scholarly journals Ceftaroline Activity against Bacterial Pathogens Frequently Isolated in U.S. Medical Centers: Results from Five Years of the AWARE Surveillance Program

2015 ◽  
Vol 59 (4) ◽  
pp. 2458-2461 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Jennifer M. Streit ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Bacterial Pathogens ◽  
Surveillance Program ◽  
Broth Microdilution ◽  
Methicillin Resistant ◽  
Content Type ◽  
Medical Centers ◽  
Resistant Strains

ABSTRACTA total of 84,704 isolates were collected from 191 medical centers in 2009 to 2013 and tested for susceptibility to ceftaroline and comparator agents by broth microdilution methods. Ceftaroline inhibited allStaphylococcus aureusisolates at ≤2 μg/ml and was very active against methicillin-resistant strains (MIC at which 90% of the isolates tested are inhibited [MIC90], 1 μg/ml; 97.6% susceptible). AmongStreptococcus pneumoniaeisolates, the highest ceftaroline MIC was 0.5 μg/ml, and ceftaroline activity against the most commonEnterobacteriaceaespecies (MIC50, 0.12 μg/ml; 78.9% susceptible) was similar to that of ceftriaxone (MIC50, ≤0.25 μg/ml; 86.8% susceptible).

scholarly journals Antimicrobial Susceptibility Trends among Staphylococcus aureus Isolates from U.S. Hospitals: Results from 7 Years of the Ceftaroline (AWARE) Surveillance Program, 2010 to 2016

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Helio S. Sader ◽  
Rodrigo E. Mendes ◽  
Jennifer M. Streit ◽  
Robert K. Flamm
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Susceptibility ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Broth Microdilution ◽  
Methicillin Resistant ◽  
Content Type ◽  
Medical Centers

ABSTRACT We evaluated trends in Staphylococcus aureus antimicrobial susceptibility in U.S. hospitals in the 2010–2016 period. A total of 21,056 clinical isolates from 42 medical centers were tested for susceptibility by broth microdilution methods. Methicillin-resistant S. aureus (MRSA) rates decreased from 50.0% (in 2010) to 42.2% (in 2016). Susceptibility to erythromycin, levofloxacin, and clindamycin increased slightly, whereas susceptibility to ceftaroline, trimethoprim-sulfamethoxazole, and tetracycline remained stable. Ceftaroline retained potent activity against methicillin-susceptible S. aureus (MSSA) and MRSA (97.2% susceptible) with no marked variations.

scholarly journals Antimicrobial Activity of Ceftaroline-Avibactam Tested against Clinical Isolates Collected from U.S. Medical Centers in 2010-2011

2013 ◽  
Vol 57 (4) ◽  
pp. 1982-1988 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Streptococcus Pneumoniae ◽  
Enterobacter Cloacae ◽  
Broth Microdilution ◽  
Methicillin Resistant ◽  
Content Type ◽  
Microdilution Method ◽  
Medical Centers ◽  
Broth Microdilution Method

ABSTRACTCeftaroline-avibactam and comparator agents were tested by the broth microdilution method against 20,089 isolates consecutively collected in 2010 and 2011 from 75 U.S. medical centers. Ceftaroline-avibactam was active againstEnterobacteriaceae(4,908 strains; MIC90, 0.25 μg/ml; highest MIC, 4 μg/ml), including meropenem-nonsusceptibleKlebsiellaspp. and ceftazidime-nonsusceptibleEnterobacter cloacaestrains (MIC90, 1 μg/ml for both). Ceftaroline-avibactam was also active against ceftriaxone-nonsusceptibleStreptococcus pneumoniae(MIC90, 0.25 μg/ml) and methicillin-resistantStaphylococcus aureus(MIC90, 1 μg/ml).

scholarly journals Missense Mutations in PBP2A Affecting Ceftaroline Susceptibility Detected in Epidemic Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Clonotypes ST228 and ST247 in Western Switzerland Archived since 1998

2015 ◽  
Vol 59 (4) ◽  
pp. 1922-1930 ◽  
Author(s):  
William L. Kelley ◽  
Ambre Jousselin ◽  
Christine Barras ◽  
Emmanuelle Lelong ◽  
Adriana Renzoni
Keyword(s):  
Staphylococcus Aureus ◽  
University Hospital ◽  
Surveillance Program ◽  
Missense Mutations ◽  
Unknown Parameters ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistant Strains ◽  
Mrsa Strains

ABSTRACTThe development and maintenance of an arsenal of antibiotics is a major health care challenge. Ceftaroline is a new cephalosporin with activity against methicillin-resistantStaphylococcus aureus(MRSA); however, no reports concerning MRSA ceftaroline susceptibility have been reported in Switzerland. We tested thein vitroactivity of ceftaroline against an archived set of 60 MRSA strains from the University Hospital of Geneva collected from 1994 to 2003. Our results surprisingly revealed ceftaroline-resistant strains (MIC, >1 μg/ml in 40/60 strains; EUCAST breakpoints, susceptible [S], ≤1 μg/ml; resistant [R], >1 μg/ml) were present from 1998 to 2003. The detected resistant strains predominantly belonged to sequence type 228 (ST228) (South German clonotype) but also to ST247 (Iberian clonotype). A sequence analysis of these strains revealed missense mutations in the penicillin-binding protein 2A (PBP2A) allosteric domain (N146K or E239K and N146K-E150K-G246E). The majority of our ST228 PBP2A mutations (N146K or E150K) were distinct from ST228 PBP2A allosteric domain mutations (primarily E239K) recently described for MRSA strains collected in Thailand and Spain during the 2010 Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) global surveillance program. We also found that similar allosteric domain PBP2A mutations (N146K) correlated with ceftaroline resistance in an independent external ST228 MRSA set obtained from the nearby University Hospital of Lausanne, Lausanne, Switzerland, collected from 2003 to 2008. Thus, ceftaroline resistance was observed in our archived strains (including two examples of an MIC of 4 µg/ml for the Iberian ST247 clonotype with the triple mutation N146K/E150K/G246E), at least as far back as 1998, considerably predating the commercial introduction of ceftaroline. Our results reinforce the notion that unknown parameters can potentially exert selective pressure on PBP2A that can subsequently modulate ceftaroline resistance.

scholarly journals Regional Resistance Surveillance Program Results for 12 Asia-Pacific Nations (2011)

2013 ◽  
Vol 57 (11) ◽  
pp. 5721-5726 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Myrna Mendoza ◽  
Kirnpal K. Banga Singh ◽  
Mariana Castanheira ◽  
Jan M. Bell ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Streptococcus Pneumoniae ◽  
South Korea ◽  
Geographic Region ◽  
Asia Pacific ◽  
Surveillance Program ◽  
Broth Microdilution ◽  
Content Type

ABSTRACTThe Regional Resistance Surveillance program monitored susceptibility rates and developing resistance by geographic region, including 12 Asia-Pacific (APAC) countries. Reference broth microdilution methods for susceptibility/interpretations were applied, processing 5,053 strains. AmongStaphylococcus aureusisolates (37% methicillin-resistantS. aureus[MRSA], highest in South Korea [73%]), linezolid (LZD), tigecycline (TIG), and vancomycin were 100% active, but 33 and 34% of strains were levofloxacin (LEV) or macrolide resistant, respectively.Streptococcus pneumoniaewas most resistant to β-lactams and macrolides (45%) but was LZD, LEV, and TIG susceptible (>98%). Extended-spectrum β-lactamase (ESBL) phenotype rates inEscherichia coliandKlebsiellaspp. were 48 and 47%, respectively, and were highest in Taiwan, at 75 to 91%. The best anti-ESBL-phenotype agents were amikacin (81 to 96% susceptible), colistin (COL; >98%), TIG (>98%), and carbapenems (81 to 97%).Pseudomonas aeruginosashowed ≥20% resistance to all drugs except COL (99% susceptible). In conclusion, endemic evolving antimicrobial resistances in APAC nations show compromised roles for many commonly used antimicrobials.

scholarly journals 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)

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Michael A. Pfaller ◽  
Rodrigo E. Mendes ◽  
Leonard R. Duncan ◽  
Robert K. Flamm ◽  
Helio S. Sader
Keyword(s):  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
Content Type ◽  
Medical Centers ◽  
Extensively Drug Resistant

ABSTRACT 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.

scholarly journals Disarming Pore-Forming Toxins with Biomimetic Nanosponges in Intraocular Infections

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Phillip S. Coburn ◽  
Frederick C. Miller ◽  
Austin L. LaGrow ◽  
Craig Land ◽  
Huzzatul Mursalin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Bacillus Cereus ◽  
Enterococcus Faecalis ◽  
Vision Loss ◽  
Retinal Function ◽  
Bacterial Invasion ◽  
Methicillin Resistant ◽  
Content Type ◽  
Ocular Pathology

ABSTRACTIntraocular infections are prevalent after traumatic injuries or after common ocular surgeries. Infections cause inflammation that can damage the retina and architecture of the eye, often resulting in poor visual outcomes. Severe cases may result in blindness or require enucleation of the eye. Treatments for intraocular infections include intravitreal antibiotics and corticosteroids or surgical vitrectomy in serious cases. The increase in multidrug-resistant infections calls for novel treatment options. In the present study, a biomimetic erythrocyte-derived nanosponge was tested for the ability to neutralize pore-forming toxins from the most frequent Gram-positive bacterial causes of intraocular infections (Staphylococcus aureus,Enterococcus faecalis,Streptococcus pneumoniae, andBacillus cereus). Nanosponge pretreatment of supernatants reduced hemolytic activityin vitro.In a murine sterile endophthalmitis model, nanosponge pretreatment of injected supernatants resulted in greater retinal function and less ocular pathology compared to that in eyes injected with untreated supernatants from all pathogens except methicillin-resistantS. aureus. In a murine bacterial endophthalmitis model, treatment with gatifloxacin and gatifloxacin-nanosponges reduced intraocular bacterial burdens, except in the case of methicillin-sensitiveS. aureus. For all pathogens, eyes in both treatment groups showed decreased ocular pathology and inflammation. Overall, reductions in retinal function loss afforded by gatifloxacin-nanosponge treatment were significant forE. faecalis,S. pneumoniae, and methicillin-resistantS. aureusbut not forB. cereusand methicillin-sensitiveS. aureus. These results suggest that clinical improvements in intraocular infections following nanosponge treatment were dependent on the complexity and types of toxins produced. Nanosponges might serve as an adjunctive therapy for the treatment of ocular infections.IMPORTANCEEndophthalmitis is a blinding consequence of bacterial invasion of the interior of the eye. Because of increases in the numbers of ocular surgeries and intraocular injections, the incidence of endophthalmitis is steadily increasing.Staphylococcus aureus,Enterococcus faecalis,Streptococcus pneumoniae, andBacillus cereusare leading causes of infection following ocular procedures and trauma and are increasingly more difficult to treat due to multidrug resistance. Each of these pathogens produces pore-forming toxins that contribute to the pathogenesis of endophthalmitis. Treatment of these infections with antibiotics alone is insufficient to prevent damage to the retina and vision loss. Therefore, novel therapeutics are needed that include agents that neutralize bacterial pore-forming toxins. Here, we demonstrate that biomimetic nanosponges neutralize pore-forming toxins from these ocular pathogens and aid in preserving retinal function. Nanosponges may represent a new form of adjunct antitoxin therapy for serious potentially blinding intraocular infections.

scholarly journals Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening for Patients with a Diabetic Foot Infection

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Kari A. Mergenhagen ◽  
Michael Croix ◽  
Kaitlyn E. Starr ◽  
John A. Sellick ◽  
Alan J. Lesse
Keyword(s):  
Staphylococcus Aureus ◽  
Diabetic Foot ◽  
International Classification Of Diseases ◽  
Methicillin Resistant ◽  
Content Type ◽  
Diabetic Foot Infection ◽  
Entire Cohort ◽  
Diabetic Foot Infections ◽  
Medical Centers ◽  
Classification Of Diseases

ABSTRACT Treatment of suspected methicillin-resistant Staphylococcus aureus (MRSA) is a cornerstone of severe diabetic foot infections; however, antibiotics can be associated with toxicity. The objective of this study was to determine the negative predictive value (NPV) of MRSA nares screening in the determination of subsequent MRSA in patients with a diabetic foot infection. This was a retrospective cohort study across Veterans Affairs (VA) medical centers from 1 January 2007 to 1 January 2018. Data from patients with an International Classification of Diseases (ICD) code for a diabetic foot infection with MRSA nares screening, and subsequent cultures were evaluated for the presence of MRSA. NPVs were calculated for the entire cohort, as well as for a subgroup representing deep cultures. Additionally, the distribution of all pathogens isolated from diabetic foot infections was determined. A total of 8,163 episodes were included in the analysis for NPV. The NPV of MRSA nares screening for MRSA diabetic foot infection was 89.6%. For the deep cultures, the NPV was 89.2%. The NPV for cultures originating from the foot was 89.7%, and the NPV for those originating from the toe was 89.4%. There were 17,822 pathogens isolated from the diabetic foot cultures. MRSA was isolated in 7.5% of cultures, and methicillin-susceptible S. aureus was isolated in 24.8%. Enterococcus was identified in 14.7% of cultures, Proteus in 7.3%, and Pseudomonas in 6.8% of cultures. Given the high NPVs, the use of MRSA nares screening may be appropriate as a stewardship tool for deescalation and avoidance of empirical anti-MRSA therapy in patients who are not nasal carries of MRSA.

scholarly journals Activity of Ceftaroline and Epidemiologic Trends in Staphylococcus aureus Isolates Collected from 43 Medical Centers in the United States in 2009

2011 ◽  
Vol 55 (9) ◽  
pp. 4154-4160 ◽  
Author(s):  
Sandra S. Richter ◽  
Kristopher P. Heilmann ◽  
Cassie L. Dohrn ◽  
Fathollah Riahi ◽  
Andrew J. Costello ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Surveillance Program ◽  
Content Type ◽  
Type Iv ◽  
Medical Centers ◽  
High Level ◽  
Resistance Rates

ABSTRACTAStaphylococcus aureussurveillance program was initiated in the United States to examine thein vitroactivity of ceftaroline and epidemiologic trends. Susceptibility testing by Clinical and Laboratory Standards Institute broth microdilution was performed on 4,210 clinically significant isolates collected in 2009 from 43 medical centers. All isolates were screened formecAby PCR and evaluated by pulsed-field gel electrophoresis. Methicillin-resistantS. aureus(MRSA) were analyzed for Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosomemec(SCCmec) type. All isolates had ceftaroline MICs of ≤2 μg/ml with an MIC50of 0.5 and an MIC90of 1 μg/ml. The overall resistance rates, expressed as the percentages of isolates that were intermediate and resistant (or nonsusceptible), were as follows: ceftaroline, 1.0%; clindamycin, 30.2% (17.4% MIC ≥ 4 μg/ml; 12.8% inducible); daptomycin, 0.2%; erythromycin, 65.5%; levofloxacin, 39.9%; linezolid, 0.02%; oxacillin, 53.4%; tetracycline, 4.4%; tigecycline, 0%; trimethoprim-sulfamethoxazole, 1.6%; vancomycin, 0%; and high-level mupirocin, 2.2%. ThemecAPCR was positive for 53.4% of the isolates. The ceftaroline MIC90s were 0.25 μg/ml for methicillin-susceptibleS. aureusand 1 μg/ml for MRSA. Among the 2,247 MRSA isolates, 51% were USA300 (96.9% PVL positive, 99.7% SCCmectype IV) and 17% were USA100 (93.4% SCCmectype II). The resistance rates for the 1,137 USA300 MRSA isolates were as follows: erythromycin, 90.9%; levofloxacin, 49.1%; clindamycin, 7.6% (6.2% MIC ≥ 4 μg/ml; 1.4% inducible); tetracycline, 3.3%; trimethoprim-sulfamethoxazole, 0.8%; high-level mupirocin, 2.7%; daptomycin, 0.4%; and ceftaroline and linezolid, 0%. USA300 is the dominant clone causing MRSA infections in the United States. Ceftaroline demonstrated potentin vitroactivity against recentS. aureusclinical isolates, including MRSA, daptomycin-nonsusceptible, and linezolid-resistant strains.

scholarly journals Summary of Ceftaroline Activity against Pathogens in the United States, 2010: Report from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Surveillance Program

2012 ◽  
Vol 56 (6) ◽  
pp. 2933-2940 ◽  
Author(s):  
Robert K. Flamm ◽  
Helio S. Sader ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Bloodstream Infections ◽  
The United States ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Medical Centers ◽  
Therapeutic Decision Making ◽  
Tract Infections

ABSTRACTTheAssessingWorldwideAntimicrobialResistanceEvaluation (AWARE) surveillance program is a sentinel resistance monitoring system designed to track the activity of ceftaroline and comparator agents. In the United States, a total of 8,434 isolates were collected during the 2010 surveillance program from 65 medical centers distributed across the nine census regions (5 to 10 medical centers per region). All organisms were isolated from documented infections, including 3,055 (36.2%) bloodstream infections, 2,282 (27.1%) respiratory tract infections, 1,965 (23.3%) acute bacterial skin and skin structure infections, 665 (7.9%) urinary tract infections, and 467 (5.5%) miscellaneous other infection sites. Ceftaroline was the most potent β-lactam agent tested against staphylococci. The MIC90values were 1 μg/ml for methicillin-resistantStaphylococcus aureus(MRSA; 98.4% susceptible) and 0.5 μg/ml for methicillin-resistant coagulase-negative staphylococci (CoNS). Ceftaroline was 16- to 32-fold more potent than ceftriaxone against methicillin-susceptible staphylococcal strains. All staphylococcus isolates (S. aureusand CoNS) were inhibited at ceftaroline MIC values of ≤2 μg/ml. Ceftaroline also displayed potent activity against streptococci (MIC90, 0.015 μg/ml for beta-hemolytic streptococci; MIC90, 0.25 μg/ml for penicillin-resistantStreptococcus pneumoniae). Potent activity was also shown against Gram-negative pathogens (Haemophilus influenzae,Haemophilus parainfluenzae, andMoraxella catarrhalis). Furthermore, wild-type strains ofEnterobacteriaceae(non-extended-spectrum β-lactamase [ESBL]-producing strains and non-AmpC-hyperproducing strains) were often susceptible to ceftaroline. Continued monitoring through surveillance networks will allow for the assessment of the evolution of resistance as this new cephalosporin is used more broadly to provide clinicians with up-to-date information to assist in antibiotic stewardship and therapeutic decision making.

scholarly journals In VitroActivity of Dalbavancin against Drug-Resistant Staphylococcus aureus Isolates from a Global Surveillance Program

2015 ◽  
Vol 59 (8) ◽  
pp. 5007-5009 ◽  
Author(s):  
Sandra P. McCurdy ◽  
Ronald N. Jones ◽  
Rodrigo E. Mendes ◽  
Sailaja Puttagunta ◽  
Michael W. Dunne
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Drug Resistant ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTIn over a decade (2002 to 2012) ofStaphylococcus aureussurveillance testing on 62,195 isolates, dalbavancin was demonstrated to be active against isolates that were either susceptible or nonsusceptible to daptomycin, linezolid, or tigecycline. Nearly all (99.8%) multidrug-resistant methicillin-resistantS. aureusisolates were inhibited by dalbavancin at ≤0.12 μg/ml (MIC50/90, 0.06/0.06 μg/ml), the current U.S. Food and Drug Administration (U.S. FDA) breakpoint. Overall, only 0.35% of the monitoredS. aureusisolates had a dalbavancin MIC of either 0.25 or 0.5 μg/ml (i.e., were nonsusceptible).

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