Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Clinical Outcomes of Eravacycline in Patients Treated Predominately for Carbapenem-Resistant Acinetobacter baumannii.

Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE Acinetobacter baumannii, particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii, where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection.

Impact of Extended- Versus Intermittent-Infusion Cefepime on Clinical Outcomes in Hospitalized Patients.

Background: Pharmacodynamic models support potential improved antimicrobial pharmacokinetic and pharmacodynamic goal attainment in patients treated with extended-infusion (EI) versus intermittent-infusion (II) cefepime. Small clinical studies demonstrate inconsistent findings in patient outcomes, necessitating a deeper review of this administration method. Methods: This was a retrospective cohort study comparing patients receiving EI versus II cefepime between September 1, 2017, and March 31, 2018. The primary outcome was in-hospital all-cause mortality. Secondary objectives included length of hospital and ICU stay, time to defervescence, duration of therapy, duration of mechanical ventilation, and readmission rate. Subgroup analyses for the primary objective were conducted based on comorbid burden and isolate susceptibilities. Results: No statistically significant differences were noted in the 645 included patients for the primary outcome between the EI and II groups (7.8% vs 10.4%, P = .32). Median length of stay was 9 days (IQR 12) versus 11 days (IQR 14) (P = .30), respectively. In addition, statistical significance was not seen in any of the subgroups for the primary outcome including patients with APACHE II score ≥ 20 (17.4% vs 30.6%, P = .26) and for infections caused by Pseudomonas aeruginosa (5.9% vs 20.0%, P = .23) or Enterobacteriaceae (11.1% vs 20.0%, P = .13) with minimum inhibitory concentration (MIC) ≥ 4. Conclusion: No statistically significant differences were noted between EI and II groups, although benefits in specific subpopulations may exist when these results are correlated with findings from studies examining alternative antipseudomonal beta lactams.

Treatment of Staphylococcal Device Infections: Synergistic Daptomycin With Ceftaroline Versus Rifampin-Adjunct Therapy.

This is a single-center retrospective observational cohort study comparing daptomycin/ceftaroline combination therapy with rifampin-adjunct therapy for the treatment of staphylococcal device infections. The results of this study support use of the daptomycin/ceftaroline as an alternative or salvage option to standard of care.

Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review.

Ceftaroline is approved by the Food and Drug Administration for acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia, including cases with concurrent bacteremia. Use for serious methicillin-resistant Staphylococcus aureus (MRSA) infections has risen for a multitude of reasons. The aim of this article is to review the literature evaluating clinical outcomes and safety of ceftaroline prescribed for serious MRSA infections. We conducted a literature search in Ovid (Medline) and PubMed for reputable case reports, clinical trials, and reviews focusing on the use of ceftaroline for treatment of MRSA infections. Twenty-two manuscripts published between 2010 and 2016 met inclusion criteria. Mean clinical cure was 74% across 379 patients treated with ceftaroline for severe MRSA infections. Toxicities were infrequent. Ceftaroline treatment resulted in clinical and microbiologic cure for severe MRSA infections. Close monitoring of hematological parameters is necessary with prolonged courses of ceftaroline.