ABSTRACT
OBJECTIVES: It is known that prophylaxis with imipenem reduces the risk of infection accompanying severe acute pancreatitis. In this study,we modified a rat experimental model of severe acute pancreatitis for antibiotic evaluation, and the effect of biapenem was compared with that of imipenem to determine the usefulness of biapenem. METHODS: Severe acute pancreatitis was induced by 5% sodium taurocholate. Antibiotics were subcutaneously administered at 3 and 6 hours and evaluated at 12 hours after the pancreatitis induction. For pharmacokinetic evaluation, antibiotics were subcutaneously administered at 3 hours after the pancreatitis induction. RESULTS: From 3 hours after the induction, bacteria were detected from the pancreas. The total bacterial count increased in a time-dependent manner for 12 hours. Biapenem administration reduced the total bacterial count in the pancreas, as observed in imipenem administration. The plasma concentration of biapenem was almost equivalent to that of imipenem; however, the pancreatic penetration of biapenem was approximately twice that of imipenem in this model. CONCLUSIONS: Biapenem was suggested to be effective in prophylactic treatment of infectious complications as much as imipenem because of its superior penetration to the pancreas in severe acute pancreatitis.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Bacterial Infections/prevention & control , Imipenem/pharmacokinetics , Pancreas/drug effects , Pancreatitis/drug therapy , Thienamycins/pharmacokinetics , Acute Disease , Animals , Anti-Bacterial Agents/administration & dosage , Ascites/microbiology , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Disease Models, Animal , Dose-Response Relationship, Drug , Imipenem/administration & dosage , Injections, Subcutaneous , Intestines/microbiology , Lymph Nodes/microbiology , Male , Pancreas/metabolism , Pancreas/microbiology , Pancreatitis/chemically induced , Pancreatitis/metabolism , Pancreatitis/microbiology , Rats , Rats, Wistar , Severity of Illness Index , Taurocholic Acid , Thienamycins/administration & dosageABSTRACT
The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing beta-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillinsusceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.
Subject(s)
Cephalosporins/pharmacology , Haemophilus influenzae/drug effects , Ketolides/pharmacology , Staphylococcus aureus/drug effects , Streptococcus pneumoniae/drug effects , Streptococcus pyogenes/drug effects , Administration, Oral , Humans , Methicillin Resistance , Microbial Sensitivity TestsABSTRACT
Combined effects of arbekacin (ABK) with biapenem (BIPM) were examined on both in vitro and in vivo model of a mixture of MRSA and Pseudomonas aeruginosa. As a result, significant effect in vitro was observed in combined use of ABK (1/2 MIC) with BIPM (1/4 and 1/2 MIC) against MRSA as compared with ABK or BIPM alone. Against P. aeruginosa combined effect was also observed, showing reduction of viable cells to the limitation of detection within 2 hours. Moreover, with respect to the protective effect on mixed systemic infection of MRSA and P. aeruginosa, the combined treatment with ABK and BIPM showed more excellent efficacy as compared with the single use of each drug.
