The main finding in this study is that IE is found in 10% of a population-based cohort of patients with CIED and NBHSB and extraction of the CIED was not performed unconditionally in cases of CIED IE. Further, a low rate of recurrent infections (5%) was encountered. Finally, three patients were diagnosed with IE during the recurrent infections, all related to an HVP.
The role of CIED in the pathogenesis of IE is debated. Whether CIED is a risk factor for IE, most likely depends on the species of the causing bacterium. In studies of patients with S. aureus bacteremia it was demonstrated that CIED was a risk factor for IE (7, 24) while in Enterococcus faecalis bacteremia, the presence of a CIED was not shown to be associated with IE (16). In a previous study of NBHSB (9), CIED was not significantly associated with IE (but with a p-value close to 0.05). In that study CIED covaried with HVP, which was shown to predict IE (unpublished data). In another NBHSB and IE study, CIED was associated to IE in univariable analysis but in multivariable analysis, an odds ratio of 0.66 was found (11). Chamat-Hedemand et al. described a large cohort of patients with patients with CIED and NBHSB but in the calculation resulting in CIED being a significant risk factor for IE, the patients with bacteremia with species addressed in this study only constitute a minority (approximately 30%).
In two alternative IE diagnostic criteria systems (1, 13), CIED is included among the different conditions constituting the predisposition minor criterium, resulting in that all patients in this cohort have that minor criterion. This change in the diagnostic criteria did not result in any profound differences in the rates of definite and possible IE. The data presented in this study neither indicate CIED to be a strong risk factor for IE in NBHSB nor contributes to result in a better performance for the diagnostic criteria if introduced as a minor criterion.
The results of this study were in line with the findings in several studies (9, 21, 25), showing that the risk of IE was diverse between groups of NBHS. S. sanguinis, S. bovis, and S. mutans are prone to cause IE, S. mitis and S. salivarius are connected to an intermediate risk, and S anginosus is unlikely to cause IE.
In only four patients (5%) in the entire cohort, the CIED was extracted and in patients fulfilling the criteria for definite IE, two out of 8 (25%) of the patients had the CIED extracted. None of the patients with IE had a recurrent infection that would indicate treatment failure. The guidelines recommend extraction of the CIED in cases diagnosed with CIED infection or CIED IE (6) but this was not performed in our cohort, challenging the necessity to follow the recommendations.
Four out of 71 patients (6%) not diagnosed with IE had a recurrent infection with NBHSB, and none was found to have CIED changes. However, three patients had suspected missed left sided HVP IE. Although beyond the scope of this study, the three missed HVP IE with recurrent infections illustrate the importance of continuing the evaluation of a patient with HVP, NBHSB, and a negative TEE. Such patients could be subjected to PET-CT, cardiac CT, repeated TEE, or followed clinically for early detection of relapse (6, 12, 13).
Based on our results, we suggest a management strategy that includes that all patients should be evaluated with TEE and, if negative, a PET-CT or possibly cardiac CT could be considered if the suspicion of CIED IE remains. The size of our study does not permit us to identify specific risk factors for IE in patients with CIED and thus the HANDOC score is suggested to be used to direct the management after a negative TEE. None of the diagnosed episodes of definite IE, nor any of the patients with a recurrent infection, had a negative HANDOC-score. Thus, we propose that the risk of IE would be negligible with both a negative TEE and a negative HANDOC score and further evaluation for IE could be omitted (Fig. 2). Another line of inquiry would be to test the hypothesis that TEE can be omitted in patients with CIED, NBHSB, and a negative HANDOC score. However, this suggestion has to be tested in future prospective studies.
Although this is the largest study cohort focusing on CIED-carrying patients with NBHSB, it has obvious limitations. The retrospective design and the far from complete evaluation using TEE (49%), make it possible that some patients with changes on the CIED could have been missed. Moreover, only four patients were subjected to PET-CT, also possibly contributing to under-diagnosis. Furthermore, despite the long follow up and thorough evaluation of the medical records, some patients could have died of an undiagnosed IE, another undiagnosed NBHS infection, or a recurrent infection. Finally, we do not know if the recurrent infections were true relapses or reinfection with another clone from the same group NBHS.
Despite the shortcomings, we believe that the observation of low frequency of CIED infections in NBHSB and the suggestion of a management algorithm has implications for the management of the patients.