Limitations of our study are stratification of infection control

practices by institution, retrospective data collection, and the fact

that it was conducted at two hospitals in the same healthcare

network, potentially limiting the generalizability of our results.

Antibiotic prophylaxis after LVAD implantation was associated with

increased rates of antibacterial resistance without decreased rates

of infectious complications.

As we gain more knowledge regarding the effects of antibiotic

administration on cutaneous microbiota, sampling of the driveline

exit site to analyze its microbiome could help elucidate the

complex microbial dynamics of LVAD-associated infections.

Prospective studies of LVAD-infections, using standardized

definitions to analyze patient-level clinical and microbiologic data

are needed.

Dimitrios Farmakiotis, MD1,2 , Alyssa R. Letourneau, MD, MPH3, Alicia Galar, Pharm D, PhD1,

Sophia Koo, MD1, James H. Maguire, MD1, Michael M. Givertz, MD4, Lindsey R. Baden, MD1

Patients and Methods

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We retrospectively studied patients with continuous flow-LVADs placed at Brigham and Women’s Hospital (BWH) and Massachusetts General Hospital (MGH), between 1/1/2007 and 11/30/2014.

We compared two different strategies after implantation, with sterile dressings and: (1) topical care alone: chlorhexidine skin cleanser (BWH), or (2) antimicrobial prophylaxis: oral doxycycline with topical polymyxin-trimethoprim drops (MGH). We assessed LVAD-specific or related infection rates, according to the ISHLT criteria, identified factors associated with LVAD-infections, and analyzed pathogen susceptibilities during first episodes of infection.

A new “episode” of LVAD-infection was defined as an infection event prompting modification of management, such as change of antibiotic regimen or hospital admission, if they were caused by a different organism, or by the same organism, but with evidence of clinical resolution of the initial episode, at least 30 days apart and, for bacteremia, with documented negative blood cultures in between.

Conclusions and Limitations

• We studied 191 patients. More patients in the prophylaxis

group received an LVAD as bridge to transplant (p=0.01) and

had a HeartWare HVAD device (p<0.01).

• Independent predictors of LVAD-infection included male sex

(Rate ratio [RR] 1.8, p=0.04; sub-distribution hazard ratio

[sHR, after adjustment for death or transplant as competing

events] 2.8, p=0.02) and diabetes (RR 1.7, p<0.01; sHR 1.9,

p=0.02), but not antibiotic prophylaxis.

• While there were no inter-institutional differences in

antibiogram susceptibility rates of Staphylococci to

tetracycline or trimethoprim/sulfamethoxazole, antibiotic

prophylaxis was associated with increased rates of resistance

to both agents (p<0.01 and p=0.05, respectively).

• All-cause mortality was not affected by infection or

prophylaxis.

• Among patients with bridge-LVADs, there were no differences

in transplant rates between patients with and without LVAD-

infection, or between those who received antibiotic

prophylaxis and those who did not.

• Infection as a time-varying parameter was associated with

shorter time to transplant in all transplant candidates (HR 1.7,

95% CI 1-2.9, p=0.04), and after exclusion of those who died

before transplant (HR 1.8, 95% CI 1.1-3.1, p=0.02).

In heart failure patients with left ventricular-assist devices (LVADs),

infections cause significant morbidity and frequent hospitalizations.

The marked heterogeneity in methods and results across different

studies of LVAD infections led the International Society for Heart

and Lung Transplantation (ISHLT) to propose uniform definitions

for infections in patients with LVADs.

There are few studies describing the epidemiology, risk factors for

and outcomes of continuous-flow (CF)-LVAD-(associated)

infections, by application of these standardized criteria. Also, the

effects of prolonged antibiotic prophylaxis after LVAD implantation

on the incidence of LVAD-associated infection and antibacterial

resistance have not been adequately described.

• Aims of the present study were to:

1.Describe the spectrum of LVAD-infections and pathogen species

distribution, using the ISHLT definitions, in a contemporary cohort

of patients with CF-LVADs

2.Identify predictors of infection and its impact on clinical outcomes

3.Assess the effects of prolonged antibiotic prophylaxis after

device implantation on LVAD-infection rates, outcomes and

antibacterial resistance.

Figure 1. Cumulative incidence of LVAD-associated infections, after adjustment for

death or transplantation as competing events; sHR: sub-distribution hazard ratio.

Divisions of 1Infectious Diseases and 4Cardiovascular Medicine, Brigham and Women’s Hospital, and 3Division of Infectious Diseases, Massachusetts General Hospital,

Harvard Medical School, Boston, MA, 2Division of Infectious Diseases, Warren Alpert Medical School of Brown University, Providence, RI

Continuous variables were compared with Student’s t-test or the Mann-

Whitney U-criterion for variables that were not normally distributed.

Proportions were compared with the χ2 test or Fisher’s exact test, if

expected counts were <5 in >50% of all cells.

Cases were censored at death or transplant. Because of multiple

infection episodes in the same patients, we applied generalized

estimating equations with a Poisson distribution to calculate event rates

and rate ratios (RR) with 95% confidence intervals (CI). We also

estimated sub-distribution hazard ratios (sHR) for first episodes of

infection with death or transplantation as competing events.

All-cause mortality and transplantation (limited to LVADs placed as

bridge to transplantation or candidacy) were compared by means of

log-rank test and Cox regression, with infection as a time-varying

variable.

Figure 2. Pathogen distribution (absolute numbers and % bars) among initial

and subsequent episodes of LVAD-associated infection: SA, Staphylococcus

aureus; CONS, coagulase-negative Staphylococcus species; OS, other

Staphylococcus species; GPC, other Gram-positive cocci; GPR, Gram-positive rods;

Ps, Pseudomonas aeruginosa; GNR, enteric Gram-negative rods; CAND, Candida

species. Beveled bars represent gram-positive, and regular ones gram-negative

bacteria.

Background - Objective Results

N (%) unless otherwise

indicated

Antibiotic prophylaxis

(N=60)

No antibiotic prophylaxis

(N=131)

Age (mean±S.D.) 55±11 55±12

Men 54 (90) 105 (80)

Patient-days of LVAD support

(median, IQR) 300 (105, 504) 379 (148, 688)

Destination LVAD * 9 (15) 51 (39)

Heartware 2 HVAD ** 22 (37) 14 (11)

Diabetes 11 (18) 24 (18)

LVAD-infections (95% CI)

First 58 (37, 86) 29 (21, 39)

All 71 (51, 96) 39 (31, 50)

Bacteremia (95% CI)

First 9 (3-21) 15 (9, 23)

All 24 (13-39) 17 (12, 24)

Tetracycline susceptibility **

All isolates 1/22 (5) 19/33 (58)

Staphylococcus spp. 1/9 (11) 16/19 (84)

TMP/SMX susceptibility *

All isolates 4/22 (14) 15/34 (44)

Staphylococcus spp. 3/9 (33) 12/19 (63)

Table footnotes: LVAD, left ventricular-assist device; IQR, Interquartile range,

25th-75th percentiles; CI, confidence interval; TMP/SMX,

trimethoprim/sulfamethoxazole; *p<0.05; **p<0.001

Table 1. Patient characteristics, LVAD-infection rates and susceptibiltity

patterns