Ceftaroline activity against pathogens associated with complicated skin and skin structure infections: results from an international surveillance study.
OBJECTIVE
To assess the spectrum and potency of ceftaroline, a novel anti-methicillin-resistant staphylococcal cephalosporin, against a 2008 surveillance collection of clinical isolates from patients in the USA and Europe.


METHODS
A collection of 14 169 isolates of various bacterial species from complicated skin and skin structure infections (cSSSIs) was tested for susceptibility to ceftaroline and 19 comparator agents in a central reference laboratory using CLSI broth microdilution methods. Organisms were received from 55 medical centres; 27 in the USA and 28 in Europe (12 countries, including Israel). The clonality of isolates of Staphylococcus aureus with elevated ceftaroline MICs (4 mg/L) was determined by PFGE and single and multilocus sequence typing, and the mechanism of ceftaroline non-susceptibility was assessed by molecular methods (PCR amplification and sequencing).


RESULTS
Ceftaroline, the active component of the parenteral prodrug ceftaroline fosamil, was active against 2988 methicillin-resistant S. aureus (MRSA) isolates, with an MI₉₀ of 1 mg/L. The MIC₉₀ for methicillin-susceptible strains was 0.25-0.5 mg/L. Ceftaroline was additionally active against coagulase-negative staphylococci (MIC₉₀, 0.5-1 mg/L), Enterococcus faecalis (MIC₅₀, 2 mg/L), β-haemolytic and viridans group streptococci (MIC₉₀, 0.015-0.25 mg/L) and three commonly isolated Enterobacteriaceae (Escherichia coli, Klebsiella spp. and Proteus mirabilis; MIC₉₀ values of 0.25 to > 16 mg/L). All but four isolates of MRSA (0.13%) had ceftaroline MIC values of ≤ 2 mg/L. The isolates for which ceftaroline MICs were 4 mg/L were clonal (single Greek hospital) and had detectable mecA mutations (N146K, N204K, E150K and H351N).


CONCLUSIONS
The ceftaroline yearly (2008) surveillance for the USA and Europe documented low MIC₅₀/₉₀ values for MRSA isolates at 1/1 and 1/2 mg/L, respectively. Ceftaroline demonstrated promising potency and coverage against Gram-positive and -negative pathogens known to cause cSSSIs, including MRSA and β-haemolytic streptococci.
JMI Laboratories, North Liberty, IA 52317, USA. ronald-jones@jmilabs.com
Ronald N
RN
Jones
Rodrigo E
RE
Mendes
Helio S
HS
Sader
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D005060:Europe; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006095:Gram-Positive Cocci / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D011159:Population Surveillance / Q000379:methods; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014481:United States; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097583:Ceftaroline