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In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days)., Competing Interests: Potential conflicts of interest. E. K. M. reports consulting fees for Advisory Boards from AbbVie, Merck, Shionogi, Cidara, Ferring, Summit, La Jolla, Venatorx, Entasis, LabSimply, and Basilea; participation on DSMB for Wockhardt and on DMBD for A Phase I, Randomized, Double-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous Ertapenem in Combination with Zidebactam (WCK 6777) in Healthy Adult Subjects; speaking honorarium for UTI symposium at ECCMID 2023 from GlaxoSmithKlein (GSK) and speaking honorarium for COVID-19 symposium at IDWeek 2022; travel support to attend ECCMID 2023 from GSK. E. S. has received grant funding from Merck & Co and bioMérieux, Inc. 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: Ceftobiprole is a cephalosporin that may be effective for treating complicated Staphylococcus aureus bacteremia, including methicillin-resistant S. aureus ., Methods: In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated S. aureus bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new S. aureus bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trial-group assignments. Safety was also assessed., Results: Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed S. aureus bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population). A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], -7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, -6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, -2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45 patients (22.7%), respectively. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole., Conclusions: Ceftobiprole was noninferior to daptomycin with respect to overall treatment success in patients with complicated S. aureus bacteremia. (Funded by Basilea Pharmaceutica International and the U.S. Department of Health and Human Services; ERADICATE ClinicalTrials.gov number, NCT03138733.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: National guidelines for pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) do not address treatment duration for infections associated with bacteremia. We evaluated clinical outcomes of patients receiving shorter (5-9 days) versus longer (10-15 days) duration of antibiotics., Methods: This was a multicenter retrospective cohort study of inpatients with uncomplicated PNA, UTI, or ABSSSI and associated bacteremia. The primary outcome was clinical failure, a composite of rehospitalization, reinitiation of antibiotics, or all-cause mortality within 30 days of antibiotic completion. Secondary outcomes included individual components of the primary outcome, Clostridioides difficile infection, and antibiotic-related adverse effects necessitating change in therapy. A propensity score-weighted logistic regression model was used to mitigate potential bias associated with nonrandom assignment of treatment duration., Results: Of 408 patients included, 123 received a shorter treatment duration (median 8 days) and 285 received a longer duration (median 13 days). In the propensity-weighted analysis, the probability of the primary outcome was 13.5% in the shorter group and 11.1% in the longer group (average treatment effect, 2.4%; odds ratio [OR], 1.25; 95% confidence interval [CI], .65-2.40; P = .505). However, shorter courses were associated with higher probability of restarting antibiotics (OR, 1.62; 95% CI, 1.01-2.61; P = .046) and C. difficile infection (OR, 4.01; 95% CI, 2.21-7.59; P < .0001)., Conclusions: Shorter courses of antibiotic treatment for PNA, UTI, and ABSSSI with bacteremia were not associated with increased overall risk of clinical failure; however, prospective studies are needed to further evaluate the effectiveness of shorter treatment durations., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown., Objective: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events., Design, Setting, and Participants: A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization., Interventions: Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care., Main Outcomes and Measures: Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia., Results: Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6])., Conclusions and Relevance: Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm., Trial Registration: ClinicalTrials.gov Identifier: NCT01191840.

Streptomycin has been available for over 60 years, yet optimal dosing in hemodialysis (HD) patients is not well defined. We report the successful treatment of enterococcal bacteremia in an HD patient with intravenous (IV) penicillin G and IV streptomycin at a dose of 7.5 mg/kg after HD sessions.

Objective: To describe the epidemiology of bloodstream infection caused by USA300 strains of methicillin-resistant Staphylococcus aureus (MRSA), which are traditionally associated with cases of community-acquired infection, in the healthcare setting., Design: Retrospective cohort study., Setting: Three academically affiliated hospitals in Denver, Colorado., Methods: Review of cases of S. aureus bloodstream infection during the period from 2003 through 2007. Polymerase chain reaction was used to identify MRSA USA300 isolates., Results: A total of 330 cases of MRSA bloodstream infection occurred during the study period, of which 286 (87%) were healthcare-associated. The rates of methicillin resistance among the S. aureus isolates recovered did not vary during the study period and were similar among the 3 hospitals. However, the percentages of cases of healthcare-associated MRSA bloodstream infection due to USA300 strains varied substantially among the 3 hospitals: 62%, 19%, and 36% (P<.001) for community-onset cases and 33%, 3%, and 33% (P=.005) for hospital-onset cases, in hospitals A, B, and C, respectively. In addition, the number of cases of healthcare-associated MRSA bloodstream infection caused by USA300 strains increased during the study period at 2 of the 3 hospitals. At each hospital, USA300 strains were most common among cases of community-associated infection and were least common among cases of hospital-onset infection. Admission to hospital A (a safety-net hospital), injection drug use, and human immunodeficiency virus infection were independent risk factors for healthcare-associated MRSA bloodstream infection due to USA300 strains., Conclusions: The prevalence of USA300 strains among cases of healthcare-associated MRSA bloodstream infection varied dramatically among geographically clustered hospitals. USA300 strains are replacing traditional healthcare-related strains of MRSA in some healthcare settings. Our data suggest that the prevalence of USA300 strains in the community is the dominant factor affecting the prevalence of this strain type in the healthcare setting.

Background: Staphylococcus aureus bacteremia causes considerable morbidity and mortality, and strategies to improve management and outcomes of this disease are needed., Methods: Routine consultation with an infectious diseases specialist for cases of S. aureus bacteremia was mandated at our institution in May 2005. We compared the evaluation, management, and outcomes of cases before and after this policy change. All comparisons are by period (i.e., before or after initiation of the policy of routine consultation)., Results: In the year before and the year after after the implementation of routine consultation, 134 and 100 cases of S. aureus bacteremia, respectively, were evaluated. Consultation rates increased from 53% of cases before to 90% of cases after the policy change (p < .001). Echocardiography (57% vs. 73%; p = .01) and radiographic studies (81% vs. 91%; p = .04) were used more frequently during the period of routine consultation, and infective endocarditis or metastatic infections were diagnosed more frequently (33% vs. 46%; p = .04). All 4 standards of care (removal of intravascular foci of infection, obtaining follow-up blood culture samples, use of parenteral beta-lactam therapy when possible, and administration of >/=28 days of therapy for complicated infections) were adhered to more frequently with routine consultation (40% vs. 74%; P <.001). Treatment failure (microbiological failure, recurrent bacteremia, late metastatic infection, or death) occurred less often during the intervention year (17% vs. 12%), but this difference was not statistically significant (p = .27)., Conclusions: A policy of routine consultation with an infectious diseases specialist for patients with S. aureus bacteremia resulted in more-detailed evaluation, more-frequent detection of endocarditis and metastatic infection, and improved adherence to standards of care.

Background Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions. Methods Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds. Results Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable. Conclusions In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario. [ABSTRACT FROM AUTHOR]

Background Patients frequently remain in the hospital for prolonged intravenous (IV) antibiotic therapy for serious infections when outpatient IV antibiotic therapy is unsafe or unfeasible. A protocol was developed to facilitate early discharge by administering one dose of dalbavancin 7 – 10 days prior to the planned end of treatment, allowing patient discharge the same day as the infusion. The purpose of this analysis was to describe the effectiveness, safety, and financial impact by using dalbavancin to facilitate early discharge. Methods This is a retrospective observational analysis of all inpatients who received dalbavancin at Denver Health Medical Center from April 2018 to April 2019. One dose of dalbavancin 1,500 mg was administered over 30 minutes to each patient. The medical record was reviewed 30 days after discharge to determine safety (adverse reaction to dalbavancin) and effectiveness (readmission or receipt of additional antibiotics). The estimated cost of one hospital day was $1,800; one dose of dalbavancin costs $3,000. Results Sixteen patients (69% male; average age 45 years) received dalbavancin. The majority of patients were homeless (81%), injection drug users (75%), and infected with HCV (56%). One patient was infected with HIV (6%) and none had diabetes, kidney disease, or cirrhosis. Antibiotics administered prior to dalbavancin were vancomycin or cefazolin, based on organism, for a median duration of 25 days (IQR 11–34). Patients were infected with methicillin-resistant S. aureus (n = 8), methicillin-susceptible S. aureus (n = 7), and one co-infection with S. epidermidis and S. pyogenes. The infections included complicated bacteremia (n = 6), uncomplicated bacteremia (n = 4), osteomyelitis (n = 2), right-sided endocarditis (n = 2), and osteomyelitis with bacteremia (n = 2). No adverse reactions were noted. Readmission 30 days from discharge occurred for two patients for reasons unrelated to the infection or dalbavancin. None received additional antibiotics. 115 hospital days were averted (average of 7 days per patient). Cost savings to the hospital were estimated to be $159,000. Conclusion A standardized approach to use dalbavancin for serious infections to facilitate early hospital discharge appears to be safe and effective and led to substantial cost savings. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) are the most common infections treated in the inpatient setting and often are associated with bacteremia. Though short courses of treatment are advocated for these infections in general, no established guidelines exist for cases involving bacteremia. We evaluated the clinical outcomes of patients receiving short (5–9 days) vs. long (10–15 days) duration of antibiotic treatment. Methods A retrospective study was conducted at 3 area hospitals comprising a university-based tertiary center, a public safety net hospital, and a Veterans' Affairs hospital. We included hospitalized adult patients with transient bacteremia associated with uncomplicated cases of PNA, UTI, or ABSSSI. The primary outcome consisted of a composite of rehospitalization or resumption of antibiotic treatment attributed to the original infection or death due to any cause within 30 days of the antibiotic start date. Secondary outcomes included the individual composite components, Clostridioides difficile infection, and antibiotic-related adverse effects leading to change in antibiotic therapy. A propensity score weighted logistic regression model was used to mitigate factors which could bias a patient toward receiving a shorter or longer treatment duration. Results Of 411 patients included in the study, 123 (29.9%) received a short duration of therapy and 288 (70.1%) received a long duration of therapy. The median duration of treatment was 8 days in the short group and 13 days in the long group. In the propensity-weighted analysis, the probability of meeting the composite primary outcome was not statistically different between the short and long groups (Table 1). However, receiving a short course was associated with a higher probability of restarting antibiotics and Clostridioides difficile infection. Conclusion Shorter vs. longer courses of antibiotic treatment for bacteremia associated with PNA, UTI, and ABSSSI were not significantly different in a composite of readmission, restart of antibiotics, and mortality; however, further study is needed to evaluate the safety and effectiveness of short-course therapy. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]