Permanent pacemaker-associated actinomycetemcomitans endocarditis: a case report.
Over the past five decades, cardiovascular implantable electronic devices (CIED), including permanent pacemakers (PPMs) and cardioverter-defibrillators, have become an important part of the management of several cardiac diseases. Although these devices have dramatically increased patient survival and quality of life, they carry a significant risk for infection. (1) The average rate of infection is estimated at around 4%. (24) Currently there is a disproportion between the steady increase of CIED implants and the much greater increase in CIED-related infections. (5) CIED infection can present as a generator pocket infection, a blood stream infection, or both. (6) The most common source of endocarditis appears to be an infection acquired at the device generator site with subsequent infection involving the leads. (7) Frank PPM endocarditis accounts for approximately 10% of PPM infections. CIED infections are most commonly caused by Staphylococcus species which account for 60-80% of the reported cases. (8) Non-staphylococcal bacterial endocarditis is a less prevalent but treatable disease, thus clinical awareness is imperative. (1) Clinicians should consider this infection in susceptible patients with positive blood cultures. On the other hand, HACEK (Haemophilus species, actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella species) associated endocarditis has not been reported in patients with CIEDs. Here we present a rare case of CIED associated endocarditis caused by Aggregatibacter actinomycetemcomitans, a member of the HACEK group.
The patient is a 25-year-old Hispanic male who came to the emergency room complaining of a sudden onset of dizziness for one day. He described feeling lightheaded but did not experience syncope. Associated symptoms included shortness of breath with minimal exertion, fever and nausea without vomiting. He denied headache, blurry vision and chest pain, but admitted having chills and fatigue worsening over the past several days. Review of systems revealed a decreased appetite with a loss of 10 pounds, from 165 lbs (74.8 kg) to 155 lbs (70.3 kg) over the previous month (6%). He denied any recent travel or sick contacts. No recent dental procedures in the past 3 years.
His past medical history is significant for a permanent pacemaker implanted 12 years ago for an unknown childhood arrhythmia after the patient had been found to have several episodes of syncope. He has no known allergies to food and medication. He takes metoprolol 12.5 mg twice daily. He denies cigarette smoking, alcohol consumption and illicit drug use.
On physical examination, he did not appear acutely distressed. He was alert and orientated to person, place and time. He was afebrile with a blood pressure of 113/70 mm Hg, pulse 92 beats per minute and respiratory rate 16 breaths per minute. The patient's periodontal condition was good, without caries or any signs of infection. Cardiopulmonary exam was within normal limits. No murmurs, rubs or gallops were appreciated. Neurological exam was also within normal limits.
Laboratory findings were significant for leukocytosis, with a white blood cell (WBC) count of 17.3 K/cmm and anemia with a hematocrit of 23%. Coagulation panel and serum electrolytes were within normal limits. Cardiac markers were also within normal limits. Erythrocyte sedimentation rate (ESR) was significantly elevated, reported as greater than 140 mm/h. Electrocardiography revealed normal sinus rhythm at 98 beats per minute, normal axis and no acute ST-T wave changes. Chest radiography showed a left lung base haziness consistent with a developing infiltrate.
Computed tomography (CT) of the chest, with contrast, revealed multiple bilateral necrotizing pulmonary lesions. Some of these lesions contained cavitations. Alveolar and interstitial infiltrates were observed with air bronchograms and cystic bronchiectasis (Figure 1). The differential diagnosis includes septic emboli, of either fungal or bacterial origin, tuberculosis or neoplasm. There was no significant adenopathy. Splenomegaly was also noted with a measured length of 19 cm. The liver was also enlarged, measuring 24 cm. The rest of the abdominal organs were unremarkable.
Due to the high clinical suspicion for infective endocarditis (fever, chills and history of permanent pacemaker placement), blood cultures were drawn and transthoracic echocardiography (TTE) was performed. The TTE showed an ejection fraction of 60% and no clear evidence of vegetations. On the other hand, transesophageal echocardiography (TEE) revealed several small to moderate size (0.6 to 0.9 cm) mobile masses on the atrial and ventricular leads of the PPM consistent with the vegetations. A small mobile vegetation was also seen on the posterior leaflet of the tricuspid valve. Moderate tricuspid regurgitation was noted but otherwise the valvular functions were unremarkable (Figures 2a and 2b). Gram stain from the blood culture showed Gram-variable mixed with Gram-negative rods (later on identified as Aggregatibacter actinomycetemcomitans). He was treated empirically with IV vancomycin, 1 gram every 12 hours and piperacillin with tazobactam, 4.5 grams every eight hours. The next day after the patient begun treatment with antibiotics, the WBC count went back to normal range and the patient became afebrile.
After five days of hospitalization his hematocrit dropped to 21.5%, requiring transfusion of two units of packed red blood cells. After stabilization he was transferred to another hospital for PPM lead extraction. PPM was not replaced or removed due to patient's preference. The patient was discharged home on intravenous antibiotics through a peripherally inserted central catheter (PICC). Two weeks later, the patient was again admitted to our hospital complaining of worsening shortness of breath with chills. CT showed new septic emboli in the lungs. He was given cefepime 2 grams every eight hours and vancomycin 1 gram every 12 hours. After two days he felt better and was transferred to another facility for PPM removal. PPM was removed. There was no need for pacemaker replacement according to the cardiologist.
After 10 days from the first admission, both the anaerobic and aerobic blood cultures on blood and chocolate agar plate with the presence of 5% carbon dioxide at 37[degrees]C grew Aggregatibacter actinomycetemcomitans, a member of the HACEK group of bacteria. The diagnosis of subacute infective endocarditis was confirmed. On a 3-months follow-up the patient's clinical condition significantly improved.
The increased use of CIEDs has led to an increasing prevalence of their associated infections. Unfortunately, infection rates are increasing faster than implantation rates. (5) These infections include CIED pocket infections and CIED-related endocarditis. While staphylococcal species account for the majority of reported cases, non-staphylococcal species also need to be considered. (8) Non-staphylococcal CIED-related infections usually have a more subacute onset and lower mortality rates. These organisms tend to cause late-onset infections, usually several years after placement of the device. Gram-negative bacteria and fungi can seed a device during hematological spread, thus there should be a high suspicion for these infections in any patient with bacteremia and a CIED. Surprisingly, through a retrospective review of hospital records, one study found that the diversity of non-staphylococcal species associated with CIED is rather extensive, the most common being Pseudomonas aeruginosa. (1) Although this study identified several organisms, including Gram-negative bacteria, atypical bacteria and fungi, no species from the HACEK group were identified in the 504 patients in the study. CIED associated infections caused by the HACEK group, as presented in this case report, are very rare.
The members of the HACEK group are slow growing bacteria that are part of the oropharyngeal flora. They account for 5% to 10% of endocarditis infections in native heart valves. (9) Risk factors for HACEK associated endocarditis include previous dental procedures and underlying heart disease. (10) Previous valve replacement, congenital heart disease, and dilated cardiomyopathy are known predisposing risk factors for infection. The course is subacute and patients generally present with non-specific symptoms such as fatigue, mild fever and shortness of breath. Acute congestive heart failure, a new murmur and evidence of septic emboli are more specific signs that alert the clinician and should be sought out. Due to their slow growth, these bacteria should be included in the differential diagnosis of culture-negative endocarditis. Identification is needed for diagnosis and generally requires prolonged incubation of blood cultures (typically several weeks). (11) Alternatively, the organism can be identified from the vegetation using molecular techniques. Among the bacteria of the HACEK group, Aggregatibacter actinomycetemcomitans, the organism identified in this case, is most commonly involved in infective endocarditis. (10) It is commonly associated with severe oral infections such as periodontitis. Underlying valve disease and prosthetic valves are leading risk factors for endocarditis from this species. The patients are generally young to middle-aged and blood cultures are positive in the majority of cases, consistent with this case report. (10) Medical treatment alone can cure endocarditis caused by the HACEK group when there is no involved hardware. (12) In the case we have reported, due to the presence of a PPM, medical treatment was not sufficient and hardware removal was indicated. Due to the increasing prevalence of beta-lactamase-producing organisms, empirical treatment with a cephalosporin, rather than ampicillin, is recommended. (13) The Infectious Diseases Society of America (IDSA) endorses ceftriaxone and ampicillin-sulbactam as initial choices. (16) Treatment duration is generally 4 to 6 weeks. The American Heart Association (AHA) recommends treatment with ceftriaxone 2 grams, intravenously, every 24 hours for 4 weeks. Alternatively, ampicillin-sulbactam 12 grams daily intravenously divided into 4 doses or ciprofloxacin 1 gram orally or 800 mg intravenously every 24 hours for 4 weeks. Enterococcal species are relatively resistant to penicillin and ampicillin and even when these cell wall-active agents inhibit enterococci, they often do not kill them. (14) These organisms pose a unique problem because they are resistant to cephalosporins. Due to synergistic effects and the presence of a beta-lactamase inhibitor, ampicillin-sulbactam 3 grams IV every 6 hours plus gentamicin 1.0 mg/kg IV every 8 hours can be used as empirical therapy. Vancomycin and daptomycin should be considered in refractory cases. (15)
Prompt hardware removal and prolonged parenteral antibiotics are the standard management for infected CIEDs. Removal of the device is needed due to the high risk for reinfection and associated device failure. Developing methods and tools for safely extracting leads from patients with long-standing implanted devices has been an ongoing area of research for decades. (17) One retrospective study showed decreased mortality associated with prompt lead extraction (either percutaneously or surgically) and an average of 28 days of intravenous antibiotics for patients with CIED associated endocarditis. (18)
Due to the increasing incidence and mortality associated with CIED associated infections, preventative measures are imperative. As part of the initiative to enhance prevention, an impregnated implantable antibacterial envelope has been developed. The envelope is a polymer mesh implanted in the generator pocket with the CIED. After implantation it releases antibiotics, such as minocycline and rifampin, which are known to reduce infections associated with medical devices. (19) A retrospective cohort study looked at CIED infection rates in patients receiving the envelope. (20) The results showed a marked reduction in CIED infections when compared to a matched control cohort. This method has shown promise to improve safety, cost and reduce mortality in patients at high risk for infection.
This case report describes the rare occurrence of CIED associated endocarditis caused by Aggregatibacter actinomycetemcomitans, a member of the HACEK group. These are slow growing bacteria that account for 5%
to 10% of endocarditis infections in native heart valves. There is no known association with implantable devices. The presentation is subacute and blood cultures tend to take weeks to become positive, underlying the importance of close follow-up. Clinicians need to keep these organisms in mind, particularly in patients with implantable hardware, as hardware removal is imperative for good clinical outcome.
Conflicts of interest All authors--none to declare.
Author contribution: All authors contributed to the manuscript. ZL and JM contributed equally.
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Zhenhong Li,  * Jennifer Madeo,  Shadab Ahmed,  Alex Vidal,  Amgad Makaryus,  Jose Mejia,  Tabassum Yasmin 
Received: July 1, 2013; accepted: August 30, 2013.
 MD, PhD, Department of Medicine, Nassau University Medical Center, East Meadow, New York, USA;  DO, PhD, Department of Medicine, Nassau University Medical Center, East Meadow, New York, USA;  MD, Division of Infectious Disease, Department of Medicine, Nassau University Medical Center, East Meadow, New York, USA;  MD, Division of Cardiology, Department of Medicine, Nassau University Medical Center, East Meadow, New York, USA;  MD, Division of Cardiology, Department of Medicine, Nassau University Medical Center, East Meadow, New York, USA;  MD, Department of Medicine, Nassau University Medical Center, East Meadow, New York, USA;  MD, Division of Infectious Disease, Department of Medicine, Nassau University Medical Center, East Meadow, New York, USA.
* Corresponding author: Zhenhong Li, MD, PhD, Department of Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike East Meadow, East Meadow, New York, 11554, USA; email@example.com
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|Title Annotation:||Case report|
|Author:||Li, Zhenhong; Madeo, Jennifer; Ahmed, Shadab; Vidal, Alex; Makaryus, Amgad; Mejia, Jose; Yasmin, Tab|
|Article Type:||Clinical report|
|Date:||Sep 1, 2013|
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