Clinical failures: the tip of the iceberg?

In pneumococcal meningitis, it is well accepted that resistance in Streptococcus pneumoniae compromises clinical outcome. However, the clinical impact of increasing resistance on community-acquired respiratory tract infections (RTIs) is less clear. Bacteriological eradication should be the aim of antimicrobial therapy. The pharmacodynamics (potency and pharmacokinetics) of an antimicrobial agent against the infecting pathogen can be used to predict the potential for bacterial eradication. Surveillance of clinical isolates from community-acquired RTIs shows that, in many countries, there is a trend towards an increasing prevalence of drug-resistant S. pneumoniae. Results from a number of published clinical trials suggest that resistance has not compromised the clinical efficacy of aminopenicillins when used at the correct dose. However, emerging data indicate that resistance is compromising the efficacy of some other routinely used antimicrobials. There are reports of clinical and bacteriological failure with macrolides and fluoroquinolones in patients with community-acquired pneumonia. Recent retrospective analyses and increasing sporadic reports of clinical failure with these agents may be more representative of the true situation. These reports suggest a need to reassess current empirical therapeutic recommendations for the treatment of community-acquired RTIs.