Left ventricular assist device (LVAD) infections

INTRODUCTION — A durable left ventricular assist device (LVAD) can be used to treat advanced heart failure as a bridge to heart transplantation in eligible patients or as destination therapy for patients who are not eligible for transplant [1,2]. Infection is an important cause of morbidity and mortality in patients supported with an LVAD [3,4].

This topic will discuss the epidemiology, clinical manifestations, diagnosis, management, and prevention of LVAD infections.

Indications for LVAD placement and other associated complications are discussed in detail separately. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".)

HARDWARE COMPONENTS — An LVAD consists of a continuous-flow pump within a metal housing that is typically anastomosed to the apex of the heart (figure 1). The pump housing is connected to an external power source via a driveline cable that tunnels through the abdominal wall before exiting the skin in the left or right subcostal region. The driveline has a roughened velour material to facilitate adhesion to the subcutaneous tissues along the course of the tract.

TYPES OF LVAD INFECTION — The types of LVAD infection include driveline infection, extravascular pump infection, and endovascular pump infection; one or more types of infection may coexist simultaneously:

●Driveline infection – An infection of the driveline and/or its surrounding tissues (picture 1 and picture 2). (See 'Driveline infection' below.)

●Extravascular pump infection – An infection of the extravascular components of the LVAD (picture 3). (See 'Extravascular pump infection' below.)

●Endovascular pump infection – An infection of any surface of the device that interfaces with the bloodstream. This can include the inflow cannula, blood contacting surfaces of the pump, and the outflow graft. (See 'Endovascular pump infection' below.)

The International Society for Heart and Lung Transplant (ISHLT) Infectious Disease Working Group published standardized diagnostic criteria and definitions of LVAD infections in 2011 [3]. The ISHLT definitions are as follows:

●VAD-specific infections – Ventricular assist device (VAD)-specific infections include infections that are related to the device hardware; these include driveline infection, extravascular pump infection, and endovascular pump infection.

●VAD-related infections – VAD-related infections refer to infections that can also occur in patients who do not have VADs; however, there may be unique considerations in patients with VADs with respect to making the correct diagnosis or determining the cause-and-effect relationship (examples include mediastinitis and infective endocarditis).

●Non-VAD infections – Non-VAD infections are unlikely related to the VAD but are included to encourage comprehensive and comparable data recording of all infections among VAD recipients.

EPIDEMIOLOGY

Incidence — The incidence of LVAD infection is illustrated by the following studies:

●In a study including 10,171 patients with mechanical circulatory support devices and 6758 infection episodes (classified based on the International Society for Heart and Lung Transplant definitions), rates of LVAD infection (eg, driveline infection) and LVAD-related infections (eg, mediastinitis) over a three-year period were 25.9 and 7.4 percent, respectively [5].

●In a study including 14,607 LVAD recipients, the risk of infection was comparable in the early (within 90 days) and later periods (>90 days) following LVAD implantation (0.16 versus 0.175 events per patient year, respectively) [6].

●In a review including 132 studies of LVAD recipients, the frequency of infection (by type) at one-year postimplant was [7]:

•Driveline infection − 7 to 71 percent

•Extravascular pump infection − 0.4 to 10 percent

•Endovascular pump infection − 2.2 to 13 percent

Risk factors — The patient and device factors that increase the risk of infection include the following:

●Age – Age <50 years may be associated with increased risk of driveline infection, due to higher level of physical activity and consequent mechanical trauma at the exit site [8].

●Comorbidities – Comorbidities such as diabetes and obesity may increase the risk of LVAD infection [9-11]. In a meta-analysis including 15 studies and more than 17,000 patients with LVAD implants, obesity was associated with increased risk of device-related infection (risk ratio 1.48, 95% CI 1.25-1.75) [12]. Another analysis including 341 patients who underwent LVAD implantation found that those with diabetes had a higher risk of device infection (hazard ratio [HR] 2.1, 95% CI 1.4-3.1) [10].

●Psychosocial factors – A number of psychosocial factors may be associated the risk of LVAD infection. In an analysis including more than 15,000 patients who received a continuous-flow LVAD, presence of one or more psychosocial risk factors (eg, limited social support, limited cognition, substance use disorder, severe psychiatric disease; HR 1.23, 95% CI 1.10-1.37) and repeated noncompliance (HR 1.49, 95% CI 1.27-1.76) were associated with a higher risk of device infection [13]. Presence of two or more psychosocial risk factors was associated with a higher risk of driveline infection compared with patients with one risk factor (adjusted HR 1.22, 95% CI 0.80-0.91).

●Prior cardiac procedures – Prior cardiac surgery and temporary mechanical circulatory support may increase the risk of LVAD infection [11]. In a post hoc analysis of a randomized trial that included 515 patients implanted with a HeartMate 3 and 505 patients with a HeartMate II, preimplant use of an intra-aortic balloon pump and history of cardiac surgery were independently associated with an increased risk of infection (HR 1.33, 95% CI 1.12-1.69 and HR 1.28, 95% CI 1.06-1.55, respectively) [11].

However, in a subsequent analysis that included 112 patients with a continuous-flow LVAD, the rates of sternal wound infection and overall infection were not statistically different between patients who had a prior sternotomy and those without prior sternotomy (8.3 versus 3.8 percent, and 8.3 versus 24.5 percent, respectively) [14].

●Driveline placement – At implantation, the velour portion of the driveline can be placed internally, such that it does not protrude into the driveline exit site. This approach to driveline placement (“silicone interface”) may reduce the risk of driveline infection by 50 percent in the first year [15,16].

PATHOGENIC MECHANISMS

●Driveline infection – Drivelines are designed with a roughened velour material to facilitate adherence to host tissues, which is intended to create a seal against the environment, but given the course of the driveline between the environment and the body, the potential for driveline infections exists. Mechanisms of driveline infection include:

•Incomplete incorporation of the driveline – Adherence between the driveline and the skin tract does not always occur. In patients who have incomplete incorporation of the driveline, organisms may more easily ascend via the driveline.

•Driveline trauma or movement – In addition, trauma to the driveline from shearing traction or torsion injury can disrupt driveline integration into the tissue, which increases the risk for infection.

•Biofilm formation – Whenever organisms colonize the driveline, biofilm can develop that allows organisms to remain dormant for months or years before clinical manifestations of infection develop. Biofilm formation creates a sanctuary from host defense mechanisms and antibiotics, making cure very challenging [17,18].

●Pump infection (extravascular or endovascular) – Pump infection may be caused by hematogenous seeding due to bacteremia originating from another primary site or by contamination during initial placement [17,19].  

MICROBIOLOGY

●Bacteria

•Gram-positive organisms – Gram-positive organisms are the leading cause of LVAD infections, responsible for half of all reported cases. Staphylococcus aureus is the predominant pathogen, followed by coagulase-negative staphylococci (CoNS) [20,21]. Gram-positive infections that occur ≤90 days after LVAD implantation are likely acquired from contamination with skin flora at the time of implantation [22,23].

•Gram-negative organisms – Gram-negative pathogens are the second most common group of organisms associated with LVAD infection, responsible for 41 percent of cases. Among these, Pseudomonas aeruginosa is the most prevalent, followed by Enterobacterales [20].

Infections due to gram-negatives typically occur >90 days following LVAD implantation [23]. Acquisition of gram-negative pathogens in these patients is thought to occur after frequent contact with health care or humid environments [21,24].

•Multidrug-resistant organisms – LVAD infections involving multidrug-resistant organisms have been described [25]. Risk factors include prolonged duration of LVAD support, obesity, and exposed velour portion of the driveline through the exit site. The most common organisms with multidrug resistance include S. aureus, P. aeruginosa, CoNS, Escherichia coli, and Klebsiella spp.

●Fungi – LVAD infections due to fungal organisms are relatively rare (<7 percent) [26]. LVAD infections due to Aspergillus and Mucor spp are exceedingly rare [27-29].

●Nontuberculous mycobacteria – LVAD infections due to nontuberculous mycobacteria have been reported sporadically; one series included eight cases [30]. Causative organisms in this report included Mycobacterium abscessus (n = 2), Mycobacterium fortuitum (n = 2), Mycobacterium chimaera (n =2), Mycobacterium chelonae (n = 1), and Mycobacterium intracellulare (n = 1). There were six driveline infections. The timing of presentation ranged from 5 to 60 months.

CLINICAL MANIFESTATIONS

●General symptoms and signs – Most patients with LVAD infection present with erythema and/or purulent discharge at the driveline exit site, pain along the driveline tract, or pain involving the left chest wall (the typical LVAD pump site) (picture 1 and picture 2). Patients may also present with fever or other systemic symptoms (eg, anorexia, fatigue) [20,21,31].

Vascular (eg, septic emboli and cerebrovascular accidents) and immunologic phenomena (eg, glomerulonephritis) may develop [32]. These are described separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Clinical manifestations'.)

●Cardiac and/or device abnormalities – Patients with LVAD infection may present with heart failure exacerbation or other cardiac abnormalities (eg, arrhythmias).

It is rare for LVAD infection to cause abnormal device function. However, patients with dehydration, systemic inflammatory response syndrome, or other sequelae of infection may have low pulsatility index or low-flow alarms.

●Laboratory abnormalities – Patients with an LVAD infection may have a rising white blood cell count or evidence of deterioration of end-organ function (eg, acute kidney injury).

EVALUATION — The initial assessment consists of the following components:

●History and physical examination – The history should review any changes to the driveline exit site or changes in wound care regimen prior to presentation, history of driveline or device trauma, and signs or symptoms that may localize an infection to a site other than the device (eg, urinary symptoms, respiratory symptoms).

The physical examination should be focused on assessment of the driveline exit site and the skin and deep tissues along the course of the driveline tunnel. We inspect and palpate the area for signs of inflammation, exudate, tenderness, swelling, or fluctuation. There may also be discharging sinuses, distinct from the driveline exit site, related to the course of the driveline. A sinus tract from the pump to the skin may occasionally develop in the lateral chest wall; this is more typically encountered in patients where the device had been implanted through a left thoracotomy [3,21].  

In addition, patients should be evaluated for symptoms and signs of infective endocarditis. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Symptoms and signs'.)

●Initial evaluation – The initial evaluation includes:

•Blood cultures – At least two sets of blood cultures should be obtained from separate anatomic sites. Ideally, blood cultures should be obtained from peripheral veins via separate venipuncture sites.

•Drainage cultures – If purulent drainage is present at the driveline exit site, drainage material should be sent for bacterial, mycobacterial, and fungal stain and culture. If radiographic imaging demonstrates abscess, image-guided aspiration or surgical drainage should be pursued and material should be sent for culture.

•Laboratory tests – A complete blood count and complete metabolic panel should be obtained. Inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein, and procalcitonin can be obtained, but there are no data to support their use.

•Additional studies – Additional studies to rule out alternative causes of infection should be guided by symptoms; these may include urinalysis, chest radiograph, and sputum Gram stain and culture.

●Further evaluation – Further evaluation should be guided by the clinical assessment:

•Suspected driveline and/or extravascular pump infection – For patients with inflammation at the driveline and/or pocket sites, we typically obtain computed tomography (CT) of the chest and abdomen to define the extent of infection, evaluate for drainable fluid collection or abscess, and assess for complications that may require surgical intervention [33].

Typical radiographic signs of a driveline infection consist of stranding and induration around the driveline. Rim-enhancing fluid collections around the pump, outflow graft, or driveline are suggestive of extravascular pump infection, mediastinal infection, or driveline abscess, respectively.

If an operation is performed to treat a driveline or extravascular pump infection, tissue and any extracted hardware should be submitted for bacterial, mycobacterial, and fungal stain and culture, as well as histopathology.

•Suspected endovascular pump infection – For patients with systemic symptoms such as hemodynamic instability, bacteremia, device malfunction, and/or vascular or immunologic phenomena, additional tools for further evaluation include echocardiography and radiographic imaging:

-Echocardiography – Transthoracic echocardiography (TTE) should be pursued to evaluate for echodensity, intracardiac mass, or abscess. If the initial TTE is unrevealing, a transesophageal echocardiogram (TEE) may be useful to evaluate for masses around the inflow cannula (which could represent vegetations) and to exclude heart valve or pacemaker lead endocarditis (as alternative sources of bacteremia).

-Radiographic imaging – The sensitivity of CT for diagnosis of infection involving the inner surface of the device is low; in one study that included 66 patients with endovascular LVAD infection, CT was normal in 55 percent of cases [20].

If available, fluorodeoxyglucose positron emission (FDG PET)/CT may be useful for evaluation of patients with suspected LVAD-specific infection in whom CT or echocardiography are nondiagnostic. In a pooled analysis of 10 studies including 256 FDG PET/CT scans, the sensitivity and specificity for diagnosis of LVAD infection were 95 and 91 percent, respectively [34].

However, reactive uptake around the LVAD can persist for months or years after LVAD implantation, leading to false-positive findings [35]; for this reason, the FDG PET/CT should be used only when there is a high pretest probability for infection (as opposed to a ‘screening test’ for an LVAD infection).

•Tissue and device cultures – For patients who undergo surgery for management of infection, intraoperative cultures should include samples from tissue around the pump and cannulas, aspirates from the inflow and outflow cannulas, and culture of saline instilled into the pump. These samples should be submitted for bacterial, mycobacterial, and fungal stain and culture, as well as histopathology.

•Patients with negative cultures – For patients with negative cultures (including blood and operative cultures) in the setting of high clinical suspicion for LVAD infection, molecular diagnostic testing (such as 16S ribosomal ribonucleic acid [rRNA] polymerase chain reaction/sequencing) is warranted. While thus far the utility of this approach has not been well described for LVAD infection, it has been used in the setting of culture-negative endocarditis.

DIAGNOSIS

Driveline infection — A definitive diagnosis of driveline infection is based on culture results from drainage material obtained from the driveline exit site. A presumptive clinical diagnosis may be made in the setting of signs of infection at the driveline site that are not otherwise explained (such as traumatic injury or hypersensitivity reaction).

Driveline infections may be classified further as follows:

●Uncomplicated infection – Uncomplicated driveline infection refers to the presence of inflammation (erythema, edema, and warmth) and drainage at the driveline exit site or surrounding tissues, in the absence of abscess, necrosis, or systemic inflammatory response syndrome criteria [3,21,36]. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis".)

●Complicated infection – Complicated driveline infection refers to the presence of inflammation and drainage, in addition to systemic inflammatory response syndrome criteria or abscess, necrosis, or sepsis [18]. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis".)

Extravascular pump infection — A definitive diagnosis of extravascular pump infection is based on positive operative cultures or histopathologic findings.

For patients who do not undergo operative intervention, a presumptive clinical diagnosis may be made in the setting of radiographic imaging demonstrating findings consistent with an infection (including fluid collection, enhancement, gas, or sinus tract) and positive culture of image-guided aspiration material [3]. Aspirate cultures must be interpreted carefully. As an example, growth of common skin colonizers (such as coagulase-negative staphylococci or Cutibacterium spp) in small quantities may not necessarily reflect infection; such data should be reviewed in the context of other clinical and radiographic findings.

Endovascular pump infection — The diagnosis of endovascular pump infection may be established clinically by positive blood cultures as well as echocardiographic and/or radiographic findings (including echodensity, intracardiac mass, mass around the inflow cannula, or abscess). If the device is removed, additional diagnostic criteria include positive operative cultures and histopathologic criteria [3].

Evaluation for alternative causes of bacteremia (including heart valve endocarditis, pacemaker lead endocarditis, or catheter infection) is also warranted. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis" and "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis".)

MANAGEMENT

Driveline infection — Outpatient management is appropriate for patients with uncomplicated driveline infection (with oral antibiotic therapy, if susceptibility data permits), while patients with a complicated driveline infection require inpatient management. In general, the management of driveline infections consists of collecting blood and drainage cultures, followed by initiation of antibiotic therapy; surgical debridement or image guided drainage is warranted in some circumstances [4].

●Uncomplicated driveline infection

•Empiric antibiotic therapy – For patients who are clinically stable but have substantial erythema, drainage, or skin warmth , we initiate empiric oral antibiotic therapy with a regimen active against methicillin-resistant S. aureus (MRSA; such as trimethoprim-sulfamethoxazole or doxycycline) and Pseudomonas spp (such as ciprofloxacin or levofloxacin).

Uncomplicated driveline infections can usually be managed in the outpatient setting. However, in the setting of rapid progression of erythema or drainage, positive blood cultures, or lack of clinical improvement within 48 hours of starting oral antibiotic therapy, we pursue inpatient admission for parenteral therapy (outlined below).

•Tailoring antibiotic therapy – Antibiotic therapy should be tailored to culture results and susceptibility data when available. If cultures are negative but clinical improvement is observed on the empiric regimen, this regimen (or an alternative regimen with comparable spectrum of activity) may be continued.

For patients with uncomplicated driveline infection confined to the incision site and subcutaneous tissue, we treat with oral antibiotic therapy for at least two to four weeks, after which the duration should be guided by clinical improvement [4]. Prior to discontinuation of antibiotic therapy, patients should be evaluated to ensure complete resolution of symptoms. Patients with persistent symptoms should be managed as complicated infection (outlined below).

●Complicated driveline infection with negative blood cultures

•Antibiotic therapy

-Empiric antibiotic therapy − For patients who present with hemodynamic instability and/or progressive inflammation at the driveline site, we initiate empiric parenteral antibiotic therapy with a regimen active against MRSA (such as vancomycin) and Pseudomonas spp (such as cefepime or ceftazidime); for patients with hemodynamic instability in the setting of underlying immunosuppression, some also include empiric antifungal treatment with an echinocandin.

-Tailoring antibiotic therapy − Antibiotic therapy should be tailored to culture and susceptibility data when available. Parenteral therapy is preferred in cases of complicated driveline infection; if drainage culture susceptibility data permit, highly bioavailable oral agents may be considered.

We treat patients with deep or complicated driveline infection until clinical stabilization and improvement of infection (usually six to eight weeks) with close follow-up [4,37]. Prior to discontinuation of antibiotic therapy, patients should be evaluated to ensure complete resolution of symptoms.

•Surgical debridement − In addition to antibiotic treatment, surgical intervention is warranted in patients with driveline infection who have radiographic evidence of abscess, fluid collection, tissue gas, or progressive erythema and drainage despite appropriate antibiotic therapy. Surgical options include debridement of the driveline site, re-siting of the driveline, and drainage of abdominal wall abscesses (picture 2).

In patients who undergo surgery, operative cultures should be collected as described above. (See 'Evaluation' above.)

•Patients who do not respond to antibiotics − For patients with persistent signs and symptoms of driveline infection despite antibiotic treatment, repeat imaging should be pursued to evaluate for interval change (including drainable fluid collection or abscess), and to assess for complications that may require surgical intervention.

If imaging excludes a drainable collection, options for management of refractory infection include palliative antibiotic therapy, device replacement, device explant (if there is sufficient underlying cardiac function), or urgent cardiac transplantation (for eligible patients). A full cardiac assessment, surgical assessment, and multidisciplinary discussion is required to determine which strategy to pursue.

•Role of suppressive antibiotic therapy − In general, we do not favor routine use of chronic suppressive antibiotic therapy for patients with driveline infection associated with a retained device who respond to therapy. Following cessation of antibiotic treatment, patients should be monitored closely for relapse of signs or symptoms consistent with infection.

Use of suppressive antibiotic therapy may be reasonable in select patients who are awaiting heart transplantation, such as patients whose intraoperative cultures or histopathology demonstrate active infection. In addition, suppressive antibiotic therapy may be reasonable for patients with prior history of driveline infection who have completed antibiotic treatment for a repeat episode.

●Driveline infection with positive blood cultures – The approach to treatment of patients with driveline infection and positive blood cultures is as outlined for patients with endovascular (pump) infection. (See 'Endovascular pump infection' below.)

Extravascular pump infection — Extravascular pump infections are managed in the hospital and therapy consists of antibiotic therapy and surgical intervention [4]:

●Antibiotic treatment – For patients with symptoms or signs of systemic infection, we initiate therapy with an empiric parenteral antibiotic regimen active against MRSA (such as vancomycin) and Pseudomonas spp (such as cefepime or ceftazidime); for patients with hemodynamic instability in the setting of underlying immunosuppression, some also include empiric antifungal treatment with an echinocandin.

If there is coexisting discharge from a driveline or skin sinus, cultures should be obtained prior to initiation of antibiotics. If possible, antibiotic therapy should be deferred until tissue or fluid is obtained for culture (in the absence of driveline infection, this would be after a surgical debridement).

Antibiotic therapy should be tailored to culture and susceptibility data when available. We treat patients with extravascular pump infection for at least six to eight weeks of parenteral antibiotic therapy, tailored to clinical improvement.

●Surgical management − Surgical intervention is required for definitive management of extravascular pump infection; in some circumstances, device replacement may be required (picture 3). Surgery consists of drainage and evacuation of fluid and debris around the pump, saline washout, debridement of any inflamed tissue, and placement of drainage tubes. Antibiotic impregnated beads using absorbable calcium sulfate may be placed in the pocket. Surgery is undertaken through either an incision directly over the pump (typically a thoracotomy) or via a sternotomy (the latter carrying higher morbidity). Operative cultures should be collected as described above. (See 'Evaluation' above.)

For patients with extensive abdominal or chest wall infection manifesting as discharging sinuses or extensive soft tissue destruction, device exchange is indicated. For patients whose device has eroded through the skin and is exposed, adjunctive surgical interventions may be required; these include use of a vacuum dressing and/or tissue flap coverage.

For patients who are not surgical candidates for device exchange, serial debridement and washout of the pump pocket with antibiotic bead placement or cardiac transplantation are alternative approaches [38].

●Suppressive antibiotic therapy − Following completion of parenteral therapy, we administer suppressive oral antibiotic therapy, even if the device is replaced, since the procedure involves an infected operative bed. We tailor decisions regarding the duration of antibiotic suppression to individual clinical circumstances including the reliability of source control, operative findings, and culture data.

Endovascular pump infection — Endovascular (pump) infection is managed in the hospital and consists of antibiotic therapy; in addition, patients should be evaluated for device replacement [4]:

●Antibiotic treatment – We initiate empiric parenteral antibiotic treatment with a regimen active against MRSA (such as vancomycin) and Pseudomonas spp (such cefepime or ceftazidime); for patients with hemodynamic instability in the setting of underlying immunosuppression, some also include empiric antifungal treatment with an echinocandin.

Antibiotic therapy should be tailored to culture and susceptibility data when available. We treat patients for at least six to eight weeks of parenteral antibiotic therapy, tailored to clinical improvement.

●Surgical management – Typically surgery is considered only for patients with persistent signs and symptoms of infection in the setting of parenteral antibiotic therapy. The optimal approach in such cases is uncertain.

Options include palliative antibiotic therapy, device replacement, device explant (if there is sufficient underlying cardiac function), or urgent cardiac transplantation (for eligible patients). A full cardiac assessment, surgical assessment, and multidisciplinary discussion is required to determine which strategy to pursue.

If surgery is pursued, operative cultures should be collected as described above. (See 'Evaluation' above.)

●Suppressive antibiotic therapy − Following completion of parenteral therapy, we administer suppressive oral antibiotic therapy, even if the device is replaced, since the procedure involves an infected operative bed. We tailor decisions regarding the duration of antibiotic suppression to individual clinical circumstances including the reliability of source control, operative findings, and culture data.

Patients who undergo transplantation — The approach to antibiotic therapy after transplantation depends on the type of LVAD infection:

●Driveline infection − For patients who undergo cardiac transplantation while receiving antibiotic treatment for driveline infection, the final duration of antibiotic treatment should be guided by operative findings, culture results, and histopathology.

In the absence of evidence for infection, we continue antibiotics for one week after device removal; in the presence of evidence for infection, we continue antibiotics for two weeks after device removal.

●Extravascular or endovascular pump infection − For patients who undergo cardiac transplantation while receiving antibiotic treatment for extravascular or endovascular pump infection, we continue antibiotics for two weeks after device removal and confirmation of sterilization of blood cultures. For patients who require further debridement or develop complications, a longer duration of antibiotic therapy may be warranted [39].

PREVENTION

●Antimicrobial prophylaxis – Antimicrobial prophylaxis at the time of LVAD placement consists of an anti-staphylococcal agent (such as cefazolin or cefuroxime); for patients with methicillin-resistant S. aureus colonization, vancomycin should be used (table 1). We discontinue antimicrobial prophylaxis after 24 to 48 hours, irrespective of whether drains remain in place [4,40]. There is no role for additional gram-negative or fungal prophylaxis unless guided by institutional epidemiology data [4].

Prospective trials are needed to further define the optimal approach to prophylaxis. In a retrospective review including 239 patients who underwent LVAD implantation, 199 patients received a single-drug prophylaxis regimen (vancomycin or cefazolin) and 40 received a multidrug prophylaxis regimen (vancomycin, ciprofloxacin or cefepime, and fluconazole, with or without rifampin); the rate of LVAD infection at 90 days was comparable between the groups (3 versus 2 patients), and there was no difference in all-cause mortality at one year [41].

●Surgical technique – Strict aseptic surgical and anesthetic technique is necessary to prevent introduction of bacteria at time of LVAD surgery. Pump preparation and handling must be performed in a strictly sterile manner.

●Driveline site care – The driveline should be immobilized using a binder or anchoring device; fixation of the driveline to the skin for two to three weeks after implantation may facilitate healing and decrease potential for trauma or irritation. The driveline should be covered with a sterile dressing at all times. The dressing should be changed one to three times a week; patients should be instructed to do this with aseptic technique [42]. Showering prior to healing of the driveline site (eg, during the first month after implantation) should be minimized as this may increase risk for infection.

OUTCOMES — Morbidity and mortality varies by the type of LVAD infection. In one study including more than 10,000 LVAD recipients, one-year survival rates after initial diagnosis of driveline infection, extravascular pump infection, and endovascular pump infection were 87, 58, and 66 percent, respectively [5]. In another study including more than 12,000 patients, ventricular assist device (VAD)-specific infection was associated with death hazard of 2.92 (95% CI 2.57-3.32) [43].

In an international multicenter study including 10,171 patients with VAD (after first VAD-specific infection), 12-month survival was lower among patients with endovascular or extravascular pump infection (58 and 66 percent, respectively) than among patients with driveline infection (86 percent) [5].

Compared with patients with LVADs who do not undergo transplantation due to infection, patients who undergo transplantation due to infection have similar outcomes [44].

SUMMARY AND RECOMMENDATIONS

●Definitions – A left ventricular assist device (LVAD) can be used to treat advanced heart failure, as a bridge to heart transplantation in eligible patients, or as destination therapy for patients who are not eligible for transplant. LVAD components are shown in the figure (figure 1). Types of LVAD infection include driveline infection, extravascular pump infection, and endovascular pump infection; driveline infection is the most common. (See 'Types of LVAD infection' above and 'Epidemiology' above.)

●Microbiology – The microbiology of LVAD infections consist largely of gram-positive organisms (Staphylococcus aureus, coagulase-negative staphylococci) and Gram-negative pathogens (including Pseudomonas spp); less common organisms include fungi and nontuberculous mycobacteria. (See 'Microbiology' above.)

●Clinical manifestations – Most patients with LVAD infection present with erythema and/or purulent discharge at the driveline exit site, pain along the driveline tract, or pain involving the left chest wall (the typical LVAD pump site) (picture 1 and picture 2). Other manifestations may include fever or other systemic symptoms, heart failure exacerbation, or other cardiac abnormalities such as arrhythmia. (See 'Clinical manifestations' above.)

●Evaluation – The initial evaluation includes blood cultures, drainage cultures (if drainage is present at the driveline exit site), and additional studies guided by symptoms. For patients with inflammation at the driveline and/or pocket sites, we obtain computed tomography of the chest and abdomen to evaluate for drainable collection and assess for complications that may require surgical intervention. For patients with systemic symptoms (such as hemodynamic instability, bacteremia, device malfunction, and/or vascular or immunologic phenomena), we obtain echocardiography. For patients who undergo surgery, operative material should be submitted for bacterial, mycobacterial, and fungal stain and culture, as well as histopathology. (See 'Evaluation' above.)

●Diagnosis (see 'Diagnosis' above):

•Driveline infection – A definitive diagnosis is based on drainage culture obtained from the driveline exit site (picture 1). A presumptive clinical diagnosis may be made in the setting of signs of infection at the driveline site. Uncomplicated infection is limited to inflammation and drainage at the driveline exit site or surrounding tissues; complicated infection includes these findings as well as abscess, necrosis, or sepsis. (See 'Driveline infection' above.)

•Extravascular pump infection – A definitive diagnosis is based on positive operative cultures or histopathologic findings. For patients who do not undergo surgery, a presumptive clinical diagnosis may be made in the setting of radiographic imaging demonstrating findings consistent with an infection (including fluid collection, enhancement, gas, or sinus tract) and positive culture of image-guided aspiration material (picture 3). (See 'Extravascular pump infection' above.)

•Endovascular pump infection – The diagnosis may be established clinically by positive blood cultures as well as echocardiographic and/or radiographic findings (including echodensity, intracardiac mass, mass around the inflow cannula, or abscess). If the device is removed, additional diagnostic criteria include positive operative cultures and histopathologic criteria. Evaluation for alternative causes of bacteremia should also be pursued. (See 'Endovascular pump infection' above.)

●Management

•Driveline infection (see 'Driveline infection' above):

-Uncomplicated – For patients who are clinically stable but have substantial erythema, drainage, or skin warmth, we suggest initiation of empiric oral antibiotic therapy with a regimen active against methicillin-resistant S. aureus (MRSA) and Pseudomonas spp (Grade 2C).

-Antibiotic therapy should be tailored to culture results and susceptibility data when available. We continue treatment for at least two to four weeks, after which the duration should be guided by clinical improvement. Prior to discontinuation of antibiotic therapy, patients should be evaluated to ensure complete resolution of symptoms.

-Complicated – For patients with hemodynamic instability and/or progressive inflammation at the driveline site, we suggest initiation of empiric parenteral antibiotic therapy with a regimen active against MRSA and Pseudomonas spp (Grade 2C); for those with underlying immunosuppression, some also include empiric antifungal treatment with an echinocandin.

For patients with persistent signs and symptoms of driveline infection despite antibiotic treatment, we pursue repeat imaging to evaluate for interval change and to assess for complications.

Surgical intervention is warranted in patients with radiographic evidence of abscess, fluid collection, tissue gas, or progressive erythema and drainage despite appropriate antibiotic therapy (picture 2).

Completion of antibiotic therapy with parenteral therapy is preferred; if drainage culture susceptibility data permit, highly bioavailable oral agents may be considered. We continue treatment until clinical stabilization is observed (usually six to eight weeks).

In general, we do not favor routine use of chronic suppressive antibiotic therapy for patients with driveline infection and retained device who respond to initial therapy.

•Extravascular pump infection – Management of extravascular pump infection consists of antibiotic therapy and surgical intervention. The approach to empiric antibiotic therapy is as described above for complicated driveline infection. We continue parenteral antibiotic therapy for at least six to eight weeks, tailored to clinical improvement. Thereafter, we administer suppressive oral antibiotic therapy, even if the device is replaced, since the procedure involves an infected operative bed. (See 'Extravascular pump infection' above.)

•Endovascular pump infection – Management of endovascular pump infection consists of antibiotic therapy; in addition, patients should be evaluated for device replacement. (See 'Endovascular pump infection' above.)

The approach to empiric therapy is as described above for complicated driveline infection. (See 'Driveline infection' above.)

Typically, we consider surgery only for patients with persistent signs and symptoms of infection in the setting of parenteral antibiotic therapy. The optimal approach in such cases is uncertain; options include palliative antibiotic therapy, device replacement, device explant (if there is sufficient underlying cardiac function), or urgent cardiac transplantation (for eligible patients). A full cardiac assessment, surgical assessment, and multidisciplinary discussion is required to determine which strategy to pursue.

We continue treatment for at least six to eight weeks of parenteral antibiotic therapy, tailored to clinical improvement. Thereafter, we administer suppressive oral antibiotic therapy, even if the device is replaced, since the procedure involves an infected operative bed.