Sputum antibiotic concentrations: implications for treatment of cystic fibrosis lung infection.
BACKGROUND
The success of antibiotic therapy may be predicted based on the achievement of pharmacodynamic indices (PDIs), which are determined by the susceptibility of the infecting bacteria and the concentrations of antibiotics achieved at the site of infection. The aim of this study was to determine whether PDIs associated with clinical effectiveness for ceftazidime and tobramycin were achieved at the site of infection in the lungs of cystic fibrosis (CF) patients following intravenous administration during treatment of an acute exacerbation.


METHODS
Serum and sputum samples were collected from 14 CF patients and the concentration of both antibiotics in the samples determined. The susceptibility of bacteria cultured from sputum samples to both antibiotics alone and in combination was also determined.


RESULTS
A total of 22 Pseudomonas aeruginosa isolates and 4 Burkholderia cepacia complex isolates were cultured from sputum samples with 55% and 4% of isolates susceptible to ceftazidime and tobramycin, respectively. Target PDIs for ceftazidime and tobramycin, an AUC/MIC ratio of 100 and a C(max)/MIC ratio of 10, respectively, were not achieved in serum or sputum simultaneously or even individually for any patient. Although the combination of ceftazidime and tobramycin was synergistic against 20 of the 26 isolates cultured, the concentrations of both antibiotics required for synergy were achieved simultaneously in only 38% of serum and 14% of sputum samples.


CONCLUSIONS
Key PDIs associated with clinical effectiveness for ceftazidime and tobramycin were not achieved at the site of infection in the lungs of CF patients.
Moriarty
T F
TF
The Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, Belfast, UK.
McElnay
J C
JC
Elborn
J S
JS
Tunney
M M
MM
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D019121:Burkholderia Infections / Q000188:drug therapy*; D016956:Burkholderia cepacia / Q000187:drug effects; D002442:Ceftazidime / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007262:Infusions, Intravenous; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy*; D013183:Sputum / Q000187:drug effects / Q000382:microbiology; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D002442:Ceftazidime; D014031:Tobramycin