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1.
Plants (Basel) ; 13(17)2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39274007

RESUMEN

Preharvest fruit drop is one of the main challenges in apple production as it can lead to extensive crop losses in commercially important cultivars including 'Honeycrisp'. Plant growth regulators, such as aminoethoxyvinylglicine (AVG) and 1-methylcyclopropene (1-MCP), which hinder ethylene biosynthesis and perception, respectively, can control preharvest fruit drop, but an assessment of their effects in 'Honeycrisp' fruit grown under US mid-Atlantic conditions is lacking. In this study, we evaluated the effects of AVG (130 mg a.i. L-1) and 1-MCP (150 mg a.i. L-1) on preharvest fruit drop, ethylene production, fruit physicochemical parameters, skin color, and transcript accumulation of ethylene and anthocyanin-related genes in 'Honeycrisp' apples throughout on-the-tree ripening. We showed that both AVG and 1-MCP significantly minimized preharvest fruit drop with respect to the control fruit. Additionally, AVG was the most effective in decreasing ethylene production, downregulating ethylene biosynthesis and perception-related gene expression, and delaying fruit maturity. Nevertheless, AVG negatively impacted apple red skin color and exhibited the lowest expression of anthocyanin-biosynthesis-related genes, only allowing apples to reach the minimum required 50% blush at the last ripening stage. Conversely, 1-MCP-treated fruit displayed an intermediate behavior between AVG-treated and control fruit, decreasing ethylene production rates and the associated gene expression as well as delaying fruit maturity when compared to the control fruit. Remarkably, 1-MCP treatment did not sacrifice red skin color development or anthocyanin-biosynthesis-related gene expression, thus exhibiting > 50% blush one week earlier than AVG.

3.
Am J Public Health ; : e1-e4, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39197140

RESUMEN

In 2021, the Maricopa County Department of Public Health in Maricopa County, Arizona, modified its subcontracting process to engage more community-based organizations that serve populations disproportionately affected by COVID-19. The change allowed subrecipients to receive 40% of grant funding up front. An evaluation found that providing up-front funding engaged smaller-budget organizations. However, factors such as administrative requirements and formal policies associated with government partnerships limited the perceived benefits of up-front funding. These findings are relevant for entities seeking to improve access to federal funding. (Am J Public Health. Published online ahead of print August 28, 2024:e1-e4. https://doi.org/10.2105/AJPH.2024.307740).

4.
J Infect Dis ; 230(Supplement_1): S82-S86, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140718

RESUMEN

Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted by Ixodes spp ticks. The rise in Lyme disease cases since its discovery in the 1970s has reinforced the need for a vaccine. A vaccine based on B burgdorferi outer surface protein A (OspA) was approved by the Food and Drug Administration (FDA) several decades ago, but was pulled from the market a few years later, reportedly due to poor sales, despite multiple organizations concluding that it was safe and effective. Newer OspA-based vaccines are being developed and are likely to be available in the coming years. More recently, there has been a push to develop vaccines that target the tick vector instead of the pathogen to inhibit tick feeding and thus prevent transmission of tick-borne pathogens to humans and wildlife reservoirs. This review outlines the history of Lyme disease vaccines and this movement to anti-tick vaccine approaches.


Asunto(s)
Borrelia burgdorferi , Ixodes , Vacunas contra Enfermedad de Lyme , Enfermedad de Lyme , Enfermedad de Lyme/prevención & control , Enfermedad de Lyme/inmunología , Humanos , Animales , Borrelia burgdorferi/inmunología , Vacunas contra Enfermedad de Lyme/inmunología , Ixodes/microbiología , Vacunación , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Antígenos de Superficie/inmunología , Lipoproteínas/inmunología
5.
JAMA Neurol ; 81(9): 996-999, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39037821

RESUMEN

Importance: Epilepsy is a highly treatable condition for many people, but there are large treatment gaps with suboptimal seizure control in minoritized groups. The sexual and gender minority (SGM) community is at risk for health disparities, yet the burden of epilepsy in this community is not known. Objective: To estimate the prevalence of active epilepsy among SGM people in the United States. Design, Setting, and Participants: This was a cross-sectional, nationally representative survey study of community-dwelling US adults who answered questions about epilepsy, sexual orientation, and gender identity in the 2022 National Health Interview Survey (NHIS). Exposure: Self-identification of transgender or gender-diverse identity, or sexual orientation including gay, lesbian, bisexual, or other orientation, excluding straight (ie, heterosexual). Main Outcomes and Measures: Participants self-reported epilepsy status, medical treatment, seizure frequency, demographic characteristics, sexual orientation, and gender identity. Logistic regression was used to estimate the association of epilepsy with SGM identification. Results: A total of 27 624 participants (15 050 [54%] women; 3231 [12%] Black; mean [SD] age, 48.2 [18.5] years) completed the NHIS and were included. Active epilepsy was present in 1.2% (95% CI, 1.0%-1.3%) of the population. A higher proportion of SGM adults than non-SGM adults reported active epilepsy (2.4% [95% CI, 1.4%-3.3%] vs 1.1% [95% CI, 1.0%-1.3%], respectively). After adjusting for age, race, ethnicity, income, and education, SGM people were more than twice as likely to report active epilepsy than were non-SGM adults (adjusted odds ratio, 2.14; 95% CI, 1.35-3.37). Conclusions and Relevance: The findings suggest that SGM adults in the United States have a disproportionate prevalence of epilepsy. The reasons for this disparity are likely complex and may be associated with biological and psychosocial determinants of health unique to this population; as such, these individuals are in need of protected access to medical care.


Asunto(s)
Epilepsia , Minorías Sexuales y de Género , Humanos , Epilepsia/epidemiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Prevalencia , Minorías Sexuales y de Género/estadística & datos numéricos , Estudios Transversales , Estados Unidos/epidemiología , Adulto Joven , Anciano , Adolescente , Encuestas Epidemiológicas
6.
Contemp Clin Trials ; 145: 107642, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39079613

RESUMEN

BACKGROUND: Symptoms of depression and anxiety are prevalent among adults with chronic health conditions, contributing to reduced quality of life, morbidity, and mortality. Mind-body wellness interventions (i.e. psychology programming, mindful movement, breathwork, meditation) may impact mental health symptoms, with online delivery offering access and scalability. Whether online mind-body wellness interventions are effective in improving patient outcomes across a broad range of chronic conditions remains uncertain. METHODS: This three-armed, pragmatic, randomized controlled trial will use a nested mixed methods approach to assess the effectiveness of an online mind-body wellness intervention (eMPower), offered at two levels of personnel support, on symptoms of anxiety and depression in adults with chronic health conditions. Inclusion criteria require a self-reported chronic condition and access to an internet-connected device. Eligible participants will be randomized 1:1:1 to [1] waitlist control; [2] eMPower; [3] eMPower + weekly 1-to-1 check-in. The primary analysis will compare the Hospital and Anxiety Depression Scale (HADS) total score between eMPower + weekly 1-to-1 check-in versus controls, with secondary and exploratory outcomes including HADS subscales, health-related quality of life, fatigue, program engagement, and frailty. CONCLUSION: With online intervention delivery, a range of outcomes, mixed method evaluation, and automated intervention tracking, findings are anticipated to enhance our understanding of how individuals living with chronic health conditions engage with and are impacted by online mind-body wellness programming. Six hundred and fifty-six participants have been enrolled as of April 5, 2024, and 598 patients have completed 12-week follow-up.


Asunto(s)
Ansiedad , Depresión , Terapias Mente-Cuerpo , Calidad de Vida , Humanos , Enfermedad Crónica/psicología , Terapias Mente-Cuerpo/métodos , Depresión/terapia , Depresión/psicología , Ansiedad/terapia , Ansiedad/psicología , Adulto , Intervención basada en la Internet , Atención Plena/métodos , Femenino , Masculino , Meditación/métodos
7.
JAMA Netw Open ; 7(7): e2421102, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38990572

RESUMEN

Importance: The Centers for Medicare & Medicaid Services Innovation Center Independence at Home (IAH) demonstration, a test of home-based primary care operating in a value-based shared-savings payment model, ended December 2023 after a decade of consistently showing savings to Medicare. It is important to assess whether high-need, IAH-qualified beneficiaries continue to pose a growing challenge to traditional Medicare (TM) or if Medicare Advantage (MA), with programmatic features favorable to caring for this subset of the general Medicare population, can disproportionately provide such care. Objective: To examine the size and share of IAH-qualified beneficiaries in TM and MA. Design, Setting, and Participants: This cohort study used all Medicare claims data and MA encounter data for 2014 and 2021. IAH qualifying criteria were applied to the TM populations enrolled in Parts A and B in 2014 and 2021, and to MA enrollees in 2021. Growth in the number of IAH-qualified TM beneficiaries from 2014 to 2021 was calculated, and the proportions and numbers of IAH-qualified enrollees in the total 2021 TM and MA populations were compared. Data were analyzed between April and June 2023. Main Outcomes and Measures: The number and share of beneficiaries meeting IAH criteria in TM and MA; the share of TM spending among IAH-qualified beneficiaries. Results: Among 64 million Medicare beneficiaries in 2021, there were 30.55 million beneficiaries in TM with Parts A and B coverage, down from 33.82 million in 2014. The number of IAH-qualified beneficiaries in TM grew 51%, from 2.16 million to 3.27 million, while their proportionate share in TM grew 67% from 6.4% to 10.7% of TM between 2014 and 2021. IAH-qualified beneficiaries represented $155 billion in 2021 Medicare Parts A and B spending, 44% of all TM spending, up from 29% of total spending in 2014. In 2021, 2.15 million IAH-qualified beneficiaries represented 8.0% of Medicare Advantage enrollees. Combining TM and MA, 5.42 million IAH-qualified beneficiaries represented 9.3% of all Medicare beneficiaries, with 3.27 million (60.3%) being insured by TM. Conclusions and Relevance: In this cohort study of IAH-qualified Medicare beneficiaries, the share of IAH-qualified beneficiaries in TM grew between 2014 and 2021, with 60% of Medicare high-need beneficiaries accounting for 44% of TM spending. The Centers for Medicare & Medicaid Services should continue to operate value-based programs like IAH that are specifically designed for these high-needs individuals.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Medicare , Humanos , Estados Unidos , Masculino , Femenino , Anciano , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Servicios de Atención de Salud a Domicilio/economía , Medicare/estadística & datos numéricos , Anciano de 80 o más Años , Estudios de Cohortes , Prevalencia , Atención Primaria de Salud/estadística & datos numéricos , Atención Primaria de Salud/economía , Medicare Part C/estadística & datos numéricos , Medicare Part C/economía
8.
Am J Surg ; 238: 115829, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39024726

RESUMEN

BACKGROUND: Debate continues over chest tube (CT) size for traumatic hemothorax (HTX) and pneumothorax (PTX). We compared CT failure and opioid use between large-bore chest tubes (LB-CT) and small-bore chest tubes (SB-CT). METHODS: A retrospective study comparing trauma patients with SB-CT (≤14Fr) or LB-CT (≥24Fr) was performed. CT failure includes HTX, PTX, or empyema requiring intervention. Secondary outcomes included opioid use (MME), mortality, and favorable discharge. RESULTS: Of 252 patients, 65.1 â€‹% had SB-CT. SB-CT were older with lower ISS. Failure rate was lower for SB-CT (9.2 vs 22.7 â€‹%, p â€‹= â€‹0.003), as was opioid use (332 vs 767, p â€‹< â€‹0.001). In adjusted analysis there was no difference in CT failure between SB-CT and LB-CT. Subgroup analysis found SB-CT had lower total MME (234 vs 342, p â€‹= â€‹0.018). CONCLUSIONS: This study found no major differences in CT failure or opioid use by CT size, suggesting SB-CT are a safe, and effective alternative to LB-CT in trauma.

9.
Cell ; 187(15): 4113-4127.e13, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38876107

RESUMEN

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.


Asunto(s)
Interacciones Huésped-Patógeno , Humanos , Animales , Enfermedad de Lyme/microbiología , Enfermedades Transmitidas por Vectores , Interacciones Microbiota-Huesped , Borrelia burgdorferi/patogenicidad , Borrelia burgdorferi/metabolismo
10.
PLoS One ; 19(6): e0303894, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38941338

RESUMEN

OBJECTIVE: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented. METHODS: Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants. RESULTS: Study is ongoing and open to enrollment. CONCLUSION: The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.


Asunto(s)
Demencia , Terapia Electroconvulsiva , Agitación Psicomotora , Humanos , Terapia Electroconvulsiva/métodos , Agitación Psicomotora/terapia , Demencia/terapia , Demencia/complicaciones , Método Simple Ciego , Femenino , Masculino , Resultado del Tratamiento , Anciano , Conducta Motora Aberrante en la Demencia
11.
Neurol Clin Pract ; 14(5): e200354, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38919934
12.
Psychol Serv ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842851

RESUMEN

Rural women veterans are less likely than men and nonrural veterans to access Veterans Health Administration (VHA) care. This qualitative study describes rural women veterans' barriers to accessing care and explores whether participants viewed a peer specialist intervention as having the potential to facilitate access to care. We recruited rural veterans who identified as women with psychological distress and social needs, women peer specialists, and VHA primary care professionals working with rural veterans. We conducted two veteran focus groups, two peer specialist focus groups, and 11 individual Patient Aligned Care Team professional interviews using semistructured interview questions. One of the veteran focus groups was exclusive to veterans of color. We used a rapid qualitative data analysis approach to analyze the results. Data analysis revealed barriers affecting perceived access to services for rural women veterans, especially veterans of color, including transportation, finances, childcare, long travel distance to clinics, lack of access to gender-specific services, ineligibility for services, and lacking information about available resources. Participants also reported challenges accessing community services outside of the VHA. The rural women veterans reported a strong preference for gender-specific services. Leveraging existing VHA resources with rural women veterans may mitigate some of the identified barriers. In particular, participants agreed that increasing availability of peer specialists who are both women and veterans could bridge some perceived barriers to accessing care among rural women veterans. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

13.
J Addict Nurs ; 35(2): 76-85, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38829997

RESUMEN

BACKGROUND: Alcohol use disorder (AUD), the problematic consumption of alcohol, affects 107 million people worldwide. Individuals with AUD experience high morbidity and increased mortality. Nurses practicing in acute care are ideally positioned to deliver quality interventions to patients with AUD, including screening and brief intervention; formal training and assessment of baseline knowledge, attitudes, and perceptions are necessary. AIMS AND OBJECTIVES: The aim of this study was to explore the knowledge, attitudes, and perceptions of acute care nurses caring for patients with AUD. DESIGN: This study used a cross-sectional survey design. METHODS: The Survey of Attitudes and Perceptions was completed by 93 nurses working in six acute care centers (seven medicine units) across Alberta. Data were analyzed using descriptive and inferential statistics. RESULTS: Few participants reported receiving any prior structured training on AUD, with the majority reporting limited knowledge of alcohol and the effects of alcohol consumption. Although most participants said that caring for patients with AUD was a part of their professional role, few felt satisfied or motivated to work with this group of patients. Responses to individual questions or subdomains of the survey did not significantly differ by length of time in professional role, employment status, or sex. CONCLUSION: Our results indicate that nurses need to learn more about caring for patients with AUD. Developing tailored educational interventions that are mindful of the importance of knowledge, support, satisfaction, and motivation is necessary to improve the quality of care for patients with AUD.


Asunto(s)
Alcoholismo , Actitud del Personal de Salud , Humanos , Estudios Transversales , Femenino , Masculino , Adulto , Alcoholismo/enfermería , Alberta , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/psicología
14.
J Psychiatr Res ; 175: 160-169, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38735261

RESUMEN

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors when they discovered and reported to the editors that articles containing population samples drawn from similar cohorts of healthy participants without psychosis were erroneously included in the psychosis subgroup of the meta-analysis. This error in the systematic review processes ultimately affects the findings in the meta-analysis. The authors deeply apologize for this error.

15.
Adv Drug Deliv Rev ; 210: 115344, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38810702

RESUMEN

Brain organoids hold great potential for modeling human brain development and pathogenesis. They recapitulate certain aspects of the transcriptional trajectory, cellular diversity, tissue architecture and functions of the developing brain. In this review, we explore the engineering strategies to control the molecular-, cellular- and tissue-level inputs to achieve high-fidelity brain organoids. We review the application of brain organoids in neural disorder modeling and emerging bioengineering methods to improve data collection and feature extraction at multiscale. The integration of multiscale engineering strategies and analytical methods has significant potential to advance insight into neurological disorders and accelerate drug development.


Asunto(s)
Encéfalo , Organoides , Humanos , Encéfalo/metabolismo , Encéfalo/citología , Animales , Modelos Biológicos , Enfermedades del Sistema Nervioso/patología , Ingeniería de Tejidos/métodos , Bioingeniería/métodos
16.
Clin Pract ; 14(3): 906-914, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38804403

RESUMEN

The Revised Cardiac Risk Index (RCRI) and the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) preoperative risk assessment tools are the most widely used methods for quantifying the risk of major negative perioperative cardiac outcomes that a patient may face during and after noncardiac surgery. However, these tools were created to include as wide a range of surgical factors as possible; thus, some predictive accuracy is sacrificed when it comes to certain surgical subpopulations. In this review, we explore the various surgical oncology patient populations for whom these assessment tools can be reliably applied and for whom they demonstrate poor reliability.

18.
bioRxiv ; 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38559142

RESUMEN

Flexible behavior depends on abstract rules to generalize beyond specific instances, and outcome monitoring to adjust actions. Cortical circuits are posited to read out rules from high-dimensional representations of task-relevant variables in prefrontal cortex (PFC). We instead hypothesized that converging inputs from PFC, directly or via basal ganglia (BG), enable primate-specific thalamus to select rules. To test this, we simultaneously measured spiking activity across PFC and two connected thalamic nuclei of monkeys applying rules. Abstract rule information first appeared in the ventroanterior thalamus (VA) - the main thalamic hub between BG and PFC. The mediodorsal thalamus (MD) also represented rule information before PFC, which persisted after rule cues were removed, to help maintain activation of relevant posterior PFC cell ensembles. MD, a major recipient of midbrain dopamine input, was first to represent information about behavioral outcomes. This persisted after the trial (also in PFC). A PFC-BG-thalamus model reproduced key findings, and thalamic-lesion modeling disrupted PFC rule representations. These results suggest a revised view of the neural basis of flexible behavior in primates, featuring a central role for thalamus in selecting high-level cognitive information from PFC and implementing post-error behavioral adjustments, and of the functional organization of PFC along its anterior-posterior dimension.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38605223

RESUMEN

Perinatal mood and anxiety disorders (PMADs), perinatal substance use disorders (PSUDs), and intimate partner violence (IPV) are leading causes of pregnancy-related deaths in the United States. Screening and referral for PMADs, PSUDs and IPV is recommended, however, racial disparities are prominent: Black pregnant and postpartum people (PPP) are less likely to be screened and attend treatment compared to White PPP. We conducted qualitative interviews to better understand the experience of Black PPP who used a text/phone-based screening and referral program for PMADs/PSUDs and IPV-Listening to Women and Pregnant and Postpartum People (LTWP). We previously demonstrated that LTWP led to a significant reduction in racial disparities compared to in-person screening and referral, and through the current study, sought to identify facilitators of PMAD/PSUD symptom endorsement and treatment attendance. Semi-structured interviews were conducted with 68 Black PPP who were or had been pregnant within the last 24 months, and who either had or did not have a PMAD or PSUD. Participants were enrolled in LTWP and provided feedback on their experience. Using a grounded theory approach, four themes emerged: usability, comfort, necessity, and recommendations. Ease of use, brevity, convenience, and comfort in discussing mental health and substance use via text were highlighted. Need for a program like LTWP in Black communities was discussed, given the reduction in perceived judgement and access to trusted information and resources for PMADs/PSUDs, which may lessen stigma. These qualitative findings illuminate how technology-based adaptations to behavioral health screening and referral can reduce perceived negative judgment and facilitate identification and referral to treatment, thereby more adequately meeting needs of Black PPP.

20.
Clin Infect Dis ; 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630890

RESUMEN

BACKGROUND: The treatment of carbapenem-resistant Acinetobacter baumannii/calcoaceticus complex (CRAB) presents significant treatment challenges. METHODS: We report the case of a 42-year-old woman with CRAB meningitis who experienced persistently positive cerebrospinal fluid (CSF) cultures for 13 days despite treatment with high-dose ampicillin-sulbactam and cefiderocol. On day 13, she was transitioned to sulbactam-durlobactam and meropenem; four subsequent CSF cultures remained negative. After 14 days of sulbactam-durlobactam, she was cured of infection. Whole genome sequencing investigations identified putative mechanisms that contributed to reduced cefiderocol susceptibility observed during cefiderocol therapy. Blood and CSF samples were collected pre-dose and 3-hours post initiation of a sulbactam-durlobactam infusion. RESULTS: The CRAB isolate belonged to sequence type 2. An acquired blaOXA-23 and an intrinsic blaOXA-51-like (i.e., blaOXA-66) carbapenemase gene were identified. The paradoxical effect (i.e., no growth at lower cefiderocol dilutions but growth at higher dilutions) was observed by broth microdilution after 8 days of cefiderocol exposure but not by disk diffusion. Potential markers of resistance to cefiderocol included mutations in the start codon of piuA and piuC iron transport genes and a A515V substitution in PBP3, the primary target of cefiderocol. Sulbactam and durlobactam were detected in CSF at both timepoints, indicating CSF penetration. CONCLUSIONS: This case describes successful treatment of refractory CRAB meningitis with the administration of sulbactam-durlobactam and meropenem and highlights the need to be cognizant of the paradoxical effect that can be observed with broth microdilution testing of CRAB isolates with cefiderocol.

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