European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
Ceftazidime-avibactam as monotherapy or in combination for targeted treatment of KPC-producing Klebsiella pneumoniae infections in ICUs: a comparative analysis through counterfactual framework and desirability of outcome ranking.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеСравнительное исследованиеНазвание и аннотация: Перевод в очереди
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Marino Andrea, Maraolo Alberto Enrico, Mazzitelli Maria, Oliva Alessandra, Geremia Nicholas, De Vito Andrea, Cosentino Federica, Gullotta Chiara, Scaglione Vincenzo, Vania Eleonora, Lo Menzo Sara, Navalesi Paolo, Volpicelli Lorenzo, Fiori Andrea, Prestifilippo Pamela, Cattelan Annamaria, Mastroianni Claudio Maria, Madeddu Giordano, Cacopardo Bruno, Nunnari Giuseppe
Аннотация
PURPOSE: To evaluate the causal effect of ceftazidime/avibactam (C/A) combination therapy versus monotherapy on mortality and clinical success in patients with KPC-producing Klebsiella pneumoniae (KPC-Kp) infections in intensive care unit.
METHODS: This multi-centre, retrospective observational study (2021-2023) included adults with KPC-Kp bloodstream infections or pneumonia treated with C/A-based regimens. We employed a counterfactual framework using inverse probability of treatment weighting (IPTW) to estimate the average treatment effect on 30-day mortality. Clinical success was further assessed using Desirability of Outcome Ranking (DOOR) analysis and partial credit scoring based on patient-perspective scenarios.
RESULTS: Among 123 included patients, 77 (62.6%) received monotherapy and 46 (37.4%) received combination therapy. The combination group presented with significantly higher baseline severity, including higher APACHE II scores and rates of septic shock. In the IPTW-adjusted analysis, 30-day survival was 73.8% (95% CI: 56-92%) with combination therapy compared with 60.8% (95% CI: 46.8-77%) with monotherapy. The survival probability ratio was 1.21 (95% CI: 0.80-1.45), indicating no statistically significant survival benefit. The DOOR analysis showed a 54.7% (95% CI: 48.9%-60.4%) probability of a more favourable outcome with combination therapy, which was not statistically significant. Mean partial credit scores did not differ significantly across scenarios prioritizing survival or adverse event avoidance.
CONCLUSIONS: In this cohort, C/A-based combination therapy did not provide a significant survival advantage or an improved clinical desirability ranking compared with monotherapy, after adjusting for confounding factors.
METHODS: This multi-centre, retrospective observational study (2021-2023) included adults with KPC-Kp bloodstream infections or pneumonia treated with C/A-based regimens. We employed a counterfactual framework using inverse probability of treatment weighting (IPTW) to estimate the average treatment effect on 30-day mortality. Clinical success was further assessed using Desirability of Outcome Ranking (DOOR) analysis and partial credit scoring based on patient-perspective scenarios.
RESULTS: Among 123 included patients, 77 (62.6%) received monotherapy and 46 (37.4%) received combination therapy. The combination group presented with significantly higher baseline severity, including higher APACHE II scores and rates of septic shock. In the IPTW-adjusted analysis, 30-day survival was 73.8% (95% CI: 56-92%) with combination therapy compared with 60.8% (95% CI: 46.8-77%) with monotherapy. The survival probability ratio was 1.21 (95% CI: 0.80-1.45), indicating no statistically significant survival benefit. The DOOR analysis showed a 54.7% (95% CI: 48.9%-60.4%) probability of a more favourable outcome with combination therapy, which was not statistically significant. Mean partial credit scores did not differ significantly across scenarios prioritizing survival or adverse event avoidance.
CONCLUSIONS: In this cohort, C/A-based combination therapy did not provide a significant survival advantage or an improved clinical desirability ranking compared with monotherapy, after adjusting for confounding factors.