**2. Perioperative antibiotic therapy**

#### **2.1. Introduction**

Since the beginning of cardiac implantable electronic devices (CIED) prevention of device infection is a serious issue and is under permanent discussion [22-24].

Despite "optimal implantation procedure" concerning optimal sterility and hygienic con‐ ditions in terms of materials, implant room and process, there are several factors that pose a higher risk for CIED infections: device/pocket revision, use of temporary pacing leads before placement of the permanent device, central venous catheters, longer opera‐ tive time and operator inexperience, development of postoperative pocket hematoma, diabetes mellitus, long-term use of corticosteroids and other immunosuppressive drugs and seperated focus of primary infection [25]. The use of perioperative antibiotics or the therapy of choice, as well as necessity and effect of flushing the wound with antiinfec‐ tive detergents is under debate [26, 27]. There are newly developed antimicrobial device coatings which are not yet available [28, 29].

Described rates of implant related device infections in published studies have a wide range reaching from 0.13% to 19.9% with 0.5% of the patients developing endocarditis or sepsis as a major complication [24, 30]. In addition to the severe or even lethal complication there is also an impact on health economics with estimated costs of up to 50.000\$ per case [31, 32].

be operated with an INR close to 2.5 or heparin bridging therapy. We do not perform bridg‐ ing with any type of heparin as a routine protocol. Oral Anticoagulation should be stopped approximately 3-5 days before the procedure, depending on the used substance as well the individual maintenance dose. Local haemostiptics or drainage will be used by the judgment

**Thromboembolic risk assessment in patients on oral anticoagulation**

Medium thromboembolic risk (5-10%/year)

AF patients with CHA2DS2-VASc-Score 3-5 Mechanical aortic valves + AF Malignancy ass. venous thromboembolism Multiple or current thromboembolism Valve repair/-exchange (<3months)

**Table 3.** Relative Risk assessment of perioperative thromboembolic events without anticoagulation therapy. Modified after Douketis JD, et al (2008) The perioperative management of antithrombotic therapy (ACCP Evidence-based clinical practice guidelines, 8th Edition). Chest 133:299–339 and De Caterina R, Husted S, Wallentin L et al (2007)

Since the beginning of cardiac implantable electronic devices (CIED) prevention of device

Despite "optimal implantation procedure" concerning optimal sterility and hygienic con‐ ditions in terms of materials, implant room and process, there are several factors that pose a higher risk for CIED infections: device/pocket revision, use of temporary pacing leads before placement of the permanent device, central venous catheters, longer opera‐ tive time and operator inexperience, development of postoperative pocket hematoma, diabetes mellitus, long-term use of corticosteroids and other immunosuppressive drugs and seperated focus of primary infection [25]. The use of perioperative antibiotics or the therapy of choice, as well as necessity and effect of flushing the wound with antiinfec‐ tive detergents is under debate [26, 27]. There are newly developed antimicrobial device

Described rates of implant related device infections in published studies have a wide range reaching from 0.13% to 19.9% with 0.5% of the patients developing endocarditis or sepsis as

Anticoagulants in heart disease: current status and perspectives. Eur Heart J 28:880–913

infection is a serious issue and is under permanent discussion [22-24].

High thromboembolic risk (>10%/ year)

AF patients with CHA2DS2-VASc-Score 5-6 (or TIA/CVA <3months) Mechanical mitral valves Mechanical aortic valves + AF (CHA2DS2-VASc ≥2) Mechanical aortic valves (older models) Known thrombophilic disorder LV-thrombus

of the operator.

114 Cardiac Defibrillation

Low thromboembolic risk (<5%/year)

AF patients with CHA2DS2-VASc-Score 0-2 (but no TIA/CVA) Mechanical aortic valves (> 3 months) Post venous thromboembolism (>12 month)

**2. Perioperative antibiotic therapy**

coatings which are not yet available [28, 29].

**2.1. Introduction**

The daily routine of perioperative antibiotic administration to prevent infections of CIED is highly variable in terms of agents and dosage. It is generally accepted that a reduction of device infections can be achieved by this approach [33]. Regiments based on vancomycin, imipenem or cephazolin administered either perioperative as single shot or up to 3 days are known. In terms of evidence based medicine there are just 7 trials dealing with periopera‐ tive antibiotics in CIEDS up to 2009 [27, 30, 34]. They were consisted of small number of pa‐ tients with very variable designs in terms of follow up duration, inclusion criteria, used antibiotic agent and definition of events. Thus varying results were reported and a definite conclusion could hardly be found. Four of those trials described a benefit in terms of reduc‐ tion of device/system infections. Three did not describe any difference, however, in one study there was no infection at all in the included 106 patients [35]. Those trials were mainly conducted in the 1980´s – another limitation since implanted systems (generators and leads) as well as implant techniques underwent marked developments in the last 3 decades.

The most recent and relevant study was a double-blinded randomized trial by Oliveira et al. in 2009 [36]. In this study 649 consecutive ICD and pacemaker patients (first implant and generator replacement) were included and followed (fixed schedule for 6 month and addi‐ tionally when clinically indicated). Randomization was made to either 1g of cephazolin or placebo directly prior operation. Allergic patients were excluded. The primary endpoint was the occurrence of infection, classified being one of the following: superficial, pocket or sys‐ temic infection. The two groups were balanced and no differences concerning the known risk factors for CIED infections were present. The study was interrupted after 26.5 month by the safety committee because of significant differences in the primary endpoint. CIED relat‐ ed infections occurred in 0.64% in the cephazolin group and 3.28% in the placebo group (p=0.016). The 13 patients that developed infections showed the typically germs all from the Staphylococcus-family. The time until infection after implantation was 11-33 days without a difference between the cephazolin and the placebo group. The multivariate analysis identi‐ fied pocket hematoma and lack of antibiotic prophylaxis as independent risk factors for any kind of infection. Odds ratios were not calculated.

Based on the results of this study as well as previously published non randomized data antibiotic prophylaxis should be performed in any device related operation (implantation as well as generator replacement). In our institution cephazolin is administered - being the only evidence based antibiotic drug until now. In case of known allergy against cephazolin a single shot of 1g vancomycin seems the most appropriate alternative as most common species in CIED infection are staphylococci or streptococci [37, 38]. If the implanting hospital has a high prevalence of methicilin-resistant staphylococci (MRSA) vancomycin should be considered to be the first choice [33]. Some authors argue that in some regions with a very high prevalence of MRSA vancomycin should be even general‐ ly the first choice, however, this is not evidence based and should be considered careful‐ ly together with the local infectologist [33].

An interesting, newly developed approach of device coatings seems to be able to control local bacterial growth and thus is supposed to be able to prevent system infections [28, 29]. The study by Matl et al. describes the use of gentamycin and teicoplanin in a lipidbased drug delivery-system which was able to deliver high local concentrations over 96h and inhibit completely the growth of S. aureaus in vivo [28]. Wong et al. published data on a dual layer device coating, consisting of gentamycin to control local colonization/ infection and diclofenac to control local inflammation due to tissue injury on top of a mi‐ crobicidal base film [29]. In vitro they could show excellent results in terms of S. aureus control (figure 1). No data on extended in vivo use of any coating is yet available but the idea and techniques are promising.

**Author details**

University of Giessen and Marburg, Medical Clinic I, Department of Cardiology, Giessen, Germany and Kerckhoff Heart and Thorax Center, Department of Cardiology, Bad Nau‐

ICD and PM Implantation Procedure: Relevant Periprocedural Issues

http://dx.doi.org/10.5772/54203

117

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Joern Schmitt

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**References**

**Figure 1.** Media-borne assay with *S. aureus* with increasing time of incubation in bacterial solution; top row shows bare substrates completely colonized by bacteria (light beige colored dots); bottom row shows (DMLPEI/PAA)10 films with degradable top films completely eroded with no sign of colonization by bacteria (black colored substrate). From Wong et al., Journal of the American Chemical Society 2010.

#### **3. Conclusion / recommendation**

Concerning the severe consequences arising from an infected implanted pacemaker or defibrillator and the data available there should be no discussion on the use of preven‐ tive perioperative antibiotics. Randomized data were reported only on the use of a single shot cephfazolin although some other antibiotic agents are supposed to be equally effi‐ cient as almost every perioperative device infection is caused by staphylococci or strepto‐ cocci. In some hospitals with a high rate of methicillin resistant staphylococci vancomycin may be the most proper choice. There is an interesting new approach with coated devices that needs further evaluation.
