In vitro activity of cefiderocol and comparator antibiotics against multidrug-resistant non-fermenting Gram-negative bacilli.

Background: This study evaluated the in vitro activity of cefiderocol, ceftazidime/avibactam, and aztreonam/avibactam against clinically important multidrug-resistant non-fermenting Gram-negative bacilli. Methods: Bacteraemic isolates of 126 multidrug-resistant Acinetobacter baumannii (MDRAB), 110 imipenem-resistant Pseudamoas aeruginosa [including 14 difficult-to-treat resistant P. aeruginosa (DTRPA)], 45 beta-lactam-non-susceptible Burkholderia cepacia complex (BCC), 47 levofloxacin or trimethoprim/sulfamethoxazole-non-susceptible Stenotrophomonas maltophilia and 22 ciprofloxacin-non-susceptible Elizabethkingia spp. collected between 2019 and 2021 were subjected to MIC determination for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam. Results: The MIC50/90s of cefiderocol for drug-resistant A. baumannii, P. aeruginosa, BCC, S. maltophilia and Elizabethkingia spp. were 0.25/2, 0.25/1, ≤0.06/≤0.06, ≤0.06/0.25 and >32/>32 mg/L, respectively. Cefiderocol inhibited 94.4% (119/126) of MDRAB, 100% of imipenem-resistant P. aeruginosa, 100% of DTRPA and 100% of BCC at an MIC ≤4 mg/L, and 97.9% (46/47) of S. maltophilia at ≤1 mg/L. Ceftazidime/avibactam inhibited 76.4% (84/110) of imipenem-resistant P. aeruginosa, 21.4% (3/14) of DTRPA and 68.9% (31/45) of BCC at an MIC ≤8 mg/L. Aztreonam/avibactam had MIC50/90s of 16/>32, 8/16 and 4/8 mg/L for imipenem-resistant P. aeruginosa, BCC and S. maltophilia, respectively. At ≤8 mg/L, aztreonam/avibactam inhibited 7.1% (1/14) of DTRPA and 93.6% (44/47) of S. maltophilia isolates. Elizabethkingia spp. demonstrated high MICs for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam, with all MIC50s and MIC90s > 32 mg/L. Conclusion: Cefiderocol may serve as an alternative treatment for multidrug-resistant A. baumannii, P. aeruginosa, BCC and S. maltophilia when other antibiotics have been ineffective or intolerable. The role of ceftazidime/avibactam and aztreonam/avibactam in the management of BCC or S. maltophilia infections warrants further investigation.

[Improving the Pap Smear Screening Rate for Cervical Cancer in a Health Management Center: A Quality Improvement Program].

BACKGROUND & PROBLEMS: Early detection tests are highly effective in helping adult women prevent the onset of cervical cancer. However, the cervical Pap smear screening rate in a health management center was only 54.3% in 2020. PURPOSE: This project was developed to improve the Pap smear screening rate for cervical cancer in a health management center. RESOLUTION: The strategies developed included revising the health examination lists, developing an online appointment booking system, designing a patient decision aid, creating a standardized simulation moulage for education, and rechecking patient's National Health Insurance cards. RESULTS: After implementation of these strategies, the Pap smear screening rate for cervical cancer rose from 54.3% to 81.2%. The screening rate at the health management center in 2022 reached 96.6%. CONCLUSIONS: Shared decision-making can elucidate the comprehensive options available to clients and support them in considering their options and achieving informed choices regarding Pap smear preferences.

In Vitro Activities and Inoculum Effects of Cefiderocol and Aztreonam-Avibactam against Metallo-ß-Lactamase-Producing Enterobacteriaceae.

Cefiderocol and aztreonam-avibactam (ATM-AVI) both had activity against carbapenem-resistant Gram-negative bacilli, including those that produce metallo-ß-lactamases (MBLs). We compared the in vitro activities and inoculum effects of these antibiotics against carbapenemase-producing Enterobacteriaceae (CPE), especially MBL-producing isolates. The MICs of cefiderocol and ATM-AVI were determined using broth microdilution method for a 2016 to 2021 collection of Enterobacteriaceae isolates which produced MBL, KPC, or OXA-48-like carbapenemases. MICs with high bacteria inoculum were also evaluated for susceptible isolates. A total of 195 CPE were tested, including 143 MBL- (74 NDM, 42 IMP, and 27 VIM), 38 KPC-, and 14 OXA-48-like-producing isolates. The susceptible rates of MBL-, KPC-, and OXA-48-like producers to cefiderocol were 86.0%, 92.1%, and 92.9%, respectively, and that to ATM-AVI were 95.8%, 100%, and 100%, respectively. NDM producers displayed lower susceptibility and higher MIC50s/MIC90s of cefiderocol (78.4%, 2/16 mg/L) than IMP (92.9%, 0.375/4 mg/L) and VIM (96.3%, 1/4 mg/L) producers. NDM- and VIM-producing Escherichia coli showed lower susceptibility to ATM-AVI (77.3% and 75.0%, respectively) compared to MBL-CPE of other species (100% susceptible). Inoculum effects for cefiderocol and ATM-AVI were observed among 95.9% and 95.2% of susceptible CPE, respectively. A switch from susceptible to resistant category was observed in 83.6% (143/171) of isolates for cefiderocol and 94.7% (179/189) for ATM-AVI. Our results revealed that NDM-producing Enterobacteriaceae had lower susceptibility to cefiderocol and ATM-AVI. Prominent inoculum effects on both antibiotics were observed for CPE, which suggested a risk of microbiological failure when they were used for CPE infections with high bacteria burden. IMPORTANCE The prevalence of infections caused by carbapenem-resistant Enterobacteriaceae is increasing worldwide. Currently, therapeutic options for metallo-ß-lactamase (MBL)-producing Enterobacteriaceae remain limited. We demonstrated that clinical metallo-ß-lactamase (MBL)-producing Enterobacteriaceae isolates were highly susceptible to cefiderocol (86.0%) and aztreonam-avibactam (ATM-AVI) (95.8%). However, inoculum effects on cefiderocol and ATM-AVI were observed for over 90% of susceptible carbapenemase-producing Enterobacteriaceae (CPE) isolates. Our findings highlight a potential risk of microbiological failure when using monotherapy with cefiderocol or ATM-AVI to treat severe CPE infection.

[Using Team Resource Management and Situational Simulation to Improve the Resuscitation Performance Completion Rate].

BACKGROUND & PROBLEMS: Cardiopulmonary resuscitation is an important issue in patient safety. After investigation, we identified the causes of the low rate of resuscitation completion in our emergency department as: incomplete utilization of available first-aid equipment, lack of standards related to task allocation, unclear moving line and instrument placement, lack of teamwork, and poor resuscitation-related communications during the COVID-19 pandemic. PURPOSE: The project aimed to improve the resuscitation performance completion rate. RESOLUTION: The project included designing equipment reminder cards and an airway car, designating specific responsibilities for each team member, establishing standard layouts and traffic flows, and providing situational simulation and team resource management training. RESULTS: After the intervention, the resuscitation performance completion rate had risen to 91.6% from the pre-intervention rate of 69.1%. This has since further risen to a relatively constant completion rate of 98.1%. CONCLUSIONS: The implementation of the team resource management and situational simulation training intervention in our ED improved both the resuscitation completion rate and the rate of return of spontaneous circulation (ROSC).

Fibroblasts Drive Metabolic Reprogramming in Pacemaker Cardiomyocytes.

BACKGROUND: The sino atrial node (SAN) is characterized by the microenvironment of pacemaker cardiomyocytes (PCs) encased with fibroblasts. An altered microenvironment leads to rhythm failure. Operable cell or tissue models are either generally lacking or difficult to handle. The biological process behind the milieu of SANs to evoke pacemaker rhythm is unknown. We explored how fibroblasts interact with PCs and regulate metabolic reprogramming and rhythmic activity in the SAN. METHODS: Tbx18 (T-box transcription factor 18)-induced PCs and fibroblasts were used for cocultures and engineered tissues, which were used as the in vitro models to explore how fibroblasts regulate the functional integrity of SANs. RNA-sequencing, metabolomics, and cellular and molecular techniques were applied to characterize the molecular signals underlying metabolic reprogramming and identify its critical regulators. These pathways were further validated in vivo in rodents and induced human pluripotent stem cell-derived cardiomyocytes. RESULTS: We observed that rhythmicity in Tbx18-induced PCs was regulated by aerobic glycolysis. Fibroblasts critically activated metabolic reprogramming and aerobic glycolysis within PCs, and, therefore, regulated pacemaker activity in PCs. The metabolic reprogramming was attributed to the exclusive induction of Aldoc (aldolase c) within PCs after fibroblast-PC integration. Fibroblasts activated the integrin-dependent mitogen-activated protein kinase-E2F1 signal through cell-cell contact and turned on Aldoc expression in PCs. Interruption of fibroblast-PC interaction or Aldoc knockdown nullified electrical activity. Engineered Tbx18-PC tissue sheets were generated to recapitulate the microenvironment within SANs. Aldoc-driven rhythmic machinery could be replicated within tissue sheets. Similar machinery was faithfully validated in de novo PCs of adult mice and rats, and in human PCs derived from induced pluripotent stem cells. CONCLUSIONS: Fibroblasts drive Aldoc-mediated metabolic reprogramming and rhythmic regulation in SANs. This work details the cellular machinery behind the complex milieu of vertebrate SANs and opens a new direction for future therapy.

Biomaterial-induced conversion of quiescent cardiomyocytes into pacemaker cells in rats.

Pacemaker cells can be differentiated from stem cells or transdifferentiated from quiescent mature cardiac cells via genetic manipulation. Here we show that the exposure of rat quiescent ventricular cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics and biochemistry could facilitate the scalable production of biological pacemakers for human use.

[Project to Improve Satisfaction in the Conscription Physical Examinations Service].

BACKGROUND & PROBLEMS: In response to a decrease in satisfaction to 69.3%, we resolved to optimize the process of conducting conscription physical examinations. After an investigatory panel conducted an analysis, the following problems were identified. Firstly, the poorly designed route lead to dense queues between exam stations. Secondly, the procedures for changing the dates of conscription physical examinations were cumbersome. Lastly, unexpected contacts between examinees and the patients in the hospital occurred from time to time, which increases the risk of cross infection. PURPOSE: This project was developed to improve the level of satisfaction in conscription physical examinations and increase the quality of medical services provided. RESOLUTION: After brainstorming and reviewing the related literature, we identified several actions to address and resolve the problems. We adopted non-crossing lines, divided the servicemen's cabins for inspection, simplified the information system process, relocated the physical examination venue, and planned education and training. RESULTS: Satisfaction with the examination process increased from 69.3% to 90.3%. CONCLUSIONS: A survey-based review of the conscription physical examination process should be conducted annually to ensure the procedures are as smooth as possible and to improve the quality of medical services provided.

[Reducing Abnormal Culture Rates of Digestive Endoscopy in a Health Management Center].

BACKGROUND: Endoscopic evaluation plays an indispensable role in medical treatments designed to prevent, diagnose, and cure gastrointestinal disease. Surveillance culture monitoring may be useful in monitoring the outcome of reprocessing. PURPOSE: In this project, microbiologic surveillance cultures were employed to improve the quality of flexible endoscope disinfection. RESOLUTION: This project, implemented from February 1st, 2018 to February 28th, 2019, used several approaches to improve the positive culture rate. We redesigned and implemented the standard operating procedures for endoscope reprocessing, established an in-service training course, provided education materials on reprocessing, and installed a storage cabinet that custom-built to accommodate the endoscope. RESULTS: The positive culture rate was reduced from 5.8% to 0%. CONCLUSIONS: Endoscopy culturing is a useful method to assess the effectiveness of standard reprocessing procedures. The development of guidelines and skill practices should follow current, evidence-based practice and infection prevention principles, and related documents should be organized. We suggest regularly deploying quality-improvement techniques to improve performance and service delivery.

[An Experience Providing Hospice Care to a Terminal Cancer Patient].

This study discusses a case in which corneal-donation care was provided to a 57-year-old patient with terminal salivary gland cancer. Nursing care was provided from June 1 to June 28, 2017. The overall nursing assessment (covering physiological, psychological, social, and spiritual aspects) confirmed that the three main issues faced by the patient were chronic pain, dysfunctional family processes, and spiritual disturbances. Effective pain treatment was applied during the care process in order to stabilize the patient's physical condition. A hospice shared care team then worked together to help the patient mend his relationships with family members, fulfill his wish to donate his cornea, find meaning in his life, affirm his contribution to his family and society, and die a peaceful death. With regard to clinical practice, an explanation of corneal donation should be included in the conventional educational guidelines for hospice care. In addition to referrals to the relevant medical teams, it is recommended that nursing personnel who deal with patients like this participate in organ donation courses and develop positive attitudes and grief counseling skills. These actions will enable them to build up the professionalism, confidence, patience, and organ procurement-related skills required for the provision of care to these patients, which will in turn lead to better-quality palliative care. It is hoped that the nursing experience shared herein provides nursing personnel with a reference for palliative cancer care.

Do-not-resuscitate consent signed by patients indicates a more favorable quality of end-of-life care for patients with advanced cancer.

PURPOSE: Do-not-resuscitate (DNR) consent is crucial in end-of-life (EOL) care for patients with advanced cancer. However, DNR consents signed by patients (DNR-P) and surrogates (DNR-S) reflect differently on patient autonomy and awareness. METHODS: This retrospective study enrolled advanced cancer patients treated at National Taiwan University Hospital, Hsin-Chu Branch between 2012 and 2014. Patients who signed DNR consent at other hospitals were excluded; the remaining patients were subsequently classified into DNR-S and DNR-P groups. RESULTS: We enrolled 1495 patients. The most prevalent primary cancers were hepato-biliary-pancreatic (26.9 %), lung (16.3 %), and colorectal (14.0 %) cancers. We classified 965 (64.5 %) and 530 (35.5 %) patients into the DNR-S and DNR-P groups, respectively. Significant differences were observed between both groups regarding gender (p = 0.002), age (p < 0.001), and the Eastern Cooperative Oncology Group performance (p < 0.001) and educational (p < 0.001) status levels. The median survival times after DNR consent signature were 5.0 days (95 % confidence interval [CI] 4.4-5.6 days) and 14.0 days (95 % CI 12.1-15.9 days) in the DNR-S and DNR-P groups, respectively (p < 0.001). The median good death evaluation (GDE) scores were 5.4 (95 % CI 4.9-6.0) and 13.7 (95 % CI 12.7-14.6) in the DNR-S and DNR-P groups, respectively (p < 0.001). Univariate and multivariate analyses revealed that DNR-S was an independent factor for significantly low GDE scores (i.e., poor EOL care quality). CONCLUSION: The DNR concept is emerging; however, the DNR-P percentage remains low (35.6 %) in patients with advanced cancer. DNR-P significantly improves the EOL care quality.

[A project to improve the "do not resuscitation" consent completeness rate for terminal cancer patients].

BACKGROUND: Signed do-not-resuscitate (DNR) consent is the essential first step for terminal cancer patients to choose palliative care and a quality marker of terminal care. DNR consent completeness helps deliver correct information, ensure consent legal validity, reduce medical disputes, and protect patient and family rights. The DNR consent completeness rate during May and June 2005 was only 33.9% in our hospital. Reasons indicated for this low rate included: (1) lack of a standard operating procedure for DNR consent; (2) multiple DNR consent versions; (3) lack of DNR-related education; and (4) lack of monitoring procedures. Our team developed a project to resolve these problems and improve terminal care quality. PURPOSE: The goal of this project was to increase the rate of DNR consent completeness from 33.9% to 80%. RESOLUTION: The plan, implemented between August and December 2009, included the following components: (1) establish standard guidelines for DNR consent; (2) simplify and unify DNR consent procedures; (3) provide DNR education for hospital staff; and (4) establish a DNR consent monitoring system. RESULTS: The DNR consent completeness rate rose from 33.9% to 90%. The goal of this project was thus achieved. CONCLUSION: This project effectively improved the DNR consent completeness rate at our hospital. The project ensured patients a good death and enhanced terminal care quality and patient satisfaction. Our experience may provide a reference to help other hospitals increase DNR their consent completeness rates.

Insights into Chinese perspectives on do-not-resuscitate (DNR) orders from an examination of DNR order form completeness for cancer patients.

PURPOSE: Discussing end-of-life care with patients is often considered taboo, and signing a do-not-resuscitate (DNR) order is difficult for most patients, especially in Chinese culture. This study investigated distributions and details related to the signing of DNR orders, as well as the completeness of various DNR order forms. METHODS: Retrospective chart reviews were performed. We screened all charts from a teaching hospital in Taiwan for patients who died of cancer during the period from January 2010 to December 2011. A total of 829 patient records were included in the analysis. The details of the DNR order forms were recorded. RESULTS: The DNR order signing rate was 99.8%. The percentage of DNR orders signed by patients themselves (DNR-P) was 22.6%, while the percentage of orders signed by surrogates (DNR-S) was 77.2%. The percentage of signed DNR forms that were completely filled out was 78.4%. The percentage of DNR-S forms that were completed was 81.7%, while the percentage of DNR-P forms that were completely filled out was only 67.6%. CONCLUSION: Almost all the cancer patients had a signed DNR order, but for the majority of them, the order was signed by a surrogate. Negative attitudes of discussing death from medical professionals and/or the family members of patients may account for the higher number of signed DNR-S orders than DNR-P orders. Moreover, early obtainment of signed DNR orders should be sought, as getting the orders earlier could promote the quality of end-of-life care, especially in non-oncology wards.