EV0074 ePoster Viewing Antimicrobials: antimicrobial PK/PD, pharmacogenomics, pharmacoeconomics and general pharmacology, drug interaction studies Synergistic action of ceftaroline with other beta-lactams against Staphylococcus aureus

S. Martinez-Puchol1, N. Palma1, F. Marco1, A. Soriano2, J. Vila1, J. Mensa2, J. Ruiz Blazquez1 1ISGlobal-CRESIB, Barcelona, Spain 2Hospital Clinic, Barcelona, Spain

Objectives: The aim of this study was to determine the in vitro potential of ceftaroline (CPT) combined with ceftazidime (CAZ), meropenem (MER) and piperacillin-tazobactam (PTZ) for the treatment of S. aureus infections in order to facilitate the design of new and more effective treatment schemes that may limit or avoid the development of antimicrobial resistance. Methods: Two MRSA and 3 MSSA were included in the study. Minimal inhibitory Concentrations (MIC) to CPT, CAZ, PTZ, MER and CAZ were determined by broth microdilution method, while MIC to vancomycin (VAN) was established by E-test. Additionally the Minimal Bactericide Concentration (MBC) of CPT was also established. The presence of synergies between CPT and PTZ, MER and CAZ was evaluated by killing curves in which the antibiotics were tested at 1xMIC (1x) and 1/2xMIC (1/2X) when the MIC was under the resistance breakpoint or using the breakpoint when resistance was established. Results: No differences were observed when the MIC and MBC values were assessed at 24 and 48h. The MIC levels of CPT ranged from 0.125 µg/ml to 0.5 µg/ml in four isolates (strains 1, 3, 4, 5) while, in the remaining isolate (MRSA - strain 2), the MIC was 2 µg/ml, being classified as CPT-resistant (EUCAST). Meanwhile, the MBC of CPT of the isolates ranged from 0.125 to 4 µg/ml. Regarding VAN, 2 MRSA (strain 1 and 2) were considered intermediate because they presented MIC levels higher than 2 µg/ml. Remaining MICs are presented in Table 1. Synergic effects were observed in MRSA isolates, irrespective of the VAN MIC, when CPT (1x or 1/2x) was combined with MER (1x and 1/2x) or PTZ (1x and 1/2x). On testing a CPT resistant strain (strain 2), synergies were also detected when CPT 1x was combined with MER and PTZ, irrespectively of the concentrations used (also corresponding to the resistance breakpoint). No antagonism was observed and no relation was found with the VAN susceptibility levels. Conclusions: These data show that the concomitant use of MER and PTZ does not negatively affect the anti-staphylococcal activity of CPT, being able to provide a broad spectrum of protection to the patients. Present data show the presence of synergies in MRSA isolates, irrespective of presenting resistance to CPT. Studies with isolates exhibiting higher levels of CPT and VAN resistance are needed.

Microorganisms MIC (R/I/S) MBC No MRSA VAN CPT MER PTZ CAZ CPT 1 Y 4(I) 0.5(S) 4(S) 1(S) 64(R) 1 2 Y 3(I) 2(R)* 64(R) >256(R) >256(R) 4 3 Y 2(S) 0.5(S) 8(I) 16(R) 64(R) 1 4 N 1.5(S) 0.25(S) 0.007(S) 0.125(S) 16(I) 0.5 5 N 1(S) 0.125(S) 0.015(S) 0.125(S) 8(S) 0.125