Appropriate antibiotic therapy has long been linked with better outcomes in hospitalized patients, but a new scoping review suggests the term is still defined inconsistently in clinical research – and most often in a way that may not align with modern antimicrobial stewardship priorities.
In the review, the University Hospital Tübingen-based researchers examined how studies defined appropriate antibiotic therapy (AAT), and whether those varying definitions affected associations with patient outcomes. They found that nearly all definitions relied primarily on in vitro susceptibility testing, with far less attention paid to other stewardship-relevant elements such as dosing, route of administration, treatment duration, and guideline adherence.
The review, published in Infection in January 2026, included 288 observational studies published between 2011 and 2021 that evaluated the impact of appropriate antibiotic therapy on outcomes in hospitalized adults with bacterial infections. Most studies focused on bloodstream infections, and outcomes most commonly reported were mortality, length of stay, and clinical failure.
Across the included studies, 98.6% provided a definition of AAT. However, the researchers found that those definitions varied widely, with many studies missing details on how appropriateness was assessed in practice. For empiric therapy, 41% of definitions were based on in vitro susceptibility alone; for definite therapy, 32% used in vitro susceptibility alone. The most frequently included additional criterion for empiric therapy was timely initiation, while dosing was the most common additional criterion for definite therapy. Guideline-based therapy, treatment duration, and route of administration were included only inconsistently.
The researchers note that susceptibility-based definitions may fail to capture important stewardship concerns, including antibiotic overtreatment. A clinician could prescribe broad-spectrum antibiotics that are technically “susceptible” but still unnecessarily wide in spectrum – an approach that can increase adverse events and antimicrobial resistance risk.
Despite the variability in definitions, empiric appropriate antibiotic therapy was independently associated with improved outcomes in 63% of multivariable analyses. Definite appropriate therapy was associated with improved outcomes in 81% of analyses, with the strongest associations seen for long-term mortality and intensive care unit mortality.
However, the researchers found few consistent differences in outcomes based on whether studies used simple susceptibility-only definitions or more complex, multidimensional ones. One exception was when minimum treatment duration was included as a criterion. Studies that incorporated duration were more likely to report an association with reduced mortality. The researchers cautioned, however, that this finding may reflect bias, including immortal time bias, rather than a true causal effect.
The review goes on to highlight that guideline adherence – often considered central to antimicrobial stewardship – was included in fewer than 5% of empiric therapy definitions. The researchers argued that guidelines may be particularly important early in treatment, when culture results are not yet available. They also noted that guideline-based definitions may be more applicable in culture-negative infections, where susceptibility data are not available.
Another concern raised by the review was incomplete adjustment for confounding. The authors also highlight incomplete adjustment for confounding, noting that roughly one-third of included studies lacked multivariable analyses. The researchers emphasize the need for more standardized approaches that incorporate disease severity, comorbidities, and other key variables influencing both antibiotic choice and outcomes, concluding that more standardized and multidimensional definitions of appropriate antibiotic therapy are needed, incorporating clinical, pharmacologic, and stewardship-based criteria. They argue that improving how appropriateness is defined and reported could strengthen comparability across studies, helping clinicians to better understand the true impact of antibiotic prescribing quality on patient outcomes.
The authors declared no competing interests.
Source: Infection