Abstract：
UNASSIGNED: The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards.
UNASSIGNED: To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, plazomicin, eravacycline, imipenem-relebactam-cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics).
UNASSIGNED: Retrospective cohort.
UNASSIGNED: 619 U.S. hospitals.
UNASSIGNED: Adult inpatients.
UNASSIGNED: Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections.
UNASSIGNED: Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane-tazobactam (approved 2014) and ceftazidime-avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including \"reserve\" antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage.
UNASSIGNED: Residual confounding.
UNASSIGNED: Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety-efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization.
UNASSIGNED: U.S. Food and Drug Administration; NIH Intramural Research Program.
UNASSIGNED: To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, plazomicin, eravacycline, imipenem-relebactam-cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics).
UNASSIGNED: Retrospective cohort.
UNASSIGNED: 619 U.S. hospitals.
UNASSIGNED: Adult inpatients.
UNASSIGNED: Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections.
UNASSIGNED: Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane-tazobactam (approved 2014) and ceftazidime-avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including \"reserve\" antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage.
UNASSIGNED: Residual confounding.
UNASSIGNED: Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety-efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization.
UNASSIGNED: U.S. Food and Drug Administration; NIH Intramural Research Program.
摘要：
■美国抗生素市场失灵已经威胁到未来的创新和供应。了解临床医生何时以及为何未充分利用最近批准的革兰氏阴性抗生素可能有助于在未来的抗生素开发和潜在的市场进入奖励中优先考虑患者。
■为了确定最近美国食品和药物管理局（FDA）批准的革兰氏阴性抗生素（头孢他啶-阿维巴坦，头孢洛赞-他唑巴坦,美罗培南-瓦巴坦,plazomicin,eravacycline,亚胺培南-来巴坦-西司他丁，和头孢地洛），并确定与它们的优先使用相关的因素（相对于传统的仿制药）在革兰氏阴性感染患者中表现出难以治疗的耐药性（DTR；也就是说，对所有一线抗生素的耐药性)。
■回顾性队列。
■619家美国医院。
■成人住院患者。
■使用加权线性回归计算抗生素使用的季度百分比变化。机器学习选择的候选变量，和混合模型确定了与新(vs.传统)抗生素在DTR感染中的使用。
■在2016年第1季度至2021年第2季度之间，头孢特洛扎-他唑巴坦（2014年批准）和头孢他啶-阿维巴坦（2015年）主导了新的抗生素使用，而随后批准的革兰氏阴性抗生素的吸收相对缓慢。在革兰氏阴性感染住院患者中，0.7%(2551[2631发作]，共362142次)显示DTR病原体。在2631例DTR发作中，有1091例患者仅使用传统药物治疗（41.5%），包括“储备”抗生素，如多粘菌素，氨基糖苷类,和替加环素在1091例发作中的865例（79.3％）。有菌血症和慢性疾病的患者有更大的调整概率和那些没有复苏状态的患者，急性肝功能衰竭,和鲍曼不动杆菌复合体和其他非假性非发酵罐病原体接受更新的调整概率较低(与传统的)用于DTR感染的抗生素，分别。新抗生素药敏试验的可用性增加了使用的可能性。
■残余混杂。
■尽管FDA在2014年至2019年之间批准了7种下一代革兰氏阴性抗生素，但临床医生仍经常使用老年人治疗耐药革兰氏阴性感染，安全性-疗效欠佳的通用抗生素。未来抗生素具有针对未开发病原体生态位的创新机制，广泛可用的敏感性测试，证明耐药感染结局改善的证据可能会提高利用率。
■美国食品和药物管理局；NIH校内研究计划。
■为了确定最近美国食品和药物管理局（FDA）批准的革兰氏阴性抗生素（头孢他啶-阿维巴坦，头孢洛赞-他唑巴坦,美罗培南-瓦巴坦,plazomicin,eravacycline,亚胺培南-来巴坦-西司他丁，和头孢地洛），并确定与它们的优先使用相关的因素（相对于传统的仿制药）在革兰氏阴性感染患者中表现出难以治疗的耐药性（DTR；也就是说，对所有一线抗生素的耐药性)。
■回顾性队列。
■619家美国医院。
■成人住院患者。
■使用加权线性回归计算抗生素使用的季度百分比变化。机器学习选择的候选变量，和混合模型确定了与新(vs.传统)抗生素在DTR感染中的使用。
■在2016年第1季度至2021年第2季度之间，头孢特洛扎-他唑巴坦（2014年批准）和头孢他啶-阿维巴坦（2015年）主导了新的抗生素使用，而随后批准的革兰氏阴性抗生素的吸收相对缓慢。在革兰氏阴性感染住院患者中，0.7%(2551[2631发作]，共362142次)显示DTR病原体。在2631例DTR发作中，有1091例患者仅使用传统药物治疗（41.5%），包括“储备”抗生素，如多粘菌素，氨基糖苷类,和替加环素在1091例发作中的865例（79.3％）。有菌血症和慢性疾病的患者有更大的调整概率和那些没有复苏状态的患者，急性肝功能衰竭,和鲍曼不动杆菌复合体和其他非假性非发酵罐病原体接受更新的调整概率较低(与传统的)用于DTR感染的抗生素，分别。新抗生素药敏试验的可用性增加了使用的可能性。
■残余混杂。
■尽管FDA在2014年至2019年之间批准了7种下一代革兰氏阴性抗生素，但临床医生仍经常使用老年人治疗耐药革兰氏阴性感染，安全性-疗效欠佳的通用抗生素。未来抗生素具有针对未开发病原体生态位的创新机制，广泛可用的敏感性测试，证明耐药感染结局改善的证据可能会提高利用率。
■美国食品和药物管理局；NIH校内研究计划。
