Antibacterial synergism of polymyxin B nonapeptide and hydrophobic antibiotics in experimental gram-negative infections in mice.
Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diaminobutyric acid from polymyxin B, is considerably less toxic, lacks bactericidal activity, and retains its ability to render gram-negative bacteria susceptible to several antibiotics by permeabilizing their outer membranes. The peptide rendered all 53 polymyxin-susceptible strains tested more susceptible to novobiocin, lowering the MIC of novobiocin eightfold or more. The combination of polymyxin B nonapeptide with novobiocin or with erythromycin administered intraperitoneally in multiple doses synergistically protected mice infected with gram-negative bacteria. This combination may be clinically useful because of the apparent rarity of the acquisition of resistance.
Ofek
I
I
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Cohen
S
S
Rahmani
R
R
Kabha
K
K
Tamarkin
D
D
Herzig
Y
Y
Rubinstein
E
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004917:Erythromycin / Q000494:pharmacology; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009675:Novobiocin / Q000494:pharmacology; D011112:Polymyxin B / Q000031:analogs & derivatives* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D009675:Novobiocin; D004917:Erythromycin; C038934:polymyxin B nonapeptide; D011112:Polymyxin B