Spangler S K, Jacobs M R, Appelbaum P C
Department of Pathology (Clinical Microbiology), Hershey Medical Center, Hershey, Pennsylvania 17033.
Antimicrob Agents Chemother. 1994 Nov;38(11):2599-604. doi: 10.1128/AAC.38.11.2599.
The National Committee for Clinical Laboratory Standards agar dilution method was used to compare the in vitro activity of WY-49605 (also called SUN/SY 5555 and ALP-201), a new broad-spectrum oral penem, to those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 clinically isolated anaerobes. These anaerobic organisms included 90 strains from the Bacteroides fragilis group, 87 Prevotella and Porphyromonas strains, non-B. fragilis group Bacteroides strains, 56 fusobacteria, 55 peptostreptococci, 49 gram-positive non-spore-forming rods, and 47 clostridia. Overall, WY-49605 had an MIC range of 0.015 to 8.0 micrograms/ml, an MIC at which 50% of the isolates are inhibited (MIC50) of 0.25 microgram/ml, and an MIC at which 90% of the isolates are inhibited (MIC90) of 2.0 micrograms/ml. Good activity against all anaerobe groups was observed, except for Clostridium difficile and lactobacilli (MIC50s of 4.0 and 2.0 micrograms/ml, respectively, and MIC90s of 8.0 and 2.0 micrograms/ml, respectively). Imipenem had an MIC50 of 0.03 microgram/ml and an MIC90 of 0.25 microgram/ml. Ciprofloxacin was much less active (MIC50 of 2.0 micrograms/ml and MIC90 of 16.0 micrograms/ml). By comparison, all oral beta-lactams were less active than WY-49605, with susceptibilities as follows: amoxicillin MIC50 of 8.0 micrograms/ml and MIC90 of > 256.0 micrograms/ml), amoxicillin-clavulanate MIC50 of 1.0 microgram/ml and MIC90 of 8.0 micrograms/ml, cefaclor MIC50 of 8.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, cefpodoxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, and cefuroxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml. Clindamycin was active against all groups except some members of the B. fragilis group, Fusobacterium varium, and some clostridia ( overall MIC50 of 0.5 micrograms/ml and overall MIC90 of 8.0 micrograms/ml). Metronidazole was active (MIC of less than or equal to 4.0 micrograms/ml) against all gram-negative anaerobic rods, but most gram-positive non-spore-forming rods, some peptostreptococci, and some clostridia were less susceptible. To date, WY-49605 is the most active oral beta-lactam against anaerobes: these results suggest clinical evaluation for clinical indications suitable for oral therapy.
采用美国国家临床实验室标准委员会琼脂稀释法，比较新型广谱口服青霉烯类药物WY-49605（也称为SUN/SY 5555和ALP-201）与阿莫西林、阿莫西林-克拉维酸、亚胺培南、环丙沙星、头孢克洛、头孢泊肟、头孢呋辛、克林霉素和甲硝唑对384株临床分离厌氧菌的体外活性。这些厌氧菌包括90株脆弱拟杆菌属菌株、87株普雷沃菌属和卟啉单胞菌属菌株、非脆弱拟杆菌属的拟杆菌属菌株、56株梭杆菌、55株消化链球菌、49株革兰氏阳性无芽孢杆菌和47株梭菌。总体而言，WY-49605的最低抑菌浓度（MIC）范围为0.015至8.0微克/毫升，50%菌株被抑制时的MIC（MIC50）为0.25微克/毫升，90%菌株被抑制时的MIC（MIC90）为2.0微克/毫升。观察到WY-49605对所有厌氧菌均有良好活性，但对艰难梭菌和乳酸杆菌除外（其MIC50分别为4.0和2.0微克/毫升，MIC90分别为8.0和2.0微克/毫升）。亚胺培南的MIC50为0.03微克/毫升，MIC90为0.25微克/毫升。环丙沙星的活性则低得多（MIC50为2.0微克/毫升，MIC90为16.0微克/毫升）。相比之下，所有口服β-内酰胺类药物的活性均低于WY-49605，其药敏情况如下：阿莫西林的MIC50为8.0微克/毫升，MIC90>256.0微克/毫升；阿莫西林-克拉维酸的MIC50为1.0微克/毫升，MIC90为8.0微克/毫升；头孢克洛的MIC50为8.0微克/毫升，MIC90>32.0微克/毫升；头孢泊肟的MIC50为4.0微克/毫升，MIC90>32.0微克/毫升；头孢呋辛的MIC50为4.0微克/毫升，MIC90>32.0微克/毫升。克林霉素对除脆弱拟杆菌属的一些成员、多变梭杆菌和一些梭菌外的所有菌群均有活性（总体MIC50为0.5微克/毫升，总体MIC90为8.0微克/毫升）。甲硝唑对所有革兰氏阴性厌氧杆菌均有活性（MIC小于或等于4.0微克/毫升），但大多数革兰氏阳性无芽孢杆菌、一些消化链球菌和一些梭菌对其敏感性较低。迄今为止，WY-49605是对厌氧菌活性最强的口服β-内酰胺类药物：这些结果提示，对于适合口服治疗的临床指征，有必要进行临床评估。
