Efficacy of cefoperazone/sulbactam for ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and the factors associated with poor outcomes.

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.

Multicenter study on clinical outcomes and poor prognostic factors in patients with Klebsiella pneumoniae bacteremia receiving cefoperazone/sulbactam treatment.

BACKGROUND: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied. OBJECTIVES: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates. METHODS: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed. RESULTS: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes. CONCLUSION: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.

The Epidemiological Analysis of COVID-19 Outbreaks in Nursing Homes during the Period of Omicron Variant Predominance.

BACKGROUND: The main purpose of this study was to evaluate the epidemic trend and risk factors associated with COVID-19 outbreaks in nursing homes during the period of Omicron variant predominance. METHODS: The study analyzed the risk factors associated with SARS-CoV-2 infection and death among the 327 residents and 129 healthcare workers (HCWs) in three hospital-affiliated nursing homes through a multivariate Cox regression model. RESULTS: The rates of receiving a COVID-19 booster dose were 70.3% for the residents and 93.0% for the healthcare workers (HCWs), respectively. A number of asymptomatic individuals, including 54 (16.5%) residents and 15 (11.6%) HCWs, were detected through mass screening surveillance tests. The COVID-19 infection rates during the outbreaks were 41.6% among residents and 48.1% among HCWs, respectively. The case fatality rate among residents was 10.3%. None of the HCWs were hospitalized or died. The multivariate Cox regression model showed that the risk of COVID-19 infection increased in males (HR 2.46; 95% CI 1.47-4.11; p = 0.001), Barthel index ≥ 61 (HR 1.93; 95% CI 1.18-3.17; p = 0.009), and dementia (HR 1.61; 95% CI 1.14-2.27; p = 0.007). The risk of COVID-19 death increased with pneumonia (HR 11.03; 95% CI 3.02-40.31; p < 0.001), hospitalization (HR 7.18; 95% CI 1.97-26.25; p = 0.003), and admission to an intensive care unit (HR 8.67; 95% CI 2.79-26.89; p < 0.001). CONCLUSIONS: This study highlighted the high infection rates with a substantial proportion of asymptomatic infections for both residents and HCWs, as well as a high case fatality rate for the residents among nursing homes during the Omicron epidemic period. We suggest implementing mass screening through regular surveillance testing as an effective strategy for early detection of COVID-19 and for preventing transmission during an epidemic period. Pneumonia is the primary risk associated with COVID-19 death. Early detection and prompt treatment of pneumonia for vulnerable residents in nursing homes are crucial to protect them from potential mortality.

Agreement assessment of tigecycline susceptibilities determined by the disk diffusion and broth microdilution methods among commonly encountered resistant bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2008 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 µg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Trends in susceptibility of vancomycin-resistant Enterococcus faecium to tigecycline, daptomycin, and linezolid and molecular epidemiology of the isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006 to 2010.

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC(90)s) from 2006-2007 (0.06 µg/ml) to 2008-2010 (0.12 µg/ml). The MIC(90)s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.

Trends in the susceptibility of clinically important resistant bacteria to tigecycline: results from the Tigecycline In Vitro Surveillance in Taiwan study, 2006 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n = 423), vancomycin-resistant enterococci (VRE) (n = 219), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 1,141), ESBL-producing Klebsiella pneumoniae (n = 1,330), Acinetobacter baumannii (n = 1,645), and Stenotrophomonas maltophilia (n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC(90), 0.03 µg/ml), and only one MRSA isolate (MIC(90), 0.5 µg/ml) and three VRE isolates (MIC(90), 0.125 µg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC(90), 0.5 µg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC(90), 2 µg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC(90), 4 µg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii.

Susceptibilities to amphotericin B, fluconazole and voriconazole of Trichosporon clinical isolates.

A total of 35 Trichosporon isolates were collected from the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) project from 1999 to 2006, and their identifications as well as drug susceptibilities were determined. The most frequently isolated species was T. asahii (62.9%), and the most common clinical sample that yielded Trichosporon isolates was urine (37.1%). The etiology of all seven invasive trichosporonosis was T. asahii. For the 22 T. asahii isolates, the MIC(50) and MIC(90) for amphotericin B were 0.25 and 1 µg/mL, respectively. Those for fluconazole were 2 and 4 µg/mL, respectively, and for voriconazole 0.031 and 0.063 µg/mL, respectively. When the intraclass correlation coefficients (ICCs) and agreements were calculated, we found that the MICs of fluconazole obtained from different methods were similar and the inter-method discrepancies were low. Nevertheless, no unanimous MIC of amphotericin B and voriconazole was obtained among different methods.

Wound repair using discarded skin tissue from the rolled edge of pressure injury: a feasibility study of five cases.

INTRODUCTION: New techniques are needed to manage chronic wounds in patients with contraindications to standard of care treatment. OBJECTIVE: This case series investigated the viability and proliferative activity of split skin cells harvested from the discarded rolled edge of PIs for use in promoting reepithelialization in chronic wounds. MATERIALS AND METHODS: The harvested skin was minced into particles with a scalpel. The structure of the skin particle was shown with hematoxylin-eosin staining. The viability of cells, isolated from skin particles, was identified with MTT. Skin particles were transferred to PIs. The size of PI was recorded before grafting and 1 month after grafting. RESULTS: From January 2018 to January 2019, 5 patients (1 female, 4 males; mean age, 72.6 years ± 6.1) were enrolled in this study. The mean ulcer size was 27.8 cm2 ± 17.7. The cells from particles could survive and be amplified in vitro. One month after grafting, the average ulcer size was 16.2 cm2 ± 7.3. CONCLUSION: The split skin particles harvested from the rolled edge of the wound consisted of keratinocytes and keratinized tissues and were found to be viable and proliferative. These particles had the capacity to survive and expand on the granulation tissue surface of PIs, which indicates this procedure could accelerate reepithelization in chronic wounds.

The complete chloroplast genome of Abies ernestii Rehder (Pinaceae) and its phylogenetic implications.

Abies ernestii Rehder is endemic to the montane regions of Southwest China. Till now, phylogenetic relationships between A. ernestii and other closely related species remain unclear. In this study, we first characterized the complete chloroplast (cp) genome of A. ernestii. The whole cp genome was 121,841 bp in size, including one hundred and thirteen genes. Results of comparative cp genome revealed that only ycf1 and ycf2 was characterized by a considerable variation. Our phylogenetic analyses supported the monophyly of the genus Abies and revealed a clear separation between A. ernestii and A. chensiensis Tiegh. This study highlights the significance of using cp genomes to examine species boundaries among closely related fir species.

Case report of acute encephalitis following the AstraZeneca COVID-19 vaccine.

Coronavirus disease 2019 (COVID-19) vaccines have proven to be safe, effective and life-saving. However, little information is available on the neurological complications of COVID-19 vaccine. Here, we report a case who developed acute encephalomyelitis 1 week after being vaccinated with AstraZeneca COVID-19 vaccine (AZ vaccine). Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was also suspected. After intravenous dexamethasone and subcutaneous fondaparinux therapy, he returned to normal life without neurological sequelae. Four months later, he received Moderna COVID-19 vaccine without any sequelae.

Evolution of trimethoprim/sulfamethoxazole resistance in Shewanella algae from the perspective of comparative genomics and global phylogenic analysis.

OBJECTIVE: Shewanella algae is a zoonotic marine bacterium that causes a variety of infections in immunocompromised patients or those who have been exposed to seawater. The development of trimethoprim/sulfamethoxazole (TMP/SMX) resistance in S. algae are found in human and environment isolates during the past ten years, and thus the treatment options are decreasing. METHODOLOGY: In the study, we conduct a comparative genomic study to identify the resistant mechanism of TMP/SMX-resistance in S. algae. RESULTS: We found the resistance of TMP/SMX in S. algae is associated with the existence of sul1 and dfrA12 within the class 1 integron. The gene cassette dfra12-aadA2-qacEΔ1/sul1 within the class 1 integron is highly conserved. In addition, the class 1 integron and encapsulated sul1 are significantly enriched in Enterobacteriaceae in NCBI and UniProt databases. CONCLUSION: Our study suggests that the horizontal transfer of TMP/SMX resistance via class 1 integron is most frequently occurred within Enterobacteriaceae and has spread to a wide range of sources including soil, poultry, and marine water.

Sustaining Improvements of Surgical Site Infections by Six Sigma DMAIC Approach.

BACKGROUND: SSIs (surgical site infections) are associated with increased rates of morbidity and mortality. The traditional quality improvement strategies focusing on individual performance did not achieve sustainable improvement. This study aimed to implement the Six Sigma DMAIC method to reduce SSIs and to sustain improvements in surgical quality. The surgical procedures, clinical data, and surgical site infections were collected among 42,233 hospitalized surgical patients from 1 January 2019 to 31 December 2020. Following strengthening leadership and empowering a multidisciplinary SSI prevention team, DMAIC (Define, Measure, Analyze, Improve, and Control) was used as the performance improvement model. An evidence-based prevention bundle for reduction of SSI was adopted as performance measures. Environmental monitoring and antimicrobial stewardship programs were strengthened to prevent the transmission of multi-drug resistant microorganisms. Process change was integrated into a clinical pathway information system. Improvement cycles by corrective actions for the risk events of SSIs were implemented to ensure sustaining improvements. We have reached the targets of the prevention bundle elements in the post-intervention period in 2020. The carbapenem resistance rates of Enterobacteriaceae and P. aeruginosa were lower than 10%. A significant 22.2% decline in SSI rates has been achieved, from 0.9% for the pre-intervention period in 2019 to 0.7% for the post-intervention period in 2020 (p = 0.004). Application of the Six Sigma DMAIC approach could significantly reduce the SSI rates. It also could help hospital administrators and quality management personnel to create a culture of patient safety.

Correlation Between Cefoperazone/Sulbactam MIC Values and Clinical Outcomes of Escherichia coli Bacteremia.

INTRODUCTION: The clinical efficiency of cefoperazone/sulbactam (CPZ/SUL) against Escherichia coli bacteremia was unknown. This study aimed to explore the relationship between CPZ/SUL MIC values and clinical outcomes in Escherichia coli bacteremia. METHODS: A multicenter, retrospective, observational cohort study was conducted in Taiwan between January 2015 and December 2020. Patients treated with CPZ/SUL for E. coli bacteremia were enrolled in the analysis. The CPZ/SUL MICs were determined by using the agar dilution method. The primary outcome was 30-day mortality. RESULTS: Among 247 isolates, 160 (64.8%) isolates were susceptible, 8 (3.2%) were intermediate, and 79 (32.0%) were resistant to cefoperazone. The activity of cefoperazone against cefoperazone-non-susceptible E. coli (n = 87) was restored upon combination with sulbactam, with susceptibility ranging from 0% to 97.7%. The 30-day mortality was 4.5% (11/247) and overall clinical success rate was 91.9% (227/247). Multivariate Cox proportional-hazards model revealed that heart failure [adjusted relative risk (ARR), 5.49; 95% confidence interval (CI) 1.31-23.02; p = 0.020], malignancy (ARR 7.50; 95% CI 2.02-27.80; p = 0.003), SOFA score (ARR 1.29; 95% CI 1.09-1.52; p = 0.003), and CPZ/SUL MIC ≥ 64 mg/L (ARR 11.31; 95% CI 1.34-95.52; p = 0.026) were independently associated with 30-day mortality. No statistically significant differences in 30-day mortality were found between groups with or without cefoperazone susceptibility (3.4% vs. 5.0%, p = 0.751, respectively). CONCLUSIONS: Patients with E. coli bacteremia who were treated with CPZ/SUL had a favorable outcome when the MICs of the isolates were ≤ 16 mg/L and a high risk of mortality with MICs ≥ 64 mg/L.

In vitro activity of cefiderocol, cefepime/enmetazobactam, cefepime/zidebactam, eravacycline, omadacycline, and other comparative agents against carbapenem-non-susceptible Pseudomonas aeruginosa and Acinetobacter baumannii isolates associated from bloodstream infection in Taiwan between 2018-2020.

BACKGROUND/PURPOSE: This study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel ß-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics. METHODS: In total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data. RESULTS: Among the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC50/90, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC50/90, 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC50/90, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC50/90, 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC50/90, 4/8 mg/L). CONCLUSIONS: The spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance.

Nationwide surveillance of antimicrobial resistance in invasive isolates of Streptococcus pneumoniae in Taiwan from 2017 to 2019.

BACKGROUND/PURPOSE: Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. METHODS: A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. RESULTS: Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. CONCLUSION: Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Comparing visual inspection and performance observation for evaluation of hospital cleanliness.

BACKGROUND: Environmental cleaning is an effective measure to prevent infections. However, performance observation has been rarely delineated. This study aimed to compare correlations among visual inspection, performance observation, and effectiveness by using adenosine triphosphate bioluminescence (ATP bioluminescence) as a comparator to find out which method is better to assess hospital cleanliness. METHODS: This prospective study was conducted at a medical center from April 2019 to October 2020. Seven high-touch surfaces were evaluated during and after terminal cleaning by performance observation, visual inspection, and ATP bioluminescence. RESULTS: The scores by performance observation, visual inspection, and ATP were 55.4%, 87.5%, and 26.6% after cleaning. The correlations between performance observation and visual inspection and between performance observation and ATP interpretation were weak positive (φ = 0.300, 0.324, P < .001). No correlation was between the visual inspection and ATP interpretation (φ=0.137). The median of ATP readings was lower in "compliant" group by performance observation and "clean" group by visual inspection than "not compliant" group and "not clean" group (P < .001). CONCLUSIONS: Performance observation combined with ATP would be preferred to include to audit cleanliness on high-risk surfaces. Visual inspection would be a rapid and time-saving assessment tool on low-risk surfaces.

The first imported case of extensively drug-resistant Salmonella enterica serotype Typhi infection in Taiwan and the antimicrobial therapy.

The first imported case of XDR typhoid fever in Taiwan contracted with a bacterial strain, which was most closely related to the blaCTX-M-15-carrying strains linked to Pakistan. Meropenem, in combination with an antimicrobial with intracellular activity against Salmonella, should be used for the treatment of XDR typhoid fever.

Detection of S83V GyrA mutation in quinolone-resistant Shewanella algae using comparative genomics.

BACKGROUND: Shewanella algae is a zoonotic pathogen that poses a serious health threat to immunocompromised hosts. Treatment of S. algae infections is challenging due to the pathogen's intrinsic resistance to a variety of ß-lactam antibiotics. Therapeutic options have become further limited by the emergence of quinolone-resistant strains. Currently, there are few studies concerning the genetic and molecular mechanisms underlying acquired quinolones resistance in S. algae. qnrA was once proposed as the candidate gene related to quinolones resistance in S. algae. However, recent studies demonstrated qnrA are highly conservative and does not confer resistance to quinolones in S. algae. METHODS: A total of 27 non-duplicated isolates of S. algae strains were examined. MICs of ciprofloxacin were determined using Vitek 2. Whole genome sequencing was performed using MiSeq platform. Comprehensive Antibiotic Resistance Database and ResFinder were used for annotation of quinolones resistance genes. Multiple sequence alignment by EMBOSS Clustal Omega were used to identified mutation in quinolone resistance-determining regions. To investigation of the alteration of protein structure induced by mutation, in silico molecular docking studies was conducted using Accryl Discovery studio visualizer. RESULTS: All S. algae harbored the quinolone-resistance associated genes (qnrA, gyrA, gyrB, parC, and parE) regardless its resistance to ciprofloxacin. Comparison of these genomes identified a nonsynonymous mutation (S83V) in chromosome-encoded gyrase subunits (GyrA) in quinolone-resistant strain. We found this mutation disrupts the water-metal ion bridge, reduces the affinity of the quinolone-enzyme complex for the metal ions and therefore decrease the capability of quinolones to stabilize cleavage complexes. CONCLUSIONS: The study provides insight into the quinolone resistance mechanisms in S. algae, which would be helpful for the evolution of antibiotic resistance in this bacterium.

In-vitro activity of cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents against carbapenem-nonsusceptible Enterobacterales: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2017-2020.

This study examined the susceptibility of carbapenem-nonsusceptible Enterobacterales (CNSE) to cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents. Non-duplicate Enterobacterales isolates from 16 Taiwanese hospitals were evaluated. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibility results were interpreted based on relevant guidelines. In total, 201 CNSE isolates were investigated, including 26 Escherichia coli isolates and 175 Klebsiella pneumoniae isolates. Carbapenemase genes were detected in 15.4% (n=4) of E. coli isolates and 47.4% (n=83) of K. pneumoniae isolates, with the most common being blaKPC (79.3%, 69/87), followed by blaOXA-48-like (13.8%, 12/87). Cefiderocol was the most active agent against CNSE; only 3.8% (n=1) of E. coli isolates and 4.6% (n=8) of K. pneumoniae isolates were not susceptible to cefiderocol. Among the carbapenem-resistant E. coli and K. pneumoniae isolates, 88.5% (n=23) and 93.7% (n=164), respectively, were susceptible to ceftazidime/avibactam. For cefepime/zidebactam, 23 (88.5%) E. coli isolates and 155 (88.6%) K. pneumoniae isolates had MICs ≤2/2 mg/L. For cefepime/enmetazobactam, 22 (84.6%) E. coli isolates and 85 (48.6%) K. pneumoniae isolates had MICs ≤2/8 mg/L. The higher MICs of K. pneumoniae against cefepime/enmetazobactam were due to only one (1.5%) of the 67 blaKPC-carrying isolates being susceptible. MICs of omadacycline were significantly higher than those of eravacycline and tigecycline. In summary, cefiderocol, ceftazidime/avibactam and cefepime/zidebactam were more effective against carbapenem-nonsusceptible E. coli and K. pneumoniae than other drugs, highlighting their potential as valuable therapeutics.