Variation of alkaloid contents and antimicrobial activities of Papaver rhoeas L. growing in Turkey and northern Cyprus.

CONTEXT: Papaver rhoeas L. (Papaveraceae) corn poppy, widely distributed in Turkey, is used to make a cough syrup for children, as a tea for disturbed sleep, for pain relief and as a sedative in folk medicine. OBJECTIVE: Samples of P. rhoeas collected from eight different locations in Turkey and three from northern Cyprus were investigated for their alkaloid content and screened for their antimicrobial activities. MATERIALS AND METHODS: From the aerial parts of P. rhoeas samples, alkaloids were isolated by column and preparative thin-layer chromatography. The alkaloids were identified by comparing their spectral data (UV, IR and 1H-NMR) and TLC Rf values with those of authentic samples. The antimicrobial study was carried out by microbroth dilution technique against six strains of bacteria and three strains of fungi. RESULTS: Twelve different alkaloids belonging to proaporphine (mecambrine), aporphine (roemerine), promorphinan (salutaridine), protopine (coulteropine and protopine) and rhoeadine (epiglaucamine, glaucamine, glaudine, isorhoeadine, isorhoeagenine, rhoeadine and rhoeagenine) groups were isolated. The most significant activity was observed with the alkaloid extract of P8 against Staphylococcus aureus with a MIC value of 1.22 µg/mL and against Candida albicans with a MIC value of 2.4 µg/mL. DISCUSSION: The results indicate that P. rhoeas samples (P8 and P9), which contain roemerine as their major alkaloid, were the most active extracts.

Comparative in vitro efficacies of various antipseudomonal antibiotics based catheter lock solutions on eradication of Pseudomonas aeruginosa biofilms.

Antibiotic lock technique (ALT) may be an adjunct therapy in treating catheter-related infections. The aim of this study was to determine the in vitro stability and efficacy of colistin, meropenem and levofloxacin alone or in combination with clarithromycin or heparin lock solutions against biofilm embedded Pseudomonas aeruginosa strains. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against P. aeruginosa isolated from catheter-related bacteremia. We observed that the use of meropenem, levofloxacin or colistin as a lock solution had potent bactericidal effects and could be prevented bacterial regrowth at 96 or 72 hours, respectively. When the tested antibiotics were used in combination with clarithromycin, the combinations were significantly more effective and rapid in eliminating P. aeruginosa colonization in biofilm than each of the antibiotics were used alone. Moreover, tested antibiotics in combination with heparin were not significantly different for killing effect against PA-1 and PA-27853 compared with that of each antibiotics alone. Tested catheter lock solutions may have promising adjuvants for treating infections caused by P. aeruginosa.

In vitro activities of colistin, tigecycline and tobramycin, alone or in combination, against carbapenem-resistant Enterobacteriaceae strains.

The aim of this study was to investigate the activities of various antibiotics, alone or in combination, against carbapenem-resistant Enterobacteriaceae (CRE). Minimum inhibitory concentrations (MICs) of meropenem, colistin, tigecycline and tobramycin were determined by microbroth dilution against 40 clinical strains. Carbapenemase-encoding genes were detected by PCR using specific primers. The in vitro synergistic activities of tigecycline, colistin and tobramycin in double antibiotic combinations were determined by the microbroth chequerboard technique, and results were interpreted using the fractional inhibitory concentration index (FICI). To confirm the results acquired by the chequerboard method, time-kill assays were performed on eight isolates representing four different susceptibility patterns. Based on MIC90 values, colistin was the most potent agent, followed by tigecycline and tobramycin. According to PCR studies, carbapenem resistance in tested Enterobacteriaceae isolates was most often mediated by OXA-48-type carbapenemases. With an FICI of ≤0.5 as the cut-off, synergistic interactions were most frequent with tigecycline+tobramycin (30%); other results for synergistic interactions were 23% for colistin+tobramycin and 9% for colistin+tigecycline. By time-kill assays, all tested antibiotic combinations demonstrated synergistic activity against at least three of the eight strains at 1× or 4× MIC. Overall, the combinations used in this study were effective regimens, demonstrating synergy or no interaction (indifference) against all tested strains. No antagonism was observed with either of the techniques. The findings of this study might play a useful role in selecting appropriate combinations when a single agent is inadequate against CRE strains.

In vitro effectiveness of colistin, tigecycline and levofloxacin alone and combined with clarithromycin and/or heparin as lock solutions against embedded Acinetobacter baumannii strains.

OBJECTIVES: To determine the in vitro stability and efficacy of colistin, tigecycline and levofloxacin alone or in combination with clarithromycin and/or heparin as lock solutions against biofilm-embedded Acinetobacter baumannii strains. METHODS: Candidate antibiotics (colistin, tigecycline and levofloxacin) were investigated in vitro, either alone or in combination with clarithromycin and/or heparin in solution. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against A. baumannii isolated from catheter-related bacteraemia. RESULTS: Candidate antibiotics at 400× MICs combined with clarithromycin (200 mg/mL) and/or heparin (1000 U/mL) were compatible. Colistin, tigecycline and levofloxacin and their combinations with clarithromycin demonstrated bactericidal activity against the biofilm-embedded A. baumannii strains. Compared with other antibiotics alone, the lock solution including only colistin was the best agent to eradicate A. baumannii embedded in the catheter model. When tested antibiotics were used in combination with clarithromycin, the combinations were significantly more effective and more rapid in reducing the live cell number or eliminating A. baumannii colonization in biofilms than each of the antibiotics alone. CONCLUSIONS: Catheter lock solutions containing colistin may have the most promise for treating or preventing biofilm-producing catheter infections caused by A. baumannii. Clarithromycin was ultimately effective with the studied antibiotics to reduce live cell number or eradicate A. baumannii colonization in biofilms and could serve as an antibiotic enhancer. Our in vitro model findings now warrant clinical trials to investigate their real role in the management of catheter-related bacteraemia.

Postantibiotic effects of tigecycline, colistin sulfate, and levofloxacin alone or tigecycline-colistin sulfate and tigecycline-levofloxacin combinations against Acinetobacter baumannii.

BACKGROUND: Colistin sulfate and levofloxacin, alone and in combination with tigecycline, were investigated for their in vitro activities and postantibiotic effects (PAEs) on6 meropenem-resistant Acinetobacter baumannii. METHODS: The in vitro activities of colistin sulfate and levofloxacin in combination with tigecycline were determined using a microbroth checkerboard technique. The results were interpreted based on the fractional inhibitory concentration index. To determine the PAEs, A. baumannii strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation. RESULTS: One synergistic interaction was observed for each of the tigecycline-colistin sulfate and tigecycline-levofloxacin combinations. Colistin sulfate produced a strong PAE ranging from 2.50 to 7.0 h in a concentration-dependent manner. PAEs were induced by levofloxacin (ranging from 0.35 to 2.45 h) and tigecycline (ranging from 0.05 to 1.40 h). In combination, tigecycline slightly changed the PAE of colistin sulfate and levofloxacin against the studied strains. CONCLUSION: This study's findings could have important implications for the timing of doses during antimicrobial therapy with tigecycline, colistin sulfate, and levofloxacin alone and in combination.

Post-antibiotic effect of levofloxacin and tobramycin alone or in combination with cefepime against Pseudomonas aeruginosa.

BACKGROUND: Levofloxacin and tobramycin, alone and in combination with cefepime, were investigated for their in vitro activities and post-antibiotic effects (PAEs) on Pseudomonas aeruginosa. METHODS: The in vitro activities of tobramycin and levofloxacin in combination with cefepime were determined by microbroth chequerboard technique against six P. aeruginosa strains that were isolated from patients with bacteremia. The results were interpreted by fractional inhibitory concentration index. To determine the PAEs, P. aeruginosa strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation. RESULTS: Three synergistic interactions were observed with cefepime-tobramycin and one with cefepime-levofloxacin combinations against tested strains.No antagonism was observed. Levofloxacin produced a PAE ranging from 1.9 to 4.5 h in a concentration-dependent manner. Similar PAEs were induced by tobramycin (ranging from 1.5 to 3.1 h). However, negative PAE values were obtained with cefepime. In combination, cefepime slightly reduced the PAE of tobramycin and levofloxacin against studied strains. CONCLUSION: The finding of this study may have important clinical implications for the timing of doses during therapy with cefepime, levofloxacin and tobramycin alone and in combination.

Synthesis and antimicrobial activity of some novel derivatives of benzofuran: part 1. Synthesis and antimicrobial activity of (benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl) ketoxime derivatives.

The reaction of salicylaldehyde with 1-phenyl-1-methyl-3-(2-chloro-1-oxoethyl) cyclobutane (1) and potassium carbonate was used to prepare (benzofuran-2-yl)(3-methyl-3-phenylcyclobutyl) methanone (2) for the starting reagent purposes. (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl) ketoxime (3) was synthesized from the reaction of the compound (2) with hidroxylamine. New derivatives of (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl) ketoxime (3) such as, O-glycidylketoxime (4) and O-phenylacylketoxime (5a-c) were obtained very high yields. Alkyl, allyl and aryl substituted N-oxime ethers (6a-e) were obtained from the reaction compound 3 and various halogen contained compounds. The syntheses of the compounds (7a-f) were carried out from the reaction of the compound (4) and different amines such as, isopropyl amine, natrium azide, morpholine and piperazine. All of the synthesized compounds were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153 and Candida albicans ATCC 10231. Among the synthesized compounds (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl)-O-[2-hydroxy-3-(N-methylpiperazino)] propylketoxime (7d) was found the most active derivative against S. aureus ATCC 6538. The compounds 2, 5b, 6b, 6c, 7b and 7f showed very strong and the same antimicrobial effect against C. albicans ATCC 10231. Similarly (benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl)-O-benzylketoxime 6a showed good antimicrobial effect against C. albicans ATCC 10231. None of the other compounds exhibited activity against the other test microorganisms.