Enterococcus faecalis bacteremia, cardiac implantable electronic device, extraction, and the risk of recurrence

Information on all consecutive blood cultures positive for E. faecalis from January 2014 to November 2018, were obtained from the laboratory databases of Clinical Microbiology, Region Skåne, Lund, Sweden, the only laboratory in the region with a catchment area of 1.3 million inhabitants. All medical records of patients with monomicrobial EfsB older than 18 years were studied retrospectively and from patients with a CIED, detailed information was collected and stored after ethical approval obtained from the Swedish Ethics Committee (2020–00,314). Data were collected by LA and were validated by AB and MR. Some of the episodes of the present cohort have been previously described in Berge et al. or Oldberg et al. [11, 13].

The definition of IE and CIED infection were from Blomström-Lundqvist et al. [3], a contemporary adaptation to patients with CIED, based on the modified Duke criteria [17]. The minor criterium predisposition to IE is use according to Dajani et al. [18]. All changes seen on TTE or TEE, indicating IE, was considered to be caused by infection due to the difficulty to differentiate from changes due to other causes [19]. All infections fulfilling the criteria for definite IE were referred to as CIED IE irrespective whether changes were found on the CIED or heart valves [3, 17].

An episode of monomicrobial EfsB was defined by the start of the clinical symptoms and signs in a patient resulting in blood culture taken showing growth of only E. faecalis, however, growth of coagulase negative staphylococci in one bottle was accepted. An episode was delimited by at least 7 days of effective treatment and clinical improvement. A later clinical condition resulting in a positive blood culture with growth of E. faecalis within the study period of 365 days is referred to as a “recurrent infection” or “recurrence” and was not included in the study as an episode. The expression “recurrent infection” or “recurrence” is used in this study since we cannot tell whether the infection was caused by the same bacterium, indicating relapse, or by another E. faecalis clone indicating a reinfection.

The primary endpoint was recurrent infection with EfsB during the observation period. Origin of infection and other focal infections caused by E. faecalis were defined as described [11]. Comorbidities were retrieved from registrations in the medical records prior to the episode and classified according to the Charlson index modified by Quan et al. [20, 21]. The NOVA and DENOVA scores were calculated as described [7, 8, 11].

The collection of the microbiological and clinical data of an episode was from 365 days before its start until 365 days after the first positive blood culture during that episode and the extracted parameters are listed in Supplementary material. The number of CIED carriers in the Region was taken from the Swedish Pacemaker and Implantable Cardioverter-Defibrillator Registry.

In the Region Skåne, 1087 episodes of EfsB were retrieved from January 2014 to November 2020. Of these, 654 were found to be monomicrobial. The criteria for inclusion as an episode in the study were fulfilled in 72 of the monomicrobial EfsB episodes. There were 9044 patients with CIED (average in 2014–2020 in the population) giving an approximate incidence of 1.1 monomicrobial EfsB episodes/1000 CIED/year (Fig. 1). The first column of Table 1 summarizes the characteristics of the cohort. In five episodes the patients were diagnosed with CIED IE, two with findings only on the CIED, two with findings on the CIED and the left side, and one with findings only on the left side of the heart. No patients were diagnosed with definite IE without having any structural findings. No patient with monomicrobial EfsB was diagnosed with a generator pocket infection (Table 1).

In the cohort of 72 episodes, four patients had the CIED extracted, three of whom were diagnosed with CIED IE. One patient with EfsB due to urinary tract infection (UTI) had the CIED extracted, without any IE diagnosis. The patient had a recent CIED implantation, 14 days prior to the EfsB, negative TEE, no signs of pocket infection, slow response to treatment without an explanation found, and a negative culture from the explanted CIED. The clinical characteristics of the four patients are shown, Supplementary table 1. All four had a new CIED implanted and were treated 37–62 days. None of these patients was given longtime suppressive antibiotic treatment. Clinical characteristics of those that were subjected to extraction of the CIED and those not subjected to extraction is shown in Table 1. In the 68 patients not subjected to extraction, two patients were diagnosed with IE, one of them had changes on the CIED. In both patients, the decision was taken not to extract the CIED based on the risks connected to the intervention. The patients were given 26 and 38 days of treatment in total and did not have a recurrent infection. One patient survived the study period and the other died during treatment for the IE, due to progressive cardiac failure caused by mitral valve regurgitation, massive embolization, and was not eligible for extraction of the CIED or cardiac surgery. Thirty-three (49%) of the patients were investigated with transthoracic echocardiography (TTE) and 16 (24%) with a transesophageal echocardiography (TEE) (Table 1). None of the patients who had their CIED extracted had a recurrent infection whereas seven recurrences were noted in 68 patients not subjected to extraction (the difference was not statistically significant, Table 1).

Clinical variables in patients, not subject to extraction, who had recurrent or did not have recurrent monomicrobial EfsB were compared. Univariate analysis identified community acquisition and predisposing condition to be significantly associated to recurrent monomicrobial EfsB (Table 2). Significantly more patients were subjected to TEE in the group that got a recurrent infection. No difference in the treatment time was seen between the groups (Table 2). None of the 68 patients was given longtime antibiotic suppressive therapy. Five patients were given more than 42 days of treatment and the longest duration of therapy was 104 days.

Of the seven patients with recurrent infections, four had two episodes and three patients had three or more episodes. The characteristics of patients with recurrent infections are shown (Table 3). The recurrent infection episodes were diagnosed at a median of 55 days (range 18–130 days) after the end of therapy for the preceding EfsB episode.

Three patients were diagnosed with UTI during the first episode. In one of the patients, a urinary tract malignancy was diagnosed during the recurrent infection and the patient died due to that on day 299.

In four patients, no origin of infection was diagnosed during the first episode. During the following episodes, one patient was diagnosed with spondylodiscitis (patient 1). Patient 4 was diagnosed with a CIED IE, during the second episode, utilizing PET-CT to indicate involvement of an aortic prosthetic valve and the aortic graft but not of the CIED. That patient was neither subjected to CIED extraction nor thoracic surgery due to the infection and was treated for CIED IE followed by lifelong suppressive antibiotic treatment. She survived during the study period. Patient 3, had a prosthetic valve and suffered three episodes of bacteremia without known focus. During the third episode, the CIED was extracted but with negative culture. The patient was given lifelong oral suppressive therapy and survived the study period.