Evaluation of the Revised Ceftaroline Disk Diffusion Breakpoints When Testing a Challenge Collection of Methicillin-Resistant Staphylococcus aureus Isolates

Sader, Hélio S.; Rhomberg, Paul R.; Doyle, Timothy B; Flamm, Robert K.; Mendes, Rodrigo E.

doi:10.1128/jcm.00777-18

Cited by 8 publications

(9 citation statements)

References 20 publications

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“…These results highlighted different interpretations of the two institutes. Results from both CLSI methods were comparable, as already showed by Sader et al [ 18 ], while EUCAST demonstrated higher differences between disk diffusion and MIC interpretations. Our data confirmed discrepancies in EUCAST disk diffusion assays compared to MIC determination (both with broth microdilution or a MIC test strip) as reported before [ 19 ], and further suggested the need of a revision of disk diffusion criteria.…”

Section: Resultssupporting

confidence: 82%

Characterization and Clonal Diffusion of Ceftaroline Non-Susceptible MRSA in Two Hospitals in Central Italy

et al. 2021

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Background: Ceftaroline represents a novel fifth-generation cephalosporin to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Ceftaroline susceptibility of 239 MRSA isolates was assessed by disk diffusion and a MIC test strip following both EUCAST and CLSI guidelines. Non-susceptible isolates were epidemiologically characterized by pulsed-field gel electrophoresis, spa typing, and multilocus sequence typing, and further investigated by PCR and whole genome sequencing to detect penicillin-binding protein (PBP) mutations as well as antibiotic resistance and virulence genes. Results: Fourteen isolates out of two hundred and thirty-nine (5.8%) were non-susceptible to ceftaroline (MIC > 1 mg/L), with differences between the EUCAST and CLSI interpretations. The characterized isolates belonged to seven different pulsotypes and three different clones (ST228/CC5-t041-SCCmecI, ST22/CC22-t18014-SCCmecIV, and ST22/CC22-t022-SCCmecIV), confirming a clonal diffusion of ceftaroline non-susceptible strains. Mutations in PBPs involved PBP2a for ST228-t041-SCCmecI strains and all the other PBPs for ST22-t18014-SCCmecIV and ST22-t022-SCCmecIV clones. All isolates harbored antibiotic resistance and virulence genes with a clonal distribution. Conclusion: Our study demonstrated that ceftaroline non-susceptibile isolates belonged not only to ST228 strains (the most widespread clone in Italy) but also to ST22, confirming the increasing role of these clones in hospital infections.

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Section: Resultssupporting

confidence: 82%

Characterization and Clonal Diffusion of Ceftaroline Non-Susceptible MRSA in Two Hospitals in Central Italy

et al. 2021

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“…We found that 30% of the CF MRSA isolates we tested were CPT-resistant. Considering that CPT was FDA-approved in 2010 14,15,26,[52][53][54] , i.e. after the collection of these strains, these findings are worrisome.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, CPT demonstrated a high clinical cure rate (>70%) in pneumonia caused by both MSSA and MRSA 13 . CPT is active against MRSA with reduced susceptibility to vancomycin (VAN), linezolid (LZD), and daptomycin (DAP) 14,15 . The Clinical and Laboratory Standards Institute (CLSI) has established CPT breakpoints of ≤1 mg/L for susceptible MRSA strains, 2 mg/L for intermediate strains, and ≥4 mg/L for resistant strains 16,17 .…”

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confidence: 99%

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

et al. 2020

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Chronic airways infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with worse respiratory disease cystic fibrosis (CF) patients. Ceftaroline is a cephalosporin that inhibits the penicillin-binding protein (PBP2a) uniquely produced by MRSA. We analyzed 335 S. aureus isolates from CF sputum samples collected at three US centers between 2015–2018. Molecular relationships demonstrated that high-level resistance of preceding isolates to carbapenems were associated with subsequent isolation of ceftaroline resistant CF MRSA. In vitro evolution experiments showed that pre-exposure of CF MRSA to meropenem with further selection with ceftaroline implied mutations in mecA and additional mutations in pbp1 and pbp2, targets of carbapenems; no effects were achieved by other β-lactams. An in vivo pneumonia mouse model showed the potential therapeutic efficacy of ceftaroline/meropenem combination against ceftaroline-resistant CF MRSA infections. Thus, the present findings highlight risk factors and potential therapeutic strategies offering an opportunity to both prevent and address antibiotic resistance in this patient population.

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“…Although the data presented by Urban and Stone are of great interest [1], they do not include MRSA isolates from the USA, and do not evaluate the impact of recent breakpoint changes for ceftaroline in either the Clinical Laboratory Standard Institute (CLSI) or the US Committee on Antimicrobial Susceptibility Testing (USCAST) [3,4]. The evaluation of S. aureus isolates from different regions is important because it has been demonstrated that the in vitro activity of ceftaroline against MRSA varies based on the SCCmec clonal types that predominate in a particular geographic location [5].…”

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confidence: 99%

Impact of EUCAST, CLSI and USCAST ceftaroline breakpoint changes on the susceptibility of methicillin-resistant Staphylococcus aureus isolates collected from US medical centres (2015–2018)

Sader

Jones

2020

Clinical Microbiology and Infection

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Evaluation of the Revised Ceftaroline Disk Diffusion Breakpoints When Testing a Challenge Collection of Methicillin-Resistant Staphylococcus aureus Isolates

Cited by 8 publications

References 20 publications

Characterization and Clonal Diffusion of Ceftaroline Non-Susceptible MRSA in Two Hospitals in Central Italy

Characterization and Clonal Diffusion of Ceftaroline Non-Susceptible MRSA in Two Hospitals in Central Italy

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

Impact of EUCAST, CLSI and USCAST ceftaroline breakpoint changes on the susceptibility of methicillin-resistant Staphylococcus aureus isolates collected from US medical centres (2015–2018)

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