Published papers

An 88-year-old woman was admitted to our hospital with a diagnosis of acute kidney injury (AKI, stage 3) in May 20XX, attributed to rapidly progressive glomerulonephritis caused by anti-glomerular basement membrane disease. Emergent hemodialysis (HD) was performed for the rapidly progressing AKI, and she was also treated with PSL combined with plasma exchange (PE). On the fifth day of hospitalization, she showed a decreased level of consciousness. We suspected antibiotic-associated encephalopathy (AAE) due to ceftriaxone (CTRX), which had been administered since admission. The next day, plasma CTRX concentration was high (198.7 μg/mL). We discontinued CTRX. We predicted that PE would promote the removal of CTRX due to its low distribution volume and high protein-binding affinity rate；however, plasma CTRX concentration did not decrease after PE. Although a temporary decrease in plasma CTRX concentration was observed after HD, effective drug elimination was not achieved the next day due to redistribution of the drug from the tissue to the blood (rebound phenomenon). After discontinuation of CTRX, the patientʼs level of consciousness improved to the same level as on admission on the 13th day. Hypoalbuminemia and the presence of the rapidly progressing AKI in the present patient may have led to a decrease in the protein-binding affinity rate of CTRX, resulting in the plasma CTRX concentration being unchanged after HD and PE. As elderly AKI patients have multiple risks for AAE, we need to take this background into account.

We aimed to assess the frequency of acute kidney injury (AKI) in different areas under the concentration-time curve (AUC) values of vancomycin (VAN) using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. This multicenter retrospective observational study was conducted in eight hospitals. We retrospectively analyzed the data of patients who had received VAN in an intensive care unit (ICU) between January 2020 and December 2022. The primary outcome was the incidence of AKI. Patients were classified into three groups according to the AUC24-48h at the initial therapeutic drug monitoring (TDM) as follows: <500, 500-600, and ≥600 µg·h/mL. The AUC24-48h values were calculated using the Bayesian estimation software Practical AUC-guided TDM. Among 146 patients [median age (interquartile range), 67 (56-78) years; 39% women], the AUC24-48h <500 µg·h/mL had an AKI rate of 6.5% (7/107), the AUC24-48h 500-600 µg·h/mL had an AKI rate of 28.0% (7/25), and the AUC24-48h ≥600 µg·h/mL had an AKI rate of 42.9% (6/14). In multivariate Cox proportional hazard analysis, the AUC24-48h 500-600 µg·h/mL [hazard ratio 5.4, 95% confidence interval (CI) 1.64-17.63] and the AUC24-48h ≥600 μg·h/mL (hazard ratio 7.0, 95% CI 2.31-21.18) significantly correlated with a higher incidence of AKI compared with the AUC24-48h <500 μg·h/mL. In conclusion, we identified an association between AUC on day 2 and the risk of AKI in ICU patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI. IMPORTANCE: Vancomycin (VAN) is a glycopeptide antibiotic and one of the most commonly used antibiotics for severe infections caused by methicillin-resistant Staphylococcus aureus. However, higher VAN concentrations have been associated with an increased risk of acute kidney injury (AKI). Herein, we aimed to assess the frequency of AKI in different areas under the concentration-time curve (AUC) values of VAN using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. We identified an association between AUC on day 2 and the risk of AKI in intensive care unit patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI. Therefore, individualized dosing is feasible, with pharmacists being able to optimize VAN doses to attain appropriate targets.

The 23-valent pneumococcal polysaccharide (PPSV23) and 13-valent pneumococcal conjugate (PCV13) vaccines are available for the prevention of infections caused by Streptococcus pneumoniae. This systematic review and meta-analysis evaluated the immunogenicity and safety of PPSV23 and PCV13 co-vaccination (PCV13/PPSV23) compared with PPSV23 monotherapy in adult populations. PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing PCV13/PPSV23 co-vaccination with PPSV23 monotherapy published until September 15, 2023. Immunogenicity was assessed using the geometric mean titer ratio (GMTR) of opsonophagocytic activity (OPA), which reflects bactericidal activity against each serotype. The safety outcomes included local and systemic adverse events. The risk ratios and 95% confidence intervals were calculated using the inverse variance-weighted method. The meta-analysis included 4 RCTs involving 2739 participants. The OPA GMTRs for 11 of the 13 evaluated serotypes were significantly higher in the PCV13/PPSV23 group than those in the PPSV23 group. The safety analysis showed no statistically significant differences in the incidence of adverse events between the 2 groups across all assessed outcomes. PCV13/PPSV23 showed significantly higher immunogenicity against the pneumococcal serotypes and maintained a safety profile comparable to that of PPSV23. These results support the potential utility of PCV13/PPSV23 as an effective strategy for preventing pneumococcal diseases in older adults.

Objectives To clarify the relationship between acute kidney injury (AKI) and vancomycin use in patients with renal impairment and to establish a risk score for AKI. Methods In this retrospective, multicentre, observational cohort study, trough and peak blood samples were collected from patients who initiated vancomycin therapy. The cumulative incidence of AKI within 14 days was compared among three groups classified according to renal function (estimated glomerular filtration rate ≥ 60, 30-59 and <30 mL/min/1.73 m2). The risk score and predicted probability of AKI incidence were calculated. AKI was defined in accordance with the Kidney Disease Improving Global Outcomes criteria. Results The incidence of AKI was 11.7% (99/847). No statistically significant difference was detected in the cumulative incidence of AKI among the three groups (P = 0.103). Cox proportional hazard analysis showed that the use of tazobactam/piperacillin [HR: 3.3, 95% CI (2.18-4.99), 2 points], vasopressors/inotropes [HR: 3.0, 95% CI (2.02-4.51), 2 points] and area under the concentration-time curve (AUC) on Day 2 [500-600 µg·h/mL: HR, 2.4, 95% CI (1.50-3.89), 1 point; >600 µg·h/mL: HR, 4.4, 95% CI (2.62-7.37), 3 points] were significantly related to the development of AKI. The predicted probabilities of AKI incidence were <5% (low-risk), 5% to <20% (moderate-risk), 20% to <40% (high-risk) and 40% to 67% (very high-risk), with total points of 0, 1-2, 3-4 and ≥5, respectively. Conclusions A risk prediction model was developed for AKI based on AUC exposure and concomitant medications, and no difference in AKI risk was observed across renal function categories.

Practical Antimicrobial Therapeutic Drug Monitoring (PAT) for vancomycin using Bayesian estimation is recommended for calculating the area under the concentration–time curve (AUC). In 2025, PAT was updated from version 3 to version 4, but differences in AUC estimations between these versions have not been examined. This study aimed to compare AUC estimations from both versions in the same patients.We conducted a multicenter, retrospective, observational study involving adult patients who received vancomycin treatment between September 2020 and December 2023, who underwent two-point sampling for initial TDM. AUC was calculated using both versions in three phases: 0–24 h (AUC0–24), 24–48 h (AUC24–48), and at steady state (AUCss).The sample included 894 cases. AUC values from versions 3 and 4 showed a high correlation (r = 0.947–0.964), but phase-related differences emerged. Version 4 yielded significantly lower AUC0–24 and AUC24–48 values (median: 420.7 μg h/mL vs 373.5 μg h/mL, p < 0.001; 398.9 μg h/mL vs 379.8 μg h/mL, p < 0.001), while AUCss was significantly higher in version 4 (448.4 μg h/mL vs 498.2 μg h/mL, p < 0.001).Since differences in population pharmacokinetic models can affect estimation results, clinicians should be aware that AUC estimations may vary depending on the PAT version used, and the results should be interpreted with caution.

健康セミナー参加者247名を対象に、セルフメディケーション税制に対する認知、理解度や関心などの実情に関するアンケートを実施し、本税制を取り巻く国民の実状と本税制の課題を明らかにすることを目的とした。調査の結果、過半数の調査対象者がドラッグストアを1ヵ月間に複数回利用しており、ドラッグストアを頻繁に利用している現状が示された。しかし、1年間のOTC医薬品の合計購入額が1万2千円以上10万円未満の調査対象者は11.8%(29人)と少なく、1年間のOTC医薬品の合計購入額が10万円以上の調査対象者はいなかった。セルフメディケーション税制の認知度について調査したところ、理解度に差はあるものの60%以上の調査対象者が本税制を認知していた。さらに、OTC医薬品の年間合計購入金額別に認知度を集計した。その結果、合計購入金額が1万2千円未満の調査対象者と合計購入金額が1万2千円以上の調査対象者で認知度は変わらなかったものの、合計購入金額が1万2千円以上の調査対象者のほうがセルフメディケーション税制について「知っている」と回答した割合が多かった。しかし、認知度に比べて申告件数は著しく少なかった。セルフメディケーション税制については、約50%(43人)が興味を示すとともに申告要件が揃っていれば控除を受けたいと回答した。

ドラッグストアまたはドラッグストア併設の保険薬局に勤務し、在学中にセルフメディケーション税制(以下、本税制)が施行されていた薬剤師を対象に、本税制に関する認知・見解実態把握調査(アンケート)を実施した。調査対象者は、男性138名(44.5%)、女性172名(55.5%)の合計310名であった。本税制の認知度と理解度について調査したところ、284名(91.6%)の調査対象者が「よく知っている(説明できる)」または「聞いたことはあるが、内容はよく知らない」と回答し、理解度に差はあるものの、ほとんどの調査対象者が本税制について見聞があった。これらの調査対象者は、主に「テレビ」、「雑誌本」、「インターネット」などのメディアを通して本税制に関する情報を得ていた。また、教育現場や職場で本税制について知った調査対象者も多かった。調査対象者の97名(31.3%)が本税制に関する講義を受講したと回答した。本税制の認知度を集計した結果、大学で本税制の講義を受けたことのあると回答した調査対象者において、「よく知っている(説明できる)」と回答した割合が顕著に高かった。今後、薬剤師として働くうえで、多くの調査対象者(86.4%)が本税制の知識が必要だと感じており、半数の調査対象者が本税制に関する情報を収集するうえで携帯アプリを活用したいと回答した。

The target therapeutic ranges of vancomycin, teicoplanin, and arbekacin have been determined, and therapeutic drug monitoring (TDM) is performed in clinical practice. However, TDM is not obligatory for daptomycin, linezolid, or tedizolid. In this study, we examined whether TDM will be necessary for these 3 drugs in the future. There was no significant difference in therapeutic effects on acute bacterial skin and skin structure infection between linezolid and tedizolid by meta-analysis. Concerning the therapeutic effects on pneumonia, the rate of effectiveness after treatment with tedizolid was significantly lower than with linezolid. With respect to safety, the incidences of gastrointestinal adverse events and blood/lymphatic system disorders related to tedizolid were significantly lower than those related to linezolid. Linezolid exhibits potent therapeutic effects on pneumonia, but the appearance of adverse reactions is indicated as a problem. There was a dose-dependent decrease in the platelet count, and the target trough concentration (Ctrough) was estimated to be 4–6 or 2–7 µg/mL in accordance with the patient’s condition. The efficacy of linezolid may be obtained while minimizing the appearance of adverse reactions by performing TDM. The target therapeutic range of tedizolid cannot be achieved in immunocompromised or severe patients. Therefore, we concluded that TDM was unnecessary, considering step-down therapy with oral drugs, use in non-severe patients, and high-level safety. Concerning daptomycin, high-dose administration is necessary to achieve an area under the curve (AUC) of ≥666 as an index of efficacy. To secure its safety, Ctrough (<20 µg/mL) monitoring is important. Therefore, TDM is necessary.

Patients with chronic kidney disease (CKD) who develop sepsis experience worse prognoses; however, the impact of CKD on the incidence of sepsis has not been systematically investigated. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Medical Literature Analysis and Retrieval System Online, Web of Science, the Cochrane Register of Controlled Trials, and ClinicalTrials.gov was performed for literature published prior to May 22, 2025, comparing the onset of sepsis in patients with or without CKD. The risk of bias was determined using the Risk of Bias in Nonrandomized Studies of Interventions tool. This study was registered with the International Prospective Register of Systematic Reviews (CRD42023465075). A total of 14 studies met the inclusion criteria for the systematic review. Of these, 5 examined community-acquired sepsis, 2 focused on intensive care unit-acquired sepsis, and the rest investigated surgery-acquired sepsis. Most studies enrolled populations aged over 65 years; 2 assessed age-related sepsis risk. One study evaluated sepsis occurrence in patients with end-stage CKD, while 3 studies stratified this association by estimated glomerular filtration rate (eGFR). Nearly all studies demonstrated an increased risk of sepsis among patients with CKD, with the risk progressively increasing as eGFR declined. Additionally, 2 studies reported that CKD elevated the risk of sepsis regardless of age, and all included studies indicated a low risk of bias. We indicate that patients with CKD may have a higher risk of developing sepsis than individuals without CKD.

Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H1-receptor blockers are routinely used as the first-line symptomatic treatment for urticaria. Nevertheless, not much research has directly examined the second-generation histamine H1-receptor blockers’ ability to reduce edema. In this study, we directly evaluated the anti-edematous activities of three second-generation histamine H1-receptor blockers available in the market (epinastine hydrochloride, cetirizine hydrochloride, and levocetirizine hydrochloride) using a λ-carrageenan-induced footpad edema model. One hour before the induction of edema with 1% λ-carrageenan injection, all second-generation histamine H1-receptor blockers (5, 10, 50 and 100 mg/kg) were subcutaneously administered to rats. At 0.5 and 3 hours after λ-carrageenan administration, the edema volume was evaluated using a Plethysmometer. Epinastine hydrochloride significantly suppressed the edema growth in a dose-dependent manner. Cetirizine hydrochloride showed a slight anti-edematous effect, while levocetirizine significantly inhibited the development of edema in a dose-dependent manner. On the other hand, dextrocetirizine did not prevent edema from growing. In summary, second-generation histamine H1-receptor blockers, at least those examined in this study, may be able to reduce the clinical symptoms of urticaria associated with edema. Levocetirizine hydrochloride is also anticipated to have stronger anti-edematous effects than cetirizine hydrochloride because levocetirizine is responsible for cetirizine’s anti-edematous activity.

Proper use of antimicrobials in hospital and outpatient settings is critical for minimizing the occurrence of antimicrobial resistance. Some hospitals have intervened in the inappropriate use of third-generation oral cephalosporins. However, there have been no such studies in community pharmacy settings. This study aimed to investigate how the use of oral third-generation cephalosporins in community pharmacies affects the amount of antimicrobials used. Patients who visited Nakanomaru Pharmacy after being prescribed antimicrobials at target medical institutions between February 2021 and January 2023 were identified. The number of oral antimicrobials used, duration of use, number of prescriptions, patient age and sex, and infectious diseases in the target patients before and after the intervention for the proper use of oral third-generation cephalosporins were retrospectively investigated based on the patients’ medication history and prescription receipts. Through efforts to ensure the proper use of oral third-generation cephalosporins, the amount of oral third-generation cephalosporins used has decreased, and the use of penicillins and oral first-generation cephalosporins has increased. There was no increase in the antimicrobial change or relapse rates associated with treatment failure before and after the initiation of appropriate antimicrobial use. By working toward the proper use of oral third-generation cephalosporins in community pharmacies, we were able to reduce the doses of oral third-generation cephalosporins without compromising their therapeutic efficacy. We believe that recommending the selection of narrow-spectrum antimicrobials based on these guidelines will contribute to their proper use.

We herein report a case of bacterial meningitis and bacteremia in a 3-month-old boy caused by Streptococcus pneumoniae serotype 35B multidrug resistance. Intravenous ampicillin was administered on admission. However, when pneumococcal meningitis was suspected, the antibiotic treatment was changed to ceftriaxone (CTRX) and vancomycin (VCM). However, owing to difficulties in achieving sufficient serum trough levels of VCM, this treatment was again switched to linezolid (LZD). The patient recovered without complications after 16 days of CTRX and LZD treatment. This case suggests that LZD is a viable treatment option for bacterial meningitis.

This study aimed to clarify the optimal value for the unbound cefmetazole concentration to remain above the minimum inhibitory concentration (MIC) (fT ≥ MIC) for efficacy of de-escalation to cefmetazole in patients with bacteremic urinary tract infection by extended-spectrum β-lactamase-producing Escherichia coli. This double-center retrospective observational study was conducted at Tokyo Bay Urayasu Ichikawa Medical Center and Keio University Hospital from January 2012 to October 2022. Efficacy was determined via clinical evaluation (mortality rate, recurrence rate, vital changes) and bacteriological evaluation, and the optimal fT ≥ MIC was calculated via receiver operating characteristic curve analysis. As a result, the number of patients evaluated were 40 (35 and 5 in the treatment success and treatment failure groups, respectively). Univariate analysis showed that fT ≥ MIC, recurrence rate, and MIC for cefmetazole against bacteria were significantly different for the two groups (p < 0.05). Receiver operating characteristic curve analysis showed that the optimal fT ≥ MIC indicating efficacy was 57% (area under the curve: 0.94, 95% confidence interval: 0.86–1.00, p = 0.002). All patients with fT ≥ MIC ≥ 57% had successful treatment, whereas the frequency of treatment failure was high among those with fT ≥ MIC <57%. The optimal fT ≥ MIC for the clinical efficacy of de-escalation to cefmetazole in patients with bacteremic urinary tract infection by extended-spectrum β-lactamase-producing E. coli was fT ≥ MIC ≥ 57%. This finding would be useful for optimal dosing of cefmetazole.

Background: Vancomycin infusion reaction (VIR) is a common adverse reaction to vancomycin. We aimed to investigate the effects of infusion rate, age, infusion time, renal function and history of allergy on the incidence of VIR. Methods: We conducted a single-centre retrospective cohort study with 153 patients (aged 0–92.7 years) who received a single intravenous dose of vancomycin for perioperative prophylaxis. Patients treated for active infections were excluded. Medical records were retrospectively evaluated for VIR occurrence, defined as itching, flushing or rash documentation. Results: VIR incidence was 46.7% (7/15) in patients aged <10 years, 47.4% (9/19) in those aged 10–20 years and 44.4% (4/9) in those aged 20–30 years, versus 2.7% (2/74) in those aged ≥60 years. Multivariable logistic regression identified younger age [adjusted odds ratio (aOR) 0.95, 95% CI 0.93–0.97] and higher weight-adjusted infusion rate (aOR 1.22 per mg/kg/h increase, 95% CI 1.04–1.43) as independent risk factors for VIR. Receiver operating characteristic analysis of the infusion rate by age group showed that the optimal cut-off value for patients aged 30–60 years was 14.8 mg/kg/h, whereas for those aged <30 years, it was 14.0 mg/kg/h. No patients developed VIR when the infusion rate was <9.4 mg/kg/h. Conclusions: Age and higher weight-adjusted infusion rate were key risk factors for VIR. Tailoring infusion rate to age and weight may reduce VIR incidence without unnecessarily prolonging administration time.

Introduction: This study aimed to develop and evaluate a population pharmacokinetic model and optimal dosing regimen for vancomycin in overweight and obese adults. Methods: A population pharmacokinetic model using a two-compartment system was constructed using a nonlinear mixed-effects approach, incorporating 527 data points from 184 participants. External validation of the model was carried out using an additional 55 data points from 21 participants; these were not used in the construction of the model. Monte Carlo simulations were used to determine the dosage that achieved the steady state area under the curve value falling between 400 μg h/mL and 600 μg h/mL. Results: In the final model, vancomycin clearance was found to be a significant predictor of blood vancomycin levels, alongside creatinine clearance (CCr), blood urea nitrogen levels, and incidence of heart failure. CCr was calculated with adjusted body weight (AdjBW). AdjBW was selected as a predictor of the volume of distribution in the central and peripheral compartments. External validation showed that the highest proportion of cases had deviations of less than 15 % between measured and predicted values in the final model developed in this study. This indicates that our model outperforms previously developed models (five for obese patients and four for non-obese patients). Conclusions: Our model shows that determining effective vancomycin doses for overweight and obese patients depend on estimated CCr rates, AdjBW, BUN levels, and incidence of heart failure.

Veterinary medicine has made tremendous progress for domestic dogs, which are irreplaceable family members enriching human life. Nevertheless, no adequate supply system exists for their blood products. This study examined the synthesis, structure, safety, and efficacy of poly(2-ethyl-2-oxazoline)-conjugated porcine serum albumin (POx-PSA) as an artificial plasma expander for dogs. The aqueous POx-PSA solution showed moderately high colloid osmotic pressure and good blood cell compatibility. Actually, lyophilized powder stored for 1 year can regenerate into a homogeneous solution. The circulation half-life of POx-PSA in rats was 2.1-fold longer than that of naked PSA. Rats produced neither anti-PSA IgG antibody nor anti-POx IgG antibody, which suggests excellent immunological stealth properties of POx-PSA. Complete resuscitation of hemorrhagic shock in rats was achieved soon after injection of POx-PSA solution. Serum biochemistry tests and histopathological observations indicated no abnormality in the related organs. When POx-PSA was administered to dogs intravenously, (i) no serum biochemical or hematological alteration was observed, also (ii) no overt deterioration of animal health was observed. These results indicate that POx-PSA has potential as an artificial plasma expander for dogs.

© 2021 John Wiley & Sons Ltd What is known and objective: It has been recommended that the trough concentration (Cmin) of teicoplanin should be maintained at ≥20 μg/ml for difficult-to-treat complicated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Conversely, Cmin of teicoplanin of at least 10 μg/ml is required for non-complicated MRSA infections. Considering the low incidence of nephrotoxicity for teicoplanin, Cmin = 15–30 μg/ml has been suggested for most MRSA infections. Thus, we assessed the clinical efficacy and adverse effects of teicoplanin at this target Cmin. Methods: We searched electronic databases (PubMed, Cochrane Central Register of Controlled Trials and Ichushi-Web) to identify eligible studies. Studies were included if they provided the incidence of treatment success, mortality in patients with MRSA infection, and/or hepatotoxicity and nephrotoxicity according to the Cmin range. Results and discussion: Four trials assessing clinical success (n = 299) and three studies assessing adverse effects (n = 546) were included. Cmin = 15–30 μg/ml significantly increased the probability of treatment success compared with Cmin < 15 μg/ml (odds ratio [OR] = 2.68, 95% confidence interval [CI] = 1.14–6.32, p = 0.02). The all-cause mortality rate did not differ between the groups (OR = 0.46, 95% CI = 0.13–1.61, p = 0.22). Cmin = 15–30 μg/ml did not increase the risks of nephrotoxicity (OR = 0.91, 95% CI = 0.49–1.69, p = 0.76) or hepatotoxicity (OR = 0.67, 95% CI = 0.18–2.44, p = 0.54). What is new and conclusion: Teicoplanin therapy using a Cmin target of 15–30 μg/ml is likely to be associated with better clinical responses than Cmin < 15 μg/ml without increasing the risk of adverse effects.

© 2021, The Author(s). Background: This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety. Methods: We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). Results: Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47–0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15–20 μg/mL (OR 2.39, 95% CI 1.78–3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18–0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13–3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28–1.01); however, it was not significant in the analysis of mortality. Conclusions: We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.

© 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases We carried out a systematic review and meta-analysis exploring the relationship between vancomycin (VCM) trough concentrations and its effectiveness and nephrotoxicity in pediatric patients. We conducted our analysis using MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials as electronic databases (June 29, 2019). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified 16 studies that were eligible for the meta-analysis. A total of 351 and 3,266 patients were included in the analysis for effectiveness and nephrotoxicity, respectively. Pediatric MRSA infection patients with VCM trough concentrations ≥ 10 μg/mL had significantly lower treatment failure rates (OR 0.54, 95% CI 0.30–0.96). The incidence of nephrotoxicity was significantly higher in trough concentrations ≥ 15 μg/mL than when they were < 15 μg/mL (OR 3.02, 95% CI 2.08–4.38). We identified the optimal VCM trough concentrations associated with effectiveness and nephrotoxicity in pediatric patients with MRSA infection. Further prospective studies are needed to find optimal dosing and monitoring strategy on VCM in pediatric population.