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D O Andrey, P François, C Manzano, E J Bonetti, S Harbarth, J Schrenzel, W L Kelley, A Renzoni
Ceftaroline is a broad-spectrum antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Ceftaroline susceptibility of an MRSA set archived between 1994 and 2003 in the Geneva University Hospitals detected a high percentage (66 %) of ceftaroline resistance in clonotypes ST228 and ST247 and correlated with mutations in PBP2a. The ceftaroline mechanism of action is based on the inhibition of PBP2a; thus, the identification of PBP2a mutations of recently circulating clonotypes in our institution was investigated...
October 15, 2016: European Journal of Clinical Microbiology & Infectious Diseases
Vaishali Gaikwad, Tejash Gohel, Shrijeet Panickar, Vijay Chincholkar, Santosh Mangalkar
INTRODUCTION: Staphylococcus is one of the most common causes of nosocomial infection, especially pneumonia, surgical site infections, blood stream infections, and continues to be a major cause of community-acquired infections. The emergence of penicillin resistance followed by the development and spread of strains resistant to the semisynthetic penicillins such as methicillin, oxacillin and nafcillin, macrolides, tetracycline, and aminoglycosides has made the treatment of staphylococcal infection a global challenge...
October 2016: Indian Journal of Pathology & Microbiology
M Angeles Argudín, M Dodémont, M Taguemount, S Roisin, R de Mendonça, A Deplano, C Nonhoff, O Denis
OBJECTIVES: The aim of this study was to estimate the in vitro activity of ceftaroline against clinical Staphylococcus aureus isolates collected during national surveillance in Belgian acute-care hospitals. Ceftaroline-resistant isolates were further investigated for their resistance mechanisms. METHODS: From October 2013 to March 2014, 155 laboratories of Belgian acute-care hospitals were invited to send to the National Reference Centre-Staphylococcus aureus (Belgium) up to five non-duplicate S...
September 15, 2016: Journal of Antimicrobial Chemotherapy
Matthew Dryden, Yingyuan Zhang, David Wilson, Joseph P Iaconis, Jesus Gonzalez
OBJECTIVES: Increasing the ceftaroline fosamil dose beyond 600 mg every 12 h may provide additional benefit for patients with complicated skin and soft tissue infections (cSSTIs) with severe inflammation and/or reduced pathogen susceptibility. A Phase III multicentre, randomized trial evaluated the safety and efficacy of ceftaroline fosamil 600 mg every 8 h in this setting. METHODS: Adult patients with cSSTI and systemic inflammation or comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g every 8 h) for 5-14 days...
September 1, 2016: Journal of Antimicrobial Chemotherapy
D J Biedenbach, J P Iaconis, D F Sahm
OBJECTIVES: Ceftaroline fosamil is indicated for the treatment of community-acquired bacterial pneumonia and ceftriaxone has an indication for lower respiratory tract infections. This study was conducted to compare the relative in vitro activities of these two agents against bacterial species associated with community-associated respiratory tract infections. METHODS: In all, 13 005 isolates of Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected in 2012-14 from 39 countries in the Asia-Pacific region, Europe, Latin America and Africa-Middle East from respiratory tract specimens...
August 23, 2016: Journal of Antimicrobial Chemotherapy
Ana Belen García, Francisco Javier Candel, Laura López, Flavia Chiarella, Jose Manuel Viñuela-Prieto
We studied in vitro ceftaroline combinations against 61 methicillin-resistant Staphylococcus aureus (MRSA) isolates, 18 of them also resistant to linezolid, using overlapping E-test method. Daptomycin-Ceftaroline combination obtained lower Fractional Inhibitory Concentration (FIC) values, in comparison with those including vancomycin or linezolid against MRSA (p<0.05). All methicillin and linezolid resistant Staphylococcus aureus (MLRSA) strains were resistant to ceftaroline, nevertheless, combinations with vancomycin or daptomycin showed higher synergy or addtion rates than those with linezolid...
August 22, 2016: Journal of Medical Microbiology
Vasilios Athans, Rachel M Kenney, Jacob Wong, Susan L Davis
OBJECTIVES: There are few convenient intravenous options for long-term outpatient treatment of osteoarticular infection (OAI) and limited effectiveness and safety data exist for this off-label use of ceftaroline. The objective of this study was to describe the long-term effectiveness and safety of ceftaroline for the treatment of OAI. METHODS: This was a matched retrospective cohort study of patients receiving ceftaroline- or vancomycin-based therapy for OAI in the outpatient setting...
August 15, 2016: Journal of Antimicrobial Chemotherapy
Silvia D'Arezzo, Antonio Mazzarelli, Carolina Venditti, Carla Nisii, Nicola Petrosillo, Chiara De Giuli, Antonella Vulcano, Maria Grazia Paglia, Eugenio Bordi, Antonino Di Caro, Fabrizio Taglietti
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...
August 15, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Yvonne J Burnett, Kelly Echevarria, Kristi A Traugott
OBJECTIVE: To summarize published data regarding the use of ceftaroline as salvage monotherapy for persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. DATA SOURCES: PubMed (January 1980-June 2016) was searched using combinations of the search terms methicillin-resistant Staphylococcus aureus, MRSA, bacteremia, ceftaroline, refractory, and persistent Supplemental references were generated through review of identified literature citations. STUDY SELECTION AND DATA EXTRACTION: Available English-language, full-text articles pertaining to the use of ceftaroline for persistent MRSA bacteremia (MRSAB) were included...
August 12, 2016: Annals of Pharmacotherapy
Todd A Riccobene, Tatiana Khariton, William Knebel, Shampa Das, James Li, Alena Jandourek, Timothy J Carrothers, John S Bradley
Ceftaroline, the active form of the pro-drug ceftaroline fosamil, is approved for use in adults with community-acquired bacterial pneumonia (CABP) or acute bacterial skin and skin structure infections (ABSSSI) in the United States and similar indications in Europe. Pharmacokinetic (PK) data from five pediatric (birth to <18 years) studies of ceftaroline fosamil were combined with PK data from adults to update a population PK model for ceftaroline and ceftaroline fosamil. This model, based on a dataset including 305 children, was used to conduct simulations to estimate ceftaroline exposures and percentage of time that free drug concentrations were above the minimum inhibitory concentration (%fT>MIC) for pediatric dose regimens...
August 11, 2016: Journal of Clinical Pharmacology
Sushmita D Lahiri, Richard A Alm
OBJECTIVES: Ceftaroline (the active metabolite of ceftaroline fosamil) is a cephalosporin that possesses activity against MRSA due to its differentiating high affinity for PBP2a. It is known that PBP2a sequence variations, including some outside of the transpeptidase-binding pocket, impact ceftaroline susceptibility and recent evidence suggests involvement of non-PBP2a mechanisms in ceftaroline resistance. This study evaluated the potential of ceftaroline to select for resistant Staphylococcus aureus clones during serial passage...
August 5, 2016: Journal of Antimicrobial Chemotherapy
James A Karlowsky, Douglas J Biedenbach, Samuel K Bouchillon, Meredith Hackel, Joseph P Iaconis, Daniel F Sahm
The objective of this report was to document antimicrobial susceptibility testing surveillance data for ceftaroline and comparative agents from the AWARE (Assessing Worldwide Antimicrobial Resistance Evaluation) global surveillance program for bacterial pathogens causing skin and soft tissue and respiratory tract infections in African and Middle Eastern countries from 2012 through 2014. Pathogen identities were confirmed by MALDI-TOF and antimicrobial susceptibility testing performed by CLSI broth microdilution methodology in a central laboratory...
October 2016: Diagnostic Microbiology and Infectious Disease
Hong Fang, Inga Fröding, Boisan Gian, Sara Hæggman, Ulla-Britt Tollström, Måns Ullberg, Carl Erik Nord
Methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide. The aim of the present study was to investigate the molecular epidemiology and antimicrobial susceptibilities of MRSA strains in Stockholm, Sweden in 2014. Pulsed-field gel electrophoresis (PFGE) was used to characterise the strains. Antimicrobial susceptibilities to ceftaroline, linezolid and mupirocin were determined by the disc diffusion method. Etest was used to determine vancomycin susceptibility and to confirm resistance to ceftaroline, mupirocin and linezolid in non-susceptible strains...
June 2016: Journal of Global Antimicrobial Resistance
Marc Armengol-Porta, Alberto Tenorio-Abreu, Dirk Bandt, David C Coleman, Dolores Gavier-Widen, Helmut Hotzel, Peter Kinnevey, Alexandros Lazaris, Martin Peters, Lena Rangstrup-Christensen, Katharina Schlotter, Anna C Shore, Ralf Ehricht, Stefan Monecke
Ceftaroline is a new cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). A collection of 17 clinical and veterinary mecC-positive MRSA isolates was tested to evaluate the in vitro efficacy of ceftaroline against recently emerged mecC-MRSA isolates. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of ceftaroline for the 17 isolates were determined by broth microdilution using the methodology and interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI)...
June 2016: Journal of Global Antimicrobial Resistance
Todd A Riccobene, Richard Pushkin, Alena Jandourek, William Knebel, Tatiana Khariton
Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to (i) evaluate ceftaroline concentrations in human plasma and epithelial lining fluid (ELF) and (ii) develop a population pharmacokinetic (PK) model for plasma and ELF to be used in PK/pharmacodynamic (PD) target attainment simulations. Ceftaroline concentrations in ELF and plasma at steady state (day 4) were measured in healthy adult subjects for two dosages: 600 mg every 12 h (q12h) and 600 mg every 8 h (q8h)...
October 2016: Antimicrobial Agents and Chemotherapy
Daniel G Meeker, Karen E Beenken, Weston B Mills, Allister J Loughran, Horace J Spencer, William B Lynn, Mark S Smeltzer
We used in vitro and in vivo models of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) in the specific context of an established biofilm. The results demonstrated that, under in vitro conditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1...
October 2016: Antimicrobial Agents and Chemotherapy
Matthew E Falagas, Andreas D Mavroudis, Konstantinos Z Vardakas
INTRODUCTION: A real concern in the medical community is the increasing resistance of bacteria, especially that of Gram-negative types. New antibiotics are currently under clinical development, promising to tackle severe infections caused, especially, by multi-drug resistant (MDR) bacteria and broaden the armamentarium of clinicians. AREAS COVERED: We searched PUBMED and GOOGLE databases. Combinations of already approved β-lactams or monobactams with new β-lactamase inhibitors [imipenem-cilastatin/MK-7655 (relebactam), meropenem/RPX7009 (vaborbactam), ceftaroline/avibactam, aztreonam/avibactam], new β-lactams (S-649266, BAL30072), aminoglycosides (plazomicin), quinolones (finafloxacin) and tetracyclines (eravacycline) were included in the review...
August 2016: Expert Review of Anti-infective Therapy
E Pace, M Ferraro, S Di Vincenzo, L Siena, M Gjomarkaj
The tobacco smoking habit interferes with the innate host defence system against infections. Recurrent infections accelerated the functional respiratory decline. The present study assessed the effects of ceftaroline on TLR2 and TLR4 and on pro-inflammatory responses in airway epithelial cells (16HBE cell line and primary bronchial epithelial cells) with or without cigarette smoke extracts (CSE 10%). TLR2, TLR4, LPS binding and human beta defensin 2 (HBD2) were assessed by flow cytometry, NFkB nuclear translocation by western blot analysis, IL-8 and HBD2 mRNA by Real Time PCR; the localization of NFkB on the HBD2 and IL-8 promoters by ChiP Assay...
September 6, 2016: Toxicology Letters
Tommaso Giani, Antonio Cannatelli, Vincenzo Di Pilato, Raymond Testa, Wright W Nichols, Gian Maria Rossolini
Avibactam restored the in-vitro antibacterial activity of ceftazidime, ceftaroline, and aztreonam against isogenic Escherichia coli expressing class A, class C, and class D β-lactamases. The enzymes included TEM and CTX-M extended spectrum β-lactamases, ACT, CMY and FOX AmpC-type enzymes, and carbapenemases including rarer KPC variants and OXA-139.
September 2016: Diagnostic Microbiology and Infectious Disease
Helio S Sader, Rodrigo E Mendes, Ronald N Jones, Robert K Flamm
Among 8437 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 143 medical centers in the United States (2012-2014), 7116 and 1321 were reported as community-acquired (CA) and hospital-acquired (HA) MRSA, respectively. CA-/HA-MRSA were most often isolated from patients with skin and skin structure infections (SSSI; 68.4/26.9%), pneumonia (13.7/49.0%) and bacteremia (10.0/17.7%). Overall, susceptibility rates were generally lower among HA-MRSA compared to CA-MRSA strains, especially for clindamycin (44...
September 2016: Diagnostic Microbiology and Infectious Disease
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