title: Ceftaroline Plus Ampicillin Against Gram-Positive Organisms: Results from E-Test Synergy Assays.
abstract: In an era of increasing drug resistance and limited numbers of antimicrobials in the drug production pipeline, healthcare-associated infections represent a growing public health threat. When therapeutic options are limited, clinicians often resort to using antimicrobial combinations that produce a synergistic effect on the target pathogen. Novel antibiotics are therefore welcome in the daily practice of medicine. For example, ceftaroline is a broad-spectrum cephalosporin active against a variety of bacteria, including methicillin-resistant Staphylococcus aureus, but with limited activity against enterococci, particularly Enterococcus faecium. In this study, we tested the efficacy of ceftaroline against clinical isolates of gram-positive bacteria (S. aureus, Enterococcus faecalis, and E. faecium) by the broth microdilution and E-test assays, and then evaluated the synergistic effect of ceftaroline and ampicillin using the E-test method. The time-kill assay was used to confirm the data on selected strains. This drug combination has been recently shown to be effective against E. faecalis and could offer the advantage of cost-effectiveness (compared to other synergistic associations) as well as good tolerability. The E-test was chosen because of its relative simplicity of use that makes it suitable for routine clinical laboratories as a quick tool to guide clinicians when confronted with difficult-to-treat infections that may require an empirical approach. Our results indicate the presence of a synergistic effect of ceftaroline and ampicillin on most of the strains used, especially E. faecium and E. faecalis. The fact that two of those Enterococcus strains were vancomycin resistant suggests that the possible use of this combination for combating the spread of vancomycin-resistant enterococci should be explored.
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Silvia
authors.initials: S
authors.lastname: D'Arezzo
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Antonio
authors.initials: A
authors.lastname: Mazzarelli
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Carolina
authors.initials: C
authors.lastname: Venditti
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Carla
authors.initials: C
authors.lastname: Nisii
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Nicola
authors.initials: N
authors.lastname: Petrosillo
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Chiara
authors.initials: C
authors.lastname: De Giuli
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Antonella
authors.initials: A
authors.lastname: Vulcano
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Paglia
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Eugenio
authors.initials: E
authors.lastname: Bordi
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Antonino
authors.initials: A
authors.lastname: Di Caro
authors.affiliation: "Lazzaro Spallanzani" National Institute for Infectious Diseases IRCCS , Rome, Italy .
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Taglietti
mesh_terms: D000667:Ampicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001681:Biological Assay; D002511:Cephalosporins / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D016984:Enterococcus faecium / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D020713:Vancomycin Resistance / Q000187:drug effects; D000097583:Ceftaroline
chemical_list: D000667:Ampicillin; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004338:Drug Combinations; D000097583:Ceftaroline
keywords: E-test; VRE; antibiotic resistance; ceftaroline; enterococci; synergy