Insights into the enigma of oral streptococci in carcinogenesis.

SUMMARYThe genus Streptococcus consists of a taxonomically diverse group of Gram-positive bacteria that have earned significant scientific interest due to their physiological and pathogenic characteristics. Within the genus Streptococcus, viridans group streptococci (VGS) play a significant role in the oral ecosystem, constituting approximately 80% of the oral biofilm. Their primary role as pioneering colonizers in the oral cavity with multifaceted interactions like adherence, metabolic signaling, and quorum sensing contributes significantly to the complex dynamics of the oral biofilm, thus shaping oral health and disease outcomes. Perturbations in oral streptococci composition drive oral dysbiosis and therefore impact host-pathogen interactions, resulting in oral inflammation and representing VGS as an opportunistic pathogen. The association of oral streptococci in tumors across distant organs, spanning the esophagus, stomach, pancreas, and colon, illuminates a potential association between oral streptococci, inflammation, and tumorigenesis. This finding emphasizes the need for further investigations into the role of oral streptococci in mucosal homeostasis and their involvement in carcinogenesis. Hence, here, we review the significance of oral streptococci in biofilm dynamics and how the perturbation may impact mucosal immunopathogenesis in the context of cancer, with a vision of exploiting oral streptococci for cancer intervention and for the development of non-invasive cancer diagnosis.

The epidemiological and clinical features of odontogenic infective endocarditis.

Antibiotic prophylaxis (AP) of infective endocarditis (IE) in dental practice is a controversial topic. We evaluated the characteristics of the odontogenic IE and assessed the practice and sources of information pertaining to the topic utilized by the Croatian dentists. We conducted a retrospective review of consecutive medical charts of adult patients with IE, admitted to the University Hospital for Infectious Diseases in Zagreb, Croatia, between January 2007 and December 2017. In addition, a cross-sectional, self-reporting questionnaire survey was conducted with participation of 348 Croatian dentists. Of the 811 admissions for suspected IE (40.3% of all Croatian and 92.1% of all Zagreb hospitals), 386 patients were confirmed as definite IE: 68 with odontogenic IE and 318 with IE of other origin. Their first hospital admissions were analyzed. Definite odontogenic IE was defined as a positive echocardiographic result in conjunction with two separate positive blood cultures showing exclusive oral cavity pathogen or Streptococcus viridans associated with current or recent (< 1 month) dental, periodontal, or oral cavity infection. The annual number of new odontogenic IE patients appeared constant over time. In 91.2% of the cases, odontogenic IE was not preceded by a dental procedure; poor oral health was found in 51.5% of patients, and 47.1% had no cardiac condition that increases the IE risk. In-hospital mortality was 5.1% with conservative treatment and 4.5% with cardiac surgery and was much lower for odontogenic IE than in non-odontogenic IE (14.6% and 34.4%, respectively). An increasing number of admissions for non-odontogenic IE were observed in parallel with an increasing number of staphylococcal IE. Surveyed dentists (500 invited, 69.6% responded) were aware of the AP recommendations, but were largely reluctant to treat patients at risk. In people with poor oral health, AP should be considered regardless of cardiac risk factors. Improvement of oral health should be the cornerstone of odontogenic IE prevention.

Clinical Significance of Isolates Known to Be Blood Culture Contaminants in Pediatric Patients.

Background and objectives: The objective of this study was to investigate the clinical significance of isolates from blood stream infection known to be blood culture contaminants in pediatric patients. Materials and Methods: Microbiological reports and medical records of all blood culture tests issued from 2002 to 2012 (n = 76,331) were retrospectively reviewed. Evaluation for potential contaminants were done by reviewing medical records of patients with the following isolates: coagulase-negative Staphylococcus, viridans group Streptococcus, Bacillus, Corynebacterium, Micrococcus, Aerococcus, and Proprionibacterium species. Repeated cultures with same isolates were considered as a single case. Cases were evaluated for their status as a pathogen. Results: Coagulase-negative Staphylococcus had clinical significance in 23.8% of all cases. Its rate of being a true pathogen was particularly high in patients with malignancy (43.7%). Viridans group Streptococcus showed clinical significance in 46.2% of all cases. Its rate of being a true pathogen was similar regardless of the underlying morbidity of the patient. The rate of being a true pathogens for remaining isolates was 27.7% for Bacillus and 19.0% for Corynebacterium species. Conclusions: Coagulase-negative Staphylococcus and viridans group Streptococcus isolates showed high probability of being true pathogens in the pediatric population, especially in patients with underlying malignancy.

The clinical impact of patients with bloodstream infection with different groups of Viridans group streptococci by using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

The accuracy of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for identifying viridans group streptococcus (VGS) was improving. However, the clinical impact of identifying VGS had not been well recognized. Our study had comprehensively studied the clinical manifestations and outcome of VGS blood stream infection by using MALDI-TOF MS for identification.This retrospective study enrolled 312 adult patients with a monomicrobial blood culture positive for VGS. Blood culture was examined through MALDI-TOF MS.The most common VGS species were the Streptococcus anginosus group (38.8%) and Streptococcus mitis group (22.8%). Most species showed resistance to erythromycin (35.6%), followed by clindamycin (25.3%) and penicillin (12.5%). Skin and soft tissue infection and biliary tract infection were significantly related to S. anginosus group bacteremia (P = .001 and P = .005, respectively). S. mitis group bacteremia was related to infective endocarditis and bacteremia with febrile neutropenia (P = .005 and P < .001, respectively). Infective endocarditis was also more likely associated with S. sanguinis group bacteremia (P = .009). S. anginosus group had less resistance rate to ampicillin, erythromycin, clindamycin, and ceftriaxone (P = .019, <.001, .001, and .046, respectively). A more staying in intensive care unit, underlying solid organ malignancy, and a shorter treatment duration were independent risk factors for 30-day mortality. This study comprehensively evaluated different VGS group and their clinical manifestations, infection sources, concomitant diseases, treatments, and outcomes. Categorizing VGS into different groups by MALDI-TOF MS could help clinical physicians well understand their clinical presentations.

In vitro effects of commercial mouthwashes on several virulence traits of Candida albicans, viridans streptococci and Enterococcus faecalis colonizing the oral cavity.

Oral microbiota consists of hundreds of different species of bacteria, fungi, protozoa and archaea, important for oral health. Oral mycoses, mostly affecting mucosae, are mainly caused by the opportunistic pathogen Candida albicans. They become relevant in denture-wearers elderly people, in diabetic patients, and in immunocompromised individuals. Differently, bacteria are responsible for other pathologies, such as dental caries, gingivitis and periodontitis, which affect even immune-competent individuals. An appropriate oral hygiene can avoid (or at least ameliorate) such pathologies: the regular and correct use of toothbrush, toothpaste and mouthwash helps prevent oral infections. Interestingly, little or no information is available on the effects (if any) of mouthwashes on the composition of oral microbiota in healthy individuals. Therefore, by means of in vitro models, we assessed the effects of alcohol-free commercial mouthwashes, with different composition (4 with chlorhexidine digluconate, 1 with fluoride, 1 with essential oils, 1 with cetylpyridinium chloride and 1 with triclosan), on several virulence traits of C. albicans, and a group of viridans streptococci, commonly colonizing the oral cavity. For the study here described, a reference strain of C. albicans and of streptococci isolates from pharyngeal swabs were used. Chlorhexidine digluconate- and cetylpyridinium chloride-containing mouthwashes were the most effective in impairing C. albicans capacity to adhere to both abiotic and biotic surfaces, to elicit proinflammatory cytokine secretion by oral epithelial cells and to escape intracellular killing by phagocytes. In addition, these same mouthwashes were effective in impairing biofilm formation by a group of viridans streptococci that, notoriously, cooperate with the cariogenic S. mutans, facilitating the establishment of biofilm by the latter. Differently, these mouthwashes were ineffective against other viridans streptococci that are natural competitors of S. mutans. Finally, by an in vitro model of mixed biofilm, we showed that mouthwashes-treated S. salivarius overall failed to impair C. albicans capacity to form a biofilm. In conclusion, the results described here suggest that chlorhexidine- and cetylpyridinium-containing mouthwashes may be effective in regulating microbial homeostasis of the oral cavity, by providing a positive balance for oral health. On the other side, chlorhexidine has several side effects that must be considered when prescribing mouthwashes containing this molecule.

Bacteria endocarditis consolidation with vertebra bone tuberculosis: a case report.

BACKGROUND: The clinical features of bacteria endocarditis became atypical when consolidated with other conditions such as tuberculosis (TB). Especially, the symptoms of bacteria endocarditis (BE) which were hidden behind the TB fever often lead to misdiagnosis and missed diagnosis. CASE PRESENTATION: A 56-year-old male with thoracic vertebra bone TB history presented with low-grade fever, shortness of breath and cardiac souffle. After conventional antibiotic therapy and strengthen anti-tuberculosis treatment condition did not be improved. Further inspection, there were bacteria endocarditis with the vegetation across the mitral valve. But the other valves were not involved. He was treated with intravenous penicillin for 4 weeks in all including during surgery, and following with oral antibiotic for another 2 weeks. The patient improved clinically eventually. CONCLUSION: It is the first reported case of isolated thoracic vertebra tuberculosis with valve endocarditis caused by streptococcus viridans and was successfully managed by combination therapy of internal medicine and surgery. It was suggested in tuberculosis patients, the possibility of bacterial endocarditis should be considered when came into fever and unexplained cardiac soufflé (in tuberculosis patients).

Clinical features of infective endocarditis: comparison between the 1990s and 2000s.

BACKGROUND: The circumstances surrounding infective endocarditis (IE) are under constant change due to an increase in drug-resistant organisms, a decrease in rheumatic valve disease, progress in surgical treatment, and aging society. The purpose of this study was to compare clinical features of IE between the 1990s and 2000s and to elucidate the determinants of death or clinical event. METHODS: All hospital admission records between January 1990 and December 2009 were retrospectively analyzed. The definition of IE was based on modified Duke criteria. Clinical presentation, blood culture, laboratory results, and echocardiography findings were compared between the 1990s and 2000s. RESULTS: There were 112 patients with definite or probable IE according to modified Duke criteria. The most frequent organism causing IE was Streptococcus viridians both in the 1990s and 2000s. The determinants of in-hospital death were hemodialysis and congestive heart failure. The in-hospital mortality of IE was 5.4% in the 1990s and 13.3% in the 2000s. Composite events of in-hospital death and central nervous system disorders were significantly higher in the 2000s compared with the 1990s. CONCLUSION: The most frequent causative organism of IE was S. viridians, both in the 1990s and 2000s. Independent predictors of in-hospital mortality in IE were hemodialysis and congestive heart failure.

[Apoptogenic activity of microbes-associants during Epstein-Barr virus infection].

AIM: Study apoptogenic activity of-microbes-associants during Epstein-Barr virus infection (EBVI) on the model of mice peritoneal macrophages in vitro. MATERIALS AND METHODS: Evaluation of apoptosis induced by bacteria isolated from EBVI patients was carried out by characteristic morphological changes of macrophages in smears stained by May-Grunwald with additional staining by Romanowsky-Giemsa. RESULTS: All the EBVI microbes-associants were established to have apoptogenic activity, however, the highest pathogenic potential was noted in Streptococcus pyogenes. CONCLUSION: The presence of apoptogenic activity in bacterial microflora accompanying EBVI against immune system cells could serve as means of their survival and be the pathogenetic basis for prolonged persistence in the organism.

Two weeks of postsurgical therapy may be enough for high-risk cases of endocarditis caused by Streptococcus viridans or Streptococcus bovis.

The duration of antimicrobial therapy after surgery for infective endocarditis (IE) is controversial. A short course of postsurgical therapy is currently accepted only for patients with negative valve culture. We performed a retrospective (1994-2008) analysis of patients who underwent surgery for IE in our hospital and had a high risk of complications ( one of more of the following: <2 weeks of antibiotic treatment before surgery; embolism; perivalvular extension; and positive valve culture) to compare outcomes of patients who received short-course antimicrobial therapy (SAT) (median 15 days) or long-course antimicrobial therapy (LAT) (median 32 days), irrespective of the results of valve culture. Our endpoints included length of hospital stay, renal and hepatic failure, relapse, re-infection, and mortality rates 1 year after surgery. During the study period, 140 patients underwent surgery for IE (valve replacement, 87.9%). Of these, 133 fulfilled the high-risk group criteria and 92 completed the antimicrobial schedule. Comparison of patients receiving SAT (37) and LAT (55) showed that the SAT group had a shorter length of hospital stay (29 vs. 40 days, p 0.01), and a trend towards lower frequency of renal failure (5.4% vs. 18.2%, p 0.11) and hepatic failure (5.4% vs. 9.1%, p 0.69), whereas mortality (5.4% vs. 3.6%, p 1), relapse (0% vs. 1.8%, p 1) and re-infection (5.4% vs. 3.6%, p 1) rates were similar between both groups. Multivariate analysis showed that IE caused by Streptococcus viridans or Streptococcus bovis was independently associated with SAT. Postsurgical SAT is safe, especially when IE is caused by Streptococcus viridans or Streptococcus bovis, even in patients at high risk of complications.

Population structure and characterization of viridans group streptococci (VGS) including Streptococcus pneumoniae isolated from adult patients with cystic fibrosis (CF).

A study was undertaken to examine the population structure of viridans group streptococci (VGS) in the sputum of adult patients with cystic fibrosis (CF). Freshly expectorated sputa (n=58) from 45 adult CF patients were examined by selective conventional culture on Mitis-Salivarius agar and yielded 190 isolates of VGS. Sequence analyses of the rpnB and 16-23S rRNA ITS genes identified these isolates to belong to 12 species of VGS and included S. anginosus, S. australis, S. cristatus, S. gordonii, S. infantis, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. pneumoniae, S. salivarius and S. sanguinis. The most frequently VGS organism isolated was S. salivarius (47/190; 24.7%), followed by S. mitis (36/190; 19%), S. sanguinis (25/190; 13.2%), S. oralis (20/190; 11.0%), S. pneumoniae (19/190; 10.0%), S. parasanguinis (16/190; 8.4%), S. infantis (11/190; 5.8%), S. gordonii (7/190; 3.7%), S. anginosus (4/190; 2.1%), S. cristatus (2/190; 1.1%), S. australis (1/190; 0.5%), S. mutans (1/190; 0.5%) and S. agalactiae (1/190; 0.5%). All, but four, patients harboured at least one VGS species, which ranged from one to five streptococcal species, with a mean of 2.85 species per patient. There was no clonality at the subspecies level employing ERIC RAPD PCR. Antibiotic susceptibility was determined by Minimum Inhibitory Concentration (MIC) testing against penicillin, erythromycin and ciprofloxacin. Overall, resistance to penicillin with all VGS was 73/190 (38.4%) and 167/190 (87.9%) for erythromycin. With regard to ciprofloxacin, 27/190 (14.2%) were fully resistant, whilst a further 21/190 (11.1%) showed intermediate resistance, which equated to approximately three quarters (74.7%) of isolates being fully sensitive to this agent. In addition, as a comparator control population, we examined antibiotic susceptibility, as above, in a non-CF population comprising 12 individuals (50 VGS isolates), who were not receiving chronic antibiotics. In comparison, 8% and 38% of VGS isolates from non-CF individuals were resistant by disk susceptibility testing to penicillin and erythromycin, respectively. None of the non-CF VGS organisms were resistant to ciprofloxacin, but 42% showed intermediate resistance.

Results of annular reconstruction with a pericardial patch in active infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: Annular reconstruction in active infective endocarditis (IE) is technically difficult, and results in a high mortality and morbidity. The study aim was to determine the midterm results of annular reconstruction with a pericardial patch in active IE. METHODS: A total of 57 operations was performed in 56 patients (38 men, 18 women; mean age 48.3 +/- 16.9 years) with active IE. Twenty-five cases (44%) were included in whom the preoperative NYHA class was III or IV. RESULTS: Bovine pericardium was used in 52 cases, autologous pericardium in three, and bovine + autologous pericardium in two. The aortic annulus was reconstructed in 18 cases, combined with aortomitral continuity in 13 cases, and both aortic and mitral annulus were combined with aortomitral continuity in three cases. The mitral annulus was reconstructed in 21 cases, and the complete cardiac skeleton was reconstructed in one case. There were three operative deaths. Postoperative complications included reexploration due to bleeding in two cases, mediastinitis in one case, complete atrioventricular block in five cases, and cerebral hemorrhage in six cases. The follow up was 93% complete (52/56); the mean duration of follow up was 45.1 +/- 32.6 months (range: 2-138 months). There were two late deaths, at three and eight months postoperatively. Endocarditis recurred five times in four patients. Re-do surgery was performed in four cases due to endocarditis recurrence in three patients at two, three, and 29 months after surgery, respectively, and to a pseudoaneurysm in one patient at one month postoperatively. The mean survival at two years was 91 +/- 3.9%; the two-year event-free survival was 82 +/- 5.4%. CONCLUSION: Annular reconstruction with a pericardial patch in active IE can be performed safely, and showed good durability at the mid-term follow up examination.

Dual ANCA positivity in subacute bacterial endocarditis.

Nine cases of subacute bacterial endocarditis (SBE) associated with anti-PR3 ANCA have been described in the literature to date. We describe 2 cases of SBE associated with dual ANCA positivity (anti-PR3 and anti-MPO ANCA.) To our knowledge, these are the first such reported cases. One case was associated with cutaneous vasculitis, and the second with predisposing factors for SBE. ANCA titers resolved or decreased in both during initial corticosteroid therapy for suspected vasculitis. Follow-up of these patients revealed no evidence of the common ANCA associations such as Wegener granulomatosis. Rheumatologists, if aware of ANCA association with SBE, can avoid inappropriate immunosuppressive treatments.

"Full house" proliferative glomerulonephritis: an unreported presentation of subacute infective endocarditis.

A severely ill 65-year-old man presented with symptoms of shortness of breath, edema and vasculitidic purpura over his lower extremities. He had severe mitral regurgitation which had not been surgically treated. Hematologic examination demonstrated leukocytosis with profound anemia. Other blood tests revealed impaired renal function, hypoalbuminemia, hypocomplementemia and mixed-type cryoglobulinemia. Urinalysis showed proteinuria, hematuria and pyuria, typical of a nephritic sediment. Renal biopsy indicated diffuse proliferative glomerulonephritis and a "full house" deposition in immunofluorescence study (positive for C3, C4, C1q, IgG, IgA and IgM), resembling the pathologic findings in class IV lupus nephritis. Although subacute bacterial endocarditis was initially suspected owing to a history of a predisposing valvular heart disease, probable vegetation shown by cardiac sonography and a clinical picture suggestive of a chronic infection, it was thought unlikely due to the entire afebrile course and initial sterile blood cultures. However, the blood cultures repeated 2 weeks after admission grew 3 sets of viridans streptococci. Following a course of penicillin and gentamicin treatment, his renal function, anemia and abnormal urine sediments improved gradually. Diffuse proliferative glomerulonephritis is well known to occur in infective endocarditis. However, the "full house" immunostaining in immunofluorescence study has never been reported. This case adds a new entity to the differential diagnosis of "full house" immune complex-related glomerulonephritis and exemplifies the need to maintain a high index of suspicion for underlying infectious disorders when facing glomerulonephritic or vasculitic syndrome.

Infective endocarditis caused by nutritionally variant streptococci.

BACKGROUND: Infective endocarditis caused by nutritionally variant streptococci (NVS) has a higher rate of complications than endocarditis caused by other streptococci. The bacteriologic failure rate and the mortality rate are high. However, current knowledge on this disease derives from previous patient data from 1987. Recent case reports showed successful antibiotic treatment in the absence of surgery. Here, we report the clinical outcome of infective endocarditis caused by NVS in our hospital. METHODS: Data were collected by retrospective case note review. RESULTS: Between 1996 and 2006, there were 8 cases of NVS endocarditis: 4 patients had infection caused by Abiotrophia defectiva and 4 patients had infection caused by Granulicatella adiacens. Vegetation size on echocardiography was large (10 mm) in 7 patients, and embolization occurred in 3 patients. Patients were treated with penicillin and gentamicin initially, and 3 of them were successfully treated. The regimens were shifted to vancomycin, teicoplanin, or cefotaxime in 2 cases because of poor therapeutic responses. A total of 4 patients underwent early valve replacement successfully because of severe heart failure. Three patients underwent mitral valve repair successfully at the time of 2, 4, and 7 months after the diagnosis of endocarditis. The valve cultures at surgery were negative. There was no mortality or relapse. The bacteriologic failure rate was zero. CONCLUSIONS: Antibiotic treatment with penicillin and gentamicin had a high rate of success in patients with infective endocarditis caused by NVS. Early surgical intervention should be considered in those patients with deteriorating heart failure due to valve destruction.

Glucosyltransferases of viridans group streptococci modulate interleukin-6 and adhesion molecule expression in endothelial cells and augment monocytic cell adherence.

Recruitment of monocytes plays important roles during vegetation formation and endocardial inflammation in the pathogenesis of infective endocarditis (IE). Bacterial antigens or modulins can activate endothelial cells through the expression of cytokines or adhesion molecules and modulate the recruitment of leukocytes. We hypothesized that glucosyltransferases (GTFs), modulins of viridans group streptococci, may act directly to up-regulate the expression of adhesion molecules and also interleukin-6 (IL-6) to augment monocyte attachment to endothelial cells. Using primary cultured human umbilical vein endothelial cells (HUVECs) as an in vitro model, we demonstrated that GTFs (in the cell-bound or free form) could specifically modulate the expression of IL-6, and also adhesion molecules, in a dose- and time-dependent manner. Results of inhibition assays suggested that enhanced expression of adhesion molecules was dependent on the activation of nuclear factor kappaB (NF-kappaB) and extracellular signal-regulated kinase and that p38 mitogen-activated protein kinase pathways also contributed to the release of IL-6. Streptococcus-infected HUVECs or treatment with purified IL-6 plus soluble IL-6 receptor alpha enhanced the expression of ICAM-1 and the adherence of the monocytic cell line U937. These results suggest that streptococcal GTFs might play an important role in recruiting monocytic cells during inflammation in IE through induction of adhesion molecules and IL-6, a cytokine involved in transition from neutrophil to monocyte recruitment.

Prospective national survey of viridans streptococcal bacteraemia risk factors, antibacterial susceptibility and outcome of 120 episodes.

The aim of this study was to prospectively investigate 120 cases of viridans streptococcal bacteraemia (VSB) in 117 patients in major university hospitals in Slovakia in 2000-2002 (3 y) for antibacterial susceptibility, risk factors and outcome. From 127 episodes, 16 (13%) of VSB were caused by PEN-R strains and 13 (10%) by ERY-R strains. 32 cases had cancer as underlying disease (20 haematological), 41 had endocarditis and 35 were elderly (>65 y of age) patients. Concerning mortality, 29 of 127 patients died (24%). There were several risk factors associated with mortality. Solid tumour as underlying disease (p<0.02), stroke (p<0.002), concomitant lung infection (p<0.01), endoscopic procedure (p<0.036), intubation (p<0.0008), ventilatory support (p<0.002), and coma (p<0.009) were associated with more deaths. A comparison of 115 bacteraemias to 13 bacteraemias caused by erythromycin-resistant strains of Streptococcus viridans was performed. There were no significant differences in underlying disease, risk factors and mortality. Erythromycin resistance in bacteraemias caused by S. viridans did not have significant impact on outcome of the patients, nor did it show specific relation to analysed risk factors in our study. 14.5% of VSB were cause by PEN-resistant viridans streptococci. Risk factors for penicillin resistance were ventilatory support (p<0.01), intubation (p<0.001) and resistance to other antibiotics: 8 of 16 (50%) of PEN-R VSB were resistant also to erythromycin or cotrimoxazole or tetracycline compared with 9% of PEN-R VSB (p<0.005). Endoscopic procedures in the upper respiratory system were at risk for development of PEN-R VSB. There was also difference in outcome; 71% vs 22.5% (p<0.0002) of cases infected with PEN-R VSB died compared to PEN-S VSB. PEN-R is therefore clinically significant in VSB.

Glucosyltransferases of viridans streptococci are modulins of interleukin-6 induction in infective endocarditis.

The glucosyltransferases (GTFs) of viridans streptococci, common pathogens of infective endocarditis, are extracellular proteins that convert sucrose into exopolysaccharides and glucans. GTFs B, C, and D of Streptococcus mutans are modulins that induce, in vitro and in vivo, the production of cytokines, in particular interleukin-6 (IL-6), from monocytes. The roles of S. mutans GTFs in infectivity and inflammation in situ were tested in a rat experimental model of endocarditis. No significant differences in infectivity, in terms of 95% infective dose and densities of bacteria inside vegetations, were observed between laboratory strain GS-5 and two clinical isolates or isogenic mutant NHS1DD, defective in the expression of GTFs. In aortic valves and surrounding tissues, IL-6 was detected by Western blots and immunostaining 24 h after GS-5 infection, was maintained over 72 h, and was followed by production of tumor necrosis factor alpha but not IL-1beta. Animals infected with NHS1DD showed markedly lower levels of IL-6 (less than 5% of that of parental GS-5-infected rats), while tumor necrosis factor alpha was unaffected. In contrast, animals infected with NHR1DD, another isogenic mutant expressing only GtfB, showed a much smaller reduction (down to 56%). These results suggest that GTFs are specific modulins that act during acute inflammation, inducing IL-6 from endothelial cells surrounding the infected valves without affecting bacterial colonization in vegetations, and that IL-6 might persist in chronic inflammation in endocarditis.

[Clinical study and analysis of risk factors for mortality in 86 cases of infectious endocarditis in children and adolescents in Argentina: 1988-2000]. / Análisis clínico y de los factores de riesgo de mortalidad de 86 casos de endocarditis infecciosa en niños y adolescentes en Argentina (1988-2000).

INTRODUCTION: IE is a rare infection in children. Scarce reports with large number of patients are published. METHODS: Between January 1988 to December 2000 we analyzed all cases of IE cases admitted to our hospital. RESULTS: 86 cases of IE (4.9/10,000 admissions) in 86 children were diagnosed. The median age was 7.6 years. In 77% of patient previous cardiac disease was detected, interventricular defects and Tetralogy of Fallot were the more frequent. Three percent of children had rheumatic heart disease. Thirty-six percent of children had previous heart surgery. Fifty-seven percent have been received previous antibiotics. Eighty-seven percent had positive blood cultures, being the S. aureus and S. viridans the predominantly. Forty-eight percent of children had complications. The metabolic disorders and the nosocomial infections were the most frequent. Twenty-four percent required surgery, 24% of them in the first week of the diagnosis. The mortality in operated children was 19%. In the multivariate analysis we could observe that children with more than 7 years and S. aureus isolation in blood cultures had more incidence of complications and posterior surgery (p < 0.05). Children with S. aureus IE had longer duration of fever, more incidence of complications than patients with S. viridans IE (p < 0.05). Ten percent of children were treated as outpatients. The global mortality was 12,8%. Previous surgery (OR = 6.89; IC 95% 1.54-30.7) and previous antibiotic treatment (OR = 9.98; IC 95% 1.12-88.8) were the factors related with higher mortality in the multivariate analysis. S. aureus was the predominat pathogen and caused more morbidity and mortality than S. viridans IE. CONCLUSION: Children with IE with previous surgery and previous antibiotic treatment died with more frequency.

El riñón en la endocarditis infecciosa / The kidney in infectious endocarditis

Se discuten las diferentes manifestaciones renales (estructurales, funcionales e inmunológicas) de la Endocarditis Infecciosa asociadas a casos clínicos vividos.