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Background: Efforts to promote antimicrobial stewardship aimed at reducing antimicrobial resistance are necessary regardless of hospital scale owing to delays in new antimicrobial development. We aimed to evaluate the effects of pharmacist-driven interventions on broad-spectrum antimicrobial usage and the prognosis of patients with bacteremia in a medium-sized hospital lacking infectious disease physicians and a microbiology laboratory., Methods: This single-center, retrospective, pragmatic, quasi-experimental study was conducted to compare pre- and post-intervention effects at Saiseikai Futsukaichi Hospital. We analyzed the days of therapy (DOT) for carbapenems and days of antibiotic spectrum coverage (DASC) for antimicrobials using an interrupted time series analysis. Cox proportional hazards analysis was performed to assess 30-day mortality using propensity score and inverse probability of treatment weighting in patients with bacteremia., Results: Pharmacist-driven interventions significantly reduced the DOT (incidence rate ratio [IRR]: 0.53, 95 % confidence intervals [CI]: 0.33-0.81, p = 0.003) and DASC (IRR: 0.87, 95 % CI: 0.78-0.97, p = 0.016). The 30-day mortality due to bacteremia did not significantly differ between pre- and post-intervention in all patients (adjusted hazard ratio [HR]: 0.92, 95 % CI: 0.56-1.51, p = 0.74). Conversely, pharmacist-driven interventions significantly reduced the 30-day mortality owing to bacteremia with Pitt bacteremia score (PBS) ≥4 (adjusted HR: 0.52, 95 % CI: 0.28-0.99, p = 0.047)., Conclusions: Pharmacist-driven interventions may represent a valuable approach for optimizing antimicrobial treatment and improving prognosis, especially in patients with PBS ≥4, which will potentially benefit patients in similar healthcare environments facing challenges related to antimicrobial stewardship and patient prognosis., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: People living with human immunodeficiency virus (PLWH) have higher mortality rates from COVID-19 than those without HIV. Additionally, the seroconversion rate of antibodies following a second dose of SARS-CoV-2 vaccine is lower in PLWH than non-infected individuals, indicating the need for booster vaccination. Here, we evaluated the humoral and cellular immune responses to booster SARS-CoV-2 vaccination in PLWH., Methods: The dynamics of anti-spike IgG titers and antigen-specific interferon (IFN)-γ levels to SARS-CoV-2 vaccination were assessed over a 6-month period following a third vaccination of 34 PLWH., Results: Antibody titers for humoral immunity were 50 % lower at 24 weeks post-vaccination than those at 12 weeks. However, those at 24 weeks after the booster vaccination were approximately eight times higher than before. Regarding cellular immunity, IFN-γ levels at 24 weeks after the third vaccination were lower than those at 12 weeks, but nearly 90 % of participants maintained a cut-off value of ≥0.15 IU/mL. A comparison between two groups with CD4 + T lymphocytes counts of <500/μL or ≥500/μL exhibited no statistically significant differences in antibody or IFN-γ levels. However, in the group with CD4 + T lymphocyte counts of <500/μL, the rate of IFN-γ above the cut-off value at 24 weeks after the booster vaccination was lower than that of ≥500/μL., Conclusion: An immune response is expected in PLWH given successful antiretroviral therapy with booster SARS-CoV-2 vaccination. However, caution should be exercised for cases with low CD4 + T-lymphocyte counts. (240/250 words)., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: Pretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR)., Methods: Clients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV., Results: In total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80-0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14-0.63) were significantly associated with YFV., Conclusions: Preventive interventions other than YFV should be offered to older adults., Competing Interests: Declaration of competing interest K.Y. received research grants from Fujirebio, Inc.; Mizuho Medy, Co., Ltd.; VisGene, Co., Ltd.; Canon Medical Systems, Corp.; Sanyo Chemical Industries, Ltd.; and CarbGeM Inc. Outside the submitted work. The authors therefore declare no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The association between lipoprotein subclasses and carotid intima-media thickness (cIMT) progression has yet to be fully evaluated. We assessed which lipoprotein subclasses were associated with maximum cIMT levels in the general population., Methods: In this study, cholesterol and triglyceride content of 20 lipoprotein subclasses were analyzed using gel permeation high-performance liquid chromatography (GP-HPLC) in 864 Japanese women and men (mean age 57 y, free of chronic liver or kidney diseases and off lipid-lowering, hormone replacement, or adrenocorticosteroid medications). Univariate and multivariate regression analyses and univariate and partial correlation analyses were performed to examine the relationships between lipoprotein subclasses and maximum cIMT levels., Results: After adjusting for age, sex, systolic blood pressure, smoking, diabetes, and anti-hypertensive agents, elevated low-density lipoprotein (LDL)-2 and -3 cholesterol (particle diameter 25.5 nm and 23.0 nm, respectively; medium and small LDL) were associated with higher maximum cIMT levels in both women and men (all p for trend < 0.05). These associations were significant even after participants taking anti-diabetic or anti-hypertensive agents were excluded. No significant associations were found between any triglyceride subclasses and maximum cIMT levels., Conclusions: Smaller LDL particle cholesterol values are the most atherogenic lipoprotein parameter., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A 53-year-old male Japanese patient with COVID-19 was admitted to our hospital after his respiratory condition worsened on day 9 of the disease. With the diagnosis of severe COVID-19, treatment with remdesivir, dexamethasone, and unfractionated heparin was started for the prevention of thrombosis. Although the patient's respiratory status data improved after treatment, severe respiratory failure persisted. Thrombocytopenia and D-dimer elevation were observed on day 8 after heparin therapy initiation. Heparin-induced thrombocytopenia (HIT) antibody measured by immunological assay was positive, and contrast computed tomography showed pulmonary artery thrombus. The patient was diagnosed with HIT because the pre-test probability score (4Ts score) for HIT was 7 points. Heparin was changed to apixaban, a direct oral anticoagulant, which resulted in a reduction of the pulmonary thrombus and improvement of the respiratory failure. In patients with COVID-19, anticoagulant therapy with heparin requires careful monitoring of thrombocytopenia and elevated D-dimer as possible complications related to HIT. (151/250 words)., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Daptomycin is used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend higher daptomycin doses (8-10 mg/kg) for severe infections; however, pharmacokinetic (PK) and pharmacodynamic-based dosing strategies are still limited. Therefore, we designed a new optimal daptomycin dosing regimen for patients with MRSA infections using a population PK modeling approach. A total of 110 plasma concentrations from 47 adult patients who received daptomycin in general wards were enrolled for population PK modeling. The target area under the concentration-time curve/minimum inhibitory concentration (MIC) ratio, target peak/MIC ratio, and threshold of the trough concentration for safety were set to >666, >60, and 24.3 mg/L, respectively. Renal function was indicated as a significant covariate for daptomycin clearance. The simulated probability of target attainment was more than 90% at MIC values of 0.25 and 0.5 mg/L in all patients at the standard dose (6 mg/kg). In contrast, comprehensive simulation assessments recommended 10 mg/kg every 24 h in patients with creatinine clearance >60 mL/min for MIC values of 1.0 mg/L. We propose a new simplified daptomycin dosing regimen stratified by renal function and MIC values based on PK model-based simulation analyses. The proposed regimen is expected to maximize clinical efficacy and minimize adverse events., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Introduction: Many countries are administering a third dose of COVID-19 vaccines, but the evaluation of vaccine-induced immunity is insufficient. In addition, there are few reports of long-term observation of anti-spike IgG antibody titers after the vaccination in the Japanese population. This study aimed to evaluate anti-spike IgG levels in the Japanese health care workers six months after the BNT162b2 vaccination., Methods: Dynamics of anti-spike IgG levels were assessed over a six-month period following the second vaccination in 49 participants (Analysis-1). A cross-sectional assessment of anti-spike IgG levels six months after the second vaccination was performed in 373 participants (Analysis-2)., Results: In Analysis-1, the geometric mean titer of anti-spike IgG was lower in the older age group and decreased consistently after the second vaccination regardless of age. In Analysis-2, the anti-spike IgG level was significantly negatively associated with age (r = -0.35, p < 0.01). This correlation remained statistically significant (r = -0.28, p < 0.01) after adjustment for sex, BMI, smoking habits, alcohol drinking habits, allergies, and fever or other adverse reactions at the time of vaccination. Additionally, participants who drank alcohol daily had significantly lower anti-spike IgG levels than participants who had never drunk alcohol. Sex, smoking habits, allergy, and fever and other side effects after vaccination did not show a significant association with anti-spike IgG levels., Conclusions: Six months post-vaccination, the anti-spike IgG level was substantially lower in older persons and daily alcohol drinkers. This may be an indication for an additional vaccine dose for these at-risk categories., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT), post-transplant lung infection is critical for their prognosis. Mycobacterium abscessus complex is not fully recognized as a nontuberculous mycobacteria (NTM) pathogen of post-SCT lung infection. Here, we present three post-allogeneic SCT patients who developed pulmonary infection caused by M. abscessus complex including M. abscessus and M. massiliense. In all three cases, macrolide antibiotics had been administered for bronchiolitis obliterans syndrome (BOS) before the confirmation of their infection, and macrolide resistance was noted in the M. abscessus isolates, one of which resulted in an unfavorable treatment outcome. It is important to consider M. abscessus lung infection as well as other NTM in patients receiving allo-SCT, particularly those receiving macrolide therapy for BOS., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Fungus balls have been rarely implicated as a cause of urinary tract obstruction. Here, we report a case of Candida albicans fungus balls in the urinary tract after the treatment of Candida endophthalmitis that has enough periods and adequate amount of antifungal agents. The patient completely recovered from this rare complication by irrigating through single-J stent and changing antifungal agents. Here we emphasize that we should take into account not only the susceptibility test results but also the difference in excretion route and tissue distribution of antifungal agents., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Ninety-four episodes of Klebsiella pneumoniae bloodstream infection were identified at a university hospital in Japan. After excluding extended-spectrum beta lactamase-producing strains, 83 blood isolates from these patients were assayed in terms of their bacterial phenotypes such as the mucoid and hypermucoviscosity phenotypes. Bacterial phenotypes were correlated with the patients' clinical manifestations. The hypermucoviscosity phenotype was significantly associated with septic shock at the onset of infections (odds ratio, 15.92; 95% confidence interval, 1.27-468.12), but was not associated with liver abscess formation. Mortality was determined by the presence of septic shock. RmpA gene was associated with the induction of the hypermucoviscosity phenotype. These results reveal unique roles of bacterial phenotypes on the patient's clinical condition in K. pneumoniae bacteremia., (Copyright © 2015. Published by Elsevier Ltd.)

Candida tropicalis is one of the most important Candida species causative of candidemia that is isolated from the blood of patients with hematological malignancies. Candidemia caused by C. tropicalis is known to be highly virulent in neutropenic patients. C. tropicalis has been shown to be favorably sensitive to azole agents in general. Here we discuss 5 cases of candidemia caused by C. tropicalis in patients with hematological malignancies in our unit, and we note that 4 isolates were resistant to azole agents, including fluconazole, itraconazole, and voriconazole. In addition, 2 patients developed breakthrough candidemia caused by C. tropicalis while receiving prophylaxis with azole agents. Interestingly, 2 of the 4 patients with azole-resistant C. tropicalis isolates had never received any antifungal drugs. We also examined the susceptibilities of C. tropicalis to antifungal agents, using 39 non-blood isolates detected from 2003 to 2009. Around 40 % of the isolates were resistant to azole agents, and all of them were highly sensitive to amphotericin B and micafungin. The resistance to azoles was not associated with previous exposure to those agents. In our unit, 2 of the 4 cases of candidemia caused by azole-resistant C. tropicalis resulted in a poor prognosis. These findings suggested that empirical therapeutic strategies for candidemia should be modified based on the local antifungal resistance pattern.

Allogeneic hematopoietic stem cell transplantation (SCT) is a curative therapy for various hematologic disorders. Graft-versus-host disease (GVHD) and infections are the major complications of SCT, and their close relationship has been suggested. In this study, we evaluated a link between 2 complications in mouse models. The intestinal microbial communities are actively regulated by Paneth cells through their secretion of antimicrobial peptides, α-defensins. We discovered that Paneth cells are targeted by GVHD, resulting in marked reduction in the expression of α-defensins, which selectively kill noncommensals, while preserving commensals. Molecular profiling of intestinal microbial communities showed loss of physiologic diversity among the microflora and the overwhelming expansion of otherwise rare bacteria Escherichia coli, which caused septicemia. These changes occurred only in mice with GVHD, independently on conditioning-induced intestinal injury, and there was a significant correlation between alteration in the intestinal microbiota and GVHD severity. Oral administration of polymyxin B inhibited outgrowth of E coli and ameliorated GVHD. These results reveal the novel mechanism responsible for shift in the gut flora from commensals toward the widespread prevalence of pathogens and the previously unrecognized association between GVHD and infection after allogeneic SCT.

An outbreak of Bacillus cereus (B. cereus) bacteremia occurred in our neonatal intensive care unit (NICU) in July 2005. Many strains of B. cereus were cultured from patient specimens, as well as from environmental samples such as the surfaces of instruments and air in the NICU. Some of these strains were analyzed by pulsed field gel electrophoresis, and several were confirmed to be identical. We speculated that the bacterial load in the environment had initially increased and then possibly spread throughout the NICU facility via the airflow of the ventilation system. For this reason, besides maintaining standard precautions, we performed a vigorous clean of the NICU, and covered the vents to prevent dust falling from them. These protective measures ended the outbreak. In the hospital environment, adequate ventilation is important, especially in single-occupancy isolation rooms and operating theaters. However, the criteria for the adequate ventilation of multioccupancy rooms for acute care environments such as the NICU have not yet been defined. We need to pay more attention to these environmental factors in order to avoid cross contamination and infectious outbreaks.

An outbreak of Pseudomonas aeruginosa infections occurred after thoracic surgeries performed between May and June 2003. Clinical data of seven patients were reviewed and the fact was revealed that bronchoscopes were used during endotracheal intubation for one-lung ventilation in most patients. P. aeruginosa was recovered from the sputum of these patients at a very early stage post-operation. Environmental samples from bronchoscopes and an automated endoscope reprocessor (AER) were cultured and P. aeruginosa strains were recovered from all of them. All of these strains were confirmed to be identical by pulsed-field gel electrophoresis (PFGE). Inspection of the sterilization cycles of bronchoscopes revealed inappropriate management of bronchoscopes and a flaw in the AER; once its detergent tank was contaminated, it was not possible to disinfect it. After all the bronchoscopes had been disinfected, and the washing machine had been remodeled, with the washing process confirmed to be appropriate, the outbreak finally ended. This outbreak had two causes, a flaw in the AER and inappropriate disinfection procedures. Outbreaks associated with bronchoscopic examinations have been reported elsewhere. Bronchoscopes are widely used to facilitate endotracheal intubation, especially for one-lung anesthesia. Although they are used for only a short time during anesthetic procedures, we should handle them more carefully.

Pseudomonas aeruginosa is a pathogen which is known to be responsible for nosocomial infection. The appropriate use of antibiotics has become important for preventing the spread of drug-resistant P. aeruginosa. In Hara-doi Hospital, two carbapenem antibiotics, imipenem (IPM) and meropenem (MEPM), are used for patients aged 65 years or older at a daily dosage of 1.0 g and 0.5 g, respectively. Of P. aeruginosa samples isolated in 2003, the sensitivity to IPM was 54% and to MEPM it was 58%. In 2004, the sensitivity to IPM was 55%, i.e., not significantly different from 2003. In 2004, the daily dosage of MEPM was increased to 1.0 g/day, and the sensitivity to MEPM increased to 71%. Based on the Pharmacokinetics/Pharmacodynamics (PK/PD) theory, even though the patients were elderly, a sufficient dosage of antibiotics given over a shorter period of time was effective against MEPM-resistant P. aeruginosa in a hospital ward, and there were no side effects.

Three hundred and seventy-one strains of Pseudomonas aeruginosa were isolated at the laboratory of Kyushu University Hospital in Japan from May 2002 through January 2003. Large proportions of isolated strains were resistant to carbapenems: 37.5% to imipenem, 21.3% to biapenem, and 18.3% to meropenem. A survey of injectable antibacterial agents used in our hospital during the corresponding period showed that carbapenems were most frequently used. Multidrug-resistant P. aeruginosa (MDRP) strains and metallo-beta-lactamase producing strains were isolated at frequencies of 1.6% (6 strains) and 0.81% (3 strains), respectively. By molecular epidemiological analysis, neither MDRP nor metallo-beta-lactamase producing strains were molecularly related, whereas some imipenem-resistant strains appeared to be epidemic strains, suggesting a possibility that they might spread by nosocomial infection. To control nosocomial infection, it is important to know a trend in drug-resistant P. aeruginosa and to prevent the spread of not only MDRP and metallo-beta-lactamase producing strains but also imipenem-resistant P. aeruginosa strains.

The properties of internal-surface reversed-phase silica packings developed for use in high-performance liquid chromatography, were investigated with regard to the effects of mobile phase conditions (pH, ionic strength, nature and concentration of organic modifiers, ion-pairing agent and surfactant) on the retention of some selected compounds having different polarities. The results indicated that pi-electron interactions play the main role in solute retention, although it is weaker than that on phenylsilica supports, and that weak cation-exchange properties exert a secondary effect on the retention of ionic solutes. The ion-pairing effect was found to be markedly weakened in mobile phases containing an anionic counter ion. In contrast, the addition of a surfactant (SDS) caused a marked increase in the retention of certain drugs at low pH and expanded the pH range of the mobile phase applicable to plasma samples. Based on these findings, the separation and recovery of several drugs (probenecid, lidocaine, cefpiramide and cefaclor) from human plasma were investigated, with emphasis on their protein bindings. The contour chromatogram of human plasma is also demonstrated in relation to the selection of the detection wavelength.