Comparison of eravacycline and cefiderocol in the treatment of multidrug-resistant Acinetobacter baumannii infections

Comparison of eravacycline and cefiderocol in the treatment of multidrug-resistant Acinetobacter baumannii infections | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of eravacycline and cefiderocol in the treatment of multidrug-resistant Acinetobacter baumannii infections Justin Halim, Madeline King, Dejan Nikolic, Carlo Foppiano Palacios This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6727622/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A. baumannii is a common cause of drug-resistant hospital-associated infections. Eravacycline and cefiderocol are two recently introduced antibiotics that have demonstrated in vitro activity against drug-resistant A. baumannii , but data regarding the clinical utility of these drugs against multi-drug resistant A. baumannii infections (MDRAI) is lacking. In this study, we performed a retrospective chart review of patients with MDRAI who were treated with cefiderocol or eravacycline to compare clinical outcomes associated with each antibiotic. 40 patients were included, of which 30 patients received cefiderocol, 9 received eravacycline, and 1 received both. We collected data on demographics, risk factors for MDRAI, and infection characteristics. The primary outcomes assessed were hospital mortality rates. Secondary outcomes assessed were readmission rates, ICU admission, shock requiring vasopressors, mechanical intubation, and drug-related adverse events. No significant differences in the primary outcomes of 30-day and 90-day mortality rates were observed between the two groups. Introduction Acinetobacter baumannii is a common cause of drug-resistant hospital-associated infections (HAI) [ 1 ]. A. baumannii poses a significant threat in large part due to its ability to rapidly develop antibiotic resistance via various mechanisms [ 1 ]. Multi-drug resistant A. baumannii infections (MDRAI) are associated with high mortality rates, with crude mortality rates exceeding 50% [ 2 – 3 ]. Until recently, there were limited antimicrobial options for MDRAI due to common resistance against antibiotics typically reserved as last-line agents, particularly carbapenems, colistin, and tigecycline [ 4 ]. As antibiotic resistance rates increase further, there is an urgent need to identify new antibiotics against increasingly drug-resistant strains [ 1 ]. Two new drugs, eravacycline and cefiderocol, were approved by U.S. Food and Drug Administration (FDA) in past 6 years. Eravacycline is a fluorocycline tetracycline and is indicated primarily for treatment of intra-abdominal infection caused by Gram-negative bacteria [ 5 ]. Cefiderocol is a novel siderophore cephalosporin approved for treating hospital-associated bacterial pneumonia and ventilator-associated pneumonia (VAP) caused by Gram-negative bacteria [ 6 – 7 ]. While both are not specifically marketed for treatment of A. baumannii infections, they have demonstrated in vitro activity against drug-resistant A. baumannii , as well as clinical effectiveness in patients with A. baumannii infections [ 8 – 11 ]. However, data comparing the clinical utility of these drugs against MDRAI is lacking. We compared clinical outcomes of patients with MDRAI treated with eravacycline or cefiderocol. Methods Study Population A retrospective chart review of patients with MDRAI was conducted from 2019-2023 at Cooper University Hospital, an academic tertiary care center in Camden, New Jersey. We included patients who received either eravacycline or cefiderocol for treatment of MDRAI. MDR infections were defined as clinical isolates found to have resistance or intermediate susceptibility to either meropenem or ampicillin-sulbactam. Patients were excluded if age less than 18 years old or MDR A. baumannii was not considered causing infection per infectious diseases consultation. Cooper University Hospital Investigational Review Board approved our study. Data Collection Demographics, risk factors for MDRAI (chronic dialysis in the past 30 days, colonization with any resistant organism, home infusion therapy, home wound care, prior antimicrobials in the past 90 days, prior infection with any resistant organism, prior hospitalization in the past 90 days, and prior surgery in the past 90 days), microbiological culture and antimicrobial sensitivity testing, and antibiotic treatment information were obtained. Additionally, we collected data on intensive care unit (ICU) admission, shock requiring vasopressor administration, mechanical intubation, and any drug-related adverse events, including diarrhea, liver function test (LFT) elevation, nausea, rash, or any other reaction, hospital readmission, and death. Data was collected over the period from 6/1/2023-6/1/2024. Outcomes & Statistical Analysis Our primary outcome was hospital mortality. Secondary outcomes included were mortality and re-admission at 30- and 90-days post-discharge, intensive care unit (ICU) admission, shock requiring vasopressor administration, mechanical intubation, and any drug-related adverse events. Demographic and clinical data were summarized with descriptive statistics. Counts and percentages were calculated for categorical variables. While for continuous variables medians and inter-quartile ranges (IQR) were calculated. Chi-square tests were used to assess primary and secondary outcomes and to compare associations between risk factors for candidemia, culture and antifungal susceptibility results, antifungal treatment, and mortality outcomes. Bivariate testing of categorical variables was done with Fisher’s exact test. Statistical testing was performed using R version 4.0.2. A p-value less than 0.05 was considered statistically significant. Results Patient Characteristics 110 patients were found to have had a MDRAI between 2019-2023, of which 40 patients received either eravacycline or cefiderocol. 30 patients received cefiderocol, 9 received eravacycline, and 1 received both drugs. 27 patients received either cefiderocol or eravacycline monotherapy. Among the 40 patients included: median age was 59.5 years (IQR 15.5), 80.0% (N=32/40) were male, 57.5% (N=23/40) were white, and 17. % (N=7/40) were Latinx (Table 1). MDR Acinetobacter Infection 97.5% (N=39/40) of infections were due to a carbapenem-resistant A. baumannii (CRAB) strain. Prior to hospital admission, 38.5% (N=15/40) of patients were admitted from home; 38.5% (N=15/40) were transferred from an outside hospital; and 23.1% (N=9/40) were admitted from a nursing home, skilled nursing facility (SNF), or long-term care facility. All patients had received some form of antibiotic treatment in the past 90 days (N=40). Most patients had been hospitalized in the past 90 days (95.0%, N=38/40), a history of colonization with resistant organisms (87.5%, N=35/40), prior infection with resistant organism (80.0%, N=32/40 or underwent surgery in the past 30 days (55.0%, N=22/40). The most common infections were ventilator-associated pneumonia (47.5%, N=19/40), hospital-acquired pneumonia (20.0%, N=8/40), and soft tissue infection (15.0%, N=6/40). One patient in the cefiderocol group was treated for concomitant A. baumannii and Pseudomonas aeruginosa infections. 13 patients received combination therapy of either cefiderocol or eravacycline with colistin (N=6), tigecycline (N=3), ampicillin-sulbactam (N=2), trimethoprim/sulfamethoxazole (N=2), or tobramycin (N=1). Median length of antibiotic administration was 6.5 days (IQR 6.5). Minimum inhibitory concentration (MIC) values against cefiderocol were determined for 20 strains in the cefiderocol group, of which 17 were susceptible (MIC ≤ 4), one had intermediate susceptibility (MIC >4 and <16), and two were resistant (MIC ≥ 16). No MIC values against eravacycline were available, as reference laboratories were not evaluating eravacycline susceptibility at the time. Mortality and Readmission Outcomes One patient who received both cefiderocol and eravacycline was excluded from further analysis. Patients who received cefiderocol (43.3%) had higher hospital mortality than patients on eravacycline (22.2%, p=0.44). There was no difference with 30-day mortality between cefiderocol and eravacycline groups (p=0.12). 90-day mortality was elevated in the cefiderocol group (53.3%) compared to eravacycline group (22.2%) with p-value approaching significance (p=0.14). Of the three patients in the cefiderocol group with isolates non-susceptible to cefiderocol (one intermediate, two resistant), one patient with an intermediate isolate died during hospitalization, and one patient with a resistant isolate was readmitted within 30 days for a reason unrelated to A. baumannii infection. Hospital readmission at 30- (p=1.0) and 90-days (p=1.0) post discharge were similar between both groups (Table 2). Complications of Acinetobacter Infection Patients treated with cefiderocol were more likely to be admitted to ICU (70.0%) compared to those treated with eravacycline (44.4%, p=0.24). Additionally, cefiderocol group was more likely to have required mechanical intubation than eravacycline group (70.0% vs. 33.3%, p=0.06). Cefiderocol was associated with elevations in liver function tests (LFT), with 60.0% of cefiderocol patients experiencing LFT elevation compared to 11.1% of eravacycline patients (p=0.02). Discussion We sought to compare outcomes among patients with MDRAI receiving eravacycline versus cefiderocol. In our limited cohort, we found no significant differences in mortality between patients receiving eravacycline or cefiderocol for MDRAI. This is the first study to evaluate mortality outcomes between eravacycline or cefiderocol in patients with MDRAI. MDRAI is an emerging infection with rising resistance rates to commonly used antibiotics [ 1 ]. In our cohort, patients receiving cefiderocol were more likely to receive mechanical ventilation than eravacycline but otherwise had similar complications from their MDRAI. No statistically significant difference in the primary mortality outcome was demonstrated between the cefiderocol and eravacycline groups. Prior studies have compared mortality rates in patients treated with cefiderocol and those treated with other antibiotic regimens, primarily colistin-based regimens, with conflicting results [ 11 – 14 ]. In the CREDIBLE-CR trial, patients with carbapenem-resistant Gram-negative infections, including A. baumannii , treated with cefiderocol demonstrated similar rates of infection resolution but higher mortality rates when compared to those treated with the best available therapy (BAT) for Acinetobacter spp. infections. However, these findings may also represent an uneven distribution of patients similar to our findings, as patients treated with cefiderocol demonstrated higher rates of ICU admission and septic shock at randomization [ 12 ]. Conversely, the APEKS-NP trial, published in 2021, found that cefiderocol was non-inferior to meropenem in the treatment of nosocomial pneumonia, with similar mortality rates observed, although A. baumannii infections only comprised 16% of patients studied [ 13 ]. Additionally, a recent retrospective cohort study conducted in Italy found a lower 30-day mortality rate in patients with CRAB bloodstream infections treated with cefiderocol (34%) than in patients treated with standard colistin-based regimens (55.8%, P = 0.018), but this difference was not consistent in patients with VAP [ 11 ]. However, a different retrospective cohort study conducted in Italy in patients with CRAB VAP infections demonstrated a significantly lower 28-day mortality rate in patients treated with cefiderocol-containing regimens compared with non-cefiderocol-containing regimens (44% vs. 67%, P = 0.011) [ 15 ]. Furthermore, a recent meta-analysis including 18 studies (733 patients) comparing cefiderocol with BAT found a significantly lower 30-day mortality rate in the cefiderocol group compared to the BAT group (RR: 0.74; 95% CI: 0.57–0.95, P = 0.02) [ 14 ]. Given the conflicting results, the Infectious Disease Society of America (IDSA) currently advises caution when using cefiderocol to treat CRAB infections that are resistant to other antibiotics. They only recommend its use only in combination with other antibiotics [ 16 ]. It is also important to note that the studies primarily compared cefiderocol with colistin-containing regimens. Although colistin is still utilized for CRAB urinary tract infections, it is generally avoided due to its narrow therapeutic window and high risk for nephrotoxicity [ 17 ]. This emphasizes the necessity for additional clinical studies to compare cefiderocol to other available antibiotic options. There is limited clinical data on the efficacy of eravacycline in treating MDRAI. A recent retrospective report described the treatment of 46 patients with A. baumannii infections, mainly pulmonary infections. It found an overall 30-day mortality rate of 23.9%, and a mortality rate of 21.9% in patients with CRAB infections [ 9 ]. However, a retrospective cohort study comparing eravacycline-based regimens with BAT in patients with MDRAI reported significantly higher 30-day mortality rates in the eravacycline-based regimen group (33% vs. 15%, P = 0.048). The study also noted a significantly longer median duration of mechanical ventilation (10.5 days vs. 6.5 days, P = 0.016) and lower rates of microbiological cure (17% vs. 59%, P = 0.004) in the eravacycline-based regimen group [ 18 ]. Notably, the outcomes for patients with bloodstream infections in the eravacycline-based group was poor; all four patients who received eravacycline monotherapy ultimately died within 30 days. When excluding of patients with bloodstream infections, similar 30-day mortality rates were observed between eravacycline and BAT groups (22% vs. 16%, P = 0.506), raising concerns that eravacycline’s relatively large volume of distribution [ 18 – 19 ]. Our study did not include any cases of bacteremia in the eravacycline group. Due to the lack of clinical data supporting the use of eravacycline against CRAB infections, the IDSA currently recommends limiting its use to cases in which other agents are not effective, cannot be tolerated, or are unavailable [ 16 ]. Currently, IDSA recommends sulbactam/durlobactam as the first-line treatment choice for CRAB infections [ 16 ]. Sulbactam/durlobactam was recently approved by the FDA for the treatment of hospital-acquired pneumonia and VAP following the publication of the ATTACK trial in 2023, which showed sulbactam/durlobactam was non-inferior to colistin in the treatment of CRAB infections [ 20 – 21 ]. On adverse events, cefiderocol showed was a significantly association with higher rates of LFT elevation (60% vs. 11.1%, P = 0.02). It is worth noting that these elevations were mild, and none led to clinically apparent liver injury. Like other cephalosporins, cefiderocol is associated with mild LFT elevation, with previous trials reporting rates of liver-related adverse events ranging from 0.7–29.7% [ 7 ]. There were no significant differences in the prevalence of other adverse events between groups, including nausea, diarrhea, and rash. This study has a few limitations. First, it is important to note that the study is retrospective in nature and the small sample is relatively small. Second, since our study was conducted at a single urban academic center, the generalizability of our findings to other settings may be limited. Additionally, the median treatment duration for patients in both groups was 6.0 days, which was influenced by several patient deaths during the treatment period. Additionally, MIC values were not reported for eravacycline against any isolates, and only 12 isolates for cefiderocol were included, making it challenging to ascertain the susceptible of the causative strain to each drug. Conclusion There is a growing need for effective treatment options for MDRAI. Cefiderocol and eravacycline have displayed potential in combating this difficult pathogen. Our findings reveal no significant disparity between the two antibiotics in the treatment of MDRAI. Nevertheless, additional prospective research is essential for a more comprehensive comparing of these two antibiotics. Declarations Author Contribution JH conceived and designed the study, collected data, contributed to data analysis, and drafted the manuscript. MK and DN contributed to study design, data collection, and manuscript revision. CFP contributed to data collection and manuscript writing, and performed the statistical analysis. All authors reviewed and approved the final manuscript. 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Lancet Infect Dis, 23(9), 1072-1084. https://doi.org/10.1016/s1473-3099(23)00184-6 Tables Table 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1and2.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6727622","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":463403173,"identity":"cbee5f82-b74b-40a7-820a-f26e7f1c766a","order_by":0,"name":"Justin Halim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACAwbmhgMMPP/r++FCBwhqYQRpYWac2UCKFiDFzLgBrpKQFnP2g42HbsiwMRvfPnxM4ucOBjm+Gwn4tVj2JDYczuHhYTM7l5Ym2XuGwViSkBaDA2AtEjxmZ3jMbvC2MSRuIKjl/EOQFgMJ4x4es5t/2xjqCWu5AbYlwcCAh8fsNtCWBAPCWsC2HEiQOMOW/lu2TcJw5pkHhByWfPhzbs+BBP4e5sOGb9ts5PmOE7AFDBh74EwJIpSDwQ9iFY6CUTAKRsGIBACTLUojci9hXQAAAABJRU5ErkJggg==","orcid":"","institution":"Cooper Medical School of Rowan University","correspondingAuthor":true,"prefix":"","firstName":"Justin","middleName":"","lastName":"Halim","suffix":""},{"id":463403174,"identity":"54c3c3dd-4127-4aff-aaee-45a8032c0162","order_by":1,"name":"Madeline King","email":"","orcid":"","institution":"Cooper University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Madeline","middleName":"","lastName":"King","suffix":""},{"id":463403175,"identity":"4c68ccb0-af9f-45bc-b2c0-445c6904ec37","order_by":2,"name":"Dejan Nikolic","email":"","orcid":"","institution":"Cooper University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dejan","middleName":"","lastName":"Nikolic","suffix":""},{"id":463403176,"identity":"5beda1aa-a165-447a-bef0-56181050f01d","order_by":3,"name":"Carlo Foppiano Palacios","email":"","orcid":"","institution":"Cooper University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Carlo","middleName":"Foppiano","lastName":"Palacios","suffix":""}],"badges":[],"createdAt":"2025-05-22 19:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6727622/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6727622/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84986239,"identity":"9d87dab9-a152-49a5-8491-25d3ffed038b","added_by":"auto","created_at":"2025-06-19 14:23:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":403296,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6727622/v1/1090e16c-44ab-4d2c-9a5c-bcc710b63493.pdf"},{"id":83664938,"identity":"574bf038-933a-4684-9ece-a1a4d5e4b0a9","added_by":"auto","created_at":"2025-05-30 11:17:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17367,"visible":true,"origin":"","legend":"","description":"","filename":"Table1and2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6727622/v1/e395f64ede6bcd9b23b300fc.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of eravacycline and cefiderocol in the treatment of multidrug-resistant Acinetobacter baumannii infections","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e is a common cause of drug-resistant hospital-associated infections (HAI) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. \u003cem\u003eA. baumannii\u003c/em\u003e poses a significant threat in large part due to its ability to rapidly develop antibiotic resistance via various mechanisms [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Multi-drug resistant \u003cem\u003eA. baumannii\u003c/em\u003e infections (MDRAI) are associated with high mortality rates, with crude mortality rates exceeding 50% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Until recently, there were limited antimicrobial options for MDRAI due to common resistance against antibiotics typically reserved as last-line agents, particularly carbapenems, colistin, and tigecycline [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As antibiotic resistance rates increase further, there is an urgent need to identify new antibiotics against increasingly drug-resistant strains [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTwo new drugs, eravacycline and cefiderocol, were approved by U.S. Food and Drug Administration (FDA) in past 6 years. Eravacycline is a fluorocycline tetracycline and is indicated primarily for treatment of intra-abdominal infection caused by Gram-negative bacteria [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Cefiderocol is a novel siderophore cephalosporin approved for treating hospital-associated bacterial pneumonia and ventilator-associated pneumonia (VAP) caused by Gram-negative bacteria [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. While both are not specifically marketed for treatment of \u003cem\u003eA. baumannii\u003c/em\u003e infections, they have demonstrated \u003cem\u003ein vitro\u003c/em\u003e activity against drug-resistant \u003cem\u003eA. baumannii\u003c/em\u003e, as well as clinical effectiveness in patients with \u003cem\u003eA. baumannii\u003c/em\u003e infections [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, data comparing the clinical utility of these drugs against MDRAI is lacking. We compared clinical outcomes of patients with MDRAI treated with eravacycline or cefiderocol.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective chart review of patients with MDRAI was conducted from 2019-2023 at Cooper University Hospital, an academic tertiary care center in Camden, New Jersey. We included patients who received either eravacycline or cefiderocol for treatment of MDRAI. MDR infections were defined as clinical isolates found to have resistance or intermediate susceptibility to either meropenem or ampicillin-sulbactam. Patients were excluded if age less than 18 years old or MDR \u003cem\u003eA. baumannii\u003c/em\u003e was not considered causing infection per infectious diseases consultation. Cooper University Hospital Investigational Review Board approved our study. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographics, risk factors for MDRAI (chronic dialysis in the past 30 days, colonization with any resistant organism, home infusion therapy, home wound care, prior antimicrobials in the past 90 days, prior infection with any resistant organism, prior hospitalization in the past 90 days, and prior surgery in the past 90 days), microbiological culture and antimicrobial sensitivity testing, and antibiotic treatment information were obtained. Additionally, we collected data on intensive care unit (ICU) admission, shock requiring vasopressor administration, mechanical intubation, and any drug-related adverse events, including diarrhea, liver function test (LFT) elevation, nausea, rash, or any other reaction, hospital readmission, and death. Data was collected over the period from 6/1/2023-6/1/2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes \u0026amp; Statistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur primary outcome was hospital mortality. Secondary outcomes included were mortality and re-admission at 30- and 90-days post-discharge, intensive care unit (ICU) admission, shock requiring vasopressor administration, mechanical intubation, and any drug-related adverse events. Demographic and clinical data were summarized with descriptive statistics. Counts and percentages were calculated for categorical variables. While for continuous variables medians and inter-quartile ranges (IQR) were calculated. Chi-square tests were used to assess primary and secondary outcomes and to compare associations between risk factors for candidemia, culture and antifungal susceptibility results, antifungal treatment, and mortality outcomes. Bivariate testing of categorical variables was done with Fisher\u0026rsquo;s exact test. Statistical testing was performed using R version 4.0.2. A p-value less than 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e110 patients were found to have had a MDRAI between 2019-2023, of which 40 patients received either eravacycline or cefiderocol. 30 patients received cefiderocol, 9 received eravacycline, and 1 received both drugs. 27 patients received either cefiderocol or eravacycline monotherapy. Among the 40 patients included: median age was 59.5 years (IQR 15.5), 80.0% (N=32/40) were male, 57.5% (N=23/40) were white, and 17. % (N=7/40) were Latinx (Table 1). \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMDR \u003cem\u003eAcinetobacter\u003c/em\u003e Infection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e97.5% (N=39/40) of infections were due to a carbapenem-resistant \u003cem\u003eA. baumannii\u0026nbsp;\u003c/em\u003e(CRAB) strain. Prior to hospital admission, 38.5% (N=15/40) of patients were admitted from home; 38.5% (N=15/40) were transferred from an outside hospital; and 23.1% (N=9/40) were admitted from a nursing home, skilled nursing facility (SNF), or long-term care facility. All patients had received some form of antibiotic treatment in the past 90 days (N=40). Most patients had been hospitalized in the past 90 days (95.0%, N=38/40), a history of colonization with resistant organisms (87.5%, N=35/40), prior infection with resistant organism (80.0%, N=32/40 or underwent surgery in the past 30 days (55.0%, N=22/40). The most common infections were ventilator-associated pneumonia (47.5%, N=19/40), hospital-acquired pneumonia (20.0%, N=8/40), and soft tissue infection (15.0%, N=6/40). One patient in the cefiderocol group was treated for concomitant \u003cem\u003eA. baumannii\u003c/em\u003e and \u003cem\u003ePseudomonas aeruginosa\u0026nbsp;\u003c/em\u003einfections. 13 patients received combination therapy of either cefiderocol or eravacycline with colistin (N=6), tigecycline (N=3), ampicillin-sulbactam (N=2), trimethoprim/sulfamethoxazole (N=2), or tobramycin (N=1). Median length of antibiotic administration was 6.5 days (IQR 6.5). Minimum inhibitory concentration (MIC) values against cefiderocol were determined for 20 strains in the cefiderocol group, of which 17 were susceptible (MIC \u0026le; 4), one had intermediate susceptibility (MIC \u0026gt;4 and \u0026lt;16), and two were resistant (MIC \u0026ge; 16). No MIC values against eravacycline were available, as reference laboratories were not evaluating eravacycline susceptibility at the time. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMortality and Readmission Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne patient who received both cefiderocol and eravacycline was excluded from further analysis. Patients who received cefiderocol (43.3%) had higher hospital mortality than patients on eravacycline (22.2%, p=0.44). There was no difference with 30-day mortality between cefiderocol and eravacycline groups (p=0.12). 90-day mortality was elevated in the cefiderocol group (53.3%) compared to eravacycline group (22.2%) with p-value approaching significance (p=0.14). Of the three patients in the cefiderocol group with isolates non-susceptible to cefiderocol (one intermediate, two resistant), one patient with an intermediate isolate died during hospitalization, and one patient with a resistant isolate was readmitted within 30 days for a reason unrelated to \u003cem\u003eA. baumannii\u0026nbsp;\u003c/em\u003einfection. Hospital readmission at 30- (p=1.0) and 90-days (p=1.0) post discharge were similar between both groups (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComplications of \u003cem\u003eAcinetobacter\u003c/em\u003e Infection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients treated with cefiderocol were more likely to be admitted to ICU (70.0%) compared to those treated with eravacycline (44.4%, p=0.24). Additionally, cefiderocol group was more likely to have required mechanical intubation than eravacycline group (70.0% vs. 33.3%, p=0.06). Cefiderocol was associated with elevations in liver function tests (LFT), with 60.0% of cefiderocol patients experiencing LFT elevation compared to 11.1% of eravacycline patients (p=0.02).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe sought to compare outcomes among patients with MDRAI receiving eravacycline versus cefiderocol. In our limited cohort, we found no significant differences in mortality between patients receiving eravacycline or cefiderocol for MDRAI. This is the first study to evaluate mortality outcomes between eravacycline or cefiderocol in patients with MDRAI.\u003c/p\u003e \u003cp\u003eMDRAI is an emerging infection with rising resistance rates to commonly used antibiotics [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In our cohort, patients receiving cefiderocol were more likely to receive mechanical ventilation than eravacycline but otherwise had similar complications from their MDRAI. No statistically significant difference in the primary mortality outcome was demonstrated between the cefiderocol and eravacycline groups. Prior studies have compared mortality rates in patients treated with cefiderocol and those treated with other antibiotic regimens, primarily colistin-based regimens, with conflicting results [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In the CREDIBLE-CR trial, patients with carbapenem-resistant Gram-negative infections, including \u003cem\u003eA. baumannii\u003c/em\u003e, treated with cefiderocol demonstrated similar rates of infection resolution but higher mortality rates when compared to those treated with the best available therapy (BAT) for \u003cem\u003eAcinetobacter\u003c/em\u003e spp. infections. However, these findings may also represent an uneven distribution of patients similar to our findings, as patients treated with cefiderocol demonstrated higher rates of ICU admission and septic shock at randomization [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Conversely, the APEKS-NP trial, published in 2021, found that cefiderocol was non-inferior to meropenem in the treatment of nosocomial pneumonia, with similar mortality rates observed, although \u003cem\u003eA. baumannii\u003c/em\u003e infections only comprised 16% of patients studied [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Additionally, a recent retrospective cohort study conducted in Italy found a lower 30-day mortality rate in patients with CRAB bloodstream infections treated with cefiderocol (34%) than in patients treated with standard colistin-based regimens (55.8%, P\u0026thinsp;=\u0026thinsp;0.018), but this difference was not consistent in patients with VAP [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, a different retrospective cohort study conducted in Italy in patients with CRAB VAP infections demonstrated a significantly lower 28-day mortality rate in patients treated with cefiderocol-containing regimens compared with non-cefiderocol-containing regimens (44% vs. 67%, P\u0026thinsp;=\u0026thinsp;0.011) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Furthermore, a recent meta-analysis including 18 studies (733 patients) comparing cefiderocol with BAT found a significantly lower 30-day mortality rate in the cefiderocol group compared to the BAT group (RR: 0.74; 95% CI: 0.57\u0026ndash;0.95, P\u0026thinsp;=\u0026thinsp;0.02) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Given the conflicting results, the Infectious Disease Society of America (IDSA) currently advises caution when using cefiderocol to treat CRAB infections that are resistant to other antibiotics. They only recommend its use only in combination with other antibiotics [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It is also important to note that the studies primarily compared cefiderocol with colistin-containing regimens. Although colistin is still utilized for CRAB urinary tract infections, it is generally avoided due to its narrow therapeutic window and high risk for nephrotoxicity [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This emphasizes the necessity for additional clinical studies to compare cefiderocol to other available antibiotic options.\u003c/p\u003e \u003cp\u003eThere is limited clinical data on the efficacy of eravacycline in treating MDRAI. A recent retrospective report described the treatment of 46 patients with \u003cem\u003eA. baumannii\u003c/em\u003e infections, mainly pulmonary infections. It found an overall 30-day mortality rate of 23.9%, and a mortality rate of 21.9% in patients with CRAB infections [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, a retrospective cohort study comparing eravacycline-based regimens with BAT in patients with MDRAI reported significantly higher 30-day mortality rates in the eravacycline-based regimen group (33% vs. 15%, P\u0026thinsp;=\u0026thinsp;0.048). The study also noted a significantly longer median duration of mechanical ventilation (10.5 days vs. 6.5 days, P\u0026thinsp;=\u0026thinsp;0.016) and lower rates of microbiological cure (17% vs. 59%, P\u0026thinsp;=\u0026thinsp;0.004) in the eravacycline-based regimen group [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Notably, the outcomes for patients with bloodstream infections in the eravacycline-based group was poor; all four patients who received eravacycline monotherapy ultimately died within 30 days. When excluding of patients with bloodstream infections, similar 30-day mortality rates were observed between eravacycline and BAT groups (22% vs. 16%, P\u0026thinsp;=\u0026thinsp;0.506), raising concerns that eravacycline\u0026rsquo;s relatively large volume of distribution [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Our study did not include any cases of bacteremia in the eravacycline group. Due to the lack of clinical data supporting the use of eravacycline against CRAB infections, the IDSA currently recommends limiting its use to cases in which other agents are not effective, cannot be tolerated, or are unavailable [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Currently, IDSA recommends sulbactam/durlobactam as the first-line treatment choice for CRAB infections [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Sulbactam/durlobactam was recently approved by the FDA for the treatment of hospital-acquired pneumonia and VAP following the publication of the ATTACK trial in 2023, which showed sulbactam/durlobactam was non-inferior to colistin in the treatment of CRAB infections [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOn adverse events, cefiderocol showed was a significantly association with higher rates of LFT elevation (60% vs. 11.1%, P\u0026thinsp;=\u0026thinsp;0.02). It is worth noting that these elevations were mild, and none led to clinically apparent liver injury. Like other cephalosporins, cefiderocol is associated with mild LFT elevation, with previous trials reporting rates of liver-related adverse events ranging from 0.7\u0026ndash;29.7% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. There were no significant differences in the prevalence of other adverse events between groups, including nausea, diarrhea, and rash.\u003c/p\u003e \u003cp\u003eThis study has a few limitations. First, it is important to note that the study is retrospective in nature and the small sample is relatively small. Second, since our study was conducted at a single urban academic center, the generalizability of our findings to other settings may be limited. Additionally, the median treatment duration for patients in both groups was 6.0 days, which was influenced by several patient deaths during the treatment period. Additionally, MIC values were not reported for eravacycline against any isolates, and only 12 isolates for cefiderocol were included, making it challenging to ascertain the susceptible of the causative strain to each drug.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThere is a growing need for effective treatment options for MDRAI. Cefiderocol and eravacycline have displayed potential in combating this difficult pathogen. Our findings reveal no significant disparity between the two antibiotics in the treatment of MDRAI. Nevertheless, additional prospective research is essential for a more comprehensive comparing of these two antibiotics. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJH conceived and designed the study, collected data, contributed to data analysis, and drafted the manuscript. MK and DN contributed to study design, data collection, and manuscript revision. CFP contributed to data collection and manuscript writing, and performed the statistical analysis. All authors reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHoward, A., O\u0026apos;Donoghue, M., Feeney, A., \u0026amp; Sleator, R. D. (2012). Acinetobacter baumannii: an emerging opportunistic pathogen. Virulence, 3(3), 243-250. https://doi.org/10.4161/viru.19700\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eXiao, D., Wang, L., Zhang, D., Xiang, D., Liu, Q., \u0026amp; Xing, X. (2017). Prognosis of patients with Acinetobacter baumannii infection in the intensive care unit: A retrospective analysis. Exp Ther Med, 13(4), 1630-1633. https://doi.org/10.3892/etm.2017.4137\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSong, J. Y., Cheong, H. J., Choi, W. S., Heo, J. Y., Noh, J. Y., \u0026amp; Kim, W. J. (2011). 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Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother, 58(2), 256-265. https://doi.org/10.1093/jac/dkl224\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKeam, S. J. (2023). Sulbactam/Durlobactam: First Approval. Drugs, 83(13), 1245-1252. https://doi.org/10.1007/s40265-023-01920-6\u003c/li\u003e\n \u003cli\u003eKaye, K. S., Shorr, A. F., Wunderink, R. G., Du, B., Poirier, G. E., Rana, K., et al. (2023). Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK). Lancet Infect Dis, 23(9), 1072-1084. https://doi.org/10.1016/s1473-3099(23)00184-6\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6727622/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6727622/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cem\u003eA. baumannii\u003c/em\u003e is a common cause of drug-resistant hospital-associated infections. Eravacycline and cefiderocol are two recently introduced antibiotics that have demonstrated \u003cem\u003ein vitro\u003c/em\u003e activity against drug-resistant \u003cem\u003eA. baumannii\u003c/em\u003e, but data regarding the clinical utility of these drugs against multi-drug resistant \u003cem\u003eA. baumannii\u003c/em\u003e infections (MDRAI) is lacking. In this study, we performed a retrospective chart review of patients with MDRAI who were treated with cefiderocol or eravacycline to compare clinical outcomes associated with each antibiotic. 40 patients were included, of which 30 patients received cefiderocol, 9 received eravacycline, and 1 received both. We collected data on demographics, risk factors for MDRAI, and infection characteristics. The primary outcomes assessed were hospital mortality rates. Secondary outcomes assessed were readmission rates, ICU admission, shock requiring vasopressors, mechanical intubation, and drug-related adverse events. No significant differences in the primary outcomes of 30-day and 90-day mortality rates were observed between the two groups.\u003c/p\u003e","manuscriptTitle":"Comparison of eravacycline and cefiderocol in the treatment of multidrug-resistant Acinetobacter baumannii infections","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-30 11:17:07","doi":"10.21203/rs.3.rs-6727622/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4b907851-2676-4e17-8bde-d536f8c0594d","owner":[],"postedDate":"May 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-19T14:23:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-30 11:17:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6727622","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6727622","identity":"rs-6727622","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}