Relationship between the dose titration and adherence of mirogabalin in patients with peripheral neuropathic pain depending on renal function: a nationwide electronic medical record database study.

BACKGROUND: Mirogabalin has been attracting attention for treating peripheral neuropathic pain. The package insert recommends that mirogabalin should be titrated depending on renal function. Here, we investigated the relationship between dose titration patterns and adherence, and persistence of mirogabalin treatment. RESEARCH DESIGN AND METHODS: Peripheral neuropathic pain patients who initiated mirogabalin between March 2020 and May 2021 were identified using an electronic medical record database. The dose titration pattern was described according to degrees of renal function. Regression analyses were performed to compare adherence and persistence between the patients with and without titration. RESULTS: Of the 4,138 identified patients, 1,696 (41.0%) titrated the dose within 45 days and were more adherent than those without titration (Adjusted odds ratio: 1.75, 95% CI 1.21, 2.54). Of the total 952 patients with renal function parameters, 229 (24.1%) titrated to the effective dose within 45 days and were less likely to discontinue than those without titration (Adjusted hazard ratio: 0.57, 95% CI 0.40, 0.81). CONCLUSION: Mirogabalin dose titration was associated with better adherence and persistence. It is important for mirogabalin treatment to determine the initial prescription dose based on renal function and subsequent dose titration according to the package insert. TRIAL REGISTRATION: UMIN000047313.

Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation.

BACKGROUND: Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. METHODS: We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. RESULTS: Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. CONCLUSIONS: The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.

Regional Spread of CTX-M-2-Producing Proteus mirabilis with the Identical Genetic Structure in Japan.

AIMS: In this study, we analyzed the molecular epidemiology of extended-spectrum ß-lactamase (ESBL)-producing Proteus mirabilis isolates collected from the central region of Japan. MATERIALS AND METHODS: Between 2005 and 2012, 820 clinical P. mirabilis isolates were obtained from ten acute care hospitals in Japan. We characterized ESBL confirmatory test-positive isolates by sequencing the ESBL genes and their flanking regions, detecting plasmid replicons, and performing pulsed-field gel electrophoresis (PFGE). RESULTS: Ninety-six isolates (12%) were positive according to the ESBL confirmatory test; all these isolates possessed blaCTX-M-2 with the same flanking structure of upstream ΔISEcp1 and a downstream region identical to downstream blaKLUA-1. IncT was the prevalent, and only, replicon found in 63 isolates. PFGE analysis detected eight clusters with more than one isolate, among which three included 56 isolates and six included isolates from multiple hospitals. CONCLUSION: CTX-M-2-producing P. mirabilis with an identical genetic structure flanking blaCTX-M-2 is dominant in this Japanese region, and there is evidence for the clonal spread of isolates.

Genetic, phenotypic and matrix-assisted laser desorption ionization time-of-flight mass spectrometry-based identification of anaerobic bacteria and determination of their antimicrobial susceptibility at a University Hospital in Japan.

The accuracies of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the phenotypic method using VITEK 2 were compared to the accuracy of 16S rRNA sequence analysis for the identification of 170 clinically isolated anaerobes. The antimicrobial susceptibility of the isolates was also evaluated. Genetic analysis identified 21 Gram-positive species in 14 genera and 29 Gram-negative species in 11 genera. The most frequently isolated genera were Prevotella spp. (n = 46), Bacteroides spp. (n = 25) and Clostridium spp. (n = 25). MALDI-TOF MS correctly identified more isolates compared with VITEK 2 at the species (80 vs. 58%, respectively; p < 0.01) and genus (85 vs. 71%, respectively; p < 0.01) levels. More than 90% of the isolates of the three major genera identified (Prevotella, Bacteroides, and Clostridium species other than Clostridium difficile) were susceptible to beta-lactam/beta-lactamase inhibitor combinations, carbapenems, metronidazole and chloramphenicol. MALDI-TOF MS provided better identification results than VITEK2. Commonly used anti-anaerobic agents indicated that the isolates of the three most frequently identified anaerobic genera exhibited good antimicrobial susceptibility.

Oral administration and younger age decrease plasma concentrations of voriconazole in pediatric patients.

Voriconazole is used for treating or preventing invasive aspergillosis and other invasive fungal infections. To minimize adverse reactions and to maximize treatment effects, therapeutic drug monitoring should be performed. However, it is challenging to optimize daily voriconazole dosing because limited data have been published so far on pediatric patients. We retrospectively analyzed voriconazole concentrations in patients aged 0-18 years. In addition, a literature review was conducted. In our study cohort, younger age and oral administration were significantly associated with lower plasma voriconazole concentrations (P < 0.01). An unfavorable outcome was associated with low concentrations of voriconazole (P = 0.01). Reports of voriconazole administration in pediatric patients show that higher doses are required in younger children and in patients receiving oral administration. Hence, the current data suggest that we should escalate both initial and maintenance doses of voriconazole in pediatric patients, particularly in patients of younger age receiving an oral administration of voriconazole.

Risk factors and outcomes of Stenotrophomonas maltophilia bacteraemia: a comparison with bacteraemia caused by Pseudomonas aeruginosa and Acinetobacter species.

Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen that exhibits intrinsic resistance to various antimicrobial agents. However, the risk factors for SM bacteraemia have not been sufficiently evaluated. From January 2005 to September 2012, we retrospectively compared the clinical backgrounds and outcomes of SM bacteraemic patients (SM group) with those of bacteraemic patients due to Pseudomonas aeruginosa (PA group) or Acinetobacter species (AC group). DNA genotyping of the SM isolates using the Diversilab system was performed to investigate the genetic relationships among the isolates. The SM, PA, and AC groups included 54, 167, and 69 patients, respectively. Nine of 17 patients in the SM group receiving trimethoprim-sulfamethoxazole prophylaxis developed SM bacteraemia. Independent risk factors for SM bacteraemia were the use of carbapenems and antipseudomonal cephalosporins and SM isolation within 30 days prior to the onset of bacteraemia. Earlier SM isolation was observed in 32 of 48 patients (66.7%) with SM bacteraemia who underwent clinical microbiological examinations. Of these 32 patients, 15 patients (46.9%) had the same focus of bacteraemia as was found in the previous isolation site. The 30-day all-cause mortality rate among the SM group (33.3%) was higher than that of the PA group (21.5%, p = 0.080) and the AC group (17.3%, p = 0.041). The independent factor that was associated with 30-day mortality was the SOFA score. DNA genotyping of SM isolates and epidemiological data suggested that no outbreak had occurred. SM bacteraemia was associated with high mortality and should be considered in patients with recent use of broad-spectrum antibiotics or in patients with recent isolation of the organism.

Differentiation of vanA-positive Enterococcus faecium from vanA-negative E. faecium by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.

Vancomycin-resistant enterococci are important nosocomial pathogens that require rapid and accurate detection for infection control. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) has begun to be used in many clinical laboratories because it is a rapid, simple and inexpensive method for identifying micro-organisms. In this study, the performance of MALDI-TOF/MS to differentiate vanA-positive Enterococcus faecium (VPEF) from vanA-negative E. faecium (VNEF) was evaluated. A total of 61 VPEF isolates collected during regional surveillance in Kyoto (Japan) and 71 VNEF isolates collected from bacteraemia patients were analysed using MALDI-TOF/MS with three ClinProTools models. All of the isolates were correctly identified as E. faecium using the MALDI Biotyper system. To discriminate between VPEF and VNEF, all three ClinProTools models yielded >90% recognition capability (basic sensitivity) and cross-validation (reliability of the models); the genetic algorithm model exhibited the highest performance (99.18% and 92.40%, respectively). The high detection performance of MALDI-TOF/MS for VPEF offers the potential for routine laboratory use.

[Risk factors and clinical charasteristics of Stenotrophomonas maltophilia bacteremia: a comparison with bacteremia due to other glucose-non fermenters].

Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen. Due to its intrinsic resistance to various therapeutic drugs, the optimal antimicrobial therapy is often delayed. From January 2005 to September 2012, we retrospectively compared drug susceptibilities, clinical backgrounds, and outcome of SM bacteremic patients (SM group) with these of other non fermentative gram negative bacilli bacteremic patients (non-SM group), at a tertiary-care hospital in Kyoto, Japan. Among the SM group, risk factors of 30-day mortality were evaluated. The SM group and non-SM group included 54 and 237 cases, respectively. Among the non-SM group, bacteremic patients due to Pseudomonas aeruginosa, Acinetobacter species, and other non-fermentative gram negative bacilli included 156, 68, and 13 patients, respectively. SM isolates were susceptible to trimethoprim-sulfamethoxazole and minocycline (82.0% and 100%, respectively). Non-SM isolates were susceptible to meropenem (88.6%), ceftazidime (88.6%), cefepime (85.2%), and amikacin (97.0%). Both SM and non-SM isolates were susceptible to levofloxacin (87.5% and 82.0%, respectively). The use of carbapenems, antipseudomonal cephalosporins, and isolation of SM within 30 days represented an independent risk factor for SM bacteremia. The 30 day mortality rate among the SM group was significantly higher compared with the non-SM group (35% vs 18%, odds ratio: 2.2, 95% CI: 1.2-4.3 p = 0.012). Among the SM group, an independent factor which was associated with 30-day mortality was the SOFA score. SM bacteremia showed a worse outcome compared with bacteremia due to non-SM. For the patients who present risk factors for SM bacteremia, empirical antimicrobial therapy including trimethoprim-sulfamethoxazole, minocycline or levofloxacin should be considered.