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... Okada · H. Tsukada Y. Imai · Y. Honma · K. Nishikawa · T. Yamamoto A. Kawai · T. Kashiwabara · Y. Takesue · Y. Wada K. Nakajima · T. Miyara · H. Toda · N. Mitsuno H. Sugimura · S. Yoshioka · M. Kurokawa · Y. Munekawa H. Nakajima · S.... more
... Okada · H. Tsukada Y. Imai · Y. Honma · K. Nishikawa · T. Yamamoto A. Kawai · T. Kashiwabara · Y. Takesue · Y. Wada K. Nakajima · T. Miyara · H. Toda · N. Mitsuno H. Sugimura · S. Yoshioka · M. Kurokawa · Y. Munekawa H. Nakajima · S. Kubo · Y. Ohta · K. Mikasa · K. Maeda ...
This systematic review and meta-analysis compares the efficacy of daptomycin and vancomycin in adult patients with bacteremia by methicillin-resistant Staphylococcus aureus (MRSA) with vancomycin minimum inhibitory concentration (MIC)... more
This systematic review and meta-analysis compares the efficacy of daptomycin and vancomycin in adult patients with bacteremia by methicillin-resistant Staphylococcus aureus (MRSA) with vancomycin minimum inhibitory concentration (MIC) > 1 µg/mL. We searched the PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov databases on 12 May 2020. All-cause mortality (primary outcome) and treatment success rates were compared and subgroups stratified by infection source risk level and method of vancomycin susceptibility testing were also analyzed. Seven studies (n = 907 patients) were included in this efficacy analysis. Compared with vancomycin, daptomycin treatment was associated with significantly lower mortality (six studies, odds ratio (OR) 0.53, 95% confidence interval (CI) 0.29–0.98) and higher treatment success (six studies, OR 2.20, 95% CI 1.63–2.96), which was consistent regardless of the vancomycin MIC test method used. For intermediate-risk sources, daptomycin was a...
This systematic review and meta-analysis examined the optimal trough concentration of voriconazole for adult patients with invasive fungal infections. We used stepwise cutoffs of 0.5–2.0 μg/mL for efficacy and 3.0–6.0 μg/mL for safety.... more
This systematic review and meta-analysis examined the optimal trough concentration of voriconazole for adult patients with invasive fungal infections. We used stepwise cutoffs of 0.5–2.0 μg/mL for efficacy and 3.0–6.0 μg/mL for safety. Studies were included if they reported the rates of all-cause mortality and/or treatment success, hepatotoxicity, and nephrotoxicity according to the trough concentration. Twenty-five studies involving 2554 patients were included. The probability of mortality was significantly decreased using a cutoff of ≥1.0 μg/mL (odds ratio (OR) = 0.34, 95% confidence interval (CI) = 0.15–0.80). Cutoffs of 0.5 (OR = 3.48, 95% CI = 1.45–8.34) and 1.0 μg/mL (OR = 3.35, 95% CI = 1.52–7.38) also increased the treatment success rate. Concerning safety, significantly higher risks of hepatotoxicity and neurotoxicity were demonstrated at higher concentrations for all cutoffs, and the highest ORs were recorded at 4.0 μg/mL (OR = 7.39, 95% CI = 3.81–14.36; OR = 5.76, 95% CI ...
Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify... more
Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye p...
Background Intensive glycemic control is recommended to prevent surgical site infections (SSI). Our aim was to evaluate retrospectively the effect of improvement in hyperglycemia irrespective of insulin use on the incidence of SSI in... more
Background Intensive glycemic control is recommended to prevent surgical site infections (SSI). Our aim was to evaluate retrospectively the effect of improvement in hyperglycemia irrespective of insulin use on the incidence of SSI in non-diabetic patients. Methods The highest blood glucose (BG) concentration within 12 h (early peak BG) and the final BG from 12 to 24 h after surgery were evaluated in patients who underwent gastrointestinal surgery. Patients with an early peak BG of ≥150 mg/dL were divided into those with persistent (final BG of ≥150 mg/dL) and improved hyperglycemia (final BG of <150 mg/dL). Patients without hyperglycemia and those with late-onset hyperglycemia were also assessed for SSI risk. Results Overall, 1612 patients were studied (diabetes, n = 293). Although hyperglycemia increased the SSI rates in non-diabetic patients, no correlation was demonstrated in patients with diabetes at any cutoff final BG defining htperglycemia except for 180 mg/dL. Hyperglycem...
The Epidemiological Investigation Committee for Human Mycoses in Japan performed a retrospective epidemiological survey of candidemia and causative Candida species. Data from 2003 to 2014 were collected from 10 Japanese university... more
The Epidemiological Investigation Committee for Human Mycoses in Japan performed a retrospective epidemiological survey of candidemia and causative Candida species. Data from 2003 to 2014 were collected from 10 Japanese university hospitals. A total of 328,318 blood cultures were included. The prevalence of fungi in all cultures and in positive cultures were 0.58±0.09% and 4.46±0.66%, respectively. Among the results that were positive for Candida species (N=1,921), Candida albicans was the most common species (39.5%) and was followed by Candida parapsilosis (23.3%), Candida glabrata (13.2%), Candida tropicalis (7.1%), Candida krusei (3.2%), and others (13.7%). During the last 6 years, the frequency of C. albicans has significantly decreased in Japan, while that of C. glabrata has increased. Additional surveys are needed to continuously monitor the trends in the distribution of candidemia.
The purpose of this study was to assess the point at which the postoperative infection has occurred in order to decide upon the proper duration of prophylactic antibiotic use. Another goal of this study was to determine whether prediction... more
The purpose of this study was to assess the point at which the postoperative infection has occurred in order to decide upon the proper duration of prophylactic antibiotic use. Another goal of this study was to determine whether prediction for the development of postoperative infections in major surgery such as esophagectomy should be the same as that in routine gastroenterological surgery. Twenty-five patients who underwent transthoracic esophagectomy and 127 patients who underwent gastrectomy were studied. On the third day after gastric surgery, the body temperature of patients who developed an infection was higher than that of the patients who did not develop an infection. The relative changes in peripheral white blood count (WBC), and C-reactive protein (CRP) concentration on the third and fourth days were more predictive of the development of infection than the absolute values. Almost all patients with systemic inflammatory response syndrome (SIRS) on the third day after gastric...
We studied the characteristics of methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains that caused enteritis. In a previous report, we demonstrated that both phenotypic and genotypic changes were associated with MRSA... more
We studied the characteristics of methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains that caused enteritis. In a previous report, we demonstrated that both phenotypic and genotypic changes were associated with MRSA enteritis; and we hypothesized that the accessory gene regulator ( agr ), which is a global regulator of staphylococcal virulence and upregulates several exoproteins, is the key factor associated with the development of MRSA enteritis. In this study, we examined 12 MRSA isolates associated with enteritis from stool samples and 17 MRSA isolates not associated with enteritis that had the following characteristics: the strains associated with enteritis had the same genotype (genotype A), as detected by pulsed-field gel electrophoresis, or the strains were isolated from stools. The differences between strains that caused enteritis and those that did not cause enteritis strains were examined by quantitative reverse transcription-PCR to assess RNAII, agrA ,...
Although antibiotic heterogeneity has been proposed as a strategy to limit the emergence of antibiotic resistance, few clinical studies have been conducted to validate the concept. This paper evaluates a hospital-wide strategy of... more
Although antibiotic heterogeneity has been proposed as a strategy to limit the emergence of antibiotic resistance, few clinical studies have been conducted to validate the concept. This paper evaluates a hospital-wide strategy of heterogeneous antibiotic use intended to reduce infections caused by resistant Gram-negative rods (GNR). A strategy termed 'periodic antimicrobial monitoring and supervision' (PAMS) was implemented between September 2006 and February 2008. The 18 month intervention period was compared with the preceding 18 months (12 months pre-establishment and 6 months preparation). During PAMS, recommended, restricted and off-supervised classes of antibiotics active against more resistant GNR were changed every 3 months according to the antimicrobial usage density and rates of resistance to those antibiotics in Pseudomonas aeruginosa during the preceding term. Usage of five categories of antibiotics was supervised by four full-time staff. Antibiotic heterogeneity was estimated using the Peterson index (AHI). AHI estimates were 0.66 and 0.74 during the observation period but rose after the introduction of PAMS (period 1: 0.84; period 2: 0.94; period 3: 0.88). The incidence of patients from whom resistant GNR were isolated decreased significantly (P<0.001), whereas isolation of multidrug-resistant (MDR) GNR decreased from 1.7% to 0.5% (P<0.001). There was no significant difference in the incidence of extended spectrum beta-lactamase-producing organisms. Rates of imipenem resistance among Pseudomonas aeruginosa improved during PAMS2. PAMS facilitated hospital-wide heterogeneous antibiotic usage which was associated with reduced rates of resistant GNR.
Antibody tests for the varicella zoster virus (VZV) include neutralization, fluorescent antibody to membrane antigen (FAMA), immune adherence hemagglutination (IAHA), enzyme immunoassay (EIA), glycoprotein-based enzyme-linked... more
Antibody tests for the varicella zoster virus (VZV) include neutralization, fluorescent antibody to membrane antigen (FAMA), immune adherence hemagglutination (IAHA), enzyme immunoassay (EIA), glycoprotein-based enzyme-linked immunosorbent assay (gpELISA), and complement fixation (CF) tests. Of these, FAMA is considered the most sensitive. However, in Japan, the EIA method is most frequently employed. The VZV antibody detection rate of the FAMA, EIA, gpELISA, and IAHA methods was compared. Four types of antibody tests were conducted with sera collected from 83 college students. The relationships between two antibody tests were examined using Pearson's correlation coefficients. All 83 subjects were observed to be VZV antibody-positive using the FAMA method. The Pearson correlation coefficients of gpELISA, EIA, and IAHA relative to FAMA were 0.808, 0.782, and 0.356, respectively. The positive agreement rate of IAHA relative to FAMA was 88.0% (73/83), whereas those of gpELISA and EIA were both 97.6% (81/83). Furthermore, EIA showed 100% positive agreement with gpELISA and a high correlation coefficient of 0.911, whereas these values for IAHA compared to gpELISA were much lower (90.1% and 0.530). The calculated Pearson correlation coefficient for comparison of the EIA and IAHA methods was 0.498, with a positive agreement rate of 90.1% (73/81). The EIA method should be employed in Japan based on the similarity of the positivity between EIA and gpELISA, as it is more available and practical than gpELISA.
The aim of this study was to confirm the effect of implementing a hospital-wide project for appropriate use of antimicrobial prophylaxis (AMP) to reduce the rate of antibiotic-resistant organisms. Fifteen different manuals for each... more
The aim of this study was to confirm the effect of implementing a hospital-wide project for appropriate use of antimicrobial prophylaxis (AMP) to reduce the rate of antibiotic-resistant organisms. Fifteen different manuals for each surgical department have been simultaneously implemented since February 2007. Compliance rate was compared between pre- and postintervention periods (3 months for each period). As an effect of this intervention, we analyzed changes in the rates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus among organisms isolated postoperatively. The number of operations was 1,627 in both periods. Among patients whose surgeries were longer than 3 h in duration, 75% received an additional intraoperative antimicrobial dose in the postintervention period and 23% in the preintervention period (P < 0.001). Although most patients received postoperative AMP with an interval of q12 h in the preintervention period, 63% of the patients received AMP with an interval of q8 h in the postintervention period. The duration of AMP use was reduced from 2.4 ± 1.9 to 1.6 ± 1.5 days (P < 0.001). Forty-seven percent of patients discontinued AMP within 24 h and 81% within 48 h. Isolation rates of P. aeruginosa among all gram-negative organisms significantly decreased from 13% (68/538 patients) to 7.3% (37/509 patients) (P = 0.004). Execution of a hospital-wide project to promote the appropriate use of AMP, including shortening the duration of AMP use, was useful to decrease the rate of P. aeruginosa isolated postoperatively.
Recent studies demonstrated that mortality associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was high when vancomycin was used to treat infections with strains that had a high vancomycin minimum inhibitory... more
Recent studies demonstrated that mortality associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was high when vancomycin was used to treat infections with strains that had a high vancomycin minimum inhibitory concentration (MIC). This study compared several characteristics of vancomycin MIC 2 μg/ml strains isolated from bacteremia with those isolated from infections other than bacteremia. A total of 128 episodes of MRSA bacteremia between 2005 and 2008 were followed-up, and compared with 631 MRSA infections other than bacteremia. The isolation of strains with a 2 μg/ml MIC accounted for 32.0% of isolates from MRSA bacteremia, whereas strains with a 2 μg/ml MIC comprised 9.0% of MRSA isolated from other sites (p < 0.001). The incidence of pneumonia as the source of infection was significantly higher in patients with bacteremia from strains with a 2 μg/ml MIC than in those with ≤1 μg/ml MIC. Prior vancomycin use did not correlate with the isolation of 2 μg/ml strains. The efficacy of glycopeptides as 1st line therapy in patients infected with 2 μg/ml strains was significantly lower than that for patients infected with ≤1 μg/ml strains (30.0 vs. 78.8%, p < 0.001) in bacteremia. In the analysis of infections other than bacteremia, efficacy did not reveal a significant difference according to MIC (69.0 vs. 79.6%, p = 0.109). In bacteremia, mortality was 65.8% in patients with 2 μg/ml strains and 19.5% in patients with ≤1 μg/ml strains (p < 0.001), whereas there was no significant difference in mortality from infections other than bacteremia (10.7 vs. 7.8%, p = 0.617). In multivariate analysis, bacteremia with 2 μg/ml strains, intensive care unit (ICU) stay, and liver cirrhosis were independent risk factors for death in patients with bacteremia, and initial appropriate therapy lowered the risk. Several characteristics such as a higher incidence than at other infection sites, a high incidence of pneumonia as a source of infection, a low success rate of vancomycin therapy, and poor prognosis were confirmed in 2 μg/ml MIC MRSA isolated from bacteremia; however, a low success rate of vancomycin and poor prognosis were not apparent in 2 μg/ml MIC MRSA strains isolated from infections other than bacteremia.
PURPOSE The purpose of this study was to identify the optimum dosing regimen of linezolid in sepsis patients with and without renal dysfunction and sepsis patients on low-dose continuous renal replacement therapy (CRRT) using a... more
PURPOSE The purpose of this study was to identify the optimum dosing regimen of linezolid in sepsis patients with and without renal dysfunction and sepsis patients on low-dose continuous renal replacement therapy (CRRT) using a pharmacokinetics/pharmacokinetics (PK/PD) approach. METHODS Sepsis patients with and without renal dysfunction (creatinine clearance < 50 mL/min), and sepsis patients on low-dose CRRT (dose: 800 mL/h) were studied. The PK data were modeled using a two-compartment model, and then used for simulation. The target PK/PD was the 24-h area under the concentration-time curve to minimum inhibitory concentration ratio of ≥ 80. Dosing regimens were evaluated using cumulative fraction of response (CFR) and safety probability (trough level < 7 µg/mL) by Monte Carlo simulation. RESULTS Twenty-seven patients, including 8 patients with preserved renal function, 9 patients with renal dysfunction, and 10 patients on CRRT, were studied. The proposed regimen to attain CFR ≥ 90% was 800 mg every 12 h (safety probability 82.4%) for patients with preserved renal function. By contrast, the target CFR was attained with a decreased regimen in patients with renal dysfunction and those on CRRT [600 mg every 24h (safety probability 68.6%) and 800 mg every 24h (42.1%)]. CONCLUSIONS We identified different dosage strategies to achieve target linezolid concentrations according to renal function and use of CRRT in sepsis patients. Because of unassured safety probability in patients without preserved renal function, dosing regimens should be adjusted based on the therapeutic drug monitoring.
The major adverse event associated with linezolid treatment is thrombocytopenia. This study investigated risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy. This was a retrospective... more
The major adverse event associated with linezolid treatment is thrombocytopenia. This study investigated risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy. This was a retrospective study of patients treated with linezolid 600 mg q12h, by the oral or parenteral route, between July 2007 and June 2009. Thrombocytopenia was defined as a ≥ 10 × 10⁴ cells/mm³ decrease from the baseline or a ≥ 30% reduction. Thirty-three variables were analyzed as risk factors associated with thrombocytopenia. Multivariate analysis was performed with SPSS version 16 software. This study included 331 patients (221 male, 58.0 ± 20.2 years). The mean duration of linezolid therapy was 10.5 ± 8.7 days. Thrombocytopenia occurred in 128 patients (38.7%), of whom 21 required platelet transfusion. Thrombocytopenia developed 7.4 ± 4.8 days after linezolid initiation, and the platelet count recovered 12.3 ± 7.8 days after withdrawal. In the final steps of stepwise logistic regression analysis, 5 variables were selected: duration of linezolid therapy ≥ 14 days [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.73-5.34, P < 0.001], creatinine clearance < 50 mL/min (OR 2.32, 95% CI 1.45-3.74, P < 0.001), chronic liver disorders (OR 1.63, 95% CI 0.92-2.86, P = 0.092), and respiratory tract infections (OR 1.75, 95% CI 1.05-2.91, P = 0.031). In contrast to findings with parenteral administration, oral administration of linezolid decreased the risk of thrombocytopenia (OR 0.38, 95% CI 0.15-0.97, P = 0.042). The time to the onset of thrombocytopenia in patients with creatinine clearance <50 mL/min was significantly shorter than that in patients with creatinine clearance ≥ 50 mL/min (6.7 ± 4.4 and 8.5 ± 5.2 days, P = 0.039), and in patients administered orally the time to the onset of thrombocytopenia was 10.4 ± 6.6 days. Several factors influenced the occurrence of linezolid-induced thrombocytopenia. Dose adjustment may be required in at-risk patients, especially those with renal dysfunction.

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