Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa
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Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa. / Herrmann, Gloria; Yang, Liang; Wu, Hong; Song, Zhijun; Wang, Hengzhuang; Høiby, Niels; Ulrich, Martina; Molin, Søren; Riethmüller, Joachim; Döring, Gerd.
In: The Journal of Infectious Diseases, Vol. 202, No. 10, 15.11.2010, p. 1585-92.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa
AU - Herrmann, Gloria
AU - Yang, Liang
AU - Wu, Hong
AU - Song, Zhijun
AU - Wang, Hengzhuang
AU - Høiby, Niels
AU - Ulrich, Martina
AU - Molin, Søren
AU - Riethmüller, Joachim
AU - Döring, Gerd
PY - 2010/11/15
Y1 - 2010/11/15
N2 - BACKGROUND: Antibiotic combination therapy might be more efficient than single antibiotics to combat Pseudomonas aeruginosa biofilms in the airways of patients with cystic fibrosis. We tested the ability of colistin sulphate-tobramycin combinations and single antibiotics to kill P. aeruginosa biofilms.METHODS: P. aeruginosa biofilms were generated in vitro and in rat lungs. In a pilot study, 5 patients with cystic fibrosis inhaled colistin and then tobramycin for 4 weeks. The changes in P. aeruginosa counts and lung function were assessed before and after therapy.RESULTS: Antibiotic combination therapy significantly reduced the number of P. aeruginosa cells in P. aeruginosa biofilm models in vitro. When rats were challenged with 1 x 10(7) cfu of P. aeruginosa, which was embedded in alginate beads, mortality rates, lung pathologic findings, and bacterial colony-forming unit counts were significantly lower after 7 days in animals receiving antibiotic combination than in animals receiving single antibiotics. In patients with cystic fibrosis, inhaled colistin-tobramycin was well tolerated and resulted in a mean decrease of 2.52 + /- 2.5 log(10) cfu of P. aeruginosa per milliliter of sputum (P = .027). Measurements of forced expiratory volume in 1 s, obtained both before and after the study, did not differ significantly.CONCLUSION: Colistin-tobramycin combinations are more efficient than respective single antibiotics for killing P. aeruginosa in biofilms in vitro, and they significantly reduced P. aeruginosa cell counts in a rat lung infection model and in patients with cystic fibrosis.
AB - BACKGROUND: Antibiotic combination therapy might be more efficient than single antibiotics to combat Pseudomonas aeruginosa biofilms in the airways of patients with cystic fibrosis. We tested the ability of colistin sulphate-tobramycin combinations and single antibiotics to kill P. aeruginosa biofilms.METHODS: P. aeruginosa biofilms were generated in vitro and in rat lungs. In a pilot study, 5 patients with cystic fibrosis inhaled colistin and then tobramycin for 4 weeks. The changes in P. aeruginosa counts and lung function were assessed before and after therapy.RESULTS: Antibiotic combination therapy significantly reduced the number of P. aeruginosa cells in P. aeruginosa biofilm models in vitro. When rats were challenged with 1 x 10(7) cfu of P. aeruginosa, which was embedded in alginate beads, mortality rates, lung pathologic findings, and bacterial colony-forming unit counts were significantly lower after 7 days in animals receiving antibiotic combination than in animals receiving single antibiotics. In patients with cystic fibrosis, inhaled colistin-tobramycin was well tolerated and resulted in a mean decrease of 2.52 + /- 2.5 log(10) cfu of P. aeruginosa per milliliter of sputum (P = .027). Measurements of forced expiratory volume in 1 s, obtained both before and after the study, did not differ significantly.CONCLUSION: Colistin-tobramycin combinations are more efficient than respective single antibiotics for killing P. aeruginosa in biofilms in vitro, and they significantly reduced P. aeruginosa cell counts in a rat lung infection model and in patients with cystic fibrosis.
KW - Administration, Inhalation
KW - Adult
KW - Animals
KW - Anti-Bacterial Agents
KW - Biofilms
KW - Colistin
KW - Cystic Fibrosis
KW - Drug Therapy, Combination
KW - Female
KW - Humans
KW - Lung
KW - Male
KW - Microbial Sensitivity Tests
KW - Pilot Projects
KW - Pseudomonas Infections
KW - Pseudomonas aeruginosa
KW - Rats
KW - Rats, Inbred Lew
KW - Tobramycin
KW - Treatment Outcome
U2 - 10.1086/656788
DO - 10.1086/656788
M3 - Journal article
C2 - 20942647
VL - 202
SP - 1585
EP - 1592
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 10
ER -
ID: 113179749