Odou M-F, Muller C, Calvet L, Dubreuil L
Faculty of Pharmacy, 3 rue du Professeur Laguesse, BP83, 59006 Lille Cedex, France.
J Antimicrob Chemother. 2007 Apr;59(4):646-51. doi: 10.1093/jac/dkm019. Epub 2007 Mar 9.
Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections. The aim of this study was to determine the antimicrobial activity of retapamulin by determining the minimal inhibitory concentration (MIC) values of this new drug and comparators against a wide range of anaerobic bacteria of human origin.
The in vitro activity of retapamulin and six comparators (amoxicillin, amoxicillin/clavulanic acid, ceftriaxone, imipenem, clindamycin and metronidazole) was evaluated against 232 anaerobic clinical isolates. MICs were determined by the CLSI reference agar dilution method (M11-A6).
Ceftriaxone, clindamycin and amoxicillin/clavulanic acid resistance rates were 54%, 42% and 9.6%, respectively, within the Bacteroides fragilis group. Despite high resistance rates to various antibiotics, retapamulin inhibited 37/52 (71%) strains of the B. fragilis group and 85/87 (98%) of the other Gram-negative bacilli at a concentration of 2 mg/L or less. All the investigated strains of Clostridium perfringens were inhibited by 1 mg/L retapamulin. Three strains of C. difficile and one strain of C. clostridioforme demonstrated decreased susceptibility to retapamulin. Based on inhibitory concentrations, retapamulin was more active than clindamycin, metronidazole and ceftriaxone against Propionibacterium acnes and anaerobic Gram-positive cocci, as all isolates were inhibited by <or=2 mg/L.
At <or=2 mg/L, retapamulin inhibited 90% of all 232 anaerobes tested, whereas overall resistance rates for the comparators were as follows: co-amoxiclav, 2%; metronidazole, 12%; clindamycin, 15% and ceftriaxone, 20%. The broad anaerobic spectrum demonstrated by retapamulin in vitro is attractive. Pending further clinical investigation, retapamulin may offer an alternative treatment for anaerobic skin infections in this era of increasing resistance.
瑞他帕林是截短侧耳素类中首个被制成局部用抗菌剂用于治疗皮肤感染的药物。本研究的目的是通过测定这种新药及对照药对多种人体来源厌氧菌的最低抑菌浓度（MIC）值，来确定瑞他帕林的抗菌活性。
评估了瑞他帕林和六种对照药（阿莫西林、阿莫西林/克拉维酸、头孢曲松、亚胺培南、克林霉素和甲硝唑）对232株厌氧临床分离株的体外活性。MIC通过CLSI参考琼脂稀释法（M11 - A6）测定。
在脆弱拟杆菌组中，头孢曲松、克林霉素和阿莫西林/克拉维酸的耐药率分别为54%、42%和9.6%。尽管对各种抗生素耐药率较高，但瑞他帕林在浓度为2mg/L或更低时能抑制52株脆弱拟杆菌组菌株中的37株（71%）以及87株其他革兰氏阴性杆菌中的85株（98%）。所有检测的产气荚膜梭菌菌株均被1mg/L的瑞他帕林抑制。三株艰难梭菌和一株梭状芽孢杆菌对瑞他帕林的敏感性降低。基于抑菌浓度，瑞他帕林对痤疮丙酸杆菌和厌氧革兰氏阳性球菌的活性比克林霉素、甲硝唑和头孢曲松更强，因为所有分离株均被≤2mg/L的瑞他帕林抑制。
在≤2mg/L时，瑞他帕林抑制了所检测的全部232株厌氧菌中的90%，而对照药的总体耐药率如下：阿莫西林/克拉维酸，2%；甲硝唑，12%；克林霉素，15%；头孢曲松，20%。瑞他帕林在体外显示出的广泛厌氧谱很有吸引力。在进一步临床研究之前，在这个耐药性不断增加的时代，瑞他帕林可能为厌氧性皮肤感染提供一种替代治疗方法。
