Combination of High Dose Daptomycin with Tigecycline as Treatment of Persistent Vancomycin Resistant Enterococcus Bacteremia

Background: There is limited data based on case reports that combining tigecycline with daptomycin could result in synergistic effect against Enterococcus. Two case reports of successful treatment of vancomycin resistant enterococcus (VRE) endocarditis that failed treatment with daptomycin monotherapy, with the use of daptomycin at a dose of 6-8 mg/kg daily combined with tigecycline, have been previously reported. However, this potential synergy has yet to be confirmed and further data from in vitro or in vivo studies are needed.

Objective: To describe in vivo and in vitro data from 2 cases that demonstrate that high dose daptomycin in combination with tigecycline may be a treatment option for VRE bacteremia caused by a persistent source of infection.

Methods: We report 2 cases of successful treatment of persistent VRE bacteremia using combination therapy with high dose daptomycin and tigecycline.

Results:

The 2 cases are summarized in table 1. Both patients were males, had renal failure, and a persistent source of bacteremia with E. faecium with daptomycin MIC of 4 mg/L (endocarditis in case 1 and abscess in case 2). They were both receiving daptomycin at a dose of 6 mg/kg IV every 48 hours when the bacteremia recurred. High dose daptomycin (10 mg/kg) in combination with tigecycline lead to resolution of bacteremia in < 48 hours in both cases. In vitro endpoint synergy testing of the VRE isolates by broth macrodilution confirmed the synergy between daptomycin and tigecycline. No synergy between daptomycin and gentamicin was seen for the isolate in case 1, this was not tested for case 2. 

Case	Age	Comorbidities	Infection	Duration of bacteremia (days) while on daptomycin	Duration of treatment (weeks)	Outcome
1	52	Cirrhosis, renal disease	Endocarditis	4	8	Recovered
2	28	End stage renal disease	Abscess	4	4	Recovered

Conclusions: High dose daptomycin in combination with tigecycline may be a treatment option for VRE bacteremia caused by a persistent source such as endovascular infection or abscess. This may be especially important in patients with renal failure where possible underdosing of daptomycin may occur and for treatment of VRE isolates with an elevated daptomycin MIC (4 mg/L). Further studies are needed to confirm this possible synergy.