High Mortality from Blood Stream Infection in Addis Ababa, Ethiopia, Is Due to Antimicrobial Resistance

BACKGROUND Managing blood stream infection in Africa is hampered by lack of bacteriological support needed for antimicrobial stewardship, and background data needed for empirical treatment. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa. METHODS Outcome and characteristics including age, HIV infection, pancytopenia and bacteriological results were studied in 292 adult patients with two or more SIRS criteria using univariate and confirming multivariate logistic regression models. Expected randomly distributed resistance covariation was compared with observed co-resistance among gram-negative enteric bacteria in 92 paediatric blood culture isolates that had been harvested in the same hospital during the same period of time. RESULTS Mortality was fivefold increased among patients with positive blood culture results [50.0% vs. 9.8%; OR 11.24 (4.38-25.88), p < 0.0001], and for this group of patients mortality was significantly associated with antimicrobial resistance [OR 23.28 (3.3-164.4), p = 0.002]. All 11 patients with Enterobacteriaceae resistant to 3rd. generation cephalosporins died. Eighty-nine patients had pancytopenia grade 3-4. Among patients with negative blood culture results, mortality was significantly associated with pancytopenia [OR 3.12 (1.32-7.39), p = 0.01]. HIV positivity was not associated with increased mortality. Antimicrobial resistance that concerned gram-negative enteric bacteria, regardless of species, was characterized by co-resistance between third generation cephalosporins, gentamicin, chloramphenicol, and co-trimoxazole. CONCLUSION Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived. Because of co-resistance, alternative efficient antibiotics would not have been available in Ethiopia for 8/11 Enterobacteriaceae-infected patients with isolates resistant to third generation cephalosporins. Strong and significant resistance covariation between 3rd. generation cephalosporins, chloramphenicol, gentamicin, and co-trimoxazole was identified. Pronounced pancytopenia was common and associated with increased mortality. HIV positive patients had no excess mortality.