Evaluating the association of body mass index with COVID-19 severity and mortality using Japanese administrative claims data.

INTRODUCTION: Obesity is a risk factor for aggravation of and mortality from coronavirus disease 2019 (COVID-19). We aimed to investigate the relationship between COVID-19 and Body Mass Index (BMI) in the Japanese population. METHODS: We used administrative claims data from an advanced treatment hospital in Japan and extracted data from patients hospitalized for COVID-19. The exposure variable was BMI measured at the time of admission, and the study outcomes were progression to critical illness and death. Analyses were performed for each age group. RESULTS: Overall, 58,944 patients met the inclusion criteria. The risk of critical illness increased monotonically with higher BMI. In contrast, the relationship between BMI and mortality follows a J-shaped curve; being underweight and obese are risk factors for mortality. When stratified by age, similar trends were observed for both critical illness and mortality. CONCLUSION: A higher BMI is a risk factor for the progression of COVID-19 severity, whereas both lower and higher BMIs are risk factors for mortality in the Japanese population.

Evaluation of predictors of third-generation cephalosporin non-susceptibility and factors affecting recurrence or death in bacteremia caused by Citrobacter freundii complex, Enterobacter cloacae complex, and Klebsiella aerogenes.

Factors involved in the susceptibility of third-generation cephalosporins (3GCs) to bacteremia caused by Citrobacter freundii complex, Enterobacter cloacae complex, and Klebsiella aerogenes were investigated based on a case-case-control design. Antimicrobial therapy administered 30 days prior to bacteremia and hospitalization within 90 days were common risk factors for the 3GC susceptible and 3GC non-susceptible groups, while hospitalization from an institution or another hospital was a specific risk factor for the 3GC non-susceptible group. We also attempted to examine the factors affecting the clinical outcome of bacteremia. Hospitalization more than 14 days before the onset of bacteremia was an independent factor indicating poor clinical outcome. In contrast, the implementation of source control was an independent predictor of successful treatment. Although a longer hospital stay before the onset of bacteremia was associated with worse clinical outcomes, implementation of source control may have contributed to improved treatment outcomes for bacteremia.

Factors associated with the outcome of patients with COVID-19 requiring mechanical ventilation: A single-center observational study in Japan.

Aim: Coronavirus disease (COVID-19) spread worldwide, and was declared as a pandemic by the World Health Organization. Despite numerous studies in the last few years, the factors associated with the outcomes of patients with COVID-19 requiring mechanical ventilation remain unclear. The prediction of ventilator weaning and mortality using the data obtained at the time of intubation could be beneficial for establishing appropriate treatment strategies and obtaining informed consent. In this study, we aimed to clarify the association between patient information at the time of intubation and the outcomes of intubated COVID-19 patients. Methods: This retrospective observational study used single-center data from patients with COVID-19. Patients with COVID-19 who were admitted to Osaka Metropolitan University Hospital from April 1, 2020, to March 31, 2022, and under mechanical ventilation were included. The main outcome was defined as the factors related to ventilator weaning; a multivariate analysis was carried out to evaluate the association between patient information at the time of intubation and the outcome. Results: In total, 146 patients were included in this study. The factors significantly associated with ventilator weaning were age (65-74 years old, adjusted odds ratio [OR], 0.168; 75 years and older, adjusted OR, 0.121), vaccination history (adjusted OR, 5.655), and Sequential Organ Failure Assessment (SOFA) respiration score (adjusted OR, 0.007) at the time of intubation. Conclusion: Age, SOFA respiration score, and COVID-19 vaccination history at the time of intubation could be associated with outcomes in patients with COVID-19 requiring mechanical ventilation.

Mental health complaints among healthcare workers engaged in the care of COVID-19 patients: A prospective cohort study from Japan.

Background: Healthcare workers (HCWs) caring for patients with coronavirus disease-2019 (COVID-19) can experience physical and mental health burdens. It is imperative that hospitals reduce such burdens on frontline HCWs, protect them, and support their healthcare. This study aimed to investigate the association between occupation and the manifestation of physical or psychological symptoms among HCWs during the current COVID-19 pandemic. Methods: A twice-weekly survey using questionnaires targeting HCWs who care for COVID-19 patients was performed at Osaka Metropolitan University Hospital (tertiary hospital). The demographic characteristics of the participants, exposure level, and physical and psychological complaints were evaluated. Results: Seventy-one HCWs participated in this study, of whom 27 (38.0%) were doctors, 25 (35.2%) were nurses, and 19 (26.8%) were technicians. Among the HCWs, the proportions of those who experienced any physical or psychological symptoms were 28.2% and 31.0%, respectively. The frequency of depression and anxiety was obviously higher among the nurses than that among the doctors (both p < 0.01). Multivariate analysis revealed that being a nurse (odds ratio 4.90; p = 0.04) and having physical complaints (odds ratio 4.66; p = 0.02) might be independent predictors of the manifestation of psychological symptoms. Conclusion: Our results indicate that the follow-up of HCWs experiencing physical symptoms, especially nurses engaged in the care of COVID-19 patients, may require more careful management to improve the psychological outcomes. We believe that this study is the first step toward establishing a psychological health management strategy for HCWs caring for COVID-19 patients.

Predictors of mortality from extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia.

ABSTRACTExtended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from ESBL-PE bacteremia is very important. The present systematic review and meta-analysis aimed to evaluate studies to determine predictors associated with ESBL-PE bacteremia mortality. We searched PubMed and Cochrane Library databases for all relevant publications from January 2000 to August 2022. The outcome measure was mortality rate. In this systematic review of 22 observational studies, 4607 patients with ESBL-PE bacteremia were evaluated, of whom 976 (21.2%) died. The meta-analysis showed that prior antimicrobial therapy (RR, 2.89; 95% CI, 1.22-6.85), neutropenia (RR, 5.58; 95% CI, 2.03-15.35), nosocomial infection (RR, 2.46; 95% CI, 1.22-4.95), rapidly fatal underlying disease (RR, 4.21; 95% CI, 2.19-8.08), respiratory tract infection (RR, 2.12; 95% CI, 1.33-3.36), Pitt bacteremia score (PBS) (per1) (RR, 1.35; 95% CI, 1.18-1.53), PBS ≥ 4 (RR, 4.02; 95% CI, 2.77-5.85), severe sepsis (RR, 11.74; 95% CI, 4.68-29.43), and severe sepsis or septic shock (RR, 4.19; 95% CI, 2.83-6.18) were found to be mortality predictors. Moreover, urinary tract infection (RR, 0.15; 95% CI, 0.04-0.57) and appropriate empirical therapy (RR, 0.39; 95% CI, 0.18-0.82) were found to be a protective factor against mortality. Patients with ESBL-PE bacteremia who have the aforementioned require prudent management for improved outcomes. This research will lead to better management and improvement of clinical outcomes of patients with bacteremia caused by ESBL-PE.

Impact of antimicrobial stewardship with the Xpert MRSA/SA BC assay at a tertiary hospital in Japan.

INTRODUCTION: Genetic testing is gaining increasing importance as a part of antimicrobial stewardship (AS). Rapid identification and determination of methicillin susceptibility using the Xpert MRSA/SA BC assay can improve the management of Staphylococcus aureus bacteremia (SAB) and reduce inappropriate antibiotic use. However, few reports have described the effectiveness of this approach. METHODS: The present study aimed to assess the influence of AS using the Xpert MRSA/SA BC assay. Cases were classified into the pre-intervention group (n = 98 patients), in which SAB was identified by traditional culture (November 2017 to November 2019), and the post-intervention group (n = 97 patients), in which the Xpert MRSA/SA BC assay was performed when necessary (December 2019 to December 2021). RESULTS: Patient characteristics, prognosis, duration of antimicrobial use, and length of hospital stay were compared between the groups. The Xpert assay was performed in 66 patients in the post-intervention group (68.0%). The two groups showed no significant differences in severity and mortality. The rate of cases treated with anti-MRSA agents reduced following the intervention (65.3% vs. 40.4%, p = 0.008). The number of cases involving definitive therapy within 24 h was higher in the post-intervention group (9.2% vs. 24.7%, p = 0.007). The hospitalization rate at >60 days was lower in Xpert implementation cases among MRSA bacteremia cases (28.6% vs. 0%, p = 0.01). CONCLUSIONS: Thus, the Xpert MRSA/SA BC assay has potential as an AS tool, especially for early definitive treatment to SAB and reduction of long-term hospitalization in MRSA bacteremia cases.

Differences in severity of bacteraemia caused by hypermucoviscous and non-hypermucoviscous Klebsiella pneumoniae.

BACKGROUND: Klebsiella pneumoniae strains pose a significant threat to public health. Currently, it is inconclusive whether hypermucoviscous K. pneumoniae (hmKp; semi-quantitatively defined by a positive 'string test') bacteraemia is clinically more severe than non-hmKp bacteraemia. Hence, this systematic review and meta-analysis was conducted with the aim of drawing some conclusions on hypermucoviscosity and bacteraemia. METHODS: PubMed and Web of Science databases were searched for all relevant publications from January 2000 to March 2022. The outcome measures were mortality rate and abscess formation. RESULTS: Fourteen observational studies were included in this systematic review, comprising a total of 3092 patients with K. pneumoniae bacteraemia, including 746 (24.1%) patients with hmKp strains. The meta-analysis showed that hmKp bacteraemia did not account for a significant increase in the incidence of all-cause mortality compared with non-hmKp bacteraemia [pooled hazard ratio 1.30, 95% confidence interval (CI) 0.79-2.12; P=0.30]. However, hmKp bacteraemia was associated with a significant increase in the incidence of abscess formation compared with non-hmKp bacteraemia (pooled odds ratio 7.74, 95% CI 4.96-12.06; P<0.00001). CONCLUSIONS: Although mortality may not be dependent on the causative agent, this review reaffirms the importance of the string test to detect hmKp. There is a need for prudent management, especially for patients with hmKp, that should include investigations for liver abscess and/or metastatic spread, and measures for early and proper source control as this can improve the prognosis.

Fulminant Metastatic Cellulitis Caused by Stenotrophomonas Maltophilia Infection and Subsequent Candida Parapsilosis Fungemia After Cord Blood Transplantation.

Stenotrophomonas maltophilia is known to be an opportunistic pathogen with intrinsic and acquired resistance mechanisms to multiple antibiotics. Bloodstream infection caused by S. maltophilia is a potentially fatal complication, especially in recipients of umbilical cord blood transplantation (CBT). Infrequent reports of S. maltophilia skin and soft tissue infections (SSTIs), including metastatic cellulitis and ecthyma gangrenosum, have been reported as wound infections. Metastatic cellulitis lesions due to S. maltophilia are typically reported to be tender, erythematous, and to show warm subcutaneous infiltration. There are only a few available reports about the clinical course of metastatic cellulitis due to S. maltophilia. We experienced a case involving the development of metastatic cellulitis with fulminant and extensive exfoliation in a patient who underwent CBT. Despite controlling the bloodstream infection caused by S. maltophilia, the patient succumbed to secondary fungal infection due to the devastation of the skin barrier. Our case highlights that SSTIs due to S. maltophilia can cause the unexpected development of fulminant metastatic cellulitis with systemic epidermal peeling in severely immunocompromised hosts, including CBT recipients undergoing steroid therapy.

Characterization of Aspergillus spp. isolated from patients with coronavirus disease 2019.

INTRODUCTION: Invasive pulmonary aspergillosis (IPA) is an important complication of coronavirus disease 2019 (COVID-19), and while there are case reports and epidemiological studies, few studies have isolated Aspergillus strains from patients. Therefore, we analyzed the strains, sensitivities, and genetic homology of Aspergillus spp. Isolated from patients with COVID-19. METHODS: We investigated the Aspergillus strains detected from patients with COVID-19 hospitalized in Osaka Metropolitan University Hospital from December 2020 to June 2021. A molecular epidemiological analysis of Aspergillus spp. was performed using drug susceptibility tests and TRESPERG typing, and data on patient characteristics were collected from electronic medical records. RESULTS: Twelve strains of Aspergillus were detected in 11 of the 122 patients (9%) with COVID-19. A. fumigatus was the most common species detected, followed by one strain each of Aspergillus aureolus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus. A. aureolus was resistant to voriconazole, and no resistance was found in other strains. All A. fumigatus strains were genetically distinct strains. Six of the 11 patients that harbored Aspergillus received antifungal drug treatment and tested positive for ß-D-glucan and/or Aspergillus galactomannan antigen. The results indicated that Aspergillus infections were acquired from outside the hospital and not from nosocomial infections. CONCLUSION: Strict surveillance of Aspergillus spp. is beneficial in patients at high-risk for IPA. When Aspergillus is detected, it is important to monitor the onset of IPA carefully and identify the strain, perform drug sensitivity tests, and facilitate early administration of therapeutic agents to patients with IPA.

COVID-19 vaccination benefits in preventing severe disease in mild-to-moderate cases: An analysis in the first specialized hospital for COVID-19 in Japan.

BACKGROUND: In Japan, the fourth round of coronavirus disease (COVID-19) vaccination is ongoing and is targeted at medical staff and nursing home workers, individuals aged ≥60 years, and those with comorbidities or other high-risk factors, including body mass index (BMI) ≥30 kg/m2. The incidence of severe COVID-19 decreased markedly after widespread COVID-19 vaccination drives, and our hospital experienced a similar trend. We, therefore, examined the characteristics of our patients to clarify who benefited the most from vaccination. METHODS: We retrospectively investigated all patients hospitalized for COVID-19 in Osaka City Juso Hospital between March 1, 2021, and June 30, 2022. Using multivariable logistic analysis, we calculated the adjusted odds ratios (aORs) for severe disease after vaccination in the whole dataset and in subsets stratified by age, sex, BMI, smoking history, pre-hospitalization location, and comorbidities. RESULTS: The analysis included 1041 patients. Multivariable logistic analysis showed that vaccination was associated with a low risk of severe disease, with an aOR of 0.21 (95% confidence interval: 0.12-0.36, p < 0.001). On stratifying the analysis according to background characteristics, lower aORs for severe COVID-19 were found for patients aged ≥60 years and for those with diabetes or hypertension. Notably, patients with BMI >30 kg/m2 and those with BMI ≥18 kg/m2 and ≤30 kg/m2 benefited from vaccination. CONCLUSIONS: Individuals with diabetes or hypertension and those of age ≥60 years benefited more from vaccination than did their counterparts. We recommend extending the fourth round of vaccinations to individuals with a BMI of 18-30 kg/m2.

Two cases of Clostridium ramosum bacteremia with intestinal perforation: The antimicrobial susceptibility of clinical strains.

Clostridium ramosum is one of the obligate anaerobes that constitute the intestinal microbiota, and one of the rare Clostridia. With Clostridium ramosum, very few data have been reported to investigate antimicrobial susceptibility for clinical isolates that have caused bacteremia. Here, we report two cases of Clostridium ramosum bacteremia. The first case was a 54-year-old Japanese man with taking 20mg hydrocortisone for hypopituitarism. He presented to the emergency department for an unknown cause cardiopulmonary arrest. At the hospital day 36, he had fever and a drop in blood pressure. Abdomen computed tomography (CT) revealed free air around the ascending colon, we diagnosed with intestinal perforation, and peritonitis. Blood culture revealed Clostridium ramosum. We administered conservative management by 6-week of antibiotic treatment. The second case was a 78-year-old Japanese man with no significant medical history. He was referred to our hospital with fever and abdominal pain. Abdomen CT revealed perforated appendicitis, and blood cultures revealed Clostridium ramosum. We performed emergency surgery, and administered one-week course of antibiotic treatment. This report demonstrates two cases of Clostridium ramosum bacteremia with intestinal perforation, and the antimicrobial susceptibility of each clinical strain. For the future, it is necessary to accumulate data on the susceptibility of clinical isolates in order to find an appropriate treatment.

Rifampicin exerts anti-mucoviscous activity against hypervirulent Klebsiella pneumoniae via binding to the RNA polymerase ß subunit.

OBJECTIVES: In hypervirulent Klebsiella pneumoniae (hvKP), the hypermucoviscous capsule is known to be a major virulence determinant. We previously discovered that rifampicin (RFP), a bactericidal drug that binds to and inhibits the ß subunit of RNA polymerase (RpoB), elicits anti-mucoviscous activity against hvKP by suppressing rmpA, a regulator of capsule production. Here, we aimed to determine whether RFP exerts this effect at sub-growth-inhibitory concentrations via its binding to RpoB. METHODS: Five spontaneous RFP-resistant mutants (R1-R5) were prepared from an hvKP clinical isolate and subjected to whole genome sequencing and mucoviscosity analyses. Subsequently, a two-step allelic exchange procedure was used to create a rpoB mutant R6 and revertants with wild-type rpoB from R1-R5 (named R1'-R5'). Transcription levels of rmpA and the capsular polysaccharide polymerase gene magA and capsule thickness of R1-R5 and R1'-R5' grown without or with RFP were evaluated by quantitative reverse transcription polymerase chain reaction and microscopic observation using India ink staining. RESULTS: R1-R5 all had non-synonymous point mutations in rpoB and were highly resistant to the bactericidal effects and anti-mucoviscous activity of RFP. While the properties of R6 were similar to those of R1-R5, the responses of R1'-R5' to RFP were identical to those of the wild type. rmpA and magA transcription levels and capsule thickness correlated well with the mucoviscosity levels. CONCLUSIONS: RFP exerts anti-mucoviscous activity by binding to RpoB. The mechanism of how this causes rmpA suppression remains to be explored.

First report of Mycobacterium virginiense-induced synovitis and tenosynovitis of flexor digitorum superficialis and profundus muscles in Japan.

Mycobacterium virginiense, a species of the Mycobacterium terrae complex, was first identified in 2016. Although M. virginiense has only been reported to cause tenosynovitis, there have been only a few reports. Moreover, there is no established standard treatment, and no cases of M. virginiense infection have been reported in Japan. A 70-year-old Japanese man with a history of hand injury and wound contamination was diagnosed with synovitis and tenosynovitis of the left flexor digitorum superficialis and profundus muscles. M. virginiense was detected in perisynovial reservoirs and surgically removed synovium and was identified by hsp65 and rpoB sequencing. Postoperative chemotherapy with clarithromycin, rifabutin, and ethambutol was administered. Infection with M. virginiense can occur in patients with synovitis and tenosynovitis who have experienced injury or wound contamination, requiring surgery and long-term treatment with multiple antibiotics.

Successful treatment of proven coronavirus disease 2019-associated pulmonary aspergillosis with liposomal amphotericin B in a patient with bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is being increasingly recognized as a severe complication that contributes to poor prognoses among patients with COVID-19. However, little is known regarding the clinical course of CAPA with hematological malignancies, especially after allogeneic hematopoietic stem cell transplantation (HSCT). A 29-year-old woman was diagnosed with proven CAPA with an Aspergillus fumigatus identified by cultures of bronchoalveolar lavage and lung biopsy four years after haploidentical HSCT for acute myelogenous leukemia. She had been taking oral prednisolone for bronchiolitis obliterans syndrome that developed after HSCT. Although prolonged RT-PCR positivity for SARS-CoV-2 (133 days after the onset of COVID-19) without shedding of viable virus was observed, the COVID-19 was treated with favipiravir, remdesivir, dexamethasone, and enoxaparin. However, the CAPA did not respond to combination therapy, which included triazole (voriconazole, itraconazole, posaconazole) and echinocandin (caspofungin, micafungin), even though the Aspergillus fumigatus isolate was found to be susceptible to these agents in vitro. Nevertheless, a total of 16 weeks of liposomal amphotericin B (L-AMB) therapy led to a favorable response, and the patient was discharged from the hospital on day 213. This case provided essential experience of CAPA treated with L-AMB in a recipient with chronic respiratory disease after HSCT.

The Clinical Evaluation of Third-generation Cephalosporins As Definitive Therapy for Enterobacter spp. and Klebsiella aerogenes Bacteremia.

Objective Third-generation cephalosporins (3GCs) may be susceptible in vitro to Enterobacter spp. and Klebsiella aerogenes. However, treatment with mainly fourth-generation cephalosporins or carbapenems is currently recommended. Diversification of antimicrobial agents in therapy is required to avoid the selection pressure of resistant organisms by broad-spectrum antimicrobial agents. This study investigated the clinical efficacy of 3GC therapy for Enterobacter spp. and Klebsiella aerogenes bacteremia in a multicenter, retrospective, observational study. Methods Patients with Enterobacter spp. or Klebsiella aerogenes detected in blood cultures and treated with a susceptible antimicrobial agent were included in the study. Propensity score matching was performed to align patient background bases, and clinical outcomes between the 3GC and non-3GC groups were compared. Treatment success was defined as having no need for treatment escalation or the addition of other antimicrobial agents, no recurrence, or no death within 30 days. Results The study included 188 cases, of which 57 and 131 were included in the 3GC and non-3GC treatment groups, respectively; 53 patients in each group were matched by propensity score matching. There were no significant differences between groups in rates of switching to a susceptible antimicrobial or adding another agent, relapse within 30 days, or death within 30 days. In the 3GC group, source control was associated with favorable clinical outcomes. Conclusion Definitive 3GC therapy for susceptible Enterobacter spp. and Klebsiella aerogenes bacteremia is as clinically effective and valuable a targeted therapy as non-3GC therapy and can be implemented under conditions in which infection source control measures are in place.

Muscle Biopsy-proven Drug-induced Microscopic Polyangiitis in a Patient with Tuberculosis.

We herein report a case of muscle biopsy-proven microscopic polyangiitis (MPA) in a patient with tuberculosis. The patient had developed a persistent fever after the initiation of treatment for tuberculosis and was positive for myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA). However, because conventional symptoms were lacking, determination of the biopsy site was difficult. Based on the findings of a biopsy of the biceps femoris, which confirmed small vessel vasculitis, the patient was diagnosed with MPA. The fever was alleviated by glucocorticoids. Tuberculosis and antituberculosis drugs can cause ANCA-associated vasculitis (AAV). A muscle biopsy is useful for the diagnosis of AAV.

A cross-sectional, multicenter survey of the prevalence and risk factors for Long COVID.

Long-term sequelae of the coronavirus disease (COVID-19) constitute Long COVID. Although Long COVID has been reported globally, its risk factors and effects on quality of life (QOL) remain unclear. We conducted a cross-sectional study using questionnaires and electronic medical records of COVID-19 patients who were diagnosed or hospitalized at five facilities in Japan. Responses were obtained from 285 out of 1,150 patients. More than half of the participants reported Long COVID symptoms of varying severity 1 year after COVID-19. Common sequelae included fatigue, dyspnea, alopecia, concentration problems, memory problems, sleeplessness, and joint pain, which often significantly reduced their QOL. COVID-19 severity was strongly associated with sputum production, chest pain, dyspnea, sore throat, and diarrhea, but not with fatigue, dysgeusia, anosmia, alopecia, and sleeplessness. Fatigue, dysgeusia, anosmia, alopecia, and sleeplessness affected the QOL among participants with asymptomatic or mild COVID-19 during the acute phase. Moreover, these sequelae persisted for prolonged periods.

Population pharmacokinetics of linezolid and its major metabolites PNU-142300 and PNU-142586 in adult patients.

INTRODUCTION: Only a few reports are available on the population pharmacokinetic (PK) analysis of linezolid and its main metabolites. Therefore, we investigated the population PK of linezolid and its metabolites in adult patients treated with intravenous linezolid to identify the causative factors affecting pharmacokinetics, and evaluated the relationship between the parent compound and major metabolites PNU-142300 and PNU-142586. METHODS: Population PK analysis was performed using medical data collected from patients who were treated with intravenous linezolid (600 mg twice daily). We examined the impact of covariate candidates such as demographic characteristics and laboratory parameters. Simulations using the final model were investigated and used to estimate the plasma concentrations, trough concentrations (Cmin ), and area under the curve (AUC) of linezolid and its metabolites, and the metabolite-to-parent ratios for Cmin and AUC were used to assess the accumulation of metabolites over linezolid. RESULTS: A total of 82 plasma concentrations from 23 patients were analyzed. The volume of distribution was estimated to be 47.1 L, assuming that linezolid and its metabolites were the same. The total clearance (CL) of linezolid, and CLs of PNU-142300 and PNU-142586 were influenced by creatinine clearance (CLcr), with population mean CLs of 3.86, 7.27, and 13.54 L/h, respectively. The Cmin and AUCs of linezolid and its metabolites and the ratios of metabolites per linezolid were predicted to increase exponentially with decreasing renal function. CONCLUSION: We developed the first population PK model in which CLcr was incorporated as a covariate in the CL of linezolid and its metabolites. Using the final model, it was possible to predict the plasma concentration, Cmin , and AUC appropriately. The model was found to be a potentially useful tool for future studies on optimal dosing and toxicity analysis.

Body Mass Index of Elderly Patients with Normal Renal Function as a Determining Factor for Initial Vancomycin Regimen Designing.

INTRODUCTION: Currently, the use of actual body weight is recommended for dosing in vancomycin regimen designs, and it is important to perform therapeutic drug monitoring for efficacy and safety. However, the method to determine the appropriate vancomycin regimen for underweight or obese patients remains controversial. The aim of this study was to evaluate the impact of body mass index (BMI) on the relationship among vancomycin doses, trough concentration, and area under the curve (AUC). In addition, we identified the group of patients who were potentially more affected by BMI and evaluated the optimal dosing regimen to achieve the target AUC. METHODS: We retrospectively collected data from 462 patients who received vancomycin at the Osaka City University Hospital between January 2013 and September 2019. Patients were classified by their BMI group (underweight <18.5, normal weight 18.5-24.9, and obese ≥25.0 kg/m2). We assessed the association between vancomycin dose versus trough concentration or AUC as well as dose-adjusted trough concentration and AUC in each BMI subgroup to determine the doses for achieving the target AUC. RESULTS: The dose-adjusted trough concentration and AUC in elderly patients with normal renal function appeared to increase significantly with an increase in BMI (p < 0.05). Vancomycin doses that enabled the achievement of AUC400 in elderly patients with normal renal function decreased with increasing BMI: 17.7, 15.8, and 12.9 mg/kg per time in the underweight, normal weight, and obesity groups, respectively (p < 0.05). CONCLUSION: Elderly patients with normal renal function were the most affected by BMI on vancomycin trough concentration and AUC. The vancomycin regimen design in these patients should be adjusted carefully, not only based on the patient's renal function but also based on BMI.