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The effect of cilofungin (LY 121019) in combination with amphotericin B or flucytosine against Candida species.

Cilofungin was combined with amphotericin B or flucytosine to determine if synergistic inhibition or killing occurred against 50 strains of various Candida species. Synergistic inhibition of growth occurred only once with amphotericin B and cilofungin and only 2 times with flucytosine and cilofungin. Synergistic killing occurred in 5 strains with the amphotericin B-cilofungin combination and in 7 strains with the flucytosine-cilofungin combination. Antagonism occurred frequently with both the amphotericin B-cilofungin and the flucytosine-cilofungin combinations.

Amphotericin B↗

Involvement of potassium ions in the action of various antineoplastic drugs on the growth of Saccharomyces cerevisiae.

The involvement of potassium ions in the action of some antineoplastic drugs on the growth of Saccharomyces cerevisiae was studied by incubating yeast cells in the presence of drugs at various concentrations and KCl at concentrations of 50 mmol l-1 and 100 mmol l-1. The presence of 6.25-50 micrograms ml-1 amsacrine or melphalan alone in the culture medium had no significant effect on yeast growth. Addition of KCl significantly increased the sensitivity to these drugs. On the contrary, incubation of yeast cells with KCl had no effect on the cytotoxic action of doxorubicin, methotrexate or 5-fluorouracil.

Amsacrine↗

Antimicrobial activity of carvacrol related to its chemical structure.

AIMS: To investigate the relation between the chemical structure and the antimicrobial activity of carvacrol, eugenol, menthol and two synthesized carvacrol derivative compounds: carvacrol methyl ether and carvacryl acetate against bacteria, Escherichia coli, Pseudomonas fluorescens, Staphylococcus aureus, Lactobacillus plantarum, Bacillus subtilis, a yeast Saccharomyces cerevisiae and one fungi Botrytis cinerea. METHODS AND RESULTS: The antimicrobial activity was tested in liquid and vapour phases, by both broth liquid and microatmosphere methods, respectively. The same classification of the compound's antimicrobial efficiency was found with both methods. Eugenol and menthol exhibited a weaker antimicrobial activity than carvacrol, the most hydrophobic compound. Carvacryl acetate and carvacrol methyl ether were not efficient, indicating that the presence of a free hydroxyl group is essential for antimicrobial activity. CONCLUSIONS: The different extents of antimicrobial aroma compounds' efficiency showed that hydrophobicity is an important factor and the presence of a free hydroxyl group and a delocalized system allows proton exchange. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has identified the importance of the hydrophobicity and the chemical structure of phenolic aroma compounds for antimicrobial activity and may contribute to a most rational use of these compounds as antimicrobial agent.

Anti-Infective Agents↗

The role of ranitidine bismuth citrate in significantly reducing the emergence of Helicobacter pylori strains resistant to antibiotics.

BACKGROUND: This study was carried out to investigate the clinical observation that the emergence of antibiotic resistance can be reduced in Helicobacter pylori if agents are administered in combination with bismuth salts. MATERIALS AND METHODS: Two H. pylori clinical isolates were grown on chocolate Columbia agar containing either ranitidine bismuth citrate (RBC) at one-half lethal concentration (8 micrograms/ml) or no drug control for 22 subcultures. After 1, 5, 8, 14, 17, and 22 subcultures, the emergence of antibiotic resistance to metronidazole, clarithromycin, and streptomycin was calculated and statistically analyzed. RESULTS: Acquisition of resistance to metronidazole was reduced significantly for both strains (p = .007 and 0.014) and for one strain against clarithromycin (p = .037). However, spontaneous emergence of resistance to streptomycin was not altered significantly. In an analysis of the effect of long-term exposure of the isolates to RBC, susceptibility to bismuth was unaltered in one strain and had risen by only twofold in the other at experiment termination. CONCLUSION: RBC significantly decreased resistance acquisition in an inherently sensitive strain and also decreased resistance emergence in a strain that readily became metronidazole-resistant.

Anti-Bacterial Agents↗

Role of temperature and shear forces on microbial detachment.

A flow cell system was used to assess the effects of shear stress and temperature on adhesion and retention of oral microorganisms from unstimulated whole human saliva. The saliva passed between two parallel mounted test plates, prepared and calibrated to present a surface energetic state similar to that of natural teeth and most restorative materials. The initial attachment of microorganisms occurred at a constant flow rate of 1 ml/min. Microbiota and biofilm material associated with the surface after 15 min of exposure were then challenged by introducing a cell-free rinsing fluid at increased flow rates. The remaining population was counted in a reflected light microscope and correlated to the calculated shear stress for each experiment. A reduction of 70-80% of attached microorganisms was seen after a 30-fold increase of the detaching force. No statistically significant differences could be detected in the proportions of initially attached or the remaining cocci and rods. The experiments were conducted at two temperature levels, both within a physiologic range representative of the oral environment. Temperature did not significantly affect the total numbers of attached or retained microorganisms, within the range of 22-37 degrees C. These findings demonstrate that non-specific attachment and detachment processes are important in the initial stage of microbial adhesion. Although biologically specific adhesive interactions were not addressed in this study, the data suggest that these may occur only after a minimum contact time of non-specifically surface associated cells.

Bacterial Adhesion↗

The effect of bacitracin and Mn(II)ions upon the producer strain Bacillus licheniformis.

The peptide antibiotic bacitracin is inhibitory to growth of the producer strain Bacillus licheniformis only in the presence of excess manganese(II)ions. Both the early and the late growth are inhibited in a similar manner upon addition of bacitracin and manganese(II)ions. Thus, B. licheniformis does not develop resistance to its own antibiotic during growth. Added bacitracin is stimulatory to growth of B. licheniformis in media with a very low content of manganese(II)ions. These results support the hypothesis that bacitracin participates in the manganese transport of the producer strain B. licheniformis.

Bacillus↗

Pirbenicillin: comparison with carbenicillin and BL-P1654, alone and with gentamicin, against Pseudomonas aeruginosa.

Minimum inhibitory concentrations (MIC) of pirbenicillin against 135 clinical isolates of Pseudomonas aeruginosa were one-fourth of those required for carbenicillin but two times higher than those for BL-P1654. Increasing the inoculum size produced an adverse effect on the bactericidal activity for all three antibiotics. This was more apparent for pirbenicillin than for carbenicillin, but less than the effect on BL-P1654. When concentrations of antibiotics likely to be achieved clinically were used, gentamicin increased the inhibitory and bactericidal effects of all three semisynthetic penicillins for the majority of isolates. Strains highly resistant to the aminoglycoside antibiotic, however, were inhibited no more by the penicillin-gentamicin combinations than by the most effective of the antibiotics alone.

Carbenicillin↗

Rifampin plus trimethoprim: bactericidal activity and suppression of resistance in human urine in vitro.

The bactericidal effect of a combination of rifampin (Ramp) and trimethoprim (Tmp) was studied using dense cultures of test organisms, including some urinary pathogens, growing in human urine. Drug concentrations used were similar to those attainable in human urine. The combination was more effective than the individual drugs and than a combination of Tmp plus sulfamethoxazole (Smx). Tmp was bactericidal in urine and blocked the emergence of Ramp-resistant bacteria. Ramp was responsible for most of the bactericidal action of the combination but also potentiated the bactericidal activity of Tmp. Ramp suppressed the selection of thy- (Tmp-resistant) bacteria. Under the experimental conditions, Smx+Tmp was not more bactericidal than Tmp alone for most of the test organisms, despite strong synergy between the two at subinhibitory concentrations.

Bacteria↗

Lethal effect of a heterologous murein hydrolase on penicillin-treated Streptococcus sanguis.

Nine strains of Streptococcus sanguis exhibited tolerance to benzylpenicillin: the growth of each strain was susceptible to penicillin with minimal inhibitory concentrations of 0.1 mug/ml or lower, but the bacteriolytic and bactericidal effects were limited in each case. The tolerance of these bacteria was also reflected in the large discrepancies between the minimal inhibitory and minimal bactericidal concentrations for benzylpenicillin. The hypothesis that a natural deficiency of endogenous murein hydrolase (autolysin) in this species accounts for the penicillin tolerance was tested by using a heterologous murein hydrolase, the C-phage-associated lysin. In seven of the strains, addition of the lysin to the culture together with penicillin or other cell wall inhibitors resulted in lysis and rapid loss of viability. The enzyme alone did not appreciably affect normally growing cultures. The irreversible effects of penicillin plus lysin were drastically reduced in the presence of the bacteriostatic agents chloramphenicol and cerulenin. Speculations based on experiments are presented for the mechanisms by which penicillin treatment sensitizes these bacteria to an exogenous lytic enzyme. Similar phenomena requiring cooperation of host factors and penicillin may occur during infection, since somewhat similar although less pronounced results were obtained by addition of human lysozyme to penicillin-treated S. sanguis.

Amidohydrolases↗

Antibacterial activity of ceftizoxime, a beta-lactamase-stable cephalosporin.

The in vitro activity of ceftizoxime was compared with that of other beta-lactam antibiotics against 538 isolates. Ceftizoxime was the most active agent tested against Escherichia coli and Klebsiella, inhibiting 80% at 0.025 microgram/ml. It was more active than cefotaxime against Enterobacter cloacae and E. aerogenes. Ceftizoxime was more active than cefoxitin, cefotaxime, cefoperazone, and carbenicillin against Proteus mirabilis and indole-positive Proteus. It inhibited 97% of multiresistant Serratia isolates at 12.5 microgram/ml, whereas cefotaxime inhibited only 19%. Ceftizoxime was less active than cefotaxime and cefoperazone against Pseudomonas aeruginosa, but was more active than carbenicillin. It was more active than cefotaxime and cefoxitin against Bacteroides. It was not appreciably destroyed by beta-lactamases of Staphylococcus aureus, Enterobacteriaceae, or Pseudomonas.

Acinetobacter↗

Comparative susceptibilities of clinical isolates of Serratia marcescens to newer cephalosporins, alone and in combination with various aminoglycosides.

We examined 100 clinically significant isolates of Serratia marcescens for susceptibility to newer cephalosporin and cephamycin antibiotics, alone and in combination with various aminoglycosides. Moxalactam and cefotaxime were the most effective agents; all isolates were inhibited by 25 and 50 micrograms/ml, respectively. All strains were susceptible to amikacin at concentrations safely achievable in serum, whereas gentamicin, netilmicin, and tobramycin inhibited 63, 63, and 16% of the isolates, respectively. Moxalactam, cefotaxime, and amikacin were active against gentamicin-susceptible and gentamicin-resistant strains. Studies of synergy revealed that moxalactam and cefotaxime, in combination with netilmicin or amikacin, were often synergistic and infrequently antagonistic against cephalothin- and gentamicin-resistant strains. These results suggest that moxalactam and cefotaxime, alone or in combination, may be efficacious in treating infections due to multiply antibiotic-resistant S. marcescens.

Aminoglycosides↗

Comparative in vitro activities of beta-lactam-tobramycin combinations against Pseudomonas aeruginosa and multidrug-resistant gram-negative enteric bacilli.

Piperacillin was more consistently active than tobramycin, carbenicillin, moxalactam, or ceftriaxone against strains of Pseudomonas aeruginosa isolated from blood cultures and against multidrug-resistant strains. Moxalactam and ceftriaxone were more consistently active than tobramycin, carbenicillin, or piperacillin against multidrug-resistant Enterobacteriaceae. Synergy between beta-lactam antibiotics and tobramycin was frequently observed against strains of P. aeruginosa isolated from blood cultures but not against multidrug-resistant organisms. Piperacillin plus tobramycin was the most active antibiotic combination against P. aeruginosa. Moxalactam plus tobramycin and ceftriaxone plus tobramycin were the most active antibiotic combinations against Enterobacteriaceae.

Anti-Bacterial Agents↗

In vitro activity of the two principal oxidative metabolites of metronidazole against Bacteroides fragilis and related species.

Metronidazole and its two principal oxidative metabolites were tested in vitro against 20 clinical isolates of the Bacteroides fragilis group. Both metabolites were bactericidal, and the exhibited 65 and 5%, respectively, of the inhibitory effect of metronidazole. Additive or weak synergistic effects resulted in combination with the parent compound.

Bacteroides fragilis↗

In vitro activity and beta-lactamase stability of cefmenoxime.

The activity of cefmenoxime, an aminothiazolyl cephalosporin, was studied against 650 bacteria. It was slightly less active than cefotaxime and more active than moxalactam against staphylococci. It had activity similar to that of cefotaxime and ceftizoxime against group A and B streptococci and Streptococcus pneumoniae. It did not inhibit Streptococcus faecalis or Listeria spp. Cefmenoxime had activity similar to that of cefotaxime, ceftizoxime, ceftazidime, and moxalactam against Escherichia coli, Citrobacter diversus, Klebsiella, Proteus mirabilis, Salmonella, and Shigella. It inhibited beta-lactamase-positive and -negative isolates at less than or equal to 0.4 microgram/ml. Cefmenoxime was somewhat less active than moxalactam or ceftizoxime against Enterobacter cloacae, Enterobacter aerogenes, and Enterobacter agglomerans, but was more active than cefotaxime, ceftizoxime, or ceftazidime against Morganella (minimum inhibitory concentration for 90% of isolates, 0.1 microgram/ml.), Proteus vulgaris and Providencia spp. It was as active as ceftizoxime was against Serratia. Pseudomonas spp. and Bacteroides spp. were relatively resistant (minimum inhibitory concentration for 90% of isolates, greater than 100 micrograms/ml). The compound was stable to the common plasmid beta-lactamases, such as that of TEM. It was stable to most chromosomally mediated beta-lactamases, which act primarily as cephalosporinases, but was hydrolyzed by Bacteroides and Acinetobacter.

Aminoglycosides↗

Antimicrobial activity of amikacin combinations against Enterobacteriaceae moderately susceptible to third-generation cephalosporins.

Enterobacteriaceae strains having elevated minimal inhibitory concentrations (greater than or equal to 2.0 to less than or equal to 32 micrograms/ml) of cefoperazone, cefotaxime, ceftazidime, and moxalactam were synergistically inhibited by amikacin combinations (54.1 to 69.6% occurrence). Indifference was rare (8.1% for moxalactam), and true antagonistic interactions were not observed. Strains resistant or susceptible to these new cephalosporins were also synergistically inhibited by the addition of amikacin, reducing resistant cephalosporin minimal inhibitory concentrations to clinically achievable levels.

Amikacin↗

In vitro activities of ureidopenicillins alone and in combination with amikacin and three cephalosporin antibiotics.

The MIC and MBC activity of mezlocillin alone and in combination with two concentrations of ceftizoxime, moxalactam, and amikacin and a single concentration of cefoxitin was studied in a broth microdilution partial checkerboard against 472 strains of aerobic gram-negative and gram-positive bacteria. Azlocillin was tested alone and in the same combinations against Pseudomonas aeruginosa. Of the gram-negative bacilli tested, 38% were gentamicin resistant. Antagonism (less than or equal to a fourfold ureidopenicillin MIC increase) was observed frequently with combinations of ureidopenicillins plus cefoxitin and sporadically with ureidopenicillins plus ceftizoxime or moxalactam. Partial synergism (less than or equal to a fourfold ureidopenicillin MIC decrease) was evident with both combinations of ureidopenicillins plus amikacin and ureidopenicillins plus ceftizoxime or moxalactam, the percentage being dependent upon the individual species and combinations.

Amikacin↗

Enhancement of the in vitro activity of amphotericin B against Aspergillus spp. by tetracycline analogs.

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activity was seen, especially with combinations of amphotericin B and minocycline. Synergistic activity between amphotericin B and minocycline was observed in each of five isolates of each species when tested in a checkerboard dilution scheme. Time-kill curves demonstrated killing an A. fumigatus isolated at concentrations of amphotericin B that were four- or eightfold lower in the presence of 5 or 15 micrograms of minocycline per ml than with amphotericin B alone. Of the tetracycline analogs tested, minocycline has the greatest activity against A. fumigatus, A. flavus, and A. niger conidia when potentiated by amphotericin B.

Amphotericin B↗

In vitro evaluation of various antifungal agents alone and in combination by using an automatic turbidimetric system combined with viable count determinations.

A new method combining automatic turbidimetry and sequential viable count determinations was developed to evaluate the in vitro activity of various antifungal agents alone and in combination against three clinical isolates of Candida spp. (two Candida albicans and one C. tropicalis) at two inocula (10(-5) and 10(-6) CFU/ml). Specific parameters were derived from the time-kill curves: the maximal rate of killing, the lowest biomass, and the overnight biomass. Their intra-assay and between-assay reproducibilities were high, with respective standard deviations of 0.4 and 0.25 to 1.4 log CFU/ml. Amphotericin B alone showed a linear relationship between rate of killing or lowest biomass and the log of concentration from 0.03 to 4 mg/liter that was similar for the three strains tested. 5-Fluorocytosine (flucytosine) alone showed a dose-related reduction of overnight biomass for concentrations up to 8 mg/liter with no further increase at higher concentrations for one strain of C. albicans and a paradoxical decrease for one strain of C. tropicalis. Ketoconazole alone was found to be only fungistatic with no increased activity at concentrations up to 16 mg/liter. Amphotericin B plus flucytosine interacted synergistically in 46 to 60% of the combinations tested against C. tropicalis depending on the initial inoculum. Indifference was observed for the two strains of C. albicans. Amphotericin B or flucytosine plus ketoconazole was usually indifferent against the three tested strains.

Amphotericin B↗