Update on Cardiovascular Implantable Electronic Device Infections and Their Prevention, Diagnosis, and Management: A Scientific Statement From the American Heart Association: Endorsed by the International Society for Cardiovascular Infectious Diseases.

The American Heart Association sponsored the first iteration of a scientific statement that addressed all aspects of cardiovascular implantable electronic device infection in 2010. Major advances in the prevention, diagnosis, and management of these infections have occurred since then, necessitating a scientific statement update. An 11-member writing group was identified and included recognized experts in cardiology and infectious diseases, with a career focus on cardiovascular infections. The group initially met in October 2022 to develop a scientific statement that was drafted with front-line clinicians in mind and focused on providing updated clinical information to enhance outcomes of patients with cardiovascular implantable electronic device infection. The current scientific statement highlights recent advances in prevention, diagnosis, and management, and how they may be incorporated in the complex care of patients with cardiovascular implantable electronic device infection.

Nondental Invasive Procedures and Risk of Infective Endocarditis: Time for a Revisit: A Science Advisory From the American Heart Association.

There have been no published prospective randomized clinical trials that have: (1) established an association between invasive dental and nondental invasive procedures and risk of infective endocarditis; or (2) defined the efficacy and safety of antibiotic prophylaxis administered in the setting of invasive procedures in the prevention of infective endocarditis in high-risk patients. Moreover, previous observational studies that examined the association of nondental invasive procedures with the risk of infective endocarditis have been limited by inadequate sample size. They have typically focused on a few potential at-risk surgical and nonsurgical invasive procedures. However, recent investigations from Sweden and England that used nationwide databases and demonstrated an association between nondental invasive procedures, and the subsequent development of infective endocarditis (in particular, in high-risk patients with infective endocarditis) prompted the development of the current science advisory.

Management of Infective Endocarditis in People Who Inject Drugs: A Scientific Statement From the American Heart Association.

BACKGROUND: The American Heart Association has sponsored both guidelines and scientific statements that address the diagnosis, management, and prevention of infective endocarditis. As a result of the unprecedented and increasing incidence of infective endocarditis cases among people who inject drugs, the American Heart Association sponsored this original scientific statement. It provides a more in-depth focus on the management of infective endocarditis among this unique population than what has been provided in prior American Heart Association infective endocarditis-related documents. METHODS: A writing group was named and consisted of recognized experts in the fields of infectious diseases, cardiology, addiction medicine, and cardiovascular surgery in October 2021. A literature search was conducted in Embase on November 19, 2021, and multiple terms were used, with 1345 English-language articles identified after removal of duplicates. CONCLUSIONS: Management of infective endocarditis in people who inject drugs is complex and requires a unique approach in all aspects of care. Clinicians must appreciate that it requires involvement of a variety of specialists and that consultation by addiction-trained clinicians is as important as that of more traditional members of the endocarditis team to improve infective endocarditis outcomes. Preventive measures are critical in people who inject drugs and are cured of an initial bout of infective endocarditis because they remain at extremely high risk for subsequent bouts of infective endocarditis, regardless of whether injection drug use is continued.

Discriminative Ability and Reliability of Transesophageal Echocardiography in Characterizing Cases of Cardiac Device Lead Vegetations Versus Noninfectious Echodensities.

BACKGROUND: Approximately one-third of cases of cardiovascular implantable electronic device (CIED) infection present as CIED lead infection. The precise transesophageal echocardiographic (TEE) definition and characterization of "vegetation" associated with CIED lead infection remain unclear. METHODS: We identified a sample of 25 consecutive cases of CIED lead infection managed at our institution between January 2010 and December 2017. Cases of CIED lead infection were classified using standardized definitions. Similarly, a sample of 25 noninfected patients who underwent TEE that showed a defined lead echodensity during the study period was included as a control group. TEEs were reviewed by 2 independent echocardiologists who were blinded to all linked patient demographic, clinical, and microbiological information. Reported echocardiographic variables of the infected vs noninfected cases were compared, and the overall diagnostic performance was analyzed. RESULTS: Descriptions of lead echodensities were variable and there were no significant differences in median echodensity diameter or mobility between infected vs noninfected groups. Among infected cases, blinded echocardiogram reports by either reviewer correctly made a prediction of infection in 6 of 25 (24%). Interechocardiologist agreement was 68%. Sensitivity of blinded TEEs ranged from 31.5% to 37.5%. CONCLUSIONS: Infectious vs noninfectious lead echodensities could not be reliably distinguished on the basis of size, mobility, and general shape descriptors obtained from a retrospective blinded TEE examination without knowledge of clinical and microbiological parameters. Therefore, a reanalysis of criteria used to support a diagnosis of CIED lead infection may be warranted.

Detection of Pathogenic Bacteria From Septic Patients Using 16S Ribosomal RNA Gene-Targeted Metagenomic Sequencing.

BACKGROUND: Conventional blood cultures were compared to plasma cell-free DNA-based 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR)/next-generation sequencing (NGS) for detection and identification of potential pathogens in patients with sepsis. METHODS: Plasma was prospectively collected from 60 adult patients with sepsis presenting to the Mayo Clinic (Minnesota) Emergency Department from March through August 2019. Results of routine clinical blood cultures were compared to those of 16S rRNA gene NGS. RESULTS: Nineteen (32%) subjects had positive blood cultures, of which 13 yielded gram-negative bacilli, 5 gram-positive cocci, and 1 both gram-negative bacilli and gram-positive cocci. 16S rRNA gene NGS findings were concordant in 11. For the remaining 8, 16S rRNA gene NGS results yielded discordant detections (n = 5) or were negative (n = 3). Interestingly, Clostridium species were additionally detected by 16S rRNA gene NGS in 3 of the 6 subjects with gastrointestinal sources of gram-negative bacteremia and none of the 3 subjects with urinary sources of gram-negative bacteremia. In the 41 remaining subjects, 16S rRNA gene NGS detected at least 1 potentially pathogenic organism in 17. In 15, the detected microorganism clinically correlated with the patient's syndrome. In 17 subjects with a clinically defined infectious syndrome, neither test was positive; in the remaining 7 subjects, a noninfectious cause of clinical presentation was identified. CONCLUSIONS: 16S rRNA gene NGS may be useful for detecting bacteria in plasma of septic patients. In some cases of gram-negative sepsis, it may be possible to pinpoint a gastrointestinal or urinary source of sepsis based on the profile of bacteria detected in plasma.

D-index as a marker of bloodstream infections in patients with allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Neutropenia is a risk factor for development of infections; however, the direct effect of neutropenia on development of bloodstream infection (BSI) is not known. D-index, which is area between the neutrophil time curve and a neutrophil count of 0.5 × 109 /L, incorporates the combined effect of severity and duration of neutropenia. We aimed to evaluate whether D-index can be used as a marker for BSI in patients with allogeneic stem cell transplantation. METHOD: We conducted a retrospective cohort study of patients undergoing allogeneic stem cell transplantation between January 1, 2005, and September 30, 2015. The primary outcome measure was the development of BSI within 30 days of transplantation. RESULTS: A total of 714 patients were included in the study of whom 101 developed BSI. Patients with BSI had a significantly higher median D-index value compared with patients who did not have BSI (4990 vs. 3570, P < .001). As a marker, the performance of the D-index was similar to that of the duration of profound neutropenia (P = .18) and significantly better than the total duration of neutropenia (P = .001). CONCLUSION: The D-index performed better than the total duration of neutropenia as a marker for BSI in patients with allogeneic stem cell transplantation. There was no difference between D-index and, a more easily calculable indicator, duration of profound neutropenia.

Spinal Cord Stimulator Infection: Approach to Diagnosis, Management, and Prevention.

Spinal cord stimulation (SCS) is the most utilized invasive electrical neuromodulation treatment for the management of refractory chronic pain syndromes. Infection is one of the most dreaded complications related to SCS implantation and may prevent patients from receiving adequate pain treatment, adding to the initial cost and disability. Most SCS infections present as generator pocket infection. However, delay in diagnosis may lead to complications such as meningitis, epidural abscess, and/or vertebral osteomyelitis. Early recognition of SCS-related infections and associated complications is based on clinical suspicion, laboratory testing, and appropriate diagnostic imaging. While superficial surgical site infection following SCS implant may be treated with antibiotic therapy alone, deep infection involving implant warrants device removal to achieve cure. Duration of antimicrobial therapy depends on severity of clinical presentation and presence or absence of associated complications. Several preventive strategies can be incorporated in surgical practice to reduce the risk of SCS infection.

Molecular Approach to Diagnosis of Cardiovascular Implantable Electronic Device Infection.

BACKGROUND: Sonicate fluid (SF), a solution derived from vortexing and sonication of explanted cardiovascular implantable electronic devices (CIEDs), is a higher-yield specimen compared with swabs or tissues for culture-based detection of microorganisms associated with CIED infection. Despite this, SF culture fails to identify a causative organism in ~50% of cases. We aimed to evaluate the diagnostic performance of 16S ribosomal RNA gene (rRNA) polymerase chain reaction (PCR)/sequencing of SF and compare it with that of SF culture. METHODS: We identified 322 SF specimens from extracted CIEDs and reviewed clinical data for each patient. Subjects were classified as having or not having CIED infection. Cases were subcategorized as culture negative if no significant growth was reported from SF cultures and as culture positive if an organism was detected above predefined thresholds. 16S rRNA PCR/sequencing was performed, with the organisms identified reported according to Clinical and Laboratory Standards Institute guidelines for sequence data interpretation. RESULTS: A total of 278 SF samples corresponded to infected cases, of which 160 were culture positive and 118 culture negative. The remaining 44 were from noninfected cases, of which 2 were culture positive. Compared with SF culture, the sensitivity of 16S rRNA PCR/sequencing was higher (64% vs 57.5%, P = .003). 16S rRNA PCR/sequencing detected a potential pathogen in 28 of 118 culture-negative cases, identifying staphylococci in the majority (18/28). CONCLUSIONS: 16S rRNA PCR/sequencing has higher sensitivity to detect bacteria in SF from extracted CIEDs than does SF culture.

Preclinical evaluation of efficacy and pharmacokinetics of gentamicin containing extracellular-matrix envelope.

BACKGROUND: Using synthetic antibiotic-eluting envelope (ABE) is an effective intervention for prevention of cardiovascular implantable electronic device (CIED) infection. The biologic extracellular-matrix envelope (ECME), may offer potential advantages over the synthetic ABE. To further minimize the risk of infection, the ECME can be hydrated in gentamicin prior to CIED implantation. We aimed to evaluate the efficacy and pharmacokinetics (PK) of gentamicin containing ECME in an animal model. METHODS: For all experiments, the ECME was hydrated in gentamicin (40 mg/Ml) (treatment) for 2 min. In vitro antimicrobial efficacy against six different bacterial species was assessed. In vivo experiments were conducted using a rabbit model of CIED pocket infection. Serum and ECM gentamicin concentrations were measured. Five different organisms were inoculated into the device pocket of control (ECME hydrated in 0.9% saline) and treatment groups. Macroscopic appearance and colony forming units from CIED, ECME, and tissue were determined. RESULTS: No bacteria were recovered from any culture after 12 h of exposure to the gentamicin containing ECME. Serum gentamicin levels dropped below the limit of quantification at 15 h after implant. Gentamicin concentration in the ECME remained relatively stable for up to 7 days. Signs of clinical infection were observed in the control but not in the treatment group. In the presence of gentamicin, statistically significant reduction was demonstrated across all tested bacterial species. CONCLUSIONS: In this preclinical animal infection model, gentamicin containing ECME was highly effective in reducing bacterial burden in the implant pocket, while systemic exposure after implantation remained low.

Linezolid and fentanyl: An underrecognized drug-to-drug interaction.

WHAT IS KNOWN AND OBJECTIVE: Despite its frequent use in clinical practice, fentanyl's pro-serotonergic effects are underrecognized, especially in combination with linezolid. Life-threatening reactions can occur. CASE SUMMARY: We report a case of serotonin syndrome developed shortly after the initiation of linezolid in a 63-year-old patient in whom selective serotonin reuptake inhibitor therapy was discontinued for the duration of antibiotic therapy. However, fentanyl transdermal patch treatment was inadvertently continued. Noteworthy, 24 hours following discontinuation of linezolid, the patient experienced complete resolution of symptoms. WHAT IS NEW AND CONCLUSION: Fentanyl can increase the intrasynaptic release of serotonin through their effects on y-amino butyric acid and its phenylpiperidine chemical structure. We illustrate the importance of thorough medication reconciliation and review of all potential drug-to-drug interactions when indicating linezolid therapy to ensure patient safety. We believe that our case provides novel observations and insight that could help recognize similar cases in clinical practice.

Diagnostic evaluation and management of culture-negative cardiovascular implantable electronic device infections.

BACKGROUND: Culture-negative (CN) cardiovascular implantable electronic device (CIED) infections represent a significant management challenge for clinicians with no specific guidelines addressing this subgroup of patients. The aim of the current investigation is to report our institutional experience of CN CIED infections and propose a systematic approach to diagnostic evaluation and management of these complicated cases based on our observations. METHODS: We retrospectively screened all CIED infection cases at Mayo Clinic from 2005 through 2017. Using standardized criteria to define significant microbial growth, all patients with positive blood or pocket/device cultures were excluded. RESULTS: A total of 835 cases of CIED infection were screened, and of these, 47 (6%) met CN-CIED infection criteria. Majority of patients (77%) in this cohort had received antimicrobial therapy prior to device cultures with a median duration of 8 days. The most common presentation was device pocket infection (81%). All patients underwent device removal. Route of antibiotics was switched from oral to parenteral and spectrum of activity expanded from initial therapy in 23% of patients despite negative cultures. Majority of patients (80%) were dismissed on parenteral therapy. Adverse events attributed to intravenous antibiotic therapy were documented in 63% of the cases. No recurrence was reported and 6-month survival was 94.8%. CONCLUSIONS: Pocket and device cultures in suspected CIED infections may be negative due to preextraction oral antibiotics. However, frequently these patients are managed with broad-spectrum parenteral therapy postextraction.

Infective Endocarditis Involving Implanted Cardiac Electronic Devices: JACC Focus Seminar 1/4.

Cardiac implantable electronic device-related infective endocarditis (CIED-IE) encompasses a range of clinical syndromes, including valvular, device lead, and bloodstream infections. However, accurately diagnosing CIED-IE remains challenging owing in part to diverse clinical presentations, lack of standardized definition, and variations in guideline recommendations. Furthermore, current diagnostic modalities, such as transesophageal echocardiography and [18F]-fluorodeoxyglucose positron emission tomography-computed tomography have limited sensitivity and specificity, further contributing to diagnostic uncertainty. This can potentially result in complications and unnecessary costs associated with inappropriate device extraction. Six hypothetical clinical cases that exemplify the diverse manifestations of CIED-IE are addressed herein. Through these cases, we highlight the importance of optimizing diagnostic accuracy and stewardship, understanding different pathogen-specific risks for bloodstream infections, guiding appropriate device extraction, and preventing CIED-IE, all while addressing key knowledge gaps. This review both informs clinicians and underscores crucial areas for future investigation, thereby shedding light on this complex and challenging syndrome.

COVID-19 Pathogenesis and Clinical Manifestations.

In this review, we summarize the current knowledge about the virology, the host-pathogen interactions and pathogenesis of coronavirus disease 2019 in humans. We also describe the various clinical presentations of the disease including respiratory system and extrapulmonary manifestations.

Routine Donor and Recipient Screening for Mycoplasma hominis and Ureaplasma Species in Lung Transplant Recipients.

Background: Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum may cause post-transplant infections in lung transplant recipients. We evaluated routine pretransplant screening for these Mollicutes. Methods: We retrospectively reviewed records of lung transplant recipients at our tri-site institution from 01/01/2015 to 11/15/2019. M. hominis and/or Ureaplasma polymerase chain reaction (PCR) was performed on pretransplant recipient urine specimens and donor bronchial swabs at the time of transplantation. Development of Mollicute infection and hyperammonemia syndrome (HS) was recorded. Results: A total of 268 patients underwent lung transplantation during the study period, of whom 105 were screened with at least 1 Mollicute PCR. Twelve (11%) screened positive; 10 donors, 1 recipient, and 1 both. Among positive donors, 3 were positive for M. hominis, 5 for U. urealyticum, and 4 for U. parvum. Preemptive therapy included doxycycline, levofloxacin, and/or azithromycin administered for 1-12 weeks. Despite therapy, 1 case of M. hominis mediastinitis and 1 case of HS associated with Ureaplasma infection occurred, both donor-derived. Of those screened before transplant, cases with positive screening were more likely (P < 0.05) to develop Mollicute infection despite treatment (2/12, 17%) than those who screened negative (1/93, 1%). Conclusions: Pretransplant recipient urine screening had a low yield and was not correlated with post-transplant Mollicute infection, likely because most M. hominis and U. parvum/urealyticum infections in lung transplant recipients are donor-derived. Routine donor bronchus swab PCR for M. hominis, U. urealyticum, and U. parvum followed by preemptive therapy did not obviously impact the overall incidence of Mollicute infection or HS in this cohort.

Increased rates of blood culture contamination during the coronavirus disease 2019 pandemic.

We observed a higher rate of blood-culture contamination during the COVID-19 pandemic at our institution compared to a prepandemic period. Given the potential implications of blood contamination in antibiotic and diagnostic test utilization as well as added cost, it is imperative to continue efforts to minimize these episodes during the pandemic.

Metagenomic shotgun sequencing of blood to identify bacteria and viruses in leukemic febrile neutropenia.

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever. Blood samples underwent sample preparation, sequencing and analysis using the iDTECT® Dx Blood v1® platform (PathoQuest, Paris, France). Clinically relevant viruses or bacteria were detected in three cases each by metagenomic shotgun sequencing and blood cultures, albeit with no concordance between the two. Further optimization of sample preparation methods and sequencing platforms is needed before widespread adoption of this technology into clinical practice.

Lawsonella clevelandensis: an emerging cause of vascular graft infection.

Lawsonella clevelandensis, an emerging pathogen, was first described in 2016, and has been implicated in abdominal, breast and spinal abscesses in a limited number of cases. Being a fastidious organism, it is primarily identified with molecular methods. With the incorporation of broad-range PCR testing in clinical diagnostics, L. clevelandensis has been increasingly reported in the literature. We describe a case of a 65-year-old man who presented with bilateral psoas abscesses secondary to aorto-bi-iliac vascular graft infection with L. clevelandensis identified using 16S rRNA/PCR sequencing. The patient underwent surgical resection and replacement of infected graft, followed by 6 weeks of intravenous antibiotic therapy and then chronic suppression with doxycycline and cefadroxil. He was infection-free at last follow-up.

Antibiotic-Eluting Envelopes to Prevent Cardiac-Implantable Electronic Device Infection: Past, Present, and Future.

OBJECTIVE: Cardiac-implantable electronic device (CIED) infections are associated with significant morbidity and mortality. In this review, we describe the risk factors and pathogenesis of CIED infections and review the rationale and the evidence for the use of antibiotic-eluting envelopes (ABEs) in patients at increased risk for CIED infections. FINDINGS: The majority of CIED infections are caused by staphylococci that involve generator pocket and occur due to contamination of the device or the pocket tissues at the time of implantation. Clinical trials have shown that extending the duration of post-operative systemic antibacterial therapy is not beneficial in reducing CIED infection rate. However, ABEs that reduce device migration after implantation and provide sustained local delivery of prophylactic antibiotics at the pocket site, may provide benefit in reducing infection. Currently, there are two types of commercially available CIED envelope devices in the United States. The first ABE device (TYRX™, Medtronic Inc., Monmouth Junction, NJ) is composed of a synthetic absorbable mesh envelope that elutes minocycline and rifampin and has been shown to reduce CIED pocket infections in a large multi-center randomized clinical trial. The second ABE device (CanGaroo-G™, Aziyo Biologics, Silver Spring, MD) is composed of decellularized extracellular matrix (ECM) and was originally designed to stabilize the device within the pocket, limiting risk for migration or erosion, and providing a substrate for tissue ingrowth in a preclinical study. This device has shown promising results in a preclinical study with local delivery of gentamicin. Compared with artificial materials, such as synthetic surgical mesh, biologic ECM has been shown to foster greater tissue integration and vascular ingrowth, a reduced inflammatory response, and more rapid clearance of bacteria. CONCLUSIONS AND RELEVANCE: ABE devices provide sustained local delivery of antibiotics at the generator pocket site and appear beneficial in reducing CIED pocket infections. Given the continued increase in the use of CIED therapy and resultant infectious complications, innovative approaches to infection prevention are critical.