Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis.
Pseudomonas aeruginosa endobronchial infection causes significant morbidity and mortality among cystic fibrosis patients. Microbiology results from two multicenter, double-blind, placebo-controlled trials of inhaled tobramycin in cystic fibrosis were monitored for longitudinal changes in sputum microbial flora, antibiotic susceptibility, and selection of P. aeruginosa isolates with decreased tobramycin susceptibility. Clinical response was examined to determine whether current susceptibility standards are applicable to aerosolized administration. Treatment with inhaled tobramycin did not increase isolation of Burkholderia cepacia, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans; however, isolation of Candida albicans and Aspergillus species did increase. Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin group compared with that in the placebo group, there was no evidence of selection for the most resistant isolates to become most prevalent. The definition of resistance for parenteral administration does not apply to inhaled tobramycin: too few patients had P. aeruginosa with a tobramycin MIC >/=16 microgram/mL to define a new break point on the basis of clinical response.
Burns
J L
JL
Division of Infectious Disease, Children's Hospital and Regional Medical Center, 4800 Sand Point Way N.E., CH-32, Seattle, WA 98105, USA. jburns@chmc.org
Van Dalfsen
J M
JM
Shawar
R M
RM
Otto
K L
KL
Garber
R L
RL
Quan
J M
JM
Montgomery
A B
AB
Albers
G M
GM
Ramsey
B W
BW
Smith
A L
AL
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001230:Aspergillus / Q000187:drug effects / Q000302:isolation & purification; D001419:Bacteria / Q000187:drug effects / Q000302:isolation & purification; D002176:Candida albicans / Q000187:drug effects / Q000302:isolation & purification; D002648:Child; D003550:Cystic Fibrosis / Q000382:microbiology*; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D005541:Forced Expiratory Volume; D006801:Humans; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013183:Sputum / Q000382:microbiology*; D014031:Tobramycin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D014031:Tobramycin