Bacterial Infection in Ebola Virus Disease, Marburg Virus Disease, Crimean-Congo Hemorrhagic Fever, and Lassa Fever.

BACKGROUND: Concern for bacterial coinfection in patients with high consequence viral infections (HCVIs) has made empiric antibiotic administration the standard of care. However, the incidence, microbiology, and clinical significance of bacterial coinfection in HCVIs remain unclear. METHODS: We conducted a systematic review of case reports, cohort studies, and cross-sectional analyses describing bacterial coinfection in Ebola virus disease (EVD), Marburg virus disease (MVD), Crimean-Congo hemorrhagic fever (CCHF), and Lassa fever (LF). Data were extracted on study design, setting, diagnostic methods, pathogens, antibiotic use, and outcomes. RESULTS: Thirty publications met inclusion criteria. Bacteremia was most commonly reported among patients with CCHF (n = 46), followed by EVD (n = 16), MVD (n = 16), and LF (n = 2). Of 27 EVD patients treated outside Africa, 7 (26%) had bacterial coinfection. Across HCVIs, bacteremia was detected a median of 11 days after symptom onset (range 0-23) and was associated with features of sepsis. Pathogens included enteric flora, healthcare-associated organisms, opportunistic pathogens, and zoonotic bacteria-most notably Brucella spp. in CCHF. Ceftriaxone was the most common empiric antibiotic but is predicted to have activity against a minority of bloodstream isolates. Mortality among coinfected patients with EVD or MVD was similar to those without bacterial coinfection, whereas coinfected CCHF patients had higher mortality than those without coinfection (15.5%; 95% CI 8.0%-25.9% vs 5.7%; 95% CI 5.1%-6.4%). CONCLUSIONS: Despite being a major concern driving empiric antibiotic use, bacterial coinfection in HCVIs remains poorly described, precluding determination of its incidence or clinical significance. Prospective studies with standardized protocols for bacterial diagnosis and characterization of antimicrobial resistance are needed to guide antimicrobial strategies.