Giamarellou H
Am J Med. 1986 Jun 30;80(6B):126-37. doi: 10.1016/0002-9343(86)90490-0.
Combination antibiotic therapy has been used mainly to broaden the antibacterial spectrum and prevent the development of resistance. Antibiotic combinations proven to be synergistic in vitro are associated with a significantly better in vivo response, particularly in the compromised host in whom traditional treatment combines an antipseudomonal penicillin plus an aminoglycoside. Several investigators have examined combining new agents, such as the third-generation cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefoperazone, and moxalactam), aztreonam, or the ureidopenicillins, with amikacin. When compared with combinations of an older cephalosporin, carbenicillin or ticarcillin, plus gentamicin or tobramycin, these newer combinations produce higher rates of clinically meaningful synergy and rapid enhancement of in vitro bactericidal activity against the difficult-to-treat Enterobacteriaceae (i.e., Serratia, Citrobacter, Enterobacter, Providencia, and indole-positive Proteus species). This effect, without any evidence of antagonism, has been reported even for strains moderately or completely resistant to the former antibiotics. Unsatisfactory and unpredictable synergistic interactions against both resistant and susceptible strains of Pseudomonas aeruginosa--the most difficult nosocomial pathogen to treat--have been noted with combinations of tobramycin or gentamicin plus cefotaxime, moxalactam, or cefoperazone. Conversely, the use of amikacin plus various beta-lactams against multi-resistant strains is more frequently synergistic. Agents have been observed to exhibit such synergy in the following order of activity, from most to least synergistic: ceftazidime, ceftriaxone, moxalactam, aztreonam, cefotaxime, azlocillin, cefoperazone, cefsulodin, and carbenicillin. The combination of amikacin plus imipenem or ciprofloxacin against strains of P. aeruginosa resistant to the former and moderately resistant to the latter was recently reported to have a low probability of synergy; the combination of two of the newer beta-lactams had mostly an unpredictable or even antagonistic result. In vitro studies have also demonstrated that high concentrations of the antipseudomonal penicillins can inactivate the aminoglycosides. Among the latter compounds, the inactivation order, from most to least inactivated, was as follows: tobramycin, gentamicin, netilmicin, and amikacin. To date, the reports of aminoglycoside inactivation by the newer cephalosporins have been rather contradictory; only moxalactam has been shown produce a significant decrease in activity.
联合抗生素治疗主要用于扩大抗菌谱和防止耐药性的产生。已证实在体外具有协同作用的抗生素联合用药与显著更好的体内反应相关，特别是在传统治疗采用抗假单胞菌青霉素加氨基糖苷类药物的免疫功能低下宿主中。几位研究人员研究了将新的药物，如第三代头孢菌素（头孢噻肟、头孢曲松、头孢唑肟、头孢他啶、头孢哌酮和拉氧头孢）、氨曲南或脲基青霉素，与阿米卡星联合使用。与 older cephalosporin、羧苄西林或替卡西林加庆大霉素或妥布霉素的联合用药相比，这些新的联合用药产生更高的具有临床意义的协同作用率，并能快速增强对难治疗的肠杆菌科细菌（即沙雷菌属、柠檬酸杆菌属、肠杆菌属、普罗威登斯菌属和吲哚阳性变形杆菌属）的体外杀菌活性。即使对于对前一种抗生素中度或完全耐药的菌株，也报道了这种没有任何拮抗证据的效果。对于铜绿假单胞菌（最难治疗的医院病原体）的耐药和敏感菌株，妥布霉素或庆大霉素加头孢噻肟、拉氧头孢或头孢哌酮的联合用药已被注意到有不令人满意且不可预测的协同相互作用。相反，阿米卡星加各种β-内酰胺类药物用于多重耐药菌株时更常具有协同作用。已观察到药物按以下活性顺序表现出这种协同作用，从协同作用最强到最弱：头孢他啶、头孢曲松、拉氧头孢、氨曲南、头孢噻肟、阿洛西林、头孢哌酮、头孢磺啶和羧苄西林。最近报道，阿米卡星加亚胺培南或环丙沙星用于对前者耐药且对后者中度耐药的铜绿假单胞菌菌株时，协同作用的可能性较低；两种较新的β-内酰胺类药物联合使用大多产生不可预测甚至拮抗的结果。体外研究还表明，高浓度的抗假单胞菌青霉素可使氨基糖苷类药物失活。在后者化合物中，失活顺序从失活最多到最少如下：妥布霉素、庆大霉素、奈替米星和阿米卡星。迄今为止，关于较新的头孢菌素使氨基糖苷类药物失活的报道相当矛盾；仅拉氧头孢已被证明会使活性显著降低。
