Babich Tanya, Naucler Pontus, Valik John Karlsson, Giske Christian G, Benito Natividad, Cardona Ruben, Rivera Alba, Pulcini Celine, Abdel Fattah Manal, Haquin Justine, MacGowan Alasdair, Grier Sally, Gibbs Julie, Chazan Bibiana, Yanovskay Anna, Ami Ronen Ben, Landes Michal, Nesher Lior, Zaidman-Shimshovitz Adi, McCarthy Kate, Paterson David L, Tacconelli Evelina, Buhl Michael, Mauer Susanna, Rodriguez-Bano Jesus, Morales Isabel, Oliver Antonio, Ruiz de Gopegui Enrique, Cano Angela, Machuca Isabel, Gozalo-Marguello Monica, Martinez Luis Martinez, Gonzalez-Barbera Eva M, Alfaro Iris Gomez, Salavert Miguel, Beovic Bojana, Saje Andreja, Mueller-Premru Manica, Pagani Leonardo, Vitrat Virginie, Kofteridis Diamantis, Zacharioudaki Maria, Maraki Sofia, Weissman Yulia, Paul Mical, Dickstein Yaakov, Leibovici Leonard, Yahav Dafna
Sackler Faculty of Medicine, Tel Aviv University, Israel.
Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet and Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
J Antimicrob Chemother. 2021 Jul 15;76(8):2172-2181. doi: 10.1093/jac/dkab134.
Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality.
This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009-15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy.
Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64-1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens.
In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.
铜绿假单胞菌血症是一种常见且严重的感染。对于确定性联合治疗是否优于单一疗法，目前尚无共识。我们旨在评估联合治疗对死亡率的影响。
这是一项多中心回顾性研究（九个国家，25个中心），纳入了2009年至2015年间1277例铜绿假单胞菌血症患者。我们评估了β-内酰胺类药物联合氨基糖苷类药物或喹诺酮类药物的联合治疗与β-内酰胺类单一疗法与死亡率之间的关联。主要结局是30天全因死亡率。进行了单变量和多变量Cox回归分析，将联合治疗作为时间依赖性变量引入。采用倾向评分法对选择联合治疗而非单一疗法的混杂因素进行调整。
在纳入的1119例患者中，843例接受了确定性单一疗法，276例接受了联合治疗（59%为氨基糖苷类药物，41%为喹诺酮类药物）。30天死亡率为16.9%（189/1119），联合治疗组（45/276；16.3%）和单一疗法组（144/843；17.1%）相似（P = 0.765）。在多变量Cox回归中，联合治疗与死亡率降低无关（风险比0.98，95%置信区间0.64 - 1.53）。联合治疗在临床失败、微生物学失败或复发性/持续性菌血症方面未显示出优势。同样，两种治疗方案的不良事件和耐药性发展相似。
在这项回顾性队列研究中，对于铜绿假单胞菌血症，联合治疗相对于单一疗法未显示出死亡率优势。联合治疗未改善临床或微生物学失败率，也未影响不良事件或耐药性发展。我们关于联合治疗无益处的发现需要在设计良好的随机对照试验中得到证实。
