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1 Microbiology for implant related infections Hui Wang M.D, Professor, Director Department of Clinical Laboratory Peking University People s Hospital Beijing, wanghui@pkuph.edu.cn

2 Outline Epidemiology of implant related infections Implants include cardiovascular grafts, orthopedic devices, ventricular shunts, mammary implants, and penile implants, etc. Risk factors and mortality Etiology of implant related infections Microbiological detection of implant related infections Antimicrobial susceptibility 2

3 Implant related infections: common nosocomial infections Implant related infections 3

4 Implant related infections: high clinical and economic burden Darouiche RO, N Engl J Med, 2004, 350(14):

5 16-Year Trends in the Implantation of pacemakers and Implantable cardioverter-defibrillators in the United States: dramatically increased 96% 45% 504% Greenspon et al. JACC, 2011, 58(10):

6 Rate of cardiac implantable electrophysiological device (CIED) infection increased in the US. Greenspon et al. JACC, 2011, 58(10):

7 Source of bloodstream infection Infection can present as either local involvement at the device pocket or a systemic syndrome that is associated with bloodstream infection, with or without lead and valve endocarditis. The CIED wound or CIED device site: common source of infection in early lead-associated endocarditis Greenspon et al. JACC, 2012, 59 (7):

8 Incidence of CIED infection in China Incidence of CIED complications was 1.4%- 1.9% from 1997 to 2005 in China Incidence of CIED infection >50 cases of implantation a year <50 cases of implantation a year 1.0% 1.8% Xuebin Li et al. Adv Cardiovasc Dis, 2014, 35(2). 8

9 Clinical outcomes of CIED infection The increased infection burden was associated with increased financial costs and higher inpatient mortality. In-hospital charges increased to over $146,000 by 2008, which represents an increase of 47% decade. This paralleled both the observed increase in CIED and the increased infection rate. Incidence of comorbidities in patients with CIED infection Greenspon et al. JACC, 2011, 58(10):

10 CIED-IE patients were more likely to die of cardiac or respiratory failures after discharge By 30 days, multi-organ failure (8.8%), sepsis (4.5%), or cardiac arrest (5.2%) were common causes of death, with the majority (95.7%) occurring among bloodstream infection or CIED-IE cases. From 30 days to 1 year, death from multi-organ failure (9.2%) and sepsis (5.1%) continued among patients with extended hospitalizations. After discharge, those who initially presented with bloodstream infection or CIED-IE were more likely to die of cardiac or respiratory failures than those with pocket infections (7.4% vs. 0%). Le KY, et al. Heart Rhythm. 2011, 8(11):

11 Risk factors for CIED infection A systematic review and meta-analysis was conducted to summary the potential risk factors for CIED infections. Significant host-related risk factors included diabetes mellitus, renal disease, COPD, corticosteroid use, malignancy, heart failure, and anticoagulant drug use. Procedure-related risk factors included lack of antibiotic prophylaxis, replacement/revision procedures, non-infectious postoperative complications (including lead dislodgement and haematoma), temporary pacing, and procedure duration. Regarding device characteristics, abdominal generator pocket, dual-chamber system, and positioning of two or more leads were identified as significant predictors of CIED infection. Polyzos KA. et al. Europace. 2015, 17(5):

12 Risk factors for CIED mortality Mortality is high in the first year following CIED infection, but many deaths are not infection related. Abnormal renal function is the most consistently identified risk factor for mortality. CIED-IE has a higher mortality than localized generator pocket infection. Sandoe JA. et al. JAC. 2015, 70(2):

13 Increased rates of periprosthetic joint infection (PJI) in the USA Fig 1. Evolution of the numbers of hip and knee prostheses implanted in the USA between 1990 and Fig 2. Evolution of the numbers of cases of prosthesis infection in the USA between 1990 and Lima AL, et al. Interdiscip Perspect Infect Dis, 2013:

14 Risk factors for prosthetic joint infection ASA, American Society of Anesthesiologists; ASB, asymptomatic bacteriuria Sousa R, et al. Clin Infect Dis. 2014, 59(1):

15 Biofilms formation on biomaterials The process of device colonisation and tissue infection develops in a stage-wise manner: from preconditioning of the biomaterial with host matrix proteins, followed by initial microbe adhesion, growth and ultimately microcolony and, biofilm formation on the surface of the material. TF Moriarty et al. European Cells and Materials, 2014, 28:

16 Distribution of bacteria and biofilms in prosthetic joint infection McConoughey SJ, et al. Future Microbiol. 2014;9(8):

17 Outline Epidemiology of implant related infections Implants include cardivvascular grafts, ophopedic devices, ventricular shunts, mammary implants, and penile implants, etc. Risk factors and mortality Etiology of implant related infections Microbiological detection of implant related infections Antimicrobial susceptibility 17

18 Microbiology of PPM/ICD infections (n=189) Coagulase negative Staphylococcus is the most common pathogen in implant-related infections. Sohail MR et al. Clin Infect Dis, 2007, 45:

19 Summary of microbiology of CIED infection Sandoe JA, et al. JAC, 2015, 70(2):

20 Microbiology of CIED infection in PKUPH (n=145) Our data, unpublished. 20

21 Common causes of prosthetic joint infection Tande AJ, et al. Clin Microbiol Rev, 2014, 27(2):

22 Microbiology of prosthetic joint infection in PKUPH (n=52) Our data, unpublished. 22

23 Microbiological detection Sonication can be more sensitive than swab cultures or blood cultures in detecting bacteria in CIED infections. Sonication is more sensitive than conventional periprosthetic-tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection. Rohacek et al. Pacing Clin Electrophysiol, 2013, 38(2): Trampuz A, et al. N Engl J Med, 2007, 357:

24 Sensitivity of tissue and sonicate-fluid culture decreased after antimicrobials therapy Sonicate-fluid culture was more sensitive than tissue culture when antimicrobial agents were discontinued within 14 days Trampuz A, et al. N Engl J Med, 2007, 357:

25 Prosthesis sonication protocol used in the Mayo Clinic Clinical Microbiology Laboratory Tande AJ, et al. Clin Microbiol Rev, 2014, 27(2):

26 Implant sonication procedure Add stroke physiological saline solution Vortex 30 sec Sonicate 5min Vortex 30 sec Culture and smear 26

27 Sonication of prosthesis or implant: improve positive rate of culture Before Sonication After Sonication 27

28 Management of periprosthetic-tissue Periprosthetic-tissue Culture Take small pieces Cut and grind Culture and smear and joint fluid Joint Fluid Culture Blood culture BAP, CHL, SDA culture 28

29 Sensitivity of culture and multiplex PCR of sonication fluid in PJI Achermann, Y., J Clin Microbiol, 2010;48(4),

30 Detection process of blood culture Epstein et al. ACC/AHA/HRS 2008, Circulation, 117(21): e

31 Detection process of blood culture Epstein et al. ACC/AHA/HRS 2008, Circulation, 117(21): e

32 Phenotype of antimicrobial resistance USA Germany Italy France Australia MRSCoNs 50% - 33% 29% 12.5% MRSA 55% 2.6% % of S. aureus bloodstream isolates were methicillin resistant in UK. Sandoe JA, et al. JAC, 2015, 70(2):

33 Antimicrobial susceptibility of Staphylococci isolated from electrodes of CIEDs Bongiorni, et al. Europace, 2012, 14(9):

34 Antimicrobial resistance of Staphylococci of CIED infection in PKUPH Our data, unpublished. 34

35 Antimicrobial susceptibility of Staphylococci isolated from PJI R% Moran E, et al. J Infect, 2007, 55(1):

36 Empirical treatment regimens for CIED infection Sandoe JA, et al. JAC, 2015, 70(2):

37 Suggested antimicrobials for treatment of PJI Tande AJ, et al. Clin Microbiol Rev, 2014, 27(2):

38 Implant-related infections including CIED and PJI, are increasing in incidence. Implant-related infections can be life-threatening, particularly for CIED infections with IE. Coagulase-negative Staphylococcus cause the majority of implant-related infections. Sonication is sensitive and useful in detection bacteria in implant-related infections. Conclusions 38

39 Thanks for your attention! 39