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Lung disease is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. A modest number of bacterial pathogens have been correlated with pulmonary function decline; however, microbiological and molecular evidence suggests that CF airway infection is polymicrobial. To obtain a more complete assessment of the microbial community composition and dynamics, we undertook a longitudinal study by using culture-independent and microbiological approaches. In the process, we demonstrated that within complex and dynamic communities, the Streptococcus milleri group (SMG) can establish chronic pulmonary infections and at the onset of 39% of acute pulmonary exacerbations, SMG is the numerically dominant pathogen. We report the comprehensive polymicrobial community dynamics of a CF lung infection in a clinically relevant context. If a given organism, such as Pseudomonas aeruginosa, becomes resistant to antibiotic therapy, an alternative treatment avenue may mediate the desired clinical response by effectively managing the composition of the microbial community.

Background The Streptococcus anginosus group (SAG) play important roles in respiratory infections. It is ordinarily difficult to distinguish them from contaminations as the causative pathogens of respiratory infections because they are often cultured in respiratory specimens. Therefore, it is important to understand the clinical characteristics and laboratory findings of respiratory infections caused by the SAG members. The aim of this study is to clarify the role of the SAG bacteria in respiratory infections. Methods A total of 30 patients who were diagnosed with respiratory infections which were caused by the SAG bacteria between January 2005 and February 2015 were retrospectively evaluated. Results Respiratory infections caused by the SAG were mostly seen in male patients with comorbid diseases and were typically complicated with pleural effusion. Pleural effusion was observed in 22 (73.3%) patients. Empyema was observed in half of the 22 patients with pleural effusion. S. intermedius , S. constellatus and S. anginosus were detected in 16 (53.3 %), 11 (36.7 %) and 3 (10.0 %) patients, respectively. Six patients had mixed-infections. The duration from the onset of symptoms to the hospital visit was significantly longer in “lung abscess” patients than in “pneumonia” patients among the 24 patients with single infections, but not among the six patients with mixed-infection. The peripheral white blood cell counts of the “pneumonia” patients were higher than those of the “lung abscess” patients and S. intermedius was identified significantly more frequently in patients with pulmonary and pleural infections (pneumonia and lung abscess) than in patients with bacterial pleurisy only. In addition, the patients in whom S. intermedius was cultured were significantly older than those in whom S. constellatus was cultured. Conclusions Respiratory infections caused by the SAG bacteria tended to be observed more frequently in male patients with comorbid diseases and to more frequently involve purulent formation. In addition, S. intermedius was mainly identified in elderly patients with having pulmonary infection complicated with pleural effusion, and the aspiration of oral secretions may be a risk factor in the formation of empyema thoracis associated with pneumonia due to S. intermedius .

The Streptococcus Milleri/Anginosus Group (SMG) colonize mucosal surfaces, especially the airways, and are considered to be normal mucosal microbiota; however, they are a major cause of abscesses, pneumonia and pleural empyema. The production of exoenzymes and virulence factors do not correlate with SMG pathogenicity. Since SMG infections are associated with robust inflammatory responses, we hypothesized that host immune responses might distinguish strains associated with asymptomatic carriage and those associated with fulminant disease. We measured IL1β, TNF, IL10, IL12, IL23, IL17, and IL4 production from human peripheral blood mononuclear cells (PBMCs) stimulated with a panel of clinical isolates from the airways and infections and measured the ability of these isolates to stimulate TLR2. Isolates were categorized based on the levels of cytokines they induced from PBMCs (high, intermediate, low). Airway isolates predominantly induced low levels of cytokines and isolates from invasive disease induced higher levels, although about 10% of the strains produced divergent cytokine responses between donors. Interestingly, the donors were most divergent in their production of IL17, IL12 and IL23. We propose that the ability to inhibit or avoid an inflammatory response is associated with carriage in the airways and variability in responses between isolates and donors might contribute to susceptibility to disease.

Peritonsillar abscess (PTA) is conventionally considered to be a complication of acute tonsillitis, but no pathogenical association has been demonstrated. To investigate the precipitating factors in the pathogenesis of PTA, the clinical status of 117 patients with PTA and 78 patients with peritonsillar cellulitis (PC) were reviewed, comparing them with 188 cases of acute tonsillitis as a control group. The period between the onset of symptoms and the date of starting hospitalized medication was 4 to 5 days in all the three groups, with no significant differences. Higher prevalence of smoking habit was noted in the PTA group (odds ratio, 1.92; 95% confidence interval, 1.17-3.16). Bacteriological culture revealed that 55 of 67 aerobic isolates were Streptococcus subspecies, with the Streptococcus milleri group (SMG) as the most common (20 isolates). Twenty-three anaerobic species were isolated. Only 51% of the patients with neither the SMG nor anaerobic bacteria were smokers, whereas 90% of the patients with both the SMG and anaerobic bacteria were smokers. We hypothesize that delay or failure to receive medical care do not contribute to the pathogenesis of PTA or PC, and that smoking is positively correlated with the occurrence of PTA, as well as the bacteriological character.

Cavernous sinus venous thrombosis is an uncommon condition associated with high mortality rates if not recognised early. Symptoms include headache, visual loss, ophthalmoplegia, altered consciousness, proptosis and periorbital oedema. High-quality imaging is critical in early diagnosis and successful management. Primary infection (such as sinusitis) and possible complications (including meningitis) should be considered as potential aetiologies of cavernous sinus venous thrombosis, especially in those with a preceding history of localised infection. We present a case of a 50-year-old man with a bilateral cavernous sinus venous thrombosis with associated meningitis caused by Streptococcus milleri, secondary to maxillary sinusitis and otomastoiditis. He was successfully treated with antimicrobial treatment, surgical drainage and anticoagulation.

Streptococcus intermedius , S. constellatus , and S. anginosus comprise the Streptococcus Milleri/Anginosus group (SMG). They are facultative anaerobic bacteria that asymptomatically colonize the upper respiratory, gastrointestinal and urogenital tracts. They are also common pathogens in pyogenic invasive infections, as well as pulmonary and urinary tract infections. Most SMG infections are polymicrobial and associated with co-infecting obligate anaerobic bacteria. To better understand the effect of oxygen on the growth and physiology of these organisms, we compared the global metabolomic and transcriptomic profiles of S. intermedius strain B196 under aerobic and anaerobic conditions. The largest transcriptional changes were associated with induction of oxidative stress response genes under aerobic conditions. Modest changes in expression of genes associated with primary metabolism were observed under the two conditions. Intracellular and extracellular metabolites were measured using HILIC–LCMS. Differences in the abundance of specific metabolites were correlated with observed transcription changes in genes associated with their metabolism, implying that metabolism is primarily regulated at the transcriptional level. Rather than a large shift in primary metabolism under anaerobic conditions our results suggest a modest tuning of metabolism to support the accelerated growth rate of S. intermedius strain B196 in the absence of oxygen. For example, under anaerobic conditions, purine metabolism, pyrimidine de novo synthesis and pyrimidine salvage pathways were up-regulated at metabolic and transcriptional levels. This study provides a better understanding of differences between S. intermedius anaerobic and aerobic metabolism. The results reflect the organism’s predilection for anaerobic growth consistent with its pathogenic association with anaerobes in polymicrobial infections.

Background Brain abscesses continue to pose diagnostic and therapeutic challenges in developed and developing countries. Their aetiology and management remain complex and unclear, making improvement of treatments and outcome difficult. Methods To determine the demographics, management, and the variables that affect the outcome in subjects with brain abscesses treated at a single centre over an 11-year period, we retrospectively analysed data in 60 patients with brain abscesses surgically treated with stereotactically guided aspiration or open craniotomy excision in Shanghai Changzheng Hospital between January 2001 and December 2011. Such variables as age, gender, Glasgow Coma Scale (GCS) score at admission, clinical presentation, location, number of lesions, predisposing factors, mechanism of infection, aetiological agent, and therapy were analysed independently. Results Our analysis demonstrated that patient age and gender were factors that influence the occurrence of brain abscess; female patients and patients greater than 40 years of age were most likely to suffer a brain abscess. We also found that a patient’s GCS score upon admission did not influence outcome. While frequency of successful culturing of the infectious agent was low, positive cultures were obtained in only 8 of the cases (13.33%), in which the most common isolate was Streptococcus milleri. Outcome was favourable in 78.33% of the subjects, while the mortality rate was 20%. The outcome of one patient was poor due to the abscess in the basal ganglia region. Conclusions Stereotactically guided aspiration is an effective treatment for brain abscess with an overall favourable outcome. Mortality due to brain abscess was not directly related to surgery nor surgical technique. Additional studies will continue to reveal patients trends that may improve treatment for brain abscess.

Streptococcus milleri group (SMG) is a group of three streptococcal species ( S. anginosus , intermedius and constellatus ) that act as opportunist pathogens, among others in cystic fibrosis. Due to their fastidious character, they are both difficult to cultivate and to differentiate from less pathogenic streptococcal species, therefore being most probably underdiagnosed. Semi-selective McKay agar and NAS agar were developed to facilitate SMG recovery from clinical samples; however, direct comparison of recovery rates has not been published yet. We tested the performance of both media on 123 patient samples and demonstrated general superiority of NAS agar for SMG recovery during primary cultivation convincingly. This observation was also confirmed by quantitative drop tests during subculture. Despite the undisputed overall superiority of NAS agar over McKay agar, a smaller fraction of strains grew better on McKay agar. Inter-strain differences were the most probable explanation. Therefore, when economic conditions are not limiting and maximum recovery rate is desirable, both plates are advised to be used in parallel for primary cultivation of clinical samples.

Phlegmonous infection involving the digestive tract has been reported to have a poor prognosis. However, the pathogenesis and clinical features of acute phlegmonous esophagitis have remained unclear due to the rarity of the disease. We herein report a case of acute phlegmonous esophagitis that showed a fulminant course during chemoradiotherapy for uterine cancer. The patient developed septic shock 10 h after postprandial nausea and vomiting, and a computed tomographic scan showed diffuse thickening of the esophageal wall. Severe leukopenia that was refractory to the administration of granulocyte colony-stimulating factor persisted during the first few days. The patient fortunately survived after intensive treatment. The acute phlegmonous esophagitis of the present case might have been evoked and worsened by chemoradiotherapy due to its emetic and myelosuppressive adverse effects, respectively. Although its incidence is extremely rare, acute phlegmonous esophagitis may occur as a life-threatening complication of chemoradiotherapy.

Composites of gatifloxacin (GFLX)-loaded poly (lactic-co-glycolic) acid (PLGA) and β-tricalcium phosphate (βTCP) containing 0, 1, and 10 wt % GFLX (0, 1, and 10 wt % GFLX composites), and GFLX-loaded PLGA containing 1, 5, and 10 wt % GFLX (1, 5, and 10wt % GFLX-PLGA) as controls were fabricated and characterized in vitro and in vivo. On in vitro evaluation, the 10 wt % GFLX composite released GFLX over at least 28 days in Hanks’ balanced solution and exhibited clinically sufficient bactericidal activities against Streptococcus milleri and Bacteroides fragilis from 1 h to 10 days. The 0, 1, and 10 wt % GFLX composites and 10 wt % GFLX-PLGA were implanted in bone defects created by debridement of osteomyelitis lesions induced by S. milleri and B. fragilis in the mandible of rabbits ( n  = 5). Four weeks after implantation of the 10 wt % GFLX composite, inflammation in the debrided area disappeared in all the rabbits, while inflammation remained in all the rabbits after implantation of the 0 wt % GFLX composite and 10 wt % GFLX-PLGA, and in three rabbits after implantation of the 1 wt % GFLX composite. Bone formation appears to be less intense for the 10 wt % GFLX composite than for the 1 wt % GFLX composite probably owing to the rapid degradation of the 10 wt % GFLX composite. These findings show that the GFLX composite is effective for the local treatment of osteomyelitis.