Cruciani Mario, Malena Marina, Bosco Oliviero, Nardi Stefano, Serpelloni Giovanni, Mengoli Carlo
Center of Preventive Medicine/HIV Outpatient Clinic, Verona, Italy.
J Clin Oncol. 2003 Nov 15;21(22):4127-37. doi: 10.1200/JCO.2003.01.234.
Past reports and meta-analyses indicate that fluoroquinolones are highly effective in preventing Gram-negative infections in neutropenic cancer patients, but offer inadequate coverage for Gram-positive infections. We evaluated by meta-analysis the efficacy of the addition of antimicrobial agents with enhanced Gram-positive activity to prophylaxis with quinolones.
Randomized trials comparing fluoroquinolones alone (ciprofloxacin, ofloxacin, pefloxacin, or norfloxacin) with fluoroquinolone in combination with Gram-positive prophylaxis (rifampin, vancomycin, amoxicillin, roxithromycin, or penicillin) were retrieved. We pooled relative risks (RRs) using a fixed-effects model.
Nine trials (1,202 patients) published between 1993 and 2000 meet inclusion criteria. Compared with fluoroquinolone alone, Gram-positive prophylaxis reduced total bacteremic episodes (RR, 1.54; 95% CI, 1.26 to 1.88), streptococcal infections (RR, 2.20; 95% CI, 1.44 to 3.37), coagulase-negative staphylococcal infections (RR, 1.46; 95% CI, 1.04 to 2.04), and rate of febrile patients (RR 1.08; 95% CI, 1.00 to 1.16). Occurrence of clinically documented infections, unexplained fever, and infectious mortality was similar in the two groups. The addition of Gram-positive prophylaxis, however, significantly increased side effects (RR, 0.46; 95% CI, 0.28 to 0.76). Rifampin use resulted in a higher incidence of undesirable effects.
Considering the lack of cut-clear benefit on some parameters of morbidity and mortality, routine use of Gram-positive prophylaxis is not advisable. This strategy, however, should be particularly valuable in subgroups of patients at high risk of streptococcal infection (eg, those with severe and prolonged neutropenia or mucositis, and those receiving cytarabine). Problems of tolerability and the potential for the emergence of resistant microorganisms should be considered when prescribing prophylaxis with enhanced Gram-positive activity to neutropenic patients.
既往报告和荟萃分析表明，氟喹诺酮类药物在预防中性粒细胞减少的癌症患者革兰氏阴性菌感染方面非常有效，但对革兰氏阳性菌感染的覆盖不足。我们通过荟萃分析评估了在喹诺酮类药物预防基础上加用具有增强革兰氏阳性菌活性的抗菌药物的疗效。
检索比较单独使用氟喹诺酮类药物（环丙沙星、氧氟沙星、培氟沙星或诺氟沙星）与氟喹诺酮类药物联合革兰氏阳性菌预防药物（利福平、万古霉素、阿莫西林、罗红霉素或青霉素）的随机试验。我们使用固定效应模型汇总相对风险（RRs）。
1993年至2000年间发表的9项试验（1202例患者）符合纳入标准。与单独使用氟喹诺酮类药物相比，革兰氏阳性菌预防措施减少了总的菌血症发作次数（RR，1.54；95%可信区间，1.26至1.88）、链球菌感染（RR，2.20；95%可信区间，1.44至3.37）、凝固酶阴性葡萄球菌感染（RR，1.46；95%可信区间，1.04至2.04）以及发热患者的比例（RR 1.08；95%可信区间，1.00至1.16）。两组临床记录的感染、不明原因发热和感染性死亡率的发生率相似。然而，加用革兰氏阳性菌预防措施显著增加了副作用（RR，0.46；95%可信区间，0.28至0.76）。使用利福平导致不良事件的发生率更高。
考虑到在一些发病率和死亡率参数上缺乏明确的益处，不建议常规使用革兰氏阳性菌预防措施。然而，这种策略在链球菌感染高危患者亚组（例如，严重和长期中性粒细胞减少或口腔炎患者以及接受阿糖胞苷治疗的患者）中可能特别有价值。在给中性粒细胞减少患者开具具有增强革兰氏阳性菌活性的预防药物时，应考虑耐受性问题以及耐药微生物出现的可能性。
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