Background:A trough concentration of >20 mg/L is considered the optimal dosage of teicoplanin required to ensure early therapeutic effects against methicillin-resistant Staphylococcus aureus (MRSA) infections including those in patients who develop febrile neutropenia after chemotherapy. This study determines appropriate initial doses during the first 2 days of administration and evaluates the therapeutic target teicoplanin trough concentration.Method:A 2-day regimen was evaluated in patients treated with 600 mg and 1200 mg or 1200 mg and 600 mg (total 1800 mg, Group 1), 800 mg and 800 mg (total 1600 mg, Group 2), and 800 mg and 400 mg (total 1200 mg, Group 3) of teicoplanin on Days 1 and 2, respectively. We also compared the efficiency and adverse effects at trough concentrations of 15–20 mg/L (Group A, n = 28) with >20 mg/L (Group B, n = 27) of teicoplanin, and also compared them with those on the similar concentrations of vancomycin (Groups C and D, n = 50 and 34, respectively).Results:The mean trough concentrations of teicoplanin on Days 4 or 5 were 22.2, 17.5, and 16.2 mg/L in Groups 1, 2, and 3, respectively. The clinical efficiency was 85.7%, 81.5%, 92.0%, and 91.5%, in Groups A, B, C, and D, respectively. The rates of adverse effects were not high in teicoplanin (nephrotoxicity, 7.1% and 3.7%, and hepatotoxicity, 14.3% and 11.1% in Groups A and B, respectively). However, more adverse effects tended to arise in patients who received vancomycin in nephrotoxicity (14.0% and 11.8%, in Groups C and D, respectively).Conclusion:These results suggest that the 2-day regimens with total 1800 mg achieved the most effective therapeutic trough plasma concentration of teicoplanin (20 mg/L). However, 15–20 mg/L might also be an effective trough target for initial teicoplanin treatment. These teicoplanin regimens might be safer in terms of renal function than vancomycin.
Many healthcare workers are concerned about the risk of occupational exposures to hazardous drugs. The Japanese Society of Hospital Pharmacists (JSHP) revised the``Guidelines for the Handling of Antineoplastic Drugs in Hospitals'', however, the precautions and awareness of handling drugs varied in institutions. We assessed the levels of environmental contaminations in our hospital and urinary excretion of cyclophosphamide (CP) and ifosfamide (IF) in pharmacists and nurses. In environmental studies, we obtained samples by wiping the surfaces around two biological safety cabinets (BSCs) on eight days for four months. One BSC was equipped in hospital pharmacy and the other was equipped in an oncology ward, and used for preparing chemotherapeutic drugs for outpatients and for inpatients, respectively. We obtained the urine samples from 6 pharmacists and 2 nurses. We used solid phase extraction (SPE) as a convenient extraction procedure and liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) for the analysis of the samples. CP was detected on the working surfaces inside both BSCs, and detected at low levels on the back surfaces of the BSCs and at the working tables around the BSCs. IF over the LLOQ was not detected in both BSCs. CP and IF were not detected in all urine samples of pharmacists and nurses. Detection frequencies and amounts of these drugs were low levels, compared with previous reports in Japan, and our results showed that improving awareness about handling hazardous drugs could reduce the risk of the occupational exposures.
The objective of this study is to investigate an eŠect on the antimicrobial appropriate use of the antimicrobial stewardship. We investigated the consumption of injectable antimicrobials from 2001 to 2007 and the administration period of speciˆc antimicrobials (carbapenems, fourth-generation cephalosporins, anti-methicillin-resistant Staphylococcus aureus (MRSA) agents) in the individual patient. Since September 2004, the infection control team at Osaka University Hospital has been promoting appropriate use of antimicrobials through consultation, education, and weekly surveillance of speciˆc antimicrobial usage. We obtained the amount of all antimicrobial injections as titer from the medical information database of the electronic medical chart system retrospectively. Antimicrobial use densities (AUD) were evaluated by measuring the number of doses administered/1000 patient-days. Although the number of inpatient admissions and operations increased 1.53-and 1.39-fold, respectively, in the seven years from 2001 to 2007, the expenditure on speciˆc antimicrobials decreased markedly with AUD of speciˆc antimicrobials decreasing from 39.6 to 29.2. The percentage of inpatients receiving speciˆc antimicrobials decreased from 19.8% to 9.8%, and the ratio of the number of inpatients administered a speciˆc antimicrobial within seven days to the number of inpatients administered each speciˆc antimicrobial increased to over 60%. This led to reduction in the total expenditure of antimicrobials by about \100 million annually. The incidence of hospital-associated MRSA (HA-MRSA) infection decreased from 0.93% (2003) to 0.68% (2007). We can reduce the expenditure of antimicrobials without increasing incidence of the HA-MRSA by antimicrobial stewardship, and we think that appropriate use of antimicrobials is achieved progressively.
Ceftriaxone is a widely used third-generation cephalosporin showing advantageous pharmacokinetic properties and a broad antimicrobial spectrum. We herein report a case of ceftriaxone-induced neurotoxicity in a 56-year-old man on hemodialysis. Seven days after initiating high-dose ceftriaxone, the patient developed impaired consciousness along with facial myoclonus and sporadic phonation. The symptoms clearly disappeared shortly after withdrawal of the drug. Ceftriaxone is considered a safe antibiotic for patients with renal insufficiency, since it is excreted via both haptic and renal pathways. Physicians should note that antibiotic-associated encephalopathy may develop in patients administered ceftriaxone, especially in those complicated with renal dysfunction.
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