Mapping antibiotic treatment failure definitions and criteria in ambulatory care: a systematic literature review

Most antibiotic prescriptions occur in ambulatory care, making it a key setting for evaluating treatment outcomes. However, there is no consensus on how antibiotic treatment failure (ATF) is defined.

To systematically map definitions and criteria used to define ATF among patients with common bacterial infections in ambulatory care.

A systematic search was conducted in MEDLINE (PubMed), Embase, Cochrane CENTRAL, Scopus, and Web of Science Core Collection for studies published from 1 January 1996 to 7 February 2025, and reported following PRISMA guidelines. Eligible studies included patients of any age with common infections treated in ambulatory care. ATF definitions and criteria were extracted, coded, and analysed using inductive and deductive content analysis. Risk of bias was assessed with the Newcastle-Ottawa Scale, AXIS, and Cochrane Risk of Bias Tool 2.0 (PROSPERO: CRD42023484991).

Of 8979 records, 194 studies were included, mostly purely outpatient (56%), retrospective cohort (53%), and from high-income countries (84%); 65% had low-risk of bias. Terminology for ATF varied. Four main criteria were identified: 'Prescription Change' (78%), 'Clinical Condition' (54%), 'Escalation of Care' (41%), and 'Mortality' (9%), encompassing 25 unique sub-criteria. One complementary criterion, 'Diagnostic Tests' also emerged. ATF follow-up time windows differed by indication, shorter for skin, ear, and respiratory infections and longer for genitourinary or mixed infections. Limitations include coding subjectivity and ambiguous definitions.

ATF is inconsistently defined, timed, and operationalized. Our review maps common criteria and sub-criteria to support future consensus-building efforts aiming for standardization and improved study comparability.