**3. Microbiology of LVAD infections**

The microbiology of LVAD infections has been extensively reviewed [20, 26, 27, 29–31, 33, 34, 37, 39–43]. In the main, LVAD infectious etiology is related to the particular clinical syndrome e.g. driveline infection vs. pocket infection vs. endocarditis. The International Society for Heart and Lung Transplantation classifies infections as "VAD related" or "VAD specific" to refer to bacteremia, endocarditis and mediastinitis versus driveline, pocket and pump/cannula infections [13]. INTERMACS lists non-device related infections, device related infections (internal pump infections; percutaneous site infections and pocket infections (listed together)) and sepsis [12].

#### **3.1. Bacteremia and sepsis**

Bacteremia and sepsis are seen most frequently in the peri-operative period and often these infectious disease syndromes are associated with non-VAD infections such as central line associated blood stream infections (CLABSIs), ventilator and hospital associated pneumonia, urinary tract infections, *Clostridium difficile* associate diarrhea and colitis. The microbiology of these peri-operative non-VAD infections has been reviewed in the references above and will not be covered again in this chapter.

LVAD related bacteremias can also occur with associated sepsis, and may be related to device infections (pump pocket, pump/cannula), infective endocarditis and mediastinitis. The organisms detected in bacteremic patients (e.g. Staphylococci, Enterobacteriaceae, *Pseudomonas aeruginosa*, Enterococci, *Candida* spp.) are indicative of at least some of the possible device related organisms causing infection [20, 31, 34, 37, 40, 43, 44].

#### **3.2. Driveline infections**

are found in these patients for an average of 6 months post-implantation ([36], also reviewed in [33]). LVAD induced immune deficits appear to resolve in CF devices as compared to

Additional studies have looked at outcomes in transplant patients who developed LVAD infections either as BTT or DT (where the infection was treated in part by removal of the DT device, with subsequent receipt of an organ) [20, 30, 34, 37, 38]. In US studies, pretransplant LVAD infections appear to influence outcomes in cardiac transplant patients, with more infectious complications in those with prior LVAD infectious complications. Other risk factors in multivariate analysis included age, ICU length of stay and use of an anti-thymocyte agent [38]. A sub-study of the Swiss Transplant Cohort Study found that pre-transplant LVAD infections did not have an impact on post-transplant outcomes with slightly lower rates of infection and slightly higher survival rates among LVAD BTT patients [37]. Enterococcal infections including with VRE and Staphylococcal infections were most common among LVAD associated post transplant infections [30, 34]. The presence of infections with molds such as *Aspergillus* spp. are felt to be a strong relative contra-

The microbiology of LVAD infections has been extensively reviewed [20, 26, 27, 29–31, 33, 34, 37, 39–43]. In the main, LVAD infectious etiology is related to the particular clinical syndrome e.g. driveline infection vs. pocket infection vs. endocarditis. The International Society for Heart and Lung Transplantation classifies infections as "VAD related" or "VAD specific" to refer to bacteremia, endocarditis and mediastinitis versus driveline, pocket and pump/cannula infections [13]. INTERMACS lists non-device related infections, device related infections (internal pump infections; percutaneous site infections and pocket infections (listed together))

Bacteremia and sepsis are seen most frequently in the peri-operative period and often these infectious disease syndromes are associated with non-VAD infections such as central line associated blood stream infections (CLABSIs), ventilator and hospital associated pneumonia, urinary tract infections, *Clostridium difficile* associate diarrhea and colitis. The microbiology of these peri-operative non-VAD infections has been reviewed in the references above and will

LVAD related bacteremias can also occur with associated sepsis, and may be related to device infections (pump pocket, pump/cannula), infective endocarditis and mediastinitis. The organisms detected in bacteremic patients (e.g. Staphylococci, Enterobacteriaceae, *Pseudomonas aeruginosa*, Enterococci, *Candida* spp.) are indicative of at least some of the possible device related organisms

older pulsatile devices ([33] and references therein).

**2.1. Impact on post-transplant infections**

174 Advanced Concepts in Endocarditis

indication for transplantation [6].

and sepsis [12].

**3.1. Bacteremia and sepsis**

not be covered again in this chapter.

causing infection [20, 31, 34, 37, 40, 43, 44].

**3. Microbiology of LVAD infections**

Driveline infections are most common, and skin flora from patient's skin are the predominant pathogens detected (reviewed in [40]). Often, trauma of the driveline tunnel, due to rough manipulation of the driveline, and lack of skin fixation that reduces tension on the driveline, leads to infections. The microbiology includes *Staphylococcus aureus*, both methicillin susceptible (MSSA) and resistant (MRSA), coagulase negative *Staphylococci* (CNS) (*S. epidermidis*), *Corynebacterium* spp. [21, 26, 27, 33, 34, 45, 46], viridans streptococci [31], *Enterococcus faecalis* [31, 34], *E. faecium* including vancomycin resistant strains "VRE" [30], Gram negative enteric bacilli such as Enterobacteriaceae (*Enterobacter cloacae* and *E. aerogenese* [31] *Escherichia coli*, *Klebsiella* spp. [34], *Proteus mirabilis* [31], *Serratia marcescens* [21]), *Pseudomonas aeruginosa* [20, 26, 31] and *Stenotrophomonas maltophilia* [31]. There have been rare instances of fungal driveline infections with *Candida* spp. such as *C. albicans, glabrata* [20, 31, 34]. There have been recent series of reports of infections with *Mycobacterium chimaera*, related to open chest surgery and cooling units employed for cooling cardioplegia solution [47]. In rare cases, patients developed endocarditis in the setting of recent valvular surgery. To date, one case of a complicated LVAD driveline infection with abdominal wall abscess by *M. chimaera* has been reported [48].

Biofilm formation by many different organisms contributes to persistence of infections due to the poor efficacy of antibiotics against organisms within biofilms, even when drug resistance is not present [33, 40, 43, 49].

#### **3.3. Pocket infections**

Pocket infections can occur at the time of implantation, during trauma to the driveline and pocket from driveline manipulation or bleeding into the pocket from coagulopathies [20]. The microbiology of pocket infections is thus very similar to driveline infections, with skin flora such as Staphylococci and Corynebacteria predominating, as well as *Enterobacteriaceae*, Enterococci, *Pseudomonas* and *Candida* spp. [20, 26, 31, 40]. We are in the process of reporting on a patient with a HeartMate II LVAD for DT who cracked his driveline and had extensive hematoma formation in the pump pocket with subsequent persistent infection and bacteremia with *Enterobacter cloacae (*Skalweit, in preparation). Computed tomography images of this patient are shown in **Figure 1**, with hematoma, phlegmon and small air bubbles evident in the pump pocket (a) before debridement. **Figure 1b** is after debridement. **Figure 2a**–**c** shows the pump pocket wounds after debridement, with placement of a vacuum wound device and after closure of the defect. One case of a pocket infection with *M. chimaera* has been reported in a patient who developed a fluid collection contiguous with the pump pocket [48]. The patient underwent extensive debridement and omental flap coverage of the device. Operative specimens were routinely cultured and he was empirically treated with broad spectrum antibiotics but did not respond to therapy. Subsequent mycobacterial cultures revealed the pathogen and he was maintained on lifelong *M. chimaera* therapy.

#### **3.4. Mediastinitis**

As a direct extension of pocket infections or as a result of sternal wound infections, LVAD associated mediastinitis is rarely observed [34, 43, 48]. *S. aureus* (MRSA), CNS, and vancomycin

infections revealed that 3% met criteria for LVAD endocarditis (cultures of blood and explanted LVADs positive for fungal pathogens) [50]. *Candida albicans*, *C. parapsilosis* and *S. racemosum* were isolated in 3, 1 and 1 case respectively. More recently in the continuous flow era, LVAD associated endocarditis has been defined as "clinical evidence of pump and/or cannula infection along with the presence of vegetations on echocardiography or a vascular phenomenon as defined by modified Duke's criteria" ([26] and reviewed in [42]). *Staphylococcus aureus* (MRSA, MSSA) predominates, as well as CNS (MRSE, MSSE) and *Pseudomonas aeruginosa* (reviewed in [42]). Cases of linezolid resistant *Streptococcus sanguinis* [52] and *Listeria monocytogenes* [53]

Left Ventricular Assist Device Infections http://dx.doi.org/10.5772/intechopen.74621 177

Other complications related to LVAD infections can include hemorrhagic stroke and mycotic aneurysm. Patients with heart failure are already at risk of thrombosis, and increased infectious complications and coagulopathy associated with LVADs increases the risk of device thrombosis and stroke (reviewed in [54]). Aggarwal et al. [55] studied the relationship between bacteremia and stroke in LVAD patients in a retrospective chart review study. They studied 80 patients who had undergone LVAD placement in their institution, of whom 30 developed blood stream infections. Among those 30, 13 developed hemorrhagic strokes (43%) compared to 5/ 50 (10%) in LVAD recipients without bacteremia. In their report, the majority of BSI were caused by Staphylococci (CNS, MRSA). Yoshioka et al. found a similar association with hemorrhagic stroke in patients with either bacteremia or pump pocket infection [56, 57]. Organisms isolated among the nine patients in their study with hemorrhagic stroke included methicillin susceptible *S. epidermidis* (MSSE), MSSA, *Corynebacterium* spp., MRSA, CNS, *E. faecalis*, *Bacillus* sp. and *Campylobacter* sp. A rare complication in an LVAD recipient is mycotic aneurysm related to prior recurrent *Klebsiella rhinoscleromatis* bacteremia and subarachnoid

Prior treatment with antibiotics and extended therapy with narrow spectrum antibiotics did not appear to increase risk for LVAD infections with multidrug resistant organisms (MDRO) [59]; MDRO infections were related to indication (DTT > BT), obesity and driveline technique ("velour exposed" versus buried). However, a recent case series reported that high level daptomycin resistance in *Corynebacterium striatum* LVAD infections was selected for by using dap-

LVAD infections can manifest in many ways from indolent infections in patients that are minimally symptomatic to septic patients requiring intensive care. Most sources [13, 27, 39, 40, 43, 61, 62] agree on general investigations that should occur in order to diagnose an LVAD related or device specific infection. If LVAD infection is suspected, driveline and three sets

with associated leukocytoclastic vasculitis have also been reported.

**3.6. Cerebrovascular microbleeds/stroke/mycotic aneurysm**

hemorrhage [58].

**3.7. Drug resistance**

tomycin as treatment [60].

**4. Diagnosis of LVAD infections**

**Figure 1.** (a and b) Computed tomography (CT) images of pump pocket infection before (a) and after (b) surgical debridement. Solid arrows show the location of a complex hematoma, phlegmon and air bubbles. Operative cultures grew a susceptible *Enterobacter cloacae*.

**Figure 2.** (a–c) Wound care in *Enterobacter cloacae* pump pocket infection, post debridement (a), with wound vacuum device placement (b) and after healing (c). Heavy and dotted arrows indicate the pump pocket wounds, dashed arrow is the driveline.

susceptible *E. faecalis* were the reported pathogens in five patients with LVAD mediastinitis [34]. A single case of fungal mediastinitis presenting with LVAD outflow obstruction caused by growth of *Syncephalastrum racemosum* has been reported [50]. The concern with mediastinal infection is always one of extension to involve the great vessels, the pericardium and bone, requiring potential additional source control and extended antibiotic therapy.

#### **3.5. Infective endocarditis and pump/cannula infections**

Endovascular infections can occur on native valves, prosthetic valves as well as in association with the LVAD pump body and cannula and are associated with high mortality [26]. Early case reports with older generation pulsatile flow devices described LVAD valve replacement on a Novacor N100 LVAD [51]; pathology revealed Gram positive cocci. A series of fungal LVAD infections revealed that 3% met criteria for LVAD endocarditis (cultures of blood and explanted LVADs positive for fungal pathogens) [50]. *Candida albicans*, *C. parapsilosis* and *S. racemosum* were isolated in 3, 1 and 1 case respectively. More recently in the continuous flow era, LVAD associated endocarditis has been defined as "clinical evidence of pump and/or cannula infection along with the presence of vegetations on echocardiography or a vascular phenomenon as defined by modified Duke's criteria" ([26] and reviewed in [42]). *Staphylococcus aureus* (MRSA, MSSA) predominates, as well as CNS (MRSE, MSSE) and *Pseudomonas aeruginosa* (reviewed in [42]). Cases of linezolid resistant *Streptococcus sanguinis* [52] and *Listeria monocytogenes* [53] with associated leukocytoclastic vasculitis have also been reported.

#### **3.6. Cerebrovascular microbleeds/stroke/mycotic aneurysm**

Other complications related to LVAD infections can include hemorrhagic stroke and mycotic aneurysm. Patients with heart failure are already at risk of thrombosis, and increased infectious complications and coagulopathy associated with LVADs increases the risk of device thrombosis and stroke (reviewed in [54]). Aggarwal et al. [55] studied the relationship between bacteremia and stroke in LVAD patients in a retrospective chart review study. They studied 80 patients who had undergone LVAD placement in their institution, of whom 30 developed blood stream infections. Among those 30, 13 developed hemorrhagic strokes (43%) compared to 5/ 50 (10%) in LVAD recipients without bacteremia. In their report, the majority of BSI were caused by Staphylococci (CNS, MRSA). Yoshioka et al. found a similar association with hemorrhagic stroke in patients with either bacteremia or pump pocket infection [56, 57]. Organisms isolated among the nine patients in their study with hemorrhagic stroke included methicillin susceptible *S. epidermidis* (MSSE), MSSA, *Corynebacterium* spp., MRSA, CNS, *E. faecalis*, *Bacillus* sp. and *Campylobacter* sp. A rare complication in an LVAD recipient is mycotic aneurysm related to prior recurrent *Klebsiella rhinoscleromatis* bacteremia and subarachnoid hemorrhage [58].

#### **3.7. Drug resistance**

susceptible *E. faecalis* were the reported pathogens in five patients with LVAD mediastinitis [34]. A single case of fungal mediastinitis presenting with LVAD outflow obstruction caused by growth of *Syncephalastrum racemosum* has been reported [50]. The concern with mediastinal infection is always one of extension to involve the great vessels, the pericardium and bone,

**Figure 2.** (a–c) Wound care in *Enterobacter cloacae* pump pocket infection, post debridement (a), with wound vacuum device placement (b) and after healing (c). Heavy and dotted arrows indicate the pump pocket wounds, dashed arrow

**Figure 1.** (a and b) Computed tomography (CT) images of pump pocket infection before (a) and after (b) surgical debridement. Solid arrows show the location of a complex hematoma, phlegmon and air bubbles. Operative cultures

Endovascular infections can occur on native valves, prosthetic valves as well as in association with the LVAD pump body and cannula and are associated with high mortality [26]. Early case reports with older generation pulsatile flow devices described LVAD valve replacement on a Novacor N100 LVAD [51]; pathology revealed Gram positive cocci. A series of fungal LVAD

requiring potential additional source control and extended antibiotic therapy.

**3.5. Infective endocarditis and pump/cannula infections**

grew a susceptible *Enterobacter cloacae*.

176 Advanced Concepts in Endocarditis

is the driveline.

Prior treatment with antibiotics and extended therapy with narrow spectrum antibiotics did not appear to increase risk for LVAD infections with multidrug resistant organisms (MDRO) [59]; MDRO infections were related to indication (DTT > BT), obesity and driveline technique ("velour exposed" versus buried). However, a recent case series reported that high level daptomycin resistance in *Corynebacterium striatum* LVAD infections was selected for by using daptomycin as treatment [60].
