio (HR) 1.88, 95% CI [0.78-4.55]; p=0.16, and 3.59, 95% CI [1.27-10.16], p=0.02) among those with and without viral suppression, respectively.

Conclusion: Rapid point-of-care assays provide substantial clinically actionable information in the setting of suspected sepsis, even in areas with high ART coverage. Antimicrobial resistance to first-line antibiotics in high burden settings is a growing threat.