Chow A W, Hall C B, Klein J O, Kammer R B, Meyer R D, Remington J S
Vancouver General Hospital, University of British Columbia, Canada.
Clin Infect Dis. 1992 Nov;15 Suppl 1(Suppl 1):S62-88. doi: 10.1093/clind/15.supplement_1.s62.
These guidelines deal with the evaluation of anti-infective drugs for the treatment of respiratory tract infections. Five clinical entities are described: streptococcal pharyngitis and tonsillitis, otitis media, sinusitis, bronchitis, and pneumonia. A wide variety of microorganisms are potentially pathogenetic in these diseases; these guidelines focus on the bacterial infections. Inclusion of a patient in a trial of a new drug is based on the clinical entity, with the requirement that a reasonable attempt will be made to establish a specific microbial etiology. Microbiologic evaluation of efficacy requires isolation of the pathogen and testing for in vitro susceptibility. Alternatively, surrogate markers may be used to identify the etiologic agent. The efficacy of new drugs is evaluated with reference to anticipated response rates. Establishment of the microbial etiology of respiratory tract infections is hampered by the presence of "normal flora" of the nose, mouth, and pharynx, which may include asymptomatic carriage of potential pathogens. This issue is addressed for each category of infection described. For example, it is suggested that for initial phase 2 trials of acute otitis media and acute sinusitis tympanocentesis or direct sinus puncture be used to collect exudate for culture. Acute exacerbations of chronic bronchitis also present difficulties in the establishment of microbial etiology. These guidelines suggest that clinical trials employ an active control drug but leave open the possibility of a placebo-controlled trial. For pneumonia, the guidelines suggest the identification and enrollment of patients by the clinical type of pneumonia, e.g., atypical pneumonia or acute bacterial pneumonia, rather than by etiologic organism or according to whether it was community or hospital acquired. For each respiratory infection, the clinical response is judged as cure, failure, or indeterminate. Clinical improvement is not acceptable unless quantitative response measures can be applied.
这些指南涉及用于治疗呼吸道感染的抗感染药物的评估。文中描述了五种临床病症：链球菌性咽炎和扁桃体炎、中耳炎、鼻窦炎、支气管炎和肺炎。在这些疾病中，多种微生物都可能具有致病性；这些指南聚焦于细菌感染。将患者纳入新药试验是基于临床病症，要求合理尝试确定特定的微生物病因。疗效的微生物学评估需要分离病原体并进行体外药敏试验。或者，也可使用替代标志物来识别病原体。参照预期的有效率来评估新药的疗效。呼吸道感染微生物病因的确定受到鼻、口和咽部“正常菌群”的影响，这些“正常菌群”可能包括潜在病原体的无症状携带。针对所描述的每类感染都探讨了这个问题。例如，建议在急性中耳炎和急性鼻窦炎的2期初始试验中，采用鼓膜穿刺术或直接鼻窦穿刺术收集渗出液进行培养。慢性支气管炎的急性加重在确定微生物病因方面也存在困难。这些指南建议临床试验采用活性对照药物，但也保留了进行安慰剂对照试验的可能性。对于肺炎，指南建议根据肺炎的临床类型，如非典型肺炎或急性细菌性肺炎，而不是根据病原体或是否为社区获得性或医院获得性来识别和纳入患者。对于每种呼吸道感染，临床反应判定为治愈、失败或不确定。除非能够应用定量反应指标，否则临床改善不能视为有效。
