Targeted Antimicrobial Comparison for Treatment Individualization in Critically Ill Patients With CRAB Infection

The proportion of participants achieving clinical cure of the index CRAB infection at Day 14. Clinical cure is defined as resolution of infection-related symptoms, clinical signs, oxygenation or hemodynamic abnormalities, and inflammatory markers, or their return to pre-infection levels, without the need for continued or escalated targeted anti-CRAB therapy. Clinical response will be classified as cure, improvement, failure, or not evaluable.

The proportion of participants achieving clinical success, defined as either clinical cure or clinical improvement at Day 14. Clinical improvement is defined as a substantial improvement from Day 0 in infection-related clinical findings without escalation, addition, or switching of targeted anti-CRAB therapy because of inadequate infection control. Treatment modifications due to toxicity, intolerance, drug availability, cost, renal function changes, or de-escalation after clinical cure will not automatically be classified as clinical failure. Death before the assessment time point will be classified as clinical failure.

The proportion of microbiologically evaluable participants achieving microbiological clearance of CRAB from eligible infection-site specimens. Clearance is defined as the first negative follow-up culture without subsequent recovery of CRAB through the end of treatment. Two consecutive negative cultures will be additionally classified as confirmed microbiological clearance. Participants without an eligible follow-up culture will be classified as not evaluable rather than microbiologically cleared.

Proportion of microbiologically evaluable participants with a negative CRAB culture and no subsequent positive culture through the end of treatment. Two consecutive negative cultures will be classified as confirmed clearance.

Highest stage of acute kidney injury observed during follow-up, classified as Stage 1, 2, or 3 according to KDIGO 2012 criteria using serum creatinine, reliable urine output, and renal replacement therapy data.

Proportion of participants without acute kidney injury at baseline who develop acute kidney injury during follow-up, assessed according to Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria in the prespecified evaluable population.

Proportion of participants not receiving renal replacement therapy at baseline who require initiation of renal replacement therapy during the observation period.

Number of days participants are alive and free from invasive mechanical ventilation during the first 28 days after treatment initiation. Participants who die within 28 days will be assigned zero ventilator-free days.

Number of days participants are alive and not receiving care in an intensive care unit during the first 28 days. Participants who die within 28 days will be assigned zero intensive care unit-free days.

Total number of days of study-defined targeted anti-CRAB antibiotic treatment received during the observation period, based on actual medication administration records.

Total direct medical costs incurred during the index hospitalization within 28 days after treatment initiation, including antibiotics, intensive care, organ support, laboratory tests, diagnostic procedures, and management of adverse events. Costs will be reported in Chinese yuan.

Incremental cost-effectiveness ratio comparing polymyxin-based and sulbactam-based initial treatment strategies, calculated as the adjusted difference in mean direct medical costs divided by the adjusted difference in 28-day survival probability. The result will be expressed in Chinese yuan per additional 28-day survivor.

The number of days participants are alive and outside the hospital during the first 28 days after initiation of targeted anti-CRAB antibiotic therapy (Day 0). Participants who die within 28 days will be assigned zero hospital-free days.

The cumulative number of days participants spend in the intensive care unit (ICU) during the 28-day observation period after initiation of targeted anti-CRAB antibiotic therapy. ICU length of stay will be calculated using hospital admission, transfer, and discharge records.

The total number of days participants spend in the hospital during the 28-day observation period, including intensive care unit and general ward stays. Hospital length of stay will be determined from hospital admission, discharge, and transfer records.

The cumulative direct costs of targeted anti-CRAB antibiotics administered during the index hospitalization within 28 days after treatment initiation. Costs will be calculated from actual medication administration and hospital billing records and reported in Chinese yuan (CNY).

The proportion of participants developing new-onset or clinically significant worsening of liver injury after initiation of targeted anti-CRAB antibiotic therapy. Clinically significant liver injury is defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥5 times the upper limit of normal (ULN), alkaline phosphatase (ALP) ≥2 times ULN with evidence of hepatic origin, or ALT or AST ≥3 times ULN accompanied by total bilirubin ≥2 times ULN. Baseline liver abnormalities and alternative causes will be considered when assessing treatment-emergent events and drug relatedness.

The proportion of participants experiencing new-onset neurological adverse events during the observation period, including sensory disturbances, dizziness, muscle weakness, ataxia, altered consciousness, myoclonus, seizures, neuromuscular blockade, or respiratory muscle weakness. Event severity and potential relationships to antibiotic treatment will be assessed by investigators. Neurological status that cannot be reliably evaluated will be documented.

The incremental net monetary benefit (INMB) of polymyxin-based treatment compared with sulbactam-based treatment, calculated as the willingness-to-pay threshold per additional 28-day survivor multiplied by the adjusted difference in 28-day survival probability, minus the adjusted difference in mean direct medical costs. INMB will be evaluated across prespecified willingness-to-pay thresholds and reported in Chinese yuan (CNY).