Evidence map›Paper›PMID 39777519›Full record

ArticleThe Journal of infectious diseases2025

Enhanced Killing of Methicillin-Resistant Staphylococcus aureus With Ceftaroline or Vancomycin in Combination With Carbapenems.

Allen Jankeel, Gabriel Pérez-Parra, Anuj K Khetarpal, Ivan A Alvarado, Victor Nizet, George Sakoulas, Erlinda R Ulloa

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Halogenated 3-Nitro-2Antibiotics (Basel, Switzerland) · 2025
    Article
  4. Adjunctive β-lactams forTherapeutic advances in infectious disease
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Allen JankeelDepartment of Pediatrics, University of California, Irvine School of Medicine.
Gabriel Pérez-ParraDepartment of Pediatrics, University of California, Irvine School of Medicine.ORCID 0009-0006-6866-1106
Anuj K KhetarpalDepartment of Pediatrics, University of California, Irvine School of Medicine.
Ivan A AlvaradoDepartment of Pediatrics, University of California, Irvine School of Medicine.ORCID 0000-0002-5470-3639
Victor NizetDepartment of Pediatrics, Division of Host-Microbe Systems and Therapeutics.ORCID 0000-0003-3847-0422
George SakoulasCollaborative to Halt Antibiotic-Resistant Microbes (CHARM), Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla.ORCID 0000-0002-6063-6217
Erlinda R UlloaDepartment of Pediatrics, University of California, Irvine School of Medicine.ORCID 0000-0002-0330-278X

Funding

Institute for Clinical and Translational ScienceUM1TR004927 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAN M COOPER, Eric J. Vilain · 2024 to 2026
$12.2M
Surprising Efficacy of Discounted Antibiotics vs. MDR Gram-Negative Pathogens Occurring Through Innate Immune SensitizationR01AI145310 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KUMARASWAMY, MONIKA, NIZET, VICTOR · 2020 to 2023
$1.9M
Beta-Lactamase Inhibitors Sensitize Multidrug-Resistant Gram-negative Pathogens to Innate Immune ClearanceK08AI151253 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI ULLOA, ERLINDA ROSE · 2020 to 2024
$1.0M
NCATS NIH HHS UM1 TR004927NIAID NIH HHS K08 AI151253NIAID NIH HHS R01 AI145310
6 · The paper itself

Abstract

backgroundMethicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high rates of treatment failure, even when antibiotics showing in vitro susceptibility are used. Early optimization of therapy is crucial to reduce morbidity and mortality. Building on our previous research on carbapenem therapy for methicillin-susceptible S aureus bacteremia, we examined the utility of adjunctive carbapenems (ertapenem or meropenem) to enhance the efficacy of ceftaroline or vancomycin for treatment of MRSA.

methodsThe effectiveness of combination therapy versus monotherapy against MRSA was assessed using checkerboard, time-kill, and human whole blood killing assays, as well as a murine bacteremia model. Additionally, we performed transcriptomic analysis and conducted human platelet and antimicrobial peptide killing assays on MRSA pretreated with subtherapeutic concentrations of ceftaroline and carbapenems. The supernatants from these MRSA isolates were used to treat platelets, and cytotoxicity was assessed via lactate dehydrogenase release assays.

resultsAlthough not used for MRSA, we identified striking in vitro and in vivo synergy between carbapenems and ceftaroline or vancomycin. MRSA pretreated with subtherapeutic ceftaroline-carbapenem therapy revealed transcriptional shifts indicative of reduced antibiotic resistance, virulence, and host immune evasion. Supernatants from these MRSA isolates also caused less platelet injury compared to monotherapy. Furthermore, MRSA pretreated with ceftaroline and carbapenems demonstrated increased susceptibility to killing by human platelets and the antimicrobial peptide LL-37.

conclusionsThe therapeutic success of adjunctive carbapenems appears driven by multiple mechanisms, including direct drug-drug synergy with first-line anti-MRSA agents, attenuation of resistance and virulence factors, and enhancement of immune-mediated killing, each warranting further investigation.

Indexed as

Anti-Bacterial AgentsCarbapenemsCephalosporinsMethicillin-Resistant Staphylococcus aureusStaphylococcal InfectionsVancomycinAnimalsBacteremiaCeftarolineDrug SynergismDrug Therapy, CombinationHumansMiceMicrobial Sensitivity TestsAnti-Bacterial AgentsCarbapenemsCeftarolineCephalosporinsVancomycinbacteremiacarbapenemsceftarolinecombination therapyendocarditisertapenemmeropenemMRSAvancomycin

Identifiers

PMID39777519
PMCPMC12747854

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.