Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever—Reply
Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever—Reply
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中性粒细胞减少症不明原因发热患者抗菌药物使用指南——答复
DOI：
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
M. Yow
中科院分区：
文献类型：
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作者：
W. Hughes;D. Armstrong;G. Bodey;R. Feld;G. Mandell;J. Meyers;P. Pizzo;S. Schimpff;J. Shenep;James C. Wade;L. Young;M. Yow
致编辑-在他们最近的综述中，Hughes等人[1]讨论了经验性抗生素治疗在贫血患者中不明原因发热的应用。我们关注他们关于双3-内酰胺方案的建议。使用抗生素组合有三个基本原因：提供协同作用，防止耐药性的发展，以及扩大经验性治疗的范围。双3-内酰胺组合（如脲基青霉素与头孢菌素）很少被发现对革兰氏阴性杆菌有协同作用。事实上，这种组合更有可能导致拮抗作用[2，3]。β-内酰胺与氨基糖苷类药物联合使用确实对各种革兰氏阳性和革兰氏阴性微生物（包括铜绿假单胞菌）产生协同作用[4]。细菌对抗生素耐药性的发展是一个众所周知的问题[2，3]。尚未发现双3-内酰胺组合可减少耐药性的发生[5]。这在产生Richmond-Sykes 1型3-内酰胺酶的生物体如铜绿假单胞菌和阴沟肠杆菌中是一个特别的问题。与此相反，氨基糖苷类药物联合使用时可降低对3-内酰胺类药物的耐药性（反之亦然），尽管存在相互矛盾的数据。实验表明，氨基糖苷-3-内酰胺联合用药可预防耐药性的出现，而双重3-内酰胺方案并不比单独的3-内酰胺方案更好[6]。双3-内酰胺组合具有相加作用，将扩大经验覆盖范围。然而，如果病原体是头孢菌素耐药微生物，医生必须对广谱青霉素作为单一疗法感到舒适。有充分证据表明氨基糖苷类具有肾毒性。那些提倡使用双3-内酰胺组合的人声称使用氨基糖苷类的风险超过了益处。我们认识到，对于大多数粒细胞减少症患者，双3-内酰胺联合治疗是有效的。然而，在大多数情况下，头孢他啶单药治疗应该足够[7]。第一项和第四项EORTC研究[8，9]和Winston等人[10]提供了强有力的证据，证明含氨基糖苷类药物的治疗方案在重度中性粒细胞减少（<100/mm 3）或感染铜绿假单胞菌的患者中产生了更好的结果。在这些患者人群中使用氨基糖苷类药物的获益应大于风险。我们认为，拮抗潜力和对3-内酰胺抗生素耐药的微生物的出现是尽可能避免使用双3-内酰胺的原因。此外，氨基糖苷类抗生素应与广谱3-内酰胺类抗生素联合应用于严重血小板减少症患者或铜绿假单胞菌感染患者。
To THE EDITOR-In their recent review, Hughes et al. [1] discuss the use of empiric antibiotic therapy for unexplained fever in neutropenic patients. We are concerned about their recommendations regarding double 3-lactam regimens. There are three basic reasons for using antibiotic combinations: to provide synergy, to prevent the development of resistance, and to broaden the spectrum of empiric therapy. Double 3-lactam combinations (such as the ureidopenicillins with cephalosporins) have only rarely been found to provide synergy against gram-negative bacilli. In fact, the combination will more likely result in antagonism [2, 3]. A 3-lactam in combination with an aminoglycoside does produce synergy against various grampositive and gram-negative organisms, including Pseudomonas aeruginosa [4]. The development of antibiotic resistance by bacteria is a welldescribed problem [2, 3]. Double 3-lactam combinations have not been found to reduce the development of resistance [5]. This is a particular problem in organisms that produce Richmond-Sykes type 1 3-lactamases, such as P aeruginosa and Enterobacter cloacae. In contrast, aminoglycosides have been shown to decrease the resistance developed to 3-lactams when used in combination (and vice versa), although there are conflicting data. Experimentally, aminoglycoside-3-lactam combinations have been shown to prevent the emergence of resistance, whereas double 3-lactam regimens are no better than the individual 3-lactam alone [6]. A double 3-lactam combination is additive and will broaden the empiric coverage. However, the practitioner must feel comfortable with a broad-spectrum penicillin being used as monotherapy if a cephalosporin-resistant organism is the pathogen. It is well documented that the aminoglycosides are nephrotoxic. Those who promote the use of double 3-lactam combinations claim that the risk of using an aminoglycoside outweighs the benefits. We recognize that for most granulocytopenic patients double 3-lactam combinations are effective. However, in most of these cases monotherapy with ceftazidime should be sufficient [7]. The first and fourth EORTC studies [8, 9] and Winston et al. [10] provide strong evidence that aminoglycoside-containing regimens produce better results in patients with severe neutropenia (<100/mm3) or in patients infected with R aeruginosa. The benefit of using an aminoglycoside in these patient populations should outweigh the risk. It is our opinion that the antagonistic potential and the emergence of organisms resistant to 3-lactam antibiotics are reasons to avoid the use of double 3-lactams whenever possible. In addition, aminoglycosides should be used in combination with a broad-spectrum 3-lactam antibiotic in profoundly neutropenic patients or in those infected with P aeruginosa.
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DOI：
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