We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile
illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness
District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia,
and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency
antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia
(ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe
respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all
antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without
shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17–27% of participants had etiologic diagnoses that
would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin
for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline
therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies
not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracyclineresponsive
bacterial infections, were common.