Phage Therapy for Cardiac Implantable Electronic Devices and Vascular Grafts: A Targeted Literature Review.

Infections of cardiac implantable electronic devices (CIEDs) and vascular grafts are some of the most dreaded complications of these otherwise life-saving devices. Many of these infections are not responsive to conventional treatment, such as systemic antibiotics and surgical irrigation and debridement. Therefore, innovative strategies to prevent and manage these conditions are warranted. Among these, there is an increasing interest in phages as a therapeutical option. In this review, we aim to collect the available evidence for the clinical application of phage therapy for CIED and vascular graft infections through literature research. We found 17 studies for a total of 34 patients. Most of the indications were left ventricular assist device (LVAD) (n = 20) and vascular graft infections (n = 7). The bacteria most often encountered were Staphylococcus aureus (n = 18) and Pseudomonas aeruginosa (n = 16). Clinical improvements were observed in 21/34 (61.8%) patients, with microbiological eradication in 18/21 (85.7%) of them. In eight cases, an adverse event related to phage therapy was reported. Phage therapy is a promising option for difficult-to-treat CIED and vascular graft infections by means of an individualized approach. Clinical trials and expanded access programs for compassionate use are needed to further unveil the role of phage therapy in clinical application.

Risk of Infections With Long-Term Left Ventricular Assist Device Support.

The average life expectancy post-left ventricular assist device (LVAD) implantation has significantly increased in recent years. Impaired cellular immunity post-LVAD implantation has been suggested. It is not clear if a prolonged duration of LVAD support will lead to an increase in infections and possibly cause opportunistic infections, as seen in immunocompromised patients. METHODS:  We retrospectively reviewed all the patients who underwent new continuous-flow (C-F) LVAD implantation between January 1, 2013, and December 31, 2014, at the University of Nebraska Medical Center. Patients were followed until heart transplant, LVAD explantation, death, or December 31, 2017. We defined LVAD infections as per the International Society of Heart and Lung Transplantation (ISHLT) definition: VAD-specific, VAD-related, and non-VAD infections. The primary outcome was to calculate the incidence of LVAD infections per 1000 days of LVAD support. Secondary outcomes were to assess the cause of death and the effect of bloodstream infections on LVAD thrombosis, stroke, and death. RESULTS: During the study period, a total of 94 patients underwent a C-F LVAD implantation. Five patients were lost in follow-up; 89 patients were included in the study. The mean age at LVAD implantation was 54 (SD+15) years. Out of 89 patients, 67 (75%) were men, and 53/89 (71%) received LVAD as destination therapy (DT). At the time of LVAD implantation, 34/89 (38%) patients had ITERMACS (interagency registry for mechanically assisted circulatory support) score 1 (cardiogenic shock). The median duration of LVAD support was 387+493 days, with an interquartile range of 140 to 1083 days. The incidence rate of infections post-LVAD implantation decreased from 3.2 /1000 LVAD days (95% confidence interval [CI] 2.54-4.03) during the first year of LVAD support to 0.78/1000 LVAD days (95% CI, 0.38-1.65) during the following third year of LVAD support. Similarly, the incidence of VAD-specific infections in the first year post-LVAD implantation versus the third-year post LVAD implantation decreased from 0.83/1000 LVAD days (95% CI, 0.53-1.30) to 0.33/1000 LVAD days (95% CI, 0.10-1.04). On univariate survival analysis, an increased risk of death was associated with a one-year increase in age at LVAD implantation (hazard ratio (HR) 1.05 (95% CI, 1.01-1.09), p=0.01), the presence of infection within 30 days before LVAD implantation (HR 2.44 (95% CI, 1.09-5.48), p=0.03), underlying ischemic cardiomyopathy (HR 2.96 (95% CI, 1.28-6.80), p=0.01), and lower ITERMACS profile HR 3.64 (95% CI, 1.09-12.13, p=0.04). Bloodstream infections (BSIs) were not associated with an increased risk of death (HR 1.63 (95% CI, 0.56-4.80, p=0.37). Univariate survival analysis for poor outcomes (LVAD thrombosis, stroke, or death) showed BSIs increased the risk of having a poor outcome (HR 2.39 (95% CI, 1.02-5.57), p=0.04). CONCLUSIONS:  The incidence rate of post-LVAD infections decreased significantly over time. LVAD implantation may not be contributing to immune suppression as previously suggested. In our study, BSIs were found to have a significantly increased hazard ratio for a poor outcome post-LVAD implantation.

Dynamics of bacterial pathogens at the driveline exit site in patients with ventricular assist devices: A prospective, observational, single-center cohort study.

BACKGROUND: Driveline infections (DLIs) at the exit site are frequent in patients with left ventricular assist devices (LVADs). The dynamics from colonization to infection are yet to be investigated. We combined systematic swabbing at the driveline exit site and genomic analyses to study the dynamics of bacterial pathogens and get insights into DLIs pathogenesis. METHODS: A prospective, observational, single-center cohort study at the University Hospital of Bern, Switzerland was performed. Patients with LVAD were systematically swabbed at the driveline exit site between June 2019 and December 2021, irrespective of signs and symptoms of DLI. Bacterial isolates were identified and a subset was whole-genome sequenced. RESULTS: Fifty-three patients were screened, of which 45 (84.9%) were included in the final population. Bacterial colonization at the driveline exit site without manifestation of DLI was frequent and observed in 17 patients (37.8%). Twenty-two patients (48.9%) developed at least one DLI episode over the study period. Incidence of DLIs reached 2.3 cases per 1000 LVAD days. The majority of the organisms cultivated from exit sites were Staphylococcus species. Genome analysis revealed that bacteria persisted at the driveline exit site over time. In four patients, transition from colonization to clinical DLI was observed. CONCLUSIONS: Our study is the first to address bacterial colonization in the LVAD-DLI setting. We observed that bacterial colonization at the driveline exit site was a frequent phenomenon, and in a few cases, it preceded clinically relevant infections. We also provided acquisition of hospital-acquired multidrug-resistant bacteria and the transmission of pathogens between patients.

Single-Center Experience With Protocolized Treatment of Left Ventricular Assist Device Infections.

Purpose: Because of the current lack of evidence-based antimicrobial treatment guidelines, Left Ventricular Assist Device (LVAD) infections are often treated according to local insights. Here, we propose a flowchart for protocolized treatment, in order to improve outcome. Methods: The flowchart was composed based on literature, consensus and expert opinion statements. It includes choice, dosage and duration of antibiotics, and indications for suppressive therapy, with particular focus on Staphylococcus aureus (SA) (Figure 1). The preliminary treatment results of 28 patients (2 from start cephalexin suppressive therapy) after implementation in July 2018 are described. Results: Cumulative incidence for first episode of infection in a 3-year time period was 27% (26 of 96 patients with an LVAD). Twenty-one of 23 (91%) first episodes of driveline infection (10 superficial and 13 deep; nine of 13 caused by SA) were successfully treated with antibiotics according to flowchart with complete resolution of clinical signs and symptoms. For two patients with deep driveline infections, surgery was needed in addition. There were no relapses of deep driveline infections, and only 2 SA deep driveline re-infections after 6 months. Nine patients received cephalexin of whom four patients (44%) developed a breakthrough infection with cephalexin-resistant gram-negative bacteria. Conclusions: The first results of this protocolized treatment approach of LVAD infections are promising. Yet, initiation of cephalexin suppressive therapy should be carefully considered given the occurrence of infections with resistant micro-organisms. The long-term outcome of this approach needs to be established in a larger number of patients, preferably in a multi-center setting.