Effects of lung inflammation and injury on pulmonary tissue penetration of meropenem and vancomycin in a model of unilateral lung injury

被引：1

作者：

Geilen, Johannes ^{[1
]}

Kainz, Matthias ^{[1
]}

Zapletal, Bernhard ^{[1
]}

Schweiger, Thomas ^{[2
]}

Jaeger, Walter ^{[3
]}

Maier-Salamon, Alexandra ^{[3
]}

Zeitlinger, Markus ^{[4
]}

Stamm, Tanja ^{[5
,6
]}

Ritschl, Valentin ^{[5
,6
]}

Geleff, Silvana ^{[7
]}

Schultz, Marcus J. ^{[1
,8
,9
]}

Tschernko, Edda ^{[1
]}

机构：

[1] Med Univ Vienna, Dept Anaesthesia Gen Intens Care & Pain Management, Div Cardiothorac & Vasc Anaesthesia & Intens Care, Waehringer Guertel 18-20, A-1090 Vienna, Austria

[2] Med Univ Vienna, Dept Thorac Surg, Vienna, Austria

[3] Univ Vienna, Dept Pharmaceut Sci, Vienna, Austria

[4] Med Univ Vienna, Dept Clin Pharmacol, Clin Pharmacokinet Pharmacogenet & Imaging, Vienna, Austria

[5] Med Univ Vienna, Inst Outcomes Res, Ctr Med Data Sci, Vienna, Austria

[6] Ludwig Boltzmann Inst Arthrit & Rehabil, Vienna, Austria

[7] Med Univ Vienna, Dept Pathol, Vienna, Austria

[8] Univ Amsterdam, Dept Intens Care, AMC, Med Ctr, Amsterdam, Netherlands

[9] Univ Amsterdam, Lab Expt Intens Care & Anaesthesiol LEICA, AMC, Med Ctr, Amsterdam, Netherlands

来源：

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS | 2024年 / 64卷 / 01期

关键词：

Antimicrobial lung tissue penetration; Acute lung injury; Acute respiratory distress syndrome; Ventilator-associated pneumonia; INFECTIOUS-DISEASES SOCIETY; RESPIRATORY-DISTRESS-SYNDROME; HEALTH-SYSTEM PHARMACISTS; EPITHELIAL LINING FLUID; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; STAPHYLOCOCCUS-AUREUS; NOSOCOMIAL PNEUMONIA; PHARMACODYNAMIC PROPERTIES; AMERICAN SOCIETY;

D O I：

10.1016/j.ijantimicag.2024.107180

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Objective: The timing and dosing of antimicrobial therapy are key in the treatment of pneumonia in critically ill patients. It is uncertain whether the presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. The effects of lung inflammation and injury on tissue penetration of two antimicrobial drugs commonly used for pneumonia were determined in an established model of unilateral lung injury. Methods: Unilateral lung injury was induced in the left lung of 13 healthy pigs through cyclic rinsing; the right healthy lung served as control. Infusions of meropenem and vancomycin were administered and concentrations of these drugs in lung tissue, blood, and epithelial lining fluid (ELF) were compared over a period of 6 h. Results: Median vancomycin lung tissue concentrations and penetration ratio were higher in inflamed and injured lungs compared with uninflamed and uninjured lungs (AUC0-6h : P = 0.003 and AUCdialysate /AUCplasma ratio: P = 0.003), resulting in higher AUC0-24 /MIC. Median meropenem lung tissue concentrations and penetration ratio in inflamed and injured lungs did not differ from that in uninflamed and uninjured lungs (AUC0-6 : P = 0.094 and AUCdialysate /AUCplasma ratio: P = 0.173). The penetration ratio for both vancomycin and meropenem into ELF was similar in injured and uninjured lungs. Conclusion: Vancomycin penetration into lung tissue is enhanced by acute inflammation and injury, a phenomenon barely evident with meropenem. Therefore, inflammation in lung tissue influences the penetration into interstitial lung tissue, depending on the chosen antimicrobial drug. Measurement of ELF levels alone might not identify the impact of inflammation and injury. (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

引用

页数：10

共 58 条

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