**Phases of infection**

*Advanced Concepts in Endocarditis - 2021*

• Poor preparation of the skin.

• Not using antibiotic prophylaxis.

• Fever in the previous 48 hours.

• Duration of the procedure.

**2.4 Physiopathology and etiology**

• Operator experience.

replacement.

• Hematoma.

systemic antimicrobials and inflammatory cells during generator replacement. For this reason, some operators advocate the removal of the capsule in battery

• Shaving the skin with a blade (risk of disruption of the skin barrier).

• Number of electrodes and complexity of the procedure.

Factors related to other procedures and health care

• Previously carrying a transvenous transitory pacemaker.

devices in contact with the bloodstream, can potentially cause sepsis.

Human skin is very resistant to infection. This resistance is due to physical (thickness, exfoliation), chemical (pH, secretions) and immunological (cellular

The resident flora is also an important factor. This flora is made up of bacteria that live attached to the skin and under normal circumstances, they do not cause infection and prevent the proliferation of other strains as well. When the skin barrier is broken, the entry of microorganisms from the adjacent skin is facilitated. Most infections from these devices are caused by coagulase negative staphylococci

CIED infection, can have a local or a distant origin.

• Invasive procedures related to health care (nosocomial and non-nosocomial) and or hospitalization, which may produce bacteremia leading to CIED infection, were identified in the previous 6 months in about 45–50% of the IE-ICED [7–11].

According to estimates from the U.S Food and Drug Administration (FDA) and the European trade association representing the medical technology industries, (MedTech Europe), more than 500000 types of medical devices have currently entered the global market. Invasive medical devices, including indwelling and implantable devices, represent just a fraction of these [14, 15]. More than a million cardiovascular electronic devices are implanted worldwide each year [16]. Devices used in cardiovascular surgery and interventionism are inserted into the body tissues by breaching the skin or mucous membranes. No matter where the surgically invasive device is placed, it is a foreign body. Even a mild tissue response alters the local immune defenses, creating a "locus minoris resistentiae", which is vulnerable to bacterial attack. Especially the

**122**

*2.4.1 Local origin*

and humoral) factors.

• **Colonization** of the CIED pocket by microorganisms from the surgical equipment (air or personnel) or more frequently from the patient's own skin. Disinfection reduces the number of bacterial colonies, but in the presence of a foreign body, the inoculum to produce an infection is lower. The susceptibility of surgically invasive devices to bacterial colonization is due to reduced effectiveness of human immune defenses at the implant–tissue interface [12]. The longer the procedure, the higher the rate of colonization of the surgical sites.

However, colonization is not synonymous with infection, since it must occur: Adhesion and BIOFILM formation (**Figure 1**) [13, 14]. Biofilm formation occurs in five steps:


**Figure 1.** *BIOFILM formation.*

• *Dispersion.* In the last step, some cells of the mature biofilm begin to dissociate and disperse again through the environment as planktonic cells to start a new cycle and thus the infection is dispersed.

### *2.4.2 Remote origin*

During the early post-implant period, damage to the vascular wall and the formation of hematomas can favor the settlement of germs from the bloodstream in the implant area; thus, it is very important to avoid the development of bacteremia by removing unnecessary intravascular and urinary catheters.

The infection can spread to the endovascular structures, during the healing and resorption phases of hematomas, from the pacemaker pocket.

Conversely, and generally later, endovascular elements (electrodes) can present fibrin and platelet deposits on erosions produced by friction, deterioration or turbulent flows, on which bacterial colonies can settle and proliferate in a process similar to that of endocarditis, which can also spread to the adjacent endocardium.

Concomitant valve involvement is estimated in about 37.2% of cases, most frequently tricuspid valve [11], aortic or mitral valve vegetations are present in 10–15% of patients with CIED endocarditis and valve involvement in CIED infection is associated with higher in-hospital mortality.

As previously mentioned, between 40 and 50% of patients with CIED have a history of admission, manipulation or invasive procedure in the previous 6 months, potentially responsible for bacteremia. The risk is especially high when the bacteremia is due to *Staphylococcus aureus* (35–45%) [6].

In any case, given that many "presumed local" infections can progress to the intravascular components of the device and vice versa, the barrier between local and endovascular infection can be difficult to establish. Once the generator or proximal leads have eroded through the skin, a device should be considered infected, whatever the mechanism that caused the erosion.

## **2.5 Microbiology**

Gram-positive bacteria are responsible for the vast majority of CIED infections (68–93%). Staphylococci, account for 60–80% of cases. Depending on the series, there is a predominance of infections caused by S Aureus or coagulase-negative staphylococcus (CoNS), although with few differences in their prevalence. Among the CoNS, *Staphylococcus epidermidis* and Staphylococcus Saprophyticus stand out. Methicillin resistance (MR) among Staphylococci varies among studies A high rate of MR in CoNS is associated with a healthcare environment source, reaching 50% in some series. For S aureus the rates of MR range between 2.6% (Germany) and 55% (USA). Gram-negative bacteria (GNB) are also identified in a percentage close to 15%. The higher proportion of GNB may be due to the large rate of different comorbidities, which is associated to more frequent invasive diagnosis or treatment measures. Polymicrobial infection sometimes involves more than one species of CoNS, (2–24% according to series). In a percentage between 8 and 15%, it was not possible to cultivate the responsible germ. Cases related to fungi are anecdotal [5, 6, 17–19].

### **2.6 Diagnosis**

The diagnosis of IE-CEID, as in valve prostheses, is inconclusive in up to 30% of cases, according to the Duke criteria [20]. For this reason, in the guidelines published by the European Society of Cardiology in 2015, three additional criteria were proposed to increase sensitivity in diagnosis [19].

**125**

**Figure 2.** *Exteriorized device.*

*Endocarditis and Cardiac Device Infections DOI: http://dx.doi.org/10.5772/intechopen.96909*

*2.6.1 Clinical presentation*

small pocket).

In any case, the IE-CEID diagnosis is based on three points [19, 21].

dehiscence of the suture or fistulization of the skin (**Figure 2**).

dysfunction and heart failure may also appear.

vegetations of the PM leads or tricuspid valve.

also appear in local infections.

The clinical manifestations of IE-CIED can be variable, since it can combine signs

Any exteriorized device should be considered infected (although initial exteriorization was related to aseptic necrosis of the skin due to tension of the device in a

Once the pocket is infected, the electrodes are frequently affected in its subcutaneous and extravascular portion, and affect the intravascular portion as well. When there is involvement of the intravascular components, that is, endocarditis of the leads and vascular part of the system, signs and symptoms of systemic infection will appear, with fever, chills, asthenia and anorexia. These data can appear larvae and in the absence of associated involvement of the pacemaker pocket, they can be more difficult to interpret. In a low percentage of patients, signs and symptom of frank sepsis will appear. In case of associated valvular involvement, data of valvular

Clinical manifestations related to septic lung embolism may also appear from

Among laboratory results data, the acute phase reactants (C-reactive protein, increased sedimentation rate, leukocytosis and procalcitonin) increase. Although these alterations point us towards a systemic infection, acute phase reactants can

Regarding the chronology of infections, several aspects must be taken into account:

• In the first 30 days, skin or exudate or superficial erythema may appear in

• Depending on the responsible germ, the temporary clinical course may vary. In the case of S Aureus infections, parturition is usually earlier and

relation to infection of the suture or allergic reaction,

and symptoms of local infection, with symptoms and signs of systemic infection. When there is involvement of the pacemaker pocket, diagnosis can be easier since there will be typical signs of inflammation, such as pain, redness and increased temperature in the implantation area. In addition, there may be an increase in size, either due to the presence of hematoma related to the implant (which should alert to an increased risk of infection) or fluctuation due to the formation of pus, adhesion of the skin as well as spontaneous and sometimes intermittent pus drainage due to

In any case, the IE-CEID diagnosis is based on three points [19, 21].
