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The Next Step: The Role of Metagenomic Next-Generation Sequencing in Microbial Detection of Culture-Negative Cardiovascular Infections.

Cardiovascular infections, including those that involve native and prosthetic heart valves, implantable cardiac devices, mechanical circulatory assist devices, and vascular grafts, are associated with significant morbidity and mortality risks. Optimal management of these complex infections requires pathogen-directed antimicrobial therapy. However, standard culture-based methods often fail to identify causative organisms due to prior antimicrobial use, infections due to fastidious organisms, or biofilm-associated infections. Emerging evidence suggests that microbial cell-free DNA (mcfDNA) and metagenomic testing can enhance pathogen detection, particularly in culture-negative cases. However, their results require careful clinical interpretation, often necessitating input from infectious diseases specialists. In this review, we examine published evidence regarding metagenomic testing for cardiovascular infections and its impact on patient care. We propose a framework for microbiological adjudication of mcfDNA results, introduce standardized definitions for clinical impact assessment, and provide guidance on integrating mcfDNA testing into diagnostic evaluation of patients with culture-negative cardiovascular infections.

Humans↗

Antimicrobial strategies for the prevention and treatment of cardiovascular infections.

As prosthetic cardiovascular devices become more common, the risk of complicating infections increases. The confluence of high-risk procedures, prosthetic material and antibiotic-resistant bacteria has made the management of these cardiovascular infections a challenge. A limited number of new antimicrobial agents have been introduced with activity against the resistant gram-positive organisms that are responsible for such problematic cardiovascular infections. Among these are the new agents quinupristin/dalfopristin and linezolid. In addition, several new therapeutic agents (e.g. daptomycin, lysostaphin and a Staphylococcus aureus vaccine) are in varying stages of clinical trials. Other strategies, such as the use of synergistic antibiotic combinations, the prophylactic eradication of bacterial colonization and the exploration of agents specifically targeting bacterial biofilms, are potentially valuable methods that are currently under investigation.

Anti-Bacterial Agents↗

The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome.

Cardiovascular infections due to Salmonella enterica are infrequently reported, so their clinical features, prognosis, and optimal treatment are not completely known. Mortality associated with aortitis and endocarditis caused by nontyphoidal Salmonella remains exceedingly high. In this review of cases of cardiovascular infections due to Salmonella enterica studied in 2 hospitals in Madrid, we tried to assess the clinical manifestations and the procedures leading to diagnosis in addition to treatment and outcome. To complete the spectrum of infections related to cardiovascular surgery, cases of postoperative mediastinitis, pericarditis, and infections associated with cardiac devices were also included.Twenty-three patients were reviewed: 11 had mycotic aneurysms; 7 had endocarditis; 2 had device-related infections; and 3 had pericarditis, mediastinitis, and infection of an arteriovenous fistula, respectively. The risk of endovascular infection in patients older than 60 years with bacteremia due to nontyphoidal Salmonella was 23%. Most patients with aortitis had risk factors for atherosclerosis, and 6 had preexisting atherosclerotic aortic aneurysms. All except 1 patient with endocarditis had underlying cardiac disorders. Acquired immunodeficiency disease (AIDS) was a major risk factor for salmonella bacteremia in 1 patient with aortitis and 1 with endocarditis. Fever, unremitting sepsis, "breakthrough" and relapsing bacteremia were the most common clinical findings. In addition, abdominal or thoracic pain and cardiac failure and pericarditis were common features in patients with aortitis and endocarditis respectively. Computed tomography (CT) scan, arteriography, and echocardiography were the main diagnostic tools. Mortality associated with mycotic aneurysms and endocarditis due to S. enterica was 45% and 28%, respectively. Thoracic aneurysms, rupture, and shock at the time of diagnosis were associated with increased mortality in patients with aortitis. In situ bypass grafting was successfully performed in most cases. After surgery, antimicrobial therapy was continued for 4-9 weeks. No relapses were observed after a mean follow-up of 64 months. Antimicrobial therapy alone or combined with valve replacement or excision of a ventricular aneurysm was successful treatment for most patients with salmonella endocarditis. Combined medical and surgical treatment was required for patients with mediastinitis and pericarditis, and patients with device-related infections needed removal of the complete device. Diagnosis of aortitis due to nontyphoidal Salmonella should be established as early as possible to reduce mortality. Patients older than 60 years who have positive blood cultures for Salmonella along with fever and back, abdominal, or chest pain should have an extensive workup for infective aortitis. Immediate bactericidal antimicrobial therapy should be started and a CT scan should be performed on an emergency basis. If a mycotic aneurysm is found, surgical resection should follow as soon as possible. Resection of the aneurysm with in situ bypass grafting is the procedure of choice. Postoperative antimicrobial therapy for 6-8 weeks seems enough to avoid relapses. Optimal treatment of patients with endocarditis occurring on ventricular aneurysms must include resection of the aneurysmal sac. Salmonella endocarditis can be successfully treated with antimicrobials alone. Valve replacement should be reserved for patients with cardiac failure or persisting sepsis, and for those who relapse after discontinuation of antimicrobial therapy.

Acquired Immunodeficiency Syndrome↗

Septicemia and cardiovascular infections in horses.

This article first reviews cardiovascular infections, including endocarditis, myocarditis, vasculitis, and pericarditis. It then addresses what is known at this stage about the effects of sepsis on the cardiovascular system. Some information is provided from current human literature to familiarize the reader with the diagnostics and therapeutics that may eventually be used in equine practice as well.

Animals↗

The immunocompromised host and risk for cardiovascular infection.

The risk factors for cardiovascular (CV) infections are related to the immunocompetence of the host, preexisting cardiac conditions, and exposure to infectious organisms. Immunocompromised states are related to defective physical and chemical barriers and/or alterations of immune organs, cells, and substances. There are many conditions, diseases, drugs, and therapies that are associated with immunocompromised states. In-dwelling central venous catheters, prosthetic valves/devices, cardiac lesions, and conditions that create turbulent blood flow increase risk for CV infections. An understanding of the immune response, risk factors for immunocompromise, and risk factors for CV infections helps guide the CV nurse's plan of care related to assessment and interventions for prevention, identification, and treatment of CV infections. Diagnosis, monitoring, and management challenges of the immunocompromised patient with infective endocarditis and myocarditis are presented.

Adolescent↗

Determinants of prognosis of COPD in the elderly: mucus hypersecretion, infections, cardiovascular comorbidity.

In this paper, the authors update the present knowledge about three risk factors for the prognosis of chronic obstructive pulmonary disease (COPD), which may be particularly relevant in elderly people: mucus hypersecretion, respiratory infections, and cardiovascular comorbidity. Chronic mucus hypersecretion (CMH) is a common respiratory symptom in old age, the relevance of which is analysed on the basis of data collected during the first three rounds of the Copenhagen City Heart Study. In subjects aged > or = 65 yrs, CMH was a strong predictor of the incidence of respiratory infections in a 10-yr follow-up period and it was also a strong predictor of death from COPD (relative risk=2.5). However, CMH was associated with consistently lower forced expiratory volume in one second (FEV1) values, but not with an accelerated decline of FEV1 in this sample of an elderly population. Acute respiratory infections (ARI) are extremely common at all ages, mostly mild self-limiting illnesses at a young age, but severe often fatal illnesses in elderly people already affected by a chronic disease such as COPD. This paper summarises the present knowledge about aetiology, pathology, prognostic relevance, and prevention of ARI. Furthermore, the areas in which further research is needed are listed. Clinical cohort studies clearly support the relevance of cardiovascular comorbidity for the short-and long-term prognosis of elderly subjects affected by severe COPD. In this paper, the recently demonstrated association between particulate air pollution and cardiovascular events is reported to suggest the presence of an extremely susceptible cluster of elderly subjects in the population identified by the copresence of chronic obstructive pulmonary disease and cardiovascular comorbidity.

Aged↗

Cardiovascular infection by Chlamydia pneumoniae is not related to apolipoprotein E genotype.

Chlamydia pneumoniae is detectable in the blood vessels of patients suffering from arteriosclerosis. Risk for arteriosclerosis is modulated by the apolipoprotein E (apoE) allele. We assessed the significance of the apoE genotype as a risk factor for vascular C. pneumoniae infection by determining the genotype of 30 coronary heart disease patients with PCR-proven C. pneumoniae infection of coronary artery tissue. The apoE genotype is not distinctly associated with an increased risk for vascular C. pneumoniae infection.

Apolipoproteins E↗

Cardiovascular infections: bacterial endocarditis of oral origin. Pathogenesis and prophylaxis.

The diagnosis infective endocarditis describes infection of the endocardial surface of the heart and indicates the presence of micro-organisms in the lesion. In most cases, the heart valves are affected, but the disease can also occur on septal defects or on the mural endocardium. The disease has been classified as acute or subacute based on the progression of the untreated disease. The acute form has a fulminant course with high fever and leukocytosis with death in less than 6 weeks. It is most often associated with infections caused by Staphylococcus aureus, Streptococcus pneumoniae or Streptococcus pyogenes. The subacute (death within 6 weeks to 3 months) and chronic (death more than 3 months) forms are mostly described together. These forms usually occur in patients with prior valvular disease and are characterized by a slow, indolent course with low-grade fever, night sweats, and weight loss. This form is usually caused by the viridansstreptococci. The above mentioned classification does not include the nonbacterial forms of endocarditis and enterococci often give rise to a disease intermediate between acute and subacute endocarditis. It is preferable to have a classification based on the micro-organism responsible since this classification has implications for the course followed and the appropriate antimicrobial agent to use. The clinical manifestations of the disease are so varied that they may be encountered in most medical subspecialities. Successful management is also dependent on the close cooperation of medical and dental disciplines.

Endocarditis, Bacterial↗

Cardiovascular infections in dogs: epizootiology, clinical manifestations, and prognosis.

Bacteremia in dogs was found to be more prevalent than suspected and Staphylococcus aureus, Escherichia coli, and beta-hemolytic streptococci were the most commonly isolated microbes. Administration of glucocorticoids was the most common predisposing cause of infections. Subacute and chronic bacteremia often followed integumentary infections such as abscesses, cellulitis, and infected wounds and was usually the result of gram-positive microbes. Peracute and acute bacteremia was associated with internal infections and was usually the result of E coli. Many dogs with bacteremia had unusual or multisystemic signs similar to those observed with immune-mediated diseases. Hypotension, tachycardia, and weakness were features of gram-negative bacteremia, whereas gram-positive bacteremia had more chronic signs and tended to develop into diskospondylitis. The adequacy of treatment, type of bacteremia, source of infection, and delay before treatment influenced the course of illness. Cephalosporins and gentamicin were most effective against all types of bacteremia.

Alkaline Phosphatase↗

Long-term survival in Hodgkin's disease relative impact of mortality, second tumors, infection, and cardiovascular disease.

PURPOSE: Despite dramatic improvements in the survival of patients with Hodgkin's disease attributable to advances in treatment over the past 30 years, concern for the risk of treatment-related deaths has led to a number of trials to evaluate reduction of therapy. The consequences of these trials on recurrence, development of long-term complications, and survival remain unknown. We determined the causes of death in a group of patients with pathologically staged and intensively treated Hodgkin's disease who were followed for long intervals. MATERIALS AND METHODS: Between April 1969 and December 1988, 794 patients with laparotomy-staged IA to IIIB Hodgkin's disease were treated with radiation therapy alone or combined radiation therapy and chemotherapy. There were 8700 person-years of follow-up (average, 10.95 person-years/ patient). Causes of mortality were grouped into the categories Hodgkin's disease, second malignant tumors, cardiovascular, infection, and miscellaneous. Age- and gender-specific incidence rates were multiplied by corresponding person-years of observation to obtain expected numbers of events. Observed-to-expected results were calculated by type of treatment, age at treatment, sex, and time after Hodgkin's disease. Absolute (excess) risk was expressed as number of excess cases per 10,000 person-years. RESULTS: Of 124 patients who died, 56 died of Hodgkin's disease, 36 of second malignant neoplasms, 15 of cardiac causes, 9 of infection, and 8 of miscellaneous causes. The 20-year actuarial survival rate for all patients in this study is 73%. Age 40 years or older, mixed cellularity/lymphocyte-depleted histologic type, and stage-III disease were adverse independent predictors of survival. The largest differences were seen by age. The 20-year actuarial rates of survival were 78%, 78%, and 46%, respectively, for patients aged 16 or less, 17 to 39, and 40 years or older at diagnosis. Hodgkin's disease diagnosed at age 40 or older was a significant risk factor for all causes of death. The use of combined chemotherapy/ radiotherapy was a significant risk factor for second tumor and infection-related mortality. The excess risk of death from all causes, including Hodgkin's disease, remained constant with time from treatment and was approximately 1.2% per year over the first 20 years. Deaths from Hodgkin's disease decreased with time from treatment, with no patients dying after 15 years. This decrease, combined with an increased excess mortality risk with time from other causes, especially second tumors, accounted for the constant excess mortality with time after Hodgkin's disease. CONCLUSIONS: Hodgkin's disease followed by second tumors, cardiac events, and infections remain the major causes of death after treatment of Hodgkin's disease. Our findings suggest the importance of both maintaining a high disease-free survival and reducing long-term complications in designing treatments of Hodgkin's disease.

Adolescent↗