n-6 polyunsaturated fatty acids enhance the activities of ceftazidime and amikacin in experimental sepsis caused by multidrug-resistant Pseudomonas aeruginosa.
Recent in vitro and ex vivo studies disclosed an enhancement of the activity of antimicrobials on multidrug-resistant Pseudomonas aeruginosa by n-6 polyunsaturated fatty acids (PUFAS); therefore their effect was evaluated in experimental sepsis in 60 rabbits. Solutions of gamma-linolenic acid (GLA) and arachidonic acid (AA) were administered intravenously with ceftazidime and amikacin in rabbits with sepsis caused by one multidrug-resistant isolate. Therapy was started after bacterial challenge in five groups comprising 12 animals in each group: A, normal saline; B, antimicrobials; C, 99% ethanol and antimicrobials; D, GLA and antimicrobials; and E, AA and antimicrobials. Blood was sampled for the estimation of levels of endotoxins in serum (lipopolysaccharide), leukocytes, tumor necrosis factor alpha (TNF-alpha) and antimicrobials. Animals were sacrificed 210 min after bacterial challenge for tissue cultures. All animals had considerable endotoxemia and evolved leukopenia. The number of viable cells in blood, lung, and mesenteric lymph nodes was significantly reduced in groups D and E compared to that in other groups. Levels of antimicrobials in serum were inadequate to achieve bacterial killing due to the level of resistance. n-6 PUFAs did not influence TNF-alpha. It is concluded that intravenous coadministration of n-6 PUFAs and antimicrobials enhanced antimicrobial bacterial killing in experimental sepsis caused by multidrug-resistant P. aeruginosa.
Giamarellos-Bourboulis
Evangelos J
EJ
4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece. giamarel@internet.gr
Mouktaroudi
Maria
M
Adamis
Theodoros
T
Koussoulas
Vassilios
V
Baziaka
Fotini
F
Perrea
Despina
D
Karayannacos
Panayotis E
PE
Giamarellou
Helen
H
D000583:Amikacin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016718:Arachidonic Acid / Q000494:pharmacology; D002442:Ceftazidime / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D005231:Fatty Acids, Unsaturated / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000097:blood; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011817:Rabbits; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005231:Fatty Acids, Unsaturated; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; D000583:Amikacin; D002442:Ceftazidime