Abstract
BackgroundManaging 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.MethodsOutcome 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.ResultsMortality 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.ConclusionMortality 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.
Highlights
During the past few decades, antimicrobial resistance has increased worldwide, and the perspectives are alarming [1, 2]
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]
Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived
Summary
During the past few decades, antimicrobial resistance has increased worldwide, and the perspectives are alarming [1, 2]. In 2006, the proportions of resistance were 86%, 83%, 3%, 86%, 9%, and 43% to ceftriaxone, chloramphenicol, ciprofloxacin, gentamicin, kanamycin and co-trimoxazole respectively, among 76 gram-negative blood culture (GNB) isolates from paediatric patients of the same hospital [11]. There are two recent reports about the sensitivity patterns of urinary tract pathogens in Ethiopia indicating alarming figures of resistance among GNB [13, 14]. According to these studies, the proportion of strains resistant towards ceftriaxone and ciprofloxacin has increased from 33 to 48% and 24 to 36%, respectively, from 2009 to 2014 [13]. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa
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