Activities of tobramycin and six other antibiotics against Pseudomonas aeruginosa isolates from patients with cystic fibrosis.
The in vitro activity of tobramycin was compared with those of six other antimicrobial agents against 1,240 Pseudomonas aeruginosa isolates collected from 508 patients with cystic fibrosis during pretreatment visits as part of the phase III clinical trials of tobramycin solution for inhalation. The tobramycin MIC at which 50% of isolates are inhibited (MIC(50)) and MIC(90) were 1 and 8 microg/ml, respectively. Tobramycin was the most active drug tested and also showed good activity against isolates resistant to multiple antibiotics. The isolates were less frequently resistant to tobramycin (5.4%) than to ceftazidime (11.1%), aztreonam (11.9%), amikacin (13.1%), ticarcillin (16.7%), gentamicin (19.3%), or ciprofloxacin (20.7%). For all antibiotics tested, nonmucoid isolates were more resistant than mucoid isolates. Of 56 isolates for which the tobramycin MIC was > or = 16 microg/ml and that were investigated for resistance mechanisms, only 7 (12.5%) were shown to possess known aminoglycoside-modifying enzymes; the remaining were presumably resistant by an incompletely understood mechanism often referred to as "impermeability."
Shawar
R M
RM
PathoGenesis Corporation, Department of Pediatrics, University of Washington, and Children's Hospital and Regional Medical Center, Seattle, Washington 98119, USA. rshawar@pathogenesis.com
MacLeod
D L
DL
Garber
R L
RL
Burns
J L
JL
Stapp
J R
JR
Clausen
C R
CR
Tanaka
S K
SK
D042462:4-Quinolones; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000382:microbiology*; D004352:Drug Resistance, Microbial; D006801:Humans; D007769:Lactams; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D014031:Tobramycin / Q000494:pharmacology*
D042462:4-Quinolones; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D007769:Lactams; D014031:Tobramycin