Abstract
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."
MeSH Terms
4-Quinolones
Anti-Bacterial Agents/pharmacology
Anti-Infective Agents/pharmacology
Cystic Fibrosis/microbiology
Drug Resistance, Microbial
Humans
Lactams
Microbial Sensitivity Tests
Phenotype
Pseudomonas aeruginosa/drug effects,genetics,isolation & purification
Tobramycin/pharmacology
Chemicals
4-Quinolones
Anti-Bacterial Agents
Anti-Infective Agents
Lactams
Tobramycin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shawar R M
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
Garber R L
Burns J L
Stapp J R
Clausen C R
Tanaka S K
References (26)
26 references, click to expand
-
Multiple of isolates of Pseudomonas aeruginosa with differing antimicrobial susceptibility patterns from patients with cystic fibrosis.
J Infect Dis. 1979 Dec;140(6):873-80
PMID: 120383
-
Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis.
J Infect Dis. 1999 May;179(5):1190-6
PMID: 10191222
-
Comparison between the in-vitro activity of new agents on Pseudomonas aeruginosa isolates from cystic fibrosis patients and other chronic infections.
J Antimicrob Chemother. 1984 Jul;14(1):25-9
PMID: 6434504
-
Resistance surveillance programs and the incidence of gram-negative bacillary resistance to amikacin from 1967 to 1985.
Am J Med. 1986 Jun 30;80(6B):22-8
PMID: 3089003
-
In vitro susceptibility of Pseudomonas aeruginosa from bacteremic and fibrocystic patients to four quinolones and five other antipseudomonal antibiotics.
Scand J Infect Dis. 1988;20(5):525-9
PMID: 3146807
-
Comparison of inhibitory and bactericidal activity of antipseudomonal antibiotics against Pseudomonas aeruginosa isolates from cystic fibrosis patients.
Chemotherapy. 1990;36(3):222-9
PMID: 2110878
-
In vitro activity of E-1040, a 3-substituted cephalosporin, against pathogens from cystic fibrosis sputum.
Antimicrob Agents Chemother. 1990 Jul;34(7):1366-70
PMID: 2386368
-
Functional role of mucoid exopolysaccharide (alginate) in antibiotic-induced and polymorphonuclear leukocyte-mediated killing of Pseudomonas aeruginosa.
Infect Immun. 1991 Jan;59(1):302-8
PMID: 1898898
-
In vitro activity of tosufloxacin, a new quinolone, against respiratory pathogens derived from cystic fibrosis sputum.
Antimicrob Agents Chemother. 1990 Nov;34(11):2223-7
PMID: 2073112
-
Resistance to ciprofloxacin of respiratory pathogens in patients with cystic fibrosis.
Med J Aust. 1992 Jan 6;156(1):20-4
PMID: 1734188
-
Correlation between aminoglycoside resistance profiles and DNA hybridization of clinical isolates.
Antimicrob Agents Chemother. 1991 Nov;35(11):2253-61
PMID: 1803998
-
New epidemiological data on resistance to netilmicin and other aminoglycosides.
J Chemother. 1991 Dec;3(6):352-6
PMID: 1819617
-
The changing epidemiology of cystic fibrosis.
J Pediatr. 1993 Jan;122(1):1-9
PMID: 8419592
-
Emergence of antibiotic resistance amongst Pseudomonas aeruginosa isolates from patients with cystic fibrosis.
J Antimicrob Chemother. 1993 Jun;31(6):919-26
PMID: 8360129
-
Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF Center.
APMIS. 1994 Sep;102(9):674-80
PMID: 7946270
-
Comparative antimicrobial activity of FK037, cefpirome, ceftazidime and cefepime against aminoglycoside-sensitive and aminoglycoside-resistant Pseudomonas aeruginosa and Pseudomonas spp.
Chemotherapy. 1994;40(6):391-8
PMID: 7842822
-
Mechanism of amikacin resistance in Pseudomonas aeruginosa isolates from patients with cystic fibrosis.
Diagn Microbiol Infect Dis. 1995 Aug;22(4):331-6
PMID: 8582138
-
The most frequently occurring aminoglycoside resistance mechanisms--combined results of surveys in eight regions of the world. The Aminoglycoside Resistance Study Groups.
J Chemother. 1995 Jun;7 Suppl 2:17-30
PMID: 8622108
-
Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia.
Microbiol Rev. 1996 Sep;60(3):539-74
PMID: 8840786
-
Antibiotic susceptibility of multiply resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis, including candidates for transplantation.
Clin Infect Dis. 1996 Sep;23(3):532-7
PMID: 8879776
-
The most frequent aminoglycoside resistance mechanisms--changes with time and geographic area: a reflection of aminoglycoside usage patterns? Aminoglycoside Resistance Study Groups.
Clin Infect Dis. 1997 Jan;24 Suppl 1:S46-62
PMID: 8994779
-
Comparison of antibacterial activities of meropenem and six other antimicrobials against Pseudomonas aeruginosa isolates from North American studies and clinical trials.
Clin Infect Dis. 1997 Feb;24 Suppl 2:S191-6
PMID: 9126693
-
Microbiologic data overview of Italian cystic fibrosis patients.
Eur J Epidemiol. 1997 Apr;13(3):323-7
PMID: 9258532
-
Microbiology of sputum from patients at cystic fibrosis centers in the United States.
Clin Infect Dis. 1998 Jul;27(1):158-63
PMID: 9675470
-
Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group.
N Engl J Med. 1999 Jan 7;340(1):23-30
PMID: 9878641
-
Aminoglycoside resistance in Pseudomonas aeruginosa isolated from cystic fibrosis patients.
Am J Clin Pathol. 1984 Jun;81(6):742-7
PMID: 6428216