Dataset Information

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

ABSTRACT: We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant 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.

SUBMITTER: Nigo M

PROVIDER: S-EPMC5328541 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Nigo Masayuki M Diaz Lorena L Carvajal Lina P LP Tran Truc T TT Rios Rafael R Panesso Diana D Garavito Juan D JD Miller William R WR Wanger Audrey A Weinstock George G Munita Jose M JM Arias Cesar A CA Chambers Henry F HF

Antimicrobial agents and chemotherapy 20170223 3

We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant <i>S. aureus</i> (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 illust ...[more]

PMID: 28232309

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Project description:BackgroundCommunity-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA) has traditionally been related to skin and soft tissue infections in healthy young patients. However, it has now emerged as responsible for severe infections worldwide, for which vancomycin is one of the mainstays of treatment. Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone.Case presentationWe describe the occurrence of h-VISA phenotype in a case of IE caused by a strain belonging to an epidemic CA-MRSA clone, distinct from USA300, for the first time in Argentina. The isolate h-VISA (SaB2) was recovered from a patient with persistent bacteraemia after a 7-day therapy with vancomycin, which evolved to fatal case of IE complicated with brain abscesses. The initial isolate-(SaB1) was fully vancomycin susceptible (VSSA). Although MRSA SaB2 was vancomycin susceptible (? 2 ?g/ml) by MIC (agar and broth dilution, E-test and VITEK 2), a slight increase of MIC values between SaB1 and SaB2 isolates was detected by the four MIC methods, particularly for teicoplanin. Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP). In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy. Molecular typing showed that both strains, SaB1 and SaB2, belonged to ST5 lineage, carried SCCmecIV, lacked Panton-Valentine leukocidin-(PVL) genes and had indistinguishable PFGE patterns (subtype I2), thereby confirming their isogenic nature. In addition, they were clonally related to the epidemic CA-MRSA clone (pulsotype I) detected in our country.ConclusionsThis report demonstrates the ability of this epidemic CA-MRSA clone, disseminated in some regions of Argentina, to produce severe and rapidly fatal infections such as IE, in addition to its ability to acquire low-level vancomycin resistance; for these reasons, it constitutes a new challenge for the Healthcare System of this country.

Project description:The genomic evolution in vivo in persistent infection was critical information for understanding how methicillin-resistant Staphylococcus aureus (MRSA) was adapted to host environments with high antibiotic selective pressure. Thirty-two successive MRSA blood isolates with incremental non-susceptibility to vancomycin (VISA), daptomycin (DRSA), and/or linezolid (LRSA) were isolated from a patient failing multiple courses of antimicrobial therapy during 1,356 days of bacteremia. Whole genome sequencing (WGS) for all consecutive isolates were conducted to characterize the evolutionary pathways, resistance-associated mutations and their temporal relationship with antimicrobial treatment. The WGS-based phylogeny categorized the isogenic strains into three major clades, I (22 isolates), II (7 isolates), and III (3 isolates), respectively, harboring a median (range) of 7 (1-30), 62 (53-65), and 118 (100-130) non-synonymous mutations when compared to the very first isolate. Clade I strains were further grouped into early and late subclades, which, respectively, shared the most recent common ancestor with Clade III strains at day 393.7 and Clade II strain at day 662.5. Clade I and Clade III strains were characterized, respectively, with high rates of VISA (9/22, 40.9%) and VISA-and-DRSA phenotype (2/3, 66.7%). Linezolid-resistance including VISA-DRSA-and-LRSA phenotype was exclusively identified in Clade II strains after eight courses of linezolid treatment. The LRSA displayed a small colony variant phenotype and were associated with G2576T mutations in domain V region of 23S rRNA. Substantial loss of mobile elements or alleles mediating resistance or virulence were identified during the evolution of multi-resistance. However, the gene loss might not be correlated to the development of VISA, DRSA, or LRSA phenotype. In conclusion, MRSA in persistent bacteremia was adapted to harsh host environment through multiple pathways involving both resistance-associated mutations and extensive gene loss.

Dataset Information

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

Publications

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

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