Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa

Gloria Herrmann; Liang Yang; Hong Wu; Zhijun Song; Hengzhuang Wang; Niels Høiby; Martina Ulrich; Søren Molin; Joachim Riethmüller; Gerd Döring

doi:10.1086/656788

Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa

Gloria Herrmann, Liang Yang, Hong Wu, Zhijun Song, Hengzhuang Wang, Niels Høiby, Martina Ulrich, Søren Molin, Joachim Riethmüller, Gerd Döring

Department of Immunology and Microbiology

131 Citations (Scopus)

Abstract

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 × 10⁷ 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 log₁₀ 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.

Original language	English
Journal	Journal of Infectious Diseases
Volume	202
Issue number	10
Pages (from-to)	1585-92
Number of pages	8
ISSN	0022-1899
DOIs	https://doi.org/10.1086/656788
Publication status	Published - 15 Nov 2010

Keywords

Administration, Inhalation
Adult
Animals
Anti-Bacterial Agents
Biofilms
Colistin
Cystic Fibrosis
Drug Therapy, Combination
Female
Humans
Lung
Male
Microbial Sensitivity Tests
Pilot Projects
Pseudomonas Infections
Pseudomonas aeruginosa
Rats
Rats, Inbred Lew
Tobramycin
Treatment Outcome

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10.1086/656788

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title = "Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa",

abstract = "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 × 107 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 log10 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.",

keywords = "Administration, Inhalation, Adult, Animals, Anti-Bacterial Agents, Biofilms, Colistin, Cystic Fibrosis, Drug Therapy, Combination, Female, Humans, Lung, Male, Microbial Sensitivity Tests, Pilot Projects, Pseudomonas Infections, Pseudomonas aeruginosa, Rats, Rats, Inbred Lew, Tobramycin, Treatment Outcome",

author = "Gloria Herrmann and Liang Yang and Hong Wu and Zhijun Song and Hengzhuang Wang and Niels H{\o}iby and Martina Ulrich and S{\o}ren Molin and Joachim Riethm{\"u}ller and Gerd D{\"o}ring",

year = "2010",

month = nov,

day = "15",

doi = "10.1086/656788",

language = "English",

volume = "202",

pages = "1585--92",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

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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 × 107 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 log10 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 × 107 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 log10 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

SN - 0022-1899

VL - 202

SP - 1585

EP - 1592

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 10

ER -

Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa

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Keywords

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