Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013–2014 at the Geneva University Hospitals

Abstract

Ceftaroline is a broad-spectrum antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Ceftaroline susceptibility of an MRSA set archived between 1994 and 2003 in the Geneva University Hospitals detected a high percentage (66 %) of ceftaroline resistance in clonotypes ST228 and ST247 and correlated with mutations in PBP2a. The ceftaroline mechanism of action is based on the inhibition of PBP2a; thus, the identification of PBP2a mutations of recently circulating clonotypes in our institution was investigated. We analyzed ceftaroline susceptibility in MRSA isolates (2013 and 2014) and established that resistant strains correlated with PBP2a mutations and specific clonotypes. Ninety-six MRSA strains were analyzed from independent patients and were isolated from blood cultures (23 %), deep infections (38.5 %), and superficial (skin or wound) infections (38.5 %). This sample showed a ceftaroline minimum inhibitory concentration (MIC) range between 0.25 and 2 μg/ml and disk diameters ranging from 10 to 30 mm, with a majority of strains showing diameters ≥20 mm. Based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 76 % (73/96) of isolates showed susceptibility to ceftaroline. Nevertheless, we still observed 24 % (23/96) of resistant isolates (MIC = 2 μg/ml). All resistant isolates were assigned to clonotype ST228 and carried the N146K mutation in PBP2a. Only two ST228 isolates showed ceftaroline susceptibility. The decreasing percentage of ceftaroline-resistant isolates in our hospital can be explained by the decline of ST228 clonotype circulating in our hospital since 2008. We present evidence that ceftaroline is active against recent MRSA strains from our hospital; however, the presence of PBP2a variants in particular clonotypes may affect ceftaroline efficacy.

Carbapenems drive the collateral resistance to ceftaroline in cystic fibrosis patients with MRSA

“…after the collection of these strains, these findings are worrisome. Previous studies indicated that CPT resistance could be associated not just with the source country of specific isolates 19 , 21 , 22 , 24 , 25 but also with the MLST profile 55 ; conversely, however, the CPT-resistant isolates analyzed in this study had diverse MLST profiles, including ST-8, ST-5 (the most common in the USA), ST-45, ST-72, ST-105, ST-474, ST-512, and ST-1075, indicating no such specificity for sequence type. In addition, isolates in this study tended to be concurrently resistant to both MER and CPT regardless of MLST.…”

New and improved? A review of novel antibiotics for Gram-positive bacteria

“…Ceftaroline has a broad range of activity (Table 1). However, both low-level [3] and high-level [4] resistance to ceftaroline have been observed in MRSA strains; particularly concerning are recent reports of resistance discovered in clinical MRSA isolates from patients in geographic regions never exposed to the drug [5,6]. Little is known of ceftaroline's ecological impact, though it is expected to be minor, as the drug is not excreted in the faeces [7].…”

Prevalence and molecular epidemiology of ceftaroline non-susceptible methicillin-resistant Staphylococcus aureus isolates, first clinical report from Iran

“…In a study performed on 8037 S. aureus, four isolates were reported as CPT-NS strains which were susceptible to linezolid and vancomycin, and belonged to SCCmec types III [31]. In a study from Switzerland, 24% (23/96) of MRSA collected from deep infections, blood cultures, and superficial infections with MIC≥ 2 mg/L were reported as CPT-NS [32]. In the Atlas program, in which the ceftaroline susceptibility of S. aureus isolates from different countries was tested, 93.7% of the isolates were susceptible to this antibiotic, 5.9% were susceptible-dose dependent (SDD) and only 0.4% (263/61,045) were found to be resistant.…”