OBJECTIVETo observe the release of DNA from Pseudomonas aeruginosa (P. aeruginosa) induced by different concentrations of piperacillin/tazobactam (Piper) in vitro.

METHODSThe minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of Piper against 1244 strain (ATCC 27317) of P. aeruginosa were determined, respectively. This strain of P. aeruginosa was separately cultured with Piper in different concentrations at 37 degrees C for 4 h and 24 h. The samples of cultural supernatant were filtered and electrophoresis was conducted in 1.8% agarose with SYBR Gold stain. Then the images of the gel sheets were photographed.

RESULTSThis strain of P. aeruginosa was sensitive to Piper. The bacterial DNA was not detected in 4-h cultured P. aeruginosa either with or without Piper by this method. The bacterial DNA molecules could be detected in 24 h samples in cultures without Piper, and they were displayed in two zones of molecular weight over 2000 base pairs (bp) and lower than 100 bp. Similar results were observed when the MIC of piper (0.002, 0.004 g/L) were under the MIC measured at the 3rd time (0.008 g/L), but there was much more bacterial DNA with molecular weight lower than 100 bp. When Piper concentration was higher than its MIC, only smaller quantities of bacterial DNA in the area with molecular weight lower than 400 bp could be detected in 24-h culture samples.

CONCLUSIONA certain amount of bacterial DNA was released from P. aeruginosa under its natural growth circumstance. Different concentrations of Piper showed different effects on DNA release, in regard to its quantity and molecular weight, from P. aeruginosa cultures.

Anti-Bacterial Agents ; pharmacology ; DNA, Bacterial ; metabolism ; Penicillanic Acid ; analogs & derivatives ; pharmacology ; Piperacillin ; pharmacology ; Pseudomonas aeruginosa ; drug effects ; metabolism

Ambroxol ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Humans ; Infant ; Male ; Penicillanic Acid ; analogs & derivatives ; therapeutic use ; Pneumonia ; drug therapy ; etiology ; virology ; Poliomyelitis ; immunology ; Vaccines ; adverse effects ; immunology

AIMTo investigate whether tazobctam has crystallization water.

METHODSIn order to establish a method for water content determination in tazobctam, many methods including Karl Fischer titration, weight loss on drying, TGA, DSC and X-ray diffraction experiment of an orthorhombic form were studied.

RESULTSThe water content of the same batch tazobactam determined by different mthods was different.

CONCLUSIONThe results showed that one mole tazobatam contains half mole water of crystallization and the strength of attraction between tazobatam molecule and water molecule is rather strong.

Crystallization ; Enzyme Inhibitors ; chemistry ; Molecular Conformation ; Molecular Structure ; Penicillanic Acid ; analogs & derivatives ; chemistry ; Water ; X-Ray Diffraction ; beta-Lactamase Inhibitors ; beta-Lactamases ; chemistry

OBJECTIVETo evaluate the efficacy of piperacillin/tazobactam in the management of burn infection.

METHODSSixty-three burn patients were enrolled in the study with burn sepsis or burn area more than 50%TBSA or full skin loss more than 30% TBSA. The administration regime of the antibiotics was 4.5 g intravenously administered every 8 hours in the treatment of burn sepsis or in the prophylactic management. The effectiveness was identified when the septic symptoms disappeared or focal infection did not develop into sepsis.

RESULTSThe overall clinical efficacy was 90.4%, and success in sepsis (control) was 75%. Furthermore, 95.7% of the focal infection was prevented from developing into systemic infection. The bacterial clearance rates were 71.4% and 51.4% in treatment and prophylaxis groups, respectively.

CONCLUSIONPiperacillin/taxobactam was effective in the treatment and/or prophylaxis of burn sepsis caused by bacteria susceptible to it, so it could be applied empirically.

Adult ; Burns ; complications ; drug therapy ; Female ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Penicillanic Acid ; analogs & derivatives ; therapeutic use ; Piperacillin ; therapeutic use ; Sepsis ; etiology ; prevention & control ; Treatment Outcome

Immobilized penicillin acylase was used for bioconversion of penicillin PG into 6-APA in aqueous two-phase systems consisting of a light-sensitive polymer PNBC and a pH-sensitive polymer PADB. Partition coefficients of 6-APA was found to be about 5.78 in the presence of 1% NaCl. Enzyme kinetics showed that the reaction reached equilibrium at roughly 7 h. The 6-APA mole yields were 85.3% (pH 7.8, 20 degrees C), with about 20% increment as compared with the reaction of single aqueous phase buffer. The partition coefficient of PG (Na) varied scarcely, while that of the product, 6-APA and phenylacetic acid (PA) significantly varied due to Donnan effect of the phase systems and hydrophobicity of the products. The variation of the partition coefficients of the products also affected the bioconversion yield of the products. In the aqueous two-phase systems, the substrate, PG, the products of 6-APA and PA were biased in the top phase, while immobilized penicillin acylase at completely partitioned at the bottom. The substrate and PG entered the bottom phase, where it was catalyzed into 6-APA and PA and entered the top phase. Inhibition of the substrate and products was removed to result in improvement of the product yield, and the immobilized enzyme showed higher efficiency than the immobilized cells and occupied smaller volume. Compared with the free enzyme, immobilized enzyme had greater stability, longer life-time, and was completely partitioned in the bottom phase and recycle. Bioconversion in two-phase systems using immobilized penicillin acylase showed outstanding advantage. The light-sensitive copolymer forming aqueous two-phase systems could be recovered by laser radiation at 488 nm or filtered 450 nm light, while pH-sensitive polymer PADB could be recovered at the isoelectric point (pH 4.1). The recovery of the two copolymers was between 95% and 99%.
Catalysis ; Enzymes, Immobilized ; metabolism ; Hydrogen-Ion Concentration ; Kinetics ; Penicillanic Acid ; analogs & derivatives ; chemistry ; metabolism ; Penicillin Amidase ; metabolism ; Penicillin G ; chemistry ; metabolism ; Phase Transition ; Polymers ; chemistry ; Substrate Specificity

OBJECTIVE: To determine the drug resistance of Comamonas testosteroni (C. testosteroni) by the Kirby-Bauer (K-B) method without Clinical and Laboratory Standards Institute (CLSI) explanation or the minimum inhibitory concentration (MIC) method with the standard CLSI explanation to evaluate the sensitivity of K-B method in detection of C. testosteroni.
 METHODS: K-B method and MIC method was used to determine the sensitivity of C. testosteroni to Piperacillin, Cefepime, Piperacillin/tazobactam, Imipenem, Meropenem, Amikacin, Gentamicin, Tobramycin, Ceftazidime and Ciprofloxacin. The interpretation standard for Pseudomonas aeruginosa was temporary used for the K-B method. The coincident rate was compared between the two methods.
 RESULTS: The complete or partial coincident rate for K-B method and MIC method to detect Piperacillin and Cefepime was 97.4% or 2.6%; the complete coincidence rate to detect Piperacillin/tazobactam, Imipenem and Meropenem was 100%; the complete or partial coincident rate to detect Amikacin, Gentamicin and Tobramycin 94.7% or 5.3%; the complete or partial coincident rate to detect Ceftazidime was 97.4% or 2.6%; the complete or partial coincident rate to detect Ciprofloxacin 86.8% or 10.6%, and the full non-coincidence rate was 2.6%.
 CONCLUSION The results of drug sensitive test from the two methods are highly consistent. We suggest that the microbiology labs do not report the interpretive results for C. testosteroni with K-B method but report the test results.
Anti-Bacterial Agents ; Cefepime ; Cephalosporins ; Comamonas testosteroni ; Imipenem ; Meropenem ; Microbial Sensitivity Tests ; Penicillanic Acid ; analogs & derivatives ; Piperacillin ; Piperacillin, Tazobactam Drug Combination ; Pseudomonas aeruginosa ; Thienamycins

OBJECTIVETo study the concentrations and pharmacokinetics of 6 different kinds of antibiotics in rabbit bile, and evaluate their microbicidal potential.

METHODSThirty-six health rabbits were randomly divided into 6 groups, and each group was 6 rabbits. After anaesthesia, the common bile duct of rabbit was isolated and cumulated with a silicone tube. The rabbits were administered intravenously with the equal-effect dose of antibiotics. Bile (1.5 ml) was collected at different time points after administration, and the concentration of antibiotics of bile was assayed by high performance liquid chromatography. The bile drug concentration-time data were processed by software to figure out the pharmacokinetic parameters such as maximum concentration (C(max)), peak time (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of distribution (VD). The bile antibiotics concentration contrasted to the minimum inhibitory concentration (MIC), and attained the bactericidal index (C(max)/MIC) and the time when the drug concentration exceeded the MIC (T(>MIC)).

RESULTSThe C(max) and T1/2 of each antibiotic were as the followings: piperacillin (7 950 ± 3 023) mg/L and (1.97 ± 1.23) h, ceftriaxone (1 104 ± 248) mg/L and (3.14 ± 0.57) h, cefoperazone (5 215 ± 2 225) mg/L and (0.89 ± 0.13) h, meropenem (31.97 ± 12.44) mg/L and (0.36 ± 0.11) h, levofloxacin (66.3 ± 36.9) mg/L and (3.32 ± 2.57) h, metronidazole (28.2 ± 10.2) mg/L and (0.81 ± 0.33) h, respectively. Piperacillin/tazobactam and cefoperazone/sulbactam had the largest bactericidal index and the longest T(>MIC), and their bactericidal indexes were (62.1 ± 23.6) - (993.8 ± 377.9) and (164.8 ± 69.0) - (659.3 ± 275.9), their T(>MIC) were (6.00 ± 2.53) - (8.00 ± 0.00) h and (6.33 ± 1.97) - (8.00 ± 0.00) h. The bactericidal index and T(>MIC) of levofloxacin were the smallest, which were (2.1 ± 1.2) - (8.3 ± 4.6) and (0.54 ± 0.25) - (2.67 ± 1.03) h . Ceftriaxone and meropenem were as the medium, and their bactericidal indexes and T(>MIC) were (4.3 ± 1.0) - (69.2 ± 15.5) , (1.42 ± 0.65) - (8.00 ± 0.00) h and (2.0 ± 0.8) - (1 031.3 ± 401.4) , (0.29 ± 0.10) - (1.83 ± 0.26) h. The bactericidal index of metronidazole to anaerobic ranged from 7.4 to 294.9, and the T(>MIC) ranged from 1.88 to 5.00 h.

CONCLUSIONSThe bile concentrations of six antibiotics all exceed their effective bactericidal concentrations. The concentration-time curves of piperacillin, cefoperazone, meropenem and metronidazole conformed to one-compartment model, and ceftriaxone and levofloxacin are conformed to two-compartment model. Piperacillin/tazobactam and cefoperazone/sulbactam have the largest bactericidal index and the longest T(>MIC), so they can be chosen as the first choice for the therapy of hepatobiliary infection.For the anaerobic, the microbicidal potential of metronidazole is high.

Animals ; Anti-Bacterial Agents ; analysis ; pharmacokinetics ; Bile ; chemistry ; drug effects ; Cefoperazone ; analysis ; pharmacokinetics ; Drug Combinations ; Metronidazole ; analysis ; pharmacokinetics ; Microbial Sensitivity Tests ; Penicillanic Acid ; analogs & derivatives ; analysis ; pharmacokinetics ; Piperacillin ; analysis ; pharmacokinetics ; Rabbits ; Random Allocation ; Sulbactam ; analysis ; pharmacokinetics ; Thienamycins ; analysis ; pharmacokinetics

PURPOSE: Combination antibiotic treatment is preferred in nosocomial infections caused by Pseudomonas aeruginosa (P. aeruginosa). In vitro synergism tests were used to choose the combinations which might be used in clinic. The aim of this study was to investigate the synergistic efficacy of synergistic antibiotic combinations in multidrug resistant P. aeruginosa strains. MATERIALS AND METHODS: Synergistic efficacies of ceftazidime-tobramycin, piperacillin/tazobactam-tobramycin, imipenem-tobramycin, imipenem-isepamycin, imipenem-ciprofloxacin and ciprofloxacin-tobramycin combinations were investigated by checkerboard technique in 12 multiple-resistant and 13 susceptible P. aeruginosa strains. RESULTS: The ratios of synergy were observed in ceftazidime-tobramycin and piperacillin/tazobactam-tobramycin combinations as 67%, and 50%, respectively, in resistant strains, whereas synergy was not detected in other combinations. The ratios of synergy were observed in ceftazidime-tobramycin, piperacillin/tazobactam-tobramycin, imipenem-tobramycin, imipenem-ciprofloxacin and imipenem-isepamycin combinations as 31%, 46%, 15%, 8%, 8%, and respectively, in susceptible strains, whereas synergy was not detected in ciprofloxacin-tobramycin combination. Antagonism was not observed in any of the combinations. CONCLUSION: Although the synergistic ratios were high in combinations with ceftazidime or piperacillin/tazobactam and tobramycin, the concentrations in these combinations could not usually reach clinically available levels. Thus, the solution of the problems caused by multiple resistant P. aeruginosa should be based on the prevention of the development of resistance and spread of the causative agent between patients.
Anti-Bacterial Agents/*pharmacology ; Ceftazidime/pharmacology ; Ciprofloxacin/pharmacology ; Drug Resistance, Multiple, Bacterial/*drug effects ; Drug Synergism ; Imipenem/pharmacology ; Microbial Sensitivity Tests ; Penicillanic Acid/analogs & derivatives/pharmacology ; Piperacillin/pharmacology ; Pseudomonas aeruginosa/*drug effects ; Tobramycin/pharmacology

Although drug fever may develop after administration of the drug by various routes, it has not been reported with antibiotic-loaded bone cement. Here, a case of drug fever induced by piperacillin/tazobactam loaded into bone cement is reported. A 72-yr-old woman presented with fever that developed two weeks after insertion of bone cement loaded with antibiotics including piperacillin/tazobactam into the knee joint for infectious arthritis. The fever was associated with a skin rash and blood eosinophilia. The work-up of the fever excluded several causes. Drug provocation test demonstrated that the piperacillin/tazobactam, which had been loaded in the bone cement, was the cause of the fever. The findings of this case suggest that drug fever can be induced by any drug placed and released continuously within the body. Therefore, the evaluation for possible drug fever should include all drugs the patient has been exposed to regardless of the route of administration.
Aged ; Anti-Bacterial Agents/*adverse effects ; Arthritis/drug therapy/pathology/surgery ; Bone Cements/*adverse effects/*chemistry ; Drug Therapy, Combination ; Enzyme Inhibitors/adverse effects ; Female ; Fever/*chemically induced ; Humans ; Penicillanic Acid/adverse effects/*analogs & derivatives ; Piperacillin/*adverse effects

No abstract available.
Adult ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bone Marrow Transplantation ; Capnocytophaga/drug effects/genetics/*isolation & purification ; Gram-Negative Bacterial Infections/complications/*diagnosis/drug therapy ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/complications/*diagnosis ; Male ; Microbial Sensitivity Tests ; Penicillanic Acid/analogs & derivatives/pharmacology/therapeutic use ; Piperacillin/pharmacology/therapeutic use ; RNA, Ribosomal, 16S/chemistry/metabolism ; Sequence Analysis, RNA ; Sequence Homology, Nucleic Acid ; Transplantation, Homologous ; Treatment Outcome