Abu Jaber Al Maamon R, Basgut Bilgen, Hawan Ali Abdullah, Al Shehri Ali Amer, AlKahtani Sultan Ahmad, Ahmed Nehad J, Abdi Abdikarim
Department of Clinical Pharmacy, Faculty of Pharmacy, Near East University, Nicosia 99138, Northern Cyprus TR-10 Mersin, Turkey.
Department of Pharmacology, Faculty of Pharmacy, Baskent University, Ankara 06790, Turkey.
Antibiotics (Basel). 2024 Mar 16;13(3):265. doi: 10.3390/antibiotics13030265.
Ceftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients' baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI's clinical success was 42.2% ( = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; = 0.036) and infection recurrence (7.8% versus 24.0%; = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients' 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI's clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI's microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients' characteristics.
头孢他啶/阿维巴坦（CAZ-AVI）已获美国食品药品监督管理局（FDA）批准，用于治疗由耐药革兰氏阴性杆菌引起的感染，尤其是由耐碳青霉烯病原体引起的感染。目前的临床数据仍然有限，特别是在沙特阿拉伯的相关数据。本研究是一项回顾性队列研究，在沙特阿拉伯南部地区的武装部队医院开展，旨在比较CAZ-AVI作为单药治疗以及作为耐碳青霉烯类肺炎克雷伯菌（CRKP）OXA-48感染标准治疗附加用药的患者，与接受标准药物治疗的患者的临床和微生物学结局。该研究纳入了2018年8月1日至2023年5月期间接受抗生素治疗超过7天的CRKP OXA-48样感染患者。从临床记录中提取患者的基线特征和人口统计学信息，并根据相应定义评估其临床/微生物学疗效。进行单因素和多因素逻辑回归分析，以确定影响CAZ-AVI疗效的潜在独立变量。总共纳入114份患者档案进行评估。在这些患者中，64例使用CAZ-AVI联合标准治疗，纳入干预组；50例使用标准治疗，纳入对照组。分析结果显示，CAZ-AVI的临床成功率为42.2%（P = 0.028），干预组与对照组相比，30天全因死亡率降低（50.0%对70.0%；P = 0.036），感染复发率降低（7.8%对24.0%；P = 0.019），微生物清除率大幅提高（68.8%对42.0%；P = 0.007）。与标准治疗相比，CAZ-AVI附加治疗而非单药治疗在临床和微生物学结局方面具有统计学显著优势。此外，性别（女性占比）、入住重症监护病房（ICU）和发热与患者30天全因死亡率呈负相关，是独立的负性因素。只有发热、CRP生物水平、使用血管活性药物和入住ICU是影响CAZ-AVI临床疗效的显著预测因素。CAZ-AVI治疗持续时间对其微生物清除有积极影响，而白细胞计数和发热经历则是负性预测因素。本研究表明CAZ-AVI在治疗CRKP OXA-48样感染方面的有效应用。此处描述的影响独立变量提示临床医生应根据并存的危险因素个体化调整CAZ-AVI剂量，以实现最佳生存和疗效。建议开展前瞻性多中心随机对照研究，并根据患者特征实施个体化的CAZ-AVI精准给药。
