This diagnostic accuracy review is the first to synthesize the available evidence on the diagnostic accuracy of traditional cultures and sonicated fluid cultures from patients with CIED infections. A pool of nine studies (1838 cultures), showed that the diagnostic sensitivity of cultures after sonication was approximately 0.756, which was significantly higher to that observed for traditional cultures 0.493. However, the use of sonication was also related with higher rates of false positive findings (23.5% vs 16.5%), but we also found that the use of a threshold for culture positivity could decrease false positive rates. Nevertheless, these findings should be interpreted with caution considering the low number of studies on the topic.

The bivariate method is the most statistically rigorous for meta-analysis of diagnostic accuracy studies [22,23,24]. However, one of the main challenges of bivariate meta-analysis is that often only few studies are available, which may lead to unreliable parameter estimates [25, 26]. Here, we have included nine studies, eight of them including information about de diagnostic accuracy for sonicated cultures. In this situation, data can be analyzed by using the univariate model for meta-analyses [27], but unreliable conclusions may occur. Another approach is to use a Bayesian model, where additional information is incorporated into the model using priors that can stabilize the analysis [25]. For this reason, the robustness of our findings was confirmed by three different statistical approaches, including the univariate model, as well as the bivariate random-effects meta-analysis and the Bayesian approach. Our results suggest that sonication increases the diagnostic accuracy in comparison with traditional cultures, independently of the statistical method used.

It is known that bacteria can colonize the implanted synthetic material of CIEDs without obvious clinical signs of infection [28]. This colonization may occur primarily by introducing the patient’s normal skin microbiota into the wound at the time of skin incision [29], or via the hands of those implanting or assisting the procedure [30]. The meta-regression results showed that the use of sonication increased false positive rates. This would be expected since most surgical wounds are polymicrobial in nature [31], and once the wound is colonized, almost immediately planktonic bacteria attach to the device and start biofilm formation [32]. Under this premise, sonication will facilitate removal of the microorganisms from the attached biofilm, increasing false positive rates in cases of device colonization. Despite a presumed high rate of device colonization at the time of implantation, clinical signs and symptoms of infection may not appear for weeks to months later in only a small portion of patients and, noticeably, most colonized devices will not develop an infection (0–7.5%) [14, 15, 33,34,35,36]. The progression from colonized medical devices to active infections represents a significant clinical challenge, especially in immunocompromised patients or those with recurrent infections. A comprehensive evaluation of sonication results, integrating patient history, risk factors, and clinical presentation, is essential to accurately differentiate colonization from infection. This distinction is crucial for guiding appropriate therapeutic decisions and avoiding overtreatment of contaminants, while ensuring early intervention for true infections. On the other hand, if contamination occurs during sonication process, which may or may not involve serial passages such as vortexing or centrifugation, positive results may represent false positive results. In these cases, working on aseptic conditions during all the passages required for the sonication method as well as using the right container appear crucial [37]. For these reasons, routine cultures should not be obtained in the absence of signs of infection in which device removal or exchange for other reasons (disfunction or upgrade) is performed.

One option to reduce false positive rates in patients with clinical diagnosis of CIED infection is the use of culture thresholds of positivity that could differentiate colonization from infection. The results obtained from the meta-regression showed that those studies using a threshold for positivity (≥ 2 CFU/ml), presented lower rates of false positive results. However, due to the low number of studies that included a threshold for positivity [16,17,18, 20, 21] these results must be confirmed by largest prospective studies, including different positivity criteria.

The meta-regression analysis also showed that “low quality” studies, according to QUADAS2 [10], were associated with lower rates of false positive results. This paradoxical result might result from the high number of patients included in the study performed by Garrigos et al. [21], which showed a very low number of false positive results in comparison with other studies. Notwithstanding, it should be confirmed by further research.

Most patients with CIED infections received antimicrobial therapy before device extraction, which may lead to negative culture results. Nevertheless, Oliva et al. [38] demonstrated that sonication improved the sensitivity of cultures even in patients that received previous antimicrobial therapy, except those patients that received more than 14 days of treatment before device removal. An interesting strategy to overcome this challenge is the combination of sonication with molecular methods. Thus, Garrigos et al. [21] showed how the use of a 16S ribosomal RNA (rRNA) polymerase chain reaction (PCR) increased the sensitivity to detect pathogens in CIEDs samples compared with sonicated fluids, suggesting that this molecular approach could be considered in cases of suspected CIED infections with negative sonicated cultures.

There are several limitations to this study. First, the available literature on sonication of CIED samples is still limited, and this is reflected by the small number of studies included in this review. Second, variations in the sample collection methods, transport, processing and the positivity criteria of cultures could explain the variable diagnostic accuracy of previously reported values. In this sense, it’s noteworthy that sonication has a non-standard methodology. Some research methods include only sonication of CIED samples [15], others use vortex and sonication (without centrifugation) [14], while others use vortex, sonication and centrifugation as a standard method [16]. Furthermore, the time and the frequency necessary for sonication are also unclear, with times ranging from one to five minutes, and frequencies from 20 to 42 kHz. Given the above, a standardization of processes during sonication is crucial to achieve a reproducible and reliable method for the diagnosis of CIED infections.

Another limitation that should be noted is the challenge of clinical diagnosis of CIED infections. The diagnosis includes findings from physical examination, advanced imaging modalities and laboratory and microbiology techniques [3, 4]. However, the inclusion of patients with CIED infections in these studies was based on the physical examination, mainly in local sign of infection, but there is a lack of detailed data about the clinical characteristics of patients. The potential role of previous antibiotic therapy in lowering (and influencing) the colony count is also an important factor that is not adequately addressed. Furthermore, there is no information of the type of swabs used in most of studies included. Only two studies [14, 20] specified that cotton swabs were used for microbiological studies.

In conclusion, this meta-analysis highlights the utility of sonication for the clinical diagnosis of CIED infections, showing higher sensitivity values in comparison with traditional cultures, but with higher false positive rates. However, a standardized sonication protocol is lacking, and a detailed investigation using a large number of studies would be of interest in elucidating the most appropriate procedures. Furthermore, future research should strive to improve the clinical diagnosis of CIED infections by combining sonication with molecular methods.