isepamicin and flomoxef

Pseudomonas aeruginosa has eventually developed resistance against flomoxef sodium, isepamicin and cefpiramide. Therefore, in this study, the antibacterial activity and synergistic effects of the amphipathic-derived P5-18mer antimicrobial peptide were tested against pathogens associated with cholelithiasis that have developed resistance against commonly used antibiotics. The results were then compared with the activities of the amphipathic-derived peptide, P5-18mer, melittin and common antibiotics. Growth inhibition of planktonic bacteria was tested using the National Committee for Clinical Laboratory Standards (NCCLS). The bactericidal activity of the antimicrobial peptides was measured using time-kill curves. Synergistic effects were evaluated by testing the effects of P5-18mer alone and in combination with flomoxef sodium, isepamicin or cefpiramide at 0.5xMIC. P5-18mer peptide displayed strong activity against pathogens and flomoxef sodium, isepamicin and cefpiramide-resistant bacteria cell lines obtained from a patient with gallstones; however, it did not exert cytotoxicity against the human keratinocyte HaCat cell line. In addition, the results of time-kill curves indicated that P5-18mer peptide exerted bactericidal activity against four strains of P. aeruginosa. Finally, the use of P5-18mer and antibiotics exerted synergistic effects against cell lines that were resistant to commonly used antibiotics. These results indicate that this class of peptides has a rapid microbicidal effect on flomoxef sodium, isepamicin and cefpiramide-resistant strains of P. aeruginosa. Therefore, these peptides may be used as a lead drug for the treatment of acquired pathogens from patients with cholelithiasis who are affected with antibiotic-resistant bacteria.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cell Line; Cephalosporins; Cholelithiasis; Drug Resistance, Bacterial; Drug Synergism; Gentamicins; Humans; Melitten; Molecular Sequence Data; Pseudomonas aeruginosa

We developed a novel hydroxyapatite (HA) cylinder (HA-A) and compared the slow release of antibiotic in vitro as well as osteoconduction of the material in vivo to a commercially produced porous hydroxyapatite cylinder (HA-B). HA-A (4 x 4 mm) was synthesized by mixing HA powder, gelatin, and vegetable oil. The material had a bimodal pore size distribution, with intragranular (10 nm to 10 microm) and intergranular (100 microm) pores, and porosity of 40 vol %, while HA-B had pore sizes ranging from 50 to 300 microm and identical porosity. In vitro drug release was tested using antibiotics (isepamicin sulfate, vancomycin hydrochloride, and flomoxef sodium) soaked on the HA cylinders using a vacuum system. The mean adsorption efficiency was higher for HA-A (46%) than for HA-B (26%) and higher levels of antibiotic were released from HA-A. Of the antibiotics, ISP showed the longest release duration. Bone ingrowth into the pores was observed for both materials. Because the novel HA showed both the slower release of antibiotic (nanosize pores) and supported excellent osteoconduction (microsize pores), it could be useful for the treatment of osteomyelitis.

Topics: Adsorption; Animals; Anti-Bacterial Agents; Cephalosporins; Delayed-Action Preparations; Drug Carriers; Durapatite; Female; Femur; Gentamicins; Microscopy, Electron, Scanning; Nanostructures; Porosity; Prostheses and Implants; Rabbits; Vancomycin

In order to evaluate antibacterial activities of combination uses of isepamicin (ISP) and beta-lactams in vitro, minimum inhibitory concentrations (MICs) these drugs were examined singly and in combination against clinically isolated Staphylococcus aureus. The results are summarized as follows; 1. MICs of ISP + cefazolin (CEZ), ISP + cefotiam (CTM) and ISP + flomoxef (FMOX) were low and the activities against methicillin (DMPPC)-susceptible S. aureus (MSSA) were dependent on the concentration of ISP. Combined effects were observed when the concentrations of ISP were at sub-MIC levels (1/2 approximately 1/4 concentrations). 2. MICs of ISP + CEX, ISP + CTM, ISP + FMOX, ISP + imipenem and ISP + panipenem were low and the activities against DMPPC-resistant S. aureus (MRSA) were dependent on the concentration of ISP, and were similar to those against MSSA. Combined effects were observed when the concentrations of ISP were at sub-MIC levels of ISP. Lower MIC50 or MIC90 was observed at ISP concentrations of 4 approximately 16 micrograms/ml. 3. The blood Cmax of ISP exceeded 20 micrograms/ml at one-time administration of ISP 400 mg, and these results suggested that antibacterial activities of combination uses of ISP and beta-lactams was clinically effective against MRSA infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefazolin; Cefotiam; Cephalosporins; Dose-Response Relationship, Drug; Drug Therapy, Combination; Gentamicins; Humans; Methicillin Resistance; Staphylococcus aureus