857. Endocarditis Caused by MRSA with Reduced Susceptibility to Vancomycin and Daptomycin and Resistance to Ceftaroline: Treatment Approach and Evidence of Patient to Patient Transmission
Session: Poster Abstract Session: Bacteremia and Endocarditis
Friday, October 9, 2015
Room: Poster Hall
Background: Treatment of MRSA infective endocarditis (IE) is challenging due to emergence of resistance or tolerance during therapy. In particular, the emergence of MRSA strains with decreased susceptibility to both vancomycin (VAN) and daptomycin (DAP) is of particular concern because of the potential mechanistic links of the two phenotypes. Ceftaroline (CPT) has anti-MRSA bactericidal activity and is a possible option for recalcitrant cases of MRSA IE. Here, we describe our treatment strategy for a case of IE due to a CPT-resistant MRSA strain with borderline MICs to VAN and DAP, and possible transmission of the isolate to a different patient (pt).  

Methods: The index case is a 36 year old man who was admitted to the hospital with an IE due to MRSA with MICs for VAN, DAP, and CPT of 2 µg/mL, 1 µg/mL and 6 µg/mL, respectively. One week later, a second pt with ventilator associated pneumonia was identified in the same unit. MRSA was recovered from the sputum with similar susceptibilities to that of the index case. Molecular characterization (including whole genome sequencing) was performed in both isolates. Time-kill curves with DAP, CPT and the combination were performed, using concentrations mimicking the free serum concentrations of DAP and CPT (8.6 and 5 μg/ml, respectively) when given in humans at doses of 8 mg/kg for DAP and 600mg q8hr for CPT. 

Results: Both MRSA isolates exhibited PFGE patterns that were indistinguishable, and only 144 single nucleotide polymorphisms were detected between both genomes. The strains carried the SCCmec II and belonged to MLST type ST105 (clonal cluster 5). The isolate exhibited the E447K in PBP2a that has been previously associated with CPT resistance. In addition, the resistomes predicted resistance to 7 antibiotic families. DAP and CPT alone did not achieve bactericidal activity but combination of both was synergistic. Pt was successfully treated with the combination of DAP (8 mg/kg) plus CPT (600 mg q 8 h) for 6 weeks.

Conclusion: Combination of DAP and CPT may be considered for recalcitrant IE caused by MRSA isolates that exhibit decreased susceptibility to VAN, DAP and CPT. Since in hospital transmission of these MDR strains is possible, implementing infection control measures is paramount to prevent an outbreak.

Masayuki Nigo, MD1, L. Paola Carvajal, BSc2, Truc Tran, PhamD3, Rafael Rios, MSc2, Jose Munita, MD3,4, Diana Panesso, PhD1,2, Audrey Wanger, PhD5, Lorena Diaz, PhD2 and Cesar Arias, MD, PhD, FIDSA2,6, (1)Division of Infectious Disease, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, (2)Universidad El Bosque, Bogota, Colombia, (3)University of Texas Medical School at Houston, Houston, TX, (4)Clinica Alemana - Universidad Del Desarrollo School of Medicine, Santiago, Chile, (5)Department of Pathology and Lab Medicine, University of Texas Medical School at Houston, Houston, TX, (6)Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX

Disclosures:

M. Nigo, None

L. P. Carvajal, None

T. Tran, None

R. Rios, None

J. Munita, None

D. Panesso, None

A. Wanger, None

L. Diaz, None

C. Arias, Pfizer: Grant Investigator and Speaker's Bureau , Grant recipient and Speaker honorarium
Merck Sharp and Dohme: Grant Investigator and Speaker's Bureau , Grant recipient and Speaker honorarium
Cubist: Grant Investigator and Speaker's Bureau , Grant recipient and Speaker honorarium
Theravance: Grant Investigator and Speaker's Bureau , Grant recipient and Speaker honorarium
Bayer: Consultant , Consulting fee

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