PBP2a substitutions linked to ceftaroline resistance in MRSA isolates from the UK: Table 1.

Harrison, Ewan M.; Ba, Xiaoliang; Blane, Beth; Ellington, Matthew J.; Loeffler, Anette; Hill, Robert L.; Holmes, Mark A.; Peacock, Sharon J.

doi:10.1093/jac/dkv317

Cited by 19 publications

(12 citation statements)

References 9 publications

(21 reference statements)

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“…However, soon after their introduction, the efficacy of β-lactams was altered by S. aureus strains producing a β-lactamase enzyme or by horizontal acquisition of mecA , encoding the penicillin-binding protein PBP2a. PBP2a is not inhibited by β-lactams and can consequently catalyze DD-transpeptidation and cooperate with the PBP2 transglycosylase in peptidoglycan biosynthesis [3, 4]. …”

Section: Introductionmentioning

confidence: 99%

“…Recently, high-level ceftaroline resistance (MIC > 32 μg/ml) was observed during sustained MRSA bacteremia treated with ceftaroline [13]. Low-level resistance to ceftaroline is associated with mutations in PBP2a found in both the allosteric domain (N146K, E150K, N204K, E239K, G246E) or the transpeptidase domain (H351N, Y446N, E447) [3, 8, 13–17]. …”

Section: Introductionmentioning

confidence: 99%

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

Andrey

François

Manzano

et al. 2016

Eur J Clin Microbiol Infect Dis

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Andrey

François

Manzano

et al. 2016

Eur J Clin Microbiol Infect Dis

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“…PBP2a mutations can affect the activities of ceftaroline and ceftobiprole. Changes in the nonpenicillin‐binding and penicillin‐binding domains are associated with low‐level and high‐level resistance, respectively . Harrison and coworkers observed two mutations in the penicillin‐binding domain of a native peptide detected by Charretier et al.…”

Section: Antibiotic Resistance Predictionmentioning

confidence: 96%

Mass spectrometry methods for predicting antibiotic resistance

Charretier

Schrenzel

2016

Proteomics Clinical Apps

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Developing elaborate techniques for clinical applications can be a complicated process. Whole-cell MALDI-TOF MS revolutionized reliable microorganism identification in clinical microbiology laboratories and is now replacing phenotypic microbial identification. This technique is a generic, accurate, rapid, and cost-effective growth-based method. Antibiotic resistance keeps emerging in environmental and clinical microorganisms, leading to clinical therapeutic challenges, especially for Gram-negative bacteria. Antimicrobial susceptibility testing is used to reliably predict antimicrobial success in treating infection, but it is inherently limited by the need to isolate and grow cultures, delaying the application of appropriate therapies. Antibiotic resistance prediction by growth-independent methods is expected to reduce the turnaround time. Recently, the potential of next-generation sequencing and microarrays in predicting microbial resistance has been demonstrated, and this review evaluates the potential of MS in this field. First, technological advances are described, and the possibility of predicting antibiotic resistance by MS is then illustrated for three prototypical human pathogens: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Clearly, MS methods can identify antimicrobial resistance mediated by horizontal gene transfers or by mutations that affect the quantity of a gene product, whereas antimicrobial resistance mediated by target mutations remains difficult to detect.

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“…Further, the non-synonymous or nonsense mutation in mecA can usually cause a change in the amino acid sequence of PBP2a resulting in ceftaroline resistance [76,77]. It was observed that when passaged in ceftaroline the COL strain showed a mutation in PBP2, PBP4, and gdpP with a high level of resistance towards it [79].…”

Section: Mechanisms Of Antibiotic Resistance In Mrsamentioning

confidence: 99%

Antimicrobial peptides-An alternative candidates to antibiotics against Staphylococcus aureus and its antibiotic-resistant strains

Mazumdar¹,

Adam²

2021

Journal of Molecular and Clinical Medicine

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Staphylococcus aureus and its antibiotic-resistant strains are the cause of so t tissue infections representing some severe life-threatening infections. These situations have caused great concern for its treatment worldwide. Thus, the need to introduce new antibiotics or an alternative to antibiotics markedly increasing. Antimicrobial peptides (AMPs) have been shown to have various properties and uses in the biological system since their discovery. This review is based on the increasing concern for S. aureus, its resistant strains, the associated infections, pathogenicity, and the mechanism of resistance to antibiotics. Lastly, the overall significance of AMPs against S. aureus showed that they can be ideal candidates as an alternative to antibiotics with high potential for future therapeutics.

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PBP2a substitutions linked to ceftaroline resistance in MRSA isolates from the UK: Table 1.

Cited by 19 publications

References 9 publications

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

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

Mass spectrometry methods for predicting antibiotic resistance

Antimicrobial peptides-An alternative candidates to antibiotics against Staphylococcus aureus and its antibiotic-resistant strains

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