dibekacin and Sepsis

The efficacy and safety of once-daily high-dose arbekacin sulfate therapy for methicillin-resistant Staphylococcus aureus (MRSA) infection were evaluated, with analysis of their relationship to blood drug levels. The study was conducted in patients with pneumonia or sepsis, the cause of which was suspected to be MRSA, who were admitted to the Nagasaki University Hospital or its affiliated hospitals between January 2009 and December 2010. The initial drug dose was set at a level expected to yield the goal peak of 20 μg/ml and a trough level of less than 2 μg/ml, using the Habekacin Therapeutic Drug Monitoring analysis software. Thirteen patients were enrolled: 10 patients had pneumonia and 3 patients had sepsis. Patient mean age was 72.0 years; mean initial drug dose was 269.2 mg. Clinical efficacy at completion of treatment and bacterial eradication-reduction were achieved in 66.7% (6/9) and 62.5% (5/8) of patients, respectively. Incidence of adverse reactions was 38.5% (5/13). In analysis of efficacy in relationship to serum drug levels, the peak drug level was 22.7 ± 5.50 μg/ml, on average, and 15 μg/ml or higher in all 6 responders. Also, in patients with renal dysfunction, it seemed to be essential to ensure a certain peak drug level and to control the trough level appropriately. Although the number of patients was limited, once-daily high-dose arbekacin sulfate therapy may be highly effective, without posing any major safety problems. Further larger-scale studies are needed.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Dibekacin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Staphylococcal; Sepsis; Staphylococcal Infections; Treatment Outcome

Arbekacin (ABK) is an aminoglycoside and widely used in Japan for treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Although, ABK has concentration-dependent antibacterial activity, the peak serum concentration (C (peak)) of ABK has not yet been fully investigated as an indicator of the efficacy of ABK. The present study was conducted in patients admitted to hospitals affiliated with the ABK Dose Finding Study Group, between October 2008 and June 2011, who had pneumonia or sepsis, the cause of which was identified or suspected to be MRSA. The initial target C (peak) was set at 15-20 μg/mL and therapeutic drug monitoring was conducted. Then the relationship between serum concentration and efficacy/safety of ABK was prospectively examined to obtain sufficient clinical efficacy. In total, 89 patients from 11 clinical sites in Japan were enrolled and 29 of these patients were subjected to efficacy analysis. The mean initial dose and C (peak) were 306.9 mg/day and 16.2 μg/mL, respectively. The efficacy rate was 95 % (19/20 patients) at 5-6 mg/kg or higher, 87.5 % (7/8) for sepsis and 90.5 % (19/21) for pneumonia, and the overall efficacy rate was 89.7 % (26/29). There was no increase in the incidence of adverse events. In conclusion, we recommend the initial dose of ABK at 5-6 mg/kg or higher and the dosage regimen should be adjusted to achieve C (peak) at 10-15 μg/mL or higher in the treatment of patients with pneumonia or sepsis caused by MRSA. This strategy would surely achieve low incidence of adverse events while obtaining high clinical efficacy.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Dibekacin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Female; Humans; Japan; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Staphylococcal; Sepsis

Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). The population pharmacokinetics of arbekacin was investigated in the Japanese, using 353 patients infected with MRSA and 50 healthy or renally impaired volunteers. The age of the study population ranged from 8 to 95 years, and weight ranged from 10.8 to 107 kg. In total, 1,581 serum arbekacin concentrations were measured (primarily from routine patient care) and used to perform the present pharmacokinetic analysis. Drug concentration-time data were well described by a two-compartment open model. Factors influencing arbekacin pharmacokinetics were investigated using a nonlinear mixed-effect model analysis. The best-developed model showed that drug clearance (CL) was related to creatinine clearance (CL(CR)), age, and body weight (WT), as expressed by CL (liter/h) = 0.0319CL(CR) + (26.5/age) (CL(CR) < 80 ml/min) and CL (liter/h) = 0.0130 CL(CR) + 0.0342WT + (26.5/age) (CL(CR) >/= 80 ml/min). The volume of distribution for the central and peripheral compartments was different in healthy subjects and infected patients, and this difference was more pronounced among disease types. The elderly subjects (aged 80 years or over) exhibited, on average, a 19% greater volume for the central compartment. The volumes for the peripheral compartment were 50.6 liters in patients with pneumonia and 24.3 liters in patients with sepsis. The population pharmacokinetic parameters of arbekacin obtained here are useful for optimal use of this aminoglycoside in the treatment of MRSA-infected patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Aminoglycosides; Anti-Bacterial Agents; Child; Dibekacin; Dose-Response Relationship, Drug; Female; Humans; Male; Methicillin Resistance; Middle Aged; Models, Statistical; Population; Reproducibility of Results; Sepsis; Staphylococcal Infections

We report here two cases of MRSA sepsis following craniotomy. In case 1, a petroclival meningioma was subtotally removed and lumbar drainage was inserted postoperatively to prevent cerebrospinal fluid leakage. Ventriculo-peritoneal shunt was performed after meningitis was treated with vancomycin and panipenem/betamipron. Two weeks after the procedure, the patient revealed continuous spiking fevers related to MRSA sepsis, which did not improve with vancomycin and arbekacin administration. The focus of infection was found by scintigraphy and CT by 67Ga to be spondylo-diskitis at the level of L2-L3. The lesion was removed and bone from the iliac crest grafted. In case 2, seven days after surgery for multiple meningioma, the patient exhibited spiking fevers and swelling in the left leg. The central venous catheter was removed from the left femoral vein and MRSA was found from blood culture. The patient was treated with arbekacin (200 mg/day). Venous thrombosis diagnosed by CT was treated with heparin. Symptoms related to the infection and laboratory data did not improve because the concentration of arbekacin in the blood did not reach an effective level. The symptoms markedly improved when the dose of arbekacin was doubled (400 mg/day).

Topics: Adult; Aged; Alanine; Aminoglycosides; Ampicillin; Anti-Bacterial Agents; Craniotomy; Dibekacin; Drug Therapy, Combination; Female; Humans; Male; Meningeal Neoplasms; Meningioma; Methicillin Resistance; Postoperative Complications; Sepsis; Staphylococcal Infections; Sulbactam; Thienamycins; Treatment Outcome; Vancomycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Catheterization; Dibekacin; Equipment Contamination; Humans; Methicillin Resistance; Prognosis; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The in vivo efficacy of habekacin, an aminoglycoside antibiotic obtained by chemical derivation from dibekacin, was compared to that of gentamicin (GEN), tobramycin (TOB), kanamycin (KAN) and amikacin (AMI) in a protection test in mice. The 50% effective dose (ED50) was determined in groups of animals challenged with bacterial suspensions injected intraperitoneally together with mucin, and treated subcutaneously 1 h and 6 h later. The bacterial strains used were: Escherichia coli (three GEN sensitive strains and one GEN-KAN-TOB resistant strain), Enterobacter cloacae (one GEN-KAN resistant strain), Serratia marcescens and Klebsiella pneumoniae (one GEN sensitive strain and one GEN resistant strain). In this model, habekacin was found to be as active as GEN against GEN sensitive strains and more active than AMI on GEN, GEN-KAN and GEN-KAN-TOB resistant strains.

Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Dibekacin; Enterobacteriaceae Infections; Female; Gentamicins; Kanamycin; Male; Mice; Microbial Sensitivity Tests; Sepsis; Tobramycin

Cefoxitin (CFX) was administrated to a total of 12 hospitalized patients with digestive diseases, in combination with aminoglycosides. The following results were obtained: Clinical effects of CFX on 12 cases were "excellent" in 4 cases, "good" in 5, "fair" in 1 and "unknown" in 2, with the efficacy rate of 75%. All 4 cases who developed septicemia with underlying severe diseases showed "excellent" effect to CFX. Clinical results of 8 cases with hepatic biliary tract infections were "good" in 5, "fair" in 1 and "unknown" in 2, with the efficacy rate in 62.5%. As for side effects, an allergic reaction was observed in 1 case, and it is suggested renal function should be monitored carefully in a case of combination use with aminoglycosides.

Topics: Aged; Bacterial Infections; Biliary Tract Diseases; Cefoxitin; Cholecystitis; Dibekacin; Digestive System Diseases; Drug Therapy, Combination; Female; Gallstones; Gentamicins; Humans; Liver Abscess; Male; Middle Aged; Sepsis

Topics: Abortion, Induced; Adolescent; Adult; Cesarean Section; Dibekacin; Drug Therapy, Combination; Female; Gentamicins; Humans; Intrauterine Devices; Pregnancy; Sepsis

During an open multicentric trial (17 centers), we have treated 62 septicemia by dibekacin, alone or associated with other antibacterial drugs. Taking into account the degree of severity of these patients, the results are considered satisfactory in 47 patients. 15 failures were noted (including 9 deaths). General and local tolerance were good, in spite of the duration of treatment.

Topics: Adult; Aged; Anti-Bacterial Agents; Dibekacin; Drug Therapy, Combination; Female; Humans; Kanamycin; Male; Middle Aged; Sepsis