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.
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