Selection of antimicrobial agents should be based upon a number of factors, including awareness of likely pathogens, the in vitro activity of a drug, its pharmacokinetics, clinical experience and how well it is tolerated by all patients.

With regard to community-acquired pneumonia, ambulatory patients are likely to be infected with S. pneumoniae, M. pneumoniae, and H. influenzae. In more severe cases, additional pathogens include Legionella spp., and in patients requiring ICU admission, Gram-negative bacilli, S. aureus and Pseudomonas aeruginosa can be involved.

The clinician also needs to look at the in vitro activity of potential antimicrobials. Levofloxacin, shown here in comparison with ceftriaxone, azithromycin, and ciprofloxacin, is very active against all of the major RTI pathogens, including atypicals such as Legionella and Mycoplasma.

Pharmacokinetics are important determinants of an antimicrobial’s efficacy. The bioavailability of respiratory fluoroquinolones is very high, ranging from a low of 70% for grepafloxacin to an exceptional 99% for levofloxacin. Research has demonstrated Cmax and AUC to be important for the fluoroquinolones, with levofloxacin possessing the highest values for these two parameters among the newer agents.

Of even greater importance is the question of whether the drug is effective in clinical trials. Levofloxacin has been shown to fulfill this criterion, with a trial comparing levofloxacin to ceftriaxone and/or cefuroxime plus or minus erythromycin demonstrating a significant benefit in favor of levofloxacin.

Other data from 12,945 patients has confirmed that treatment with a fluoroquinolone is associated with an improved outcome compared to treatment with a 3rd generation cephalosporin and comparable outcome to a 2nd/3rd generation cephalosporin in combination with a macrolide.