In Vitro Activity of Ceftaroline against 623 Diverse Strains of Anaerobic Bacteria

102

Ceftaroline has been approved for acute bacterial skin infections and community-acquired bacterial pneumonia. Limited clinical experience exists for use outside these indications. The objective of this study was to describe the outcomes of patients treated with ceftaroline for various infections. Retrospective analyses of patients receiving ceftaroline >72 h from 2011 to 2013 were included. Clinical and microbiological outcomes were analyzed. Clinical success was defined as resolution of all signs and symptoms of infection with no further need for escalation while on ceftaroline treatment during hospitalization. A total of 527 patients received ceftaroline, and 67% were treated for off-label indications. Twenty-eight percent (148/527) of patients had bacteremia. Most patients (80%) were initiated on ceftaroline after receipt of another antimicrobial, with 48% citing disease progression as a reason for switching. The median duration of ceftaroline treatment was 6 days, with an interquartile range of 4 to 9 days. A total of 327 (62%) patients were culture positive, and the most prevalent pathogen was Staphylococcus aureus, with a frequency of 83% (271/327). Of these patients, 88.9% (241/271) were infected with methicillin-resistant S. aureus (MRSA). Clinically, 88% (426/484) achieved clinical success and hospital mortality was seen in 8% (40/527). While on ceftaroline, adverse events were experienced in 8% (41/527) of the patients and 9% (28/307) were readmitted within 30 days after discharge for the same infection. Patients treated with ceftaroline for both FDA-approved and off-label infections had favorable outcomes. Further research is necessary to further describe the role of ceftaroline in a variety of infections and its impact on patient outcomes.

Section: Discussionmentioning

confidence: 99%

Large Retrospective Evaluation of the Effectiveness and Safety of Ceftaroline Fosamil Therapy

Casapao

Davis

Barr

et al. 2014

102

“…Ceftaroline is a parenteral, broadspectrum cephalosporin with in vitro activity against resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae as well as Enterobacteriaceae, excluding isolates harboring extended-spectrum ␤-lactamases (ESBLs), cephalosporinases, and carbapenemases (1)(2)(3)(4)(5)(6). Ceftaroline also demonstrates potent in vitro activity against Gram-positive and Gram-negative anaerobic bacteria, excluding Bacteroides fragilis (7,8), but lacks activity against enterococci, Pseudomonas aeruginosa, and other nonfermentative Gram-negative bacilli (1,2,4,6). Unlike many other oxyiminocephalosporins, ceftaroline demonstrates some lability to classical TEM and SHV ␤-lactamases, is resistant to Klebsiella oxytoca hyperproducing the K1 enzyme, and produces high MICs, relative to those of other oxyimino-cephalosporins, for isolates harboring CTX-M enzymes (9).…”

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confidence: 99%

In Vitro Activity of Ceftaroline-Avibactam against Gram-Negative and Gram-Positive Pathogens Isolated from Patients in Canadian Hospitals from 2010 to 2012: Results from the CANWARD Surveillance Study

Karlowsky

Adam

Baxter

et al. 2013

The in vitro activities of ceftaroline-avibactam, ceftaroline, and comparative agents were determined for a collection of bacterial pathogens frequently isolated from patients seeking care at 15 Canadian hospitals from January 2010 to December 2012. In total, 9,758 isolates were tested by using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method (document M07-A9, 2012), with MICs interpreted by using CLSI breakpoints (document M100-S23, 2013). Ceftaroline-avibactam demonstrated potent activity (MIC 90 , <0.5 g/ml) against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Morganella morganii, Citrobacter freundii, and Haemophilus influenzae; >99% of isolates of E. coli, K. pneumoniae, K. oxytoca, P. mirabilis, M. morganii, C. freundii, and H. influenzae were susceptible to ceftaroline-avibactam according to CLSI MIC interpretative criteria for ceftaroline. Ceftaroline was less active than ceftaroline-avibactam against all species of Enterobacteriaceae tested, with rates of susceptibility ranging from 93.9% (P. mirabilis) to 54.0% (S. marcescens). All isolates of methicillin-susceptible Staphylococcus aureus (MIC 90 , 0.25 g/ml) and 99.6% of methicillin-resistant S. aureus isolates (MIC 90 , 1 g/ml) were susceptible to ceftaroline; the addition of avibactam to ceftaroline did not alter its activity against staphylococci or streptococci. All isolates of Streptococcus pneumoniae (MIC 90 , 0.03 g/ml), Streptococcus pyogenes (MIC 90 , <0.03 g/ml), and Streptococcus agalactiae (MIC 90 , 0.015 g/ml) tested were susceptible to ceftaroline. We conclude that combining avibactam with ceftaroline expanded its spectrum of activity to include most isolates of Enterobacteriaceae resistant to third-generation cephalosporins, including extended-spectrum ␤-lactamase (ESBL)-and AmpC-producing E. coli and ESBL-producing K. pneumoniae, while maintaining potent activity against staphylococci and streptococci.

“…c For bacterial groups (species) with n Ͻ 10, the MIC range and percent resistance are the only statistics listed. (1,7,9,10,11) This study was supported by a grant from Cerexa, Inc. (Oakland, CA; a wholly owned subsidiary of Forest Laboratories, Inc., New York, NY). Funding for editorial assistance was provided by Forest Laboratories, Inc.…”

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confidence: 99%

“…To date, only limited studies evaluating the in vitro antianaerobe activity of ceftaroline have been published (1,7,11 [the study by Citron et al describing the activity of ceftaroline against anaerobes was published while the manuscript was in preparation]). We conducted a comprehensive study to define the in vitro spectrum of activity of ceftaroline against a broad spectrum of recent clinical anaerobic bacteria.…”

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confidence: 99%

“…The agent has documented in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci, drug-resistant Streptococcus pneumoniae (DRSP), and ␤-lactam-resistant Haemophilus influenzae and Moraxella catarrhalis isolates. In addition, ceftaroline exhibits in vitro activity against Gram-negative bacilli, with the exception of extended-spectrum ␤-lactamase (ESBL) producers, Pseudomonas and Acinetobacter species, as well as some Gram-positive anaerobic bacteria (1,4,6,7,8,11).…”

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confidence: 99%

See 1 more Smart Citation

In Vitro Activity of Ceftaroline against a Broad Spectrum of Recent Clinical Anaerobic Isolates

Snydman¹,

Jacobus²,

McDermott³

2011

The in vitro activity of ceftaroline was compared with those of ceftriaxone, clindamycin, imipenem, metronidazole, moxifloxacin, tigecycline, and vancomycin against 514 clinical anaerobic isolates using Clinical and Laboratory Standards Institute (CLSI) standard methodology. Ceftaroline demonstrated good to excellent activity against Gram-positive anaerobic pathogens and limited activity against Gram-negative pathogens, particularly Bacteroides fragilis group isolates.