De Jongh C A, Joshi J H, Thompson B W, Newman K A, Finley R S, Moody M R, Salvatore P C, Tenney J H, Drusano G L, Schimpff S C
Am J Med. 1986 May 30;80(5C):101-11.
The double beta-lactam combination of moxalactam plus piperacillin was compared with the aminoglycoside-containing regimen of moxalactam plus amikacin in a prospective, randomized trial of empiric therapy for 302 febrile episodes in granulocytopenic cancer patients. The moxalactam/piperacillin regimen was found to be as effective as the moxalactam/amikacin regimen (70 percent overall responses); responses with moxalactam/piperacillin and moxalactam/amikacin were similar for microbiologically documented infections (24 of 37, 65 percent, versus 20 of 35, 57 percent), for the subgroup with bacteremias (19 of 32 versus 14 of 28), and for clinically documented infections (41 of 58, 71 percent, versus 40 of 48, 83 percent). Responses were similar also for bacteremia in patients with persistent, profound (less than 100/microliter) granulocytopenia. Among profoundly (less than 100/microliter) granulocytopenic patients with gram-negative bacteremia, an increase in the granulocyte count to more than 100/microliter during therapy and a peak bactericidal activity of 1:16 or more (the latter noted in seven of nine moxalactam/piperacillin trials and six of nine moxalactam/amikacin trials) correlated with a favorable clinical response in 85 percent (p less than or equal to 0.00003) and 92 percent (p less than or equal to 0.044), respectively. Although serious side effects were minimal with either regimen, the double beta-lactam combination was associated with significantly less frequent nephrotoxicity (two of 145 versus 12 of 130; p less than or equal to 0.003) and ototoxicity (none of 34 versus seven of 34; p less than or equal to 0.006). The double beta-lactam combination of moxalactam plus piperacillin was found to be as effective as moxalactam plus amikacin but to have significantly less nephro- and ototoxicity.
在一项针对粒细胞减少的癌症患者302次发热发作进行经验性治疗的前瞻性随机试验中，将拉氧头孢与哌拉西林的双β-内酰胺联合用药方案与含氨基糖苷类药物的拉氧头孢加丁胺卡那霉素方案进行了比较。结果发现，拉氧头孢/哌拉西林方案与拉氧头孢/丁胺卡那霉素方案一样有效（总体有效率为70%）；对于微生物学证实的感染（37例中的24例，65%，对比35例中的20例，57%）、菌血症亚组（32例中的19例对比28例中的14例）以及临床证实的感染（58例中的41例，71%，对比48例中的40例，83%），拉氧头孢/哌拉西林和拉氧头孢/丁胺卡那霉素的疗效相似。对于持续性严重（低于100/微升）粒细胞减少的患者，菌血症的反应也相似。在严重（低于100/微升）粒细胞减少且革兰阴性菌血症的患者中，治疗期间粒细胞计数增加至超过100/微升以及杀菌活性峰值达到1:16或更高（在9次拉氧头孢/哌拉西林试验中有7次出现，9次拉氧头孢/丁胺卡那霉素试验中有6次出现），分别与85%（p≤0.00003）和92%（p≤0.044）的良好临床反应相关。虽然两种方案的严重副作用都很少，但双β-内酰胺联合用药的肾毒性（145例中的2例对比130例中的12例；p≤0.003）和耳毒性（34例中无对比34例中的7例；p≤0.006）明显更少。结果发现，拉氧头孢与哌拉西林的双β-内酰胺联合用药方案与拉氧头孢加丁胺卡那霉素一样有效，但肾毒性和耳毒性明显更低。
