What literature exists on the practice of prescribing prophylactic antibiotics after pacemaker insertion or revision procedures?

Introduction
Cardiac implantable electronic devices (CIEDs) are devices surgically attached to the heart to treat several cardiac disorders.¹ Permanent pacemakers (PPMs) are the most common type of CIEDs and are used for the treatment of bradycardia and arrhythmia. Other CIEDs include implantable cardiac defibrillators (ICDs) used for managing tachyarrhythmia and preventing sudden death, and cardiac resynchronization therapy (CRT) used to improve heart failure.^1,2 The number of CIEDs implanted has increased significantly over the past decade, and with it, the number of infectious complications has also grown.¹ The incidence of CIED infections has been reported up to 12.6% (mostly ranging from 1% to 7%) in studies. The rising incidence is associated with substantially increased patient morbidity and mortality. The most serious type of CIED infections are subcutaneous pocket infections; these potentially life-threatening infections extend hospital length of stay, elevate medical costs, and often require re-implantation with a non-infected device.

Several studies have highlighted the importance of antibiotics to prevent CIED infections.^3-5 For example, a meta-analysis found that prophylaxis with perioperative systemic antibiotics significantly reduced the risk of infections after PPM implantation.⁴ Postoperative prophylaxis is also practiced.⁵ While postoperative prophylaxis with systemic antibiotics is generally recommended for less than 24 hours after cardiovascular surgery, it is also historically accepted for extended use (up to 48 hours after surgery).⁵ A survey assessing the use of antibiotics for CIED procedures was recently completed by 150 implanters across the United States.⁶ Approximately two-thirds (66%) of implanters reported routine use of postoperative antibiotics following CIED implantation, with half of the respondents continuing antibiotics for more than 24 hours. The 2 most common antibiotics used postoperatively were reported to be cefazolin (84%) and vancomycin (41%). Despite appearing to be common practice, however, there are limited data assessing the risks and benefits of postoperative antibiotics for different durations (>24 hours versus <24 hours).⁵ This FAQ is focused on postoperative use of systemic antibiotics to prevent infections; of note, the use of antibiotic-eluting envelopes during CIED procedures is not discussed or assessed.

Guidelines on the use of prophylactic antibiotics for pacemaker procedures
Several guidelines discuss the use of prophylactic antibiotics for pacemaker procedures.^3,7,8 The Heart Rhythm Society (HRS) published a consensus statement in 2017 on the management of CIEDs.⁷ Systemic antibiotic use is considered standard of care prior to surgical incision; the use of a first-generation cephalosporin (such as cefazolin within 1 hour before the incision) or vancomycin (within 2 hours before the incision) is recommended. However, postoperative antibiotic therapy is not recommended due to insufficient evidence. Furthermore, adverse events and selection of drug-resistant organisms are concerns when postoperative antibiotics are used.

In 2010, the American Heart Association (AHA) published an update to their 2003 statement on CIED infections and their management.⁸ The AHA states that staphylococcal species compose 60% to 80% of CIED infections, and recommends the use of a first-generation cephalosporin such as cefazolin, or vancomycin (in cases of high oxacillin resistance among staphylococci), at the time of CIED implantation. Similar to the HRS, the AHA recommends against the use of postoperative antibiotic therapy due to a lack of supporting evidence, risk of adverse events and antibiotic resistance, and cost.

Lastly, joint guidelines on surgical prophylaxis were published in 2013 by the American Society of Health-System Pharmacists (ASHP), Infectious Diseases Society of America (IDSA), Surgical Infection Society (SIS), and Society for Healthcare Epidemiology of America (SHEA).³ These guidelines focus primarily on perioperative measures. A single preoperative dose of an antibiotic (cefazolin in most situations) is recommended before surgical incision. The guidelines do not comment on the use of postoperative prophylactic antibiotics.

While multiple guidelines provide arguments against postoperative antibiotic prophylaxis (such as increased risk of adverse events and potential selection of drug-resistant organisms), the available evidence was limited at the time these statements were published. Five years have passed since the most recent guideline, allowing time for the emergence of new studies on the use of postoperative antibiotics for CIED procedures. A literature search was warranted to re-assess the relevance of guideline recommendations.

Literature on postoperative prophylactic antibiotics for pacemaker procedures
A recent systematic review and meta-analysis of 8 studies (N=26,187 patients) evaluated the use of antibiotics for postoperative prophylaxis of CIED infections.⁵ Randomized controlled trials (RCTs) or cohort studies of patients who were undergoing implantation, upgrade, or generator exchange of CIEDs (CRT, PPMs, or automated ICDs) were included. Studies that used left ventricular assist devices or non-systemic antibiotics, or that lacked the availability of the full text (ie, were abstracts only) were excluded. The included studies were published between 2012 to 2021, although the study periods ranged from 1991 to 2019.

The intervention group in the included studies received preoperative antibiotic prophylaxis, followed by postoperative antibiotic prophylaxis for ≥24 hours.⁵ Control groups received either preoperative prophylaxis alone, or preoperative prophylaxis with postoperative antibiotic prophylaxis for <24 hours. The primary outcome was CIED infection, which was defined by each study individually. The interventions and outcomes of the studies are summarized in Table 1. Participants in these studies had a mean age ranging from 63.5 to 82 years, and were composed of 45.5% to 67.8% males. All studies included PPM procedures. Across studies, the duration of postoperative antibiotic prophylaxis ranged from 2 to 14 days in the intervention group. The follow-up period ranged from 3 months to 2 years.

The meta-analysis found no difference between the 2 groups for the rate of CIED infection (relative risk [RR], 0.77; 95% confidence interval [CI], 0.42 to 1.42; p=0.40; heterogeneity [I²]=69%).⁵ When stratified by study design, the pooled RR was 0.77 (95% CI, 0.57 to 1.03; p=0.07; I²=0%) for RCTs and 0.82 (95% CI, 0.31 to 2.18; p =0.7; I²=76%) for cohort studies. The meta-analysis identified 1 outlier, Senaratne et al (2014), which was the only study that had shown benefit for the use of postoperative antibiotic prophylaxis.¹¹ The study period for this retrospective cohort began in 1991, while the study periods of the 7 other studies began in the 2000s.^9-16 Senaratne et al notes that changes in hospital practice (improved hygiene and surgical technique) started to develop around the time that postoperative antibiotics began to be used (circa 1999).¹¹ Therefore, the intervention of postoperative antibiotics may have had a falsely correlated decrease in infections in this retrospective study. When removing the outlier in a sensitivity analysis, the meta-analysis found that the pooled RRs did not change significantly, but the overall I² changed to zero.⁵

In addition to the outlier study which contributed significant heterogeneity, the meta-analysis had several other limitations.⁵ Studies used different antibiotic classes and timing of therapy, which may have impacted infection rates, and did not allow a direct comparison of patients who received preoperative prophylaxis versus those who received a similar duration of postoperative prophylaxis. The types of CIEDs, patient populations, and follow-up periods also varied among studies. There was low certainty of evidence across studies, mainly due to risk of bias from the cohort studies. Despite these limitations, the meta-analysis concluded that postoperative antibiotic prophylaxis (particularly for >24 hours) did not reduce the risk of CIED infection and is therefore unwarranted.

Literature searches did not identify newer studies relevant to postoperative antibiotic prophylaxis for CIED implantation since the publication of the meta-analysis.

Conclusion
The overall consensus of clinical guidelines is that there is no benefit to using prophylactic antibiotics postoperatively after a pacemaker or other CIED implantation/revision procedure.^7,8 A recent meta-analysis showed findings in agreement; there was no benefit to postoperative antibiotic prophylaxis (particularly for more than 24 hours) following CIED implantation.⁵ However, the meta-analysis included few RCTs, and over half of the cohort studies did not specify the antibiotics used or their durations. Future studies that compare a specified postoperative antibiotic and duration to a control are warranted to make more robust conclusions. Nonetheless, postoperative antibiotic prophylaxis following CIED procedures remains a common practice.^5,6 Furthermore, use of antibiotic-eluting envelopes (although not discussed in this FAQ) is a growing practice that is supported by several clinical trials for prophylaxis of CIED infections.⁷ This newer technology may demonstrate efficacy and be incorporated into future guideline recommendations.

References

1. Kang FG, Liu PJ, Liang LY, et al. Effect of pocket irrigation with antimicrobial on prevention of pacemaker pocket infection: a meta-analysis. BMC Cardiovasc Disord. 2017;17(1):256. doi:10.1186/s12872-017-0689-9
2. Steffen MM, Osborn JS, Cutler MJ. Cardiac implantable electronic device therapy: permanent pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization devices. Med Clin North Am. 2019;103(5):931-943. doi:10.1016/j.mcna.2019.04.005
3. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. doi:10.2146/ajhp120568
4. Da Costa A, Kirkorian G, Cucherat M, et al. Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis. Circulation. 1998;97(18):1796-1801. doi:10.1161/01.cir.97.18.1796
5. Chesdachai S, Go JR, Hassett LC, Baddour LM, DeSimone DC. The utility of postoperative systemic antibiotic prophylaxis following cardiovascular implantable electronic device implantation: a systematic review and meta-analysis. Pacing Clin Electrophysiol. 2022;45(8):940-949. doi:10.1111/pace.14561
6. Kranick S, Mishra N, Theertham A, et al. A survey of antibiotic use during insertion of cardiovascular implantable devices among united states implanters [published online ahead of print, 2022 Jul 11]. Angiology. 2022;33197221114689. doi:10.1177/00033197221114689
7. Kusumoto FM, Schoenfeld MH, Wilkoff BL, et al. 2017 HRS expert consensus statement on cardiovascular implantable electronic device lead management and extraction [published correction appears in Heart Rhythm October 2021;18(10):1814]. Heart Rhythm. 2017;14(12):e503-e551. doi:10.1016/j.hrthm.2017.09.001
8. Baddour LM, Epstein AE, Erickson CC, et al. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation. 2010;121(3):458-477. doi:10.1161/CIRCULATIONAHA.109.192665
9. Uslan DZ, Gleva MJ, Warren DK, et al. Cardiovascular implantable electronic device replacement infections and prevention: results from the REPLACE Registry. Pacing Clin Electrophysiol. 2012;35(1):81-87. doi:10.1111/j.1540-8159.2011.03257.x
10. Chiang KH, Chao TF, Lee WS, Lin YJ, Tuan TC, Kong CW. How long should prophylactic antibiotics be prescribed for permanent pacemaker implantations? One day versus three days. Acta Cardiol Sin. 2013;29(4):341-346.
11. Senaratne JM, Jayasuriya A, Irwin M, Gulamhusein S, Senaratne MP. A 19-year study on pacemaker-related infections: a claim for using postoperative antibiotics. Pacing Clin Electrophysiol. 2014;37(8):947-954. doi:10.1111/pace.12403
12. Lee WH, Huang TC, Lin LJ, et al. Efficacy of postoperative prophylactic antibiotics in reducing permanent pacemaker infections. Clin Cardiol. 2017;40(8):559-565. doi:10.1002/clc.22698
13. Krahn AD, Longtin Y, Philippon F, et al. Prevention of arrhythmia device infection trial: the PADIT trial. J Am Coll Cardiol. 2018;72(24):3098-3109. doi:10.1016/j.jacc.2018.09.068
14. Madadi S, Kafi M, Kheirkhah J, et al. Postoperative antibiotic prophylaxis in the prevention of cardiac implantable electronic device infection. Pacing Clin Electrophysiol. 2019;42(2):161-165. doi:10.1111/pace.13592
15. Kabulski GM, Northup A, Wiggins BS. Postoperative antibiotic prophylaxis following cardiac implantable electronic device placement. J Innov Card Rhythm Manag. 2019;10(8):3777-3784. doi:10.19102/icrm.2019.100804
16. Malagù M, Vitali F, Brieda A, et al. Antibiotic prophylaxis based on individual infective risk stratification in cardiac implantable electronic device: the PRACTICE study. Europace. 2022;24(3):413-420. doi:10.1093/europace/euab222

Prepared by:
Hani Said
PharmD Candidate Class of 2023
University of Illinois at Chicago College of Pharmacy

Edited by:
Honey Joseph, PharmD
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

December 2022

The information presented is current as September 30, 2022. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.