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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., Competing Interests: The authors declare no conflict of interest.

Background: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence., Methods and Results: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007., Conclusions: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

Purpose: Endodontic disease is one of the most common causes of bacterial odontogenic sinusitis (ODS). Diagnosing ODS of endodontic origin involves otolaryngologists confirming sinusitis, and dental specialists confirming endodontic sources. The purpose of this study was to conduct a multidisciplinary literature review to highlight clinical and microbiological features of ODS, and the most optimal diagnostic modalities to confirm endodontic disease., Methods: An extensive review of both medical and dental literature was performed by rhinologists, endodontists, and an infectious disease specialist. Frequencies of various clinical and microbiological features from ODS studies were collected, and averages were calculated. Different endodontic testing and imaging modalities were also evaluated on their abilities to confirm endodontic disease., Results: ODS patients most often present with unilateral sinonasal symptoms for over 3 months, purulence on nasal endoscopy, and overt dental pathology on computed tomography (CT). Subjective foul smell, and maxillary sinus cultures demonstrating anaerobes and α-streptococci (viridans group) may be more specific to ODS. For endodontic evaluations, cold pulp testing and cone-beam CT imaging are most optimal for confirming pulpal and periapical disease., Conclusion: Diagnosing ODS requires collaboration between otolaryngologists and dental specialists. Clinicians should suspect ODS when patients present with unilateral sinonasal symptoms, especially foul smell. Patients will generally have purulent drainage on nasal endoscopy, and both sinus opacification and overt dental pathology on CT. However, some patients will have subtle or absent dental pathology on CT. For suspected endodontic disease, endodontists should be consulted for at least cold pulp testing, and ideally cone-beam CT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

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 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.

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., Competing Interests: The authors have declared that no competing interests exist.

The mitis group, a member of the genetically diverse viridans group streptococci, predominately colonizes the human oropharynx. This group has been shown to cause a wide range of infectious complications in humans, including bacteremia in patients with neutropenia, orbital cellulitis and infective endocarditis. Hydrogen peroxide (H2O2) has been identified as a virulence factor produced by this group of streptococci. More importantly, it has been shown that Streptococcus oralis and S. mitis induce epithelial cell and macrophage death via the production of H2O2. Previously, H2O2 mediated killing was observed in the nematode Caenorhabditis elegans in response to S. oralis and S. mitis. The genetically tractable model organism C. elegans is an excellent system to study mechanisms of pathogenicity and stress responses. Using this model, we observed rapid H2O2 mediated killing of the worms by S. gordonii in addition to S. mitis and S. oralis. Furthermore, we observed colonization of the intestine of the worms when exposed to S. gordonii suggesting the involvement of an infection-like process. In response to the H2O2 produced by the mitis group, we demonstrate the oxidative stress response is activated in the worms. The oxidative stress response transcription factor SKN-1 is required for the survival of the worms and provides protection against H2O2 produced by S. gordonii. We show during infection, H2O2 is required for the activation of SKN-1 and is mediated via the p38-MAPK pathway. The activation of the p38 signaling pathway in the presence of S. gordonii is not mediated by the endoplasmic reticulum (ER) transmembrane protein kinase IRE-1. However, IRE-1 is required for the survival of worms in response to S. gordonii. These finding suggests a parallel pathway senses H2O2 produced by the mitis group and activates the phosphorylation of p38. Additionally, the unfolded protein response plays an important role during infection., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study provides an in vitro analysis of dalbavancin activity against isolates causing skin and skin-structure infections (SSSIs) in children., Methods: A total of 770 Staphylococcus aureus, 167 β-haemolytic streptococci (BHS), 42 coagulase-negative staphylococci (CoNS), 25 Enterococcus faecalis and 13 viridans group streptococci (VGS) were collected from children (<18years old) in the USA (2014-2015)., Results: Dalbavancin had MIC 50/90 values of 0.03/0.06μg/mL against S. aureus and CoNS, including methicillin-resistant (MRSA) and -susceptible (MSSA) isolates. Dalbavancin MICs were 8-32-fold lower than those of daptomycin (MIC 50/90 , 0.25/0.5μg/mL), vancomycin (MIC 50/90 , 0.5/1μg/mL) and linezolid (MIC 50/90 , 1/1μg/mL) against MRSA. These agents showed 100.0% susceptibility against MRSA, and clindamycin also had a high (92.7%) susceptibility rate. Dalbavancin (MIC 50/90 , 0.03/0.06μg/mL) and daptomycin (MIC 50/90 , 0.25/0.5μg/mL) were the most active agents against CoNS. When tested against E. faecalis, dalbavancin was up to 32-fold more active than ampicillin (MIC 50/90 , ≤0.5/1μg/mL), daptomycin (MIC 50/90 , 1/1μg/mL), linezolid (MIC 50/90 , 1/2μg/mL) and vancomycin (MIC 50/90 , 1/2μg/mL). Dalbavancin (MIC 50/90 , 0.008/0.03μg/mL), ceftriaxone (MIC 50/90 , ≤0.06/≤0.06μg/mL) and penicillin (MIC 50/90 , ≤0.06/≤0.06μg/mL) were the most active against BHS. VGS isolates were susceptible to dalbavancin (MIC 100 , 0.03μg/mL), with MICs 32-64-fold lower than daptomycin (MIC 50/90 , 0.5/0.5μg/mL), linezolid (MIC 50/90 , 0.5/1μg/mL) and vancomycin (MIC 50/90 , 0.5/0.5μg/mL)., Conclusions: Approved agents available for the treatment of SSSI in children are limited. Dalbavancin demonstrated potent in vitro activity against isolates causing SSSI in children. Developing dalbavancin for SSSI treatment in children is warranted, provided safety and tolerability are satisfactory., (Copyright © 2017. Published by Elsevier Ltd.)

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).

The Rostovskii state medical university of Minzdrav of Russia, 344022 Rostov-on-Don, Russia The analysis is applied concerning significance of laboratory techniques of verification of streptococcus infection (bacteriological analysis, detection of anti-streptolysin O in pair serums) in 148 patients with infectious mononucleosis aged from 3 to 15 years. The content of anti-streptolysin O exceeded standard in 41 ± 4.8% of patients with concomitant in acute period and in 49.5 ± 4.9% during period of re-convalescence. This data differed from analogous indicator in patients with negative result of examination on streptococcus infection independently of period of disease (9.3 ± 2.8%). The exceeding of standard of anti-streptolysin O was detected more frequently (t ≥ 2, P ≥ 95%) in patients with isolation of Streptococcus pyogenes (56.9 ± 5.8%) than in patients with Streptococcus viridans (31.2 ± 6.5%). The concentration of anti-streptolysin 0 in patients with concomitant streptococcus infection varied within limits 200-1800 IE/ml. The minimal level of anti-streptolysin O (C = 200 IE/mI) was detected independently of type of isolated Streptococcus and period of disease. The high levels of anti-streptolysin O were observed exclusively in patients with isolation of Streptococcus pyogenes. In blood serum ofpatient with concomitant streptococcus infection (Streptococcus pyogenes + Streptococcus viridans) increasing of level of anti-streptolysin O was detected in dynamics of diseases from minimal (C = 200 IE/ ml) to moderately high (200 < C < 400 IE/mI). It is demonstrated that to identify streptococcus infection in patients with infectious mononucleosis the anamnesis data is to be considered. The complex bacteriological and serological examination ofpatients is to be implemented This is necessary for early detection ofpatients with streptococcus infection and decreasing risk of formation of streptococcus carrier state.

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.

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., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

This study retrospectively analyzed 12 patients with brain abscesses. Half of the patients were diagnosed inaccurately in the initial stage, and 7.2 days were required to achieve the final diagnosis of brain abscess. The patients presented only with a moderately elevated leukocyte count, serum CRP levels, or body temperatures during the initial stage. These markers changed, first with an increase in the leukocyte count, followed by the CRP and body temperature. The degree of elevation tended to be less prominent, and the time for each inflammatory index to reach its maximum value tended to be longer in the patients without ventriculitis than in those with it. The causative organisms of a brain abscess were detected in 10 cases. The primary causative organisms from dental caries were Streptococcus viridians or milleri, and Fusobacterium nucleatum. Nocardia sp. or farcinica were common when the abscess was found in other regions. The primary causative organisms of unrecognized sources of infection were Streptococcus milleri and Prolionibacterium sp. Nocardia is resistant to many antibiotics. However, carbapenem, tetracycline and quinolone were effective for Nocardia as well as many other kinds of bacteria. In summary, the brain abscesses presented with only mildly elevated inflammatory markers of body temperature, leukocyte and CRP. These inflammatory markers were less obvious in the patients without ventriculitis and/or meningitis. The source of infection tended to suggest some specific primary causative organism. It was reasonable to initiate therapy with carbapenem.

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., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

The mitis group streptococci (MGS) are widespread in the oral cavity and are traditionally associated with oral health. However, these organisms have many attributes that contribute to the development of pathogenic oral communities. MGS adhere rapidly to saliva-coated tooth surfaces, thereby providing an attachment substratum for more overtly pathogenic organisms such as Porphyromonas gingivalis, and the two species assemble into heterotypic communities. Close physical association facilitates physiologic support, and pathogens such as Aggregatibacter actinomycetemcomitans display resource partitioning to favour carbon sources generated by streptococcal metabolism. MGS exchange information with community members through a number of interspecies signalling systems including AI-2 and contact dependent mechanisms. Signal transduction systems induced in P. gingivalis are based on protein dephosphorylation mediated by the tyrosine phosphatase Ltp1, and converge on a LuxR-family transcriptional regulator, CdhR. Phenotypic responses in P. gingivalis include regulation of hemin uptake systems and gingipain activity, processes that are intimately linked to the virulence of the organism. Furthermore, communities of S. gordonii with P. gingivalis or with A. actinomycetemcomitans are more pathogenic in animal models than the constituent species alone. We propose that MGS should be considered accessory pathogens, organisms whose pathogenic potential only becomes evident in the context of a heterotypic microbial community., (© 2011 Blackwell Publishing Ltd.)

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., (Copyright © 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Twelve cases of neonates admitted to the neonatal unit of our hospital, between January 1, 2000, and December 31, 2005, because of otorrhea due to spontaneous perforation of the tympanic membrane within the first 10 days of life are presented. Data were collected retrospectively from medical records. Cultures of the middle ear exudate grew PSEUDOMONAS AERUGINOSA in 10, SERRATIA MARCENSCENS in 1, and STAPHYLOCOCCUS AUREUS in 1 neonate. Cultures of nasopharyngeal secretions grew P. AERUGINOSA in nine, S. MARCENSCENS in one, S. AUREUS in one, and STREPTOCOCCUS VIRIDANS in one neonate. Middle ear versus nasopharyngeal secretions cultures grew the same organism in 11 neonates. A 10-day course of parenteral antibiotics was administered (ampicillin-ceftazidime for all neonates except for the one neonate with the S. AUREUS otitis who received netilmicin-cloxacillin). All neonates had uneventful course and were discharged home in good clinical condition. Our findings suggest that neonates with eardrum perforation should receive antibiotics parenterally, as the most common pathogens is P. AERUGINOSA, for which there are no satisfactory antibiotics for oral use., (Copyright Thieme Medical Publishers.)

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.

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.

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.

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.

The proportion of infective endocarditis (IE) caused by group D streptococci (GDS; formerly Streptococcus bovis) increased markedly in France, to account for 25% of all cases of IE by 1999. In an attempt to explain this phenomenon, a comparative analysis of GDS and oral streptococci (OS) causing IE was performed. This study was based on data collected from a large cross-sectional population-based survey that was conducted in 1999. In total, 559 cases of definite IE were recorded, of which 142 involved GDS and 79 involved OS. Patients with GDS IE were older (62.7 vs. 56.6 years, p 0.01) and had a history of valve disease less frequently than did patients with OS IE (33.8% vs. 67.1%, p <0.0001). At-risk procedures for IE were performed less frequently in patients with GDS than in patients with OS (14.8% vs. 24.1%, p 0.08), but co-morbidities were more frequent in the GDS group (59.9% vs. 32.9%, p 0.0001). Diabetes, colon diseases and cirrhosis were also more frequent in the GDS group (p 0.006, p <0.0001 and p 0.08, respectively). Rural residents accounted for 31.0% of the GDS group, but for only 15.2% of the OS group (p 0.001). Likewise, the proportion of GDS IE was higher in regions with mixed (urban and rural) populations (Franche-Comté 81.8%, Marne 68.7%, Lorraine 70.3% and Rhône-Alpes 65.3%) than in exclusively urban regions (Paris and Ile de France 58.0%). Further investigations are required to elucidate the link in France between the incidence of GDS IE, rural residency and nutritional factors.

Background: The emergence of viridans group streptococci that are relatively or fully resistant to penicillin is increasingly being recognized worldwide, but only a scant number of penicillin-resistant isolates have been described as a cause of infective endocarditis. Because of the paucity of data, it has been difficult to define optimal treatment regimens for this syndrome. Thus, recommendations for therapy have largely been made on the basis of consensus opinion., Methods: We retrospectively identified a cohort of patients with infective endocarditis due to penicillin-resistant viridans group streptococci who were seen at the Mayo Clinic (Rochester, MN) between January 1967 and April 2006. Demographic characteristics, clinical features, treatment regimens, and outcomes were analyzed. Mean values are shown with standard deviations., Results: Twenty-nine patients were identified over the 38.5-year study period. Nineteen patients with native valve endocarditis were cured; 9 of these 19 patients received a 2.3+/-0.4-week antibiotic regimen consisting of penicillin and an aminoglycoside, and 8 of these 19 patients received treatment courses of 5.1+/-1.4 weeks' duration that consisted of either a bimodal combination regimen with a penicillin or ceftriaxone and an aminoglycoside or ceftriaxone monotherapy. Nine of 10 patients with prosthetic valve infection were cured with 4.1+/-0.6-week regimens that consisted of either a combination regimen or monotherapy with vancomycin or ceftriaxone. Mean duration of follow-up after hospital discharge was 9.1 years., Conclusions: Outcomes of this relatively large population of patients with endocarditis with a prolonged duration of follow-up indicate that the application of current treatment guidelines should be successful in most patients.

The ability of pro-inflammatory cytokines to promote coagulation prompted the hypothesis that pro-inflammatory cytokines induced by oral streptococci might play a role in the pathogenesis of viridans endocarditis. We used supernatant fluids from peripheral blood mononuclear monocyte (PBMC) cultures, stimulated for just 4-6 hrs with representative streptococcal isolates, to study cytokines that promoted endothelial tissue factor (TF) activity. Neutralizing antibodies demonstrated that interleukin-1beta (IL-1beta) was a major early endothelial TF inducer, and that recombinant IL-1beta was comparable with the supernatant fluid in activity. IL-1beta-rich supernatant fluids from oral streptococci-stimulated or lipopolysaccharide-stimulated PBMC cultures up-regulated the expression of endothelial ICAM-1 and E-selectin. These molecules could help trap TF-producing monocytes or dendritic cells bearing streptococci at the site. Thus, the rapid IL-1beta-inducing capacity of oral streptococci could facilitate the early deposition of bacteria in fibrin clots and promote endocarditis.

Infections due to antimicrobial-resistant viridans group streptococci are increasing. The present study was done to determine the frequency of antibiotic resistance among community-acquired viridans group streptococci isolated from blood cultures and to identify the risk factors associated with acquiring antibiotic-resistant viridans group streptococci. Twenty-eight community-acquired viridans group streptococcal isolates were recovered from 27 patients, of which 89%, 86%, 79%, 61%, and 39% were susceptible to ceftriaxone, clindamycin, tetracycline, penicillin, and erythromycin, respectively; 100% were susceptible to levofloxacin and vancomycin. Among the patients with previous antibiotic use, 73% had penicillin non-susceptible viridans group streptococci, compared with 18% who did not receive prior antibiotics (p = 0.006). Patients with and without prior antibiotic use, 27% and 0%, respectively, had ceftriaxone non-susceptible viridans group streptococci isolates, respectively (p = 0.05). Patients with and without prior antibiotic use, 45% and 6%, respectively, had tetracycline non-susceptible viridans group streptococci isolates, respectively (p = 0.02). No other risk factors for isolation of non-susceptible viridans group streptococci were identified.

We investigated cellular and humoral immune responses to oral biofilm bacteria, including Streptococcus mutans, Streptococcus anginosus, Streptococcus sobrinus, and Streptococcus sanguinis, in NOD/SCID mice immunized with human peripheral blood mononuclear cells (hu-PBMC-NOD/SCID mice) to explore the pathogenicity of each of those organisms in dental and oral inflammatory diseases. hu-PBMC-NOD/SCID mice were immunized by intraperitoneal injections with the whole cells of the streptococci once a week for 3 weeks. FACS analyses were used to determine the percentages of various hu-T cell types, as well as intracellular cytokine production of interleukin-4 and interferon-gamma. Serum IgG and IgM antibody levels in response to the streptococci were also determined by enzyme-linked immunosorbent assay. S. anginosus induced a significant amount of the proinflammatory cytokine interferon-gamma in CD4(+) and CD8(+) T cells in comparison with the other streptococci. However, there was no significant differences between the streptococci in interleukin-4 production by CD4(+) and CD8(+) T cells after inoculation. Further, S. mutans significantly induced human anti-S. mutans IgG, IgG(1), IgG(2), and IgM antibodies in comparison with the other organisms. In conclusion, S. anginosus up-regulated Th1 and Tc1 cells, and S. mutans led to increasing levels of their antibodies, which was associated with the induction of Th2 cells. These results may contribute to a better understanding of human lymphocyte interactions to biofilm bacteria, along with their impact on dental and mucosal inflammatory diseases, as well as endocarditis.

Major predisposing conditions for infective endocarditis (IE) are the presence of a cardiac platelet-fibrin vegetation and of circulating bacteria with relatively low susceptibility to microbicidal activity of blood platelets. The influence of proinflammatory conditions on development of IE is unknown. We studied the effects of the presence of a catheter, inserted to induce platelet-fibrin vegetations, and of the proinflammatory cytokine interleukin-1alpha in rabbit experimental IE. Leaving the catheter in place after challenge with viridans streptococci predisposed for experimental IE. IE susceptibility rapidly decreased between 0 to 6 h after catheter removal. The catheter did not predispose for IE by providing a site for bacterial adherence, as almost all explanted catheters were culture negative. To mimic the proinflammatory influence of the catheter, rabbits were injected with interleukin-1alpha at 24 h after catheter removal and at 0, 1, and 3 h before bacterial challenge. Interleukin-1alpha injected 3 h prior to challenge significantly increased IE incidence due to a platelet releasate-susceptible Streptococcus oralis strain, with rapidly increasing numbers of bacteria within the vegetations. IE due to the Streptococcus sanguis strain less susceptible to platelet releasate was not enhanced. We conclude that proinflammatory stimuli, either a catheter or interleukin-1alpha, enhanced susceptibility to IE due to the platelet releasate-susceptible S. oralis. As with rabbits, temporary intravascular proinflammatory conditions may predispose for IE in humans at risk for this serious infection.

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.

Infective endocarditis in association with spondylodiscitis is rarely observed. It is sometimes difficult to distinguish between rheumatologic diseases and infective endocarditis. We reported a 61-year-old male with Streptococcus viridans endocarditis suffering from low-back pain as initial symptom. Infective endocarditis was diagnosed according to Duke Criteria. L4-5 spondylodiscitis was revealed on the lumbar magnetic resonance imaging. He responded to antibiotic treatment. Infective endocarditis should be considered in patients with fever and low-back pain due to spondylodiscitis.

Antimicrobial resistance among the Viridans group of streptococci (VGS) has emerged as a hindrance to effective antibiotic therapy. Our objective was to evaluate the prevalence of antibiotic-resistant VGS in healthy children. Plaque samples were collected from tooth and tongue surfaces of 102 healthy subjects. Serially diluted samples were inoculated onto BHI agar plates and Mitis Salivarius Agar (MSA) plates and incubated as appropriate. Representative colonies were identified to species level by standard methods. Susceptibility of the VGS was performed by determining the minimum inhibitory concentrations (MICs) of 11 antibiotics using Etest. Of the 540 VGS isolates from both sites, 58% were from the tooth surfaces and 42% from the tongue. The most prevalent were S. salivarius (21.5%) and S. sanguis (16.3%). Imipenem and vancomycin had excellent activities. Resistance rates to trimethoprim, amoxicillin, piperacillin, erythromycin, cefuroxime and cephalothin, were 60.7, 40.8, 34.7, 32.6, 27.5 and 25.3%, respectively. Resistance rates to penicillin and clindamycin were 15.9% and 15.4%, respectively. The majority of the erythromycin-resistant isolates were from the tongue; 41% versus 29%. At the species level, 26% and 23% of S. salivarius and 23% and 14% of S. mutans from the tooth and tongue, respectively were resistant to penicillin. The data show species-related and site-related variations in the susceptibility pattern and an emerging high prevalence of antibiotic-resistant VGS. The difference in the susceptibilities between the species underscores the importance of accurate-identification and the need for surveillance of antimicrobial resistance among clinical isolates in our hospitals.

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.

Resident bacteria have been implicated to play a major role in the development of inflammatory bowel disease. While luminally sterile IL-10 gene-deficient mice remain disease-free, their conventionally raised littermates develop enterocolitis associated with increased numbers of luminal and mucosal adherent bacteria. To investigate the role of defined bacteria on the initiation and development of this enterocolitis, we associated luminally sterile IL-10 gene-deficient mice with pure strains of resident bacteria. Axenic, luminally sterile mice were either monoassociated with viridans group Streptococcus or Clostridium sordellii or co-associated with Bacteroides vulgatus and Clostridium sordellii. Seven to 22 weeks later the mice were analyzed for intestinal histologic injury, epithelial permeability, and an inflammatory immune response to bacterial antigens. Despite optimal colonization none of the tested bacteria caused intestinal inflammation, release of inflammatory cytokines from the epithelia, or disruption of the epithelial barrier integrity. However, in the case of association with Bacteroides vulgatus and Clostridium sordellii, a systemic immune response to bacterial-derived antigens was measured, with a magnitude similar to that seen in conventional sick Il-10 gene-deficient mice. This response was not detected in mice associated with viridans group Streptococcus. We conclude that colonization of the intestinal lumen with individual bacterial species may not be sufficient to alter epithelial barrier integrity, increase intestinal cytokine release, or cause intestinal inflammation in susceptible IL-10 gene-deficient mice, despite the ability of these same bacteria to stimulate a systemic response.

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.

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.

Unlabelled: Gradenigo syndrome is a rare presentation of acute petrositis. The clinical triad of Gradenigo syndrome consists of acute suppurative otitis media, severe unilateral headache and abducens nerve palsy. We report the first case of Gradenigo syndrome caused by Streptococcus acidominimus, a Gram-positive coccus of the Streptococcus viridans group, which rarely causes deep-seated infection in humans., Conclusion: Gradenigo syndrome may complicate acute otitis media and should be suspected in case of unilateral headache and abducens nerve palsy. Conservative medical treatment without surgery may be considered in some patients.