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Ceftaroline

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https://www.readbyqxmd.com/read/28505331/antimicrobial-susceptibility-of-clinical-isolates-of-neisseria-gonorrhoeae-to-alternative-antimicrobials-with-therapeutic-potential
#1
P R S Lagacé-Wiens, H J Adam, N M Laing, M R Baxter, I Martin, M R Mulvey, J A Karlowsky, D J Hoban, G G Zhanel
Background: The prevalence of MDR Neisseria gonorrhoeae is increasing globally and represents a public health emergency. Development and approval of new anti-gonococcal agents may take years. As a concurrent approach to developing new antimicrobials, the laboratory and clinical evaluation of currently licensed antimicrobials not widely used for the treatment of gonorrhoea may provide new options for the treatment of gonococcal infections. Objectives: To determine the in vitro activity of nine alternative, currently licensed and late-development antimicrobials with the potential to treat gonococcal infections against 112 clinical isolates of N...
May 12, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28483961/efficacy-of-ceftaroline-in-a-rat-model-of-endocarditis-against-methicillin-susceptible-staphylococcus-aureus-exhibiting-the-cefazolin-high-inoculum-effect
#2
Kavindra V Singh, Truc T Tran, Esteban C Nannini, Vincent H Tam, Cesar A Arias, Barbara E Murray
Certain Staphylococcus aureus strains exhibit an inoculum effect (InE) with cefazolin (CFZ), which has been associated with therapeutic failures in high inoculum infections. We assessed the in vitro activity of ceftaroline (CPT), CFZ and nafcillin (NAF) against 17 type A β-lactamase (βla)-producing, methicillin-susceptible S. aureus (MSSA) strains, including the previously reported TX0117 that exhibits the CFZ InE and its β-lactamase (βla)-cured derivative, TX0117c. Additionally, we determined the pharmacokinetics of CPT in rats after single intramuscular doses of 20 and 40 mg/kg and evaluated the activity of CPT (40 mg/kg, Q 8 h), CFZ and NAF against TX0117 and TX0117c in a rat model of infective endocarditis...
May 8, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28475731/evaluation-of-daptomycin-combinations-with-cephalosporins-or-gentamicin-against-streptococcus-mitis-group-strains-in-an-in-vitro-model-of-simulated-endocardial-vegetations-sevs
#3
Juwon Yim, Jordan R Smith, Nivedita B Singh, Seth Rice, Kyle Stamper, Cristina Garcia de la Maria, Arnold S Bayer, Nagendra N Mishra, José M Miró, Truc T Tran, Cesar A Arias, Paul Sullam, Michael J Rybak
Objectives: Among viridans group streptococcal infective endocarditis (IE), the Streptococcus mitis group is the most common aetiological organism. Treatment of IE caused by the S. mitis group is challenging due to the high frequency of β-lactam resistance, drug allergy and intolerability of mainstay antimicrobial agents such as vancomycin or gentamicin. Daptomycin has been suggested as an alternative therapeutic option in these scenarios based on its excellent susceptibility profile against S...
May 5, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28419033/oral-only-linezolid-rifampin-is-highly-effective-compared-with-other-antibiotics-for-periprosthetic-joint-infection-study-of-a-mouse-model
#4
John M Thompson, Vikram Saini, Alyssa G Ashbaugh, Robert J Miller, Alvaro A Ordonez, Roger V Ortines, Yu Wang, Robert S Sterling, Sanjay K Jain, Lloyd S Miller
BACKGROUND: The medical treatment of periprosthetic joint infection (PJI) involves prolonged systemic antibiotic courses, often with suboptimal clinical outcomes including increased morbidity and health-care costs. Oral and intravenous monotherapies and combination antibiotic regimens were evaluated in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) PJI. METHODS: Oral linezolid with or without oral rifampin, intravenous vancomycin with oral rifampin, intravenous daptomycin or ceftaroline with or without oral rifampin, oral doxycycline, or sham treatment were administered at human-exposure doses for 6 weeks in a mouse model of PJI...
April 19, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28407067/evaluation-of-a-second-sign-process-for-antimicrobial-prior-authorization
#5
Aimee M Dassner, Jennifer E Girotto
Background.: A second-sign prospective restriction of select broad-spectrum antimicrobials was fully implemented in January 2015 as a pediatric antimicrobial stewardship program (ASP) initiative to help ensure the most appropriate empiric use of ceftaroline, cefepime, fidaxomicin, linezolid, and vancomycin (intravenous). The objective of this evaluation is to assess the effectiveness of a forced second-sign process in the electronic medical record as a pediatric ASP strategy. We anticipated that the second-sign process for antibiotics would increase the appropriateness of empiric antibiotic use, as defined by preapproved criteria, clinical pathways, national guidelines, and pediatric-specific infectious diseases reference texts, while not causing significant delay in the initial administration of antibiotic therapy...
April 12, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28403050/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-2012-2014
#6
MULTICENTER STUDY
Michael A Pfaller, Rodrigo E Mendes, Mariana Castanheira, Robert K Flamm, Ronald N Jones, Helio S Sader
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...
May 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28382572/current-clinical-trials-on-the-use-of-ceftaroline-in-the-pediatric-population
#7
REVIEW
Adam Corey, Tsz-Yin So
The rate of antibiotic resistance in children continues to rise requiring the use of new antibiotics. Ceftaroline fosamil, a newer-generation cephalosporin, was recently approved for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in children aged >2 months. Ceftaroline provides coverage against staphylococcal and streptococcal infections, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae...
April 5, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28373193/high-level-resistance-of-staphylococcus-aureus-to-%C3%AE-lactam-antibiotics-mediated-by-penicillin-binding-protein-4-pbp4
#8
Stephanie M Hamilton, J Andrew N Alexander, Eun Ju Choo, Li Basuino, Thaina M da Costa, Anatoly Severin, Marilyn Chung, Sandra Aedo, Natalie C J Strynadka, Alexander Tomasz, Som S Chatterjee, Henry F Chambers
PBP4, a non-essential, low molecular weight penicillin-binding protein of Staphylococcus aureus, has been implicated in low-level resistance to β-lactam antibiotics, although the mechanism is unknown. Mutations in PBP4 and its promoter were identified in a laboratory-generated mutant strain CRB, which expresses high-level resistance to β-lactams, including resistance to the new generation cephalosporins active against methicillin-resistant strains of S. aureus These mutations did not appreciably alter β-lactam antibiotic binding affinity of purified recombinant mutant PBP4 compared to wild-type...
April 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28348157/exploring-the-landscape-of-diazabicyclooctane-dbo-inhibition-avibactam-avi-inactivation-of-per-2-%C3%AE-lactamase
#9
Melina Ruggiero, Krisztina M Papp-Wallace, Magdalena A Taracila, Maria F Mojica, Christopher R Bethel, Susan D Rudin, Elise T Zeiser, Gabriel Gutkind, Robert A Bonomo, Pablo Power
PER β-lactamases are an emerging family of extended-spectrum β-lactamases (ESBL) found in Gram negative bacteria. PER β-lactamases are unique among class A enzymes as they possess an inverted Ω loop and extended B3 β-strand. These singular structural differences are hypothesized to contribute to their hydrolytic profile against oxyimino-cephalosporins (e.g., cefotaxime and ceftazidime). Here, we tested the ability of avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor to inactivate PER-2. Interestingly, the PER-2 inhibition constants (i...
March 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28314920/-new-antibiotics-standstill-or-progress
#10
J Rademacher, T Welte
The development of resistance to antibiotics has been ignored for a long time. But nowadays, increasing resistance is an important topic. For a decade no new antibiotics had been developed and it is not possible to quickly close this gap of new resistance and no new drugs. This work presents six new antibiotics (ceftaroline, ceftobiprole, solithromycin, tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam). In part, only expert opinions are given due to lack of study results.The two 5th generation cephalosporins ceftaroline and ceftobiprole have beside their equivalent efficacy to ceftriaxone (ceftaroline) and cefipim (ceftobiprole) high activity against MRSA...
March 17, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28257904/in-vitro-activity-of-ceftaroline-and-comparator-agents-against-gram-positive-and-gram-negative-clinical-isolates-from-cancer-patients
#11
Kenneth V I Rolston, Mohamed A Jamal, Lior Nesher, Samuel A Shelburne, Issam Raad, Randall A Prince
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...
April 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28242258/impact-of-defined-cell-envelope-mutations-in-escherichia-coli-on-the-in-vitro-antibacterial-activity-of-avibactam-%C3%AE-lactam-combinations
#12
Sarah M McLeod, Sara A Patey, Michael D Huband, Wright W Nichols
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...
April 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28179245/ceftaroline-for-the-treatment-of-methicillin-resistant-staphylococcus-aureus-bacteremia
#13
Bryan Pinckney White, Katie E Barber, Kayla R Stover
PURPOSE: The utility of ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is reviewed. SUMMARY: Ceftaroline was originally approved for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSIs) but recently received an additional approval for the treatment of S. aureus bacteremia (SAB) associated with ABSSSIs. Ceftaroline has demonstrated efficacy for the treatment of MRSAB, including isolates with elevated minimum inhibitory concentrations to conventional therapy when used alone or in combination with other agents...
February 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28134677/are-there-any-reasons-to-change-our-behavior-in-necrotizing-fasciitis-with-the-advent-of-new-antibiotics
#14
Francesco Menichetti, Simone Giuliano, Simona Fortunato
PURPOSE OF REVIEW: The treatment of necrotizing fasciitis requires a multifaceted approach, consisting of surgical source control with immediate surgical debridement along with life support, clinical monitoring, and antimicrobial therapy. Many drugs are now available for the treatment of this life-threatening infectious disease, and the purpose of this review is to provide the reader with an updated overview of the newest therapeutic options. RECENT FINDINGS: Because most necrotizing soft tissue infections are polymicrobial, broad-spectrum coverage is advisable...
April 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28131729/ceftaroline-fosamil-monotherapy-for-methicillin-resistant-staphylococcus-aureus-bacteremia-a-comparative-clinical-outcomes-study
#15
COMPARATIVE STUDY
Samia Arshad, Vanthida Huang, Pamela Hartman, Mary B Perri, Daniela Moreno, Marcus J Zervos
OBJECTIVES: Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, its use has been subject to scrutiny due to failure in severe infections. Ceftaroline fosamil (CPT-F) is approved for MRSA acute bacterial skin and skin structure infections, but not for bloodstream infections. The clinical outcomes of treatment with CPT-F in patients with MRSA bacteremia were evaluated. METHODS: Patients diagnosed with MRSA bacteremia at Henry Ford Hospital in Detroit, Michigan, USA, involving isolates with a vancomycin minimum inhibitory concentration ≥1...
April 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28128094/efficacy-of-ceftaroline-versus-vancomycin-in-an-experimental-foreign-body-and-systemic-infection-model-caused-by-biofilm-producing-methicillin-resistant-staphylococcus-epidermidis
#16
Juan Domínguez-Herrera, Rafael López-Rojas, Younes Smani, Gema Labrador-Herrera, Jerónimo Pachón
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...
December 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28116950/a-combination-of-ceftaroline-and-daptomycin-has-synergistic-and-bactericidal-activity-in-vitro-against-daptomycin-nonsusceptible-methicillin-resistant-staphylococcus-aureus-mrsa
#17
Iffat Shafiq, Zackery P Bulman, Sarah L Spitznogle, Justin E Osorio, Irene S Reilly, Alan J Lesse, Ganapathi I Parameswaran, Kari A Mergenhagen, Brian T Tsuji
There is an urgent need to optimize therapeutic options in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia who have failed conventional therapy. Two clinical isolates were obtained from a 68-year-old male with persistent MRSA bacteremia before and after the development of daptomycin nonsusceptibility. The pharmacodynamic activity of monotherapies and combinations of ceftaroline, daptomycin, cefoxitin, nafcillin and vancomycin were evaluated in time-kill experiments versus 10(8) CFU/mL of the pre- and post-daptomycin nonsusceptible MRSA isolates...
May 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28096164/pharmacodynamics-of-ceftaroline-plus-ampicillin-against-enterococcus-faecalis-in-an-in-vitro-pharmacokinetic-pharmacodynamic-model-of-simulated-endocardial-vegetations
#18
Brian J Werth, Laura M Shireman
The combination of ampicillin plus ceftaroline has been suggested to be more reliably synergistic against Enterococcus faecalis than ampicillin plus ceftriaxone using time-kill methods. The purpose of this study was to determine if this trend persists in a two-compartment model of simulated endocardial vegetations (SEV) using clinically relevant pharmacokinetic exposures of these antimicrobials. Three clinically derived E. faecalis strains were included in the study. The MICs of study antimicrobials were determined by broth microdilution...
April 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28069651/inhibition-by-avibactam-and-clavulanate-of-the-%C3%AE-lactamases-kpc-2-and-ctx-m-15-harboring-the-substitution-n-132-g-in-the-conserved-sdn-motif
#19
Clément Ourghanlian, Daria Soroka, Michel Arthur
The substitution N(132)G in the SDN motif of class A β-lactamases from rapidly growing mycobacteria was previously shown to impair their inhibition by avibactam but to improve the stability of acyl-enzymes formed with clavulanate. The same substitution was introduced in KPC-2 and CTX-M-15 to assess its impact on β-lactamases from Enterobacteriaceae and evaluate whether it may lead to resistance to the ceftazidime-avibactam combination. Kinetic parameters for the inhibition of the β-lactamases by avibactam and clavulanate were determined by spectrophotometry using nitrocefin as the substrate...
March 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28061827/systematic-review-and-network-meta-analysis-of-tedizolid-for-the-treatment-of-acute-bacterial-skin-and-skin-structure-infections-caused-by-mrsa
#20
Rachael McCool, Ian M Gould, Jacqui Eales, Teresa Barata, Mick Arber, Kelly Fleetwood, Julie Glanville, Teresa L Kauf
BACKGROUND: Tedizolid, the active moiety of tedizolid phosphate, is approved in the United States, the European Union, Canada and a number of other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This network meta-analysis (NMA) evaluates the comparative effectiveness of tedizolid and other antibacterials indicated for the treatment of ABSSSI caused by MRSA...
January 7, 2017: BMC Infectious Diseases
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