Factors associated with cardiac implantable electronic device-related infections, New South Wales, 2016-21: a retrospective cohort study.

OBJECTIVES: To quantify the rate of cardiac implantable electronic device (CIED)-related infections and to identify risk factors for such infections. DESIGN: Retrospective cohort study; analysis of linked hospital admissions and mortality data. SETTING, PARTICIPANTS: All adults who underwent CIED procedures in New South Wales between 1 January 2016 and 30 June 2021 (public hospitals) or 30 June 2020 (private hospitals). MAIN OUTCOME MEASURES: Proportions of patients hospitalised with CIED-related infections (identified by hospital record diagnosis codes); risk of CIED-related infection by patient, device, and procedural factors. RESULTS: Of 37 675 CIED procedures (23 194 men, 63.5%), 500 were followed by CIED-related infections (median follow-up, 24.9 months; interquartile range, 11.2-40.8 months), including 397 people (1.1%) within twelve months of their procedures, and 186 of 10 540 people (2.5%) at high risk of such infections (replacement or upgrade procedures; new cardiac resynchronisation therapy with defibrillator, CRT-D). The overall infection rate was 0.50 (95% confidence interval [CI], 0.45-0.54) per 1000 person-months; it was highest during the first month after the procedure (5.60 [95% CI, 4.89-6.42] per 1000 person-months). The risk of CIED-related infection was greater for people under 65 years of age than for those aged 65-74 years (adjusted hazard ratio [aHR], 1.71; 95% CI, 1.32-2.23), for people with CRT-D devices than for those with permanent pacemakers (aHR, 1.46; 95% CI, 1.02-2.08), for people who had previously undergone CIED procedures (two or more v none: aHR, 1.51; 95% CI, 1.02-2.25) or had CIED-related infections (aHR, 11.4; 95% CI, 8.34-15.7), or had undergone concomitant cardiac surgery (aHR, 1.62; 95% CI, 1.10-2.39), and for people with atrial fibrillation (aHR, 1.33; 95% CI, 1.11-1.60), chronic kidney disease (aHR, 1.54; 95% CI, 1.27-1.87), chronic obstructive pulmonary disease (aHR, 1.37; 95% CI, 1.10-1.69), or cardiomyopathy (aHR 1.60; 95% CI, 1.25-2.05). CONCLUSIONS: Knowledge of risk factors for CIED-related infections can help clinicians discuss them with their patients, identify people at particular risk, and inform decisions about device type, upgrades and replacements, and prophylactic interventions.

Review of management priorities for invasive infections in people who inject drugs: highlighting the need for patient-centred multidisciplinary care.

There has been a global increase in the burden of invasive infections in people who inject drugs (PWID). It is essential that patient-centred multidisciplinary care is provided in the management of these infections to engage PWID in care and deliver evidence-based management and preventive strategies. The multidisciplinary team should include infectious diseases, addictions medicine (inclusive of alcohol and other drug services), surgery, psychiatry, pain specialists, pharmacy, nursing staff, social work and peer support workers (where available) to help address the comorbid conditions that may have contributed to the patient's presentation. PWID have a range of antimicrobial delivery options that can be tailored in a patient-centred manner and thus are not limited to prolonged hospital admissions to receive intravenous antimicrobials for invasive infections. These options include discharge with outpatient parenteral antimicrobial therapy, long-acting lipoglycopeptides (dalbavancin and oritavancin) and early oral antimicrobials. Open and respectful discussion with PWID including around harm reduction strategies may decrease the risk of repeat presentations with injecting-related harms.

Role of the Staphylococcus aureus Extracellular Loop of GraS in Resistance to Distinct Human Defense Peptides in PMN and Invasive Cardiovascular infections.

GraS is a membrane sensor in Staphylococcus aureus that induces mprF and dltABCD expression to alter the surface positive charge upon exposure to cationic human defense peptides (HDPs). The sensing domain of GraS likely resides in the 9-residue extracellular loop (EL). In this study, we assessed a hospital-acquired methicillin-resistant S. aureus (HA-MRSA) strain (COL) for the specific role of two distinct EL mutations: F38G (bulk) and D/35/37/41K (charged inversion). Activation of mprF by polymyxin B (PMB) was reduced in the D35/37/41K mutant versus the D35/37/41G mutant, correlating with reduced surface positive charge; in contrast, these effects were less prominent in the F38G mutant but still lower than those in the parent. These data indicated that both electrostatic charge and steric bulk of the EL of GraS influence induction of genes impacting HDP resistance. Using mprF expression as a readout, we confirmed GraS signaling was pH dependent, increasing as pH was lowered (from pH 7.5 down to pH 5.5). In contrast to PMB activation, reduction of mprF was comparable at pH 5.5 between the P38G and D35/37/41K point mutants, indicating a mechanistic divergence between GraS activation by acidic pH versus cationic peptides. Survival assays in human blood and purified polymorphonuclear leukocytes (PMNs) revealed lower survival of the D35/37/41K mutant versus the F38G mutant, with both being lower than that of the parent. Virulence studies in the rabbit endocarditis model mirrored whole blood and PMN killing assay data described above. Collectively, these data confirmed the importance of specific residues within the EL of GraS in conferring essential bacterial responses for MRSA survival in infections.

Lipid profile and prognosis in patients with coronary heart disease: a meta-analysis of prospective cohort studies.

BACKGROUND: This meta-analysis based on prospective cohort studies aimed to evaluate the associations of lipid profiles with the risk of major adverse cardiovascular outcomes in patients with coronary heart disease (CHD). METHODS: The PubMed, Embase, and Cochrane Library electronic databases were systematically searched for prospective cohort study published through December 2019, and the pooled results were calculated using the random-effects model. RESULTS: Twenty-one studies with a total of 76,221 patients with CHD met the inclusion criteria. The per standard deviation (SD) increase in triglyceride was associated with a reduced risk of major adverse cardiovascular events (MACE). Furthermore, the per SD increase in high-density lipoprotein cholesterol (HDL-C) was associated with a reduced risk of cardiac death, whereas patients with lower HDL-C were associated with an increased risk of MACE, all-cause mortality, and cardiac death. Finally, the risk of MACE was significantly increased in patients with CHD with high lipoprotein(a) levels. CONCLUSIONS: The results of this study suggested that lipid profile variables could predict major cardiovascular outcomes and all-cause mortality in patients with CHD.

Myocarditis.

Viral myocarditis remains a prominent infectious-inflammatory disease for patients throughout the lifespan. The condition presents several challenges including varied modes of clinical presentation, a range of timepoints when patients come to attention, a diversity of approaches to diagnosis, a spectrum of clinical courses, and unsettled perspectives on therapeutics in different patient settings and in the face of different viral pathogens. In this review, we examine current knowledge about viral heart disease and especially provide information on evolving understanding of mechanisms of disease and efforts by investigators to identify and evaluate potential therapeutic avenues for intervention.

No Such Thing as Chronic Q Fever.

Modern diagnostic methods enable clinicians to look beyond a diagnosis of chronic Q fever and discern whether patients instead have persistent focalized Coxiella burnetii infection(s). Use of these methods and development of criteria to define and treat such infections, especially cardiovascular infections, will improve the prognosis for patients previously thought to have chronic Q fever.

Nosocomial Infections in Adult Patients Supported by Extracorporeal Membrane Oxygenation in a Cardiac Intensive Care Unit.

The use of venoarterial (VA) extracorporeal membrane oxygenation therapy (ECMO) in patients admitted to cardiac intensive care units (CICU) has increased. Data regarding infections in this population are scarce. In this retrospective study, we analyzed the risk factors, outcome, and predictors of in-hospital mortality due to nosocomial infections in patients with ECMO admitted to a single coronary intensive care unit between July 2013 and March 2019 treated with VA-ECMO for >48 h. From 69 patients treated with VA-ECMO >48 h, (median age 58 years), 29 (42.0%) patients developed 34 episodes of infections with an infection rate of 0.92/1000 ECMO days. The most frequent were ventilator-associated pneumonia (57.6%), tracheobronchitis (9.1%), bloodstream infections (9.1%), skin and soft tissue infections (9.1%), and cytomegalovirus reactivation (9.1%). In-hospital mortality was 47.8%, but no association with nosocomial infections was found (p = 0.75). The number of days on ECMO (OR 1.14, 95% CI 1.01-1.30, p = 0.029) and noninfectious complications were higher in the infected patients (OR: 3.8 95% CI = 1.05-14.1). A higher baseline creatinine value (OR: 8.2 95% CI = 1.12-60.2) and higher blood lactate level at 4 h after ECMO initiation (OR: 2.0 95% CI = 1.23-3.29) were significant and independent risk factors for mortality. Conclusions: Nosocomial infections in medical patients treated with VA-ECMO are very frequent, mostly Gram-negative respiratory infections. Preventive measures could play an important role for these patients.

Diversity in Phenotypes Associated With Host Persistence and Systemic Virulence in Streptococcus sanguinis Strains.

Streptococcus sanguinis is a pioneer commensal species of dental biofilms, abundant in different oral sites and commonly associated with opportunist cardiovascular infections. In this study, we addressed intra-species functional diversity to better understand the S. sanguinis commensal and pathogenic lifestyles. Multiple phenotypes were screened in nine strains isolated from dental biofilms or from the bloodstream to identify conserved and strain-specific functions involved in biofilm formation and/or persistence in oral and cardiovascular tissues. Strain phenotypes of biofilm maturation were independent of biofilm initiation phenotypes, and significantly influenced by human saliva and by aggregation mediated by sucrose-derived exopolysaccharides (EPS). The production of H2O2 was conserved in most strains, and consistent with variations in extracellular DNA (eDNA) production observed in few strains. The diversity in complement C3b deposition correlated with the rates of opsonophagocytosis by human PMN and was influenced by culture medium and sucrose-derived EPS in a strain-specific fashion. Differences in C3b deposition correlated with strain binding to recognition proteins of the classical pathway, C1q and serum amyloid protein (SAP). Importantly, differences in strain invasiveness into primary human coronary artery endothelial cells (HCAEC) were significantly associated with C3b binding, and in a lesser extent, with binding to host glycoproteins (such as fibrinogen, plasminogen, fibronectin, and collagen). Thus, by identifying conserved and strain-specific phenotypes involved in host persistence and systemic virulence, this study indicates potential new functions involved in systemic virulence and highlights the need of including a wider panel of strains in molecular studies to understand S. sanguinis biology.

High-Sensitivity Troponin T: A Potential Safety Predictive Biomarker for Discharge from the Emergency Department of Patients with Confirmed Influenza.

The purpose of the study was to analyze the relationship between the high-sensitivity troponin T levels in patients with confirmed influenza virus infection and its severity determined by mortality during the care process. In addition, a high-sensitivity troponin T cut-off value was sought to allow us to a safe discharge from the emergency department. An analytical retrospective observational study was designed in which high-sensitivity troponin T is determined as an exposure factor, patients are followed until the resolution of the clinical picture, and the frequency of mortality is analyzed. We included patients ≥ 16 years old with confirmed influenza virus infection and determination of high-sensitivity troponin T. One hundred twenty-eight patients were included (96.9% survivors, 3.1% deceased). Mean and median blood levels of high-sensitivity troponin T of survivors were 26.2 ± 58.3 ng/L and 14.5 ng/L (IQR 16 ng/L), respectively, and were statistically different when compared with those of the deceased patients, 120.5 ± 170.1 ng/L and 40.5 ng/L (IQR 266.5 ng/L), respectively, p = 0.012. The Youden index using mortality as the reference method was 0.76, and the cut-off value associated with this index was 24 ng/L (sensitivity 100%, specificity 76%, NPV 100%, PPV 4%) with AUC of 88,8% (95% CI: 79.8−92.2%), p < 0.001. We conclude that high-sensitivity troponin T levels in confirmed virus influenza infection are a good predictor of mortality in our population, and this predictor is useful for safely discharging patients from the emergency department.

Mycobacterium Wolinskyi: A New Non-Tuberculous Mycobacterium Associated with Cardiovascular Infections?

Mycobacterium wolinskyi is a rapid-growth non-tuberculous mycobacterium. Twenty-one cases of M. wolinskyi infection have been described so far, more than half as cardiovascular or postoperative cardiothoracic infections. We report the case of a patient with a cardiovascular implantable electronic device infected by M. wolinskyi, successfully treated with device removal and antimicrobials.

Immune reconstitution inflammatory syndrome in Mycobacterium chimaera mediastinitis: When clinical judgment trumps imaging.

Mycobacterium chimaera has been described in postoperative cardiovascular procedures in patients after an outbreak of contaminated 3T heater-cooler units. Immune reconstitution inflammatory syndrome (IRIS) has been mostly reported in immunocompromised patients, especially HIV after starting therapy. Our case is a 52-year-old immunocompetent male who was diagnosed with M. chimaera mediastinitis a year after Type A dissection repair and was started on quadruple antimicrobial therapy. He clinically improved but 8 months into therapy he presented with a declining kidney function, pancytopenia, and hypercalcemia which after bone marrow and kidney biopsies were attributed to IRIS. Our patient's diagnosis spared him subsequent surgery. IRIS during the treatment of nontuberculous mycobacteria must be suspected even in immunocompetent patients as reaching the diagnosis is very helpful in preventing additional diagnostic and therapeutic measures.

Antibiotic Prophylaxis and Treatment in Early Cardiac Implantable Electronic Devices Infection.

BACKGROUND: Cardiac implantable electronic devices - PM, ICD, and CRTs- are well-proven life-sustaining and the ultimate destination for many heart conditions. Based on scientific evidence, there is a worldwide incremental increase in CIED implantations numbers. OBJECTIVE: Early infection of cardiac implantable electronic devices (CIED)- pacemaker (PM), implantable cardioverter-defibrillator (ICD), and cardiac resynchronization therapy (CRT)- is a growing health challenge. We examined the effectiveness of antibiotic prophylaxis and treatment of early infection of CIED in a single center. METHODS: This is a retrospective, single-center observational study. Data were collected from patients' records from July 2017-July, 2019. All Patients received intravenous ceftriaxone 2gm before incision, Gentamicin 120mg pocket irrigation, and oral Amoxicillin/Clavulanate for 5 days post-implantation. RESULTS: A 639 consecutive CIED implantations - PM (n=474, mean age, 64yr, female=49%), ICD (n=106, mean age 56yr, female=17%) and CRT (n=59, mean age, 54yr, female=20%)- were performed over 3years. The incidence of early infection was 1.9% (12 cases), female=41%. PM=5/474, ICD=5/106, and CRT=2/59. Three out of the 12 patients had total device explant due to pocket abscess; one PM had a generator changed; one ICD who had a pneumothorax, and the third one had reimplantation after ICD lead perforation. Nine cases were managed conservatively using saline dressing and oral Amoxicillin/Clavulanate, 3/9 patients developed a hematoma, 4/9 patients developed purulent suture line infection. None of them had infection recurrence on three months follow up. CONCLUSION: Early infection of CIED is a rare complication with multiple predisposing factors. Our protocol is reassurance and prompt initiation of management protocol to prevent and treat this issue's sequences.

Outcomes of Transvenous Lead Extraction for Cardiovascular Implantable Electronic Device Infections in Patients With Prosthetic Heart Valves.

BACKGROUND: Lead-related or valve-related endocarditis can complicate cardiovascular implantable electronic device (CIED) infection in patients with both CIED and prosthetic valves. The objective of this study was to determine the outcomes of transvenous lead extraction for CIED infection in patients with prosthetic valves. METHODS AND RESULTS: We retrospectively screened 794 transvenous lead extraction procedures, between September 1, 2001 and August 31, 2012, at Mayo Clinic to identify patients with prosthetic valves who underwent lead extraction for infection. Demographic, clinical, and follow-up characteristics were analyzed. In total, 51 patients (6%) met the study inclusion criteria, of whom 20 had pocket infection and 31 had lead-related or valve-related, or both, endocarditis or bloodstream infection (mean age, 67 [18] years). Staphylococcal species were the most common pathogens, including Staphylococcus aureus in 20 cases (39%) and coagulase-negative staphylococci in 19 cases (37%). Overall, 127 transvenous leads (median lead age, 52 months) were extracted. Of these leads, 123 (97%) were removed completely. The in-hospital mortality rate was 9.8%; no deaths were attributable to the extraction procedure. Ninety-five percent of patients who survived had no evidence of recurrent device-related or valve-related infection. CONCLUSIONS: Transvenous lead extraction seems safe and curative in patients with CIED infection and prosthetic valves. Cure of infection can be achieved in the majority of patients with complete CIED removal and antimicrobial therapy and without valve surgery.