Garau Javier
Department of Medicine, Hospital Mútua de Terrassa, Barcelona, Spain.
Int J Infect Dis. 2003 Mar;7 Suppl 1:S5-12. doi: 10.1016/s1201-9712(03)90065-8.
Evidence from studies in otitis media, acute bacterial sinusitis and acute exacerbations of chronic bronchitis indicate that clinical efficacy is dependent on bacterial eradication. Failure to eradicate bacterial pathogens increases the potential for clinical failure, incurring further costs, and may also select and maintain bacteria that are resistant to a wide range of antimicrobials. Bacteriologically confirmed clinical failures have been reported in pneumococcal pneumonia with both macrolides and older fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin). These failures were due to the involvement of resistant pathogens (macrolides) or suboptimal pharmacokinetics/pharmacodynamics (PK/PD) (quinolones). However, persistent positive blood cultures have not been reported during therapy with adequate doses of benzylpenicillins or aminopenicillins. Treatment failure, driven by the failure to eradicate pathogens, leads to both economic and environmental costs, hospitalization being the major cost driver. Failure to achieve bacterial eradication may also lead to the development and spread of resistance. Different types of antimicrobials appear to be driving resistance to different extents, and this may be due to suboptimal PK/PD. In conclusion, factors to consider when prescribing include an accurate diagnosis, knowledge of local epidemiology, the role of PK/PD principles in antimicrobial choice, clinical outcomes in relation to bacteriologic efficacy, and resistance and its bacteriologic and clinical impact. The vicious cycle of infection, inappropriate therapy, bacteriologic failure, selection/spread of resistance and further infection needs to be broken by the use of appropriate treatments to achieve bacterial eradication.
中耳炎、急性细菌性鼻窦炎和慢性支气管炎急性加重期的研究证据表明，临床疗效取决于细菌清除。未能清除细菌病原体增加了临床治疗失败的可能性，会产生更多费用，还可能选择并留存对多种抗菌药物耐药的细菌。在肺炎球菌肺炎中，已报道大环内酯类药物和较老的氟喹诺酮类药物（环丙沙星、氧氟沙星和左氧氟沙星）均出现了细菌学确诊的临床治疗失败情况。这些治疗失败是由于耐药病原体（大环内酯类）的参与或药代动力学/药效学（PK/PD）不理想（喹诺酮类）。然而，在使用足够剂量的苄青霉素或氨基青霉素治疗期间，尚未报道血培养持续呈阳性的情况。因未能清除病原体导致的治疗失败会带来经济和环境成本，住院是主要的成本驱动因素。未能实现细菌清除还可能导致耐药性的产生和传播。不同类型的抗菌药物似乎在不同程度上推动了耐药性，这可能是由于PK/PD不理想所致。总之，开药时需要考虑的因素包括准确的诊断、当地流行病学知识、PK/PD原则在抗菌药物选择中的作用、与细菌学疗效相关的临床结果以及耐药性及其细菌学和临床影响。需要通过使用适当的治疗方法来实现细菌清除，从而打破感染、不适当治疗、细菌学治疗失败、耐药性选择/传播以及进一步感染的恶性循环。
