Abstract：
BACKGROUND: The optimal treatment regimen for infections caused by wild-type AmpC β-lactamase-producing Enterobacterales remains controversial. This study compared the outcomes of bloodstream infections (BSI) and pneumonia according to the type of definitive antibiotic therapy: third-generation cephalosporin (3GC), piperacillin ± tazobactam, cefepime or carbapenem.
METHODS: All cases of BSI and pneumonia caused by wild-type AmpC β-lactamase-producing Enterobacterales over 2 years in eight university hospitals were reviewed. Patients who received definitive therapy consisting of either a 3GC (3GC group), piperacillin ± tazobactam (piperacillin group), or cefepime or a carbapenem (reference group) were included in this study. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was treatment failure due to infection by emerging AmpC-overproducing strains. Propensity-score-based models were used to balance confounding factors between groups.
RESULTS: In total, 575 patients were included in this study: 302 (52%) with pneumonia and 273 (48%) with BSI. Half (n=271, 47%) received cefepime or a carbapenem as definitive therapy, 120 (21%) received a 3GC, and 184 (32%) received piperacillin ± tazobactam. Compared with the reference group, 30-day mortality was similar in the 3GC [adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.57-1.31)] and piperacillin (aHR 1.20, 95% CI 0.86-1.66) groups. The likelihood of treatment failure was higher in the 3GC (aHR 6.81, 95% CI 3.76-12.4) and piperacillin (aHR 3.13, 95% CI 1.69-5.80) groups. The results were similar when stratifying the analysis on pneumonia or BSI.
CONCLUSIONS: Treatment of included BSI or pneumonia caused by wild-type AmpC β-lactamase-producing Enterobacterales with 3GC or piperacillin ± tazobactam was not associated with higher mortality, but was associated with increased risk of AmpC overproduction leading to treatment failure compared with cefepime or a carbapenem.
METHODS: All cases of BSI and pneumonia caused by wild-type AmpC β-lactamase-producing Enterobacterales over 2 years in eight university hospitals were reviewed. Patients who received definitive therapy consisting of either a 3GC (3GC group), piperacillin ± tazobactam (piperacillin group), or cefepime or a carbapenem (reference group) were included in this study. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was treatment failure due to infection by emerging AmpC-overproducing strains. Propensity-score-based models were used to balance confounding factors between groups.
RESULTS: In total, 575 patients were included in this study: 302 (52%) with pneumonia and 273 (48%) with BSI. Half (n=271, 47%) received cefepime or a carbapenem as definitive therapy, 120 (21%) received a 3GC, and 184 (32%) received piperacillin ± tazobactam. Compared with the reference group, 30-day mortality was similar in the 3GC [adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.57-1.31)] and piperacillin (aHR 1.20, 95% CI 0.86-1.66) groups. The likelihood of treatment failure was higher in the 3GC (aHR 6.81, 95% CI 3.76-12.4) and piperacillin (aHR 3.13, 95% CI 1.69-5.80) groups. The results were similar when stratifying the analysis on pneumonia or BSI.
CONCLUSIONS: Treatment of included BSI or pneumonia caused by wild-type AmpC β-lactamase-producing Enterobacterales with 3GC or piperacillin ± tazobactam was not associated with higher mortality, but was associated with increased risk of AmpC overproduction leading to treatment failure compared with cefepime or a carbapenem.
摘要：
背景：由产生野生型AmpCβ-内酰胺酶的肠杆菌引起的感染的最佳治疗方案仍存在争议。我们根据确定性抗生素治疗的类型比较了血流感染（BSI）和肺炎的结果：第三代头孢菌素（3GC），哌拉西林±他唑巴坦，头孢吡肟,或者碳青霉烯类.
方法：我们回顾了8所大学医院在两年内所有由产生野生型AmpCβ-内酰胺酶的肠杆菌引起的BSI和肺炎病例。我们纳入了接受由3GC组成的确定性治疗的患者（3GC组），哌拉西林±他唑巴坦（哌拉西林组），或头孢吡肟或碳青霉烯（参照组）。主要终点是30天全因死亡率。次要终点是由于新出现的AmpC过度产生菌株感染而导致的治疗失败。我们使用基于倾向得分的模型来平衡组间的混杂因素。
结果：我们纳入了575例患者：302例（52%）肺炎患者和273例（48%）BSI患者。一半（271％，47％）接受头孢吡肟或碳青霉烯作为确定性治疗，120（21%）收到3GC，和184（32%）哌拉西林±他唑巴坦。与参照组相比，30日死亡率与3GC(校正HR(aHR)0.86,95CI0.57-1.31)和哌拉西林(aHR1.20,95CI0.86-1.66)相似.3GC（aHR6.81，95CI3.76-12.4）和哌拉西林（aHR3.13，95CI1.69-5.80）治疗失败的可能性更高。对肺炎或BSI的分析进行分层时，结果相似。
结论：用3GC或哌拉西林±他唑巴坦治疗包括由产生野生型AmpCβ-内酰胺酶的肠杆菌引起的BSI或肺炎与更高的死亡率无关。但与头孢吡肟或碳青霉烯相比，AmpC过量生产导致治疗失败的风险增加。
方法：我们回顾了8所大学医院在两年内所有由产生野生型AmpCβ-内酰胺酶的肠杆菌引起的BSI和肺炎病例。我们纳入了接受由3GC组成的确定性治疗的患者（3GC组），哌拉西林±他唑巴坦（哌拉西林组），或头孢吡肟或碳青霉烯（参照组）。主要终点是30天全因死亡率。次要终点是由于新出现的AmpC过度产生菌株感染而导致的治疗失败。我们使用基于倾向得分的模型来平衡组间的混杂因素。
结果：我们纳入了575例患者：302例（52%）肺炎患者和273例（48%）BSI患者。一半（271％，47％）接受头孢吡肟或碳青霉烯作为确定性治疗，120（21%）收到3GC，和184（32%）哌拉西林±他唑巴坦。与参照组相比，30日死亡率与3GC(校正HR(aHR)0.86,95CI0.57-1.31)和哌拉西林(aHR1.20,95CI0.86-1.66)相似.3GC（aHR6.81，95CI3.76-12.4）和哌拉西林（aHR3.13，95CI1.69-5.80）治疗失败的可能性更高。对肺炎或BSI的分析进行分层时，结果相似。
结论：用3GC或哌拉西林±他唑巴坦治疗包括由产生野生型AmpCβ-内酰胺酶的肠杆菌引起的BSI或肺炎与更高的死亡率无关。但与头孢吡肟或碳青霉烯相比，AmpC过量生产导致治疗失败的风险增加。
