The area under the concentration-time curve (AUC) of mycophenolic acid (MPA) in heart transplantation patients was estimated from a single plasma concentration using a population pharmacokinetic model as a substitute for the trapezoidal method that requires frequent sampling data. Plasma MPA concentrations at 2-12 h after oral administration were analyzed using a linear 1-compartment open model after intravenous injection. The individual pharmacokinetic parameters and plasma MPA concentrations were estimated from the observed single plasma MPA concentration based on the Bayesian approach. The AUC0-12h after oral administration was calculated by the trapezoidal method, using the predicted plasma MPA concentrations. The AUC0-12h value estimated from the plasma MPA concentration at 2 h after dosing adequately predicted the AUC value, calculated by frequent sampling data. These results indicate that the present estimation method for AUC0-12h is more convenient than the conventional method and is expected to be applied to clinical practice.
Several cases have reported that the plasma concentration of carbapenem antibiotics became lower than expected in patients with critical illness and/or transfusion. Therefore, in order to adjust the doses of carbapenem antibiotics, we developed and optimized the method to measure meropenem (MEPM) and doripenem (DRPM) in human plasma by a liquid chromatography-tandem mass spectrometry (LC-MS/MS). A C18 column and mobile phase consisting of 10 mM ammonium formate containing 0.1% formic acid in 70% methanol were used for chromatographic separation. DRPM for MEPM determination and vice versa were used as internal standards. Both MEPM and DRPM could be detected within 5 minutes. Regarding the stock solution, MEPM stock solution should be used within 2 weeks of preparation when stored at -30℃. The solid phase extraction Oasis® HLB was used to extract carbapenem antibiotics. Thirty mg cartridges were suitable for extraction from 100 μL plasma samples. Importantly, it should be noted that the rate of reduction of MEPM and DRPM in plasma exceeded 20% two months after freezing at -30℃. Our established method could measure MEPM and DRPM in plasma (1.0-40 μg/mL) that would be useful to adjust their dosages in clinical practice.
When microbes present on the rubber stopper in a vial or attachment part of closed system drug transfer devices (CSTD), these microbes may contaminate vials by needle puncture.
We examined the preservation of sterility in vials by different vial storage conditions on the premise of divided use of single-use vials.
Experiments were conducted using liquid medium filled vials under the following conditions A-D. [A: Removed rubber stoppers (open-vials) and placed in safety cabinet (BSC), B: Placed open-vials in preparation room (ISO class 8), C: Placed negative-pressured vials with rubber stopper punctured twice by needle in preparation room, D: Placed the vials connected to CSTD in preparation room.]
After 24 hours and 7 days, portions of the culture medium in the vial were cultured.
In conditions A, C and D, no growth of microbes was confirmed except in B.
Microbial contamination didn't occur when vials were stored in BSC.
When the vials were stored under the ISO Class 8 environment, it is suggested that microbes may adhere to the rubber stopper of the vial. Even if the inside of the vial after puncture was negative pressure, the rubber stopper showed a certain protective effect from microorganism adherence, and CSTD was similar.
Therefore, the vial storage condition in BSC (ISO class 5) is considered preferable on the premise that a single use vial is divided. However, if the rubber stopper or CSTD is connected even in an ISO class 8 environment, the sterility is retained for 7 days.
Postoperative complications in cataract surgery are associated with an unfavorable prognosis, resulting in poor visual acuity. However, the use of intravenous antibiotics for the prevention of endophthalmitis in ophthalmic surgery has not been established in the current guidelines. Likewise, there are no clear criteria set for the use of prophylactic intravenous antibiotics in our institution. For this reason, the infection control pharmacists and the infection control team (ICT) worked collaboratively to investigate whether antibiotics were properly used, and we intervened to prevent the use of intravenous antibiotics in low risk patients. To clarify the effectiveness of such intervention, we retrospectively reviewed the medical records of patients who received cataract surgery for the 8 months before and after the implementation. The incidence rate of postoperative endophthalmitis, medical expenses, antimicrobial use density (AUD), and the number of anaphylactic shocks were assessed. The incidence rate of endophthalmitis after cataract surgery was evaluated by comparing the group of 853 pre-intervened patients and the group of 996 post-intervened patients. As a result, there was no significant difference in the incidence rate of postoperative endophthalmitis between the two groups. Furthermore, medical expenses and AUD were reduced after the intervention, and no anaphylactic shock occurred during the study period. The present study indicated that the incidence rate of endophthalmitis after cataract surgery did not increase without the prophylactic administration of intravenous antibiotics. Moreover, we contributed to the rational use of antibiotics by cooperating with ICT.
In the field of bacterial infection control, improper use of antibiotics is one of the biggest factors to deteriorate the drug resistance of bacteria. Thus our hospital started AS round, which stands for ‘antimicrobial stewardship round’ once a week by the infection control team. In this report the contribution of ‘AS round’ is evaluated by the following categories:
1. Drug selection based on the sensitivity test results, 2. The dosage and administration of antibiotics use based on the pharmacokinetics/pharmacodynamics theory and renal function, 3. The induction rate of drug-resistant Pseudomonas aeruginosa, 4. Antimicrobial use density (AUD)/days of therapy (DOT), and 6. The 30-day mortality rate of patients infected by bacterial pneumonia.
The results of the AS round show that the dosage and administration of antibiotics has optimized year by year, and the submission rate of bacterial cultures has grown significantly. In addition, the requests for AS round by corresponding doctors and the proposal-acceptance-rate have also increased. Furthermore, broad-spectrum antibacterial drugs, which had been used for more than 8 days, and excessive use of narrow-spectrum antibacterial drugs has diminished. AUD/DOT, regarding carbapenem antibiotics, has also optimized. Moreover, the 30-day mortality rate of severe pneumonia has decreased significantly.
In conclusion, intervention-action by AS round, which optimizes antimicrobial drug use, has improved the outcome of infectious disease in our hospital.
Pharmacists' interventions are considered to be important at the time of starting anti-HIV therapy or changing treatment in outpatient care for HIV infection. We conducted a questionnaire survey to clarify patients' assessments of pharmacists' interventions in outpatient care for HIV infection. The survey was conducted at seven AIDS treatment center hospitals in the Kinki region, and the analysis was performed on 112 patients receiving the initial treatment and 79 patients experiencing treatment change. Pharmacists' interventions were found to be helpful by 97.3% of the initial treatment patients and 96.2% of the treatment change patients; the former often found it helpful in understanding the “necessity of receiving drugs” and “failure in taking drugs and acquisition of resistance”, while the latter often found it helpful in understanding the “difference of the new drug from the previous one” and “side effects”. Pharmacists' interventions relieved anxiety in 89.3% of the initial treatment patients and 89.9% of the treatment change patients, and produced good overall effects such as “relieving anxiety as regards receiving drugs”, “facilitating communication with doctors”, and “reducing questions for doctors”. The survey results showed that pharmacists' interventions at the time of starting anti-HIV therapy or changing treatment met patients' needs and contributed to improving the quality of medical care, such as reducing patient anxiety and the burden on doctors.
Magnesium oxide tablets are sometimes crushed prior to administration to patients having difficulties in swallowing tablets. However, the quality of magnesium oxide formulations may decrease when stored for a long time as a one-dose package, owing to the absorption of high amounts of moisture by magnesium oxide. Additionally, as magnesium oxide solution is alkaline, it can interact with other medicines, making it incompatible for one-dose packaging. There are three types of magnesium oxide powder formulations: crushed magnesium oxide tablets, magnesium oxide bulk powder, and magnesium oxide granules. However, the appropriate formulation of magnesium oxide for one-dose packages is unknown. The stability of powder formulations stored as one-dose packages at 75% RH for 3 months was evaluated by analyzing the change in weight change and dissolution. The dissolution of the three powder formulations did not change for 3 months. Although the weight had increased in all the formulations, the change in the weight of magnesium oxide granules was the lowest among the three formulations. Isoniazid and levodopa tablets have been reported to interact with magnesium oxide tablets. The incompatibility between the crushed powder of these medicines and magnesium oxide powder formulations was analyzed when stored as one-dose packages. Among the three formulations, incompatibility was the lowest for granule. In conclusion, preserving magnesium oxide and other formulations that causes incompatibility should basically be avoided. However, magnesium oxide granules can be used for storing with the other formulations that interact with magnesium oxide within a term to circumvent incompatibility.