Neu H C
Am J Med. 1985 Jun 28;78(6B):17-22. doi: 10.1016/0002-9343(85)90358-4.
Perusal of the various journals devoted to antimicrobial agents and to the chemotherapy of infectious diseases reveals an increasing number of articles devoted to the analysis of the pharmacology of antimicrobial agents and the relationships of antimicrobial activity and pharmacologic properties. However, most attention to the pharmacokinetic properties of antimicrobial agents in the past decade has focused on the toxic properties of these agents, and there has been little work devoted to improving methods of administration. The availability of nontoxic antibiotics that are extremely active at low concentrations and of agents with markedly extended half-lives should cause us to reevaluate some of our current dosing practices. In many ways, a major adverse influence on appropriate antimicrobial therapy of ordinary infections has been the febrile neutropenic patient. Lessons learned from the care of these patients are inappropriately applied to the treatment of other patients. The neutropenic patient requires frequent administration of antibiotics at maximally tolerated doses. Many patients at risk for infection do not require antimicrobial therapeutic programs in which the antibiotic always exceeds the minimal inhibitory concentration. Indeed, the concept that the drug must be present in the serum well above the minimal inhibitory concentration for the entire interval of infection is derived from studies of neutropenic patients infected with Pseudomonas aeruginosa. Increasing resistance of hospital-acquired bacteria to older antibacterial agents will alter the initial and subsequent selection of antimicrobial agent. Combination drug therapy, which has a prominent role in the neutropenic patient, frequently results in greater cost to the health care system than is seen with single agents that are active against resistant bacteria. There are clear areas in which new antibacterial agents will be beneficial. We may be at a stage in which use of the older agents can no longer be viewed as the best clinically and economically. Better use of twice- or once-daily dosing programs of new agents coupled with use of intramuscular and oral administration of antibiotics can help reduce nosocomial infections that contribute to rising health costs.
翻阅各种专门论述抗菌药物及传染病化疗的期刊可以发现，致力于分析抗菌药物药理学以及抗菌活性与药理特性之间关系的文章越来越多。然而，在过去十年里，对抗菌药物药代动力学特性的关注大多集中在这些药物的毒性方面，而致力于改进给药方法的研究却很少。低浓度时活性极高的无毒抗生素以及半衰期显著延长的药物的出现，应该促使我们重新评估目前的一些给药做法。在许多方面，发热性中性粒细胞减少患者对普通感染的适当抗菌治疗产生了重大不利影响。从这些患者的护理中吸取的经验教训被不适当地应用于其他患者的治疗。中性粒细胞减少患者需要以最大耐受剂量频繁使用抗生素。许多有感染风险的患者并不需要抗菌治疗方案中抗生素总是超过最低抑菌浓度。事实上，药物必须在整个感染期间血清中浓度远高于最低抑菌浓度的这一概念，源自对感染铜绿假单胞菌的中性粒细胞减少患者的研究。医院获得性细菌对较老抗菌药物的耐药性不断增加，将改变抗菌药物的初始选择和后续选择。联合药物治疗在中性粒细胞减少患者中发挥着重要作用，但与对耐药菌有活性的单一药物相比，往往会给医疗保健系统带来更高的成本。在一些明确的领域，新型抗菌药物将大有裨益。我们可能正处于一个阶段，即使用较老的药物在临床和经济上已不再被视为最佳选择。更好地利用新型药物的每日两次或一次给药方案，再结合肌肉注射和口服抗生素的使用，有助于减少导致医疗成本上升的医院感染。
