Alisky J, Iczkowski K, Rapoport A, Troitsky N
Department of Community and Family Medicine, St. Louis University School of Medicine, MO 63014, USA.
J Infect. 1998 Jan;36(1):5-15. doi: 10.1016/s0163-4453(98)92874-2.
The emergence of antibiotic-resistant bacteria has prompted interest in alternatives to conventional drugs. One possible option is to use bacteriophages (phage) as antimicrobial agents. We have conducted a literature review of all Medline citations from 1966-1996 that dealt with the therapeutic use of phage. There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The Polish and Soviets administered phage orally, topically or systemically to treat a wide variety of antibiotic-resistant pathogens in both adults and children. Infections included suppurative wound infections, gastroenteritis, sepsis, osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas, Shigella and Salmonella spp. Overall, the Polish and Soviets reported success rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or allergic side effects. However, efficacy of phage was determined almost exclusively by qualitative clinical assessment of patients, and details of dosages and clinical criteria were very sketchy. There were also six British reports describing controlled trials of phage in animal models (mice, guinea pigs and livestock), measuring survival rates and other objective criteria. All of the British studies raised phage against specific pathogens then used to create experimental infections. Demonstrable efficacy against Escherichia, Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage is sequestered in the spleen and removed from circulation. This can be overcome by serial passage of phage through mice to isolate mutants that resist sequestration. In conclusion, bacteriophages may show promise for treating antibiotic resistant pathogens. To facilitate further progress, directions for future research are discussed and a directory of authors from the reviewed papers is provided.
抗生素耐药菌的出现引发了人们对传统药物替代方案的兴趣。一种可能的选择是使用噬菌体作为抗菌剂。我们对1966年至1996年所有涉及噬菌体治疗用途的Medline文献进行了综述。有来自波兰、苏联、英国和美国的27篇论文。波兰人和苏联人通过口服、局部或全身给药的方式使用噬菌体,治疗成人和儿童的多种抗生素耐药病原体。感染包括化脓性伤口感染、肠胃炎、败血症、骨髓炎、皮炎、脓胸和肺炎;病原体包括葡萄球菌、链球菌、克雷伯菌、大肠杆菌、变形杆菌、假单胞菌、志贺菌和沙门氏菌属。总体而言,波兰人和苏联人报告噬菌体治疗的成功率为80%至95%,胃肠道或过敏副作用罕见且可逆。然而,噬菌体的疗效几乎完全由对患者的定性临床评估确定,剂量和临床标准的细节非常简略。还有六篇英国报告描述了噬菌体在动物模型(小鼠、豚鼠和家畜)中的对照试验,测量存活率和其他客观标准。所有英国研究都针对特定病原体培养噬菌体,然后用于制造实验性感染。在这些模型系统中,已观察到对大肠杆菌、不动杆菌、假单胞菌和葡萄球菌属有明显疗效。两篇美国论文涉及提高噬菌体的生物利用度。噬菌体被隔离在脾脏中并从循环中清除。这可以通过让噬菌体连续通过小鼠来分离抗隔离的突变体来克服。总之,噬菌体可能在治疗抗生素耐药病原体方面显示出前景。为促进进一步进展,讨论了未来研究的方向,并提供了综述论文作者的名录。