1964. Optimizing Antimicrobial Strategies to Combat Invasive Staphylococcus epidermidis Displaying the Small Colony Variant (SCV) Phenotype
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall

Background: Clinically, Staphylococcal SCVs are extremely difficult to treat as they are associated with persistent and recurrent infections. S. epidermidis SCVs also pose diagnostic and susceptibility challenges as they are rarely reported and infrequently cause invasive disease.

Methods: A clinical S. epidermidis SCV isolate (SE-SCV) recovered from the bloodstream was utilized in all experiments.  Accessory gene regulator (agr) function was assessed by cross streaking SE-SCV perpendicularly to β-hemolysin producing strain RN4220 on TSA with 5% sheep blood. Triton X-100 (0.05%) induced autolysis profiles were obtained with and without exposure to vancomycin.  The pharmacodynamic activity of combinations was assessed using 48h time-kill experiments against the following antimicrobials at simulated serum and bone concentrations alone or in combinations: penicillin, nafcillin, daptomycin, vancomycin, gentamicin, and ceftriaxone.

Results: The patient was hospitalized with native valve endocarditis and later developed metastatic vertebral infection. Laboratory testing could not accurately identify the causative organism and therefore 16s rRNA sequencing was employed, revealing the SCV as S. epidermidis (SE-SCV). Despite treatment with surgery and antibiotics (ceftriaxone, penicillin G and vancomycin) which the organism was susceptible to, the infection persisted to which the patient succumbed.  SE-SCV did not display d-hemolysin activity suggesting agr dysfunction. SE-SCV was relatively resistant to triton X-100 autolysis signifying a baseline autolysin inhibition. Triton autolysis and agr data support that SE-SCV may have been less susceptible to vancomycin than predicted by traditional MICs.  All 12 time-kill regimens using gentamicin alone or in combinations caused eradication (≥7 log10CFU/mL reduction) by 48 hrs.  All 15 regimens without gentamicin failed to eradicate. Time-kill experiments utilizing the antibiotics received by the patient revealed ~3-4 log reduction.

Conclusion: S. epidermidis SCVs warrant additional attention from a diagnostic and antimicrobial selection standpoint as they can elude conventional therapies.  Time-kill experiments may better tailor antibiotic therapy than conventional susceptibility approaches.

Zackery Bulman, Pharm.D.1, Kari Mergenhagen, Pharm.D., BCPS AQ-ID2, Alan Lesse, MD, FIDSA3, Ganapathi Parameswaran, MD3 and Brian T. Tsuji, Pharm.D.1, (1)University at Buffalo, SUNY, Buffalo, NY, (2)Pharmacy, VA Western New York Healthcare System, Buffalo, NY, (3)Infectious Diseases, University at Buffalo/Buffalo VA Medical Center, Buffalo, NY

Disclosures:

Z. Bulman, None

K. Mergenhagen, None

A. Lesse, None

G. Parameswaran, None

B. T. Tsuji, None

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