Falbo Dos Reis Pâmela, Barretti Pasqual, Marinho Laudilene, Balbi Andre Luís, Awdishu Linda, Ponce Daniela
Internal Medicine Departament, University of São Paulo State-UNESP, São Paulo, Brazil.
UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, United States.
Front Pharmacol. 2021 May 28;12:658014. doi: 10.3389/fphar.2021.658014. eCollection 2021.
The study aimed to evaluate the vancomycin and amikacin concentrations in serum and dialysate for automatic peritoneal dialysis (APD) patients A total of 558 serum and dialysate samples of 12 episodes of gram-positive and 18 episodes of gram-negative peritonitis were included to investigate the relationship between vancomycin and amikacin concentrations in serum and dialysate on the first and third days of treatment. Samples were analysed 30, 120 min, and 48 h after intraperitoneal administration of vancomycin in peritonitis caused by gram-positive agents and 30, 120 min, and 24 h after intraperitoneal administration of amikacin in peritonitis caused by gram-negative agents. Vancomycin was administered every 72 h and amikacin once a day. The target therapeutic concentration of amikacin was 25-35 mg/l at the peak moment and 4-8 mg/l at the trough moment; and after 48 h for vancomycin, 15-20 mg/l at the trough moment. For peritonitis caused by gram-negative agents, at the peak moment, therapeutic levels of amikacin were reached in dialysate in 80.7% of patients with evolution to cure and in 50% of patients evaluated as non-cure ( = 0.05). At the trough moment, only 38% were in therapeutic concentrations in the dialysate in the cure group and 42.8% in the non-cure group ( = 1). Peak plasma concentrations were subtherapeutic in 98.4% of the samples in the cure group and in 100% of the non-cure group. At the trough moment, therapeutic concentrations were present in 74.4% of the cure group and 71.4% of the non-cure group ( = 1). Regarding vancomycin and among gram-positive agents, therapeutic levels were reached at the peak moment in 94% of the cure group and 6% of the non-cure group ( = 0.007). After 48 h, 56.8% of the cure group had a therapeutic serum concentration whereas for the non-cure group it was only 33.3% ( = 0.39). Despite a small sample size, we demonstrated peak dialysate amikacin level and peak serum vancomycin level correlates well with Gram-negative and Gram positve peritonitis cure, respectively. It is suggested to study the antibiotics pharmacodynamics for a better understanding of therapeutic success in a larger sample.
该研究旨在评估接受自动腹膜透析(APD)的患者血清和透析液中的万古霉素和阿米卡星浓度。共纳入了12例革兰氏阳性腹膜炎和18例革兰氏阴性腹膜炎患者的558份血清和透析液样本,以研究治疗第1天和第3天时血清和透析液中万古霉素和阿米卡星浓度之间的关系。在革兰氏阳性菌引起的腹膜炎中,腹腔内给予万古霉素后30、120分钟和48小时对样本进行分析;在革兰氏阴性菌引起的腹膜炎中,腹腔内给予阿米卡星后30、120分钟和24小时对样本进行分析。万古霉素每72小时给药一次,阿米卡星每天给药一次。阿米卡星的目标治疗浓度在峰值时刻为25 - 35mg/L,谷值时刻为4 - 8mg/L;万古霉素在48小时后,谷值时刻为15 - 20mg/L。对于革兰氏阴性菌引起的腹膜炎,在峰值时刻,80.7%病情好转治愈的患者透析液中阿米卡星达到治疗水平,而在评估为未治愈的患者中这一比例为50%(P = 0.05)。在谷值时刻,治愈组中透析液中只有38%处于治疗浓度,未治愈组中这一比例为42.8%(P = 1)。治愈组中98.4%的样本血浆峰值浓度低于治疗水平,未治愈组中这一比例为100%。在谷值时刻,治愈组中74.4%存在治疗浓度,未治愈组中这一比例为71.4%(P = 1)。对于万古霉素和革兰氏阳性菌,治愈组中94%在峰值时刻达到治疗水平,未治愈组中这一比例为6%(P = 0.007)。48小时后,治愈组中56.8%的患者血清浓度达到治疗水平,而未治愈组中这一比例仅为33.3%(P = 0.39)。尽管样本量较小,但我们证明了透析液中阿米卡星峰值水平和血清中万古霉素峰值水平分别与革兰氏阴性和革兰氏阳性腹膜炎的治愈情况密切相关。建议在更大样本中研究抗生素的药效学,以更好地理解治疗效果。