Association between treatment with oral third‐generation cephalosporin antibiotics and mortality outcomes in Ebola virus disease: a multinational retrospective cohort study

Abstract

objective To evaluate the association between oral third-generation cephalosporin antibiotic treatment and mortality in Ebola virus disease (EVD).methods This retrospective cohort studied EVD-infected patients admitted to five Ebola Treatment Units in Sierra Leone and Liberia during 2014-15. Empiric treatment with cefixime 400 mg once daily for five days was the clinical protocol; however, due to resource variability, only a subset of patients received treatment. Data on sociodemographics, clinical characteristics, malaria status and Ebola viral loads were collected. The primary outcome was mortality compared between cases treated with cefixime within 48 h of admission to those not treated within 48 h. Propensity scores were derived using clinical covariates. Mortality between treated and untreated cases was compared using propensity-matched conditional logistic regression and bootstrapped log-linear regression analyses to calculate an odds ratio (OR) and relative risk (RR), respectively, with associated 95% confidence intervals (CI).results Of 424 cases analysed, 360 (84.9%) met the cefixime treatment definition. The mean age was 30.5 years and 40.3% were male. Median cefixime treatment duration was 4 days (IQR: 3, 5). Among cefixime-treated patients, mortality was 54.7% (95% CI: 49.6-59.8%) vs. 73.4% (95% CI: 61.5-82.7%) in untreated patients. In conditional logistic regression, mortality likelihood was significantly lower among cases receiving cefixime (OR = 0.48, 95% CI: 0.32-0.71; P = 0.01). In the bootstrap analysis, a non-significant risk reduction was found with cefixime treatment (RR = 0.82, 95% CI: 0.64-1.16, P = 0.11).conclusion Early oral cefixime may be associated with reduced mortality in EVD and warrants further investigation.

Factors associated with death in patients admitted with Ebola virus disease to Ebola Treatment Units in Guinea, Sierra Leone, and Liberia – December 2013 to March 2016

“…West Africa is endemic for this parasitic infection, and in more than 30% of the small number of patients tested there was a positive malaria diagnosis. Malaria is common and is a risk factor for death in EVD 17 and empirical antimalarial treatment may reduce case fatality. 20,21 Empiric treatment with antibiotics is frequently used as a supportive care component in the clinical management of EVD, the rationale being to mitigate the potential risk of secondary bacterial infection and gram-negative bacteraemia that arises during EVD.…”

“…7,14 Co-infection with malaria appears to be a risk factor for death. 15 Finally, there are a few studies with small numbers of patients that have found various interventions beneficial in reducing case fatality: multivitamins or vitamin A given within 48 hours of admission, 16,17 antibiotics such as thirdgeneration oral cephalosporins especially cefixime, 17 and use of empirical antimalarial treatment, especially artesunateamodiaquine rather than artemether-lumefantrine. 18,19 While existing published studies have examined risk factors for mortality, several reasons justify the need for additional research in this area.…”

Association between oral antimalarial medication administration and mortality among patients with Ebola virus disease: a multisite cohort study

“…Variable selection for inclusion in the multivariable modeling were based on identified evidence of difference (p < 0.05) in the bivariate analyses as well as on previous literature demonstrating associations with mortality in EVD. The variables included in the multivariable models, based on past literature, included: multivitamin (MVI) treatment [ 44 ], Cefixime treatment [ 45 ], clinical signs and symptoms of bleeding, diarrhea, dyspnea, and dysphagia [ 7 ], initial CT value and age [ 43 ]. Age was modeled with a cubic spline due to the previously documented quadratic relationship between age and mortality in EVD [ 43 ].…”