title: Pharmacodynamics of levofloxacin in patients with acute exacerbation of chronic bronchitis.
abstract: OBJECTIVE
  Levofloxacin is a fluoroquinolone antimicrobial agent for which pharmacodynamic relationships between the maximum serum antibiotic concentration (Cmax)/minimum inhibitory concentration (MIC) ratio and/or the area under the serum concentration-time curve during a 24-h dosing period (AUC(0-24))/MIC ratio and clinical and/or microbiological outcomes have been developed. In this study we examined the relationship between the in vitro bacterial susceptibility to levofloxacin, the achieved levofloxacin serum and sputum concentrations, and the in vivo bacterial eradication in patients with acute exacerbations of chronic bronchitis.
  
  
  METHODS
  Thirty patients received levofloxacin, 500 mg/d po for 7 days. Samples of venous blood and sputum for the determination of levofloxacin concentrations were collected on day 1 immediately prior to dosing, and then at 1, 4, 8, 12, and 24 h.
  
  
  RESULTS
  The mean peak concentration in serum (6.5 mg/L) was found 1 h after administration, and at 4 h after administration in sputum (5.1 mg/L). Levofloxacin was always detectable 24 h after administration from both samples. Successful treatment occurred in 90% (27 of 30 patients) when assessed both clinically and bacteriologically. Treatment was successful in eight patients when the AUC(0-24)/MIC ratio was > 40 for serum, and in nine patients when it was > 30 for sputum. Treatment was also successful in seven patients when the Cmax/MIC ratio was > 5.01 for serum, and in nine patients when the Cmax/MIC ratio was > 4.01 for sputum. Treatment was successful in 90% (27 of 30 patients) when the AUC(0-24)/MIC ratio was > 125 for serum and > 100 for sputum, and when Cmax/MIC was > 10.01 for serum and > 8.01 for sputum following the first dose.
  
  
  CONCLUSIONS
  The pharmacodynamics values that we have obtained in sputum with levofloxacin may be used as predictors of therapy outcomes.
authors.affiliation: Department of Pneumology, Unit of Pneumology and Allergology, A. Cardarelli Hospital, Naples, Italy. mcazzola@qubisoft.it
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
authors.forename: Giovanna
authors.initials: G
authors.lastname: Donnarumma
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Tufano
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sanduzzi
authors.forename: Federico
authors.initials: F
authors.lastname: Marchetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
mesh_terms: D000208:Acute Disease; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001991:Bronchitis / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012907:Smoking; D013183:Sputum / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin