Ceftobiprole- and Ceftaroline-Resistant Methicillin-Resistant Staphylococcus aureus

Chan, Liana C.; Basuino, Li; Diep, Binh An; Hamilton, Stephanie M.; Chatterjee, Som S.; Chambers, Henry F.

doi:10.1128/aac.05004-14

Cited by 75 publications

(66 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, ceftaroline and ceftobiprole, new cephalosporin molecules recently introduced and approved for the treatment of community-acquired pneumonia and complicated skin and soft tissue infections, are active against MRS. Ceftaroline causes an allosteric change of PBP2a so that a second molecule can bind to the newly exposed active site (Fishovitz et al, 2014) and ceftobiprole can access the active site of PBP2a through its residue R2 (Chan et al, 2015). In spite of these developments, mecA gene is still at the centre of interest for the scientific community because of recent reports on ceftaroline-and ceftobiprole-resistant MRSA isolates, mainly due to mutations in mecA (Chan et al, 2015;Schaumburg et al, 2016). This resistance is not due to a selective pressure following the introduction of these molecules but due to specific mutations in some mecA allotypes (Schaumburg et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Staphylococcal cassette chromosome mec typing and mecA sequencing in methicillin-resistant staphylococci from Algeria: a highly diversified element with new mutations in mecA

Djoudi

Bonura

Touati

et al. 2016

Journal of Medical Microbiology

View full text Add to dashboard Cite

Genetic mechanisms of methicillin resistance are still relevant in staphylococci. The aims of this study are to assess the possible exchanges of staphylococcal cassette chromosome mec (SCCmec) among isolates of methicillin-resistant staphylococci (MRS) and to check for known or new mutations in mecA DNA. A total of 35 MRS non-repetitive isolates were recovered, including 20 Staphylococcus haemolyticus, 7 Staphylococcus aureus, 4 Staphylococcus sciuri, 2 Staphylococcus saprophyticus and 1 isolate each of Staphylococcus xylosus and Staphylococcus lentus. Only 16 of the 35 strains were assigned to known SCCmec types: 7 SCCmec VII, 6 SCCmec IV and 3 SCCmec III, with possible horizontal transfer of the SCCmec VII from methicillin-resistant S. haemolyticus to methicillin-susceptible S. aureus. mecA gene sequencing in ten selected isolates allowed description of nine punctual mutations, seven of which were reported for the first time. The most frequent mutation was G246E, identified in isolates of methicillin-resistant S. aureus, S. sciuri, S. saprophyticus and S. lentus. These results emphasized the high degree of genetic diversity of SCCmec element in MRS and describe new missense mutations in mecA, which might be important in understanding the evolution of methicillin and new b-lactam resistance.

show abstract

Section: Introductionmentioning

confidence: 99%

Staphylococcal cassette chromosome mec typing and mecA sequencing in methicillin-resistant staphylococci from Algeria: a highly diversified element with new mutations in mecA

Djoudi

Bonura

Touati

et al. 2016

Journal of Medical Microbiology

View full text Add to dashboard Cite

show abstract

“…This substitution was not seen in any of the other ceftaroline-nonsusceptible isolates characterized in this study. However, the association of these substitutions with higher ceftaroline MICs has been described previously (21,22,36). These findings suggest a clonal relationship among the isolates from Thailand, with MICs of 4 g/ml, but further studies would be needed to establish this relationship.…”

Section: Discussionmentioning

confidence: 57%

“…It is of interest that in the countries with the highest ceftaroline nonsusceptibility rates (China and Thailand), ceftaroline had not been approved at the time of the study. While at least one in vitro study suggested that certain beta-lactams (e.g., ceftobiprole) could select for mutants with higher ceftaroline MICs, there are no reports of this happening in the clinical environment (22). In any case, without the availability of usage data and with insufficient year-to-year data for each region, it is difficult to conclude the reasons for differences in regional ceftaroline susceptibility rates and whether there have been any changes over time.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to inhibiting essential penicillin-binding proteins (PBPs), ceftaroline also has a high affinity for PBP2a, which confers resistance to an array of other beta-lactams characteristic of MRSA (21). Ceftaroline's special attribute of having activity against MRSA is key to this drug's contribution as a therapeutic option for treating serious infections caused by S. aureus (22)(23)(24)(25)(26).…”

mentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Activity of Ceftaroline against Staphylococcus aureus Isolated in 2012 from Asia-Pacific Countries as Part of the AWARE Surveillance Program

Biedenbach¹,

Alm

Lahiri

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

b Ceftaroline, the active metabolite of the prodrug ceftaroline-fosamil, is an advanced-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). This investigation provides in vitro susceptibility data for ceftaroline against 1,971 S. aureus isolates collected in 2012 from seven countries (26 centers) in the Asia-Pacific region as part of the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) program. Broth microdilution as recommended by the CLSI was used to determine susceptibility. In all, 62% of the isolates studied were MRSA, and the ceftaroline MIC 90 for all S. aureus isolates was 2 g/ml (interpretive criteria: susceptible, <1 g/ml). The overall ceftaroline susceptibility rate for S. aureus was 86.9%, with 100% of methicillin-sensitive S. aureus isolates and 78.8% of MRSA isolates susceptible to this agent. The highest percentages of ceftaroline-nonsusceptible MRSA isolates came from China (47.6%), all of which showed intermediate susceptibility, and Thailand (37.1%), where over half (52.8%) of isolates were resistant to ceftaroline (MIC, 4 g/ml). Thirty-eight ceftaroline-nonsusceptible isolates (MIC values of 2 to 4 g/ml) were selected for molecular characterization. Among the isolates analyzed, sequence type 5 (ST-5) was the most common sequence type encountered; however, all isolates analyzed from Thailand were ST-228. Penicillin-binding protein 2a (PBP2a) substitution patterns varied by country, but all isolates from Thailand had the Glu 239 Lys substitution, and 12 of these also carried an additional Glu 447 Lys substitution. Ceftaroline-fosamil is a useful addition to the antimicrobial agents that can be used to treat S. aureus infections. However, with the capability of this species to develop resistance to new agents, it is important to recognize and monitor regional differences in trends as they emerge.

show abstract

“…The primary source and the mode of transmission of these strains are otherwise obscure and typical. Both strains had acquired resistance to ceftaroline due to a single canonical point mutation in mecA (3,14,15) under mysterious circumstances since neither patient had been previously treated with this antibiotic. It is of more than passing interest that the one other well-documented case of infection with ST5 ceftaroline-resistant MRSA was also identified in a Houston hospital 3 years earlier (3).…”

Section: Commentarymentioning

confidence: 99%

Ceftaroline-Resistant, Daptomycin-Tolerant, and Heterogeneous Vancomycin-Intermediate Methicillin-Resistant Staphylococcus aureus Causing Infective Endocarditis

Nigo¹,

Diaz

Carvajal

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

This journal section presents a real, challenging case involving a multidrugresistant organism. The case authors present the rationale for their therapeutic strategy and discuss the impact of mechanisms of resistance on clinical outcome. An expert clinician then provides a commentary on the case. ABSTRACT We report a case of infective endocarditis (IE) caused by ceftarolineresistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillinresistant S. aureus (MRSA). Resistance to ceftaroline emerged in the absence of drug exposure, and the E447K substitution in the active site of PBP2a previously associated with ceftaroline resistance was identified. Additionally, we present evidence of patient-to-patient transmission of the strain within the same unit. This case illustrates the difficulties in treating MRSA IE in the setting of a multidrug-resistant phenotype.

show abstract

Ceftobiprole- and Ceftaroline-Resistant Methicillin-Resistant Staphylococcus aureus

Cited by 75 publications

References 19 publications

Staphylococcal cassette chromosome mec typing and mecA sequencing in methicillin-resistant staphylococci from Algeria: a highly diversified element with new mutations in mecA

Staphylococcal cassette chromosome mec typing and mecA sequencing in methicillin-resistant staphylococci from Algeria: a highly diversified element with new mutations in mecA

In Vitro Activity of Ceftaroline against Staphylococcus aureus Isolated in 2012 from Asia-Pacific Countries as Part of the AWARE Surveillance Program

Ceftaroline-Resistant, Daptomycin-Tolerant, and Heterogeneous Vancomycin-Intermediate Methicillin-Resistant Staphylococcus aureus Causing Infective Endocarditis

Contact Info

Product

Resources

About