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针对小鼠血源性耐多药肺炎的实验性噬菌体疗法

Experimental phage therapy against haematogenous multi-drug resistant pneumonia in mice.

作者信息

Oduor Joseph M Ochieng', Onkoba Nyamongo, Maloba Fredrick, Nyachieo Atunga

机构信息

Institute of Primate Research (IPR), Nairobi, Kenya.

School of Medicine, Kenyatta University, Nairobi, Kenya.

出版信息

Afr J Lab Med. 2016 Sep 30;5(1):435. doi: 10.4102/ajlm.v5i1.435. eCollection 2016.

DOI:10.4102/ajlm.v5i1.435
PMID:28879116
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5436407/
Abstract

BACKGROUND

Community-acquired haematogenous pneumonia is a rare infection, though it can be acquired nosocomially. Currently, antibiotics used against pneumonia have shown reduced efficacy. Thus, there is need for an alternative therapy against multidrug-resistant (MDRSA) strains in the community.

OBJECTIVE

We sought to determine the efficacy of environmentally-obtained lytic phage against haematogenous MDRSA pneumonia in mice.

METHODS

Phages and MDRSA were isolated from sewage samples collected within Nairobi County, Kenya. Isolated bacteria were screened for resistance against ceftazidime, oxacillin, vancomycin, netilmicin, gentamicin, erythromycin, trimethroprim-sulfamethoxazole and cefuroxime. Thirty BALB/c mice aged six to eight weeks were randomly assigned into three groups: the MDRSA-infection group ( = 20), the phage-infection group ( = 5) and the non-infection group ( = 5). Mice were infected with either MDRSA or phage (108 CFU/mL) and treated after 72 hours with a single dose of clindamycin (8 mg/kg/bwt) or 108 PFU/mL of phage or a combination therapy (clindamycin and phage). The efficacy of phage, clindamycin or clindamycin with phage combination was determined using resolution of lung pathology and bacterial load in lung homogenates.

RESULTS

The viable MDRSA count was 0.5 ± 0.2 log CFU/gm in the phage-treated group, 4.4 ± 0.2 log CFU/gm in the clindamycin-treated group and 4.0 ± 0.2 log CFU/gm in the combination-treated group. The efficacy of phage therapy was significantly different from other therapeutic modes ( = 0 < 0.0001). Histology showed that the mice treated with phage did not develop pneumonia.

CONCLUSION

Phage therapy is effective against haematogenous MDRSA infection. Thus, it can be explored as an alternative treatment method.

摘要

背景

社区获得性血源性肺炎是一种罕见的感染,尽管也可在医院获得。目前,用于治疗肺炎的抗生素疗效已有所降低。因此,需要一种针对社区中耐多药(MDRSA)菌株的替代疗法。

目的

我们试图确定从环境中获得的裂解性噬菌体对小鼠血源性MDRSA肺炎的疗效。

方法

从肯尼亚内罗毕县收集的污水样本中分离噬菌体和MDRSA。对分离出的细菌进行头孢他啶、苯唑西林、万古霉素、奈替米星、庆大霉素、红霉素、甲氧苄啶-磺胺甲恶唑和头孢呋辛耐药性筛查。将30只6至8周龄的BALB/c小鼠随机分为三组:MDRSA感染组(n = 20)、噬菌体感染组(n = 5)和非感染组(n = 5)。小鼠分别感染MDRSA或噬菌体(108 CFU/mL),72小时后用单剂量克林霉素(8 mg/kg/体重)或108 PFU/mL噬菌体或联合疗法(克林霉素和噬菌体)进行治疗。通过肺病理学的消退和肺匀浆中的细菌载量来确定噬菌体、克林霉素或克林霉素与噬菌体联合疗法的疗效。

结果

噬菌体治疗组的存活MDRSA计数为0.5±0.2 log CFU/g,克林霉素治疗组为4.4±0.2 log CFU/g,联合治疗组为4.0±0.2 log CFU/g。噬菌体疗法的疗效与其他治疗模式有显著差异(F = 0,P < 0.0001)。组织学显示,接受噬菌体治疗的小鼠未发生肺炎。

结论

噬菌体疗法对血源性MDRSA感染有效。因此,可将其作为一种替代治疗方法进行探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/e17ec83aef0d/AJLM-5-435-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/931d0023a873/AJLM-5-435-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/9db5c736a40c/AJLM-5-435-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/398df1f75048/AJLM-5-435-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/fc9bb9268dbb/AJLM-5-435-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/e17ec83aef0d/AJLM-5-435-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/931d0023a873/AJLM-5-435-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/9db5c736a40c/AJLM-5-435-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/398df1f75048/AJLM-5-435-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/fc9bb9268dbb/AJLM-5-435-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c8/5436407/e17ec83aef0d/AJLM-5-435-g005.jpg

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