VicRK and CovR polymorphisms in Streptococcus mutans strains associated with cardiovascular infections.

Introduction. Streptococcus mutans, a common species of the oral microbiome, expresses virulence genes promoting cariogenic dental biofilms, persistence in the bloodstream and cardiovascular infections.Gap statement. Virulence gene expression is variable among S. mutans strains and controlled by the transcription regulatory systems VicRK and CovR.Aim. This study investigates polymorphisms in the vicRK and covR loci in S. mutans strains isolated from the oral cavity or from the bloodstream, which were shown to differ in expression of covR, vicRK and downstream genes.Methodology. The transcriptional activities of covR, vicR and vicK were compared by RT-qPCR between blood and oral strains after exposure to human serum. PCR-amplified promoter and/or coding regions of covR and vicRK of 18 strains (11 oral and 7 blood) were sequenced and compared to the reference strain UA159.Results. Serum exposure significantly reduced covR and vicR/K transcript levels in most strains (P<0.05), but reductions were higher in oral than in blood strains. Single-nucleotide polymorphisms (SNPs) were detected in covR regulatory and coding regions, but SNPs affecting the CovR effector domain were only present in two blood strains. Although vicR was highly conserved, vicK showed several SNPs, and SNPs affecting VicK regions important for autokinase activity were found in three blood strains.Conclusions. This study reveals transcriptional and structural diversity in covR and vicR/K, and identifies polymorphisms of functional relevance in blood strains, indicating that covR and vicRK might be important loci for S. mutans adaptation to host selective pressures associated with virulence diversity.

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.

Candida Endocarditis in Patients with Candidemia: A Single-Center Experience of 14 Cases.

A retrospective, single-center analysis of 14 cases of Candida endocarditis (from 355 candidemia cases during the years 2012-2019) revealed a high in-hospital mortality (57.1%), a high proportion of healthcare-associated infections (13/14) and a high treatment preference for echinocandins. Transthoracic echocardiography and 18F-FDG PET/CT had a sensitivity of 54.5% and 57.1%, respectively. Patients were older than previously described and most patients with Candida endocarditis had persistent candidemia for ≥ 3 days despite antifungal therapy.

[Cardiovascular infections - recent progress and future challenges]. / Kardiovaskuläre Infektionen ­ ein Update.

Patients with previous endocarditis are at highest risk of infective endocarditis (266-fold compared to the general population) - preventive strategies are of particular importance in this patient subgroup. Patients with community-acquired E. faecalis bacteremia should undergo transesophageal echocardiography - according to a recent study the prevalence of endocarditis may be ≥ 20 % in this setting. Several smaller observational studies suggest an association between E. faecalis endocarditis and colorectal neoplasias - colonoscopy should therefore be offered to patients with newly diagnosed E. faecalis endocarditis (particularly in patients with unknown portal of entry). The non-inferiority of partial oral endocarditis treatment has been demonstrated in a selected subgroup of patients characterized by a stable condition/course, small vegetations and the absence of perivalvular complications. Uncritical and early oralisation of endocarditis treatment in patients not fulfilling these criteria may lead to adverse treatment outcomes. Approximately one out three patients with a left ventricular assist device (LVAD) will suffer from LVAD-related infections during the first year after implantation. Appropriate antibiotic treatment and adequate surgical debridement are essential management strategies.

Persistent Coxiella burnetii cardiovascular infection on Bentall-De Bono prosthesis.

Coxiella burnetii cardiovascular prosthetic infections are associated with high morbidity and mortality and represent a major health problem due to the lack of standardized management. We were confronted with a C. burnetii infection on Bentall-De Bono prosthesis characterized by a history of vascular infection with relapse that prompted us to screen for cases of C. burnetii on Bentall-De Bono vascular prosthesis monitored in our center. We screened patients between 1991 and 2019, from the French national reference center for Q fever. A microbiological criterion in addition to a lesional criterion was necessary to diagnose C. burnetii persistent vascular infection. Two thousand five hundred and eighty two patient were diagnosed with Coxiella burnetii infection and 160 patients with persistent C. burnetii vascular infection prosthesis, 95 of whom had a vascular prosthesis, including 12 with Bentall-De Bono prosthesis. Among patients with persistent C. burnetii prosthetic vascular infection, patients with Bentall-De Bono prostheses were significantly more prone to develop complications such as aneurysm, fistula, and abscess (62 versus 32%, two-sided Chi-square test, p = 0.04). All but one patient were treated with doxycycline and hydroxychloroquine for a mean (± standard deviation) period of 29.4 ± 13.6 months. Among the 12 patients, 5 had cardio-vascular complications, and 5 had prolonged antibiotherapy with doxycycline and hydroxychloroquine. Patients with C. burnetii vascular infection on Bentall-De Bono tend to be at high risk of developing complications (fistula, aneurysm, abscess, death). Surgery is rarely performed. Clinical, serological, and PET scanner imaging follow-up is recommended.

Dysregulation of the endothelium following Staphylococcus aureus infection.

The cardiovascular system is typically a sterile environment; however entry of a microorganism into the circulation can cause potentially life threatening cardiac and/or vascular disease. Staphylococcus aureus endothelial cell interactions are arguably the most important interactions in the pathogenesis of cardiovascular infection. These interactions can trigger cardiac valve destruction in the case of endocarditis, multi-organ dysfunction in the case of sepsis and coagulopathy. Here, we review the interactions between S. aureus and endothelial cells and discuss the implications of these interactions in the progression of cardiovascular infection.

Surgery for coincidental infected distal arch and abdominal aortic aneurysms.

A 63-year old man was admitted to hospital for the treatment of coincidental infected distal arch and abdominal aortic aneurysms. His haemodynamic state was unstable and uncontrollable because of septic shock. Group A beta-haemolytic Streptococcus pyogenes was the responsible microorganism. An emergent extra-anatomical bypass and complete aneurysm excisions were performed without extracorporeal circulation.

Prospective, multicenter study of ventricular assist device infections.

BACKGROUND: Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections. METHODS AND RESULTS: One hundred fifty patients scheduled for VAD implantation were enrolled (2006-2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073-0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001). CONCLUSIONS: This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

Primary hepatic actinomycosis presenting as purulent pericarditis with cardiac tamponade.

Cardiac tamponade constitutes an exceptional form of actinomycosis. We describe a case of primary hepatic actinomycosis presenting as purulent pericarditis with cardiac tamponade in a 20-year-old patient with previous esophagectomy and colonic interposition, successfully managed by computed tomography-guided percutaneous drainage and a prolonged course of antibiotic treatment. Actinomyces israelii was identified in the pericardial fluid by 16S rRNA gene sequencing. The literature on the simultaneous presentation of cardiac and hepatic actinomycosis is reviewed.

Pathogenesis of extrapulmonary manifestations of Mycoplasma pneumoniae infection with special reference to pneumonia.

Although pneumonia has been a hallmark of Mycoplasma pneumoniae infection, it has been revealed that this infection can cause a number of extrapulmonary manifestations in the absence of pneumonia. While the host immune response has been implicated in the pathomechanism of pneumonia, the pathomechanisms of extrapulmonary manifestations remain largely unknown. It is proposed in this review that extrapulmonary manifestations due to M. pneumoniae infection can be classified into three categories; the first is a direct type in which inflammatory cytokines locally induced by lipoproteins contained in the bacterial cell membrane must play a role, the second is an indirect type in which immune modulation such as autoimmunity through cross-reaction between the bacterial cell components and human cells must play a role, and the third is a vascular occlusion type in which vasculitis and/or thrombosis with or without systemic hypercoagulable state induced by the bacterium must play a role. Based on this classification, a literature review was carried out for extrapulmonary manifestations due to M. pneumoniae infection with special reference to pneumonia, including cardiovascular, dermatological, digestive organ, hematological/hematopoietic system, musculoskeletal, sensory organ, and urogenital tract manifestations. Consequently, most extrapulmonary manifestations due to M. pneumoniae infection can be reasonably classified into and explained by one of the three types of pathomechanisms mentioned above. Noticeably in this review, Kawasaki disease and infectious mononucleosis in association with M. pneumoniae infection, which are not unusual in Japan but have seldom been reported from Western countries, are included in the panel of extrapulmonary manifestations due to M. pneumoniae infection.

Cardiac infections: focus on molecular diagnosis.

The role of different types of infections in heart diseases is more important than commonly thought, with new and re-emerging infections (i.e., Mycobacterium tuberculosis). This review addresses the pathology of infective pericarditis, myocarditis, and endocarditis, mainly focusing on the significance of molecular techniques in the detection of infective agents. Molecular investigations represent important ancillary diagnostic tools and combined with other conventional approaches provide a more precise final diagnosis. A close collaboration and communication among cardiologists, cardiac surgeons, pathologists, and microbiologists is essential to ensure optimal diagnoses and management as well as a favorable impact on patient outcome.

Myocardial and aortal involvement in a case of disseminated infection with Fusarium solani after allogeneic stem cell transplantation: report of a case.

We describe a 57-year-old woman suffering from acute erythroblastic leukaemia. After the first course of high-dose Ara-C containing consolidation therapy, the patient developed multiple skin lesions on the left foot. A skin biopsy revealed a Fusarium infection. The lesions regressed under therapy with caspofungin and voriconazole. Leukaemia relapsed after 1 year and an allogeneic stem cell transplantation was performed for consolidation of leukaemia in second remission. Again, the patient developed macular skin lesions located on the trunk and the extremities with central pallor. Clinical examination showed fever, tachyarrhythmia and a systolic murmur. Fusarium spp. was cultured from blood samples. An antimycotic therapy with amphotericin B, voriconazole and posaconazole failed completely. The patient died in a septic shock with consecutive multiple organ failure. The autopsy (SN 1/06, Institute of Pathology, University of Greifswald) revealed a disseminated infiltration with Fusarium solani including myocardial, endocardial and aortal infection. The involvement of the cardiovascular system is uncommon in fusariosis and has not been described so far. This case confirms other reports describing the high mortality of fusariosis after allogeneic stem cell transplantation. A rapid diagnosis and antimycotics with higher activity against Fusarium spp. are necessary for successful therapy of this severe mould infection in the immunocompromised host.

Daptomycin and tigecycline: a review of clinical efficacy in the antimicrobial era.

There is a clinical need for new treatment options as a result of continued increase in the expression of resistance among bacterial pathogens. A number of compounds currently in development show promise. However, in some cases, there is concern that resistance may develop quickly to new compounds that are based on existing antimicrobial agents. Therefore, daptomycin, a novel lipopeptide with a unique mode of action, is of particular interest. It has rapid bactericidal activity against growing and stationary-phase bacteria, once-daily dosing regimen, and has a low potential for the development of resistance. It has been approved for the treatment of complicated skin and soft tissue infections caused by Gram-positive bacteria, and registration for treatment of infective endocarditis and bacteraemia is anticipated. Daptomycin is a welcome addition to the antimicrobial armamentarium for the treatment of bacterial infections. Tigecycline is a new glycyclcycline antimicrobial recently approved for use in the USA, Europe and elsewhere. While related to the tetracyclines, tigecycline overcomes many of the mechanisms responsible for resistance to this class. It is a novel broad spectrum glycylcycline with good activity against Gram-positive, many Gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need. It is efficacious in complicated skin and soft tissue infections and in intra-abdominal infections. This review aims to summarise the key clinical data of daptomycin and tigecycline which hold promise for widespread clinical use in the next decade.

Fungal infections of the heart: a clinicopathologic study of 50 autopsy cases.

Cardiac fungal infection (CFI) is relatively uncommon, but its incidence is increasing. It is associated with a grim prognosis, but some CFI patients can survive given an early diagnosis and aggressive therapy. To clarify the clinicopathologic features of CFI, a retrospective autopsy study was conducted. Among a total of 4396 autopsy cases collected over a 33-year period (1973-2005), 50 CFI patients (1.1%) were selected and studied clinicopathologically. The study subjects were 32 males and 18 females with a mean age of 65.5 years. Underlying diseases for CFI included solid malignant neoplasms (n=23), hematologic disorders (n=10), chronic renal diseases (n=7), liver diseases (n=5), diabetes mellitus (n=5), and other miscellaneous ailments. Antibiotics were given to 47 patients, while corticosteroids, antineoplastic drugs, and antifungal agents were used for 21, 12, and 12 patients, respectively. None of the patients was diagnosed to have CFI antemortem. Most patients (n=45) demonstrated multi-organ fungal infections with myocardial involvement. Causative pathogens were Candida (n=36), Aspergillus (n=9), Mucor (n=4), and Cryptococcus (n=1). Comparisons between previous CFIs (1973-1989) and recent CFIs (1990-2005) revealed an increasing proportion of non-candidal CFIs (p=0.004) in the latter. Our results point to the clinical importance of defining diagnostic criteria and therapeutic strategies for CFIs, especially for non-candidal CFIs.

Detection and serotype distribution of Actinobacillus actinomycetemcomitans in cardiovascular specimens from Japanese patients.

Actinobacillus actinomycetemcomitans, an important pathogen in periodontitis, has also been detected in cardiovascular tissues. Sixty heart valves were collected during valve replacement surgery from 60 patients (one from each), 10 were from patients with infective endocarditis (IE group) and 50 were from patients with other valvular diseases (non-IE group). In addition, 46 samples of aneurysmal tissue were taken from 46 patients with a thoracic or abdominal aneurysm (Aneurysm group, one from each). Dental plaque samples were taken from 54 of the patients, 31 in the IE and non-IE groups and 23 in the aneurysm group. First, the distribution of A. actinomycetemcomitans in all specimens was analysed using a polymerase chain reaction method, which resulted in a positive reaction in 33 (31.1%) of the cardiovascular specimens and 25 (46.3%) of the dental plaque samples. Next, using serotype-specific sets of primers, the serotype distribution of A. actinomycetemcomitans in the cardiovascular specimens and dental plaque samples was found to be significantly different compared to dental plaque samples from Japanese subjects reported previously.

Purulent pericarditis caused by group a streptococcus.

Purulent pericarditis is a rare disease that is most often caused by organisms such as Staphylococcus aureus, Streptococcus pneumoniae, viridans streptococci, Haemophilus influenzae, and anaerobic bacteria. We present an unusual case of purulent pericarditis caused by Streptococcus pyogenes, Lancefield group A streptococcus (GAS), and we provide a review of the literature.