Activity Of Ceftaroline Research Articles

In vitro synergism and anti-biofilm activity of ampicillin, gentamicin, ceftaroline and ceftriaxone against Enterococcus faecalis

Enterococci frequently cause severe biofilm-associated infections such as endocarditis. The combination of ampicillin/ceftriaxone has recently been clinically evaluated as non-inferior compared with the standard therapy of ampicillin/gentamicin for treatment of Enterococcus faecalis endocarditis. Ceftaroline is a novel cephalosporin with enhanced activity against Gram-positive bacteria. To compare the in vitro effectiveness of the ceftaroline/ampicillin combination with those of gentamicin/ampicillin and ceftriaxone/ampicillin in planktonic and biofilm cultures of clinical E. faecalis isolates. Synergistic effects at the planktonic level were analysed by chequerboard assays in 20 E. faecalis isolates. Biofilm-eradicating and biofilm-preventing activities of the antibiotics and their combinations were determined by confocal laser scanning microscopy with quantification by quantitative biofilm analysis (qBA) algorithm and cfu/mL determination. Comparable synergistic effects were observed for both β-lactam combinations in most isolates, in contrast to gentamicin/ampicillin. However, none of the antibiotic combinations succeeded in eradicating mature biofilms. Gentamicin showed promising biofilm-preventing activity, but at concentrations above those clinically tolerable. The β-lactams showed a U-shape dose-response relationship in biofilm prevention. Only exposure to cephalosporins caused alterations in cell morphology, which resulted in cell elongation and reclustering in a concentration-dependent manner. Reclustering was associated with high occurrences of small colony variants (SCVs), especially at high ceftriaxone concentrations. This study suggests that combinations of cephalosporins or gentamicin with ampicillin may be advantageous only while bacteraemia persists, whereas combinations have no advantage over monotherapy regarding the treatment of mature biofilms. The selection of SCVs at high ceftriaxone concentrations is worth further study.

Comparative in vitro activity of ceftaroline and comparator agents against nosocomial Gram-negative and Gram-positive clinically significant bacterial isolates from patients in a teaching hospital in Kuwait

The objective was to test the in vitro activities of ceftaroline and comparator agents against clinical isolates of Gram-negative and Gram-positive bacteria. Isolates were identified with VITEK II. Susceptibility testing was with E test. A total of 1264 isolates were tested. Compared to other cephalosporins, ceftaroline demonstrated excellent in vitro activities (MIC90, ≤0.5 mg/L) against Escherichia coli, Salmonella spp. and Haemophilus influenzae. When matched with the comparator cephalosporins, ceftaroline demonstrated the greatest activity against methicillin-susceptible Staphylococcus aureus (MSSA), with MIC90 of 0.25 mg/L. Ceftaroline’s MIC90s against both community-associated methicillin-resistant S. aureus (MRSA) and hospital-acquired MRSA were 0.5 and 1 mg/L, respectively. Major discrepancies were noted between E test and disc diffusion tests for ceftaroline only against 16 Gram-negative and 16 Gram-positive isolates. Ceftaroline demonstrated an excellent in vitro activity against the majority of clinically significant Gram-negative and Gram-positive isolates obtained from proven cases of bacterial infections.

In vitro activity of novel anti-MRSA cephalosporins and comparator antimicrobial agents against staphylococci involved in prosthetic joint infections.

Ceftaroline and ceftobiprole are new parenteral cephalosporins with potent activity against methicillin-resistant (MR) staphylococci, which are the leading cause of prosthetic joint infections (PJIs). The aim of this study was to determine and compare the in vitro activities of both molecules against staphylococcal isolates recovered from clinically documented PJIs. A collection of 200 non-duplicate clinical isolates [100 Staphylococcus aureus and 100 coagulase-negative staphylococci (CoNS), including 19 and 27 MR isolates, respectively] was studied. Minimum inhibitory concentrations (MICs) of oxacillin, ceftaroline, ceftobiprole, vancomycin, teicoplanin, clindamycin, levofloxacin, linezolid and daptomycin were determined by the broth microdilution method. Bactericidal activity (at 4× MIC) of ceftaroline, ceftobiprole, vancomycin, teicoplanin, linezolid and daptomycin was assessed by time-kill assay. Among the S. aureus isolates, 100% were susceptible to ceftaroline (MIC50/90, 0.25/0.5μg/mL) and 98% were susceptible to ceftobiprole (MIC50/90, 0.5/1μg/mL), regardless of their methicillin resistance. The two ceftobiprole-non-susceptible strains (including one MRSA) showed MICs at 4mg/L. Against CoNS isolates, ceftaroline and ceftobiprole exhibited in vitro potency with MIC50/90 values at 0.06/0.25μg/mL and 0.25/1μg/mL, respectively. At 4× MIC, ceftaroline and ceftobiprole showed rapid and marked bactericidal activity against both S. aureus and CoNS (after 24/12h and 12/6h of incubation, respectively), whilst none of the other molecules tested had a bactericidal effect by 24h. This study showed that ceftaroline and ceftobiprole have excellent in vitro activity against clinical isolates of staphylococci involved in PJIs. These molecules may therefore represent promising alternatives for the treatment of such infections.

In Vitro Activities of Ceftaroline and Comparators against Streptococcus pneumoniae Isolates from U.S. Hospitals: Results from Seven Years of the AWARE Surveillance Program (2010 to 2016).

We evaluated trends in Streptococcus pneumoniae antimicrobial susceptibility in United States hospitals in the 2010 to 2016 period. A total of 8,768 clinical isolates from 47 medical centers were tested for susceptibility by broth microdilution methods. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) rates decreased from 25.7% and 12.4%, respectively, in 2010 to 17.7% and 3.6%, respectively, in 2016. The susceptibilities to most comparator antimicrobial agents increased, whereas the susceptibilities to ceftaroline, levofloxacin, linezolid, and tigecycline remained stable. Ceftaroline retained potent activity against S. pneumoniae (>99.9%) with no marked variations.

Evaluation of In Vitro Activity of Ceftaroline Tested against Streptococcus pneumoniae Isolates from United States Hospitals: Results from 7 Years of the AWARE Surveillance Program (2010–2016)

BackgroundCeftaroline (CPT) is a broad-spectrum cephalosporin with activity against S. pneumoniae (SPN), including multidrug-resistant (MDR) strains. CPT fosamil is approved for clinical use in the United States (US) to treat community-acquired bacterial pneumonia (CABP). The AWARE Program monitors the in vitro activity of CPT against clinical bacteria from various infection types. We evaluated the activity of CPT against isolated SPN clinical isolates from US hospitals collected in 2010 through 2016.MethodsA total of 8,768 isolates were consecutively collected (1 per patient) from 47 medical centers in 2010–2016 and tested for susceptibility (S) to CPT and comparator agents using CLSI broth microdilution methods. Resistant subgroups included isolates that were nonsusceptible (NS) to penicillin (PCN), ceftriaxone (CRO), amoxicillin-clavulanate (AMC), erythromycin (ERY), clindamycin (CM), and levofloxacin (LEV) as well as MDR (NS to ≥3 classes of agents) and extensively drug resistant (XDR; NS to ≥5 classes).ResultsCPT inhibited 99.99% of SPN isolates at ≤0.5 mg/L (only 1 isolate had a CPT MIC of 1 mg/L) and remained active against all SPN-resistant (R) subgroups, including PCN-NS (8.7% at ≥4 mg/L), CRO-NS (6.9% at ≥2 mg/L), MDR (21.7%), and XDR (8.4%) strains. CPT activity remained stable against all R subgroups each year. MDR and XDR frequency decreased from 25.0% and 14.1% in 2011 to 17.8% and 3.2% in 2015, respectively; and S to PCN, CRO, AMC, CM, trimethoprim-sulfamethoxazole (TMX), and tetracycline (TET) increased in the same period (Table). The CPT-NS isolate had multiple substitutions in the penicillin binding proteins (PBP), mainly PBP2x, when compared with reference sequences, and showed 31 amino acid alterations in MurM. For MDR isolates, CPT (99.9%S), tigecycline (99.9%S), linezolid (100.0%S), and vancomycin (100.0%S) were the most active agents.ConclusionCPT demonstrated potent and consistent (2010–2016) activity against SPN, including several R phenotypes and the less S serotypes. SPN S to many antibiotics increased from 2011 to 2015, but remained stable in 2015–2016. Increases in S rates could be related to the anti-pneumococcal vaccine PVC-13 introduced in 2010.Disclosures M. A. Pfaller, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; H. S. Sader, Allergan: Research Contractor, Research grant

In vitro Activity of Ceftaroline Against Pathogens Collected Globally from the AWARE Surveillance Program, 2016

BackgroundCeftaroline, the active metabolite of ceftaroline fosamil, is a cephalosporin developed for treating infections caused by Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), Streptococcus pneumoniae, β-hemolytic streptococci, and some Gram-negative pathogens. This study reports the in vitro activity of ceftaroline against clinically relevant isolates collected in 2016 from the AWARE Surveillance Program.Methods22,752 non-duplicate methicillin-sensitive S. aureus (MSSA), MRSA, S. pneumoniae, β-hemolytic streptococci (S. pyogenes, S. agalactiae, S. dysgalactiae) Haemophilus influenzae, and extended spectrum β-lactamase (ESBL)-negative Enterobacteriaceae were collected from (n/%) Asia/South Pacific (4,215/18.5%), Europe (12,962/57.0%), Latin America (3,384/14.9%), and Middle East/Africa (2,191/9.6%) during 2016. Isolates were from (n/%) complicated intraabdominal (2,149/9.5%), complicated urinary tract (3,029/13.3%), complicated skin and skin structure (8,271/36.4%), blood stream (2,422/10.6%) and lower respiratory tract infections (6,881/30.2%). MIC values were determined by broth microdilution and interpreted using CLSI breakpoints.ResultsCeftaroline activity, based on % susceptibility (%S) and MIC90, is shown in the table. Ceftaroline was active in vitro against both Gram-positive (100% of MSSA, 93.6% of MRSA and 99.7% of S. pneumoniae) and Gram-negative (99.7% of H. influenzae and 91.7% of ESBL-negative Enterobacteriaceae) isolates. Organism (N) % S % I % R MIC 50 MIC 90 MRSA (5,022)93.66.00.50.51MSSA (3,675)100000.250.25 Streptococcus pneumoniae (2,024)99.7--0.30.0080.12β-hemolytic streptococci (1,713)100----0.0080.015 Enterobacteriaceae, ESBL-Negative (9,647)91.73.74.60.120.5 Haemophilus influenzae (671)99.7--0.3≤0.0150.03%S, %I, %R- percent susceptible, intermediate, resistant based on CLSI breakpoints; MIC50, MIC90 in µg/mL.ConclusionBased on these data generated with isolates collected in 2016, ceftaroline exhibited potent in vitro activity against clinically relevant isolates, with >91% of all isolates susceptible at their CLSI breakpoints. Funding: This study was sponsored by AstraZeneca. The AstraZeneca product ceftaroline fosamil was acquired by Pfizer in December 2016.Disclosures J. Iaconis, AstraZeneca: Employee and Shareholder, Salary and Shareholder in AstraZeneca

Ceftaroline Activity Tested Against Bacterial Isolates Causing Community-acquired Respiratory Tract Infections and Skin and Skin Structure Infections in Pediatric Patients From United States Hospitals

Ceftaroline fosamil has recently received US Food and Drug Administration approval for treatment of acute bacterial skin/skin structure infections (SSSIs), including those caused by methicillin-resistant Staphylococcus aureus and community-acquired bacterial pneumonia for pediatric patients ≥2 months old. We evaluated the potency and spectrum of ceftaroline and comparators when tested against community-acquired respiratory tract infection (CARTI) and SSSI pathogens from pediatric patients. A total of 3141 consecutive, unique pediatric patient isolates of clinical significance (1460 CARTI and 1681 SSSI isolates) were collected from 29 US medical centers and tested for susceptibility to ceftaroline and comparators by broth microdilution methods. The organism collection included Streptococcus pneumoniae (n = 754), Haemophilus influenzae (487), S. aureus (1399), β-hemolytic streptococci (214), Enterobacteriaceae (112), Pseudomonas aeruginosa (58), Klebsiella spp. (39), Escherichia coli (26) and miscellaneous other bacteria (52). Susceptibility results were analyzed according to patient age as follows: ≤1, 2-5, 6-12 and 13-17 years old. Overall, 99%-100% of Gram-positive isolates and H. influenzae were susceptible to ceftaroline according to Clinical and Laboratory Standards Institute clinical breakpoint criteria. Ceftaroline exhibited potent in vitro activity against bacterial pathogens from CARTI and SSSI recently (2012-2014) collected from pediatric patients in US medical centers. Ceftaroline was particularly active against methicillin-resistant S. aureus from SSSI ([minimum inhibitory concentration for 50% and 90% of isolates (MIC50/90,)] and ceftriaxone-nonsusceptible isolates of S. pneumoniae from CARTI (MIC50/90, 0.25/0.5 μg/mL; 98.3% susceptible).

Cave canem: HBO₂ therapy efficacy on Capnocytophaga canimorsus infections: a case series.

Dog bites are a frequent injury, but the incidence and type of lesions vary across countries. Although only few patients develop complications, the treatment of advanced injuries has a considerable medical, social and economic impact. A frequently isolated pathogen in dog bite wounds is Capnocytophaga canimorsus, a bacterium that can cause sepsis or meningitis. Hyperbaric oxygen (HBO₂) therapy has been shown to be useful in treating anaerobic infections, most likely because it creates an inhospitable environment for the bacterium and enhances the patient's immune response. We present a case series of C. canimorsus infections treated with HBO₂ in adjunction to antibiotic therapy. Furthermore, we tested the in vitro activity of ceftaroline against C. canimorsus, alone and in association with hyperbaric oxygen therapy. We included nine (9) patients admitted to the surgery department of "A. Cardarelli" Hospital (Naples) after dog bite, from 2010 to 2016. All were initially treated with antibiotics and required transfer to the intensive care unit due to worsening conditions. C. canimorsus was isolated from wounds, and HBO₂ therapy was administered in adjunction to antibiotics, until clinical improvement and microbiological test negativity. We tested the activity of hyperbaric oxygen therapy in adjunction to ceftaroline on cultured plates with C. canimorsus versus ceftaroline alone. Minimal inhibitory concentration was evaluated. Our findings confirm the utility of HBO₂ therapy after biting injuries. Indeed, increased oxygen supply to the wound (as well as in vitro) may be toxic for bacteria, can improve healing and may improve the effectiveness of antibiotics.

In vitro activity of ceftaroline and comparator agents against Gram-positive and Gram-negative clinical isolates from cancer patients

Bacterial infections are common in cancer patients. Ceftaroline (CFT) is a broad-spectrum cephalosporin with activity against most Gram-positive organisms (GPOs) and many Gram-negative organisms. In this study, the in vitro activity of CFT was compared with vancomycin (VAN), daptomycin (DAP), linezolid (LZD), trimethoprim/sulphamethoxazole (SXT) and tigecycline (TIG) against bacteria (predominantly blood culture isolates) isolated from cancer patients in 2014 and 2015. CFT was active against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-susceptible coagulase-negative staphylococci (MS-CoNS) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) with MIC90 values (minimum inhibitory concentration that inhibited 90% of the isolates) of 0.25, 2.0, 0.12 and 0.5 mg/L, respectively. MIC90 values for other GPOs were: Bacillus spp., >8.0 mg/L; Corynebacterium spp., 2.0 mg/L; Micrococcus spp., <0.06 mg/L; viridans group streptococci, 0.5 mg/L; Streptococcus pneumoniae, 0.25 mg/L; and Streptococcus spp., <0.06 mg/L. Among the comparator agents, VAN, DAP, TIG and LZD were active against the majority of GPOs tested. CFT also had moderate activity against common extended-spectrum β-lactamase (ESBL)-negative Gram-negative bacilli such as Enterobacter cloacae, Escherichia coli, Klebsiella spp., Proteus mirabilis and Serratia spp.

Impact of defined cell envelope mutations in Escherichia coli on the in vitro antibacterial activity of avibactam/β-lactam combinations

Avibactam is a novel non-β-lactam β-lactamase inhibitor being developed in combination with ceftazidime, ceftaroline and aztreonam for the treatment of infections caused by Gram-negative bacteria. Avibactam protects the antibacterial activity of these antibiotics by inhibiting Ambler classes A and C and some class D β-lactamases. The Gram-negative cell envelope presents a complex barrier to hydrophilic solutes and contains multiple molecular determinants of antibiotic susceptibility and resistance. To investigate the role of some of these determinants in the activity of avibactam and its partner antibiotics in Escherichia coli, an isogenic panel with deletions in specific components of the cell envelope was constructed in an E. coli W3110 strain background. The mutant constructs were also engineered to express the β-lactamase CTX-M-15 as a tool to enable assessment of the activity of avibactam. Mutations to shorten the lipopolysaccharide (LPS), to reduce efflux from the basal (i.e. non-upregulated) level or to alter the outer membrane porin composition did not have appreciable effects on the in vitro activity of ceftazidime, ceftaroline or aztreonam alone or in combination with avibactam. In conclusion, in this susceptible strain background, none of the β-lactams nor avibactam was measurably subject to efflux based on evaluating minimum inhibitory concentrations (MICs). None of the porin single or double mutations caused a decrease in susceptibility to the test compounds, implying that the compounds do not possess a strong porin preference, but instead can pass the outer membrane through a variety of routes.

In Vitro Activity of Ceftaroline Against Skin and Soft Tissue and Respiratory Pathogens Isolated From Latin America

In Vitro Activity of Ceftaroline Against Skin and Soft Tissue and Respiratory Pathogens Isolated From Latin America

In Vitro activity of Ceftaroline and Comparator Agents Against Bacterial Isolates From Cancer Patients

In Vitro activity of Ceftaroline and Comparator Agents Against Bacterial Isolates From Cancer Patients

Comparative In Vitro Activity of Ceftaroline Against Gram-Negative and Gram-Positive Clinically Significant Bacterial Isolates From Patients in a Teaching Hospital.

Comparative In Vitro Activity of Ceftaroline Against Gram-Negative and Gram-Positive Clinically Significant Bacterial Isolates From Patients in a Teaching Hospital.

Evaluation of the In Vitro Activity of Ceftaroline Tested Against Clinical Bacterial Isolates from US Hospitals: Results From 5 Years of the AWARE Surveillance Program (2011–2015)

Evaluation of the In Vitro Activity of Ceftaroline Tested Against Clinical Bacterial Isolates from US Hospitals: Results From 5 Years of the AWARE Surveillance Program (2011–2015)

Efficacy of ceftaroline versus vancomycin in an experimental foreign-body and systemic infection model caused by biofilm-producing methicillin-resistant Staphylococcus epidermidis

In this study, the efficacy of ceftaroline versus vancomycin against biofilm-producing methicillin-resistant Staphylococcus epidermidis (MRSE) in a murine model of foreign-body and systemic infection was compared. Two bacteraemic biofilm-producing MRSE strains were used (SE284 and SE385). The minimum inhibitory concentrations (MICs) for strains SE284 and SE385, were, respectively, 0.25 mg/L and 0.5 mg/L for ceftaroline and 4 mg/L and 2 mg/L for vancomycin. The in vitro bactericidal activities of ceftaroline and vancomycin were evaluated using time–kill curves. A foreign-body and systemic infection model in neutropenic female C57BL/6 mice was used to ascertain in vivo efficacy. Animals were randomly allocated into three groups (n = 15) without treatment (controls) or treated with ceftaroline 50 mg/kg every 8 h or vancomycin 110 mg/kg every 6 h. In vitro, ceftaroline showed concentration-dependent bactericidal activity, whilst vancomycin presented time-dependent activity. In the experimental in vivo model, ceftaroline and vancomycin decreased the liver and catheter bacterial concentrations (P < 0.05) and increased survival (P < 0.05) for both strains. In conclusion, ceftaroline is as effective as vancomycin in the treatment of experimental foreign-body and systemic infection caused by biofilm-producing MRSE.

In vitro activity of ceftaroline against clinical Staphylococcus aureus isolates collected during a national survey conducted in Belgian hospitals.

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. 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. aureus including three MRSA and two MSSA from hospitalized patients. Isolates were analysed by spa typing, SCCmec typing (for MRSA) and PCR for detection of 16S-mecA-nuc and 16S-mecC. MICs of oxacillin, cefoxitin and ceftaroline were determined by the broth microdilution method. The nucleotide sequences of mecA, native pbp and gdpP genes of isolates with reduced susceptibility to ceftaroline were analysed for the presence of mutations responsible for amino acid substitutions. Ninety-nine percent of isolates, including MRSA (n = 284) and MSSA (n = 131), were susceptible to ceftaroline. Only four MRSA isolates showed resistance to ceftaroline (MIC = 2 mg/L). These four isolates belonged to lineages CC5 (n = 1), CC22 (n = 2) and CC8 (n = 1). Two isolates (CC22 and CC8) carried mutations in mecA, as well as in other pbp genes. The remaining isolates carried mutations in native pbp genes or in gdpP. This is the first Belgian in vitro survey on ceftaroline activity against S. aureus. This antibiotic showed excellent activity against MRSA and MSSA, and only a few MRSA isolates with resistance were found. Reduced susceptibility to ceftaroline seems a complex phenomenon due to the accumulation of mutations in genes involved in β-lactam tolerance.

Comparative in vitro activities of ceftaroline and ceftriaxone against bacterial pathogens associated with respiratory tract infections: results from the AWARE surveillance study.

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. 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. The identification was confirmed centrally by MALDI-TOF and broth microdilution susceptibility testing and interpretation was done according to CLSI guidelines. Ceftaroline was 16-fold more potent against MSSA (MIC90 0.25 versus 4 mg/L) than ceftriaxone and ≥16-fold more potent against MRSA (MIC90 2 versus >32 mg/L). Ceftaroline was 16-fold more potent against S. pneumoniae (MIC90 0.12-0.25 mg/L) compared with ceftriaxone (MIC90 1-2 mg/L), with higher MIC values observed among penicillin-non-susceptible isolates for both agents. Similar activity (MIC90 ≤0.03 mg/L) was observed for ceftaroline and ceftriaxone against H. influenzae, with higher MIC values observed in the Asia-Pacific region for both agents compared with other regions. Ceftaroline was 4- to 8-fold more active against M. catarrhalis (MIC90 0.12-0.25 mg/L) compared with ceftriaxone (MIC90 1 mg/L). These global MIC data demonstrated that ceftaroline exhibited superior in vitro activity compared with ceftriaxone against bacterial species that commonly cause community-associated respiratory tract infections.

In vitro activity of Ceftaroline against bacterial pathogens isolated from patients with skin and soft tissue and respiratory tract infections in African and Middle Eastern countries: AWARE global surveillance program 2012–2014

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. All methicillin-susceptible Staphylococcus aureus (MSSA) (n= 923; MIC90, 0.25 μg/mL) and 91.8% of methicillin-resistant S. aureus (MRSA) (n= 1161; MIC90, 1 μg/mL) tested were susceptible to ceftaroline. The maximum ceftaroline MIC observed for isolates of MRSA was 2 μg/mL. All Streptococcus pyogenes (n= 174; MIC90, 0.008 μg/mL), Streptococcus agalactiae (n= 44; MIC90, 0.015 μg/mL), Streptococcus pneumoniae (n= 351; MIC90, 0.25 μg/mL), and Haemophilus influenzae (n= 84; MIC90, ≤0.015 μg/mL) were susceptible to ceftaroline. Rates of susceptibility to ceftaroline among ESBL-negative Escherichia coli (n= 338), Klebsiella pneumoniae (n= 241), and Klebsiella oxytoca (n= 97) were 89.1% (MIC90, 1 μg/mL), 94.2% (MIC90, 0.5 μg/mL), and 99.0% (MIC90, 0.5 μg/mL), respectively.

Multi-center and multi-method evaluation of in vitro activities of ceftaroline against S. aureus

This five-site study was performed to assess the reproducibility of ceftaroline MIC and disk results for Staphylococcus aureus. Three commercial broth microdilution, three gradient diffusion and ceftaroline 5μg disk diffusion methods were compared to a reference broth microdilution method against challenge isolates (n = 41) and isolates collected at four European sites (n = 30/site). For four MIC methods (Sensititre and three gradient diffusion methods), 99.0% of consolidated MIC results were within +/− 1 dilution of the reference MIC. Categorical agreement rates based on EUCAST breakpoints for the challenge isolates were 75.6-100% and for disk testing were 78.0-92.7%. There was no clear distinction between isolates with MIC results of 1 and 2mg/L with regard to variation in MIC or molecular genotyping results. The addition of an intermediate category for isolates with MIC results of 2mg/L would help to identify these isolates as borderline susceptible/non-susceptible isolates.

Antimicrobial Activity of Ceftaroline Tested against Staphylococcus aureus from Surgical Skin and Skin Structure Infections in US Medical Centers.

Ceftaroline fosamil is a novel cephalosporin approved by the United States Food and Drug Administration (US FDA) for treatment of acute bacterial skin and skin structure infection, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of ceftaroline and comparator agents tested against S. aureus isolated from surgical skin and skin structure infections (SSSI). Clinically substantial isolates (one/patient episode) from SSSI were consecutively collected from 64 medical centers in the United States over a 6-y period (2008-2013) and tested for susceptibility by broth microdilution methods against ceftaroline and several comparator agents. Among 794 strains tested, 50.5% were MRSA. Ceftaroline was active against all methicillin-susceptible Staphylococcus aureus (MSSA; minimal inhibitory concentration [MIC]90, 0.25 mcg/mL) and nearly all MRSA (MIC90, 1 mcg/mL). Against MSSA, ceftaroline was 16-fold more potent than ceftriaxone (MIC90, 4 mcg/mL) and the highest ceftaroline MIC was 0.5 mcg/mL. Among MRSA, 97.5% and 100.0% of strains were inhibited at ≤1 and ≤2 mcg/mL of ceftaroline. Furthermore, 27.4% and 67.5% of MRSA were resistant to clindamycin and levofloxacin, respectively. Daptomycin (MIC50/90, 0.25/0.5 mcg/mL), linezolid (MIC50/90, 1/2 mcg/mL), tigecycline (MIC50/90, 0.06/0.12 mcg/mL) and vancomycin (MIC50/90, 1/2 mcg/mL) were also highly active against S. aureus strains. Ceftaroline exhibited potent in vitro activity against S. aureus causing SSSI in a large number of US hospitals, including MRSA. On the basis of this in vitro data, ceftaroline fosamil may represent a valuable option for treatment of surgical SSSI, and should be further evaluated as an agent for surgical prophylaxis that would cover MRSA.