Tadashi Kosaka

Kyoto Prefectural University of Medicine, Kioto, Kyōto, Japan

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Publications (6)15.75 Total impact

  • N Shime, T Kosaka, N Fujita
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    ABSTRACT: PURPOSE: To examine the status and clinical outcome of de-escalating antimicrobial therapy for bacteraemia due to hospital-acquired, Gram-negative bacilli that are difficult to treat. METHODS: Among 1,610 patients presenting with positive blood cultures collected at our medical centre over a 6-year period, 133 were infected with Serratia, Pseudomonas, Acinetobacter, Citrobacter or Enterobacter sp. (SPACES). We examined the appropriateness of an empiric initial administration of antimicrobials based on in vitro sensitivity, and the success and outcomes of a pathogen-directed de-escalation of therapy. The treatment was considered to be successfully de-escalated when the antimicrobial spectrum was narrowed according to a spectrum ranking or when ≥2 antimicrobials prescribed initially were lowered to one agent. Outcome measures included persistent, recurrent and metastatic infections, infection-related deaths and cost of antimicrobials. RESULTS: The treatment was initially appropriate in 79 of 133 patients (59 %), of whom 49 (62 %) were candidates for and 28 (57 %) underwent treatment de-escalation. No treatment failure was observed among these 28 patients, while 2 of 11 patients (18 %) whose treatment was not de-escalated died (p = 0.13). The median cost of antimicrobials was 250/patient lower in the de-escalated than in the non-de-escalated group (p < 0.001). CONCLUSIONS: Antimicrobial therapy for bacteraemia due to hard-to-treat SPACES was de-escalated in 57 % of candidates, based on the in vitro sensitivity, with no deaths and significantly lower costs of antimicrobial therapy.
    Infection 12/2012; · 2.44 Impact Factor
  • Hidekazu Ito, Nobuaki Shime, Tadashi Kosaka
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    ABSTRACT: Vancomycin (VAN) and teicoplanin (TEIC) are the glycopeptide antimicrobials commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection in pediatric patients. This study examined the relationship between the initial doses of glycopeptides and the trough serum concentrations of drugs in children, with the intent to determine their optimal dosing. Consecutive patients between 0 and 18 years of age, who between June 2003 and December 2010 were treated with VAN (n = 50) or TEIC (n = 187) for >48 h, were enrolled in this study. Patients were classified into three groups depending on the dose administered: lower than, equal to, or higher than the recommended dosage by each package insert. The patient's age, body weight, dose of antimicrobial administered during the first 24 h, median trough serum concentrations between 48 and 72 h after the onset of treatment, and serum creatinine concentrations before and 3 and 7 days after its administration were recorded. Median trough concentrations for VAN and TEIC in the three dosage groups were 8.0, 8.5, and 13.0 μg/ml, and 11.8, 13.0, and 17.7 μg/ml, respectively. The median serum creatinine concentrations did not rise significantly between baseline and 3 and 7 days after the onset of treatment in any treatment group. Therapeutic serum concentrations of VAN and TEIC to treat MRSA infections, 15-20 and ≥20 μg/ml, respectively, were rarely reached by the administration of standard doses of drugs for children.
    Journal of Infection and Chemotherapy 08/2012; · 1.55 Impact Factor
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    ABSTRACT: The purpose of this investigation was to study the effects of renal function on the pharmacokinetics and pharmacodynamics (PK-PD) of free cefazolin administered prophylactically in cardiothoracic surgery. Patients received an initial 2-g dose of cefazolin, followed by 1-g doses 6, 12, 18 and 24 h after the first dose. In patients who underwent cardiopulmonary bypass, 1 g was added to the priming solution. In 35 patients with a normal estimated creatinine clearance (CLcr) ≥50 ml/min, a free cefazolin concentration <4 μg/ml was observed in 11.4, 5.7 and 54.3% of patients before the second dose, at the end and 24 h after operation, respectively. In contrast, only 7.4% of 27 patients with CLcr <49 ml/min had a free cefazolin concentration <4 μg/ml 24 h after the operation. There was a high negative correlation between CLcr and time above the target minimal inhibitory concentration (MIC) when the CLcr was <50 ml/min (r(2) = 0.807), and no correlation when the CLcr was ≥50 ml/min. Renal function has a significant impact on the PK-PD of prophylactic cefazolin in cardiothoracic surgery. The postoperative drug dosing intervals should be <6 h in order to achieve a 100% time above the MIC in patients with CLcr ≥ 50 ml/min.
    European Journal of Clinical Microbiology 05/2011; 31(2):193-9. · 3.02 Impact Factor
  • N Shime, T Kosaka, N Fujita
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    ABSTRACT: The purpose of this investigation was to examine the impact of antimicrobial regimens administered for hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia on the all-cause, 14-day mortality. We retrospectively examined the characteristics of the most effective empiric antimicrobial therapy in 87 consecutive patients, hospitalised at a single institution between April 2003 and March 2008, who presented with clinically and microbiologically confirmed MRSA bacteraemia. The all-cause mortality was measured 14 days after the diagnosis was made. The administration of an effective antimicrobial against MRSA <48 h after the collection of blood cultures was the single, significant predictor of survival (odds ratio 3.85; 95% confidence interval 1.37-10.80; p = 0.01). The survival of patients treated with vancomycin versus other antimicrobial agents was similar. Among subgroups treated with vancomycin, the lowest mortality (6%) was observed among patients treated (a) within 48 h after the collection of blood cultures and (b) with doses sufficient to keep the blood concentrations in the area under the 0-24 h curve >400 μg h/ml (≥2.0 g/day). The empiric administration of antimicrobials effective against MRSA bacteraemia within 48 h after the collection of blood cultures increased the 14-day survival. If vancomycin is chosen, ≥2.0 g/day should be administered, starting within 48 h.
    European Journal of Clinical Microbiology 12/2010; 29(12):1475-9. · 3.02 Impact Factor
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    ABSTRACT: Here we report our experience with four paediatric patients with mediastinitis due to meticillin-resistant Staphylococcus aureus (MRSA) following cardiac surgery refractory to glycopeptide treatment and treated by linezolid. The pharmacokinetics and tolerance of linezolid administered orally or intravenously were analysed. Linezolid was administered intravenously at a dosage of 10 mg/kg every 8 h and then orally. In oral administration, 10 mg/kg or 15 mg/kg was given every 8 h as a powder made by crushing tablets. The linezolid serum trough concentration was >or=3.5 mg/L in patients treated by intravenous administration. However, with oral administration lower trough levels were detected, including patients with an undetectable level (<0.1 mg/L). No significant intolerance or drug-related haematological events were reported. We conclude that linezolid, with a switch from intravenous to oral administration, could be an effective and safe option in paediatric mediastinitis refractory to conventional glycopeptides, whilst care must be taken to maintain an adequate dose by monitoring the trough concentration.
    International journal of antimicrobial agents 12/2008; 33(4):368-70. · 3.03 Impact Factor
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    ABSTRACT: To examine the evolution of serum concentrations of prophylactic glycopeptides administered during state-of-the-art cardiopulmonary bypass (CPB) and vigorous haemodiafiltration in paediatric patients undergoing cardiac surgery. We enrolled infants and children <3 years of age who, based on the preoperative microbiological screening, age and surgical complexity, were at high risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Antimicrobial prophylaxis with glycopeptides was administered to 22 patients, randomly assigned to vancomycin (VAN; n=11) versus teicoplanin (TEC; n=11). Fixed doses of each drug (15 mg/kg for VAN and 8 mg/kg for TEC) were administered immediately before the operation, at the time of priming of the extracorporeal circuit, upon admission to the intensive care unit and for 48 h thereafter, q. 8 h for VAN, and once daily for TEC. Vigorous haemodiafiltration was applied during and briefly after CPB. The second dose of drug added to the prime prevented a fall in serum drug concentrations at the onset of CPB in both groups. A 77% decrease in VAN, versus 53% in TEC concentrations, was observed after the conclusion of CPB. Serum concentrations of TEC>10 microg/ml were observed throughout the treatment period in 91% of patients, while 55% of patients assigned to VAN had serum concentrations consistently >5 microg/ml (p=0.08). Therapeutic serum concentrations were maintained throughout the intraoperative period, particularly with TEC, administered before the first surgical incision, followed by a supplemental bolus in the priming fluid of CPB. Postoperative surgical wound infections occurred in neither group. The prophylactic use of glycopeptides in paediatric patients at high risk of MRSA infection undergoing cardiac surgery was safe and effective. TEC might be the drug of choice, since stable, therapeutic serum concentrations were easily maintained throughout the treatment period.
    European Journal of Cardio-Thoracic Surgery 11/2007; 32(4):577-81. · 2.67 Impact Factor