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Background: Ceftolozane-tazobactam and ceftazidime-avibactam are preferred treatment options for multidrug-resistant Pseudomonas aeruginosa infections; however, real-world comparative effectiveness studies are scarce. Pharmacokinetic and pharmacodynamic differences between the agents might affect clinical response rates. We aimed to compare the effectiveness of ceftolozane-tazobactam and ceftazidime-avibactam for treatment of invasive multidrug-resistant P aeruginosa infections., Methods: This multicentre, retrospective, observational study was conducted at 28 hospitals in the USA between Jan 1, 2016, and Dec 31, 2023. Eligible patients were adults (age ≥18 years old) with microbiologically confirmed multidrug-resistant P aeruginosa pneumonia or bacteraemia treated with ceftolozane-tazobactam or ceftazidime-avibactam for more than 48 h. Patients were matched (1:1) by study site, severity of illness, time to treatment initiation (≤72 h or >72 h), and infection type. The primary outcome was clinical success at day 30, which was defined as survival, resolution of signs and symptoms of infection with the intended treatment course, and the absence of recurrent infection due to P aeruginosa. Secondary outcomes included all-cause mortality and development of resistance to study drug., Findings: 420 eligible patients were included (210 in each treatment group), of whom 350 (83%) had pneumonia and 70 (17%) had bacteraemia. Baseline demographics, comorbidities, and severity of illness indicators were similar between groups. On treatment initiation, 336 (80%) patients were in the intensive care unit, 296 (70%) were receiving mechanical ventilation, and 168 (40%) required vasopressor support. Clinical success was observed in 128 (61%) of 210 patients treated with ceftolozane-tazobactam and 109 (52%) of 210 patients treated with ceftazidime-avibactam. By conditional logistic regression analysis, the adjusted odds ratio (aOR) of success after treatment with ceftolozane-tazobactam compared with ceftazidime-avibactam was 2·07 (95% CI 1·16-3·70). For patients with pneumonia, clinical success was observed in 110 (63%) of 175 patients in the ceftolozane-tazobactam group and 89 (51%) of 175 patients in the ceftazidime-avibactam group (aOR 2·34 [95% CI 1·22-4·47]). Among patients with bacteraemia, rates of clinical success were 51% (18 of 35 patients) for patients treated with ceftolozane-tazobactam and 57% (20 of 35 patients) for those treated with ceftazidime-avibactam (0·76 [0·23-2·57]). There were no significant differences between groups in 30-day or 90-day mortality. Among patients whose baseline isolates were tested for susceptibility, resistance developed in 22% (38 of 173) of patients treated with ceftolozane-tazobactam and 23% (40 of 177) of patients treated with ceftazidime-avibactam., Interpretation: Treatment with ceftolozane-tazobactam resulted in higher rates of clinical success compared with ceftazidime-avibactam for invasive infections due to multidrug-resistant P aeruginosa. Differences were driven by improved response rates for patients with pneumonia who were treated with ceftolozane-tazobactam. There were no significant differences between study groups with respect to all-cause mortality; treatment-emergent resistance was common with both agents., Funding: Merck Sharp & Dohme., Competing Interests: Declaration of interests RKS has served as a consultant for AbbVie, Biomerieux, Shionogi, Menarini, Merck, Entasis, GlaxoSmithKline, and Venatorx, and has received investigator-initiated funding from Roche, Innoviva, Merck, Melinta, Shionogi, and Venatorx. LMA has served on advisory boards for bioMérieux, Roche, Pfizer, Shionogi, La Jolla/Innoviva, Ferring, and AbbVie, and has received speaker honorarium from Gilead. SLA has served on advisory boards for Shionogi, GlaxoSmithKline, Melinta, and Basilea. AB has served on an advisory board for Beckman Coulter. RB has received travel funds from bioMérieux. KCC has served as a consultant for bioMérieux. KED has served on advisory boards for Shionogi, Spero, Entasis, AbbVie, Melinta, Basilea, and GlaxoSmithKline; has received a speaker honorarium from MAD-ID; and has received travel funds from the Society of Infectious Diseases Pharmacists where she serves as Treasurer. JCG has received honoraria from MJH where he serves as Associate Editor for Clinical Infectious Diseases; has received payment for expert testimony from German, Gallagher & Murtagh; has served on advisory boards for Allergan, GlaxoSmithKline, Merck, Novavax, Qpex, Shionogi, and Spero; reports serving as Editor-in-Chief for Contagion; and has received authorship royalties from JB Learning. ELH has served as a consultant for Wolters-Kluwer. KMH has served on a speaker's bureau for Cepheid Diagnostics and has received travel funds from bioMérieux. KSK has served as a consultant for Merck, GlaxoSmithKline, Allecra, Shionogi, MicuRx, VenatoRx, and AbbVie. WDK has received funding from Merck and Shionogi. AM has received funding from F2G Biotech GmbH. EKM has served as a consultant for Abbvie, Merck, Basilea, Shionogi, Melinta, Ferring, Cidara, Entasis, LabSimply, Pfizer, and GlaxoSmithKline; has received speaker honoraria from GlaxoSmithKline, Shionogi, and Pfizer; has served as a safety monitor for the SNAP Trial and the NIAID Division of Microbiology and Infectious Diseases; and is President of the Society of Infectious Diseases Pharmacists. WRM has received funding from the National Institutes of Health and royalties from UpToDate. JMP has served as a consultant for Merck, Shionogi, Melinta, Entasis, GlaxoSmithKline, and VenatoRx; has received investigator-initiated funding from Merck; and has research grants from Merck, Shionogi, and Melinta. MJS has received funding from Merck, bioMérieux, and Selux Diagnostics; has served as a consultant for Shionogi; and has served on an advisory board for AbbVie. DV has received funding from Merck; has served as a consultant for Utility, Shionogi, Merck, Union, Roche, and Qpex; has received honoraria from Pfizer, Entasis, and Clinical Care Options; and has received fees from the British Society of Antimicrobial Chemotherapy and Universidade Federal do Rio Grande do Sul. MV has served on an advisory board for Shionogi. VV has received funding from the Florida Department of Health; has received honoraria from the American College of Clinical Pharmacy, the American Society of Health-System Pharmacists, ID Week, the American Society of Microbiologists, and Merck; and has received payment for expert testimony from Silver Golub & Teitell. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp. infections., Methods: Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016-2018 with cultures positive for carbapenemase-producing Enterobacter spp. were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed., Results: We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp. from 30 hospitals in 7 countries. Among the 136 isolates, eleven Enterobacter species were identified, with most isolates belonging to E. xiangfangensis (n=81, 60%) and E. hoffmannii (n=17, 13%), and carrying blaKPC (n=106, 78%) and blaNDM (n=12, 9%). Clinical characteristics and outcomes were similar among patients with E. xiangfangensis, E. hoffmannii or the other Enterobacter spp. 30-day mortality was 20% and older age at enrollment (adjusted odds ratio 1.42, 95% confidence interval 1.08-1.87) was associated with increased mortality. Sequence type (ST)171 E. xiangfangensis, ST78 E. hoffmannii, and ST93 E. xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination., Conclusions: Our findings demonstrated that E. xiangfangensis and E. hoffmannii are common species among international carbapenemase-producing Enterobacter spp., potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Ledaborbactam (formerly VNRX-5236), a bicyclic boronate β-lactamase inhibitor with activity against class A, C, and D β-lactamases, is under development as an orally bioavailable etzadroxil prodrug (VNRX-7145) in combination with ceftibuten for the treatment of urinary tract infections. At ceftibuten breakpoints of ≤1 mg/L (EUCAST) and ≤8 mg/L (CLSI), 92.5% and 99.0%, respectively, of 200 carbapenem-resistant Klebsiella pneumoniae isolates, predominantly K. pneumoniae carbapenemase producing, were susceptible to ceftibuten-ledaborbactam (ledaborbactam tested at a fixed concentration of 4 mg/L) compared to 4.5% and 30.5%, respectively, to ceftibuten alone., Competing Interests: Robert A. Bonomo reports a grant from Entasis and grants from Merck, Wockhardt, and Shionogi outside the submitted work.

Nontuberculous mycobacterium (NTM) infections are challenging to manage and are frequently non-responsive to aggressive but poorly-tolerated antibiotic therapies. Immunosuppressed lung transplant patients are susceptible to NTM infections and poor patient outcomes are common. Bacteriophages present an alternative treatment option and are associated with favorable clinical outcomes. Similarly, dual beta-lactam combinations show promise in vitro, but clinical use is sparse. We report here a patient with an uncontrolled Mycobacterium abscessus infection following a bilateral lung transplant and failed antibiotic therapy. Both smooth and rough colony morphotype strains were initially present, but treatment with two phages that kill the rough strain - including epigenetic-modification to overcome restriction - resulted in isolation of only the smooth strain. The rough and smooth strains have similar antibiotic susceptibilities suggesting that the phages specifically eliminated the rough strain. Dual beta-lactam therapy with meropenem and ceftazidime-avibactam provided further clinical improvement, and the phages act synergistically with meropenem in vitro., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Carbapenem-resistant Enterobacterales (CRE) are an important threat to the health of solid organ transplant recipients (SOTr); data comparing outcomes of SOTr with CRE to non-SOTr with CRE are lacking. A matched cohort study was performed within 2 prospective, multicenter, cohort studies (Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales and Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales 2). The epidemiology, desirability of outcome rankings outcomes, and mortality of SOTr and non-SOTr hospitalized in the United States (December 2011-August 2017) with clinical isolates with Centers for Disease Control and Prevention-defined CRE were compared. In total, 121 SOTr and 242 matched non-SOTr were included. Fifty-one percent of isolates met infection criteria. SOTr were younger (P < .001), less acutely ill (P = .029), less often had a malignancy history (P = .006), and more often were admitted from home (P < .001) than non-SOTr. SOTr had more favorable adjusted desirability of outcome rankings outcomes; a randomly selected SOTr had a 58% (95% confidence interval, 53%-64%) probability of a better outcome as compared to a randomly selected non-SOTr. All-cause 30-day mortality was 14% (17/121) in SOTr vs 25% (60/242) in non-SOTr, P = .018. After stabilized inverse probability weighted adjustment, SOTr had a 7% lower 30-day mortality risk than non-SOTr (95% confidence interval, -15% to 1%). SOTr with CRE do not have worse outcomes than matched patients without transplant history., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. All authors report funding support from the ARLG of the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID; UM1AI104681) during the conduct of this study. W. Dai, E. Cober, L. Komarow, L. Chen, C. Hill, M. Grant, and G. Patel have nothing to declare other than the ARLG grant paid to their institution. A.E. Boutzoukas reports NIH grants and contracts paid to her institution, research support from the Thrasher Research Foundation, and support from the Biogen Foundation. L.M. Abbo reports honorarium for ontinuing medical education (CM lectures from Pfizer Latin America and Merck Sharp & Dohme Latin America related to the study; and in the last 3 years consulting honorarium from bioMéreiux, Shionogi, Ferring pharmaceuticals, Pfizer, La Joya, Abbvie Therapeutics; and speaker honorarium for CME lectures from Medscape and Clinical Care options. M.J. Satlin reports grants/contracts to his institution from Merck, Selux Diagnostics, SNIPRBiome, and bioMéreiux; consulting fees paid directly to him from Shionogi; and compensation for participation on a data and safety monitoring board from AbbVie paid directly to him. B.C. Fries reports support from the USVeterans Affairs Merit Review Award 5I01 BX003741 and the National Institute for Allergy Infectious Diseases R01AI181830; is an attending at the US Department of Veterans Affairs, Northport Veterans Affairs (VA) Medical Center, Northport, NY; contents of this review do not represent the views of the VA or the United States Government. T.P. McCarty reports a research contract paid to his institution from T2Biosystems. C.A. Arias reports the following grants and contracts paid to his institution NIH/NIAID 1 P01 AI152999, NIH/NIAID R01 AI148342, NIH/NIAID R01 AI134637, NIH/NIAID T32 AI141349, NIH/NIAID K24 AI121296, NIH/NIAID U19 AI144297, and NIH/NIAID R01 AI150685; payments to him for UpToDate royalties; reimbursement of meeting attendance and speaking from Infectious Diseases Society of America, American Society for Microbiology, Society of Hospital Epidemiology of America, European Society for Clinical Microbiology and Infectious Diseases, Mérieux Foundation, Sociedad Argentina de Infectologia, Sociedad Chilena de Infectologia, Sociedad Colombiana de Infectologia, Panamerican Society for Infectious Diseases, and Brazilian Society for Infectious Diseases; reviewer participation as part of the NIH grant Review Study Sections; travel expenses from the Infectious Disease Society of America Board of Directors; and for Editor in Chief for Antimicrobial Agents and Chemotherapy; nonpaid participation includes World Health Organization Antibacterial Pipeline Advisory Group, and participation on the Infectious Disease Society of America Board of Directors. R.A. Bonomo reports grants and contracts, paid to his institution, by VenatoRx and Merck; payments made to him by Pfizer to moderate meeting sessions; a provisional patent with Case Western Reserve University on the development of boronic acid transition state inhibitors for beta-lactamases; served on a data and safety monitoring board as a logistics associate for Division of Microbiology and Infectious Diseases-Clinical Research Operations and Management Support, Safety Oversight Committee Support; and Technical Resources International, Inc. D. van Duin reports grants and contracts from the NIH, Merck, and Shinogi, paid to his institution, outside of the published work; consultancy for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, Qpex, Wellspring, Karius, and Utility, paid directly to him; honoraria from Pfizer; and an editor’s stipend from the British Society for Antimicrobial Chemotherapy., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The CDC reported a 35% increase in hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections during the COVID-19 pandemic. We evaluated patient outcomes following HO and community-onset (CO) CRE bloodstream infections (BSI)., Methods: Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between 30 April 2016 and 30 November 2019 with a CRE BSI were eligible. Infections were defined as CO or HO by CDC guidelines, and clinical characteristics and outcomes were compared. The primary outcome was desirability of outcome ranking (DOOR) 30 days after index culture. Difference in 30-day mortality was calculated with 95% CI., Results: Among 891 patients with CRE BSI, 65% were HO (582/891). Compared to those with CO CRE, patients with HO CRE were younger [median 60 (Q1 42, Q3 70) years versus 65 (52, 74); P < 0.001], had fewer comorbidities [median Charlson comorbidity index 2 (1, 4) versus 3 (1, 5); P = 0.002] and were more acutely ill (Pitt bacteraemia score ≥4: 47% versus 32%; P < 0.001). The probability of a better DOOR outcome in a randomly selected patient with CO BSI compared to a patient with HO BSI was 60.6% (95% CI: 56.8%-64.3%). Mortality at 30-days was 12% higher in HO BSI (192/582; 33%) than CO BSI [66/309 (21%); P < 0.001]., Conclusion: We found a disproportionately greater impact on patient outcomes with HO compared to CO CRE BSIs; thus, the recently reported increases in HO CRE infections by CDC requires rigorous surveillance and infection prevention methods to prevent added mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To evaluate causes of fever, including resistance patterns, in patients undergoing cancer treatment in Malawi., Methods: In this prospective cohort study, enrolled patients undergoing chemotherapy at Kamuzu Central Hospital in Lilongwe, Malawi were given a thermometer. If a temperature of ≥38°C was recorded, they were instructed to return for hospitalization, standardized fever workup, and antibiotics. All patients were followed through 90 days post-fever event or completion of chemotherapy., Results: One hundred and five patients were screened and 50 were enrolled. Of the enrollees, 26 (52%) were men and 26 (52%) were HIV positive, with a mean ART duration of 7 years and CD4 count of 293 cells/µL. The most common diagnoses were aggressive non-Hodgkin lymphoma (40%) and Hodgkin lymphoma (22%). Twenty-three febrile events were recorded from 15 patients. Of the 23 events, a causative agent was isolated in 13 cases: Escherichia coli (6), Plasmodium falciparum (3), Streptococcus pneumoniae (2), Pseudomonas aeruginosa (1) and Citrobacter freundii (1). Of the six E. coli isolates, all were found to be resistant to fluoroquinolones and 4/6 (66%) were resistant to cephalosporins. All patients but one survived; the death was attributed to Pseudomonas bacteraemia., Conclusions: This study describes laboratory-confirmed causes of neutropenic fever (NF) in cancer patients in Malawi. Gram-negative rods, followed by malaria, were the most common source of infection. Gram-negative rods were associated with high rates of antimicrobial resistance. Malaria and resistant bacterial infections should be considered for NF treatment and prevention in sub-Saharan Africa., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

We characterized the molecular determinants of meropenem-vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC- Klebsiella pneumoniae (KPC- KP ). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased bla KPC copy numbers. KPC- KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV., Competing Interests: The authors declare no conflict of interest.

Competing Interests: Potential conflicts of interest. D. v. D. has National Institutes of Health funding unrelated to this work and has received grants from Merck and consulting fees and honoraria from Shionogi, Merck, Union, Roche, Qpex, Pfizer, Entasis, and Clinical Care Options. J. M. C. R. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

This study aims to fine-tune the plasma composition with a particular emphasis on reactive nitrogen species (RNS) including nitrogen dioxide (NO 2 ), dinitrogen pentoxide (N 2 O 5 ), and nitrous oxide (N 2 O), produced by a self-constructed cylindrical dielectric barrier discharge (CDBD). We demonstrated the effective manipulation of the plasma chemical profile by optimizing electrical properties, including the applied voltage and frequency, and by adjusting the nitrogen and oxygen ratios in the gas mixture. Additionally, quantification of these active species was achieved using Fourier transform infrared spectroscopy. The study further extends to exploring the aerosol polymerization of acrylamide (AM) into polyacrylamide (PAM), serving as a model reaction to evaluate the reactivity of different plasma-generated species, highlighting the significant role of NO 2 in achieving high polymerization yields. Complementing our experimental data, molecular dynamics (MD) simulations, based on the ReaxFF reactive force field potential, explored the interactions between reactive oxygen species, specifically hydroxyl radicals (OH) and hydrogen peroxide (H 2 O 2 ), with water molecules. Understanding these interactions, combined with the optimization of plasma chemistry, is crucial for enhancing the effectiveness of DBD plasma in environmental applications like air purification and water treatment.

Taniborbactam, a bicyclic boronate β-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC), Verona integron-encoded metallo-β-lactamase (VIM), New Delhi metallo-β-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC β-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant K. pneumoniae and 197 multidrug-resistant (MDR) Pseudomonas aeruginosa to cefepime-taniborbactam and comparators was determined by broth microdilution. For K. pneumoniae (192 KPC; 7 OXA-48-related), MIC 90 values of β-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of K. pneumoniae were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For P. aeruginosa , MIC 90 values of β-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant P. aeruginosa isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing P. aeruginosa isolates. Of all 108 carbapenem-intermediate/resistant P. aeruginosa isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had in vitro activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant K. pneumoniae and carbapenem-intermediate/resistant MDR P. aeruginosa ., Competing Interests: Robert A. Bonomo reports grants from Venatorx, Entasis, Merck, Wockhardt, and Shionogi outside the submitted work. David A. Six, Greg Moeck, and Tsuyoshi Uehara are employees of Venatorx Pharmaceuticals, Inc.

Background: Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE)., Objectives: To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents., Methods: Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures., Results: The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients' race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%-56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group., Conclusions: Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Stenotrophomonas maltophilia is a carbapenem-resistant Gram-negative pathogen increasingly responsible for difficult-to-treat nosocomial infections., Objectives: To describe the contemporary clinical characteristics and genome epidemiology of patients colonized or infected by S. maltophilia in a multicentre, prospective cohort., Methods: All patients with a clinical culture growing S. maltophilia were enrolled at six tertiary hospitals across Japan between April 2019 and March 2022. The clinical characteristics, outcomes, antimicrobial susceptibility and genomic epidemiology of cases with S. maltophilia were investigated., Results: In total, 78 patients were included representing 34 infection and 44 colonization cases. The median age was 72.5 years (IQR, 61-78), and males accounted for 53 cases (68%). The most common comorbidity was localized solid malignancy (39%). Nearly half of the patients (44%) were immunosuppressed, with antineoplastic chemotherapy accounting for 31%. The respiratory tract was the most common site of colonization (86%), whereas bacteraemia accounted for most infection cases (56%). The 30 day all-cause mortality rate was 21%, which was significantly higher in infection cases than colonization cases (35% versus 9%; adjusted HR, 3.81; 95% CI, 1.22-11.96). Susceptibility rates to ceftazidime, levofloxacin, minocycline and sulfamethoxazole/trimethoprim were 14%, 65%, 87% and 100%, respectively. The percentage of infection ranged from 13% in the unclassified group to 86% in genomic group 6A. The percentage of non-susceptibility to ceftazidime ranged from 33% in genomic group C to 100% in genomic groups 6 and 7 and genomic group geniculate., Conclusions: In this contemporary multicentre cohort, S. maltophilia primarily colonized the respiratory tract, whereas patients with bacteraemia had the highest the mortality from this pathogen. Sulfamethoxazole/trimethoprim remained consistently active, but susceptibility to levofloxacin was relatively low. The proportions of cases representing infection and susceptibility to ceftazidime differed significantly based on genomic groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Equitable representation of members from historically marginalized groups is important in clinical trials, which inform standards of care. The goal of this study was to characterize the demographics and proportional subgroup reporting and representation of participants enrolled in randomized controlled trials (RCTs) of antibacterials used to treat Staphylococcus aureus infections., Methods: We examined randomized controlled registrational and strategy trials published from 2000 to 2021 to determine the sex, race, and ethnicity of participants. Participant to incidence ratios (PIRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the disease population in each group. Underrepresentation was defined as a PIR < 0.8., Results: Of the 87 included studies, 82 (94.2%) reported participant sex, 69 (79.3%) reported participant race, and 20 (23.0%) included ethnicity data. Only 17 (19.5%) studies enrolled American Indian/Alaskan Native participants. Median PIRs indicated that Asian and Black participants were underrepresented in RCTs compared with the incidence of methicillin-resistant S. aureus infections in these subgroups. Underrepresentation of Black participants was associated with a larger study size, international sites, industry sponsorship, and phase 2/3 trials compared with phase 4 trials (P < .05 for each). Black participants had more than 4 times the odds of being underrepresented in phase 2/3 trials compared with phase 4 trials (odds ratio, 4.57; 95% confidence interval: 1.14-18.3)., Conclusions: Standardized reporting methods for race and ethnicity and efforts to increase recruitment of marginalized groups would help ensure equity, rigor, and generalizability in RCTs of antibacterial agents and reduce health inequities., Competing Interests: Potential conflicts of interest. All authors report funding support from the ARLG of the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID; UM1AI104681). J. G. P. reports grants or contracts paid directly to her institution from NIH/NIAID (K01AI143881) and grants or contracts paid directly to her department from the Texas A&M Triads for Transformation and Montague-CTE. D. v. D. reports grants or contracts paid directly to his institution from NIH and Merck and grants or contracts paid directly to him from Shionogi Inc; consulting fees paid directly to him from Actavis, Tetraphase, Sanofi-Pasteur, Medimmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, Qpex, Wellspring, Karius, and Utility; honoraria paid directly to him from Pfizer; and an editor's stipend paid directly to him from British Society for Antimicrobial Chemotherapy. H. F. C. reports royalties from the Sanford Guide to Antimicrobial Therapy; payment for expert testimony from Nexus Pharmaceuticals; participation on a Merck Data Safety and Monitoring Board for molnupiravir, and stock ownership in Moderna and Merck. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche Astra Zeneca, and Pfizer; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius; Genentech, Regeneron, Deep Blue, Basilea, Janssen; Royalties from UpToDate, stock options from Valanbio and ArcBio, honoraria from Infectious Diseases of America for his service as Associate Editor of Clinical Infectious Diseases (2017–2022), and a patent sepsis diagnostics pending; support from Contrafect to present phase 2 data at 2019 ECCMID. M. M. P. reports grants or contracts paid directly to her institution from NIH/NIAID (R01AI019641), Centers for Disease Control and Prevention (NU50CK000488), and Green Acres Foundation; honoraria paid to directly to her from the US State Department for participation on a panel about antimicrobial resistance; payment from the American Society for Microbiology for travel to present research findings on antimicrobial resistance not directly related to this project; and unpaid participation on the Connecticut Department of Public Health Multidisciplinary Antimicrobial Resistance/Antimicrobial Stewardship Advisory Group. H. F. C. reports participation on a Data Safety Monitoring Board or Advisory Board for Merck (molnupiravir); stock from Moderna and Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale & Objective: Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation., Study Design: Single-center, retrospective cohort study., Setting & Participants: Recipients of a kidney transplant from January 2005 until May 2020 at a tertiary care university teaching hospital., Exposure: Patients with GN as their native kidney disease who received PTI for treatment of GN (n=184) were compared with nondiabetic recipients of kidney transplants who did not receive PTI (n = 579)., Outcome: First occurrence after transplantation of an infection outcome, either viral (BK or cytomegalovirus [CMV] infection) or bacterial., Analytical Approach: Cox regression analysis adjusted for age at transplant, sex, race, donor type, year of transplant surgery, dialysis vintage, receipt of T-cell depleting induction, and CMV transplant status., Results: Over a median follow-up period of 5.7 years, patients with GN PTI were not at an increased risk for developing any first viral infection compared with controls (adjusted HR [AHR] 0.69 [95% CI, 0.52-0.91]) nor at increased risk for specific viral infections: BK infection 19.6% vs 26.3% (AHR 0.72 [95% CI, 0.50-1.05]) or CMV infection, 24.5% vs 29.0% (AHR, 0.76 [95% CI, 0.54-1.07]), respectively. There was also no increased risk of developing a first bacterial infection: 54.5% vs 57.5% (AHR, 0.90 [95% CI, 0.71-1.13]). These findings of no increased risk for infection were independent of the type of PTI used (cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitor) or the type of T-cell depleting induction therapy (alemtuzumab or antithymocyte globulin) administered., Limitations: Single-center study, no data on methylprednisone use for PTI, unmeasured confounding., Conclusions: Use of PTI for the treatment of GN was not associated with an increased risk of viral (BK or CMV) or bacterial infection after transplantation. Additional surveillance for infection after transplantation for patients who received PTI may not be necessary., Plain-Language Summary: Many kidney transplant patients have glomerular disease as the cause of kidney failure. These patients may be exposed to immunosuppression before transplantation, which could increase the risk for infections after receipt of a transplanted kidney. We identified kidney transplant recipients at a university teaching hospital who received immunosuppression before transplant for the treatment of glomerular kidney disease. We examined their risk for infection after transplantation by comparing it with the risk among transplant patients who were not exposed to immunosuppression before transplant. We observed no increased risk for infection after exposure to prior immunosuppression. Therefore, patients exposed to significant amounts of immunosuppression before transplantation may not require special surveillance or medication adjustment for fear of infection after their receipt of a kidney transplant., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12 years of age, at high risk for progression to severe COVID-19., Objectives: To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system., Methods: We conducted a cohort study using electronic health records among outpatients with a positive SARS-CoV-2 PCR test between January and August 2022. We evaluated the association of nirmatrelvir/ritonavir therapy with time to hospitalization by estimating adjusted HRs and assessed the impact of nirmatrelvir/ritonavir on predicted COVID-19 hospitalizations using machine-learning methods., Results: Among 44 671 patients, 4948 (11%) received nirmatrelvir/ritonavir, and 201 (0.4%) were hospitalized within 28 days of COVID-19 diagnosis. Nirmatrelvir/ritonavir recipients were more likely to be older, white, vaccinated, have comorbidities and reside in areas with higher average socioeconomic status. The 28 day cumulative incidence of hospitalization was 0.06% (95% CI: 0.02%-0.17%) among nirmatrelvir/ritonavir recipients and 0.52% (95% CI: 0.46%-0.60%) among non-recipients. For nirmatrelvir/ritonavir versus no therapy, the age-adjusted HR was 0.08 (95% CI: 0.03-0.26); the fully adjusted HR was 0.16 (95% CI: 0.05-0.50). In the machine-learning model, the primary features reducing predicted hospitalization risk were nirmatrelvir/ritonavir, younger age, vaccination, female gender and residence in a higher socioeconomic status area., Conclusions: COVID-19 hospitalization risk was reduced by 84% among nirmatrelvir/ritonavir recipients in a large, diverse healthcare system during the Omicron wave. These results suggest that nirmatrelvir/ritonavir remained highly effective in a setting substantially different than the original clinical trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: The purpose of this review is to briefly summarize the challenges associated with the treatment of pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB), discuss its carbapenem-resistance, and review the literature supporting the current treatment paradigm and therapeutic options., Recent Findings: In a multicenter, randomized, and controlled trial the novel β-lactam-β-lactamase inhibitor sulbactam-durlobactam was compared to colistin, both in addition to imipenem-cilastatin. The drug met the prespecified criteria for noninferiority for 28-day all-cause mortality while demonstrating higher clinical cure rates in the treatment of CRAB pneumonia. In an international, randomized, double-blind, placebo controlled trial colistin monotherapy was compared to colistin combined with meropenem. In this trial, combination therapy was not superior to monotherapy in the treatment of drug-resistant gram-negative organisms including CRAB pneumonia., Summary: CRAB pneumonia is a preeminent public health threat without an agreed upon first line treatment strategy. Historically, there have been drawbacks to available treatment modalities without a clear consensus on the first-line treatment regimen. CRAB pneumonia is a top priority for the continued development of antimicrobials, adjuvant therapies and refinement of current treatment strategies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The activity of a novel β-lactamase inhibitor combination, sulbactam-durlobactam (SUL-DUR), was tested against 87 colistin-resistant and/or cefiderocol-non-susceptible carbapenem-resistant Acinetobacter baumannii clinical isolates collected from U.S. hospitals between 2017 and 2019. Among them, 89% and 97% were susceptible to SUL-DUR and imipenem plus SUL-DUR, with MIC 50 /MIC 90 values of 2 µg/mL/8 µg/mL and 1 µg/mL/4 µg/mL, respectively. The presence of amino acid substitutions in penicillin-binding protein 3, including previously reported A515V or T526S, was associated with SUL-DUR non-susceptibility., Competing Interests: The authors thank Entasis Therapeutics Inc. for provision of durlobactam for the study.

Background: Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States., Objective: Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort., Methods: CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing., Results: Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%., Conclusions: CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults., Competing Interests: Potential conflicts of interest. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681. W. C. H. is a member of an endpoint adjudication committee for Pfizer and has served as an advisory board member for ADMA Biologics. He has common stock in Pfizer, Bristol Meyers Squibb, and Zimmer Biomet. D. v. D. was supported by R01AI143910 from NIAID. B. C. F. was supported by US Veterans Affairs Merit Review Award 5I01 BX00374. She is an attending at the U.S. Department of Veterans Affairs—Northport VA Medical Center, Northport, NY. D. v. D. has received personal fees from Achaogen, Allergan, Astellas, Neumedicine, T2biosystems, Roche, Merck, Karius, Entasis, Wellspring, Qpex, Pfizer, Utility, and Union; they are all outside the submitted work. The contents is solely the responsibility of the authors and does not represent the views of the National Institute of Health, the VA, or the United States Government. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Carbapenem resistant Enterobacterales (CRE) are a major threat to global health and hospital-onset CRE infections have risen during the COVID-19 pandemic. Novel antimicrobials are now available for the treatment of CRE infections. There remains an urgent need for new antimicrobials for CRE, especially for those producing metallo-β-lactamases., Areas Covered: This article discusses previously published research supporting currently available novel antimicrobials for the treatment of CRE infections. Newer compounds currently being evaluated in clinical trials are covered. A literature search was conducted in PubMed over all available dates for relevant published papers and conference abstracts with the search terms, 'CRE,' 'carbapenem-resistant Enterobacterales,' 'β-lactam-β-lactamase inhibitor,' 'KPC,' 'NDM,' 'metallo-β-lactamase,' 'ceftazidime-avibactam,' 'meropenem-vaborbactam,' 'imipenem-cilastatin-relebactam,' 'cefiderocol,' 'eravacycline,' 'plazomicin,' 'taniborbactam,' 'zidebactam,' and 'nacubactam.', Expert Opinion: Novel antimicrobials for CRE infections have been developed, most notably the β-lactam-β-lactamase inhibitor combinations, though treatment options for infections with metallo-β-lactamase producing Enterobacterales remain few and have limitations. Development of antibiotics with activity against metallo-β-lactamase producing Enterobacterales is eagerly awaited, and there are promising new compounds in clinical trials. Finally, more clinical research is needed to optimize and individualize treatment approaches, which will help guide antimicrobial stewardship initiatives aimed at reducing the spread of CRE and development of further resistance.

Klebsiella pneumoniae has been classified into two types, classical K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP). cKP isolates are highly diverse and important causes of nosocomial infections; they include globally disseminated antibiotic-resistant clones. hvKP isolates are sensitive to most antibiotics but are highly virulent, causing community-acquired infections in healthy individuals. The virulence phenotype of hvKP is associated with pathogenicity loci responsible for siderophore and hypermucoid capsule production. Recently, convergent strains of K. pneumoniae, which possess features of both cKP and hvKP, have emerged and are cause of much concern. Here, we screen the genomes of 2,608 multidrug-resistant K. pneumoniae isolates from the United States and identify 47 convergent isolates. We perform phenotypic and genomic characterization of 12 representative isolates. These 12 convergent isolates contain a variety of antimicrobial resistance plasmids and virulence plasmids. Most convergent isolates contain aerobactin biosynthesis genes and produce more siderophores than cKP isolates but not more capsule. Unexpectedly, only 1 of the 12 tested convergent isolates has a level of virulence consistent with hvKP isolates in a murine pneumonia model. These findings suggest that additional studies should be performed to clarify whether convergent strains are indeed more virulent than cKP in mouse and human infections., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

We examined the association between multidrug resistance and socioeconomic status (SES), analyzing microbiological and ZIP-code-level socioeconomic data. Using generalized linear models, we determined that multidrug resistance is significantly and persistently more prevalent in samples taken from patients residing in low-income ZIP codes versus high-income ZIP codes in North Carolina.

Purpose of Review: Stenotrophomonas maltophilia is an emerged opportunistic pathogen. Intrinsic multidrug resistance makes treating infections caused by S. maltophilia a great clinical challenge. Herein, we provide an update on the most recent literature on treatment options for severe S. maltophilia infections., Recent Findings: Trimethoprim-sulfamethoxazole (SXT) is recognized as the first-line therapy for S. maltophilia infections. However, its clinical use is based on good in vitro activity and favorable clinical outcomes, rather than on solid minimum inhibitory concentration (MIC) correlations with pharmacokinetic/pharmacodynamics (PK/PD) and/or clinical outcomes. The same is true for other treatment options like levofloxacin (LVX) and minocycline (MIN). Recent PK/PD studies question the current clinical breakpoints for SXT, LVX, and MIN. Based on this, the latest guidance issued by the Infectious Diseases Society of America (IDSA) recommends using these agents only as part of a combination therapy. Alternatively, novel therapeutic options such as cefiderocol (FDC) and ceftazidime-avibactam plus aztreonam (CZA-ATM) are suggested, based on limited but promising clinical data., Summary: PK/PD data and controlled clinical studies are needed to optimize current treatment options. Presently, combination therapy of SXT, LVX, MIN, or FDC, or monotherapy with CZA-ATM are recommended therapeutic options for severe-to-moderate S. maltophilia infections., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Fever is frequently an early indicator of infection and often requires rigorous diagnostic evaluation., Objectives: This is an update of the 2008 Infectious Diseases Society of America and Society (IDSA) and Society of Critical Care Medicine (SCCM) guideline for the evaluation of new-onset fever in adult ICU patients without severe immunocompromise, now using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology., Panel Design: The SCCM and IDSA convened a taskforce to update the 2008 version of the guideline for the evaluation of new fever in critically ill adult patients, which included expert clinicians as well as methodologists from the Guidelines in Intensive Care, Development and Evaluation Group. The guidelines committee consisted of 12 experts in critical care, infectious diseases, clinical microbiology, organ transplantation, public health, clinical research, and health policy and administration. All task force members followed all conflict-of-interest procedures as documented in the American College of Critical Care Medicine/SCCM Standard Operating Procedures Manual and the IDSA. There was no industry input or funding to produce this guideline., Methods: We conducted a systematic review for each population, intervention, comparison, and outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as best-practice statements., Results: The panel issued 12 recommendations and 9 best practice statements. The panel recommended using central temperature monitoring methods, including thermistors for pulmonary artery catheters, bladder catheters, or esophageal balloon thermistors when these devices are in place or accurate temperature measurements are critical for diagnosis and management. For patients without these devices in place, oral or rectal temperatures over other temperature measurement methods that are less reliable such as axillary or tympanic membrane temperatures, noninvasive temporal artery thermometers, or chemical dot thermometers were recommended. Imaging studies including ultrasonography were recommended in addition to microbiological evaluation using rapid diagnostic testing strategies. Biomarkers were recommended to assist in guiding the discontinuation of antimicrobial therapy. All recommendations issued were weak based on the quality of data., Conclusions: The guidelines panel was able to formulate several recommendations for the evaluation of new fever in a critically ill adult patient, acknowledging that most recommendations were based on weak evidence. This highlights the need for the rapid advancement of research in all aspects of this issue-including better noninvasive methods to measure core body temperature, the use of diagnostic imaging, advances in microbiology including molecular testing, and the use of biomarkers., Competing Interests: Supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH). Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. Van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antibiotic Resistance Leadership Group UM1AI104681), the NIH, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics Limited, Hylomorph, BioFire, Shionogi, IDSA, NBME, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Competing Interests: Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antimicrobial Resistance Leadership Group UM1AI104681), the National Institutes of Health, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics, Hylomorph, BioFire, Shionogi, Infectious Diseases Society of America, National Board of Medical Examiners, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST Diagnostics, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections., Methods: Therapeutic drug monitoring (TDM) was performed in 3 patients with health care-associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry., Results: Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC- Kp ), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC- Ent.c ). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 μg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients., Conclusions: Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% f T > MIC, which are associated with efficient bacterial killing., Competing Interests: Potential conflicts of interest. No potential conflicts of interest exist for each contributing author as they pertain to this work. Robert A. Bonomo receives funding from VenatoRx, Shionogi, Merck, and Entasis outside the scope of the submitted work. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Addressing the treatment and prevention of antibacterial-resistant gram-negative bacterial infections is a priority area of the Antibacterial Resistance Leadership Group (ARLG). The ARLG has conducted a series of observational studies to define the clinical and molecular global epidemiology of carbapenem-resistant and ceftriaxone-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, with the goal of optimizing the design and execution of interventional studies. One ongoing ARLG study aims to better understand the impact of fluoroquinolone-resistant gram-negative gut bacteria in neutropenic patients, which threatens to undermine the effectiveness of fluoroquinolone prophylaxis in these vulnerable patients. The ARLG has conducted pharmacokinetic studies to inform the optimal dosing of antibiotics that are important in the treatment of drug-resistant gram-negative bacteria, including oral fosfomycin, intravenous minocycline, and a combination of intravenous ceftazidime-avibactam and aztreonam. In addition, randomized clinical trials have assessed the safety and efficacy of step-down oral fosfomycin for complicated urinary tract infections and single-dose intravenous phage therapy for adult patients with cystic fibrosis who are chronically colonized with P. aeruginosa in their respiratory tract. Thus, the focus of investigation in the ARLG has evolved from improving understanding of drug-resistant gram-negative bacterial infections to positively affecting clinical care for affected patients through a combination of interventional pharmacokinetic and clinical studies, a focus that will be maintained moving forward., Competing Interests: Potential conflicts of interest. All authors report funding support from the Antibacterial Resistance Leadership Group of the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID; grant UM1AI104681). M. J. S. reports grants or contracts from Merck, bioMérieux, SNIPRBiome, and Selux Diagnostics; consulting fees from Shionogi; and participation on a data safety monitoring board (DSMB) for AbbVie. D. v. D. reports grants or contracts from Merck; consulting fees from Utility, Shionogi, Merck, Union, Roche, and Qpex; payment or honoraria from Pfizer, Entasis, and Clinical Care Options; participation on an advisory board for Universidade Federal do Rio Grande do Sul; and leadership in the British Society of Antimicrobial Chemotherapy. K. A. R. reports royalties from Springer Nature Group (textbook royalties); consulting fees, outside the submitted work, as an advisory board member for Shionogi, Qpex Biopharma/Medicines, and Utility Therapeutics and a consultant for Pulmatrix, BugsResearch, Clinartis, Spero Therapeutics, Qpex Biopharma/Medicines, Genetech, Utility Therapeutics, Venatorx, Chimerix, and Debiopharm; payment or honoraria from Shionogi (speaker bureau) and Biri Bioscience (presentation/speaker); participation on a DSMB, outside the submitted work, for Janssen Pharmaceutical; voting membership on the National Antimicrobial Susceptibility Testing Committee for the United States; and membership in the Antimicrobial Stewardship Curriculum Workgroup of the Infectious Diseases Society of America. N. R. reports grants or contracts from Merck, Sanofi, Pfizer, Quidel, and Lilly; consulting fees from Krog; payment or honoraria from Virology Education; travel support from Sanofi; participation on a DSMB or advisory board for Moderna, Sanofi, EMMES, ICON, and Seqirus; advisory roles with the Antibacterial Resistance Leadership Group, Tropical Medicine Research Center (TMRC), Centers for Disease Control and Prevention (CDC), and Pertussis Challenge; an associate editor role with Clinical Infectious Diseases; and receipt of equipment, materials, drugs, medical writing, gifts or other services from the Georgia Research Alliance. S. R. E. reports grants from the NIAID, the NIH and De Gruyter (as editor-in-chief for Statistical Communications in Infectious Diseases), the National Cancer Institute/NIH, and the CDC; royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roviant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, SVB Leerink, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, and IDDI; payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); meeting support from the US Food and Drug Administration, Deming Conference on Applied Statistics, Clinical Trial Transformation Initiative, the Council for International Organizations of Medical Sciences, the International Chinese Statistical Association Applied Statistics Symposium, and the Antimicrobial Resistance and Stewardship Conference; and board member participation for the NIH, the Breast International Group, the University of Pennsylvania, Washington University, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, GSK, Eli Lilly, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, Candel, Novartis, the American Statistical Association, the Society for Clinical Trials, and the Frontier Science Foundation. V. G. F. reports personal consulting fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, The Medicines Company, MedImmune, Bayer, Basilea, Affinergy, Janssen, ContraFect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, Roche, and Pfizer (all paid to author); grants from the NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, ContraFect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the Infectious Diseases Society of America for service as associate editor of Clinical Infectious Diseases; travel support from ContraFect to 2019 ECCMID; and a sepsis diagnostics patent pending. T. H. reports consulting fees from Tanabe-Mitsubishi Pharma and honoraria from Duke University and Cancer and Chemo Therapy. R. P. reports grants or contracts from ContraFect, TenNor Therapeutics Limited, BIOFIRE, and Adaptive Phage Therapeutics; a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics through the Mayo Clinic; consulting fees from PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, HealthTrackRx, Netflix, Abbott Laboratories, Trellis Bioscience, Oxford Nanopore Technologies, and CARB-X; honoraria from the NBME, Up-to-Date, and the Infectious Diseases Board Review Course; a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, a patent on a device/method for sonication (with royalties paid by Samsung to Mayo Clinic), and a patent on an antibiofilm substance issued; and a financial relationship with Pathogenomix through the Mayo Clinic. N. S. reports grant funding from Duke University, the NIH, and the Antibacterial Resistance Leadership Group. R. A. B. reports grants and contracts from VenatoRx, Wockhardt, and Merck; payments from Pfizer to moderate meeting sessions; a provisional patent with Case Western Reserve University on the development of boronic acid transition state inhibitors for β-lactamases; and participation on a DSMB as a logistics associate for DMID-CROMS, Safety Oversight Committee Support, and Technical Resources International. Y. D. reports grants from Entasis and Shionogi; consulting fees from GSK, Moderna, Meiji Seika Pharma, Shionogi, Gilead, FujiFilm, and bioMérieux; and speaker payments from MSD, Shionogi, and Gilead. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Carbapenem-resistant Acinetobacter baumannii (CRAb) is one of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb., Methods: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis., Results: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs. 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases., Conclusions: CRAb infection types and clinical outcomes differed significantly across regions. While CG2 strains remained predominant, non-CG2 strains were associated with higher mortality., Clinicaltrials.gov: #NCT03646227., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort., Methods: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture., Results: Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec., Conclusions: Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations., Competing Interests: Potential conflicts of interest. All authors report funding support from the Antibacterial Resistance Leadership Group (ARLG) of the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID; UM1AI104681) during the conduct of this study. Additionally, during the conduct of this study, A. E. B. reports funding from the Unified Program for Therapeutics in Children (UPTiC) [1T32HD094671-01A1] from the Eunice Kennedy Shriver National institute of child health and human development. Outside of the submitted work, the authors report the following disclosures: S. S. K. reports speaker and/or advisory board payments from Pfizer, Astellas, Novartis, Merck, Menarini, and Gilead, and honoraria from UpToDate. A. E. B. reports grants or contracts from the NIH–NIAID Loan Repayment Program and Thrasher Research Foundation. B. H. reports NIH/NIAID grant K01AI148593-01 (paid to their institution). K. O. reports payments for educational events and presentations from Pfizer, MSD, and AstraZeneca; payment or honoraria from BioMerieux and Farma de Colombia; meeting support from AstraZeneca, Pfizer, MSD, and Gilead; expert testimony support from Pfizer, bioMerieux, and MSD; and payment for participation on a Data Safety and Monitoring Board (DSMB) from Pfizer. S. E. reports a Centers for Disease Control and Prevention (CDC) grant; NIH grants from the NIAID, the National Cancer Institute (NCI), and the National Heart, Lung, and Blood Institute (NHLBI); a contract with Degruter (Editor in Chief for Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickenson, Atricure, Roivant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, SVB Leerink, Medtronic, Regeneron, and Wake Forest University (all paid to the author); honorarium payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); honoraria from the US Food and Drug Administration, the Deming Conference on Applied Statistics, and the International Chinese Statistical Association Applied Statistics Symposium; travel support from the Clinical Trial Transformation Initiative, the Council for International Organizations of Medical Sciences, and the Antimicrobial Resistance and Stewardship Conference; and Data Safety Monitoring or Advisory Board member participation for the NIH, the Breast International Group, the University of Pennsylvania, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, GSK, Eli Lilly, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, Candel, and Novartis (all payments made to the author); and unpaid Board membership with the American Statistical Association, the Society for Clinical Trials, and the Frontier Science Foundation. R. A. B. reports grants and contracts, paid to his institution, by VenatoRx, Wockhardt, and Merck; payments made to him by Pfizer to moderate meeting sessions; a patent with Case Western Reserve University on the development of boronic acid transition state inhibitors for beta-lactamases; payment for participation on a DSMB, Safety Oversight Committee Support (SOCS), and Logistics Associate for Division of Microbiology and Infectious Diseases - Clinical Research Operations And Management Support (DMID-CROMS) (Contractor), with Technical Resources International, Inc (TRI). R. P. reports grants from BIOFIRE, ContraFect, Adaptive Phage Therapeutics, and TenNor Therapeutics Limited; is a consultant to Curetis, Specific Technologies, Abbott Laboratories, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Day Zero Diagnostics, Torus Biosystems, Mammoth Biosciences, HealthTrackRx, and Qvella, for which monies are paid to Mayo Clinic; is a consultant to Netflix and CARB-X; has a patent on Bordetella pertussis (parapertussis) polymerase chain reaction (PCR) issued, a patent on a device and method for sonication (with royalties paid by Samsung to Mayo Clinic), and a patent on an anti-biofilm substance issued; receives an editor's stipend from the Infectious Diseases Society of America (IDSA); and receives honoraria from the National Board of Medical Examiners, UpToDate, and the Infectious Diseases Board Review Course; other interests paid to her institution include Adaptive Phase Therapeutics and Pathogenomix. D. L. P. serves on the Scientific Advisory Board of the Antibiotic Action Fund and a Data Safety Monitoring or Advisory Board for Symvivo; has grant funding from Shionogi, Pfizer, and Merck; reports consulting fees (paid to the author) from Merck, Shinogi, Qpex, and Spero Therapeutics; payment or honoraria (paid to the author) for speaking engagements from Sumitomo, Merck, Pfizer, and bioMerieux; travel support from Shinogi (paid to the author); and serves on advisory boards or has given lectures for Pfizer, Merck, bioMerieux, Zuellig, Entasis, QPex, and VenatoRx. C. A. A. reports the following grants and contracts paid to his institution: NIH/NIAID 1 P01 AI152999, NIH/NIAID R01 AI148342, NIH/NIAID R01 AI134637, NIH/NIAID T32 AI141349, NIH/NIAID K24 AI121296, NIH/NIAID U19 AI144297, NIH/NIAID R01 AI150685, NIH/NIAID R21 AI151536, and support from MeMed Diagnostics Ltd, Entasis Therapeutics, Merck Pharmaceuticals, and Harris County Public Health; payments to him for UpToDate royalties; reimbursement for meeting attendance for speaking engagements from IDSA, American Society for Microbiology, Society of Hospital Epidemiology of America, European Society for Clinical Microbiology and Infectious Diseases, bioMerieux Foundation, Sociedad Argentina de Infectologia, Sociedad Chilena de Infectologia, Sociedad Colombiana de Infectologia, Panamerican Society for Infectious Diseases, and Brazilian Society for Infectious Diseases; reviewer participation as part of the NIH Grant Review Study Sections; travel expenses from the IDSA Board of Directors; honoraria as Editor-in-Chief for Antimicrobial Agents and Chemotherapy; and nonpaid participation in the World Health Organization Antibacterial Pipeline Advisory Group and the IDSA Board of Directors. H. F. C. reports royalties from serving as Senior Editor on the Sanford Guide to Antimicrobial Therapy; payment for expert testimony from Nexus Pharmaceuticals for patent litigation and from Eli Lilly for product liability; participation on a Merck DSMB for Molnuprivir paid directly to him, and stock ownership in Moderna and Merck. V. G. F. reports grants to his institution from the NIH, MedImmune, Allergan, Pfizer, Advance, Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Basilea, and Janssen; royalties from UpToDate; personal consulting fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche; editorial stipend from IDSA; a pending patent for a host gene expression signature diagnostic for sepsis; and stock options with Valanbio and ArcBio. D. v. D. reports grants or contracts with NIH and Merck (paid to their institution); grants or contracts with Shionogi (paid to the author); consulting fees from Actavis, Tetraphase, Sanofi-Pasteur, Medimmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, Qpex, Wellspring, Karius, Utility, and Union (all paid to the author); payment or honoraria for speaking engagements from Pfizer; and an editor's stipend from the British Society for Antimicrobial Chemotherapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. This guidance document focuses on infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document., Methods: A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR-P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States., Results: Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are also discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults., Conclusions: The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial resistant infections. This document is current as of December 31, 2022 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)