Published papers

腎機能低下患者におけるバンコマイシン(VCM)初回負荷投与の安全性は十分に検証されていない。そこで今回、腎機能低下患者に対するVCM初回負荷投与の安全性を明らかにするために、単施設(n=1489)後ろ向き観察研究を実施した。初回負荷投与実施群(n=86)と非実施群(n=206)では、腎機能障害発現割合に有意差は認めなかった。(初回負荷投与実施群:非実施群=6.98%:9.71%、P=0.46)ベースラインの腎機能別でも同様の結果であった。また、VCMの初回トラフ値(中央値)はいずれの群も推奨濃度範囲内であり、両群間に有意差はなかった。多変量ロジスティック回帰分析で腎機能障害発現の危険因子として、投与日数9日以上、フロセミド、ピペラシリン・タゾバクタムの併用、ICU入室、初回トラフ値12.2μg/mL以上が抽出され、初回負荷投与の実施は抽出されなかった。以上より、VCMの初回負荷投与は腎機能低下患者に対しても安全に行える可能性が示唆された。(著者抄録)

Therapeutic drug monitoring for voriconazole, an antifungal agent, is essential for maximizing efficacy and preventing toxicity. The aim of this study was to elucidate the optimal maintenance dose of voriconazole in patients with severe liver cirrhosis (Child-Pugh class C) by reviewing the plasma trough concentrations obtained by therapeutic drug monitoring and daily doses of voriconazole. We retrospectively evaluated 6 patients with Child-Pugh class C cirrhosis who received oral voriconazole treatment and were liver transplant recipients or were awaiting liver transplantation. We compared their voriconazole trough concentrations and daily maintenance doses to those of patients who did not have liver cirrhosis (n=56). We found that plasma voriconazole trough concentrations in all patients with Child-Pugh class C were almost within therapeutic range, and the median plasma trough concentration at steady state was not significantly different from that of patients who did not have liver cirrhosis. In addition, the median daily maintenance dose of voriconazole was significantly lower (2.13 mg/kg/d) than that of the control patients (6.27 mg/kg/d), suggesting that trough voriconazole concentrations are elevated in Child-Pugh class C patients. Thus, we conclude that oral voriconazole maintenance doses in patients with Child-Pugh class C should be reduced to approximately one-third that of patients with normal liver function, with the follow-up dose adjusted by therapeutic drug monitoring.

Based on the predictive performance in our previous study, we switched the therapeutic drug monitoring (TDM) analysis software for dose setting of vancomycin (VCM) from "Vancomycin MEEK TDM analysis software Ver2.0" (MEEK) to "SHIONOGI-VCM-TDM ver.2009" (VCM-TDM) in January 2015. In the present study, our aim was to validate the effectiveness of the changing VCM TDM analysis software in initial dose setting of VCM. The enrolled patients were divided into two groups, each having 162 patients in total, who received VCM with the initial dose set using MEEK (MEEK group) or VCM-TDM (VCM-TDM group). We compared the rates of attaining the therapeutic range (trough value; 10-20 μg/mL) of serum VCM concentration between the groups. Multivariate logistic regression analysis was performed to confirm that changing the VCM TDM analysis software was an independent factor related to attaining the therapeutic range. Switching the VCM TDM analysis software from MEEK to VCM-TDM improved the rate of attaining the therapeutic range by 21.6% (MEEK group: 42.6% vs. VCM-TDM group: 64.2%, p<0.01). Patient age ≥65 years, concomitant medication (furosemide) and the TDM analysis software used VCM-TDM were considered to be independent factors for attaining the therapeutic range. These results demonstrated the effectiveness of switching the VCM TDM analysis software from MEEK to VCM-TDM for initial dose setting of VCM.

ABSTRACT Objectives To externally validate a clinical prediction model for surgical site infection (SSI) after lower third molar (L3M) surgery and evaluate its clinical usefulness. Methods We conducted a retrospective cohort study of patients who underwent L3M surgery at Hokkaido University Hospital. The study was designed to evaluate the historical and methodological transportability. Clinical usefulness was evaluated using decision curve analysis on the data of the non‐antibiotic‐treated patients. Results We obtained 2543 validation cohorts from April 2020 to March 2023, and 640 non‐antibiotic cohorts from July 2010 to September 2023. The incidences of SSI after L3M surgery were 5.3% (135/2543) and 7.7% (49/640) in the validation and non‐antibiotic cohorts, respectively. The discrimination ability of the prediction model was acceptable for the external validation cohort (c‐statistic: 0.67; 95% CI: 0.62–0.71) and adequate for the non‐antibiotic cohort (c‐statistic: 0.72; 95% CI: 0.63–0.79). In both cohorts, the model showed excellent calibration between the observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds. Conclusion A simple risk prediction model for SSI after L3M surgery demonstrated clinical transportability and usefulness. This model may help surgeons/clinicians determine the appropriateness of prophylactic antibiotics administration for patients in L3M surgery.

OBJECTIVE: To evaluate the impact of dental antibiotic guidelines recommending amoxicillin (AMPC) over third-generation cephalosporins (3GCs) for prophylactic use in surgical site infections (SSI), prescription patterns, and cost-effectiveness across facility types, considering the presence of infection control departments and ward pharmacists. METHOD: Using a health insurance claims database of individuals aged 75 years, we performed an interrupted time-series analysis of dental visits with tooth extractions from April 2012 to March 2024. A segmented regression model was applied to assess the impact of antibiotic guidelines (December 2014, 2014 guidelines; April 2016, 2016 guidelines) on 3GCs days of therapy (DOT) and SSI rates. Antibiotic costs and in-hospital vs. out-of-hospital prescription patterns in dental clinics were also evaluated. RESULTS: Overall, the number of 3GCs DOT decreased, although the impact of the guidelines differed between facilities. After the implementation of the 2014 guidelines, 3GCs use decreased in hospitals, but not in dental clinics. After the implementation of the 2016 guidelines, it was further reduced in hospitals with infection control departments and ward pharmacists, and a decline in 3GCs use in dental clinics was initiated. No changes were observed in hospitals with infection control departments alone. The shift from 3GCs to AMPC was more evident in out-of-hospital prescriptions than in in-hospital prescriptions. SSI rates remained unchanged; however, antibiotic costs decreased significantly over time. CONCLUSION: Guideline-based antimicrobial stewardship can reduce 3GCs use and healthcare costs without compromising patient safety. Our findings highlight the importance of a multidisciplinary collaboration to enhance the impact of guidelines.

BACKGROUND: There is little evidence regarding risk prediction for surgical site infection (SSI) after lower third molar (L3M) surgery. METHODS: We conducted a nested case-control study to develop a multivariable logistic model for predicting the risk of SSI after L3M surgery. Data were obtained from Hokkaido University Hospital from April 2013 to March 2020. Multiple imputation was applied for the missing values. We conducted decision tree (DT) analysis to evaluate the combinations of factors affecting SSI risk. RESULTS: We identified 648 patients. The final model retained the available distal space (Pell & Gregory II [p = 0.05], Pell & Gregory III [p < 0.01]), depth (Pell & Gregory B [p < 0.01], Pell & Gregory C [p < 0.01]), surgeon's experience (3-10 years [p = 0.25], <3 years [p < 0.01]), and simultaneous extraction of both L3M [p < 0.01]; the concordance-statistic was 0.72. The DT analysis demonstrated that patients with Pell and Gregory B or C and simultaneous extraction of both L3M had the highest risk of SSI. CONCLUSIONS: We developed a model for predicting SSI after L3M surgery with adequate predictive metrics in a single center. This model will make the SSI risk prediction more accessible.

What is known and objectiveThird-generation oral cephalosporins, especially cefcapene-pivoxil (CFPN-PI), have been used frequently in the Japanese dental field. In December 2014 and April 2016, the newly published clinical guidelines recommended the use of amoxicillin (AMPC). Thus, it is important to evaluate the impact of these guidelines on the prescription profiles of prophylactic antibiotics, clinical outcomes and cost-effectiveness of antibiotics.MethodsWe conducted a retrospective study to analyse an interrupted time series analysis from April 2013 to March 2020 at the Department of Dentistry of Hokkaido University Hospital. A segmented regression model was used to estimate the changes in the incidence of infectious complications following tooth extraction. Prescribed antibiotic data were evaluated via days of therapy (DOT). Antibiotic costs were calculated in terms of the Japanese yen (JPY).Results and discussionWe identified 17,825 eligible patients. The incidence rates of infectious complications (SSI + dry socket) and SSI after tooth extraction were 3.2% and 2.2%, respectively, during the entire period. The extraction of impacted third molars corresponded to 5.0% and 3.4%, respectively. However, their incidence rates were not significantly different during this period. The use of prophylactic antibiotics and antibiotic cost showed consistent trends following the implementation of guidelines. The mean DOT of CFPN-PI decreased (ranging from 4893.6 DOTs/1000 patients [March 2013 to November 2014] to 3856.4 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3856.4 DOTs/1000 patients [December 2014 to March 2016] to 2293.9 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). In contrast, the mean DOT of AMPC was found to be increased (ranging from 1379.7 DOTs/1000 patients [March 2013 to November 2014] to 3236.3 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3236.3 DOTs/1000 patients [December 2014 to March 2016] to 4597.8 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). The mean monthly cost was decreased (ranging from 905.3 JPY [March 2013 to November 2014] to 788.7 JPY [December 2014 to March 2016]; p = 0.003, and from 788.7 JPY [December 2014 to March 2016] to 614.0 JPY [April 2016 to March 2020]; p < 0.001).What is new and conclusionAfter December 2014, prophylactic antibiotics were switched from CFPN-PI to AMPC, and the incidence rate of infectious complications was not significantly different over time. However, changing antibiotics is useful from a cost-effectiveness perspective.

下顎埋伏智歯抜歯術においてセフカペンピボキシル(CFPN-PI)またはアモキシシリン(AMPC)の予防投与を受けた患者の手術部位感染(SSI)発生率を比較した。解析対象となったのはCFPN-PI群129例(男性50例、女性79例、中央値24.0歳)、AMPC群164例(男性75例、女性89例、中央値25.0歳)であった。SSI発生率はCFPN-PI群において11.6%(15/129)、AMPC群において2.4%(4/164)であり、CFPN-PI群のSSI発生率は有意に高かった。次いで、SSI発生に影響する要因分析を行った。単変量解析において抗菌薬(CFPN-PIの使用)、性別(女性)、術後入院、手術難易度、反対側下顎埋伏智歯抜歯の有無、Pell-Gregory分類がP≦0.2となり、これらを多変量解析における解析対象因子として抽出した。解析対象因子のvariance inflation factorはいずれも4未満であり多重共線性はみられなかった。多変量解析の結果、抗菌薬(CFPN-PIの使用)および術後入院がそれぞれオッズ比5.61、4.66を示し、SSIに影響する独立因子として抽出された。