Geriatric Research, Education and Clinical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA.
Antimicrob Agents Chemother. 2011 Feb;55(2):546-9. doi: 10.1128/AAC.00839-10. Epub 2010 Dec 6.
Tigecycline is a broad-spectrum glycylcycline antibiotic with potent in vitro activity against Clostridium difficile. We used a mouse model to test the hypothesis that tigecycline has a low propensity to promote colonization and toxin production by C. difficile due to inhibitory activity in the colon. Mice (5 to 8 per group) received subcutaneous injections of tigecycline (low and high doses) alone or in combination with clindamycin for 6 days. Growth of and toxin production by 3 strains of C. difficile (tigecycline MICs ≤ 0.012 μg/ml) were measured in cecal contents collected 6 h or 3 days after the final antibiotic dose. Antibiotic concentrations were measured using a bioassay, and concentrations of total anaerobes and Bacteroides spp. were measured. The effects of tigecycline on rendering mice susceptible to colonization with and reducing the burden of C. difficile were also examined. In comparison to saline controls, clindamycin promoted the growth of C. difficile (P < 0.001) in cecal contents, whereas tigecycline did not. Tigecycline did not suppress total anaerobes or Bacteroides spp. in comparison to saline controls. Concurrent administration of tigecycline prevented clindamycin-induced promotion of C. difficile in cecal contents collected 6 h or 3 days (high dose only) after the final antibiotic dose. Tigecycline did not promote the establishment of colonization in mice, yet it did not reduce concentrations of C. difficile in animals with established colonization. In summary, tigecycline did not promote the growth of or toxin production by C. difficile, probably due to inhibitory activity against C. difficile and relative sparing of indigenous anaerobic microflora.
替加环素是一种广谱甘氨酰环素抗生素，对艰难梭菌具有强大的体外活性。我们使用小鼠模型来检验以下假说：由于在结肠中的抑制活性，替加环素不太可能促进艰难梭菌的定植和毒素产生。将小鼠（每组 5 至 8 只）接受替加环素（低剂量和高剂量）单独或与克林霉素联合皮下注射，持续 6 天。在最后一次抗生素剂量后 6 小时或 3 天时收集盲肠内容物，测量 3 株艰难梭菌（替加环素 MIC ≤ 0.012 μg/ml）的生长和毒素产生。使用生物测定法测量抗生素浓度，并测量总厌氧菌和拟杆菌属的浓度。还检查了替加环素对使小鼠易受定植和减少艰难梭菌负担的影响。与生理盐水对照相比，克林霉素促进盲肠内容物中艰难梭菌的生长（P < 0.001），而替加环素则没有。与生理盐水对照相比，替加环素并没有抑制总厌氧菌或拟杆菌属。在最后一次抗生素剂量后 6 小时或 3 天（仅高剂量）收集的盲肠内容物中，同时给予替加环素可预防克林霉素诱导的艰难梭菌促进。替加环素没有促进小鼠定植的建立，但在已经定植的动物中也没有降低艰难梭菌的浓度。总之，替加环素没有促进艰难梭菌的生长或毒素产生，可能是由于对艰难梭菌的抑制活性和对本土厌氧微生物区系的相对保护。
