1845. "Telavancin displays activity against Cystic Fibrosis-associated MRSA strains including those with increased resistance to Ceftaroline"
Session: Poster Abstract Session: Antibacterial Susceptibility Surveillance
Saturday, October 29, 2016
Room: Poster Hall
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important bacterial pathogen responsible for diseases ranging from skin and soft tissue infections to life-threatening endocarditis. Acquisition of penicillin binding protein PBP2a in MRSA leads to β-lactam resistance with fewer therapeutic options. MRSA has a significant clinical impact on individuals with cystic fibrosis (CF) conferring these patients a worse overall clinical outcome resulting in increased rate of declined lung function. Telavancin (TLV) is a lipoglycopeptide with a dual mode of action in S. aureus causing inhibition of the peptidoglycan synthesis and membrane depolarization. In vitro studies have demonstrated TLV activity against MRSA; however, little is known about its activity against MRSA strains isolated from CF including those exhibiting resistance to ceftaroline (CPT), an agent that specifically targets PBP2a in MRSA.

Methods: A collection of 300 MRSA strains (either wild-type or SCV phenotypes) collected from adults and children CF patients were obtained from Houston Methodist Hospital, Seattle Children’s Hospital and University of Wisconsin. TLV MICs were determined by broth dilution following the guidelines according to CLSI-M100 (CLSI 2015). S. aureus ATCC 29213 strain was used as the quality control. E-tests (BioMerieux) for ceftaroline (CPT) imipenem (IPM), and vancomycin (VAN) were performed accordingly to CLSI guidelines. Activity of TLV was evaluated by time-kill experiments performed at 2x and 10x MICs. Results were expressed by plotting mean colony counts log10 CFU vs time. Synergy was defined as ≥ 2-log10 CFU/mL increase in killing at 24 hours.

Results: TLV demonstrated activity against CF-MRSA with MIC values between 0.032-0.12 µg/ml in 90% of strains including those resistant to CPT. TLV was 5- to 15-fold more active than CPT (MIC range: 0.38- 6 µg/ml) and 15- to 21-fold more active than vancomycin (MIC range: 0.5-1.5 µg/ml) against CF-MRSA. Synergy time kill demonstrated that TLV at 10x MIC resulted in a decrease of ≥ 3log10CFU.

Conclusion: Our data suggest that TLV is active against CF-MRSA strains independent of associated CPT resistant mechanisms and may constitute a new option for the treatment of CF-MRSA infections.

Melanie Roch, PharmD1, Maria Pilar Martinez, Ph.D1, Maryam Fatouraei, BS2, Warren Rose, PharmD3, Rafael Hernandez, MD/PhD4, Lucas Hoffman, MD; PhD5, Ian Yun, PharmD6, Wesley Long, MD; Ph.D7 and Adriana E Rosato, MS; Ph.D8, (1)Pathology /Infectious Diseases, Houston Methodist Research Institute, Houston, TX, (2)Houston Methodist Research Institute, Houston, TX, (3)Infectious Diseases, University of Wisconsin School of Pharmacy, Madison, WI, (4)Infectious Diseases, Center for Global Infectious Diseases Research Seattle Children`s , Infectious Diseases, Seattle, WA, (5)Infectious Diseases, Center for Global Infectious Diseases Research University of Washington, Seattle, WA, (6)Infectious Diseases, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705-2222, , 777 Highland Avenue, Madison, Wisconsin 53705-2222, WI, (7)Pathology, Houston Methodist Research Institute, Houston, TX, (8)Pathology/Infectious Diseases, Houston Methodist Research Institute, Houston, TX

Disclosures:

M. Roch, None

M. P. Martinez, None

M. Fatouraei, None

W. Rose, Merck: Investigator , Grant recipient

R. Hernandez, None

L. Hoffman, None

I. Yun, None

W. Long, None

A. E. Rosato, Merck: Investigator and Research Contractor , Grant recipient
Allergan: Grant Investigator , Grant recipient
Theravance: Grant Investigator , Grant recipient

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