Comparison of appropriate antimicrobial monotherapy and combination therapy in patients with carbapenem-resistant gram-negative bacilli bloodstream infections: a multicenter retrospective cohort study

Whether appropriate monotherapy or combination therapy is more effective for carbapenem-resistant gram-negative bacilli bloodstream infections (CRGNB-BSI) is still a matter of debate. This multicenter retrospective study included CRGNB-BSI patients who received either appropriate monotherapy (only one active agent) or combination therapy (at least two active agents). The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical cure. Inverse probability of treatment weighting (IPTW) was used to adjust confounding factors for the choice of therapeutic strategies. Multivariable regression analysis was performed in the IPTW cohort. Of 237 patients included, 155 received appropriate monotherapy and 82 received combination therapy. The overall 28-day mortality was 40% (94/237), with no significant difference between the combination group (37%, 30/82) and the monotherapy group (41%, 64/155; <i>P</i> = 0.479). In multivariable analysis of the IPTW cohort, combination therapy was not associated with reduced 28-day mortality (aHR 0.65; 95% CI, 0.40-1.07; <i>P</i> = 0.088) or increased 14-day clinical cure rate (aOR 1.04; 95% CI, 0.71-1.51; <i>P</i> = 0.855). Subgroup analyses demonstrated significant 28-day survival benefits of combination therapy among patients who received early appropriate treatment (started within 48 hours after infection), those with septic shock, and those treated with regimens including tetracycline or polymyxin B (<i>P</i> < 0.01). In patients with CRGNB-BSI, appropriate combination therapy was not associated with improved overall survival compared to monotherapy. However, it may offer survival benefits when initiated early, in patients with septic shock, and when regimens include tetracyclines or polymyxin B.IMPORTANCECarbapenem-resistant gram-negative bacilli bloodstream infections remain a critical therapeutic challenge with high mortality and few effective options. In a real-world, multicenter cohort using inverse probability weighting to control for confounding, we found no overall benefit of appropriate combination therapy versus monotherapy in survival or early clinical cure. However, combination therapy was associated with improved 28-day survival in specific contexts: when initiated within 48 hours, in patients with septic shock, and when regimens included tetracyclines or polymyxin B. These findings highlight the importance of timely, targeted combination therapy for selected high-risk patients, while supporting judicious monotherapy use otherwise.