Winston D J, Ho W G, Bruckner D A, Gale R P, Champlin R E
Department of Medicine, University of California, Los Angeles 90024.
Am J Med. 1988 Jul 25;85(1A):21-30. doi: 10.1016/0002-9343(88)90171-4.
The efficacy and safety of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients were compared with moxalactam plus piperacillin, ceftazidime plus piperacillin, and imipenem alone in two separate clinical trials. All patients also received prophylactic vitamin K. When National Committee for Clinical Laboratory Standards breakpoints for susceptibility were used, a greater proportion of pretherapy isolates of gram-negative aerobic bacilli and gram-positive organisms were found to be susceptible to cefoperazone (94 percent) and imipenem (91 percent) than to moxalactam (84 percent), ceftazidime (85 percent), or piperacillin (85 percent). In trial I, the overall response rates for documented or possible infections were 78 percent (76 of 97 patients) for cefoperazone/piperacillin and 80 percent (72 of 90 patients) for moxalactam/piperacillin. In trial II, the overall response rates were 86 percent (25 of 29 patients) for cefoperazone/piperacillin, 74 percent (20 of 27 patients) for ceftazidime/piperacillin, and 72 percent (21 of 29 patients) for imipenem alone. There was no nephrotoxicity or hemorrhage related to the study drugs. Diarrhea was more frequent with each of the double beta-lactam regimens, whereas nausea and seizures were more common with imipenem given at a dosage of 1.0 g intravenously every six hours. Seizures occurred in three of 29 imipenem-treated patients but in none of 243 patients treated with the double beta-lactam regimens (p less than 0.001). These results suggest that cefoperazone plus piperacillin provides adequate coverage for most common bacterial pathogens and is safe and effective therapy for febrile granulocytopenic patients.
在两项独立的临床试验中，将头孢哌酮加哌拉西林的双β-内酰胺疗法与拉氧头孢加哌拉西林、头孢他啶加哌拉西林以及单独使用亚胺培南在发热性粒细胞减少患者中的疗效和安全性进行了比较。所有患者还接受了预防性维生素K治疗。当采用美国国家临床实验室标准委员会的药敏断点时，发现治疗前革兰氏阴性需氧杆菌和革兰氏阳性菌的分离株中，对头孢哌酮（94%）和亚胺培南（91%）敏感的比例高于对拉氧头孢（84%）、头孢他啶（85%）或哌拉西林（85%）敏感的比例。在试验I中，头孢哌酮/哌拉西林治疗有记录或可能感染的总体有效率为78%（97例患者中的76例），拉氧头孢/哌拉西林为80%（90例患者中的72例）。在试验II中，头孢哌酮/哌拉西林的总体有效率为86%（29例患者中的25例），头孢他啶/哌拉西林为74%（27例患者中的20例），单独使用亚胺培南为72%（29例患者中的21例）。未发现与研究药物相关的肾毒性或出血情况。每种双β-内酰胺方案导致腹泻的情况更频繁，而每6小时静脉注射1.0 g亚胺培南时，恶心和癫痫发作更为常见。29例接受亚胺培南治疗的患者中有3例出现癫痫发作，但243例接受双β-内酰胺方案治疗的患者中均未出现（p<0.001）。这些结果表明，头孢哌酮加哌拉西林对大多数常见细菌病原体具有足够的覆盖范围，是发热性粒细胞减少患者安全有效的治疗方法。
