Concept: Group A streptococcal infection
BACKGROUND: A few lineages of Group A streptococci (GAS) have been associated with a reemergence of severe invasive streptococcal disease in developed countries. However, the majority of the comparisons between invasive and non-invasive GAS isolates have been performed for collections of reduced genetic diversity or relied on limited typing information to distinguish clones. We characterized by several typing methods and compared a collection of 160 isolates recovered from normally sterile sites with 320 isolates associated with pharyngitis and recovered in the same time period in Portugal. RESULTS: Although most of the isolates belonged to clones that were equally prevalent in invasive infections and pharyngitis, we identified markers of invasiveness, namely the emm types 1 and 64, and the presence of the speA and speJ genes. In contrast, emm4, emm75, and the ssa and speL/M genes were significantly associated with pharyngitis. There was a strong agreement between the emm type, the superantigen (SAg) genes and the clusters defined by pulsed-field gel electrophoresis (PFGE) profiling. Therefore, combinations of particular emm types and SAg genes frequently co-occurred in the same PFGE cluster, but there was no synergistic or antagonistic interaction between them in determining invasiveness. Only macrolide-susceptible PFGE clones were significantly associated with invasive infections or pharyngitis, while the clones of resistant isolates sharing all other molecular properties analyzed were equally prevalent in the two groups of isolates. CONCLUSIONS: This study confirmed the importance of the widely disseminated emm1-T1-ST28 clone in invasive infections but also identified other clones linked to either invasive infections (emm64-ST164) or pharyngitis (emm4-T4-ST39), which may be more limited in their temporal and geographical spread. Clonal properties like some emm types or SAg genes were associated with disease presentation, highlighting the importance of bacterial genetic factors to the outcome of GAS infections, although other, yet unidentified factors may also play an important role.
Despite widespread use of intrapartum antibiotic prophylaxis, group B streptococcus remains a leading cause of morbidity and mortality in infants in Europe, the Americas, and Australia. However, estimates of disease burden in many countries outside of these regions is not available. We aimed to examine the current global burden of invasive disease and the serotype distribution of group B streptococcus isolates.
Streptococcus pyogenes (group A streptococci, GAS) encounter many streptococcal species of the physiological microbial biome when entering the upper respiratory tract of humans, leading to the question how GAS interact with these bacteria in order to establish themselves at this anatomical site and initiate infection. Here we show that S. oralis and S. salivarius in direct contact assays inhibit growth of GAS in a strain-specific manner, and that S. salivarius, most likely via bacteriocin secretion, also exerts this effect in transwell experiments. Utilizing SEM documentation the tested strains were identified as potent biofilm producers except for GAS M49. In mixed species biofilms, S. salivarius dominated the GAS strains while S. oralis acted as initial colonizer, building the bottom layer in mixed biofilms and thereby allowing even GAS M49 to form substantial biofilms on top. With the exception of S. oralis, artificial saliva reduced single-species biofilms and allowed GAS to dominate in mixed biofilms, although the overall two-layer structure was unchanged. When covered by S. oralis and S. salivarius biofilms, epithelial cells were protected from GAS adherence, internalization and cytotoxic effects. Apparently, these species can have probiotic effects. Employing Affymetrix Array technology on HEp-2 cell transcription levels revealed modest changes when exposed to S. oralis and S. salivarius biofilms which could explain some protective effects towards GAS attack. In summary our study revealed a protection effect of respiratory tract bacteria against an important airway pathogen and allowed a first in vitro insight into local environmental processes after GAS entering the respiratory tract.
An increased incidence and severity of invasive group A streptococcus (GAS) infections over the past decade have been reported by several authors, but GAS remains an uncommon cause of bacterial meningitis. The aim of this study was to describe and analyze the clinical and biological data of GAS meningitis by reporting 10 new cases of pediatric GAS meningitis and making a literature review. The mean age of patients, seven girls and three boys, was 3 years. There was a history of preexisting or concomitant community-acquired infection in five patients over 10. The outcome was fatal in two cases. All patients received an initial empirical antimicrobial therapy with a third generation cephalosporin switched in six cases to amoxicillin. The prognosis for this type of streptococcal meningitis is usually good, but death may occur even in children without any identified risk factor for severe infection.
TREM-1 (triggering receptor expressed on myeloid cells) is a surface molecule expressed on neutrophils and macrophages which has been implicated in the amplification of inflammatory responses triggered during infection. In the present study, we have investigated the clinical significance of TREM-1 in Streptococcus pyogenes-induced severe sepsis in both experimentally infected mice as well as in patients with streptococcal toxic shock. We found that S. pyogenes induced a dose-dependent upregulation of TREM-1 in in vitro cultured phagocytic cells and in the organs of S. pyogenes-infected mice. Furthermore, we reported a positive correlation between serum levels of soluble TREM-1 (sTREM-1) and disease severity in infected patients as well as in experimentally infected mice. Hence, sTREM-1 may represent a useful surrogate marker for streptococcal sepsis. We found that modulation of TREM-1 by administration of the TREM-1 decoy receptor rTREM-1/Fc substantially attenuated the synthesis of inflammatory cytokines. More importantly, treatment of S. pyogenes-infected septic mice with rTREM-1/Fc or the synthetically produced conserved extracellular domain LP17 significantly improved disease outcome. In summary, our data suggest that TREM-1 may not only represent a valuable marker for S. pyogenes infection severity but it may also be an attractive target for the treatment of streptococcal sepsis.
Acute pharyngitis is a non-specific symptom that can result from a number of viral and bacterial infections. For most eitiologies, symptoms are self-limited and resolve without lasting effects; however, pharyngitis resulting from infection with Streptococcus pyogenes (group A Streptococcus, GAS) can be associated with serious sequelae including acute rheumatic fever and acute glomerulonephritis. Rapid accurate detection of GAS in pharyngeal specimens from individuals suffering pharyngitis aids in management and selection of antibiotic therapy in these patients. A total of 796 pharyngeal swabs were collected at three separate clinical centers. Each specimen was analysed using the illumigene Group A Strep DNA amplification assay (Meridian, Cincinnati, OH). Results were compared to direct and extracted culture methods using Gram-stain and GAS-specific latex agglutination test to confirm GAS identification. Discrepant results were resolved using an alternative nucleic acid amplification test. The culture-based prevalence of GAS in this study was 12.8% (102/796). The illumigene assay detected GAS in 74/74 (100% sensitivity) direct culture positive and 100/102 (98.0% sensitivity) extracted culture positive specimens. GAS was detected by illumigene in an additional 42 (94.2% specificity) specimens that were direct culture negative and 16 specimens that were extracted culture negative (97.7% specificity). Discrepant analysis using an alternative molecular assay detected GAS nucleic acid in 13/16 (81.3%) “false positive” specimens and ½ “false negative” specimens, resulting in a final sensitivity of 99.0% and specificity of 99.6% for detection of GAS in pharyngeal swabs using the illumigene assay.
BACKGROUND:: Conservative treatment of acute otitis media may lead to more complications. This study evaluates changes in incidence, the clinical and microbiological findings, the complications and the outcome of acute mastoiditis in children in a country employing conservative guidelines in treating acute otitis media. METHODS:: All admitted children (0-15 years) diagnosed with acute mastoiditis during the period 1998-2007 in Eastern Denmark (population 2.2 million) were identified. Patient files were retrieved and reviewed, the data entered into a database. RESULTS:: The average incidence of admitted children with acute mastoiditis was 4.8/100.000 children pr. year and there was no change in the incidence during the 10-year period. Of the 214 children included (mean age 2.1 years, range 0.3-13.1, median 1.3 years), 100% presented with protrusion of the pinna and 95% with retroauricular swelling and redness, whereas 32% had a retroauricular abscess. Mastoidectomy had been performed in children with a retroauricular abscess. 31% had a ventilation tube inserted. The remaining group was treated with antibiotics and analgesics, and 86% also had a myringotomy performed. Streptococcus pneumoniae and group A streptococci were the bacteria most commonly cultured, 94% being susceptible to penicillin. The complication rate was low at 1.9%. All children included was initially admitted, no patients were outpatients. CONCLUSIONS:: The incidence of AM is stable in Eastern Denmark where conservative management guidelines for treating acute otitis media are used. Bacterial resistance towards penicillin is low (6%), complications are rare and the treatment outcome is good. Furthermore, no severe complications after treatment were observed.
Background: Streptococcus salivarius K12 has been shown to inhibit the growth of Streptococcus pyogenes due to bacteriocins release. Because of its ability to colonize the oral cavity, we have tested the strain K12 for its efficacy in preventing streptococcal pharyngitis and/or tonsillitis in adults. Methods: Forty adults with a diagnosis of recurrent oral streptococcal pharyngitis were enrolled in the study. Twenty of these subjects took for 90 days a tablet containing Streptococcus salivarius K12 (Bactoblis®). The other 20 subjects served as untreated controls. A 6-month follow-up was included to evaluate any persistent protective role. Results: The 20 adults who completed the 90-day course of Bactoblis® showed a reduction in their episodes of streptococcal pharyngeal infection (about 80%). The 90 days treatment was also associated with an approximately 60% reduction in the incidence of reported pharyngitis in the 6-month period following use of the product. The product was well tolerated by the subjects with no treatment-related side effects or drop-outs reported. Conclusion: Prophylactic administration of Streptococcus salivarius K12 to adults having a history of recurrent oral streptococcal pathology reduced the number of episodes of streptococcal pharyngeal infections and/or tonsillitis.
Viridans group streptococci (VGS) are a major cause of bacteraemia in neutropenic cancer patients, particularly those receiving fluoroquinolone prophylaxis. In this study, we sought to understand the molecular basis for fluoroquinolone resistance in VGS causing bacteraemia in cancer patients by assigning 115 VGS bloodstream isolates to specific species using multilocus sequence analysis (MLSA), by sequencing the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and parE, and by testing strain susceptibility to various fluoroquinolones. Non-susceptibility to one or more fluoroquinolones was observed for 78% of isolates, however only 68.7% of patients were receiving fluoroquinolone prophylaxis. All but one of the determinative QRDR polymorphisms occurred in GyrA or ParC, yet the pattern of determinative QRDR polymorphisms was significantly associated with the fluoroquinolone prophylaxis received. By combining MLSA and QRDR data, multiple patients infected with genetically indistinguishable fluoroquinolone-resistant Streptococcus mitis or Streptococcus oralis strains were discovered. Together these data delineate the molecular mechanisms of fluoroquinolone resistance in VGS isolates causing bacteraemia and suggest possible transmission of fluoroquinolone-resistant S. mitis and S. oralis isolates among cancer patients.
To develop an oral nanovaccine delivery system for lipopeptide-based vaccine candidate against group A Streptococcus.