Pacemaker lead-related endocarditis with Neisseria sicca

Abstract

We report the first known case of Neisseria sicca-associated pacemaker lead endocarditis—a disease whose incidence and mortality are growing. A woman in her 70s with a history of transcatheter aortic valve replacement and pacemaker placement 7 months earlier presented with recurrent fevers. She visited the emergency department several times during the past 2 months for these fevers, and she had been given oral antibiotics for presumed urinary tract infections. Investigations revealed blood cultures growing N. sicca. Although transthoracic echocardiogram was negative, transesophageal echocardiogram showed two vegetations on the right atrial lead which suggested pacemaker lead-associated endocarditis. A complete pacemaker and lead extraction was performed, and the patient recovered completely and was discharged home to complete 6 weeks of intravenous ceftriaxone with plans for follow-up echocardiography. We hope that this case will contribute to the growing body of literature regarding device infections, thus leading to earlier identification and treatment.

Background

Cardiac implantable electronic devices (CIEDs) such as defibrillators, pacemakers and cardiac resynchronisation devices are crucial tools for the management of various cardiac pathologies including bradycardia and tachyarrhythmias, heart failure with reduced ejection fraction and hypertrophic cardiomyopathy.¹ Unfortunately, CIEDs, being foreign bodies, are subject to infection. The reported incidence of infection is 1.7% 6 months after implantation for defibrillators and 9.7% 2 years after placement of resynchronisation devices.² Due in part to expanded indications and increased comorbidities of device recipients, use of these devices and device-related infection have increased in recent years. The CIED infection rate in the USA rose from 1.53% to 2.41% between 2004 and 2008.³ Given the growing incidence, and estimated in-hospital mortality between 5% and 15% for CIED-related infection, optimal identification and management of these patients are paramount.²

The most commonly identified causative organisms have been gram-positive bacteria such as Staphylococcus aureus and coagulase-negative Staphylococcus species.^4–7 Other gram-positive bacteria, including streptococci and enterococci, are more rare aetiologies.² Even more uncommonly, infection from fungi and from gram-negative bacteria, including the HACEK organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella and Kingella spp), has been documented.^{2 8–10} Case reports of implanted cardiac device infection and endocarditis by Pseudomonas, Burkholderia and Mycobacterium species have also been reported^{6 11 12} (figure 1).

Figure 1.

Per our review of the literature, estimated percentage of cardiac implantable electronic device-associated endocarditis cases induced by several causative organisms.^4–12

Here, we report the first known case of pacemaker lead infection by Neisseria sicca. Globally, N. sicca endocarditis is very rare and has only been reported in a few dozen patients.^13–19 Pacemaker infection attributed to other Neisseria spp is even rarer and, to our knowledge, has only been reported in a handful of cases.^{20 21} Per our review of the literature, no previous case of isolated infection of a CIED lead by N. sicca has been reported.

Case presentation

The patient is a woman in her 70s with a history of transcatheter aortic valve replacement and pacemaker placement (both placed 7 months prior to presentation) who presented to the hospital after 2 days of fevers and chills with temperature to 38.3°C on her home monitor.

She had initially presented to the emergency department (ED) approximately 2 months prior to the present episode complaining of fevers and chills. At the time, although she did not complain of dysuria, she had a urine culture that was positive for Escherichia coli and was given a 14-day course of cefdinir for treatment of a presumed urinary tract infection. Shortly after completing her course of cefdinir, she re-presented again with fevers and chills and was found to have a different strain of E. coli based on antibiotic susceptibilities. She was administered a 5-day course of trimethoprim-sulfamethoxazole—again for presumed urinary tract infection. The patient denied dysuria, and she did not have any recent oral or respiratory procedures. She also denied any history of intravenous drug use. One day prior to admission, the patient had re-presented to ED for fevers and chills at home, was prescribed another course of antibiotics and was discharged home, but she was called back and admitted to the hospital after two sets of blood cultures drawn in the ED returned positive for gram-negative diplococci.

On admission, the patient was afebrile and haemodynamically stable with a temperature of 37.1°C, a heart rate of 69 beats per minute, a blood pressure of 128/71 mm Hg, a respiratory rate of 18 breaths per minute and an oxygen saturation of 98% on room air.

Investigations

Complete blood count was notable for leucocytosis to 11.06 × 10ˆ9/L with 86.7% neutrophil predominance. Two sets of blood cultures drawn on admission returned positive for N. sicca. Blood cultures drawn 48 hours after initiation of broad-spectrum antibiotics demonstrated no growth. Antibiotic susceptibilities of N. sicca were not performed. Urinalysis was positive for large leucocyte esterase and negative for nitrites and bacteria. Urine culture grew <10,000 normal urogenital flora. Renal ultrasound was negative for signs of pyelonephritis, nephrolithiasis or obstruction in urinary flow.

A transthoracic echocardiogram (TTE) was unremarkable, but further evaluation with a transesophageal echocardiogram (TEE) revealed two 0.8 cm vegetations attached to the right atrial lead (figure 2) and a mild interval increase in regurgitant flow through the prosthetic aortic valve compared with 5 months prior. No valvular or paravalvular vegetations were evident. Dental evaluation with panoramic X-ray did not reveal any infection or dental caries.

Figure 2.

Transesophageal echocardiogram showing two mobile echodensities measuring up to 0.8 cm in length attached to the right atrial lead within the right atrium.

Treatment

The patient was started on intravenous ertapenem empirically and switched to intravenous ceftriaxone after cultures speciated. The patient had no recurrence of fevers 24 hours after initiation of ertapenem. Given the positive blood cultures and the vegetations on the lead suggesting CIED-related endocarditis, an uncomplicated complete pacemaker and lead extraction was performed. Although the pacemaker had been initially implanted for bifascicular block (right bundle branch block and left anterior fascicular block), pacemaker interrogation showed that the patient was not pacemaker dependent, so pacemaker re-implantation was not pursued. Culture of pacemaker lead was also performed but demonstrated no growth at 5 days.

Outcome and follow-up

The patient was discharged home and completed a 6-week course of intravenous ceftriaxone through a peripherally inserted central catheter for her pacemaker-associated N. sicca endocarditis. Repeat TEE after 6 weeks of antibiotics was without interval change, and the patient was planned for a surveillance TEE in another 3 months. Antibiotics were discontinued, and the patient has not experienced a recurrence of fevers in the month that she has been off of antibiotics.

Discussion

The estimated incidence of infectious complications following CIED implantation has been reported between 1% and 7%.^{3 4 22} Risk factors for CIED infection include patient comorbidities such as diabetes, renal failure and heart disease or procedural characteristics such as device replacement as opposed to new implantation, CIED pocket re-exploration, temporary pacing prior to procedure, presence of >2 leads, lack of periprocedural antibiotic prophylaxis, upgrade procedures and defibrillator as opposed to pacemaker procedure.^{5 23 24}

CIED infections and endocarditis are usually due to gram-positive organisms, and infections due to gram-negative organisms including N. sicca, as seen in this case, are rare.^{4 5}

Neisseria spp are gram-negative diplococci and uncommon causative organisms of infective endocarditis. More commonly, Neisseria gonorrhoeae and Neisseria meningitidis are identified as causative organisms in infective endocarditis, especially in sexually active patients.¹³ However, infective endocarditis attributed to the other ‘non-pathogenic’ Neisseria spp (Neisseria elongata, Neisseria flavus and Neisseria sicca) that are typically oral flora has been documented in rare case reports that are usually associated with intravenous drug use or dental procedures.^{13 25}

In this case about an immunocompetent patient who developed N. sicca pacemaker lead endocarditis without valvular involvement, such clear risk factors are absent. We hypothesise that her N. sicca pacemaker infection and subsequent bacteraemia may have been slowly progressive for several months prior to presentation during her initial visits for recurrent fevers and chills. These episodes were attributed to recurrent E. coli urinary tract infections, but in retrospect, most likely were symptoms of her endocarditis especially given her absence of urinary symptoms. Although the definite source that may have seeded the infection is still unclear, possible sources include transient bacteraemia originating from the oropharyngeal area or pacemaker contamination during initial placement 7 months prior with indolent progression. Although culture of the pacemaker lead was negative for growth, this more likely reflects the fact that the patient had already received 5 days of intravenous antibiotics prior to pacemaker extraction.

As demonstrated in this case report, TTE to help diagnose pacemaker infection is usually insufficient as it may miss smaller vegetations. TEE, although more invasive, is more sensitive for vegetations when there is a high index of suspicion for pacemaker infection/endocarditis.²⁶ Studies have found the sensitivity for detecting CIED vegetations to range from 20% to 40% in TTE compared with 82%–96% in TEE.²⁷

The usual management of pacemaker lead infection is extraction of the infected device and leads with an extended course of antibiotics. In one study, recurrent infection occurred in 8% of patients with total pacemaker system removal and 75% of patients with partial pacemaker removal.²⁸ Another study demonstrated that complete device system removal reduced risk of recurrent infection by 75%.⁷

This case represents the first reported incidence of N. sicca CIED-related endocarditis. As was evident here, an atypical presentation of a device infection can lead to a profound diagnostic delay. Although this patient, fortunately, was an otherwise healthy individual, it is known that the in-hospital mortality associated with device infection is significant, and it is conceivable that any setback in the recognition of these infections can lead to a worse outcome. Thus, it is our hope that this case, in contributing to a growing body of literature regarding these infections and their presentations, will lead to earlier identification and improved management of this important disease.

Patient’s perspective.

Coordinating appointments with so many different individuals—from infectious diseases, cardiology, the cardiothoracic surgeon after I returned home was difficult. Thankfully the fevers haven’t come back but not knowing exactly where all of this came from and that it was so unexpected was very frightening to experience.

Learning points.

• Clinicians should always avoid anchoring bias and maintain a broad differential diagnosis when evaluating patients with recurrent fevers.

• Endocarditis should be on the differential for any patient with history of cardiac implantable electronic device (CIED) placement or cardiac procedures presenting with recurrent fevers.

• Neisseria sicca is an extremely rare cause of CIED-related endocarditis.

• Transesophageal echocardiogram should be pursued to help diagnose endocarditis in patients with a high index of suspicion for endocarditis even if transthoracic echocardiogram is negative.

• Complete pacemaker and lead removal are essential in preventing recurrent endocarditis.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).