What information is available for administration of daptomycin in the perioperative period for adult liver transplant patients?

Comment by InpharmD Researcher

While not currently recommended by clinical practice guidelines, two small retrospective studies demonstrate the use of daptomycin for perioperative prophylaxis in the liver transplant setting (see Tables 1 and 2). Both studies found some reduction of vancomycin-resistant enterococcus (VRE) infection, although impact may be limited to short-term (i.e., within 14 days of operation). Notably, one study reported that none of the patients receiving prophylactic daptomycin developed VRE infections, whereas the only patient who did not receive prophylaxis experienced VRE bacteremia and succumbed within 90 days post-transplant.

Background

Relevant clinical practice guidelines for antimicrobial prophylaxis do not currently include a recommendation for use of daptomycin in liver transplant. Rather, a combination of a third-generation cephalosporin plus ampicillin or monotherapy with piperacillin-tazobactam is recommended. Alternatively, ampicillin sulbactam with or without fluconazole may be considered, as well as echinocandin or liposomal amphotericin B in patients at high risk for invasive fungal infection. [1], [2]

A 2019 retrospective, single-center analysis presented at the American Transplant Congress reviewed the incidence and outcomes of VRE infections in LTR with documented VRE colonization who had received perioperative daptomycin prophylaxis. The cohort included 18 adult patients who underwent LT between 2013 and 2017 and were colonized with VRE, as determined through perirectal swab cultures. The institutional protocol provided daptomycin prophylaxis in addition to standard surgical prophylaxis at the time of LT. Multiple clinical and demographic parameters were evaluated, including the Model for End-Stage Liver Disease (MELD) score, Charlson Comorbidity Index, type of biliary anastomosis, the use of induction immunosuppression, post-operative complications, and ICU length of stay. CDC definitions were utilized for infection classification, and outcomes were assessed up to 90 days following transplantation. Among the 18 VRE-colonized LTR receiving daptomycin prophylaxis, the median MELD score was 37, indicating a severely ill population. Most patients (88.9%) underwent duct-to-duct biliary reconstruction, and over 70% required postoperative dialysis. Despite the high prevalence of known risk factors for invasive VRE infection—such as re-operations (33.3%), ICU stays (median 8 days), and serious comorbidities—none of the patients who received daptomycin prophylaxis developed VRE-related infections post-transplant. Only one patient exhibited asymptomatic VRE bacteriuria. Notably, the singular VRE-colonized patient who did not receive daptomycin prophylaxis experienced postoperative hemorrhage, developed VRE bacteremia, and succumbed within 90 days post-LT. These findings suggest that targeted daptomycin prophylaxis in colonized individuals may play a substantial role in mitigating early post-transplant VRE infections, even among a high-risk population. [3]

References:

[1] Abbo LM, Grossi PA; AST ID Community of Practice. Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13589. doi:10.1111/ctr.13589Abbo LM, Grossi PA; AST ID Community of Practice. Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13589. doi:10.1111/ctr.13589
[2] Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. doi:10.2146/ajhp120568
[3] Sarwar S, Gleeson S, Malinis M, Azar MM. Daptomycin Perioperative Prophylaxis for Prevention of Vancomycin-Resistant Enterococcus Infection in VRE-Colonized Liver Transplant Recipients during the Early Post-Transplant Period [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/daptomycin-perioperative-prophylaxis-for-prevention-of-vancomycin-resistant-enterococcus-infection-in-vre-colonized-liver-transplant-recipients-during-the-early-post-transplant-period/. Accessed May 6, 2025.
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What information is available for administration of daptomycin in the perioperative period for adult liver transplant patients?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-2 for your response.

 

Perioperative daptomycin for prophylaxis of vancomycin-resistant Enterococcus infection in colonized liver transplant recipients

Design

Retrospective, single-center cohort study

N= 36

Objective

To investigate the outcomes of perioperative daptomycin in vancomycin-resistant Enterococcus (VRE)-colonized liver transplant recipients

Study Groups

Daptomycin (n= 19)

No daptomycin (n= 17)

Inclusion Criteria

Liver transplant recipients (LTR) ≥18 years old who were VRE-colonized from June 2018 to November 2022

Exclusion Criteria

No specific exclusion criteria mentioned

Methods

All LTR received perioperative piperacillin-tazobactam 3.375 g every 8 hours for 24 hours. If VRE-colonized, one dose of daptomycin 6 mg/kg (one dose preoperatively and one dose immediately postoperatively) was added to the antibiotic regimen or replaced vancomycin when indicated.

Duration

June 2018 to November 2022

Outcome Measures

Primary: VRE infection at 14 days and 90 days post-transplant

Secondary: Time to VRE infection, acute rejection within 90 days, 90-day mortality, ICU length of stay, overall hospital length of stay, ICU readmission within 90 days

Baseline Characteristics

  

No daptomycin (n= 17)

Daptomycin (n= 19)

 p-Value

Age, years

 53.5 + 9.8  55.2 + 11.3 0.637

Female

70.6%

47.4%

 0.192

Etiology of liver disease

          Alcoholic cirrhosis

          Nonalcoholic steatohepatitis

          Hepatitis C

          Primary biliary cholangitis

          Primary sclerosing cholangitis

 

70.6%

17.6%

11.8%

-

- 

 

63.2%

21.1%

-

5.3%

5.3%

 

-

-

-

-

-

MELD score at transplant

38 (30–40)

35 (33–40)

 0.968

Ascites at transplant

94.1%

100%

>0.999

Liver transplant alone

94.1%

73.7%

 - 

VRE colonization identification

          VRE screen

          Prior (+) culture—urine

          Prior (+) culture—blood

          Prior (+) culture—wound

 

41.2%

52.9%

-

5.9% 

 

78.9%

15.8%

5.3%

-

 

-

-

-

-

Renal replacement therapy prior to transplant

58.8%

47.4%

 0.525

ICU admission prior to transplant

35.3%

15.8%

 0.255

Abbreviation: MELD, model for end-stage liver disease.

Results

Endpoint

No daptomycin (n= 17)

Daptomycin (n= 19)

p-Value

VRE infection within 14 days post-LT

23.5%

 0%

0.040

VRE infection within 90 days post-LT

29.4%

15.8%

 0.434

Death within 90 days

 0% 5.3% 0.452

Acute rejection within 90 days

 17.6% 15.8%  >0.999 

ICU LOS, days

7 (4.5–9)

8 (7–13)

 0.039

Overall hospital LOS, days

11 (8.5–17)

14 (10–26)

 0.104

ICU readmission

 17.6%  15.8%  >0.999 

Abbreviations: ICU, intensive care unit; LOS, length of stay.

Adverse Events

No specific adverse events related to daptomycin were reported

Study Author Conclusions

Perioperative daptomycin reduced the rate of VRE infections in VRE-colonized LTR within 14 days post-transplant but not at 90 days. Future studies should evaluate if higher doses and/or longer duration of perioperative daptomycin can reduce VRE infections beyond 14 days post-transplant.

InpharmD Researcher Critique

The study was limited by its retrospective, single-center design and small sample size, which may affect the generalizability of the findings. The daptomycin dose used was relatively low and the study was not powered to detect a difference in VRE infections post-LT. Additionally, genotypic characterization of VRE isolates was not performed, limiting the ability to confirm if post-LT infections were caused by the same strains as pre-LT colonization.



References:

Mak JT, Ha S, Perloff S, Knorr JP. Perioperative daptomycin for prophylaxis of vancomycin-resistant Enterococcus infection in colonized liver transplant recipients. Transpl Infect Dis. 2024;26(1):e14186. doi:10.1111/tid.14186
Daptomycin perioperative prophylaxis for the prevention of vancomycin-resistant Enterococcus infection in colonized liver transplant recipients
Design

Retrospective chart review

N= 27
Objective To determine the incidence and outcomes of vancomycin-resistant enterococcus (VRE) infection within 90 days of transplantation in VRE-colonized LT recipients who received daptomycin perioperative prophylaxis (DPP)
Study Groups

DPP recipients (n= 25)

Non-DPP recipients (n= 2)
Inclusion Criteria Liver transplant recipients aged ≥18 years between 2013 and August 2019 with pre-LT VRE colonization
Exclusion Criteria Not specified
Methods Retrospective chart review of LT recipients with pre-LT VRE colonization. DPP involved daptomycin 6 mg/kg IV preoperatively, then every 12 hours intraoperatively, and every 24 hours postoperatively for 48 hours, adjusted for renal function
Duration 2013 to August 2019
Outcome Measures

Primary: VRE-related infection within 90 days of LT

Secondary: All-cause mortality within 90 days of LT
Baseline Characteristics Characteristic Number of recipients (n= 25)
Age (y) at transplant, median [range] 54 [32-72]
Female 12 (48%)

Race

Caucasian

Black

Hispanic

Unknown

 

72%

4%

20%

4%

MELD score at transplant

≤15

16-30

>30

 

12%

20%

68%
Charlson Comorbidity Index Score, median [range] 6 [3-9]
Prior VRE infection 3 (12%)
Presence of ascites at transplant 23 (92%)
Results Endpoint DPP recipients (n= 25) Non-DPP recipients (n= 2)
VRE-related infection within 90 days 0 2
All-cause mortality within 90 days 0 0
Adverse Events Not reported
Study Author Conclusions

Despite multiple risk factors for post-LT VRE infection, VRE-colonized recipients who received DPP did not develop VRE-related infections within 90 days post-LT. Pre-LT VRE screening and DPP may reduce VRE infection rates in the early post-LT period, warranting further evaluation in prospective studies.
Critique The study's retrospective design and small sample size limit the generalizability of the findings. The lack of a control group of LT recipients who did not receive DPP makes it difficult to draw definitive conclusions. Prospective studies are needed to confirm the effectiveness of DPP in preventing VRE infections post-LT.

 

References:

Sarwar S, Koff A, Malinis M, Azar MM. Daptomycin perioperative prophylaxis for the prevention of vancomycin-resistant Enterococcus infection in colonized liver transplant recipients. Transpl Infect Dis. 2020;22(3):e13280. doi:10.1111/tid.13280