How do antimicrobial agents lead to resistance in pathogens causing acute respiratory tract infections

Whereas the principles of successful antimicrobial treatment-hit hard, hit early, and combine drugs-are well established for infections like tuberculosis and human immunodeficiency virus infection, they are not as well established for treatment of acute respiratory infections (ARIs) in which the target organisms are typically carried as commensals in the nasopharynx, drug resistance may be all-or-none or incremental, and (except for fluoroquinolones), resistance usually requires acquisition of foreign DNA. For these pathogens, most notably Streptococcus pneumoniae, any use of an effective antibiotic is likely to promote resistance at the population level, but different antimicrobial classes do so in different ways and to different degrees. Data on the effects of different classes on susceptible and nonsusceptible bacterial flora are reviewed, and the consequences for selecting resistance are discussed. It is concluded that, with certain caveats, these considerations support prescribing of high-dose amoxicillin (when necessary) for ARIs, although continued monitoring for the emergence of strains against which this high dose has no effect (increasing minimal inhibitory concentration) is needed. Other strategies, such as reserving certain highly effective antibiotics for use in severe cases and avoiding their routine use in children who are the reservoir of transmission of many ARI pathogens, should be considered. These considerations argue strongly against the use of fluoroquinolones for routine treatment in pediatrics.