Treatment-emergent cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii is associated with insertion sequence ISAba36 in the siderophore receptor pirA.

We report the emergence of cefiderocol resistance in a blaOXA-72 carbapenem-resistant Acinetobacter baumannii isolate from a sacral decubitus ulcer. Cefiderocol was initially used; however, a newly approved sulbactam-durlobactam therapy with source control and flap coverage was successful in treating the infection. Laboratory investigation revealed cefiderocol resistance mediated by ISAba36 insertion into the siderophore receptor pirA.

Development and effectiveness of a metaverse reality-based family-centered handoff education program in nursing students.

PURPOSE: Effective patient handoffs are vital in pediatric populations. This study aimed to develop and identify the impact of a metaverse-based handoff program using ZEPETO on nursing students' handoff competence, handoff self-efficacy, learning realism, and satisfaction. DESIGN AND METHODS: This study used a non-randomized, pre-post nonequivalent group design to develop, implement, and verify a metaverse-based handoff simulation program in a nursing school in South Korea. We assigned 69 senior nursing students from a university to an experimental group or a control group. We developed a metaverse-based, handoff simulation program of family-centered care by building a pediatric intensive care unit (PICU) using ZEPETO. The program included an online lecture, a metaverse rounding discussion, and a metaverse-based handoff simulation of postoperative care for infants with congenital heart disease. We measured handoff competence, handoff self-efficacy, learning realism, and learning satisfaction pre- and post-program. RESULT(S): The experimental group showed significantly higher handoff self-efficacy than the control group (t = 3.17, p = 0.002). No significant differences were found in handoff competency, learning realism, or learning satisfaction between the groups. CONCLUSION(S): This study confirmed that a family-centered care-based handoff metaverse simulation program based on the experiential learning theory enhanced nursing students' handoff self-efficacy. The program equipped students to conduct safe and effective handoffs in real-world clinical settings by providing an immersive learning experience and emphasizing patient-centered communication. PRACTICAL IMPLICATIONS: Based on these results, family-centered, handoff education programs are recommended to be developed that focus on learning realism and learning satisfaction to enhance nursing students' handoff competence.

Isolation of AmpC- and extended spectrum ß-lactamase-producing Enterobacterales from fresh vegetables in the United States.

Vegetables may serve as a reservoir for antibiotic resistant bacteria and resistance genes. AmpC ß-lactamases and extended spectrum beta-lactamases (ESBL) inactivate commonly used ß-lactam antibiotics, including penicillins and cephalosporins. In this study, we determined the prevalence of AmpC and ESBL-producing Enterobacterales in retail vegetables in the United States. A total of 88 vegetable samples were collected for the screening of AmpC and ESBL-producing Enterobacterales using CHROMagar ESBL agar. These vegetables included washed ready-to-eat salad (23), microgreens/sprouts (13), lettuce (11), herbs (11), spinach (5), mushrooms (5), brussels sprouts (4), kale (3), and other vegetable samples (13). AmpC and ESBL activity in these isolates were determined using double disk combination tests. Two vegetable samples (2.27%), organic basil and brussels sprouts, were positive for AmpC-producing Enterobacterales and eight samples (9.09%), including bean sprouts, organic parsley, organic baby spinach, and several mixed salads, were positive for ESBL-producing Enterobacterales. Whole genome sequencing was used to identify the bacterial species and resistance genes in these isolates. Genes encoding AmpC ß-lactamases were found in Enterobacter hormaechei strains S43-1 and 74-2, which were consistent with AmpC production phenotypes. Multidrug-resistant E. hormaechei strains S11-1, S17-1, and S45-4 possess an ESBL gene, blaSHV66 , whereas five Serratia fonticola isolates contain genes encoding a minor ESBL, FONA-5. In addition, we used shotgun metagenomic sequencing approach to examine the microbiome and resistome profiles of three spinach samples. We found that Pseudomonas was the most prevalent bacteria genus in the spinach samples. Within the Enterobacteriaceae family, Enterobacter was the most abundant genus in the spinach samples. Moreover, antibiotic resistance genes encoding 12 major classes of antibiotics, including ß-lactam antibiotics, aminoglycoside, macrolide, fluoroquinolone, and others, were found in these spinach samples. Therefore, vegetables can serve as an important vehicle for transmitting antibiotic resistance. The study highlights the need for antibiotic resistance surveillance in vegetable products.

Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection.

BACKGROUND: The recent rise and spread of carbapenem-resistant pathogens pose an urgent threat to public health and has fueled the search for new therapies. Localized delivery of topical antibiotics is an alternative for the treatment of infected wounds caused by drug-resistant pathogens. In this study, we aimed to develop antimicrobial-loaded hydrogels for topical treatment of wound infections in a murine skin wound infection. RESULTS: Paenipeptin analogue 1, a linear lipopeptide, potentiated clarithromycin against multidrug-resistant Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae. Enzymatically-crosslinked gelatin hydrogels were developed to encapsulate paenipeptin analogue 1 and clarithromycin. The encapsulated antimicrobials were gradually released from hydrogels during incubation, reaching 75.43 and 53.66% for paenipeptin and clarithromycin, respectively, at 24 h. The antimicrobial-loaded hydrogels containing paenipeptin and clarithromycin synergistically resulted in 5-log reduction in carbapenem-resistant A. baumannii within 6 h in vitro. Moreover, the antimicrobial-loaded hydrogels reduced 3.6- and 2.5-log of carbapenem-resistant A. baumannii when treated at 4 or 20 h post infection, respectively, in a murine skin wound infection. CONCLUSIONS: Enzymatically-crosslinked gelatin hydrogels loaded with paenipeptin analogue 1 and clarithromycin exhibited potent therapeutic efficacy against carbapenem-resistant A. baumannii in murine skin wound infection.

Simultaneous screening of dietary supplements for 25 anti-hyperlipidemic substances using ultra-performance liquid chromatography and liquid chromatography/electrospray ionization tandem mass spectrometry.

RATIONALE: Recently, illegal dietary supplements containing unauthorized compounds have been seized and internationally publicized with a warning to avoid their consumption. This adulteration can be a serious threat to public health because of insufficient and reliable safety data as well as their undesirable side effects. It is, therefore, essential to rapidly and accurately develop and simultaneously validate analytical methods for these unauthorized anti-hyperlipidemic substances. METHODS: Dietary supplements were screened simultaneously for 25 anti-hyperlipidemic drugs using an ultra-high-performance liquid chromatography (UPLC) system with a photodiode array (PDA) detector and LC/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). The method validation, according to ICH guidelines, considered specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, matrix effects, and stability for solid and liquid blank samples. The established UPLC-PDA and LC/ESI-MS/MS methods were applied to screen 103 dietary supplements for 25 anti-hyperlipidemic substances. RESULTS: Using the validated methods, the screened samples were found to contain peaks with similar retention times and PDA spectra. By comparing the calculated precursor-product ion ratios with those of standards, lovastatin and lovastatin acid were detected at concentrations from LOQ to 4.12 mg/g and LOQ to 9.65 mg/g, respectively. CONCLUSIONS: The developed UPLC-PDA and LC/ESI-MS/MS analytical methods were applied to 103 real samples, of which 13 samples were found to contain lovastatin and lovastatin acid. In view of the increasing demand for dietary supplements in the treatment of hyperlipidemic diseases, widespread use of these methods will contribute to consumer health by ensuring the safety of dietary supplements.

Paenipeptin Analogues Potentiate Clarithromycin and Rifampin against mcr-1-Mediated Polymyxin-Resistant Escherichia coli In Vivo.

Polymyxin resistance mediated by the mcr-1 gene threatens the last-resort antibiotics. Linear lipopeptide paenipeptin analogues 1 and 15 disrupted the outer membrane of Gram-negative pathogens and potentiated clarithromycin and rifampin against mcr-1-positive Escherichia coli from the FDA-CDC Antimicrobial Resistance Isolate Bank. In the presence of paenipeptin, clarithromycin and rifampin resulted in over 3-log reduction of E. coliin vitro Moreover, paenipeptin-antibiotic combinations significantly reduced E. coli in a murine thigh infection model.

Detection and Discrimination of DNA Adducts Differing in Size, Regiochemistry, and Functional Group by Nanopore Sequencing.

Chemically induced DNA adducts can lead to mutations and cancer. Unfortunately, because common analytical methods (e.g., liquid chromatography-mass spectrometry) require adducts to be digested or liberated from DNA before quantification, information about their positions within the DNA sequence is lost. Advances in nanopore sequencing technologies allow individual DNA molecules to be analyzed at single-nucleobase resolution, enabling us to study the dynamic of epigenetic modifications and exposure-induced DNA adducts in their native forms on the DNA strand. We applied and evaluated the commercially available Oxford Nanopore Technology (ONT) sequencing platform for site-specific detection of DNA adducts and for distinguishing individual alkylated DNA adducts. Using ONT and the publicly available ELIGOS software, we analyzed a library of 15 plasmids containing site-specifically inserted O6- or N2-alkyl-2'-deoxyguanosine lesions differing in sizes and regiochemistries. Positions of DNA adducts were correctly located, and individual DNA adducts were clearly distinguished from each other.

Simultaneous separation and determination of 20 potential adulterant antigout and antiosteoporosis pharmaceutical compounds in herbal food products using LC with electrospray ionization MS/MS and LC with quadrupole-time-of-flight MS.

An analytical method for the simultaneous and reliable determination of 20 antigout and antiosteoporosis pharmaceutical compounds in adulterated health food products was developed using liquid chromatography with electrospray ionization tandem mass spectrometry and liquid chromatography with quadrupole-time-of-flight mass spectrometry. The method was validated through the determination of specificity, linearity, limit of detection, and limit of quantification, method detection limit, method quantitation limit, precision, accuracy, recovery, and stability. The matrix effect was also determined. The validation results of the developed method are as follows: for solid and liquid blank samples, limits of detection ranged from 0.05 to 5.00 ng/mL and limits of quantification ranged from 0.15 to 15.00 ng/mL. Linearity was acceptable, and the correlation coefficients (R2 ) were ≥0.99 for all target compounds. Both intra and interday precision were less than 9.16% RSD, and accuracies ranged from 95.31 to 116.68%. Mean recoveries for different types of dietary supplements classified as powders, liquids, tablets, and capsules were found to be 80.81 to 117.62% with less than 15.00% relative standard deviation. The stability of the standard mixture solution was less than 11.72% relative standard deviation after 48 h. By the proposed method, the presence of dexamethasone was determined in seized herbal food products at concentrations that ranged from 126 to 215 µg/g.

Novel linear lipopeptide paenipeptin C' binds to lipopolysaccharides and lipoteichoic acid and exerts bactericidal activity by the disruption of cytoplasmic membrane.

BACKGROUND: There is an urgent need to develop potent antimicrobials for the treatment of infections caused by antibiotic-resistant bacterial pathogens. Paenipeptin C' (C8-Pat) is a novel linear lipopeptide recently discovered by our group. The objectives of this study were to determine the time-kill kinetics of paenipeptin C' against Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 29213 and to investigate its mechanism of action. RESULTS: Paenipeptin C' was synthesized by solid-phase peptide synthesis and purified by HPLC to homogeneity. Paenipeptin C' showed concentration-dependent bactericidal activity against P. aeruginosa and S. aureus. Purified lipopolysaccharides (LPS) from the outer membrane of Gram-negative bacteria and lipoteichoic acid (LTA) from Gram-positive bacteria significantly decreased the antibacterial activity of paenipeptin C', which indicated that LPS and LTA on cell surfaces are likely the initial binding targets of this antibiotic agent. Moreover, paenipeptin C' damaged bacterial cytoplasmic membranes, as evidenced by the depolarization of membrane potential and leakage of intracellular potassium ions. Specifically, paenipeptin C' at 32-64 µg/mL caused a significant membrane potential depolarization in P. aeruginosa and S. aureus. This antibiotic at 64-128 µg/mL rapidly induced the release of intracellular potassium ions from P. aeruginosa and S. aureus. Transmission electron microscopy imaging results showed that paenipeptin C' at bactericidal concentrations perturbed the cell envelopes, leading to the loss of intracellular contents. CONCLUSIONS: Therefore, paenipeptin C' exerts its bactericidal effect through damaging bacterial cytoplasmic membrane.

Lipopeptide Paenipeptin Analogues Potentiate Clarithromycin and Rifampin against Carbapenem-Resistant Pathogens.

Two paenipeptin analogues at 4 µg/ml potentiated clarithromycin and rifampin against carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae strains. The combined treatment significantly increased their antibacterial efficacy in a microbiological medium and in human serum in vitro at therapeutically relevant concentrations. Moreover, these two paenipeptin analogues showed low cytotoxicity against a human kidney cell line. Therefore, combination therapy with paenipeptins may be an option for the treatment of antibiotic-resistant bacterial infections.

Antioxidant and anticancer effects of functional peptides from ovotransferrin hydrolysates.

BACKGROUND: Egg white is a good source for making functional peptides that can be used in the food industry. Ovotransferrin (OTF) is one of the major egg white proteins, with many functional properties, including antioxidant, antimicrobial and antiviral activities. However, enzymatic hydrolysis of ovotransferrin is known to further improve the functional activities of OTF. The aim of this study was to investigate the antioxidant and anticancer activities of functional peptides produced by two-step enzyme hydrolysis of OTF. RESULTS: OTF hydrolysates were prepared using promod 278P, thermolysin and a combination of the two enzymes. OTF and OTF hydrolysates showed strong antioxidant activities when analyzed using the DPPH assay. However, only OTF hydrolysates showed a strong free radical scavenging activity when NO- or ABTS-scavenging activity was measured. OTF hydrolysates showed stronger cytotoxic activities than the natural OTF against human cancer cell lines. Furthermore, OTF hydrolysates prepared with promod 278P + thermolysin combination showed the strongest cytotoxic activity, and their IC50 values were 0.79, 0.78, 0.92 and 0.78 mg mL-1 against AGS, LoVo, HT-29 and HeLa, respectively. CONCLUSION: These results indicated that the two-step enzyme hydrolysates of OTF have great potential for use as a food ingredient with antioxidant and anticancer activities. © 2017 Society of Chemical Industry.

Effect of Dietary Beta-Glucan on the Performance of Broilers and the Quality of Broiler Breast Meat.

A total of 400, one day-old commercial broiler chicks were divided into five diet groups (negative control, positive control group with 55 ppm Zn-bacitracin, 15 ppm ß-glucan, 30 ppm ß-glucan, and 60 ppm ß-glucan) and fed for six weeks. Ten broilers were allotted to each of 40 floor pens. Eight floor pens were randomly assigned to one of the 5 diets. Each diet was fed to the broilers for 6 weeks with free access to water and diet. The survival rate, growth rate, feed efficiency, and feed conversion rate of the broilers were calculated. At the end of the feeding trial, the birds were slaughtered, breast muscles deboned, and quality parameters of the breast meat during storage were determined. The high level of dietary ß-glucan (60 ppm) showed better feed conversion ratio and survival rate than the negative control. The survival rate of 60 ppm ß-glucan-treated group was the same as that of the antibiotic-treated group, which showed the highest survival rate among the treatments. There was no significant difference in carcass yield, water holding capacity, pH, color, and 2-thiobarbituric acid reactive substances values of chicken breast meat among the 5 treatment groups. Supplementation of 60 ppm ß-glucan to broiler diet improved the survival rate and feed conversion rate of broilers to the same level as 55 ppm Zn-bacitracin group. The result indicated that use of ß-glucan (60 ppm) can be a potential alternative to antibiotics to improve the survival and performance of broilers. However, dietary ß-glucan showed no effects on the quality parameters of chicken breast meat.

In vitro antioxidant and mineral-chelating properties of natural and autocleaved ovotransferrin.

BACKGROUND: Egg white proteins can be excellent substrates for the development of functional foods and nutraceuticals. In this study, several in vitro antioxidant methods, namely the ß-carotene linoleate model system, the ferric thiocyanate method, the 2-thiobarbituric acid-reactive substances (TBARS) method and copper/calcium ion chelation, were used to determine the antioxidant capacity of natural and autocleaved ovotransferrin. RESULTS: Autocleaved ovotransferrin was prepared by reducing natural ovotransferrin with tris(2-carboxyethyl)phosphine (TCEP) for 6 h at 37 °C. Autocleaved ovotransferrin suppressed the discoloration of ß-carotene effectively and prevented the oxidation of linoleic acid during 5 days of storage at 4 °C. However, the concentration of autocleaved ovotransferrin had no influence on its antioxidant effect. Similarly, the highest TBARS values were obtained from autocleaved ovotransferrin (>90%) and the lowest value in natural ovotransferrin (24%) during incubation at 37 °C for 48 h. The hydrolysates obtained from autocleaved ovotranferrin showed better copper/calcium-solublilizing activity than those from natural ovotransferrin. CONCLUSION: The results indicated that autocleaved ovotransferrin has the potential to be used as a natural antioxidant in foods.

Cytotoxic and antigenotoxic activities of phosvitin from egg yolk.

Egg yolk phosvitin is one of the most phosphorylated proteins in nature, and thus has a strong metal-binding ability. The objective of this study was to evaluate the cytotoxic and antigenotoxic activities of phosvitin in vitro. Using the 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of phosvitin was evaluated in human cancer cell lines of various tissue origins, including the cervix (HeLa), breast (MCF-7), stomach (AGS), lung (A549 and SK-MES-1), liver (HepG2), and larynx (Hep-2). The growth of all cancer cell lines was inhibited in a dose-dependent manner by phosvitin. Among the cancer cell lines tested, MCF-7 and SK-MES-1 were the least sensitive and HeLa, AGS, and HepG2 were the most sensitive to phosvitin. The 50% inhibition of cell viability values of phosvitin were 5.38, 11.57, 4.78, 6.98, 11.82, 3.93, and 9.97 mg/mL for HeLa, MCF-7, AGS, A549, SK-MES-1, HepG2, and Hep-2, respectively. The protective effects of phosvitin against DNA damage in human leukocytes indicated that phosvitin showed protective effects against the oxidative stress-induced DNA damages in human leukocytes. These results suggested that phosvitin has a high potential to be used as an anticancer agent for humans.

Development of a Competency-Based Triage Education Application and Usability Testing for Triage Training Based on the Korean Triage and Acuity Scale.

BACKGROUND: Improving the quality of emergency nursing care requires enhancing triage competency through education programs that integrate the content of the Korean Triage and Acuity Scale, a triage system specifically developed for the Korean context. Thus, this study developed a competency-based triage education application (CTEA), based on the Korean Triage and Acuity Scale, and evaluated its effectiveness through usability testing. METHOD: The CTEA used various teaching methods and game mechanisms, including lectures, case studies, and video-based scenarios, to improve triage competency. RESULTS: In the usability testing phase, the CTEA was refined through expert heuristic evaluation and user interviews conducted with the think-aloud method. Six themes were derived from the interviews, highlighting the need for a well-structured program with realistic scenarios, easy accessibility, gamification, functional improvements, and future triage educational applications. CONCLUSION: These findings suggest that the CTEA is effective and satisfactory for users and can contribute to improving the triage competency of emergency nurses. [J Contin Educ Nurs. 2024;55(1):33-41.].

Enhancing ACLS training effects through video-assisted boosting methods: A comparative analysis of self-simulation and model simulation videos.

AIMS: To assess the impact of learner-participation and instructor-led simulation videos on nurses' CPR skills, focusing on iterative learning to boost proficiency in ACLS. BACKGROUND: Advanced cardiac life support (ACLS) training is crucial for nurses, especially to improve cardiopulmonary resuscitation (CPR) proficiency, for which an effective training strategy is needed. DESIGN: A quasi-experimental, pretest-posttest design was implemented to assess the impact of self-simulation and model simulation videos on sustaining CPR education. METHODS: The research was carried out at a university hospital in Korea from August 2021 to July 2022. A total of 110 nurses were allocated into three groups based on the building of their workplace in the hospital. Each group watched training videos at 4-month intervals after the simulation training. The self-video group viewed simulations featuring their participation, while the model video group watched instructor-led simulations. A comparison group participated in the simulations without subsequent video boosting. RESULTS: Both the self-video and model video groups exhibited significantly superior ACLS performance compatred with the comparison group at both four months (H = 70.33, p <.001) and eight months (H = 81.52, p <.001) following the intervention, with large effect sizes (self-video vs. comparison: d = 4.73 at four months, d = 12.54 at eight months; model video vs. comparison: d = 4.53 at four months, d = 11.01 at eight months). ACLS knowledge scores also significantly increased over time in both intervention groups (self-video: χ² = 22.09, p <.001; model video: χ² = 24.13, p <.001), but not in the comparison group (χ² = 3.75, p =.153). There were no significant differences among the groups in terms of CPR self-efficacy or stress at either time point. CONCLUSION: Supplementary training using simulation videos is an effective method for maintaining and enhancing nurses' ACLS competency, offering a sustainable approach to repetitive CPR training. This study underscores the value of incorporating recorded simulation videos in clinical training, offering insights into efficient methods for continuous learning and CPR proficiency among nursing professionals.

Enhancing triage accuracy in emergency nurses: The impact of a game-based triage educational app.

INTRODUCTION: Digital technology has enabled gamification methods to enhance triage education, reflecting an evolving healthcare landscape. OBJECTIVE: To evaluate the effectiveness of a Gamification Triage Education App (GTEA) as a learning tool for emergency nurses, with a focus on creating an engaging and educationally effective platform for triage training. METHOD: The GTEA was developed using no-code based software and expanded upon previous iterations, with added features such as points, rankings, instant feedback, and quest-based stories. From December 2021 to March 2022, 27 emergency room nurses from three hospitals in Korea were instructed to use GTEA for 100 min over the course of a week. The effects were measured before and after the intervention. RESULTS: The results demonstrated a significant increase in triage accuracy from 4.3 ± 2.00 to 5.33 ± 1.47 (t = -2.18, p = 0.039), along with a substantial reduction in overtriage (t = 3.11, p = 0.004). Additionally, increases in critical thinking disposition, triage competency, and triage knowledge were observed (t = -3.11, p = 0.004; t = -2.72, p = 0.011; t = -3.14, p = 0.004, respectively). CONCLUSIONS: The findings provide robust evidence for the effectiveness of gamification in triage training within emergency nursing.

Exploring the impact of the mentoring new nurses for transition and empowerment program led by clinical nurse educators in South Korea: A mixed-methods study.

BACKGROUND: "New nurses" are those with less than a year of work experience at a hospital. To address the challenges of new nurses caused by their limited experience, the Mentoring New Nurses for Transition and Empowerment Program (MNTEP) was designed based on the Stress-Appraisal-Coping Model of Lazarus and Folkman. OBJECTIVES: This study aimed to explore the impact of the MNTEP, in which clinical nurse educators teach stress-coping strategies, on the clinical transition of new nurses in South Korea. DESIGN: This study used a mixed-methods design with a pretest-posttest non-equivalent comparison group and focus group interviews (FGIs). SETTINGS: The research was conducted at a hospital in South Korea. PARTICIPANTS: The intervention and comparison groups comprised 30 and 28 new nurses, respectively. Also, 12 MNTEP participants were subjected to three separate FGIs. METHODS: To comprehensively assess the program's effects, quantitative data were collected through self-report surveys, while qualitative data were obtained from March 2022 to March 2023 using semi-structured interviews that allowed for open-ended responses. RESULTS: There were significant differences in mean self-efficacy scores (t = 2.45, p = 0.017) and perceived social support from clinical nurse educators (F = 4.51, p = 0.038) between the intervention and comparison groups. Additionally, significant changes were observed in the field adaptation pre-test and post-test scores within the intervention group (t = -3.12, p = 0.004). However, there was no statistically significant difference between the groups in terms of active and passive coping strategies. FGIs yielded two main themes: (1) gaining positive energy through empowerment and solidarity; and (2) clinical nurse educators sharing strategies for improved role adaptation and capacity building. CONCLUSIONS: MNTEP led by clinical nurse educators positively influenced new nurses' self-efficacy and facilitated their transition to clinical settings. These findings underscore the importance of mentorship programs and clinical nurse educators.

Cefiderocol Resistance in Klebsiella pneumoniae Is Linked to SHV Extended-Spectrum ß-Lactamase Activities and Functional Loss of the Outer Membrane Porin OmpK35.

Klebsiella pneumoniae AR 0047 from the CDC and FDA Antibiotic Resistance Isolate Bank is resistant to cefiderocol, a siderophore-conjugated cephalosporin. Genomics analysis and genetic complementation revealed that a frameshift mutation in ompK35 contributed to cefiderocol resistance. Heterologous expression of blaSHV-5 or blaSHV-12 in Escherichia coli increased the host resistance to cefiderocol. Moreover, avibactam, a ß-lactamase inhibitor, enhanced cefiderocol activity against the resistant strain. Therefore, cefiderocol resistance is linked to SHV and the loss of ompK35. IMPORTANCE Understanding cefiderocol resistance mechanisms is essential for providing solutions to treat infections and to prevent resistance development. Cefiderocol resistance in Klebsiella pneumoniae AR 0047 is linked to SHV ß-lactamase activities and functional loss of outer membrane porin. The cefiderocol-avibactam combination represents an opportunity to increase potency against cefiderocol-resistant pathogens.

A Lesson from a Measles Outbreak among Healthcare Workers in a Single Hospital in South Korea: The Importance of Knowing the Prevalence of Susceptibility.

BACKGROUND: Despite the high vaccination coverage rate, in-hospital transmission of measles continues to occur in South Korea. We present a measles outbreak in which two healthcare workers (HCWs) with presumptive evidence of measles immunity were infected by a patient with typical measles at a single hospital in South Korea. This facilitated the evaluation of measles seroprevalence in all HCWs. METHODS: In 2018, suspected patients and contacts exposed during a measles outbreak were investigated based on their medical histories and vaccination status. Cases were confirmed by the detection of measles-specific immunoglobulin M or RNA. After the measles outbreak in 2018, measles IgG testing was conducted on a total of 972 HCWs for point-prevalence, including those exposed to the measles. In addition, we have routinely performed measles IgG tests on newly employed HCWs within one week of their hire date since 2019. The measles vaccine was administered to HCWs who tested negative or equivocally negative for IgG antibodies. RESULTS: An index patient who returned from China with fever and rash was diagnosed with measles at a hospital in Korea. Two additional HCWs were revealed as measles cases: one was vaccinated with the two-dose measles-mumps-rubella (MMR) vaccine, and the other, who was born in 1967, was presumed to have immunity from natural infection in South Korea. All three patients harbored the same D8 genotype. No additional measles cases were identified among the 964 contacts of secondary patients. A total of 2310 HCWs, including those tested during the 2018 outbreak, underwent measles IgG tests. The average age at the time of the test was 32.6 years, and 74.3% were female. The overall seropositivity of measles was 88.9% (95% confidence interval, 87.5-90.1). Although the birth cohorts between 1985 and 1994 were presumed to have received the measles-rubella (MR) catch-up vaccination in 2001, 175 (89.3%) HCWs were born after 1985 among the 195 seronegative cases. CONCLUSION: Despite high population immunity, imported measles transmission occurred among HCWs with presumed immunity. This report underscores the importance of understanding the prevalence of measles susceptibility among newly employed HCWs. This is important for policymaking regarding hospital-wide vaccinations to prevent the spread of vaccine-preventable diseases.