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[法国药理与治疗学会及法国麻醉与重症医学会临床指南]:优化危重病患者的beta内酰胺治疗
2019年04月15日 指南导读 暂无评论

Optimization of the treatment with beta-lactam antibiotics in critically ill patients—guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation—SFAR)

Guilhaumou et al. Critical Care (2019) 23:104

https://doi.org/10.1186/s13054-019-2378-9

Guidelines 指南

First area. Pharmacokinetic variability of beta-lactam antibiotics

第一部分:beta内酰胺抗生素的药代动力学变化

R1.1. We suggest considering systematically and daily the many sources of pharmacokinetic variability when prescribing beta-lactam antibiotics to critical care patients. 我们建议,危重病患者使用beta内酰胺抗生素时,应每天系统考虑导致药代动力学变化的因素

Optional recommendation—strong agreement

R1.2.1. We suggest determining the glomerular filtration rate by calculating creatinine clearance with the formula U x V/P at the onset of treatment with beta-lactam antibiotics, and every time the clinical condition and/or renal function of the patient significantly changes. 我们建议,在开始beta内酰胺抗生素治疗时,以及临床情况和(或)肾功能显著改变时,根据公式U x V/P计算肌酐清除率以确定肾小球滤过率。

R1.2.2. We suggest determining the glomerular filtration rate by calculating creatinine clearance with the formula U x V/P every time beta-lactam concentration is measured in order to help in interpreting the result. 我们建议,每次测定beta内酰胺抗生素浓度时,应根据公式U x V/P计算肌酐清除率以确定肾小球滤过率,以帮助结果解读。

Optional recommendation—strong agreement

R1.3.1. We suggest measuring albumin (or at least plasma proteins) at least once at the onset of treatment with beta-lactam antibiotics in order to guide the prescription. 我们建议,开始beta内酰胺抗生素治疗时,应当至少测定一次白蛋白(或至少血浆总蛋白)水平,以指导抗生素处方。

R1.3.2. We suggest measuring albumin (or at least plasma proteins) when performing beta-lactam TDM in order to help in interpreting the result. 我们建议,当进行beta内酰胺抗生素治疗药物监测(TDM)时,应测定白蛋白(或至少血浆总蛋白)水平,以帮助结果解读。

Optional recommendationstrong agreement

Second area. Pharmacokinetic-pharmacodynamic relationship of beta-lactam antibiotics

第二部分:beta内酰胺抗生素的药代动力学与药效学的关系

R2.1. We suggest considering the percentage of the dosing interval during which the free plasma concentration of beta-lactams is above a multiple (“k”) of the minimum inhibitory concentration (MIC) of the causative bacteria (%fT > k× MIC) as the therapeutic target for treatment with beta-lactam antibiotics. 我们建议,将给药间隔中游离beta内酰胺抗生素血浆浓度超过致病菌MIC的k倍的时间比例(%fT > k x MIC)作为beta内酰胺抗生素治疗目标。

Optional recommendationstrong agreement

R2.2. We suggest targeting a free plasma beta-lactam concentration between four and eight times the MIC of the causative bacteria for 100% of the dosing interval (fT ≥ 4–8 x MIC = 100%) to maximize bacteriological and clinical response in critical care patients. 我们建议,将100%的给药间隔维持游离beta内酰胺抗生素血浆浓度为致病菌MIC的4-8倍,以保证危重病患者细菌学及临床反应最佳。

Optional recommendationstrong agreement

R2.3. For beta-lactam antibiotics without validated toxicity threshold concentration, we suggest that it is useless, and even dangerous, to exceed plasma free concentrations of beta-lactam antibiotics above eight times the MIC (i.e., %fT > 8× MIC). 对于没有毒性临界值的beta内酰胺抗生素,我们建议,将beta内酰胺抗生素游离血浆浓度维持在MIC的8倍以上(%fT > 8 x MIC)并无用处,甚至有害。

Optional recommendationstrong agreement

Third area. Administration of beta-lactam antibiotics

第三部分:beta内酰胺抗生素的使用

R3.1. Pending the result of therapeutic drug monitoring (TDM), we suggest that a higher daily dose of beta-lactam antibiotics than that administered in patients outside the ICU should be administered at the onset of treatment, especially in the most critically ill patients and in those with preserved renal function. 未得到治疗药物监测(TDM)结果时,我们建议,beta内酰胺抗生素治疗初始时,每日使用较高剂量(高于非ICU患者),尤其是病情最为危重的患者及肾功能保留的患者。

Optional recommendationstrong agreement

R3.2. We suggest administering beta-lactam antibiotics by prolonged or continuous infusions for infections due to bacteria with high MIC in order to increase the probability of achieving the PK-PD targets. 我们建议,对于高MIC细菌引起的感染,应延长beta内酰胺抗生素输注时间或持续输注,以增加达到PK-PD目标的几率。

Optional recommendationstrong agreement

R3.3. We suggest administering beta-lactam antibiotics by prolonged or continuous infusions in critical care patients with septic shock and/or a high severity score in order to improve the clinical cure rate. 我们建议,对于感染性休克和(或)病情危重患者,应延长beta内酰胺抗生素输注时间或持续输注,以改善临床治愈率。

Optional recommendationstrong agreement

R3.4. We suggest administering beta-lactam antibiotics by prolonged or continuous infusions in critically ill patients suffering from lower respiratory tract infections in order to improve the clinical cure rate. 我们建议,对于下呼吸道感染的危重病患者,应延长beta内酰胺抗生素输注时间或持续输注,以改进临床治愈率。

Optional recommendationstrong agreement

R3.5. We suggest administering beta-lactam antibiotics by prolonged or continuous infusions in critically ill patients suffering from infections due to non-fermenting Gram-negative bacilli in order to improve the clinical cure rate. 我们建议,对于非发酵革兰阴性菌感染的危重病患者,应延长beta内酰胺抗生素输注时间或持续输注,以改进临床治愈率。

Optional recommendationstrong agreement

R3.6. We suggest administering an intravenous loading dose before starting the continuous or prolonged infusion at the onset of treatment with beta-lactam antibiotics, in order to achieve a concentration within the PK-PD targets as quickly as possible. 我们建议,开始beta内酰胺抗生素治疗时,在持续输注或延长输注时间前,应给予静脉负荷剂量,以尽快使血药浓度达到PK-PD目标。

Optional recommendationstrong agreement

Fourth area. Therapeutic drug monitoring of beta-lactam antibiotics

第四部分:beta内酰胺抗生素治疗药物监测

R4.1. We suggest performing therapeutic drug monitoring in ICU patients with expected beta-lactam PK variability and/or in patients with clinical signs potentially related to beta-lactams toxicity. 我们建议,对预计beta内酰胺抗生素药代动力学变化较大的ICU患者和(或)临床表现可能与beta内酰胺抗生素毒性相关的患者,应当进行治疗药物监测。

Optional recommendationstrong agreement

R4.2. We suggest performing therapeutic drug monitoring (TDM) of beta-lactam antibiotics in critical care patients undergoing renal replacement therapy. 我们建议,对于接受肾脏替代治疗的危重病患者进行beta内酰胺抗生素的治疗药物监测(TDM)。

Optional recommendationstrong agreement

R4.3. We suggest performing beta-lactam TDM by dosing plasma trough concentration in case of intermittent administration and plasma steady-state concentration in case of continuous administration. 我们建议,对于间断使用beta内酰胺抗生素患者监测药物谷浓度,对于持续用药患者监测稳态浓度。

R4.4. We suggest performing beta-lactam TDM 24 to 48 h after the onset of treatment; after any change in dosage; and in the event of a significant change in the patient’s clinical condition. 我们建议,在治疗开始后24-48小时,改变剂量后,以及患者临床情况显著变化时,应当进行beta内酰胺抗生素TDM。

Optional recommendationstrong agreement

R4.5. In case of central nervous system infection, we suggest performing beta-lactam TDM, if possible, on blood and cerebrospinal fluid samples collected concomitantly. 对于中枢神经系统感染患者,我们建议,如有可能,应同时采集血和脑脊液标本,进行beta内酰胺抗生素的TDM

Optional recommendationstrong agreement

R4.6.1. We suggest performing beta-lactam TDM according to a validated chromatographic method. 我们建议,根据经过验证的色谱法进行beta内酰胺抗生素TDM。

R4.6.2. We suggest that beta-lactam TDM results should be available to clinicians as soon as possible in order to have a real impact on ICU patient’s management. 我们建议,应当尽可能向临床医生提供beta内酰胺抗生素TDM结果,以真正影响ICU患者的治疗。

Optional recommendationstrong agreement

R4.7. We suggest considering as therapeutic targets the plasma concentrations presented in Table  2 . 我们建议以表中血浆浓度作为治疗目标。

R4.8.1. In case of non-achievement of the target beta-lactam plasma concentration, we suggest in first line: 若未能达到beta内酰胺抗生素目标血药浓度,我们建议

  • Either increasing the frequency of administration (i.e., further fractionate the dose) or switching to continuous administration, while maintaining the same daily dose; 或者增加给药频率(即进一步分解每日总剂量),或改为持续输注(维持每日总剂量不变)
  • Or increasing the unit dose administered discontinuously by 25 to 50% while maintaining the same frequency of administration. 或维持用药频率不变的情况下,将间断给药剂量增加25%到50%。

R4.8.2. In the case of persistence of below-target beta-lactam plasma concentration despite one of the previous measures, we suggest switching to prolonged or continuous administration in combination with an increase of the beta-lactam daily dose. 若采取上述措施后,beta内酰胺抗生素血药浓度仍持续低于治疗目标时,我们建议改为延长输注时间或持续输注,且增加beta内酰胺抗生素每日剂量。

Optional recommendationstrong agreement

R4.9.1. In case of supra-therapeutic plasma beta-lactam concentration, we suggest in first line: 当beta内酰胺抗生素血药浓度超过治疗目标时,我们建议:

  • Either reducing the daily dose in the case of continuous administration; 在持续输注时减少每日剂量
  • Or decreasing the unit dose administered discontinuously by 25 to 50% while maintaining the same frequency of administration. 维持每日用药频率不变的情况下,将间断用药剂量减少25%至50%

R4.9.2. In case of extremely high concentration and/or signs of toxicity consistent with beta-lactam overdose, we suggest stopping the administration and further resuming the treatment after having checked the decrease in beta-lactam concentration; then conducted under strict TDM. 如果beta内酰胺抗生素血药浓度极高和(或)出现beta内酰胺抗生素药物过量的体征时,我们建议终止药物输注,当检测beta内酰胺抗生素浓度降低后再恢复用药;此后进行严格的TDM。

R4.9.3. We suggest performing renal replacement therapy if acute renal failure is, at least partially, responsible for symptomatic beta-lactam overdose. 我们建议,当急性肾功能衰竭至少部分导致beta内酰胺抗生素过量的临床症状时,应进行肾脏替代治疗。

Optional recommendationstrong agreement

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