Kumar Simit, Bandyopadhyay Maitreyi, Mondal Soma, Pal Nupur, Ghosh Tapashi, Bandyopadhyay Manas, Banerjee Parthajit
Department of Microbiology, R. G. Kar Medical College, Kolkata, India.
Avicenna J Med. 2013 Oct;3(4):92-6. doi: 10.4103/2231-0770.120500.
[corrected] Treatment of serious life-threatening multi-drug-resistant organisms poses a serious problem due to the limited therapeutic options. Tigecycline has been recently marketed as a broad-spectrum antibiotic with activity against both gram-positive and gram-negative bacteria. Even though many studies have demonstrated the activity of tigecycline against ESBL-producing Enterobacteriaceae, its activity is not well-defined against micro-organisms producing metallo-β-lactamases (MBLs), as there are only a few reports and the number of isolates tested is limited.
The aim of the present study was to evaluate the activity of tigecycline against MBL-producing bacterial isolates.
The isolates were tested for MBL production by (i) combined-disk test, (ii) double disc synergy test (DDST), (iii) susceptibility to aztreonam (30 μg) disk. Minimum inhibitory concentration to tigecycline was determined according to agar dilution method as per Clinical Laboratory Standards Institute (CLSI) guidelines. Disc diffusion susceptibility testing was also performed for all these isolates using tigecycline (15 μg) discs.
Among the total 308 isolates included in the study, 99 were found to be MBL producers. MBL production was observed mostly in isolates from pus samples (40.47%) followed by urine (27.4%) and blood (13.09%). MBL production was observed in E. coli (41.48%), K. pneumoniae (26.67%), Proteus mirabilis (27.78%), Citrobacter spp. (41.67%), Enterobacter spp. (25.08%), and Acinetobacter spp. (27.27%). The result showed that tigecycline activity was unaffected by MBL production and it was showed almost 100% activity against all MBL-producing isolates, with most of the isolates exhibiting an MIC ranging from 0.25-8 μg/ml, except 2 MBL-producing E. coli isolates who had an MIC of 8 μg/ml.
To conclude, tigecycline was found to be highly effective against MBL-producing Enterobacteriaceae and acinetobacter isolates, but the presence of resistance among organisms, even before the mass usage of the drug, warrants the need of its usage as a reserve drug. The study also found that the interpretative criteria for the disc diffusion method, recommended by the FDA, correlates well with the MIC detection methods. So, the microbiology laboratories might use the relatively easier method of disc diffusion, as compared to the comparatively tedious method of MIC determination.
[已校正] 由于治疗选择有限，治疗严重危及生命的多重耐药菌是一个严重问题。替加环素最近作为一种对革兰氏阳性菌和革兰氏阴性菌均有活性的广谱抗生素上市。尽管许多研究已证明替加环素对产超广谱β-内酰胺酶（ESBL）的肠杆菌科细菌有活性，但其对产金属β-内酰胺酶（MBL）的微生物的活性尚未明确界定，因为仅有少数报告且测试的分离株数量有限。
本研究的目的是评估替加环素对产MBL细菌分离株的活性。
通过（i）复合纸片法、（ii）双纸片协同试验（DDST）、（iii）对氨曲南（30μg）纸片的敏感性检测分离株的MBL产生情况。根据临床实验室标准协会（CLSI）指南，采用琼脂稀释法测定替加环素的最低抑菌浓度。还使用替加环素（15μg）纸片对所有这些分离株进行纸片扩散药敏试验。
在本研究纳入的308株分离株中，发现99株为MBL产生菌。MBL产生主要见于脓液样本分离株（40.47%），其次是尿液（27.4%）和血液（13.09%）。在大肠杆菌（41.48%）、肺炎克雷伯菌（26.67%）、奇异变形杆菌（27.78%）、柠檬酸杆菌属（41.67%）、肠杆菌属（25.08%）和不动杆菌属（27.27%）中观察到MBL产生。结果表明，替加环素的活性不受MBL产生的影响，对所有产MBL分离株几乎均表现出100%的活性，大多数分离株的MIC范围为0.25 - 8μg/ml，但有2株产MBL的大肠杆菌分离株的MIC为8μg/ml。
总之，发现替加环素对产MBL的肠杆菌科细菌和不动杆菌分离株高度有效，但即使在该药物大量使用之前，生物体中存在的耐药性也表明有必要将其作为储备药物使用。该研究还发现，FDA推荐的纸片扩散法的解释标准与MIC检测方法相关性良好。因此，与相对繁琐的MIC测定方法相比，微生物学实验室可能会使用相对简便的纸片扩散法。
