Abstract
Background
Cardiac implantable electronic devices (CIEDs), including implantable cardiac defibrillators, pacemakers, and cardiac resynchronization therapy devices, are lifesaving. However, device infections can lead to morbidity and mortality. The aim of this study was to describe the outcome of Brucella CIED infections treated at our center, and to identify risk factors for Brucella infection in patients with CIEDs. Study Settings: Single-center study, Prince Sultan Military Medical City, Riyadh, KSA.
Methods
This case series included all Brucella-related CIED infections treated at a tertiary care center between 2009 and 2020. Data on patient demographics, clinical manifestations, predisposing factors, microbiology, treatment regimens, and outcomes were reviewed.
Results
Fifteen patients met the Brucella CIED infection criteria. The mean age was 62.2 years, and 80% were males. Common comorbidities included hypertension (73%), diabetes mellitus (67%), ischemic heart disease (47%), and chronic kidney disease (60%). The mean time to infection following the device implantation was 4.8 years (range: 5 months to 13 years). Fever was detected in 53% of patients, device site swelling in 47%, purulent discharge in 33%, and pain in 27%. The blood culture and serology results were positive in 73% and 80% of patients, respectively. All patients were treated with antibiotics, and the infected device was removed. Seven (46.6%) patients underwent reimplantation with a new device. One patient with dual Brucella and methicillin-sensitive Staphylococcus aureus infection died, and the other 14 patients recovered, with no recurrent infections reported to date.
Conclusion
Brucella should be considered in CIED infections, particularly in endemic areas. Proper treatment and device removal are essential for good outcomes.
Keywords: Brucellosis, Brucella infections, Cardiac implantable electronic device infections, Saudi Arabia
Abbreviations: CIED, cardiac implantable electronic device; MSSA, methicillin-sensitive Staphylococcus aureus
Highlights
-
•
Cardiac implantable electronic devices(CIED) are lifesaving procedures.
-
•
Brucellosis is endemic zoonosis in The Middle East, Mediterranean countries, and South America.
-
•
Though rare, brucella endocarditis contributes to 80% of brucella related deaths.
-
•
Pocket site tissue culture may be positive despite negative serology and blood culture.
-
•
All patients with brucella related CIED infection should receive prolonged antibiotics and whole device removal.
Researchregistry 6959
1. Introduction
Brucellosis is the most common zoonotic infection and is caused by an intracellular nonmotile gram-negative aerobic coccobacillus. Infection is frequently acquired by consuming unpasteurized milk, direct contact with infected animals, and inhaling or ingesting raw animal products [1]. Most patients present with an acute febrile illness, with or without organomegaly. However, chronic infection is detected in approximately 14% of cases, of which approximately 26% are osteoarticular brucellosis and 5% are neuroborreliosis. Although the incidence of Brucella endocarditis is rare, only occurring in 0.7–2% of cases of brucellosis, Brucella endocarditis accounts for 80% of Brucella-related deaths [2,3].
Cardiac implantable electronic device (CIED) infection is associated with increased all-cause mortality and morbidity and decreased quality of life [4,5]. The incidence of CIED infection is 1–2% over the lifetime of a device [6]. The risk of re-infection in patients with a device infection history is high [7], with incidence rates of up to 12.12/1000 device-years after device replacement, underscoring the importance of infection control measures in preventing primary infections. Of these, antibiotic prophylaxis decreases the re-infection rate by 70% [7]. Brucella CIED infections are extremely rare. In a 30-year review including 5287 patients with a CIED, only 23 patients (0.38%) developed endocarditis, and only one patient had a Brucella infection requiring device and lead removal with antibiotic therapy [8]. A recent study from the Middle East, an area endemic for brucellosis, found only 22 CIED infections over 17 years, and only one case of Brucella melitensis CIED infection [9].
2. Methods
This was a single-center retrospective cohort study conducted in a tertiary level cardiac care center in Saudi Arabia. All patients diagnosed with Brucella CIED infection who were treated at the center between 2009 and 2020 were included. Patients with other CIED infections were excluded because they were followed up in other referral centers and had incomplete data. Data were collected from the medical records, infectious disease datasheets, the electrophysiology laboratory and echocardiography database, and microbiological records. The data included demographic characteristics, risk factors, clinical presentation, laboratory investigations, echocardiographic features, and microbiological findings, including Brucella serology and blood cultures, the treatment course (medical and surgical), and outcomes. The device infection was categorized as lead infection, pocket site infection, or endocarditis. A pocket site infection was identified when local signs of inflammation at the device pocket were observed, including erythema, warmth, fluctuant swelling, wound dehiscence, erosion, tenderness, or purulent discharge. The diagnosis of CIED endocarditis was based on the Duke criteria [10], and a diagnosis of Brucella infection was based on bacterial isolation in blood or tissue cultures or a positive Brucella serology. An immunocapture assay for detecting anti-Brucella antibodies using the Brucella abortus antigen was performed using Brucellacapt® (Vircell Microbiologists, Granada, Spain). Titers of ≥1/320 were considered positive. The data was collected and reported in line with STROCSS criteria [11].
The study was approved by the hospital institutional review board. Informed consent was waived due to the retrospective nature of the study.
3. Results
A total of 134 cases of device-related infection were diagnosed in or referred to the center for device removal and were included in the analysis, of which 11.1% (15/134) were associated with brucellosis. Table 1 outlines the demographics, clinical manifestations, predisposing factors, microbiology, treatment regimens, and outcomes of the brucellosis patients. The mean age was 62.2 (range: 49–88 years), and 80% were male. The mean time to infection following device implantation was 4.8 years (range: 1–13 years). Fever was detected in 53% of patients, device site swelling in 47%, discharge in 33%, pain in 27%, and anemia in 27%. The mean C-reactive protein level and erythrocyte sedimentation rate were 36.3 mg/L and 30.2 mm/h, respectively.
Table 1.
Demographic and clinical features of brucella CIED infection.
| Characteristic | Number/(%) |
|---|---|
| Age [mean], range | 62.2 (49–88) years |
| Male | 12 (80) |
| BMI [mean] | 25 (20.5–36.8) |
| Diabetes | 10 (66.6) |
| Hypertension | 11 (73.3) |
| IHD | 7 (46.6) |
| Chronic kidney disease including dialysis | 9 (60) |
| Previous history of Brucellosis | 1 (6.6) |
| Risk factor for Brucella | 9 (60) |
| Clinical features | |
| Mean time to device infection | 4.8 (1–13years) |
| Fever | 8 (53.3) |
| Anemia | 4 (26.6) |
| Pain at site of device | 4 (26.6) |
| Swelling of site of device | 7 (46.6) |
| Discharge from the site | 5 (33.3) |
| Dyspnea | 2 (13.3) |
| Fatigue | 3 (20) |
| Night sweat | 2 (13.3) |
| Anorexia | 1 (6.6) |
| Weight loss | 1 (6.6) |
| Arthralgia | 1 (6.6) |
| Average ESR | 30.2 mm/h |
| Average CRP | 36.3 mg/l |
| Type of CIED | |
| PM | 3 (20) |
| ICD | 5 (33.3) |
| CRT-D | 7 (46.6) |
| Pocket site infection only | 3 (20) |
| Lead endocarditis only | 2 (13.3) |
| Pocket site and lead endocarditis | 10 (66.6) |
| Valve involved | 1 (6.6) |
| Management | |
| Removal of device | 15 (100) |
| Re-implant of new device | 7 (46.6) |
| Mean follow up | 40 months(9.0–77.4) |
| Mortality | 1 (6.6) |
Abbreviations: CIED: cardiovascular implantable electronic devices, BMI: Body Mass Index, IHD: Ischemic heart disease, PM: Pacemaker, ICD: Implantable Cardioverter Defibrillator, CRTD: cardiac resynchronization therapy-defibrillator. ESR: Erythrocyte sedimentation rate. CRP: C-reactive protein.
Blood culture and serology results were positive in 73% and 80% of patients, respectively. Four patients had a positive Brucella culture from the pocket site (Table 2). Only 60% of patients had a risk factor for brucellosis, such as animal contact or raw milk ingestion, recorded. One patient had concomitant methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. The most commonly infected CIEDs were cardiac resynchronization therapy defibrillators and implantable cardioverter defibrillators, while pacemakers were the least common type of CIED infected. Most patients (67%) had combined pocket and lead infection endocarditis, and five had infection at only one of the two sites. In one patient, the pocket site culture was positive, but the blood culture and serology tests were negative. Tricuspid valve endocarditis was detected in one patient, and extracardiac complications were reported in two patients with Brucella spondylodiscitis.
Table 2.
Diagnosis and treatment of CIED infection.
| # | Blood culture | Pocket site culture | Serology | Lead IE | Antibiotic | Duration | Out come |
|---|---|---|---|---|---|---|---|
| 1 | Pos. | Neg. | 1:1280 | Yes | AG, Doxy, SXT | 3 M | Missed F/U |
| 2 | Pos. | Neg. | 1:10240 | Yes | AG, Doxy, SXT | 3 M | Cured |
| 3 | Pos. | Neg. | 1:20480 | Yes | AG, Doxy, SXT | 3 M | Cured |
| 4 | Pos. | Neg. | 1:10240 | Yes | AG, Doxy, Rif | 3 M | Cured |
| 5 | Pos. | Pos. | 1:10240 | No | AG, Doxy, Cipro | 3 M | Cured |
| 6 | Pos. | Pos. | 1:10240 | No | AG, Doxy, Rif | 5 M | Cured |
| 7 | Pos. | Pos. | 1:10240 | Yes | AG, Doxy, Rif | 3 M | Cured |
| 8 | Neg. | Neg. | 1:10240 | Yes | AG, Doxy, Rif | 3 M | Mortality |
| 9 | Neg. | Neg. | 1:10240 | Yes | AG, Doxy, Rif | 3 M | Cured |
| 10 | Neg. | Neg. | 1:320 | Yes | Treated in primary center | NA | Cured |
| 11 | Pos. | Neg. | 1:10240 | Yes | AG, Doxy, SXT | 4 M | Cured |
| 12 | Pos. | Neg. | 1:10240 | Yes* | AG, Doxy, Cipro | 4 M | Cured |
| 13 | Pos. | Neg. | Negative | Yes | Treated in primary center | NA | Missed F/U |
| 14 | Pos. | Neg. | Negative | Yes | AG, Doxy, Rif | 3 M | Cured |
| 15 | No | Pos. | 1:160 | No | AG, Doxy, SXT | 3 M | Cured |
Abbreviations: CIED: cardiovascular implantable electronic devices, IE: Infective endocarditis, AG: Aminoglycosides, SXT: Co-trimoxazole, Cipro: Ciprofloxacin, Rif: Rifampicin, F/U: Follow up, *Tricuspid valve endocarditis, NA: Not available.
The most common treatment regimens were gentamycin, doxycycline, and rifampicin, and gentamycin, doxycycline, and cotrimoxazole. Most patients (67%) were treated for 12 weeks, but some were treated for longer (Table 3). The implant was removed in all patients, and only 47% (7/15) had reimplantation. Only one patient (with concomitant MSSA bacteremia) died. None of the 14 surviving patients have had a recurrent Brucella CIED infection to date, after a mean follow-up period of 40 months (range: 9.0–77.4 months).
Table 3.
Type of device, indication, timing of infection and management.
| # | Primary indication for device | Device Type | Time to infection from implant | Explanted | Re-implant | Time to Re-implant |
|---|---|---|---|---|---|---|
| 1 | secondary prevention | ICD | 1 Y | Yes | NO | |
| 2 | primary prevention | ICD | 5 M | Yes | No | |
| 3 | primary prevention | CRTD | 7 Y | Yes | No | |
| 4 | primary prevention | CRTD | 4 Y | Yes | No | |
| 5 | primary prevention | ICD | 3 Y | Yes | Right side | 2 Months |
| 6 | complete heart block | PM | 13 Y | Yes | INTRACARDIAC | 16 Days |
| 7 | primary prevention | CRTD | 4 Y | Yes | Right side | 3 Years |
| 8 | primary prevention | CRTD | 5 Y | Yes | NO | |
| 9 | complete heart block | PM | 4 Y | Yes | INTRACARDIAC | 8 Days |
| 10 | primary prevention | ICD | 11 Y | Yes | Right side | 5 Months |
| 11 | primary prevention | CRTD | 3 Y | Yes | NO | |
| 12 | primary prevention | CRTD | 5 Y | Yes | NO | |
| 13 | primary prevention | CRTD | 2 Y | Yes | NO | |
| 14 | complete heart block | PM | 8 Y | Yes | Right side | 1 Month |
| 15 | primary prevention | ICD | 2 Y | Yes | Right side | 1 Month |
Abbreviations: PM: Pacemaker, ICD: Implantable Cardioverter Defibrillator, CRTD: cardiac resynchronization therapy-defibrillator.
4. Discussion
To our knowledge, this is the largest case series of Brucella-related CIED infection. Most previous reports of Brucella CIED infection have been single case reports. In this study, Brucella was responsible for 11.1% of the CIED infections. This is a surprisingly high number as only 13 cases have previously been described in the literature (Table 4). Multiple factors may have contributed to this high incidence rate. Despite the declining incidence of brucellosis in certain parts of Saudi Arabia, the incidence rate remains high, particularly among adults aged 40–49 years [12,13]. It is noteworthy that a lack of a history of exposure to Brucella does not rule out the possibility of brucellosis. Therefore, in contrast to other centers, at our center all patients with CIED infection are routinely tested for brucellosis. Additionally, cardiac device use is increasing in Saudi Arabia, and 400–500 devices are implanted at the center annually. Moreover, the center is a national referral center for laser lead extraction of infected CIEDs, and so receives referrals of patients with CIED infections from other hospitals throughout the country.
Table 4.
Published articles on CIED Brucella Infection.
| # | Articles | Year | Age (Y)/G | device Type | Infective Endocarditis | Blood Culture | Pocket site culture | serology | Time to infection | Removal | Reimplant | Abx | Duration | Out come |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Dhand et al.(31) | 2007 | 66 M | ICD | No | Neg. | Pos. | NA | 2.5 Y | Yes | 1 Week | AG/D/Cip | 6 Weeks | cured |
| 2 | Jamil (32)N et al. | 2018 | 82 M | PM | Yes | Neg. | Pos. | NA | 2 Y | Yes | 1 Week | AG/D/Rif | 12 Weeks | cured |
| 3 | Tsyba (33) et al. | 2018 | 41 M | PM | Yes | Neg. | Pos. | Pos. | 8 Y | Yes | No | AG/D/Rif | 12 Weeks | cured |
| 4 | Dourakis et al. (34) | 2007 | 70 M | PM + TV | Yes | Pos. | Neg. | Pos. | 7 Y | Yes | Same time | D/Rif/Cip | 12 Weeks | cured |
| 5 | Al-Adsani et al. (35) | 2018 | 70 M | PM | Yes | Pos. | Neg. | NA | 1 Y | No | No | AG/D/Ri/B | 12 Weeks | cured |
| 6 | Ibrahima et al.(36) | 2019 | 52 F | PM | NA | Neg. | Pos. | Pos. | NA | Yes | No | AG/D/Rif | 12 Weeks | cured |
| 7 | de la Fuente et al.(37) | 1997 | 63 M | PM | No | Neg. | Pos. | Neg. | 1.4 Y | Yes | 1 Week | AG/D/Rif | 6 Weeks | cured |
| 8 | Gungor O et al.(38) | 2012 | 61 M | PM | No | Pos. | Pos. | NA | 2 Y | Yes | No | D/Rif | 6 Weeks | cured |
| 9 | Elmardi et al.(15)* | 2016 | 54 F | CRTD | No | Neg. | Neg. | Pos. | 7 Y | Yes | No | Unknown | Unknown | cured |
| 52 M | ICD | No | Neg. | Neg. | NA | 1 Y | Yes | No | AG/D/B | Unknown | cured | |||
| 10 | Almajed et al.(14) | 2010 | 38 M | PM | Yes | Pos. | Neg. | Pos. | 20 Y | Yes | No | D/Rif | 6 Weeks | cured |
| 11 | Miragliotta et al.(39) | 2005 | 70F | PM | No | Pos. | Pos. | Pos. | 4 Y | Yes | Same time | Min/Rif/Cipro | 12 Weeks | cured |
| 12 | Ulkar et al.(40) | 2001 | 68 M | PM | No | Neg. | Neg. | Pos. | 8 Y | Yes | Unknown | Unknown | Unknown | Cured |
Abbreviations: Y: Year, G: Gender, Abx: Antibiotic, M: male, F: Female, PM: Pacemaker, ICD: Implantable Cardioverter Defibrillator, CRTD: cardiac resynchronization therapy-defibrillator, TV = Tricuspid valve, AG: Aminoglycoside, D: Doxycycline, R: Rifampicin, Min: Minocycline, Cipro: Ciprofloxacin, B: Bactrim, NA: Not available. Pos. = Positive, Neg. = Negative,* Included in the current study.
Most patients in this study were middle-aged men. As in previous studies, hypertension, diabetes mellitus, ischemic heart disease, and chronic kidney disease were the major predisposing factors. CIED may present as a pocket site infection or lead endocarditis with or without bacteremia. Occasionally, systematic manifestations occur without focal signs or bacteremia [5]. In this study, over half the patients had Brucella infection at multiple sites. Two patients had an extracardiac infection with complicated spondylodiscitis, which underscores the importance of identifying all the infection sites. Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG PET/CT)is useful for detecting endocarditis and distant infections. The sensitivity, specificity, and overall diagnostic accuracy of 18F-FDG PET/CT for CIED infection are estimated to be 87%, 94%, and94%, respectively [14].
Staphylococci, either coagulase-negative or Staphylococcus aureus, account for 60–80% of CIED infections [15]. However, brucellosis is extremely rare, despite remaining an important pathogen to consider in endemic areas [16]. Both Brucella and staphylococci are capable of multilayered biofilm formation [17]. Several Brucella proteins, including SP41, are involved in the adhesion to different cell types or the extracellular matrix [18]. As a result, Brucella readily binds to collagen, fibronectin, vitronectin, and other extracellular matrix proteins. Biofilm formation and the intracellular location of Brucella species account for the chronicity of infection and the need for device extraction, together with prolonged antibiotic treatment. Brucella endocarditis requires prolonged treatment, with most patients receiving antibiotics for 3–6 months [19]. Device extraction followed by reimplantation is essential [19]. A study reported that the mortality rate for Brucella endocarditis patients was 32.7% in a group that was provided only medical therapy compared to 6.7% in the group provided medical and surgical therapy (p < 0.001) [20]. Therefore, all devices should be extracted within 72 h to lower mortality and decrease the hospital stay length.
In this study, one patient had a dual Brucella and MSSA bacteremia. Dual Brucella and other bacterial endocarditis have been described previously [21]. Streptococcus viridans and Coxiella burnetti have also been reported in patients with Brucella endocarditis, highlighting the importance of diagnosing Brucella infection in predisposed patients in endemic areas, even if other organisms are isolated. Both Brucella blood or tissue culture and Brucella serology should be performed if an infection is suspected. While most patients in this case series were positive on both blood culture and serology, three patients had culture-negative, serology-positive brucellosis, and a further three patients had culture-positive, serology-negative brucellosis. In one patient, both blood culture and serology tests were negative, and the diagnosis was established only on the pocket site tissue culture. These cases underscore the importance of testing cultures from multiple sites in all patients.
4.1. Limitations
Our study has several limitations. The study was retrospective and was conducted at a single specialized center. This specialized nature of the center and referral of patients from other hospitals could have contributed to the high number of cases. Patients with other bacterial infection were not included so we were unable to compare risk factors for infection and outcome in patients with Brucella CIED infection compared to other types of CIED infection.
5. Conclusion
Brucella CIED infection is infrequent yet increasing and should be considered in all patients living in or visiting endemic areas, particularly in individuals with negative cultures for other organisms. The presence of other bacterial isolates should not rule out a Brucella diagnosis, as dual infection can occur. Prompt removal of the device and appropriate antibiotic therapy improve the prognosis. Patients with CIEDs living in endemic areas ought to be informed of the risk of Brucella CIED infection and advised how to avoid contracting brucellosis.
Provenance and peer review
Not commissioned, externally peer reviewed.
Source of funding
No source of funding.
Ethical Approval
Ethical approval was obtained from PSMMC ethical committee.
Consent
Consent was waved in view of retrospective nature of the study.
Author contribution
Dr. Elzein, formed the study concept, revised the data, interpreted results and wrote the manuscript.
Dr. Ahmed Al Fagih and Dr. Yahya Al Hebaishi were the physicians following the patients and contributed to the manuscript writing and revisions. Dr. Mohammed Mosaad Collected, analysed the data and revised the manuscript.
Dr. Eid Alsufyani collected, analysed, and tabulated the data. He contributed to writing and revising the manuscript.
Registration of research studies
1. Name of the registry: Research Registry.
2. Unique Identifying number or registration ID: researchregistry6959.
3. Hyperlink to your specific registration (must be publicly accessible and will be checked): https://www.researchregistry.com/browse-the-registry#home/
Guarantor
Dr Fatehi E Elzein.
Declaration of competing interest
No conflict of interest.
References
- 1.Pappas G. Hunter's Trop. Med. Emerg. Infect. Dis. ninth ed. 2012. Brucellosis. [DOI] [Google Scholar]
- 2.Buzgan T., Karahocagil M.K., Irmak H., Baran A.I., Karsen H., Evirgen O., Akdeniz H. Clinical manifestations and complications in 1028 cases of brucellosis: a retrospective evaluation and review of the literature. Int. J. Infect. Dis. 2010;14:e469–e478. doi: 10.1016/j.ijid.2009.06.031. [DOI] [PubMed] [Google Scholar]
- 3.Erbay A.R., Turhan H., Dogan M., Erbasi S., Cagli K., Sabah I., Vahabi A., Gül F., Garakhanova S., Sipahi H., Sipahi O.R., Noman S.V.H., Visser H., Muller A.F., Limonard G.J.M., Bergendal E., Cascio A., De Caridi G., Lentini S., Benedetto F., Stilo F., Passari G., Iaria C., Spinelli F., Pappas G., Mehanic S., Baljic R., Mulabdic V., Pinjo F., Topalovic J., Hadziosmanovic V., HadzovicCengic M., Du N., Wang F., Tsyba E., Gallego-Colon E., Daum A.Z., Fishman E., Chaim Y. Pooled analysis of 1270 infective endocarditis cases in Turkey. Bone. 2018;93:827–840. doi: 10.1089/vbz.2012.0965. [DOI] [Google Scholar]
- 4.Wilkoff B.L., Boriani G., Mittal S., Poole J.E., Kennergren C., Corey G.R., Love J.C., Augostini R., Faerestrand S., Wiggins S.S., Healey J.S., Holbrook R., Lande J.D., Lexcen D.R., Willey S., Tarakji K.G. Impact of cardiac implantable electronic device infection: a clinical and economic analysis of the WRAP-IT trial, circ. Arrhythmia Electrophysiol. 2020;13:382–391. doi: 10.1161/CIRCEP.119.008280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Blomström-Lundqvist C., Traykov V., Erba P.A., Burri H., Nielsen J.C., Bongiorni M.G., Poole J., Boriani G., Costa R., Deharo J.C., Epstein L.M., Saghy L., Snygg-Martin U., Starck C., Tascini C., Strathmore N., Kalarus Z., Boveda S., Dagres N., Rinaldi C.A., Biffi M., Gellér L., Sokal A., Birgersdotter-Green U., Lever N., Tajstra M., Kutarski A., Rodríguez D.A., Hasse B., Zinkernagel A., Mangoni E. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections - endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) Europace. 2020;22:515–516. doi: 10.1093/europace/euz246. [DOI] [PubMed] [Google Scholar]
- 6.Desimone D.C., Sohail M.R., Mulpuru S.K. Contemporary management of cardiac implantable electronic device infection. Heart. 2019;105:961–965. doi: 10.1136/heartjnl-2017-312146. [DOI] [PubMed] [Google Scholar]
- 7.Polyzos K.A., Konstantelias A.A., Falagas M.E. Risk factors for cardiac implantable electronic device infection: a systematic review and meta-analysis. Europace. 2015;17:767–777. doi: 10.1093/europace/euv053. [DOI] [PubMed] [Google Scholar]
- 8.Cardiac device-related endocarditis: 31-Years’ experience | Elsevier Enhanced Reader, (n.d.). https://reader.elsevier.com/reader/sd/pii/S0914508712002419?token=7AD904E78862B02BCFDA117AD5178D3169CA4703A07E84F30F08C95F7412C37BF9EC53A10B4FD650397C94B519C54A8A&originRegion=eu-west-1&originCreation=20210514082340 (accessed May 14, 2021).
- 9.Refaat M., Zakka P., Khoury M., Chami H., Mansour S., Harbieh B., Abi-Saleh B., Bizri A.R. Cardiac implantable electronic device infections: observational data from a tertiary care center in Lebanon. Medicine (Baltim.) 2019;98 doi: 10.1097/md.0000000000014906. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Sohail M.R., Corey G.R., Wilkoff B.L., Poole J.E., Mittal S., Kennergren C., Greenspon A.J., Cheng A., Lande J.D., Lexcen D.R., Tarakji K.G. Clinical presentation, timing, and microbiology of CIED infections: an analysis of the WRAP-IT trial. JACC Clin. Electrophysiol. 2021;7:50–61. doi: 10.1016/j.jacep.2020.07.021. [DOI] [PubMed] [Google Scholar]
- 11.Agha R., Abdall-razak A., Crossley E., Dowlut N., Iosifidis C., Millham F.H., Orgill D.P., Noureldin A., James I., Alsawadi A., Bradley P.J., Giordano S., Laskin D.M., Basu S., Johnston M., Muensterer O.J., Mukherjee I., Ngu J.C., Valmasoni M., Pagano D., Vasudevan B., David R., Anthony J., Albrecht J., Hoffman J.R., Thorat M.A., Massarut S., Thoma A., Kirshtein B., Yahia R., Farooq N., Challacombe B., Pai P.S., Perakath B., Kadioglu H., Aronson J.K., Raveendran K., Machado-aranda D., Klappenbach R., Healy D., Miguel D., Rodrigues C., Ather M.H. STROCSS 2019 Guideline : strengthening the reporting of cohort studies in surgery. Int. J. Surg. 2019;72:156–165. doi: 10.1016/j.ijsu.2019.11.002. [DOI] [PubMed] [Google Scholar]
- 12.Al-Tawfiq J.A., AbuKhamsin A. A 24-year study of the epidemiology of human brucellosis in a health-care system in Eastern Saudi Arabia. J. Infect. Public Health. 2009;2:81–85. doi: 10.1016/j.jiph.2009.03.003. [DOI] [PubMed] [Google Scholar]
- 13.Alkahtani A.M., Assiry M.M., Chandramoorthy H.C., Al-Hakami A.M., Hamid M.E. Sero-prevalence and risk factors of brucellosis among suspected febrile patients attending a referral hospital in southern Saudi Arabia (2014-2018) BMC Infect. Dis. 2020;20:1–8. doi: 10.1186/s12879-020-4763-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Ahmed F.Z., Arumugam P. 18F-FDG PET/CT now endorsed by guidelines across all types of CIED infection: evidence limited but growing. J. Nucl. Cardiol. 2020;26 doi: 10.1007/s12350-017-1119-1. (n.d.) [DOI] [PubMed] [Google Scholar]
- 15.Baddour L.M., Epstein A.E., Erickson C.C., Knight B.P., Levison M.E., Lockhart P.B., Masoudi F.A., Okum E.J., Wilson W.R., Beerman L.B., Bolger A.F., Estes N.A.M., Gewitz M., Newburger J.W., Schron E.B., Taubert K.A. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the american heart association. Circulation. 2010;121:458–477. doi: 10.1161/CIRCULATIONAHA.109.192665. [DOI] [PubMed] [Google Scholar]
- 16.Biofilm S., Structure D. crossm. 2020;84:1–36. [Google Scholar]
- 17.Staphylococcal Biofilm Development, Structure . n.d.; 2020. Regulation, and treatment strategies _ microbiology and molecular biology reviews. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Bialer M.G., Sycz G., González F.M., Ferrero M.C., Baldi P.C., Zorreguieta A. Adhesins of brucella: their roles in the interaction with the host. Pathogens. 2020;9:1–20. doi: 10.3390/pathogens9110942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.G. Habib, P. Lancellotti, M.J. Antunes, M. Grazia Bongiorni, J.-P. Casalta, F. Del Zotti, R. Dulgheru, G. El Khoury, P. Anna Erba, B. Iung, J.M. Miro, B.J. Mulder, ESC GUIDELINES 2015 ESC guidelines for the management of infective endocarditis the task force for the management of infective endocarditis of the European society of cardiology (ESC) endorsed by: European association for cardio-thoracic surgery (EACTS), the European association of nuclear medicine (EANM), (n.d.). 10.1093/eurheartj/ehv319. [DOI] [PubMed]
- 20.Keshtkar-Jahromi M.M.M., Razavi S.-M.M., Gholamin S., Keshtkar-Jahromi M.M.M., Hossain M., Sajadi M.M. Medical versus medical and surgical treatment for brucella endocarditis. Ann. Thorac. Surg. 2012;94:2141–2146. doi: 10.1016/j.athoracsur.2012.07.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Elzein F.E.F.E., Alsherbeeni N., Alnajashi K., Alsufyani E., Akhtar M.Y.Y., Albalawi R., Albarrag A.M., Kaabia N., Mehdi S., Alzahrani A., Raoult D. Ten-year experience of Q fever endocarditis in a tertiary cardiac center in Saudi Arabia. Int. J. Infect. Dis. 2019;88:21–26. doi: 10.1016/j.ijid.2019.07.035. [DOI] [PubMed] [Google Scholar]