Antibiotic-associated gut dysbiosis and intestinal failure in critically ill patients: Mechanisms and interventions

Table 1 Risk factors and quantitative effects of antibiotic exposure in critically ill patients

Category	Risk factor	Metric definition	Effect size (OR/aHR)	P value	Study design	Ref.
Exposure intensity	Elevated ASI	Per 1-unit increase	aHR = 1.14 (1.09-1.19)	< 0.001	Prospective cohort (n = 422)	[5]
	Cumulative DOT	Per 1-day increase	OR = 1.05-1.08	< 0.01	ICU cohort	[6]
	Cumulative DDD	Per 10 DDD	OR = 1.12	0.02	Retrospective study	[7]
Spectrum breadth	Broad-spectrum β-lactams (carbapenems)	Vs non-broad-spectrum	OR = 2.3-3.5	< 0.001	Multicenter cohort	[1]
	Anti-anaerobic coverage (metronidazole/piperacillin-tazobactam)	Present vs absent	OR = 1.8-2.6	< 0.01	ICU microbiome study	[8]
Prescribing pattern	Combination therapy (≥ 2 agents)	Vs monotherapy	OR = 1.9-2.7	< 0.01	Retrospective study	[9]
	≥ 3 antibiotics combined	Vs monotherapy	OR = 3.1	< 0.001	Retrospective study	[10]
Exposure duration	Prolonged course (> 7 days)	Vs ≤ 7 days	OR = 2.0-2.8	< 0.01	Follow-up study	[11]
	Repeated exposure (≥ 2 courses)	Yes vs no	OR = 2.5	0.003	ICU study	[12]
Disease severity	Elevated SOFA score	Per 1-point increase	OR = 1.12-1.18	< 0.001	Multicenter study	[1]

Data were derived from the included cohort studies and meta-analyses. Risk-stratification thresholds: Antibiotic spectrum index > 3.0 = high risk (operational threshold, no universal consensus); cumulative days of therapy > 7 days associated with sustained dysbiosis (odds ratio = 2.0-2.8); defined daily dose > 30 during admission = high cumulative burden. OR: Odds ratio; aHR: Adjusted hazard ratio; ASI: Antibiotic spectrum index; DOT: Days of therapy; DDD: Defined daily dose; ICU: Intensive care unit; SOFA: Sequential Organ Failure Assessment.