Evaluation of antimicrobial stewardship activities using antibiotic spectrum coverage.

Recently, the days of antibiotic spectrum coverage (DASC) using the antibiotic spectrum coverage (ASC) score was reported as a new tool for measuring antimicrobial use. The days of therapy (DOT) are required to calculate the DASC, making it impossible to use when patient-level information is unavailable. Therefore, we have defined a new measure of antimicrobial use for antimicrobial spectrum coverage (AUSC) using antimicrobial use density (AUD) and ASC scores. In this study, we have investigated the use of antimicrobial agents retrospectively examined for monthly prescriptions between 2016 and 2022, and whether the AUSC could be used as a new measure. Our data showed that the AUD, AUSC, DOT, and DASC increased, whereas AUSC/AUD and DASC/DOT decreased over the study period. In addition, no correlation was found between DOT and DASC/DOT (ρ = - 0.093, p = 0.399), whereas there was a weak correlation between AUD and AUSC/AUD (ρ = - 0.295, p = 0.006). Therefore, in this study, the use of AUSC is considered less beneficial when DASC can be calculated based on DOT. On the other hand, in institutional settings where DOT cannot be calculated, AUSC may be useful as a new measure to evaluate antimicrobial use.

Relationship of low muscle mass and obesity with physical function in community dwelling older adults: Results from the Nagahama study.

AIM: Relationships of low muscle mass and obesity with physical function were investigated in older adults. METHODS: The participants were 1922 community dwelling persons aged 60 years or older (67.7 ± 5.2 years old, 643 men and 1279 women). One-leg standing time, knee extensor muscle strength, and maximum walking speed were assessed. Muscle mass was evaluated using the bioelectrical impedance analysis (BIA) method, and skeletal mass index (SMI) was determined. For the obesity index, waist circumference with a stronger association with visceral fat was used. Participants were classified into the following four groups based on standard values of waist circumference and SMI: non-obese low-SMI, obese low-SMI, non-obese normal-SMI, and obese normal-SMI. RESULTS: By two-way analysis of variance (obesity × SMI), the main effects of waist circumference and muscle mass were noted in the one-leg standing time. The maximum walking speed was higher in the non-obese than the obese group, and in the normal than the low SMI group. In the muscle strength, a main effect was noted only in the muscle mass of women. An interaction was noted in men and significant differences were detected between all combinations except between the non-obese low SMI and obese low SMI groups. CONCLUSION: Low muscle mass and obesity negatively influence balance and walking abilities. However, the influence of low muscle mass and obesity on muscle strength were different between the sexes. In men, the relationship between obesity and muscle strength would be different depending on whether muscle mass is retained.

Association of amniotic fluid sludge with preterm labor and histologic chorioamnionitis in pregnant Japanese women with intact membranes: A retrospective study.

AIM: The presence of amniotic fluid sludge has been identified as a risk factor for preterm birth. We sought to validate the clinical characteristics of amniotic fluid sludge in Japanese pregnant women with preterm labor and intact membranes. METHODS: This was a retrospective study of 54 patients. The presence of amniotic fluid sludge was confirmed using transvaginal ultrasonography data during pregnancy. The following data were collected: gestational age, the presence of histologic chorioamnionitis, time from the diagnosis of threatened premature labor to delivery, oncofetal fibronectin (onfFN) levels, C-reactive protein peak value levels, cervical length at the time of onset of threatened premature labor and types of neonatal complications. RESULTS: Significant differences (P = 0.03) were observed in the age at delivery in relation to the presence of amniotic sludge: delivery occurred at 28.3 ± 4.5 weeks and 31.7 ± 4.3 weeks in sludge positive patients and sludge-negative patients, respectively. Presence of sludge in patients diagnosed with histological chorioamnionitis at <37 weeks of gestation differed significantly (P = 0.01): sludge-positive, 81.8%; sludge-negative, 20.9%. Among the sludge-positive patients, 100% were positive for serum onfFN (≥50 ng/mL), whereas only 54% of sludge-negative patients were positive for serum onfFN (P = 0.03). Presence of amniotic fluid sludge did not significantly affect neonatal complications. CONCLUSION: Our results confirmed previous findings that amniotic fluid sludge is a self-determining risk factor for preterm birth and chorioamnionitis in pregnant Japanese women.

Association of Activities of Daily Living With Load During Step Ascent Motion in Nursing Home-Residing Elderly Individuals: An Observational Study.

OBJECTIVE: This study aimed to examine the association of independence in activities of daily living with the loads during step ascent motion and other motor functions in 32 nursing home-residing elderly individuals. DESIGN: Independence in activities of daily living was assessed by using the Functional Independence Measure. The loads at the upper (i.e., pulling up) and lower (i.e., pushing up) levels during the step ascent task was measured on a step ascent platform. Hip extensor, knee extensor, plantar flexor muscle, and quadriceps setting strengths; lower extremity agility using the stepping test; and hip and knee joint pain severities were measured. One-legged stance and functional reach distance for balance and maximal walking speed, timed up-and-go time, five-chair-stand time, and step ascent time were also measured to assess mobility. RESULTS: Stepwise regression analysis revealed that the load at pushing up during step ascent motion and timed up-and-go time were significant and independent determinants of Functional Independence Measure score. Functional Independence Measure score decreased with decreased load at pushing up and increased timed up-and-go time. CONCLUSIONS: The study results suggest that depending on task specificity, both one step up task's push-up peak load during step ascent motion and timed up-and-go can partially explain activities of daily living's Functional Independence Measure score in nursing home-residing elderly individuals. Lower extremity muscle strength, agility, pain, or balance measures did not add to the prediction.

Meta-analysis on the Influence of Antifungal Spectrum on Effectiveness of Empirical Antifungal Therapy for Febrile Neutropenia.

We conducted a meta-analysis to investigate the influence of antifungal spectrum on the effectiveness and adverse events of empirical antifungal therapy for febrile neutropenia. We searched PubMed and Cochrane Central Register of Controlled Trials (Central), and identified randomized controlled trials reporting mortality, efficacy, adverse events, and hepatic and renal dysfunction. Five trials assessed the efficacy and adverse events of agents with antifungal spectrum covering and those not covering Aspergillus. There were no differences in mortality [risk ratio (RR); 0.79, 95% confidence interval (Cl); 0.60-1.02], efficacy ratio (RR; 1.01, 95%Cl; 0.91-1.12), adverse event ratio (RR; 0.23, 95%Cl; 0.04-1.23), and hepatic dysfunction ratio (RR; 0.81, 95%Cl; 0.59-1.12) between two groups. Antifungals with no activity against Aspergillus were associated with lower renal dysfunction ratio (RR; 0.27, 95%Cl; 0.10-0.71). Five trials compared agents with antifungal spectrum covering versus those not covering Mucor. There were no difference in mortality (RR; 1.24, 95%Cl; 0.98-1.57), efficacy ratio (RR; 1.09, 95%Cl; 0.91-1.30), and hepatic dysfunction ratio (RR; 0.98, 95%Cl; 0.66-1.45) between two groups. Antifungals with no activity against Mucor were associated with lower adverse event ratio (RR; 0.60, 95%Cl; 0.47-0.77) and renal dysfunction ratio (RR; 0.25, 95%Cl; 0.13-0.49). Presence or absence of activity against Aspergillus or Mucor is not associated with mortality or efficacy ratio. Amphotericin B with activity against Aspergillus and Mucor has a higher adverse event ratio. Depending on the case, selection of antifungal drugs considering efficacy and side effects is necessary.

Variation in the 5'-flanking region of the neuropeptide Y2 receptor gene and metabolic parameters.

A previous report describes that neuropeptide Y (NPY)/NPY2 receptor (NPY2R) is involved in stress-induced visceral obesity. This is a report clarifying the effect on metabolic parameters of single nucleotide polymorphisms in the 5'-flanking region of NPY2R gene. Study participants are 317 people (98 men and 219 women, 40-79 years old) undergoing health checkups. The single nucleotide polymorphism typing of rs6857715 and rs6857530 located on the 5'-flanking region of the NPY2R gene was performed using allele-specific polymerase chain reaction method. Serum high-density lipoprotein cholesterol (HDL-C) level was significantly lower in men possessing rs6857715 TT genotype compared with CC and in men possessing rs6857530 GG genotype compared with AA. No significant difference was observed between each genotype and other metabolic parameters including body mass index, waist circumference, systolic and diastolic blood pressure, serum low-density lipoprotein cholesterol, triglyceride, and fasting plasma glucose. The variation in the 5'-flanking region of the NPY2R gene was associated with serum HDL-C level in men and was a predictor for serum HDL-C level independent of sex and serum triglyceride level.

Urinary lipocalin-type prostaglandin D synthase: a potential marker for early gentamicin-induced renal damage?

Urinary excretion of lipocalin-type prostaglandin D synthase (L-PGDS) has been suggested to be a useful biomarker of early diabetic nephropathy. We studied whether L-PGDS is also a marker of gentamicin (GM)-induced renal damage in the "creatinine-blind" range. A prospective study was conducted in 6 patients who were given long-term intravenous administration of GM (18-42 days in combination with a beta-lactam/carbapenem antibiotic or vancomycin) for the treatment of infective endocarditis. Urinary excretions of L-PGDS, beta2-microglobulin, and N-acetyl-beta-D-glucosaminidase were measured in the early (within 10 days from commencement) and late (thereafter) phases of GM therapy. Systemic clearance of GM (CLGM) and creatinine clearance (CLcr) was also measured concomitantly. CLGM was reduced significantly (P < 0.05) by 10% from the early to late treatment phase, whereas urinary L-PGDS excretion showed a significant (P < 0.05) increase (from 7.3 +/- 4.6 to 8.7 +/- 5.0 mg/g creatinine, mean +/- SD) concomitantly. In contrast, no significant changes were observed for urinary beta2-microglobulin and N-acetyl-beta-D-glucosaminidase concentrations. In conclusion, urinary L-PGDS may be a promising biomarker for the early phase of GM-induced renal impairment.

Relation between drug-induced taste disorder and chelating behavior with zinc ion; statistical approach to the drug-induced taste disorder, part II.

There are many reports that the drug-induced taste disorder is ascribable to the chelate reaction of a drug with zinc ion and the following zinc deficiency. As a quantitative measure of the chelating ability of drugs with zinc ions, the chelating ability was estimated from the electrode potential change of the Zn2+/Zn(Hg) system during the addition of a drug. The electrode potential was measured in a water-N,N-dimethylformamide mixed solution and in an aqueous solution depending on the solubility of the drugs. The observed electrode potential change showed a positive correlation to the frequency of the drug-induced taste disorder that was supplied from the manufacturer of the original drug. The regression analysis was carried out assuming that the frequency of the taste disorder and the electrode potential change was linear. The F-values, p-values, and R2-values were 4.29, 0.13, 0.589, and 4.15, 0.13, 0.580, respectively. The positive correlation between the drug-induced taste disorder and the electrode potential change appeared evident if the uncertainty in the frequency of the taste disorder was taken into consideration. Thus the assumption of the zinc ion chelating mechanism on the drug-induced disorder was also evident except for cisplatin. The frequency of the drug-induced taste disorder of bezafibrate was estimated to be 0.4--0.5 from the regression analysis.

Reduced vancomycin clearance despite unchanged creatinine clearance in patients treated with vancomycin for longer than 4 weeks.

Creatinine clearance-based nomograms are used routinely during the early phase of vancomycin therapy for individualizing doses. The authors studied whether such nomograms are also valid for patients receiving the drug for an extended period of longer than 4 weeks. A retrospective analysis was conducted on the therapeutic drug monitoring data obtained from 85 patients who received an intermittent intravenous infusion of vancomycin. The patients were allocated to one of five groups according to the length of drug exposure: Group 1 (4-7 days; n = 31), Group 2 (8-14 days; n = 22), Group 3 (15-21 days; n = 13), Group 4 (22-28 days; n = 8), and Group 5 (longer than 29 days; n = 11). Systemic clearance of vancomycin and estimated creatinine clearance calculated by Cockcroft & Gault's formula obtained from Groups 2 through 5 were compared with those from Group 1. Patients who had received vancomycin for longer than 4 weeks (Group 5) showed a significant (P < 0.05) reduction in systemic clearance of vancomycin by 50% compared with Group 1, whereas creatinine clearance remained unchanged. This study demonstrated that prolonged administration of vancomycin for over 4 weeks may result in a more pronounced reduction in systematic clearance of vancomycin than creatinine clearance. Our data suggest that creatinine clearance-based nomograms for individualizing vancomycin doses should be used with caution in patients who require substantially prolonged drug exposure such as those with infective endocarditis.

Statistical approach to drug-induced taste disorders based on zinc chelating ability.

Various drug-induced taste disorders have been ascribed to zinc deficiency in serum. Assuming that the zinc deficiency is caused by the chelating reaction of zinc ions with drugs, the electrode potential of the Zn(2+)/Zn(Hg) system was measured in the presence of drugs in water, ethanol, and N,N-dimethylformamide (DMF). The zinc-chelating ability was estimated based on the potential change Delta E(2) with the addition of a drug. A large potential change suggesting potent chelating ability was observed in penicillamine, furosemide, and ibuprofen in ethanol and in fluorouracil, acetazolamide, and bezafibrate in DMF. Multiple regression analysis was used to evaluate the observed Delta E(2) in mV to represent chelating ability. The regression equation to estimate the frequency of taste disorders was deduced from Delta E(2), and frequency of four drugs appeared in package inserts and interview forms. According to the regression equation, the frequency of taste disorders was successfully estimated for 14 drugs examined in this study. The result was examined in a clinical case.

Crystal structure of chartreusin derivative A132.

The crystal structure of chartreusin derivative A132 (benzilidene chartreusin) has been determined by single-crystal X-ray diffraction. The space group is C2 with unit cell dimensions, a=18.482(4), b=8.749(3), c=43.906(2) A, beta=94.87(2) degrees, and the structure was refined to R-factors of 0.2365 (6585 all unique reflections) and 0.087 (2914 reflections with F(o)>4 sigma(F(o))) by a full-matrix least-squares method. There are two molecules in an asymmetric unit. Both molecules have similar structures, which are favorable to bind with DNA in the minor groove. A modeling study of the A132-DNA complex based on the X-ray structures suggests that the sugar moiety of A132 may play an important role in recognizing the sequence of DNA base pairs.

[Creation and evaluation of the respective rank problem solution worksheet for improvement pharmaceutical management quality].

A respective rank problem solution worksheet was developed focusing on problem solution in training in pharmaceutical management. How the training influenced the instructions given to patients was then evaluated in two pharmacists in the NTT East Kanto Medical Center and three in an Ofuna central hospital. After the five pharmacists underwent the training, the records of 10 medication instructions to patients given by each before and after the training were compared. The records were analyzed based on a point calculation table, and the number of acquisition points was computed. The acquisition points increased significantly after training for all five pharmacists, from a mean of 3.56 before training to a mean of 8.34 after training. Although the acquisition points related to patient education were high, those for intervention during therapeutic monitoring, such as for adverse drug reaction or the selection of appropriate pharmaceuticals were acceptable, increasing to a mean 8.4 items after training compared with 4.4 items before. The respective rank problem solution worksheet is therefore considered useful in improving the quality of training pharmaceutical management.

Clinical estimation of vancomycin measurement method on hemodialysis patient.

The fluorescence polarization immunoassay (FPIA) method is used to perform measurement of vancomycin hydrochloride (VCM) at many institutions. However, the values measured by the FPIA method are more vulnerable to overestimation than the high performance liquid chromatography (HPLC) method. In particular, it was not reported to perform exact therapeutic drug monitoring (TDM) measurement. Since overestimation is likely in patients with renal dysfunction, the HPLC method is preferable for TDM measurement. This study investigates the clinical conditions that lead to overestimation in the FPIA method, paying attention to the relation of clinical laboratory data inspection values and the existence of hemodialysis (HD). Overestimation in the evaluation of TDM using the FPIA method was clinically examined with 116 serum samples obtained from 18 cases medicated with VCM. The relevance between overestimation of patients who had not had HD performed was 72.7 +/- 61.7% (means +/- SD). In short, the overestimation was greatest in HD patients. Since overestimation did not affect the evaluation of clinical TDM, such as an effect and a side-effect, the TDM of VCM was shown to be satisfactorily evaluated by the simple FPIA method.