用于监测抗菌药物对感染金黄色葡萄球菌小鼠疗效的99mTc标记的UBI 29-41肽。

99mTc-Labeled UBI 29-41 peptide for monitoring the efficacy of antibacterial agents in mice infected with Staphylococcus aureus.

作者信息

Nibbering Peter H, Welling Mick M, Paulusma-Annema Akke, Brouwer Carlo P J M, Lupetti Antonella, Pauwels Ernest K J

机构信息

Department of Infectious Diseases, Leiden University Medical Center C5-P, PO Box 9600, 2300 RC Leiden, The Netherlands.

出版信息

J Nucl Med. 2004 Feb;45(2):321-6.

PMID:14960656

Abstract

UNLABELLED

Based on our earlier observation that (99m)Tc-UBI 29-41, a radiolabeled peptide derived from ubiquicidin (UBI), discriminates between infections and sterile inflammatory processes, we considered the possibility that this tracer could be used for monitoring the efficacy of antibacterial agents in animals infected with Staphylococcus aureus.

METHODS

We injected (99m)Tc-UBI 29-41 into S. aureus-infected mice after treatment with various doses of cloxacillin or erythromycin. At intervals thereafter, accumulation of the radiolabeled peptide at the site of infection was assessed by scintigraphy. When S. aureus was antibiotic resistant, we evaluated the efficacy of hLF 1-11, an antimicrobial peptide derived from human lactoferrin (hLF), in rats using (99m)Tc-UBI 29-41 and scintigraphy.

RESULTS

Decreasing amounts of radiolabeled peptide at the site of the S. aureus infection in animals correlated (r(2) > 0.81; P < 0.001) with increasing doses of cloxacillin in animals. An effective dose of erythromycin resulted in reduced (P = 0.023) accumulation of the radiolabeled peptide at the site of S. aureus infection in mice. In addition, we noted decreasing amounts of (99m)Tc-UBI 29-41 at the site of infection after administration of increasing doses of hLF 1-11 peptide in rats infected with antibiotic-resistant S. aureus. Furthermore, the number of viable bacteria decreased with increasing doses of cloxacillin or hLF 1-11 peptide, and a good correlation (r(2) > 0.80; P < 0.001) between the accumulation of (99m)Tc-UBI 29-41 and the number of viable (antibiotic-resistant) S. aureus at the site of infection was seen. In an attempt to explain these results, we found that these antibacterial agents do not affect the in vitro binding of (99m)Tc-UBI 29-41 to bacteria. Furthermore, this radiolabeled peptide bound to free bacteria and to cell-adherent but not phagocytized S. aureus, suggesting that at sites of infection mainly extracellular bacteria are targeted by (99m)Tc-UBI 29-41.

CONCLUSION

(99m)Tc-UBI 29-41 allows the monitoring of the efficacy of antibacterial agents in mice and rats with S. aureus infections.

摘要

未标记

基于我们之前的观察，即（99m）Tc - UBI 29 - 41（一种源自泛菌杀菌素（UBI）的放射性标记肽）能够区分感染与无菌性炎症过程，我们考虑了这种示踪剂可用于监测金黄色葡萄球菌感染动物体内抗菌药物疗效的可能性。

方法

在用不同剂量的氯唑西林或红霉素治疗后，我们将（99m）Tc - UBI 29 - 41注入金黄色葡萄球菌感染的小鼠体内。此后每隔一段时间，通过闪烁扫描评估放射性标记肽在感染部位的蓄积情况。当金黄色葡萄球菌具有抗生素抗性时，我们使用（99m）Tc - UBI 29 - 41和闪烁扫描评估了源自人乳铁蛋白（hLF）的抗菌肽hLF 1 - 11在大鼠体内的疗效。

结果

动物体内金黄色葡萄球菌感染部位放射性标记肽的量减少与氯唑西林剂量增加相关（r² > 0.81；P < 0.001）。有效剂量的红霉素导致小鼠体内金黄色葡萄球菌感染部位放射性标记肽的蓄积减少（P = 0.023）。此外，我们注意到在给予感染抗生素抗性金黄色葡萄球菌的大鼠递增剂量的hLF 1 - 11肽后，感染部位（99m）Tc - UBI 29 - 41的量减少。此外，活菌数量随着氯唑西林或hLF 1 - 11肽剂量的增加而减少，并且在感染部位（99m）Tc - UBI 29 - 41的蓄积与活菌（抗生素抗性）金黄色葡萄球菌数量之间存在良好的相关性（r² > 0.80；P < 0.001）。为了解释这些结果，我们发现这些抗菌药物不影响（99m）Tc - UBI 29 - 41在体外与细菌的结合。此外，这种放射性标记肽与游离细菌以及细胞黏附但未被吞噬的金黄色葡萄球菌结合，这表明在感染部位，（99m）Tc - UBI 29 - 41主要靶向细胞外细菌。