Professor File began by looking at the properties of levofloxacin, with its excellent activity against key respiratory pathogens including atypicals.
Levofloxacin has excellent pharmacokinetic features, with very high bioavailability, a relatively long half-life, once-daily dosing, and exceptional penetration into respiratory tissues and secretions, including both intracellular and extracellular sites.
A study with over 500 patients comparing levofloxacin as monotherapy versus IV ceftriaxone or oral cefuroxime axetil plus or minus erythromycin in community-acquired pneumonia, revealed levofloxacin (-treated patients) achieved better bacteriological response correlating with an improved clinical response rate of 96% and a lower mortality rate. In addition, it had a better safety profile, with an adverse event rate of 5.8% compared to 8.5% for the comparators.
A second study compared levofloxacin with azithromycin plus ceftriaxone, with the bacteriological and clinical responses comparable. However, levofloxacin achieved a much higher rate of clinical cure. Another study with over 1,000 patients, demonstrated a 96% bacteriological response rate for levofloxacin and a 94% clinical response rate, again with a very low AE rate.
Increasing resistance to doxycycline and the macrolides has lead the Infectious Disease Society of America to include fluoroquinolones with enhanced activity for S. pneumoniae in the treatment of community-acquired pneumonia. For empiric treatment of outpatients, physicians should use either a fluoroquinolone, macrolide or doxycycline, with fluoroquinolones recommended for suspected DRSP, doxycycline for young adults and amoxicillin-clavulanic acid for suspected aspiration pneumonia.
Selection of the best antibiotic should be based on factors including regional resistance patterns, and patient characteristics such as age and any associated co-morbidity.
IDSA guidelines for empiric treatment of hospitalized patients with CAP recommend either monotherapy with a fluoroquinolone which has enhanced activity for S. pneumoniae or a combination of third-generation cephalosporin plus macrolide to cover atypicals. ICU patients should be managed with either a macrolide or fluoroquinolone in combination with a cephalosporin or -lactam/ -lactamase inhibitor.
Using third-generation cephalosporins as the reference, the 30-day mortality rate for hospitalized CAP patients treated with a second- or third-generation cephalosporin plus a macrolide was reduced by 26% for a hazard ratio of 0.74. An even better outcome was associated with fluoroquinolone monotherapy which achieved a reduction in mortality of 36% and a hazard ratio of 0.64. These data outline the rationale recommending fluoroquinolone monotherapy when treating hospitalized patients.