Modulation of biofilms of Pseudomonas aeruginosa by quinolones.

The interaction between four fluoroquinolones (ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin) and biofilms of Pseudomonas aeruginosa in wells of microtiter plates and on segments of vascular catheters were studied in an in vitro model of vascular catheter colonization. Subinhibitory concentrations (one-half, one-fourth, and one-eight of the MIC) of the fluoroquinolones reduced the adherence of P. aeruginosa to 30 to 33, 44 to 47, and 61 to 67% of that of controls, respectively. The addition of high concentrations of the fluoroquinolones (12.5 and 400 micrograms/ml) to preformed biofilms (grown for 48 h at 37 degrees C) decreased the adherence of P. aeruginosa to 69 to 77 and 39 to 60% of that of controls, respectively. In an in vitro model of vascular catheter colonization, subinhibitory concentrations (one-half, one-fourth, and one-eight of the MIC) of fluoroquinolones reduced the number of adherent bacteria to 21 to 23, 40 to 46, and 55 to 70% of that of the controls, respectively. Scanning electron microscopy demonstrated a significant reduction in glycocalyx formation and adherent bacteria in the presence of pefloxacin at one-half to one-eight of the MIC. Vascular catheter segments precolonized with P. aeruginosa for 24 h and exposed to the fluoroquinolones at 4 to 25 times the MIC (50 micrograms/ml) for 2 h showed <5% growth of adherent cells compared with controls. No adherent organisms were cultured in the presence of 8 to 50 times the MIC (100 micrograms/ml). Scanning electron microscopy studies of preformed biofilms exposed to pefloxacin verified the results obtained by culture. These data show that subinhibitory concentrations of ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin inhibit the adherence of P. aeruginosa to plastic surfaces and vascular catheters. Clinically achievable concentrations of fluoroquinolones (50 to 100 micrograms/ml) were able to eradicate preformed biofilms on vascular catheters.

In vitro synergism between tetracyclines and antimalarials.

The in vitro activity of various tetracyclines and antimalarials alone and in combinations against 20 clinical isolates of Escherichia coli was investigated. The minimum inhibition concentration of the tetracyclines ranged from 1.2 to 160 micrograms/ml. Demeclocycline was the highest in activity. The antimalarials were ineffective. Variable percentage of strains responded to the synergistic effect of the various antibiotics-drugs combinations. Strains which are relatively insensitive to the tetracyclines did not respond to the synergistic effect of the combinations. The bactericidal effect of the combinations was shown by the enhanced rate of killing that occurred at 6 h. Synergism was reversed by divalent cations.

Effect of carbenicillin, gentamicin and vaccines on rats experimentally burned and infected with Pseudomonas aeruginosa.

Carbenicillin and gentamicin were tested on rats experimentally burned and infected by a selected strain of Pseudomonas aeruginosa. Carbenicillin injection was found to be the best treatment as it decreased pus formation and enhanced healing. Gentamicin was less effective than carbenicillin. The use of hydrophilic base ointment containing antibiotics is contraindicated, as it probably provides a favourable environment for Pseudomonas aeruginosa growth. The administration of supernatant vaccines and cell vaccines alone and in conjunction with the antibiotics did not modify the course of infection and healing.

Effect of agar percentage, agar thickness, and medium constituents on antibiotics assay by disc diffusion method.

The factors affecting the sensitivity of nafcillin, vancomycin, oleandomycin, chloramphenicol, methacycline and novobiocin assay, using the paper disc diffusion method, were studied. Agar concentration and pour volume were found to influence the assay sensitivity of antibiotics. The type of assay medium was effective e.g. brain heart infusion agar was the best medium for nafcillin and methacycline; synthetic amino acid medium for oleandomycin; Muller Hinton agar for vancomycin and chloramphenicol; and G & R medium for novobiovicin. All additives, including inorganic ions, sugar, organic acids, complexing agents, surface active agents and blood, decreased the activities of the studied antibiotics. Higher activities of vancomycin, methacycline were observed at pH = 5, of nafcillin, chloramphenicol, and novobiocin at pH = 6, and of oleandomycin at pH = 7.

In vitro studies on drug--antibiotic interactions I: analgesics, antipyretics, antimalarials, and tranquilizers.

The antimicrobial effects of some analgesics, antipyretics, antimalarials, and tranquilizers were determined. The phenothiazines were the most active group. The effect of the chosen drugs when combined with a selected number of antibiotics was studied on Staphylococcus aureus and Escherichia coli to determine the type of interaction. Most analgesics, antipyretics, and antimalarials showed either no effect or a synergistic action. However, some exhibited antagonistic effects. All tested tranquilizers were synergistic. Preliminary studies, using electronic absorption spectrometry, indicated that the antagonistic action may be attributed to a physical interaction.

Antimicrobial activity of the volatile oil of Nigella sativa Linneaus seeds.

The antimicrobial activity of the volatile oil of Nigella sativa Linneaus seeds was studied. The antimicrobial principle has been isolated, identified as thymohydroquinone, and found to be active against gram-positive bacteria and yeasts.

Microcysts of the cellular slime mold Polysphondylium pallidum. II. Chemistry of the microcyst walls.

Methods are described for obtaining large masses of myxamoebae, for inducing these to form microcysts, and for the isolation of the microcyst walls from other cell components. The walls were fractionated into two parts, one alkali-soluble, the other alkali insoluble. The alkali-insoluble fraction is a type of cellulose and constitutes 28% of the microcyst wall by weight. The alkali-soluble fraction contains a glycogenlike material, lipids, and proteins. A possible mechanism of microcyst wall synthesis is discussed.

Microcysts of the cellular slime mold Polysphondylium pallidum. I. Factors influencing microcyst formation.

Microcyst formation can be induced by increasing the osmotic pressure of the surrounding medium. Certain ions such as K(+), Ca(++), or Mg(++) may be needed in the encystment process, and the presence of divalent cations increases the rate of encystment and cyst maturation. Chloride of potassium is optimal for encystment, but other anions of potassium are either less effective or toxic. The optimal pH for encystment was found to be pH 6.0. The use of agar plates containing KCl revealed the importance to the encystment process of inhibiting cell aggregation. When myxamoebae of Polysphondylium pallidum strain Pan-17 are deposited on KCl-agar plates, approximately 20% of the population proceeds through aggregation to sorocarp formation at the concentration of KCl optimal for microcyst formation. However, the same proportion of myxamoebae remains unaligned, or forms defective aggregation centers, if synergistic inhibitors (such as incubation in darkness or at low temperature) are employed in addition to KCl. The possibility that this is due to heterocytosis has been excluded. Accordingly, it is suggested that during the stationary phase approximately 20% of the population becomes committed to forming component cells of fruiting bodies, and that these myxamoebae cannot be induced to form microcysts by exposure to KCl. In P. pallidum strains WS-320 on the other hand, the imposition of synergistic inhibitors leads to the total encystment of the cell population. This suggests that, in contrast to Pan-17, the myxamoebae of the latter strain remain potentially equal and exhibit minimal presumptive specialization.