meropenem and pazufloxacin

The usefulness of switch therapy, from injection to oral medicine, for the treatment of peritonitis was evaluated. Thirty-five patients, who agreed to enroll the study, were randomly assigned to four treatment groups; one group treated with carbapenem antibacterial agent alone and three groups treated with switch therapy, in which injectable quinolone was switched to oral quinolone. For the intravenous administration group, if the patient showed the tendency of improvement by the third day, the intravenous injection was continued. However, if the patient did not show any improvement, the medication was changed to other medicine. For the switch therapy group, if the body temperature dropped to 37.5 degrees C or lower for at least 8 hours and if blood findings and clinical findings showed the tendency of improvement by the fourth day, the medication was switched to oral medicine. There was no difference in therapeutic effects among treatment groups. However, both duration of hospitalization and total medical costs were significantly reduced in the switch therapy groups comparing to those in the intravenous administration group. The results of this study showed that the switch therapy, from injection to oral medicine, was one of useful treatments in treating peritonitis.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Ciprofloxacin; Clindamycin; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluoroquinolones; Health Care Costs; Humans; Injections, Intravenous; Meropenem; Middle Aged; Naphthyridines; Ofloxacin; Oxazines; Peritonitis; Thienamycins

Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory mediators and renal support. Thus, it is necessary to decide the antibiotic dosage considering the CRRT clearance in addition to residual renal function. Some of the hemofilters used in CRRT are known to adsorb antibiotics, and clearance of antibiotics may differ depending on the adsorptive characteristics of hemofilters. Although assay systems for blood and CRRT filtrate concentrations are required, no method for measuring antibiotics concentrations in filtrate has been reported. We developed a UHPLC-MS/MS method for simultaneous quantification of antibiotics commonly used in ICU, comprising carbapenems [doripenem (DRPM) and meropenem (MEPM)], quinolones [ciprofloxacin (CPFX), levofloxacin (LVFX) and pazufloxacin (PZFX)] and anti-MRSA agents [linezolid (LZD), and tedizolid (TZD)] in CRRT filtrate samples.. Filtrate samples were pretreated by protein precipitation. The analytes were separated with an ACQUITY UHPLC CSH C18 column under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate.. The method showed good linearity over wide ranges. Within-batch and batch-to-batch accuracy and precision for each drug fulfilled the criteria of the US Food and Drug Administration guidance. The recovery rate was more than 87.20%. Matrix effect ranged from 99.57% to 115.60%. Recovery rate and matrix effect did not differ remarkably between quality control samples at different concentrations.. This is the first report of a simultaneous quantification method of multiple antibiotics in filtrate of CRRT circuit.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Ciprofloxacin; Continuous Renal Replacement Therapy; Doripenem; Humans; Levofloxacin; Linezolid; Meropenem; Tandem Mass Spectrometry

Critically ill patients in intensive care unit (ICU) are susceptible to infectious diseases, thus empirical therapy is recommended. However, the therapeutic effect in ICU patients is difficult to predict due to fluctuation in pharmacokinetics because of various factors. This problem can be solved by developing personalized medicine through therapeutic drug monitoring. However, when different measurement systems are used for various drugs, measurements are complicated and time consuming in clinical practice. In this study, we aimed to develop an assay using ultra-high performance liquid chromatography coupled with tandem mass spectrometry for simultaneous quantification of 12 antimicrobial agents commonly used in ICU: doripenem, meropenem, linezolid, tedizolid, daptomycin, ciprofloxacin, levofloxacin, pazufloxacin, fluconazole, voriconazole, voriconazole N-oxide which is a major metabolite of voriconazole, and posaconazole.. Plasma protein was precipitated by adding acetonitrile and 50% MeOH containing standard and labeled IS. The analytes were separated with an ACQUITY UHPLC CSH C18 column, under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate.. The method fulfilled the criteria of US Food and Drug Administration for assay validation. The recovery rate was more than 84.8%. Matrix effect ranged from 79.1% to 119.3%. All the calibration curves showed good linearity (back calculation of calibrators: relative error ≤ 15%) over wide concentration ranges, which allowed determination of C. We have developed an assay for simultaneous quantification of 12 antimicrobial agents using a small sample volume of 50 μL with a short assay time of 7 min. Our novel method may contribute to simultaneous calculation of pharmacokinetic and pharmacodynamic parameters.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Azoles; Carbapenems; Chromatography, High Pressure Liquid; Ciprofloxacin; Daptomycin; Doripenem; Drug Monitoring; Female; Fluconazole; Fluoroquinolones; Humans; Intensive Care Units; Levofloxacin; Linezolid; Male; Meropenem; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Oxazines; Oxazolidinones; Quinolones; Tandem Mass Spectrometry; Tetrazoles; Voriconazole

The effectiveness of antibacterial agents against 70 strains of clinically isolated multiple-drug resistant Pseudomonas aeruginosa (MDRP) was measured by the micro dilution method. Fifty of all strains (71%) produced metallo-beta-lactamase and the IMP-1 gene was detected by polymerase chain reaction (PCR). The MIC90 (the minimum inhibitory concentration of an antibiotic necessary to inhibit the growth of 90% of bacterial strains) values of biapenem (BIPM), meropenem (MEPM), tazobactam/piperacillin (TAZ/PIPC), sulbactam/ cefoperazone (SBT/CPZ), cefepime (CFPM), ciprofloxacin (CPFX), pazufloxacin (PZFX), amikacin (AMK) and aztreonam (AZT) were found to be 265, 512, 256, 512, 512, 64, 128, 128 and 128 microg/mL, respectively. The in vitro combination effects of antibacterial agents were examined against 62 strains of MDRP and the synergy or additive effects were evaluated by fractional inhibitory concentration (FIC) index calculated by the checkerboard method. The combination of AMK and AZT showed synergy effects on 15/59 (25.4%) strains of MDRP. The synergy and additive effects on the MDRP strains were also found by the other antibacterial agents combination such as TAZ/PIPC and AMK, CFPM and AMK, and SBT/CPZ and AZT. These results suggested the necessity of further investigation of clinical usefulness.

Topics: Amikacin; Anti-Bacterial Agents; Aztreonam; Cefepime; Cefoperazone; Cephalosporins; Ciprofloxacin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fluoroquinolones; Humans; Meropenem; Microbial Sensitivity Tests; Oxazines; Penicillanic Acid; Piperacillin; Pseudomonas aeruginosa; Sulbactam; Tazobactam; Thienamycins

We tested the drug susceptibility to 8 anti-pseudomonal agents of 97 strains of Pseudomonas aeruginosa isolated from urine between January 1998 and May 2004. The results were as follows. 1. Antimicrobial activity was, in order of superiority to biapenem (BIPM), meropenem (MEPM), ciprofloxacin (CPFX), imipenem (IPM), pazufloxacin (PZFX), amikacin (AMK), ceftazidime (CAZ), piperacillin (PIPC). 2. The resistance rate (intermediate+resistance) to carbapenem drugs was 10.3% for BIPM and MEPM, and 13.4% for IPM. Many of the IPM-resistant strains showed crossover resistance with BIPM and MEPM. 3. The resistance rate (intermediate+resistance) to fluoroquinolone drugs was 23.7% for CPFX and 20.6% for PZFX. 4. One strain showed simultaneous resistance to IPM = 16 microg/mL, CPFX = 4 microg/mL, and AMK = 32 microg/mL, and produced IMP-1 metallo-beta-lactamase. Susceptibility of P. aeruginosa isolated from urine developed resistance to fluoroquinolone drugs. It is important to promote appropriate use of antimicrobial agents and continue to survey emerging resistance in the clinical isolates.

Topics: Amikacin; Anti-Infective Agents; Carbapenems; Ceftazidime; Ciprofloxacin; Drug Resistance, Microbial; Fluoroquinolones; Humans; Imipenem; Meropenem; Oxazines; Piperacillin; Pseudomonas aeruginosa; Thienamycins; Urine

We investigated the in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), a new injectable quinolone, and obtained the following results. 1) The MIC50 and MIC90 values of PZFX against clinically isolated Gram-positive and -negative bacteria, ranged from 0.0125 to 12.5 micrograms/ml and 0.025 to 100 micrograms/ml, respectively. PZFX showed broad spectrum activity. The antibacterial activities of PZFX against quinolone-susceptible, methicillin-resistant Staphylococcus aureus, beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae, extended spectrum beta-lactamase possessing Klebsiella pneumoniae and imipenem/cilastatine (IPM/CS)-resistant Pseudomonas aeruginosa were superior to those of ceftazidime (CAZ), ceftriaxone, IPM/CS, meropenem and panipenem/betamipron. 2) PZFX showed superior bactericidal activity against S. aureus, Escherichia coli, Proteus mirabilis, Serratia marcescens and P. aeruginosa to those of CAZ and IPM/CS after treatment for 15 minutes at the drug concentration equivalent to that in human serum at clinical dose to be continued for 15 minutes. 3) CAZ and IPM/CS had no bactericidal activity at the 16 times of MIC against P. aeruginosa in human polymorphonuclear leucocytes, while PZFX exhibited potent bactericidal activity in a dose-dependent manner against such bacteria. 4) PZFX inhibited both DNA gyrase and topoisomerase IV from S. aureus at nearly the same level. PZFX showed poor inhibitory activity against topoisomerase II from human placenta and showed high selectivity to bacterial topoisomerase. 5) PZFX mesilate showed superior therapeutic activity to that of CAZ with following infection model caused by S. aureus and P. aeruginosa or each; systemic infection with cyclophosphamide-treated mice, systemic infection in mice with high challenge doses, CMC pouch infection in rat, and calculus infection in rat bladder. 6) Intravenous administration of PZFX with high plasma concentration just after administration, showed more excellent therapeutic effect against the rat intraperitoneal infection, than p.o. and s.c. administration.

Topics: 4-Quinolones; Ampicillin; Animals; Anti-Bacterial Agents; Anti-Infective Agents; beta-Alanine; Ceftazidime; Ceftriaxone; Cilastatin; Cilastatin, Imipenem Drug Combination; DNA Topoisomerase IV; Dose-Response Relationship, Drug; Drug Combinations; Female; Fluoroquinolones; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Methicillin Resistance; Mice; Microbial Sensitivity Tests; Oxazines; Rats; Thienamycins; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors