Tools
Tools
Mushtaq, Shazad, Warner, Marina, Ge, Yigong, Kaniga, Koné and Livermore, David M. 
ORCID: https://orcid.org/0000-0002-9856-3703
(2007)
In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes.
Journal of Antimicrobial Chemotherapy, 60 (2).
pp. 300-311.
ISSN 0305-7453
Abstract
Background Ceftaroline (PPI-0903M, T-91825) is a novel cephalosporin, administered as an N-phosphono prodrug. We investigated its in vitro activity and resistance selection potential. Methods MICs were determined by CLSI agar dilution, but with varied inocula. Mutant selection was investigated in single- and multi-step procedures. Results MICs for methicillin-resistant Staphylococcus aureus (MRSA) were 0.5–2 mg/L, compared with 0.12–0.25 mg/L for methicillin-susceptible S. aureus; corresponding values for coagulase-negative staphylococci were 0.25–2 and 0.06–0.12 mg/L, respectively. Even with 2% NaCl added, all MRSA were susceptible at 2 mg/L. MICs for Enterococcus faecalis were from 0.25 to 8 mg/L; E. faecium was resistant. MICs for Escherichia coli, Klebsiella spp., Morganella morganii and Proteeae without acquired resistance were 0.06–0.5 mg/L versus 0.12–1 mg/L for Enterobacter, Serratia and Citrobacter spp. and 2–8 mg/L for Acinetobacter spp. MICs rose to 1–2 mg/L for many Enterobacteriaceae with classical TEM ß-lactamases, and were much higher for those with extended-spectrum ß-lactamases (ESBLs), hyperproduced AmpC or K1 enzymes. MICs for strains with classical TEM/SHV ß-lactamases rose if the inoculum was increased to 106 cfu/spot; this effect was even more marked for those with ESBLs. Resistance due to Class A ß-lactamases was reversed by clavulanate. Geometric mean MICs were 0.005, 0.05 and 0.09 mg/L for penicillin-susceptible, -intermediate and -resistant Streptococcus pneumoniae strains, respectively—lower than for any comparator ß-lactam. Haemophilus influenzae and Moraxella catarrhalis were very susceptible, although with marginally raised MICs for ß-lactamase-positive Moraxella strains and for haemophili with chromosomal ampicillin resistance. Ceftaroline selected AmpC-derepressed Enterobacter mutants similarly to cefotaxime in single-step experiments; in multi-step procedures it selected ESBL variants of blaTEM in E. coli. Resistance selection was not seen with S. aureus, H. influenzae or pneumococci. Conclusions Ceftaroline has impressive anti-MRSA and anti-pneumococcal activity. Slight lability to classical TEM and SHV ß-lactamases is exceptional for an oxyimino-cephalosporin, but was reversible with clavulanate, as was the greater resistance mediated by ESBLs. Resistance selection occurred with Enterobacteriaceae, not MRSA.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023) Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health |
| Depositing User: | Rhiannon Harvey |
| Date Deposited: | 11 Jul 2011 09:06 |
| Last Modified: | 24 Oct 2022 01:11 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/33466 |
| DOI: | 10.1093/jac/dkm150 |
Actions (login required)
 |
View Item |