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.

Table 2 Summary of multi-level clinical interventions for intestinal failure in critically ill patients

Intervention level	Primary strategy	Key measures	Primary clinical outcomes	Effect size/results	Ref.
Microbiota	ASP	Optimize selection, shorten courses, reduce broad-spectrum coverage	Broad-spectrum antibiotic use rate, AGI incidence	Use rate ↓ 20%-30%; AGI incidence ↓ 15%-25%	[37]
Microbiota	Microbial reconstitution (probiotics/synbiotics)	Probiotic/synbiotic supplementation	Antibiotic-associated diarrhea incidence	RR = 0.70-0.80	[49]
Microbiota	Microbial reconstitution (FMT)	FMT	CDAD success rate, 30-day mortality	Success rate 80%-90%; mortality significantly reduced	[42,43]
Metabolic	Nutritional support and SCFA restoration	Fiber-enriched enteral nutrition	AGI severity, butyrate-producing bacteria abundance	OR = 0.82-0.86	[46]
Metabolic/barrier	Early enteral nutrition	Initiated within 48 hours	Bloodstream infection rate, ICU length of stay	OR = 0.73 (95%CI: 0.57-0.93)	[52]
Barrier	Barrier protection	Glutamine supplementation	Intestinal permeability	Improved in high-dose, short-course subgroup; no significant benefit otherwise	[55]
Inflammatory	Immunomodulation and anti-inflammatory therapy	Low-dose corticosteroids, etc	Mortality in sepsis	RR = 0.87 (95%CI: 0.81-0.93)	[56]
Systemic	Organ support (high-quality evidence)	Hemodynamic management, mechanical ventilation	Short-term prognosis, acute-phase mortality	Standardized implementation improves short-term outcomes; does not address upstream dysbiosis	[57]
Systemic	CRRT (moderate-quality evidence)	Continuous renal replacement therapy	Cytokine clearance, fluid balance	Some attenuation of circulating mediators; effect on gut microbiota unproven	[57]

ASP: Antibiotic stewardship program; AGI: Acute gastrointestinal injury; RR: Relative risk; FMT: Fecal microbiota transplantation; CDAD: Clostridioides difficile-associated disease; SCFA: Short-chain fatty acid; ICU: Intensive care unit; OR: Odds ratio; CI: Confidence interval; CRRT: Continuous renal replacement therapy.