gramicidin-a and Bacterial-Infections

In a randomized trial, 55 patients with acute external otitis were treated with either topical framycitin/gramicidin (Sofradex) or oxytetracycline/hydrocortisone (Terracortril) with polymyxin B (TPB) ear-drops for 1 week. Staphylococcus aureus and Pseudomonas pyocyanea were the bacteria most frequently found in the ear canal; 78% of the patients were cured. However, no significant differences in therapy were found when either of the preparations was used. S. aureus seemed to be most resistant to treatment, while P. pyocyanea was less of a therapeutic problem. Additionally, previous episodes of external otitis or other skin diseases did not seem to influence any treatment given.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Bacterial Infections; Child; Clinical Trials as Topic; Dexamethasone; Drug Combinations; Ear Canal; Female; Framycetin; Gramicidin; Humans; Hydrocortisone; Male; Middle Aged; Otitis Externa; Oxytetracycline; Polymyxin B; Polymyxins; Pseudomonas; Random Allocation; Staphylococcus aureus

A safety and efficacy study comparing the clinical and bacteriologic effectiveness of trimethoprim-sulfacetamide-polymyxin B-neomycin-gramicidin in a group of patients with surface ocular bacterial infections was conducted. The results demonstrated TSP to be as effective as the other solution (both clinically and bacteriologically), with fewer adverse experiences. A second study was conducted comparing TSP with trimethoprim-polymyxin B (TP) and found TP to be superior to TSP in effecting bacteriologic cures. Clinical response was similar in both groups, and the low incidence of mild adverse experiences was approximately the same. It appears that the combination of trimethoprim with polymyxin B is safe and highly efficacious, both clinically and microbiologically, for the treatment of surface ocular bacterial infections.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Blepharitis; Child; Conjunctivitis, Bacterial; Double-Blind Method; Drug Therapy, Combination; Eyelid Diseases; Female; Gramicidin; Humans; Male; Middle Aged; Neomycin; Ophthalmic Solutions; Polymyxin B; Polymyxins; Sulfacetamide; Trimethoprim

48 patients witha diagnosis of presumptive bacterial conjunctivitis were assessed. They had been treated with either trimethoprim-polymyxin or neomycin-polymyxin-gramicidin eye drops in a randomised double-blind trial. There were 24 patients in each treatment group. There were no significant differences between the two preparations proved with regard to the eradication of organisms or clinical improvement, and both preparations proved to be very effective. Patient compliance was good and no adverse reactions were encountered with either preparation.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Child; Clinical Trials as Topic; Conjunctivitis; Double-Blind Method; Drug Combinations; Gramicidin; Humans; Middle Aged; Neomycin; Polymyxins; Random Allocation; Trimethoprim

Georgy Gause (1910-1986) is best known for his contribution to ecology and evolutionary theory. His book "The Struggle for Existence" (1934) inspired generations of ecologists. Yet his scientific interests were diverse, embracing many aspects of the life sciences and medicine. The most notable shift in his research took place in the early 1940s when he began to study antibiotics and discovered Gramicidin S. Superficially, this shift looked like an attempt to switch from purely theoretical to applied research during the years of World War II, but Gause's decision may also have been seriously affected by the "Great Purge" and the growth of Lysenkoism. Personal factors played a significant role in his career too. In this article, we propose four factors which drove Gause to switch his focus from ecology to antibiotics: the inner logic of his scientific research, Stalin's science policy and the growth of Lysenkoism, the sociopolitical influence of World War II, and personal relationships. We will also show how all these factors are interdependent to some extent.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biological Evolution; Ecology; Gramicidin; History, 20th Century; Humans; USSR

A linear peptide, gramicidin A (GA), folds into a β(6.3) -helix, functions as an ion channel in the cell membrane, and exerts antibacterial activity. Herein we describe the rational design, synthesis, and biological evaluation of lactam-bridged GA analogues. The GA analogue with a 27-membered macrolactam was found to adopt a stable β(6.3) -helical conformation and exhibits higher ion-exchange activity than GA. Furthermore, this GA analogue retains the potent antibiotic activity of GA, but its hemolytic activity and toxicity toward mammalian cells are significantly lower than those of GA. This study thus dissociates the antibacterial and hemolytic/cytotoxic activities of GA, and charts a rational path forward for the development of new ion-channel-based antibiotics.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cell Line; Drug Discovery; Gramicidin; Hemolysis; Humans; Models, Molecular; Peptides; Protein Structure, Secondary

Gramicidin S (GS) is a cyclic cationic antimicrobial peptide (CAP) with a wide spectrum of antibiotic activities whose usage has been limited to topical applications owing to its cytotoxic side effects. We have synthesized tetrahydrofuran amino acid (Taa)-containing GS analogues, and we have carried out conformational analysis and explored their structure activity relationships by evaluating their antitubercular, antibacterial and cytotoxic properties. Two of these analogues showed impressive as well as selective activity against Mycobacterium tuberculosis (MTB) without toxicity towards mammalian Vero cells or human RBCs, and are promising as potential leads.

Topics: Animals; Anti-Bacterial Agents; Antitubercular Agents; Bacteria; Bacterial Infections; Chlorocebus aethiops; Erythrocytes; Furans; Gramicidin; Humans; Microbial Sensitivity Tests; Molecular Dynamics Simulation; Mycobacterium tuberculosis; Tuberculosis; Vero Cells

A novel antibacterial ointment using bacitracin, specific for Gram-positive bacteria, and gramicidin S, a highly toxic antibacterial peptide, was here developed showing broad-spectrum antibacterial activities against pathogenic strains with less toxicity after self-assembly into nanofiber structures. Such structures were confirmed with scanning electron microscopy and CD analyses. In addition, in silico studies using docking associated with molecular dynamics were carried out to obtain information about fiber structural oligomerization. Thus, the bacitracin and gramicidin S-based self-assembled nanopeptide ribbon may be a successful ointment formulation for bacterial infection control.

Topics: Anti-Bacterial Agents; Bacitracin; Bacteria; Bacterial Infections; Chemistry, Pharmaceutical; Circular Dichroism; Gramicidin; Microscopy, Electron, Scanning; Molecular Docking Simulation; Nanofibers; Ointments; Protein Multimerization

The substitution of each constituent amino acid residue of gramicidin S (GS), cyclo(-Val(1,1')-Orn(2,2')-Leu(3,3')-D-Phe(4,4')-Pro(5,5')-)(2) with Lys residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic activity and hemolytic activity of GS. Further, the substitution of D-Phe(4,4') and Pro(5,5') residues with basic amino acid residues as a Lys residue results the high antibiotic activity and the very low hemolytic activity. Thus, we have found novel positions on the scaffold of GS at D-Phe(4,4') and Pro(5,5') residues whose modification will significantly increase the therapeutic index.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Erythrocytes; Gramicidin; Hemolysis; Sheep

Via a Mannich reaction involving a dibenzyliminium species and the titanium enolates of Evans' chiral acylated oxazolidinones the β(2)-amino acids (R)- and (S)-Fmoc-β(2)homovaline and (R)-Fmoc-β(2)homoleucine are synthesized. These building blocks were used, in combination with commercially available α- and β(3)-amino acids, for the synthesis of the cyclo-(αβ(3)αβ(2)α)(2) peptide 2 and the cyclo-(αβ(2)αβ(3)α)(2) peptides 3-5. The peptides 2-5 were screened for their ability to inhibit a small panel of Gram-negative and Gram-positive bacterial strains.

Topics: Amino Acids; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Gramicidin; Humans; Peptides, Cyclic

To find candidates with high antimicrobial and low hemolytic activities, many gramicidin S (GS) analogs of various ring sizes have been designed and synthesized. However, syntheses of antimicrobially active analogues of GS having a disordered symmetry structure from C(2) have almost never been reported, because the stable, amphiphilic β-sheet structure of GS with C(2) symmetry is considered essential for its strong antibacterial activity. In the present studies, novel thirteen cycloundecapeptides 1-13 related to GS were synthesized and examined. Among them, cyclo(-Va1(1)-Orn(2)-Leu(3)-D-Phe(4)-X(5)-Pro(6)-Val(7)-Orn(8)-Leu(9)-D-Phe(10)-Pro(11)-) (X=Lys (10), Orn (11), Arg (12) and Lys(Lys) (13)) resulted in high antibiotic activity against both Gram-positive and Gram-negative microorganisms tested. In addition, 11 showed low toxicity against sheep blood cells compared with that of GS. Further, circular dichroism (CD) spectra of 10-13 had a curve similar to each other, suggesting that the conformations of these analogues in methanol are similar to each other. However, CD spectra of 10-13 were different from that of GS in the 190-210 nm region. These results suggest that the presences of one added amino acid residue at position 5 of 10-13 might be partially effective through a structural change in the biological activity of 10-13. In addition, the structural modifications at position 5 lower the undesirable hemolytic activity and enhance the desirable antibiotic activity.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Circular Dichroism; Gramicidin; Hemolysis; Humans; Microbial Sensitivity Tests; Sheep

In 1939, René Dubos discovered gramicidin-the first clinically tested antibiotic agent. This discovery helped revive the stalled interest in penicillin and launched the era of antibiotics.

Topics: Anti-Bacterial Agents; Bacterial Infections; Gramicidin; History, 20th Century; New York City

A 24-year-old woman suffering from post-influenza otitis media infection was initially treated with several series of a steroid (Elocon) and a combination of steroids and antibiotics (Atecortin, Dicortineff) without significant medical benefit. The isolated bacterial strains were identified as Staphylococcus homis and Staphylococcus epidermidis. Specific phage therapy applied sequentially over a period of three weeks resulted only in a partial reduction in inflammation and limited improvement in overall health condition. Oral application of lactoferrin (LF; 50-mg daily oral doses for seven days with two-week intervals) led to a complete clearance of both bacterial strains and full recovery of the patient. The recovery was associated with increased myelopoiesis and a sustained elevation of serum endogenous LF. In conclusion, specific bacteriophage therapy combined with the administration of lactoferrin proved to be effective in the treatment of antibiotic-resistant external ear infection.

Topics: Adult; Anti-Bacterial Agents; Antiviral Agents; Bacterial Infections; Drug Combinations; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fludrocortisone; Gramicidin; Humans; Lactoferrin; Neomycin; Otitis Media; Penicillin G; Staphylococcus epidermidis; Staphylococcus hominis; Treatment Outcome

Between August 1982 and August 1984 3059 intraocular operations were performed with topical prophylactic antibiotics. Results of conjunctival cultures did not influence the surgical schedule. 8179 intraocular operations were performed between September 1984 and August 1988. An intraocular operation was postponed until conjunctival cultures were negative using topical antibiotics administered at hourly intervals. The rate of postoperative intraocular infections decreased significantly (p less than 0.0001) from 21 (0.69%) of 3059 during the first to 9 (0.11%) of 8179 intraocular operations during the second observation period. In the first period 11 vitrectomies and 2 enucleations due to bacterial endophthalmitis had to be performed. In the second period 2 vitrectomies and no enucleations were necessary (p less than 0.0001). Our results indicate, that decontamination of the conjunctiva may be an import factor for the prevention of postoperative endophthalmitis following elective intraocular surgery.

Topics: Adult; Aged; Bacterial Infections; Cataract Extraction; Colony Count, Microbial; Cross-Sectional Studies; Drug Therapy, Combination; Endophthalmitis; Eye Diseases; Germany; Gramicidin; Humans; Incidence; Keratoplasty, Penetrating; Lenses, Intraocular; Middle Aged; Neomycin; Ophthalmic Solutions; Polymyxin B; Premedication; Surgical Wound Infection; Trabeculectomy; Vitrectomy

815 recent clinical isolates of different species representing pathogenic or saprophytic constituents of human microbial flora were submitted to agar dilution tests. In concentrations above 64 micrograms/ml tyrothricin is in general equally as gramicidin or slightly more effective whereas below 8 micrograms/ml gramicidin is mostly more effective than tyrothricin. Of 401 streptococci all were inhibited by tyrothricin and gramicidin in concentrations up to 96 micrograms/ml; staphylococci were more resistant. The pathogenic species of 130 strains of gram-negative cocci were more susceptible than the saprophytic species. Haemophilus strains were mostly resistant to gramicidin and to a lesser extent to tyrothricin. Enterobacteriaceae were totally resistant to both antibiotics.

Topics: Bacteria; Bacterial Infections; Gramicidin; Humans; Tyrothricin

A simple method has been developed to reduce contamination in postmortem donor human eyes in anticipation of corneal transplantation. In vivo investigation of albino rabbits demonstrates that vigorous saline solution irrigation is extremely effective in decreasing the surface bacterial counts of the postmortem eye. In vitro and in vivo studies show that Neosporin kills bacteria at room temperature and further show that a tenfold increase in the thimerosal concentration of the Neosporin will kill fungus. Postmortem eyes contaminated by pathogenic organisms can be effectively cleaned by a combination of saline solution irrigation and the new Neosporin-thimerosal solution. No substantial damage of the donor tissue was noted by scanning electron microscopy. Human eyes cultured before this procedure were all contaminated, but after cleansing and immersion, no bacterial or fungal growth occurred.

Topics: Animals; Antisepsis; Asepsis; Bacterial Infections; Corneal Transplantation; Drug Evaluation; Ethanol; Gramicidin; Neomycin; Ophthalmic Solutions; Polymyxin B; Rabbits; Temperature; Therapeutic Irrigation; Thimerosal; Tissue Preservation; Transplantation, Homologous