Observational study to determine the optimal dose of daptomycin based on pharmacokinetic/pharmacodynamic analysis.

High doses of daptomycin (DAP) (>6 mg/kg/day) have been preliminarily recommended in recent practical guidelines for methicillin-resistant Staphylococcus aureus infection, to achieve better clinical effects. While such doses can elevate the plasma trough concentration (Cmin) of DAP, there is an associated risk of creatine phosphokinase (CPK) elevation warranting further investigation. In the current study relationships between DAP Cmin and CPK elevation were investigated, and optimal DAP doses were determined. Plasma DAP concentrations were measured in 20 patients. Logistic regression analysis was performed to assess relationships between DAP Cmin and CPK elevation, then a population pharmacokinetic model of DAP was developed. To determine an optimal DAP dose a Monte Carlo simulation (MCS) was performed to minimize the risk of CPK elevation and maximize the probability of successful treatment. In logistic regression analysis DAP Cmin was significantly associated with CPK elevation (odds ratio 1.21, p = 0.048). With respect to dose-dependent increases in the probability of CPK elevation and exposure to DAP, MCS estimated an optimal DAP dose of 4-6 mg/kg/day, corresponding to a minimum inhibitory concentration (MIC) of ≤0.5 µg/mL. For an MIC of 1 µg/mL, MCS estimated an optimal DAP dose of 10 mg/kg/day. However, the probability of CPK elevation associated with high doses of DAP was higher than that associated with the approved doses. In cases where high doses of DAP are administered, close CPK monitoring is required and therapeutic drug monitoring of DAP may be desirable.

Risk factors for ventilator-associated pneumonia in neonatal intensive care unit patients.

Ventilator-associated pneumonia (VAP) is a serious complication in neonatal patients on mechanical ventilation. The objective of this study was to examine the incidence and risk factors associated with VAP, particularly in every 7-day versus every 14-day ventilator circuit changes, in a neonatal intensive care unit (NICU). Seventy-one neonates hospitalized in the NICU were enrolled. First, the neonates were divided into groups with and without VAP. On univariate logistic regression analyses, prolonged mechanical ventilation, frequent re-intubation, low gestational age, and low birth weight (BW) were significant risk factors for VAP development. After adjustments for other variables, only BW <626 g was a significant independent predictor for VAP in NICU infants. Second, to examine the effect of the frequency of changing ventilator circuits on the incidence of VAP, circuit changes were compared between the every 7-day group and the every 14-day group. The incidence of VAP per 1000 ventilator days was 9.66 for the every 7-day group and 8.08 for the every 14-day group, and there was no significant difference between the 2 groups. BW <626 g was a significant independent predictor of VAP, and decreasing the frequency of ventilator circuit changes from every 7 days to 14 days had no adverse effect on the VAP rate in the NICU.

Sites of blood collection and topical disinfectants associated with contaminated cultures: An ambidirectional cohort study.

Background: We aimed to determine whether puncture sites for blood sampling and topical disinfectants are associated with rates of contaminated blood cultures in the emergency department (ED) of a single institution. Methods: This single-center, ambidirectional cohort study of 548 consecutive patients ≥20 years of age was performed in the ED of a university hospital in Japan over a 13-month period. Pairs of blood samples were collected for aerobic and anaerobic cultures from patients in the ED. Physicians selected puncture sites and topical disinfectants according to their personal preference. Results: Potential contamination was identified in 110 of the 548 patients (20.1%). One hundred fourteen (20.8%) patients showed true-positive results for bacteremia, and 324 (59.1%) patients showed true-negative results. Multivariate analysis revealed more frequent contamination when puncture sites were disinfected with povidone-iodine (PVI) than with alcohol/chlorhexidine (ACHX) (adjusted risk difference, 19.1%; 95% confidence interval [CI]), 15.7-22.6; p < 0.001). In terms of blood collection sites, femoral and central venous (CV) catheter with PVI disinfection showed more frequent contamination than venous sites with ACHX (adjusted risk differences: 26.6%, 95% CI 21.3-31.9, p < 0.001 and 41.1%, 95% CI 22.2-59.9, p < 0.001, respectively). Conclusion: Rates of contaminated blood cultures were significantly higher when blood was collected from the CV catheter or femoral sites with PVI as the topical disinfectant.

Early diagnosis leading to improvement of critical illness polyneuropathy associated with severe Staphylococcus aureus infection in a patient on hemodialysis.

Critical illness polyneuropathy (CIP) is a very rare complication of sepsis and multi-organ failure. Herein, we report the first case of CIP reported in a patient on maintenance hemodialysis, who improved with rehabilitation. A 55-year-old male patient was emergently admitted with fever and altered consciousness and diagnosed with bacterial meningitis based on cerebral spinal fluid and cranial magnetic resonance imaging findings. Methicillin-susceptible Staphylococcus aureus was detected in blood and cerebral spinal fluid cultures. Despite treatment with appropriate antibiotics, blood cultures were positive for 9 days and serum C-reactive protein (CRP) levels were persistently elevated. Magnetic resonance imaging of hands and feet to determine infection origin revealed osteomyelitis in several fingers and toes, which required the amputation of 14 necrotic fingers and toes. Thereafter, blood cultures became negative and CRP levels declined. However, flaccid paralysis was noted in both upper and lower extremities during sepsis treatment. Nerve conduction studies showed peripheral axonal disorder in motor and sensory nerves, and CIP was determined as the cause of paralysis based on the fulfillment of all four CIP diagnostic criteria. The patient's muscle strength improved with early and appropriate medical treatment and physical therapy, and he was discharged home 147 days after admission. Prolonged high-level inflammation is a cause of CIP. Patients on hemodialysis, who are potentially immunosuppressed and vulnerable to infection, are at high risk for CIP. In patients on maintenance hemodialysis who develop flaccid paralysis during treatment for severe infection, CIP should be considered for early diagnosis and intervention.

[Effectiveness of intervention by the infection control team for cancer patients with a positive blood culture].

Cancer patients at a high risk of acquiring infectious diseases should be maintained in a facility where good infection control practices are followed. At our hospital, the infection control team(ICT)provides expertise, education, and support to the staff, helping them maintain proper standards, thereby minimizing the risks of infection. The ICT(established in 2004)has implemented infection control programs by employing an appropriate number of staff members after the revision of medical treatment fees in 2011. Our intervention program includes 2 general policies, namely, ordering and collection of blood cultures and intervention for the medical care of patients with positive blood cultures. In this study, we evaluated the effectiveness of our intervention for cancer patients with a positive blood culture. During the surveillance period(April 2011 to July 2012), 42 positive cases were determined to be infectious. ICT intervention was required in 37 cases. Our suggestions were accepted in 92%(34/37)of the cases, and improved outcome was estimated in 65%(22/34)of the cases. The results of our study contribute to the scientific bases on which routine clinical practices could be promoted in the future.

Regression discontinuity of blood culture contamination rate after changing of disinfectants: retrospective observational study.

Blood cultures are indispensable for detecting life-threatening bacteremia. Little is known about associations between contamination rates and topical disinfectants for blood collection in adults. We sought to determine whether a change in topical disinfectants was associated with the rates of contaminated blood cultures in the emergency department of a single institution. This single-center, retrospective observational study of consecutive patients aged 20 years or older was conducted in the emergency department (ED) of a university hospital in Japan between August 1, 2018 and September 30, 2020. Pairs of blood samples were collected for aerobic and anaerobic culture from the patients in the ED. Physicians selected topical disinfectants according to their personal preference before September 1, 2019; alcohol/chlorhexidine gluconate (ACHX) was mandatory thereafter, unless the patient was allergic to alcohol. Regression discontinuity analysis was used to detect the effect of the mandatory usage of ACHX on rates of contaminated blood cultures. We collected 2141 blood culture samples from 1097 patients and found 164 (7.7%) potentially contaminated blood cultures. Among these, 445 (20.8%) were true bacteremia and 1532 (71.6%) were true negatives. Puncture site disinfection was performed with ACHX for 1345 (62.8%) cases and with povidone-iodine (PVI) for 767 (35.8%) cases. The regression discontinuity analysis showed that mandatory ACHX usage was significantly associated with lower rates of contaminated blood cultures by 9.6% (95% confidence interval (CI): 5.0%-14.2%, P < 0.001). Rates of contaminated blood cultures were significantly lower when ACHX was used as the topical disinfectant.

Sites of blood collection and topical antiseptics associated with contaminated cultures: prospective observational study.

We aimed to determine whether puncture sites for blood sampling and topical disinfectants are associated with rates of contaminated blood cultures in the emergency department (ED) of a single institution. This single-center, prospective observational study of 249 consecutive patients aged ≥ 20 years proceeded in the ED of a university hospital in Japan during 6 months. Pairs of blood samples were collected for aerobic and anaerobic culture from all patients in the ED. Physicians selected puncture sites and topical disinfectants according to their personal preference. We found 50 (20.1%) patients with potentially contaminated blood cultures. Fifty-six (22.5%) patients were true bacteremia and 143 (57.4%) patients were true negatives. Multivariate analysis associated more frequent contamination when puncture sites were disinfected with povidone-iodine than with alcohol/chlorhexidine (adjusted risk difference, 12.9%; 95% confidence interval [CI] 8.8-16.9; P < 0.001). Sites of blood collection were also associated with contamination. Femoral and central venous with other sites were associated with contamination more frequently than venous sites (adjusted risk difference), 13.1% (95% CI 8.2-17.9; P < 0.001]) vs. 17.3% (95% CI 3.6-31.0; P = 0.013). Rates of contaminated blood cultures were significantly higher when blood was collected from femoral sites and when povidone-iodine was the topical antiseptic.

Filamentous invasive growth of mutants of the genes encoding ammonia-metabolizing enzymes in the fission yeast Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe undergoes a switch from yeast to filamentous invasive growth in response to certain environmental stimuli. Among them is ammonium limitation. Amt1, one of the three ammonium transporters in this yeast, is required for the ammonium limitation-induced morphological transition; however, the underlying molecular mechanism remains to be understood. Cells lacking Amt1 became capable of invasive growth upon increasing concentrations of ammonium in the medium, suggesting that the ammonium taken up into the cell or a metabolic intermediate in ammonium assimilation might serve as a signal for the ammonium limitation-induced morphological transition. To investigate the possible role of ammonium-metabolizing enzymes in the signaling process, deletion mutants were constructed for the gdh1, gdh2, gln1, and glt1 genes, which were demonstrated by enzyme assays to encode NADP-specific glutamate dehydrogenase, NAD-specific glutamate dehydrogenase, glutamine synthetase, and glutamate synthase, respectively. Growth tests on various nitrogen sources revealed that a gln1Δ mutant was a glutamine auxotroph and that a gdh1Δ mutant had a defect in growth on ammonium, particularly at high concentrations. The latter observation indicates that the NADP-specific glutamate dehydrogenase of S. pombe plays a major role in ammonium assimilation under high ammonium concentrations. Invasive growth assays showed that gdh1Δ and glt1Δ mutants underwent invasive growth to a lesser extent than did wild-type strains. Increasing the ammonium concentration in the medium suppressed the invasive growth defect of the glt1Δ mutant, but not the gdh1Δ mutant. These results suggest that the nitrogen status of the cell is important in the induction of filamentous invasive growth in S. pombe.

Estimation of total carbonyl compounds in roasted and dried foods by the tentative method using 1-butanol as a solvent.

Total carbonyl compounds in oils extracted from roasted and dried foods were estimated by the tentative method using 1-butanol instead of benzene as a solvent. Oils extracted from dried foods had generally showed higher carbonyl value (CV) than those from roasted foods. The CV estimated by the tentative method had a good correlation with that by the conventional method in oils extracted from roasted and dried foods, although the former did not always correlate with the latter for roasted and dried foods. It was expected that the tentative method using 1-butanol could be substituted for that using benzene and be useful for evaluating the quality of oils in roasted and dried foods.