Ceftaroline-Heteroresistant Staphylococcus aureus

Abstract

Heteroresistance refers to the presence, within a large population of antimicrobial-susceptible microorganisms, of subpopulations with lesser susceptibilities. Ceftaroline is a novel cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to detect the prevalence of ceftaroline heteroresistance in vitro in a select group of S. aureus strains. There were 57 isolates selected for evaluation, 20 MRSA, 20 vancomycin-intermediate S. aureus (VISA), 7 daptomycin-nonsusceptible S. aureus (DNSSA), 6 linezolid-nonsusceptible S. aureus (LNSSA), and 4 heteroresistant VISA (hVISA) isolates. MICs and minimal bactericidal concentrations were determined using the broth microdilution method according to CLSI guidelines. All of the isolates were analyzed by pulsed-field gel electrophoresis. The staphylococcal cassette chromosome mec element (SCCmec) types were determined by a multiplex PCR. Population analysis profiles (PAPs) were performed to determine heteroresistance for all of the isolates using plates made by adding various amounts of ceftaroline to brain heart infusion agar. The frequencies of resistant subpopulations were 1 in 10 4 to 10 5 organisms. We determined that 12 of the 57 (21%) isolates tested were ceftaroline-heteroresistant S. aureus (CHSA). CHSA occurred among strains with reduced susceptibilities to vancomycin, daptomycin, and linezolid but occurred in none of the USA-300 isolates tested. Evaluation of the heteroresistant strains demonstrated that the phenotype was unstable. Further studies are needed to determine whether CHSA has a role in clinical failures and to determine the implications of our study findings.

Nonredundant Roles of Interleukin-17A (IL-17A) and IL-22 in Murine Host Defense against Cutaneous and Hematogenous Infection Due to Methicillin-Resistant Staphylococcus aureus

“…As a result, infections due to MRSA represent a leading cause of infection-induced mortality in the United States, ranging from 11,000 to 18,650 deaths per year (13)(14)(15). Compounding the concerns noted above, the increasing use of antibiotics has accelerated the emergence of multidrug-resistant S. aureus strains (16)(17)(18)(19). Consequently, resistance to even the most modern antistaphylococcal agents is rising at an increasing rate (20,21).…”

Innate Immune Memory Contributes to Host Defense against Recurrent Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus

“…As a result, infections due to MRSA represent a leading cause of infection-induced mortality in the United States, resulting in 11,000 to 18,650 deaths per year (16)(17)(18). Compounding the above concerns, the increasing use of antibiotics has accelerated the emergence of multidrug-resistant S. aureus strains (19)(20)(21)(22). Consequently, resistance to even the most modern antistaphylococcal agents is rising at an alarming rate (23,24).…”

New Found Hope for Antibiotic Discovery: Lipid II Inhibitors

“…For example, oritavancin 3 carries both 4‐epi‐vancosamine and 4′‐chlorobiphenyl methyl moieties that form additional interactions with the peptidyl cross bridge and d ‐ γ ‐Gln of lipid II, thus compensating for the lost hydrogen bond observed in vancomycin‐resistant strains (Figure ) . As such, oritavancin showed enhanced antibacterial potency against MRSA and other vancomycin‐insensitive bacteria …”