Assessing Clinical Outcomes of Vancomycin Treatment in Adult Patients with Vancomycin-Susceptible Enterococcus faecium Bacteremia.

PURPOSE: Enterococcal bacteremia is associated with high mortality and long-term hospitalization. Here, we aimed to investigate the clinical outcomes and evaluate the risk factors for mortality in adult patients treated with vancomycin (VCM) for vancomycin-susceptible Enterococcus faecium (E. faecium) bacteremia. METHODS: This is a retrospective, record-based study. The data were collected from inpatients at a single university hospital between January 2009 and December 2020. The area under the curve (AUC) of VCM was calculated using the Bayesian approach. The primary outcome was a 30-day in-hospital mortality. RESULTS: A univariate analysis showed significant differences in the concomitant use of vasopressors, history of the use of no clinically relevant activity antimicrobial agents against E. faecium, VCM plasma trough concentration, and renal dysfunction during VCM administration between the 30-day in-hospital mortality and survival groups. However, the groups' AUC/minimum inhibitory concentration (MIC) were not significantly different. A multivariate analysis suggested that concomitant vasopressors may be an independent risk factor for 30-day in-hospital mortality (odds ratio, 7.81; 95% confidence interval, 1.16-52.9; p = 0.035). The VCM plasma trough concentrations and the AUC/MIC in the mortality group were higher than those in the surviving group. No association between the AUC/MIC and the treatment effect in E. faecium bacteremia was assumed, because the known, target AUC/MIC were sufficiently achieved in the mortality group. CONCLUSIONS: There may be no association between the AUC/MIC and the treatment effect in E. faecium bacteremia. When an immunocompromised host develops E. faecium bacteremia with septic shock, especially when a vasopressor is used in a patient with unstable hemodynamics, it may be difficult to treat it, despite efforts to ensure the appropriate AUC/MIC and therapeutic vancomycin concentration levels.

Impact of the COVID-19 Pandemic on Initiation of Antibiotic Treatment After Performing a Blood Culture and Intervention by the Antimicrobial Stewardship Team.

Purpose: Whether the coronavirus disease 2019 (COVID-19) pandemic had any effect on the time between blood culture collection and administration of antibiotics in the outpatient Department of Emergency Medicine in a single university hospital in Japan was investigated, and the intervention carried out by the antimicrobial stewardship team (AST) to promote the appropriate use of antibiotics was examined. Patients and Methods: The monthly percentage of patients who visited the outpatient Department of Emergency Medicine between January 2019 and December 2021 and received an intravenous antibiotic within 3 hours of blood culture collection was calculated. The AST calculated a quality indicator (QI) based on the results of the investigation and started QI monitoring and hospital feedback. Results: From January 2020 to March 2021 (the third COVID-19 wave), the implementation rate of antibiotic administration within 3 hours after blood culture collection decreased as the COVID-19 pandemic spread, and the implementation rate tended to increase as the number of COVID-19-positive patients decreased. However, when the AST started monitoring and feedback from April 2021, although there was a temporary decline in the early stages of the fifth wave when the scale of infection was large, the implementation rate rose and was maintained by AST intervention. (the fourth and the fifth COVID-19 waves) (P<0.01). Also, the implementation rate was significantly lower during the COVID-19 pandemic than during the non- pandemic (P<0.05). Conclusion: The early COVID-19 pandemic may have affected the delay in time from blood culture collection to antibiotic administration. Later, in recurring COVID-19 pandemics, AST intervention eliminated this problem. When a bacterial infection such as sepsis is suspected, delayed treatment can be prevented by promptly collecting a blood culture, irrespective of concerns about COVID-19 infection. Calculating the QI may promote AST activities and the appropriate use of antibiotics.

Successful Treatment of a Case of Metallo-Beta-Lactamase-Producing Raoultella ornithinolytica Bacteremia by Antimicrobial Stewardship Team Intervention and Therapeutic Drug Monitoring-Based Amikacin Treatment.

An 80-year-old woman underwent pancreatoduodenectomy. Post-operation, she experienced a fever, and a culture of blood revealed metallo-beta-lactamase-producing Raoultella ornithinolytica. For treatments with aminoglycoside antimicrobial agents, a therapeutic drug monitoring-based dosing design can lower the risk of adverse events and enable appropriate treatment. Key Clinical Message. When aminoglycoside antimicrobial agents are administered for MBL-producing bacteremia, prescription suggestions based on TDM by antimicrobial stewardship team can reduce the occurrence of adverse events and enable appropriate treatment.

Hematocolpos due to lower vaginal agenesis in an adolescent girl.

Background: Hematocolpos due to imperforate hymen is an important differential diagnosis of abdominal pain in early adolescent stage. However, hematocolpos due to lower vaginal agenesis must be considered because the management differs. Case Presentation: A healthy 11-year-old girl presented with a 2-day left lower abdominal pain history. Her breast development had begun, but she had not reached menarche. Computed tomography showed high absorptive value liquid filling the upper vaginal to uterine cavity, a pale highly absorptive fluid component suggestive of hemorrhagic ascites in the abdominal cavity on both sides of the uterus, and normal bilateral ovaries. Magnetic resonance imaging diagnosed hematocolpos due to lower vaginal agenesis. The blood clot was aspirated with a transabdominal ultrasound-guided transvaginal puncture. Conclusion: History-taking, imaging tests, and appropriate collaboration with obstetrician/gynecologist with awareness of secondary sexual characteristics were crucial in this case.

Evaluation of Knowledge Regarding the Use of Antibiotics among Pharmacy Undergraduates in Japan.

Antimicrobial resistance (AMR) is a global threat to human health. Education on antibiotics is essential for AMR prevention, and training should be provided for undergraduate pharmacy students. This study evaluated the knowledge regarding antibiotic use and AMR among fourth-year Japanese pharmacy students and the effect of a lecture on treating infectious diseases with antibiotics had on their knowledge. A questionnaire survey was conducted, and the responses were recorded before and after participants attended the lecture. A small subset of the prelecture survey questions was used for the postlecture survey. From a total of 540 participants, 330 and 234 responses were collected before and after the lecture, respectively. In the prelecture survey, 39.4% of the participants incorrectly answered that antibiotics can effectively treat the common cold, 13.3% had taken leftover antibiotics, and 17.3% had taken antibiotics prescribed for their family members or others. Furthermore, the prelecture survey data showed that the mean number (± standard deviation) of correct answers across the eight questions on treatment and diagnosis of infectious diseases and antibiotics was 2.21 ± 1.64. However, in the postsurvey, this figure increased to 5.00 ± 1.82. Although the lecture improved their knowledge to some extent, the results suggested that fourth-year pharmacy students have inaccurate knowledge regarding the appropriate use of antibiotics and AMR. Therefore, it is necessary to improve early-year undergraduate pharmacy education on antibiotics in Japan.

A Case of Persistent Bacillus cereus Bacteremia Responding to a Combination of Vancomycin and Gentamicin.

A 56-year-old woman with a history of connective tissue disease developed fever, and Bacillus cereus (B. cereus) was detected in blood cultures. Therefore, treatment with vancomycin (VCM) was initiated. Since her blood cultures persistently detected B. cereus despite peripheral intravenous catheter replacement and VCM treatment, concomitant treatment with gentamicin (GM) was started. Blood cultures then became negative. Persistent B. cereus bacteremia responded to combination therapy with VCM and GM. This combination therapy may increase the risk of developing renal dysfunction, but the risk can be mitigated by appropriate therapeutic drug monitoring (TDM) and dose adjustments to achieve successful treatment.

Effectiveness of a novel semi-closed barrier device with a personalized exhaust in cough aerosol simulation according to particle counts and visualization of particles.

Oxygen therapy is an essential treatment for patients with coronavirus disease 2019, although there is a risk of aerosolization of additional viral droplets occurring during this treatment that poses a danger to healthcare professionals. High-flow oxygen through nasal cannula (HFNC) is a vital treatment bridging low-flow oxygen therapy with tracheal intubation. Although many barrier devices (including devices without negative pressure in the barrier) have been reported in the literature, few barrier devices are suitable for HFNC and aerosol infection control procedures during HFNC have not yet been established. Hence, we built a single cough simulator model to examine the effectiveness of three protective measures (a semi-closed barrier device, a personalized exhaust, and surgical masks) administered in isolation as well as in combination using particle counter measurements and laser sheet visualization. We found that the addition of a personalized exhaust to a semi-closed barrier device reduced aerosol leakage during HFNC without negative pressure. This novel combination may thus reduce aerosol exposure during oxygen therapy, enhance the protection of healthcare workers, and likely reduce nosocomial infection risk.

Treatment of acute hypernatremia caused by sodium overload in adults: A systematic review.

BACKGROUND: Rapid-onset, acute hypernatremia caused by sodium overload is a rare, life-threatening condition. Although experts recommend rapid correction of sodium concentration [Na] based on pathophysiological theories, only a few reports have documented the specific details of sodium correction methods. The objective of this study was to systematically review the reported treatment regimens, achieved [Na] correction rates, and treatment outcomes. METHODS: PubMed, Ichushi-database, and references without language restrictions, from inception to January 2021, were searched for studies that described ≥1 adult (aged ≥18 years) patients with rapid-onset hypernatremia caused by sodium overload, whose treatment was initiated ≤12 hours from the onset. The primary outcome of interest was the [Na] correction rate associated with mortality. RESULTS: Eighteen case reports (18 patients; median [Na], 180.5 mEq/L) were included. The cause of sodium overload was self-ingestion in 8 patients and iatrogenic sodium gain in 10 patients; baseline [Na] and symptoms at presentation were comparable for both groups. Individualized rapid infusion of dextrose-based solutions was the most commonly adopted fluid therapy, whereas hemodialysis was also used for patients already treated with hemodialysis. The correction rates were more rapid in 13 successfully treated patients than in 5 fatal patients. The successfully treated patients typically achieved [Na] ≤160 within 8 hours, [Na] ≤150 within 24 hours, and [Na] ≤145 within 48 hours. Hyperglycemia was a commonly observed treatment-related adverse event. CONCLUSION: The limited empirical evidence derived from case reports appears to endorse the recommended, rapid, and aggressive sodium correction using dextrose-based hypotonic solutions.

Reactogenicity following two doses of the BNT162b2 mRNA COVID-19 vaccine: Real-world evidence from healthcare workers in Japan.

As the first authorized COVID-19 vaccine in Japan, the BNT162b2 mRNA COVID-19 vaccine is utilized for mass vaccination. Although efficacy has been proved, real-world evidence on reactogenicity in Japanese personnel is needed to prepare the public. Healthcare workers in a large academic hospital in Japan received two doses of the Pfizer-BioNTech vaccine from March 17 to May 19, 2021. Online questionnaires were distributed to registered recipients following each dose, from day 0 through day 8. Primary outcomes are the frequency of reactogenicity including local and systemic reactions. Length of absence from work was also analyzed. Most recipients self-reported reactogenicity after the first dose (97.3%; n = 3254; mean age [36.4]) and after the second dose (97.2%; n = 3165; mean age [36.5]). Systemic reactions following the second dose were substantially higher than the first dose, especially for fever (OR, 27.38; 95% CI, [22.00-34.06]; p < 0.001), chills (OR, 16.49; 95% CI, [13.53-20.11]; p < 0.001), joint pain (OR, 8.49; 95% CI, [7.21-9.99]; p < 0.001), fatigue (OR, 7.18; 95% CI, [6.43-8.02]; p < 0.001) and headache (OR, 5.43; 95% CI, [4.80-6.14]; p < 0.001). Reactogenicity was more commonly seen in young, female groups. 19.3% of participants took days off from work after the second dose (2.2% after the first dose), with 4.7% absent for more than two days. Although most participants reported reactogenicity, severe cases were limited. This study provides real-world evidence for the general population and organizations to prepare for BNT162b2 mRNA COVID-19 vaccination in Japan and other countries in the region.

Population Pharmacokinetic Analysis and Dose Regimen Optimization in Japanese Infants with an Extremely Low Birth Weight.

Vancomycin is a synthetic antibiotic effective against Gram-positive pathogens. Although the clinical applicability of vancomycin for infants has been increasing, the pharmacokinetic data for vancomycin in extremely low-birth-weight infants are limited. The aim of this study was to construct a population pharmacokinetics model for vancomycin in extremely-low-birth-weight infants and establish an optimal dosage regimen. We enrolled children aged less than 1 year with a birth weight of less than 1,000 g and body weight at vancomycin prescription of less than 1,500 g. Pharmacokinetic data from 19 patients were analyzed, and a population pharmacokinetics model was developed using nonlinear mixed-effects modeling software. Goodness-of-fit plots, a nonparametric bootstrap analysis, and a prediction-corrected visual predictive check were employed to evaluate the final model. The dosage regimen was optimized based on the final model. The pharmacokinetic data fit a one-compartment model with first-order elimination, and body weight and estimated serum creatinine level were used as significant covariates. In a simulation using the final model, the optimal dosage regimen, especially when the serum creatinine level (>0.6 mg/dl) was high, was 5.0 to 7.5 mg/kg of body weight twice a day every 12 h; this was required to reduce the dosage compared with that in previous studies. The recommended doses based on the current target time course concentration curves may not be appropriate for extremely-low-birth-weight infants.

Rapidly progressive acute necrotizing encephalopathy associated with influenza A in an elderly adult.

BACKGROUND: Among the influenza-associated encephalopathies, acute necrotizing encephalopathy (ANE) has a particularly poor prognosis. While it usually progresses within 48 h, we encountered a rapidly evolving case with the patient falling into coma from lucidity within 10 min. CASE PRESENTATION: A 71-year-old man was found unconscious after taking a 10-min bath and brought to the emergency room. The head computed tomography (HCT) was normal, and he was diagnosed with heatstroke as a complication of influenza A. Despite effective therapy to correct his temperature, his consciousness did not improve, and within 24 h he progressed to multiple organ injury. Repeat HCT and subsequent magnetic resonance imaging revealed irreparably progressed ANE. CONCLUSION: To effectively treat ANE, early recognition and diagnosis are critical. Our case suggests that ANE should be considered and added to the differential diagnosis for adult patients with rapid cognitive deterioration.

Rapid and easy detection of low-level resistance to vancomycin in methicillin-resistant Staphylococcus aureus by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

Vancomycin-intermediately resistant Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with treatment failure. hVISA contains only a subpopulation of cells with increased minimal inhibitory concentrations, and its detection is problematic because it is classified as vancomycin-susceptible by standard susceptibility testing and the gold-standard method for its detection is impractical in clinical microbiology laboratories. Recently, a research group developed a machine-learning classifier to distinguish VISA and hVISA from vancomycin-susceptible S. aureus (VSSA) according to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) data. Nonetheless, the sensitivity of hVISA classification was found to be 76%, and the program was not completely automated with a graphical user interface. Here, we developed a more accurate machine-learning classifier for discrimination of hVISA from VSSA and VISA among MRSA isolates in Japanese hospitals by means of MALDI-TOF MS data. The classifier showed 99% sensitivity of hVISA classification. Furthermore, we clarified the procedures for preparing samples and obtaining MALDI-TOF MS data and developed all-in-one software, hVISA Classifier, with a graphical user interface that automates the classification and is easy for medical workers to use; it is publicly available at https://github.com/bioprojects/hVISAclassifier. This system is useful and practical for screening MRSA isolates for the hVISA phenotype in clinical microbiology laboratories and thus should improve treatment of MRSA infections.

Monitoring of recurrent and superior laryngeal nerve function using an Airwayscope™ during thyroid surgery.

In thyroid surgery, intraoperative identification and preservation of the recurrent laryngeal nerve (RLN) and superior laryngeal nerve external branch (SLNEB) are crucial. Several reports have proposed that electromyography (EMG) monitoring is an acceptable adjunct for identification and preservation of the RLN. However, a limited number of hospitals have access to an EMG monitoring system. Therefore, the development of another viable monitoring method is required. The aim of the present study was to design a new RLN and SLNEB monitoring method combining an Airwayscope™ (AWS) and a facial nerve stimulator. The facial nerve-stimulating electrode stimulates the RLN or SLNEB, so that the movement of the vocal cord may be observed with an AWS. This monitoring method was performed on 10 patients with a thyroid tumor. In all the cases, RLN and SLNEB were identified and vocal cord function was preserved. All the patients exhibited normal vocal cord function following surgery. Thus, the new RLN and SLNEB monitoring method using an AWS and a facial nerve stimulator is useful in thyroid surgery, and this method may be used as a reliable and available alternative to EMG monitoring to ensure the normal function of the vocal cord.

Prevalence of Slow-Growth Vancomycin Nonsusceptibility in Methicillin-Resistant Staphylococcus aureus.

We previously reported a novel phenotype of vancomycin-intermediate Staphylococcus aureus (VISA), i.e., "slow VISA," whose colonies appear only after 72 h of incubation. Slow-VISA strains can be difficult to detect because prolonged incubation is required and the phenotype is unstable. To develop a method for detection of slow-VISA isolates, we studied 23 slow-VISA isolates derived from the heterogeneous VISA (hVISA) clinical strain Mu3. We identified single nucleotide polymorphisms (SNPs) in genes involved in various pathways which have been implicated in the stringent response, such as purine/pyrimidine synthesis, cell metabolism, and cell wall peptidoglycan synthesis. We found that mupirocin, which also induces the stringent response, caused stable expression of vancomycin resistance. On the basis of these results, we developed a method for detection of slow-VISA strains by use of 0.032 µg/ml mupirocin (Yuki Katayama, 7 March 2017, patent application PCT/JP2017/008975). Using this method, we detected 53 (15.6%) slow-VISA isolates among clinical methicillin-resistant S. aureus (MRSA) isolates. In contrast, the VISA phenotype was detected in fewer than 1% of isolates. Deep-sequencing analysis showed that slow-VISA clones are present in small numbers among hVISA isolates and proliferate in the presence of vancomycin. This slow-VISA subpopulation may account in part for the recurrence and persistence of MRSA infection.

Tidal volume and airway pressure under percutaneous transtracheal ventilation without a jet ventilator: comparison of high-flow oxygen ventilation and manual ventilation in complete and incomplete upper airway obstruction models.

PURPOSE: Percutaneous transtracheal ventilation (PTV) can be life-saving in a cannot ventilate, cannot intubate situation. The aim of this study was to investigate the efficacy of PTV by measuring tidal volumes (VTs) and airway pressure (Paw) in high-flow oxygen ventilation and manual ventilation using a model lung. METHODS: We examined 14G, 16G, 18G, and 20G intravenous catheters and minitracheotomy catheters. In high-flow oxygen ventilation, the flow was set to 10 L/min, while the inspiratory:expiratory phases (I:E) were 1 s:4 s in the complete upper airway obstruction model and 1 s:1 s in the incomplete obstruction model. In manual ventilation, I:E were 2 s:4 s in the complete obstruction model and 2 s:3 s in the incomplete obstruction model. We ventilated through each catheter for 2 min and measured VT and Paw. RESULTS: In high-flow ventilation, the average VTs were approximately 150 ml and <100 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. The VTs obtained were reduced when the bore size was decreased. In manual ventilation, the average VTs were over 300 ml and approximately 260 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. In high-flow ventilation, the airway pressure tended to be higher. The minitracheotomy catheters produced over 800 ml of VT and created almost no positive end-expiratory pressure. CONCLUSIONS: High-flow ventilation tends to result in higher airway pressure despite a smaller VT, which is probably due to a PEEP effect caused by high flow.

Markedly elevated procalcitonin in early postoperative period in pediatric open heart surgery: a prospective cohort study.

BACKGROUND: We encountered markedly elevated procalcitonin (PCT) among pediatric patients during the early postoperative period of open heart surgery. The purpose of this study is to investigate what factors are associated with the PCT elevation. METHODS: Fifty-two pediatric patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) were enrolled. Plasma PCT, aspartate aminotransferase/alanine aminotransferase (AST/ALT), creatinine, lactate, and C-reactive protein (CRP) were measured on admission to ICU and during the postoperative period. The patients were categorized into high (group H) and low (group L) groups according to their peak PCT levels. Aorta cross-clamp (ACC), CPB time, ICU stay, mechanical ventilation period, peak AST/ALT, creatinine, lactate, and CRP levels were compared. RESULTS: ACC and CPB times, ICU stay period, and mechanical ventilation period were significantly longer in group H compared with group L (118.7 ± 51.6 vs. 49.4 ± 43.5 min, 244.5 ± 65.7 vs. 122.9 ± 63.0 min, 7.9 ± 4.6 vs. 4.0 ± 4.5 days, and 6.3 ± 4.1 vs. 2.9 ± 4.2 days, respectively; p < 0.01). Peak AST and creatinine were significantly higher in group H compared with group L (999.0 ± 1,990.3 vs. 88.3 ± 43.0 U/l and 0.84 ± 0.77 vs. 0.41 ± 0.17 mg/dl, respectively; p < 0.05). CONCLUSIONS: ACC and CPB time-related perioperative stress is associated with elevated PCT; an association between ICU stay and mechanical ventilation period, liver enzymes, and creatinine levels was observed. PCT may be a good predictor of postoperative severity and organ dysfunction.

Spinal cord stimulation for a woman with complex regional pain syndrome who wished to get pregnant.

A woman with complex regional pain syndrome (CRPS) in the right lower extremity who wished to discontinue medications to get pregnant underwent implantation of a spinal cord stimulation system (SCS). An electrode lead was placed at Th(10-11) in the epidural space, accessed via the L(2-3) interspace with a paramedian approach, and a pulse generator was implanted in the left buttock. She kept the SCS on 24 h a day. After she had experienced several chemical abortions, finally she got pregnant via artificial insemination. She had an uneventful delivery of a healthy baby by cesarean resection under spinal anesthesia. In a patient with CRPS who has an implanted SCS system and wishes to get pregnant, the electrode lead into the low thoracic epidural space should be accessed via the high lumbar intervertebral space in consideration of a future requirement for spinal or epidural anesthesia for cesarean section. The generator should be placed in the buttock to prevent impairment of the SCS system being caused by the enlarged abdomen during pregnancy. Although we were apprehensive of adverse effects owing to the electromagnetic field force and change of blood flow in the pelvic viscera, our patient had a successful delivery. SCS is a favorable option for patients with CRPS who wish to get pregnant.

[Interscalene block combined with general anesthesia under spontaneous breathing in a patient with a giant bulla].

Respiratory management for patients with a giant bulla during anesthesia should avoid positive-pressure ventilation to reduce the risk of barotraumas. We report a case of anesthetic management of a 42-year-old man with a giant bulla who had an elective surgery for biopsy of a tumor on his left elbow. Balanced anesthesia consisting of general anesthesia was given under spontaneous breathing combined with interscalene brachial plexus blockade for intra- and postoperative analgesia for the elbow surgery. The patient was monitored by electrocardiography, non-invasive arterial pressure, SpO2, endtidal CO2 tension and bispectral index. Ultrasound-guided interscalene block was performed with the patient awake. After injection of 0.75% ropivacaine 20 ml and 1% lidocaine 16 ml for brachial plexus block, general anesthesia was induced with a bolus of fentanyl 100 microg to reduce cough reflex and propofol using target control infusion with a 2 microg x ml(-1) plasma concentration. The airway was maintained with a size 4 LMA-Proseal, which was inserted with care under spontaneous breathing. There were no serious complications such as pneumothorax in perioperative period. We performed successful anesthetic management, without any complications, combined with interscalene brachial plexus block and spontaneous breathing in a patient with a giant bulla.