Effect of xanthan gum-based food thickeners on the dissolution profile of fluoroquinolones oral formulations.

BACKGROUND: Xanthan gum-based food thickeners (XG-FTs) are often ingested by patients with dysphagia to prevent aspiration during drug treatment. Reportedly, XG-FTs affect tablet disintegration, drug dissolution rates, and reduce the efficacy of postprandial antihyperglycemic agents. The absorption rate and quantity of fluoroquinolone antimicrobial agents correlate with drug efficacy, raising concern about the impact of XG-FTs. Previously, we reported that film-coated tablets were less susceptible to the effects of XG-FT than conventional and orally disintegrating tablets. Here, we compare the effect of XG-FTs on dissolution profiles of three oral fluoroquinolone-based film-coated tablets by evaluating the dissolution of crushed products, fine granules, and film-coated fine granules. METHODS: We examined formulations of tosufloxacin tosylate monohydrate (TFLX), levofloxacin hemihydrate (LVFX), and ciprofloxacin hydrochloride hydrate (CPFX). The formulations were immersed in 20 mL of 1.5% (w/v) XG-FT aqueous solution for 2.5 min followed by a dissolution test using the paddle method according to the Japanese Pharmacopoeia (dissolution test solution pH 1.2; volume 900 mL; temperature 37 ± 0.5 °C). The dissolution profile was evaluated according to the dissolution quantity indicated in product specifications and guidelines for bioequivalence testing of generic drugs. The 15-min mean dissolution rate was determined for a formulation immersed in 1.5% (w/v) XG-FT aqueous solution and compared with that for a non-immersed formulation (control). Fluoroquinolone film-coated tablets were mixed with starch-based FTs, guar gum-based FTs, or XG-FTs to observe their appearances. RESULTS: The dissolution profile of LVFX film-coated tablets was not affected by XG-FTs, but the dissolution of TFLX and CPFX was delayed. For crushed film-coated tablets, the 15-min mean dissolution rate was significantly delayed for all three fluoroquinolones when compared with that of uncrushed products. The dissolution profile of TFLX film-coated fine granules was unchanged by XG-FTs. CPFX film-coated tablets and crushed products produced a gel-like precipitate when mixed with XG-FTs and failed to meet product-dissolution specifications. A gel-like precipitate was also observed with guar gum-based FTs. CONCLUSION: The effect of XG-FTs on the dissolution profile of film-coated fluoroquinolone formulations varied depending on the formulation. The CPFX formulation formed a gel-like precipitate when immersed in XG-FTs resulting in a significantly delayed dissolution.

A case of Degos disease: demonstration of C5b-9-mediated vascular injury.

A 68-year-old Japanese male presented with atrophic erythematous white lesions with peripheral dark reddish rims on his back. Multiple ulcers were detected from his stomach to his large intestine using endoscopy. Although the patient was given high doses of a steroid, aspirin, dipyridamole, and intravenous immunoglobulin therapy, he died of gastrointestinal hemorrhage, perforation and septic shock. An autopsy examination revealed pauci-inflammatory thrombotic microangiopathy with endothelial cell injury, fibrous occlusive arteriopathy, and vascular C5b-9 deposition in the wall of the gastrointestinal tract from the esophagus to the large intestine as well as in the dermis of the skin.

Characterization of two mobilizable plasmids isolated from enterobacter cloacae.

We isolated two plasmids, pS51A and pS51B which were 5782 bp and 4854 bp in size, respectively, from the third generation cephalosporin-resistant E. cloacae suspected to express metallo-beta-lactamase, and analyzed their structures. These two plasmids encode RNA I/RNA II genes for replication origin, relaxase genes of mobABCD for plasmid transfer, and several open reading frames. According to the classification of mobilizable plasmids by gene organization of the relaxases, pS51A and pS51B belong to the ColE1 superfamily of mobilizable plasmids, commonly detected in Enterobacteriaceae. The metallo-beta-lactamase gene was not identified in either pS51A or pS51B by homology search of the putative open reading frames. Open reading frames encoded in pS51A include E. coli protein L-like, E. coli heat shock protein-like, and E. coli plasmid replication initiation protein-like, and those encoded in pS51B include helix-turn-helix protein-like, E. coli plasmid replication initiation protein-like, and Salmonella replication initiation protein-like. These plasmids are stably maintained in one strain of E. cloacae, thus, the encoded gene functions may confer growth advantage to the host cell.

[Validity of using imipenem as a representative carbapenems and levofloxacin as a representative fluoroquinolones in antibiotics susceptibility test for enterobacteriaceae].

In antimicrobial susceptibility test for enterobacteriaceae, the efficacies of carpapenems are predicted by the minimum inhibitory concentration (MIC) of imipenem, and that of fluoroquinolones are predicted by the MIC of levofloxacin. To assess its judgement, we compared the MICs of imipenem, meropenem, panipenem, and doripenem for carbapenems, and ciprofloxacin, levofloxacin, tosufloxacin and pazufloxacin for fluoroquinolones of clinically isolated enterobacteria, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Enterobacter cloacae and Citrobacterfreundii, those resistant to the third generation cephalosporin. MIC distributions in low concentration range are estranged in some strains, conspicuously S. marcescens, E. cloacae and C. freundii: meropenem and doripenem displayed low MIC value than imipenem and panipenem. Since the estrangements are appeared MIC value of less than 8 microg/ml, the interpretive results (susceptible, intermediate, resistant) are not affected. In fluoroquinolones, all 4 agents showed almost identical MIC distributions, thus the MIC of levofloxacin is accepted to use the reference for other fluoroquinolones. The existence of the strains harboring carbapenem-resistant gene displaying low MIC value of carbapenems was reported. For the sensitive detection of the candidate of carbapenem-resistant strains, cut-off value of each carbapenem should be reconsidered, and also other phonotype analysis should be applied. Genomic analysis also would be required to detect the carbapenem-resistant gene.

[Analysis of the antibiotic resistant gene in multidrug-resistant Enterobacter cloacae isolated at Showa University Hospital].

We analyzed the antibiotic resistant genes, metallo-beta-lactamase and extended-spectrum beta-lactamase (ESBL), in highly resistant Enterobacter cloacae isolated at Showa University Hospital from April to June 2008. Thirty eight strains of E. cloacae were isolated. Of these strains, 35 demonstrating resistant to either cefotaxime (Minimum inhibitory concentration: MIC > or = 32 microg/ml), ceftadizime (MIC > or = 16 microg/ml), or aztreonam (MIC > or = 16 microg/ml) were selected for the analysis. The strains were subjected to a Double-disk synergy test (DDST) using sodium mercaptoacetic acid (SMA) and ceftadizime. As a result, 7 strains showed an enlargement of inhibition zone diameter by SMA. Among 7 SMA responded strains, 6 strains carried the bla(IMP-1) or bla(IMP-11) gene. There were 2 strains sensitive to imipenem (MIC < 1 microg/ml) in SMA responded strains, and one carried bla(IMP-11) gene. ESBL genes were detected in 5 strains, bla(CTX-M3) gene from 3 strains, and bla(CTX-M14) gene from 2 strains. All of the ESBL harboring strains showed an enlargement of inhibition zone diameter in DDST using clavulanic acid and ceftadizime, cefotaxime, aztreonam or cefepime. Among 35 strains, one strain carried both bla(IMP-1) and bla(CTX-M3) genes. In addition to the AmpC beta-lactamase, increase of the E. cloacae strains carrying these resistant genes cause the complex antibiotic resistant patterns. Especially, strains carrying bla(IMP) gene, which exhibit low imipenem MIC value may be induced to be resistant strains under the existence of imipenem. Analysis of resistant genes would be a beneficial for the measure the spread of drug-resistant E. cloacae.