Malik I A, Abbas Z, Karim M
Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan.
Lancet. 1992 May 2;339(8801):1092-6. doi: 10.1016/0140-6736(92)90674-r.
Prompt treatment with empirical antibiotics in neutropenic febrile patients reduces morbidity and mortality. Most patients have been treated with parenteral combination antibiotics, but newer antibiotics with broad-spectrum bactericidal activity have made monotherapy feasible. Ofloxacin, a broad-spectrum fluoroquinolone, has the additional advantage that bactericidal concentrations can be achieved with oral administration. We have compared ofloxacin as an oral single agent with standard parenteral combination antibiotics for the management of neutropenic febrile patients in a prospective, randomised trial. Patients with severe neutropenia (absolute neutrophil count less than or equal to 0.5 x 10(9)/l), fever above 38 degrees C, and ability to take drugs by mouth were eligible for the study. After initial investigations, 60 patients were randomly assigned to oral ofloxacin 400 mg twice daily and 62 to parenteral combination antibiotic therapy (amikacin 15 mg/kg daily, plus, at various times in the trial, carbenicillin, cloxacillin, or piperacillin). Patients were examined 72 h and 7 days after the start of treatment and when neutropenia resolved. 24 (40%) ofloxacin-treated and 26 (42%) combination-treated patients had pyrexia of unknown origin (PUO). In both treatment groups, the treatment success rate was higher for such patients than for those with clinically or microbiologically documented infections (92% vs 67% [p less than 0.05] for ofloxacin; 85% vs 64% for combination). There were no significant differences in success rates of ofloxacin and combination treatment for these subgroups or overall (77% vs 73%). Patients with neutropenia for less than 1 week had better responses to both treatments than patients with longer-lasting neutropenia. There were 4 (7%) deaths in the ofloxacin group and 6 (10%) in the combination group. Both regimens were well tolerated. We conclude that oral single-agent ofloxacin is as effective as parenteral combination antibiotic therapy in neutropenic febrile patients, especially those expected to have short durations of neutropenia.
对中性粒细胞减少伴发热的患者尽早给予经验性抗生素治疗可降低发病率和死亡率。大多数患者接受了胃肠外联合抗生素治疗，但具有广谱杀菌活性的新型抗生素使单药治疗成为可能。氧氟沙星是一种广谱氟喹诺酮类药物，还有一个额外的优点，即口服给药即可达到杀菌浓度。在一项前瞻性随机试验中，我们比较了氧氟沙星作为口服单一药物与标准胃肠外联合抗生素治疗中性粒细胞减少伴发热患者的效果。严重中性粒细胞减少（绝对中性粒细胞计数小于或等于0.5×10⁹/L）、体温高于38℃且能够口服药物的患者符合研究条件。经过初步检查，60例患者被随机分配至每日两次口服400mg氧氟沙星组，62例患者接受胃肠外联合抗生素治疗（阿米卡星每日15mg/kg，在试验的不同时间加用羧苄西林、氯唑西林或哌拉西林）。在治疗开始后72小时、7天以及中性粒细胞减少症缓解时对患者进行检查。24例（40%）接受氧氟沙星治疗的患者和26例（42%）接受联合治疗的患者有不明原因发热（PUO）。在两个治疗组中，此类患者的治疗成功率均高于有临床或微生物学记录感染的患者（氧氟沙星组为92%对67%[p<0.05]；联合治疗组为85%对64%）。这些亚组或总体的氧氟沙星治疗成功率与联合治疗成功率无显著差异（77%对73%）。中性粒细胞减少持续时间少于1周的患者对两种治疗的反应均优于中性粒细胞减少持续时间较长的患者。氧氟沙星组有4例（7%）死亡，联合治疗组有6例（10%）死亡。两种治疗方案耐受性均良好。我们得出结论，口服单药氧氟沙星在中性粒细胞减少伴发热的患者中与胃肠外联合抗生素治疗同样有效，尤其是那些预计中性粒细胞减少持续时间较短的患者。
