When microbiology is missing: A prospective observational study on empirical first-line antibiotic treatment (FLAT) in Ethiopia

Abstract

Background: Antimicrobial resistance (AMR) is a growing public health threat, particularly in low- and middle-income countries (LMICs) where diagnostic capacity is limited. In such settings, empirical first-line antibiotic treatment (FLAT) is often the only feasible therapeutic approach, but real-world evidence on its effectiveness in adult populations is scarce.

Methods: We conducted a prospective observational cohort study at St. Luke Hospital, Wolisso, Ethiopia, from May 2024 to February 2025. Patients aged ≥5 years, admitted to the medical or surgical wards and prescribed antibiotics upon admission, were enrolled. Those on antimicrobial therapy prior to admission or receiving anti-tubercular treatment alone were excluded. Sociodemographic, clinical, and treatment data were collected. FLAT failure-defined as lack of clinical improvement within 48-72 h without non-infectious explanations-was the primary outcome. Associations with FLAT failure were assessed using univariate and multivariable logistic regression.

Results: A total of 118 patients (49.2 % female; median age 42.0 years) were included; 81.4 % were admitted to the medical ward. Pneumonia was the most common diagnosis (55.9 %). Ceftriaxone, alone or in combination, was the predominant empirical regimen (96.6 %). FLAT failure occurred in 11 patients (10.2 %; 95 % CI 4.7-16.1 %), resulting in additional antibiotic exposure, prolonged hospitalisation, referral to tertiary facilities (27.3 %), and one death (9.1 %). In multivariable analysis, admission to the surgical ward was associated with higher odds of FLAT failure (OR 5.6, 95 % CI 1.1-35.1; p = 0.045). No other consistent patient-level predictors were identified.

Conclusions: In a low-resource hospital setting without microbiological support, empirical FLAT achieved a relatively low failure rate. However, failures were clinically significant, leading to escalation of therapy and adverse outcomes. Strengthening antimicrobial stewardship through context-specific empirical treatment protocols, alongside efforts to improve diagnostic capacity, is essential to optimise patient care and mitigate AMR in similar settings.

Keywords: Antimicrobial resistance; Antimicrobial stewardship; Empirical therapy; Ethiopia; First-line antibiotics; Low-resource settings.