Cornelissen J J, de Graeff A, Verdonck L F, Branger T, Rozenberg-Arska M, Verhoef J, Dekker A W
Department of Haematology, University Hospital Utrecht, The Netherlands.
Antimicrob Agents Chemother. 1992 Apr;36(4):801-7. doi: 10.1128/AAC.36.4.801.
A prospective randomized study was conducted to determine the efficacy of imipenem-cilastatin (hereafter referred to as imipenem) (500 mg four times daily) versus combination therapy for febrile neutropenic patients receiving either no prophylaxis or ciprofloxacin for prevention of infections. Combination therapy consisted of gentamicin (80 mg every 8 h) plus either cefuroxime (1,500 mg every 8 h) or cephalothin (1,000 mg every 4 h) for suspected catheter-related infections. Ninety-four neutropenic fever episodes in 87 patients were evaluable for efficacy. The overall clinical rate of response to imipenem was significantly higher than that to combination therapy (91 versus 74%; P = 0.05). The difference in efficacy was most pronounced in patients with microbiologically documented infections (89 versus 53%; P = 0.025), which were predominantly caused by gram-positive bacteria. Differences in susceptibility may have caused the better rate of response to imipenem. Two of 29 gram-positive bacteria were imipenem resistant, whereas 10 were resistant to cephalothin and cefuroxime and 12 were resistant to gentamicin. No causative gram-negative bacterium and 24 gram-positive bacteria were isolated in 61 fever episodes with ciprofloxacin prophylaxis (oral). In contrast, nine causative gram-negative and five gram-positive bacteria were isolated in 33 episodes without prophylaxis. The difference in distribution proved to be statistically significant for gram-negative (P = 0.0001) as well as gram-positive (P = 0.025) bacteria, indicating that ciprofloxacin effectively prevented the occurrence of gram-negative bacteria and may have contributed to the relatively large number of gram-positive bacteria isolated. Empirical initial therapy with imipenem may be a valuable alternative to combination therapy for neutropenic fever episodes.
进行了一项前瞻性随机研究，以确定亚胺培南-西司他丁（以下简称亚胺培南）（每日4次，每次500毫克）与联合治疗对未接受任何预防措施或接受环丙沙星预防感染的发热性中性粒细胞减少患者的疗效。联合治疗包括庆大霉素（每8小时80毫克）加头孢呋辛（每8小时1500毫克）或头孢噻吩（每4小时1000毫克）用于疑似导管相关感染。87例患者中的94次中性粒细胞减少发热发作可评估疗效。亚胺培南的总体临床反应率显著高于联合治疗（91%对74%；P = 0.05）。疗效差异在微生物学确诊感染的患者中最为明显（89%对53%；P = 0.025），这些感染主要由革兰氏阳性菌引起。敏感性差异可能导致了亚胺培南更好的反应率。29株革兰氏阳性菌中有2株对亚胺培南耐药，而10株对头孢噻吩和头孢呋辛耐药，12株对庆大霉素耐药。在61次接受环丙沙星预防（口服）的发热发作中，未分离出致病性革兰氏阴性菌，分离出24株革兰氏阳性菌。相比之下，在33次未进行预防的发作中，分离出9株致病性革兰氏阴性菌和5株革兰氏阳性菌。革兰氏阴性菌（P = 0.0001）和革兰氏阳性菌（P = 0.025）的分布差异具有统计学意义，表明环丙沙星有效地预防了革兰氏阴性菌的发生，可能导致了分离出相对较多的革兰氏阳性菌。对于中性粒细胞减少发热发作，亚胺培南经验性初始治疗可能是联合治疗的一种有价值的替代方案。
