Cometta A, Zinner S, de Bock R, Calandra T, Gaya H, Klastersky J, Langenaeken J, Paesmans M, Viscoli C, Glauser M P
Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Antimicrob Agents Chemother. 1995 Feb;39(2):445-52. doi: 10.1128/AAC.39.2.445.
Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory. Thus, new antibiotics with better activity against gram-positive bacteria should be tested. The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients. A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy. The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group. A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05). A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02). This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients. Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.
革兰氏阳性菌已成为粒细胞减少的癌症患者主要的感染病原体。发热性中性粒细胞减少患者使用的经验性抗生素治疗方案通常包括一种广谱头孢菌素，但革兰氏阳性球菌菌血症的治疗效果一直不尽人意。因此，应测试对革兰氏阳性菌具有更好活性的新型抗生素。这项前瞻性随机对照研究的目的是评估和比较哌拉西林-他唑巴坦加丁胺卡那霉素与欧洲癌症研究与治疗组织国际抗菌治疗协作组的标准方案头孢他啶加丁胺卡那霉素在发热性粒细胞减少癌症患者经验性治疗中的疗效和耐受性。共有858例符合本研究条件，706例可评估疗效。哌拉西林-他唑巴坦-丁胺卡那霉素组342例中有210例（61%）抗生素治疗成功，而头孢他啶加丁胺卡那霉素治疗的364例中有196例（54%）成功（P = 0.05）。哌拉西林-他唑巴坦-丁胺卡那霉素组的退热时间明显更短（P = 0.01），失败时间明显更长（P = 0.02）。发现两组患者对菌血症感染的反应存在显著差异：哌拉西林-他唑巴坦加丁胺卡那霉素在80例中有40例（50%）成功，头孢他啶加丁胺卡那霉素在101例中有35例（35%）成功（P = 0.05）。多因素分析显示，头孢他啶加丁胺卡那霉素治疗失败的概率显著高于哌拉西林-他唑巴坦加丁胺卡那霉素（P = 0.02）。该试验表明，哌拉西林-他唑巴坦加丁胺卡那霉素在粒细胞减少癌症患者发热和菌血症的经验性治疗中比头孢他啶加丁胺卡那霉素更有效。虽然皮肤反应与哌拉西林-他唑巴坦加丁胺卡那霉素的相关性比与头孢他啶-丁胺卡那霉素更高，但这种不良影响相对较轻，其发生率与其他青霉素类化合物相当。
