Letter to the Editor: From antibiotic exposure to antibiotic intensity: Rethinking inpatient stewardship in inflammatory bowel disease

Abstract

The study by Zeng et al, published in the recent issue of the World Journal of Gastroenterology, present a 10-year real-world analysis of antibiotic use among hospitalized patients with inflammatory bowel disease (IBD) (2015-2024) and provide probabilistic forecasts through 2027. Their data highlight a pivotal stewardship message: Antibiotic exposure prevalence and antibiotic consumption intensity are not interchangeable metrics. Although the proportion of admissions receiving antibiotics declined in 2020-2024 compared with 2015-2019, antibiotic consumption intensity (DDD/100 bed-days) increased significantly, accompanied by a recent rise in broad-spectrum and traditionally “last-resort” agents, including carbapenems and vancomycin. Antibiotic-exposed admissions clustered in older patients and were associated with longer length of stay and higher costs, suggesting that antibiotic burden concentrates in high-acuity episodes rather than being evenly distributed across the inpatient IBD population. The forecasting component showed wide uncertainty but consistently indicated upward pressure on antibiotic burden if current practices and policies remain unchanged. This letter argues that inpatient stewardship in IBD should pivot from counting “exposed admissions” to monitoring intensity, escalation patterns, and indication-specific use, and proposes an IBD-tailored stewardship roadmap integrating diagnostic stewardship, standardized perioperative and intra-abdominal infection pathways, early reassessment with de-escalation, and structured metrics to curb avoidable escalation while preserving clinical outcomes.

Key Words: Inflammatory bowel disease; Antibiotic stewardship; Antibiotic consumption; Antimicrobial resistance; Inpatients; Last-resort antibiotics

Core Tip: Although fewer hospitalized patients with inflammatory bowel disease now receive antibiotics, those treated are exposed to increasingly intensive regimens, with a growing use of broad-spectrum and last-resort agents. This disconnect between exposure prevalence and antibiotic consumption intensity challenges traditional stewardship metrics. An inflammatory bowel disease-tailored inpatient stewardship framework focused on antibiotic intensity, escalation patterns, and indication-specific use, with measurable process and outcome indicators, is urgently needed to preserve antimicrobial effectiveness while safeguarding patient outcomes.

TO THE EDITOR

Antibiotic stewardship in inflammatory bowel disease (IBD) occupies a uniquely complex clinical space. Although antibiotics are not disease-modifying therapies for IBD itself, hospitalized patients with ulcerative colitis or Crohn’s disease are frequently exposed to antimicrobial agents because of diagnostic uncertainty during acute flares, immunosuppression-related infections, perioperative management, and extraintestinal complications. In their observational study spanning a full decade of inpatient care, Zeng et al[1] provide a detailed analysis of antibiotic consumption patterns in hospitalized IBD patients, complemented by probabilistic forecasts extending to 2027. Their findings underscore a critical stewardship insight: Antibiotic exposure prevalence and antibiotic consumption intensity are not interchangeable metrics.

Persisting in the use of exposure-based indicators risks misclassifying stewardship success in hospitalized IBD at a time when antibiotic consumption intensity – and its downstream consequences – are demonstrably increasing. Indeed, although population-level antibiotic exposure has been associated with IBD onset across age groups[2], and cumulative antibiotic prescriptions show a dose–response relationship with incident disease, the clinical relevance of how antibiotics are used once prescribed has received comparatively less attention. The study by Zeng et al[1], published in the recent issue of the World Journal of Gastroenterology, show that although the proportion of admissions receiving antibiotics declined in recent years, antibiotic consumption intensity, expressed as defined daily doses per 100 bed-days (DDD/100 bed-days), increased significantly, accompanied by a discernible rise in the use of broad-spectrum and traditionally last-resort agents, including carbapenems and vancomycin[1].

DEFINING STEWARDSHIP METRICS AND THEIR LEVELS OF INFERENCE

To avoid misinterpretation of stewardship signals, explicit definitions are necessary. Antibiotic exposure prevalence refers to the proportion of admissions receiving any antibiotic and represents an admission-level metric. Antibiotic consumption intensity, measured as DDD/100 bed-days, is an ecological metric reflecting aggregate antibiotic burden at the hospital or ward level. Antibiotic pressure (or antibiotic burden) denotes the aggregate selection pressure for antimicrobial resistance at the institutional level. These metrics capture different dimensions of antibiotic use and operate at different levels of inference.

Critically, DDD/100 bed-days is useful for facility-level monitoring and interfacility comparisons but has important limitations. Because it is an ecological metric, conclusions drawn from DDD/100 bed-days reflect institutional-level antibiotic pressure and cannot be directly extrapolated to individual patient-level risk without additional patient-level data. This distinction is essential to avoid ecological fallacy – inappropriately attributing population-level characteristics to individual patients. Furthermore, DDD may overestimate consumption for certain antibiotics, particularly beta-lactams, and in specific settings such as intensive care units. The Infectious Diseases Society of America recommends days of therapy (DOT) over DDD when patient-level data are available, as DOT is not affected by dose adjustments and better reflects individual patient exposure[3-5].

EXPOSURE VS INTENSITY: INTERPRETING DIVERGENT TRENDS

The distinction between whether antibiotics are prescribed and how intensively they are used is not semantic but mechanistic. Antimicrobial resistance selection pressure correlates more closely with aggregate antibiotic burden at the ward or hospital level than with the simple proportion of patients exposed. This is particularly relevant in contemporary IBD care, where evolving admission patterns – such as short-stay hospitalizations for biologic infusions – may artifactually reduce exposure prevalence while leaving antibiotic consumption intensity unchanged or increased. Zeng et al[1] appropriately contextualize this issue by highlighting that a substantial proportion of non-antibiotic admissions in their cohort consisted of one-day hospitalizations.

However, divergence in DDD/100 bed-days may reflect multiple scenarios beyond stewardship quality. Denominator effects occur when short-stay admissions reduce bed-days while antibiotic consumption remains stable, artificially inflating DDD/100 bed-days. Changes in case-mix, including increasing patient acuity, comorbidity burden, or surgical complexity, can legitimately increase antibiotic consumption intensity. Structural breaks, such as the coronavirus disease 2019 pandemic, may alter admission patterns and infection epidemiology. These confounders must be considered when interpreting consumption intensity trends and underscore the need for complementary metrics rather than reliance on DDD alone[4,6,7].

ANTIBIOTIC BURDEN CLUSTERS IN HIGH-ACUITY EPISODES

Another key signal from the study is that antibiotic exposure is not evenly distributed across the inpatient IBD population. Antibiotic-treated admissions involved older patients and were associated with longer lengths of stay and higher hospitalization costs, suggesting that antibiotic pressure concentrates in frailer, high-acuity episodes[1]. This observation is clinically relevant, as antibiotic-related adverse effects – including Clostridioides difficile infection (CDI) – is particularly consequential in IBD. Prior studies have demonstrated a strong association between antibiotic exposure and increased risk of CDI in IBD patients, with corresponding increases in morbidity and healthcare utilization. This relationship is complex[8], as IBD-associated dysbiosis itself increases CDI susceptibility even without antibiotics through loss of colonization resistance[9-13].

ESCALATION SIGNALS AND LAST-RESORT DEPENDENCE

Perhaps the most consequential observation by Zeng et al[1] is the temporal shift in antibiotic class utilization. While β-lactams and cephalosporins remained predominant overall, carbapenems and glycopeptide antibacterials emerged and increased during the most recent years of observation[1]. This pattern is consistent with broader evidence indicating that antibiotic exposure intensity, rather than duration alone, is a key determinant of CDI risk and resistance selection[9]. Similar associations between high-intensity antibiotic exposure and adverse microbiome-related outcomes have been observed even outside gastroenterology[10].

FORECASTS AS A STEWARDSHIP STRESS TEST

The Monte Carlo projections presented by Zeng et al[1] extend the analysis beyond description into anticipation. Although the projected increases in antibiotic consumption through 2027 are accompanied by wide uncertainty intervals, their directionality is consistent: Under assumptions of unchanged practice and policy, upward pressure on antibiotic burden is likely to persist[1]. These forecasts should be interpreted as a stress test rather than a deterministic prediction, reinforcing the need for proactive stewardship intervention. Failure to recalibrate stewardship frameworks accordingly may contribute to a progressive escalation toward last-resort dependence, with foreseeable implications for antimicrobial resistance, patient safety, and health system sustainability.

TOWARD AN IBD-TAILORED INPATIENT STEWARDSHIP ROADMAP

Taken together, the findings of Zeng et al[1] argue for a disease-specific approach to inpatient stewardship in IBD. Diagnostic stewardship aimed at early exclusion of infection, indication-specific pathways for ulcerative colitis flares and Crohn’s disease complications, and structured reassessment with de-escalation are essential components. Importantly, stewardship metrics must evolve beyond exposure prevalence to incorporate antibiotic consumption intensity and escalation patterns, which more accurately reflect microbiological risk[4,6].

To operationalize this framework, IBD-specific stewardship programs should implement measurable process and outcome indicators. Process indicators should include: (1) Proportion of patients with documented antibiotic plan at therapy initiation; (2) Compliance with IBD-specific infection management guidelines; (3) Proportion receiving pathogen-directed therapy after culture results; (4) Proportion with documented reassessment at 48-72 hours; and (5) Proportion with appropriate intravenous-to-oral conversion. Outcome indicators should include: (1) DOT per admission for specific indications; (2) Days of antibiotic spectrum coverage; (3) Redundant therapy events; (4) Healthcare-facility-onset CDI incidence as a secondary outcome; and (5) Proportion of patients requiring escalation to last-resort agents. These indicators provide actionable targets for quality improvement while accounting for the limitations of aggregate consumption metrics[1,4,11,14,15].

CONCLUSION

Zeng et al[1] provide a timely and conceptually important contribution to the stewardship literature in IBD. Their data demonstrate that declining antibiotic exposure prevalence can coexist with rising antibiotic consumption intensity and increasing use of broad-spectrum, last-resort agents. This disconnect challenges conventional stewardship metrics and calls for a reframing of success – from counting how many patients receive antibiotics to understanding how intensively antibiotics are used, for which indications, and with what escalation patterns. In hospitalized IBD, stewardship effectiveness will not be defined by fewer prescriptions alone, but by the degree of biological pressure averted and the therapeutic precision achieved. Implementation of measurable, IBD-tailored process and outcome indicators is essential to translate conceptual stewardship principles into sustained clinical practice.