Streptococcal Antigen Research Articles

Prospective Evaluation of Xpert® Xpress Strep A Automated PCR Assay vs. Solana® Group A Streptococcal Nucleic Acid Amplification Testing vs. Conventional Throat Culture.

In our laboratory, the negative rapid group A streptococcal (GAS) antigen assays are backed up by the Solana® GAS Assay by Quidel instead of a Group A streptococcal throat culture. Another FDA cleared RT-PCR assay is the Xpert® Xpress Strep A, which detects Streptococcus pyogenes DNA, and is performed on the Cepheid GeneXpert instrument. Three hundred seventy-five positive and negative specimens were randomly selected from 5489 throat specimens that had been tested by the Solana® GAS Assay during January 2018 and were tested with the Xpress Strep A assay. A throat culture was also set up (sheep blood agar at 35 °C in 5% CO2). All beta-hemolytic streptococci were purified and identified by MALDI-TOF mass spectrometry. Of the 375 samples, 185 were positive by Solana® GAS Assay, and 187 were positive by the Xpress Strep A. The total agreement between the Solana® GAS Assay and the Xpert® Xpress Strep A was 99.5%. The agreement of the Xpert® Xpress Strep A assay with culture was 90.1%. The sensitivity and specificity for Xpress Strep A versus culture were 100% and 83.5%, respectively. The Xpert® Xpress Strep A assay’s performance was equivalent to the Solana® GAS Assay, and was highly sensitive. The lower specificity was likely due to the Xpress Strep A assay having higher sensitivity as compared to throat culture.

Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae.

BackgroundThe neuropsychiatric disorders due to post‐streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies. Since age, gender, strain differences, and genotypes impact on the development of autoimmunity, we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts (<6 weeks and >12 weeks) under normal husbandry conditions and following exposure to group A streptococcus (GAS).MethodsStandard behavioral assessments were performed to determine the impairments in fine motor control (food manipulation test), gait and balance (beam walking test), and obsessive‐compulsive behavior (grooming and marble burying tests). Furthermore, electrocardiography, histology, and behavioral assessments were performed on male and female Lewis rats injected with GAS antigens.ResultsFor control Lewis rats there were no significant age and gender dependent differences in marble burying, food manipulation, beam walking and grooming behaviors. In contrast significant age‐dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation. Therefore, Lewis rats were selected for further experiments to determine the effect of GAS. After exposure to GAS, Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD, respectively.ConclusionWe have characterised a new model that provides longitudinal stability of age‐dependent behavior, to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post‐streptococcal complications.

Dysphagia and Epigastric Pain in an Adolescent Boy.

1. Senthil Velan Bhoopalan, MBBS, PhD* 2. Rabea Alhosh, MD† 1. *St. Jude Children’s Research Hospital, Memphis, TN 2. †University of Nevada Las Vegas, Las Vegas, NV A 17-year-old previously healthy boy presents with a history of epigastric abdominal pain associated with some difficulty in swallowing for the past 3 days. He denies any emesis but reports nausea. The abdominal pain is localized to the epigastric area without any radiation. Pain is reported at 7 on a scale of 1 to 10. He denies any diarrhea but had noticed a few episodes of black tarry stool for the past 2 days. His sexual history is significant for oral sex with a single female partner, but he denies any genital or oral lesions. He was seen by his pediatrician 2 days ago. His pediatrician suspected a gastric ulcer and prescribed him pantoprazole, which the patient never obtained. On presentation he has a temperature of 103°F (39.4°C) and appears mildly dehydrated. His vital signs are otherwise within normal limits. On physical examination the patient has dry lips and mucosa, but no oral lesions are noted. Mild epigastric tenderness without any rigidity or rebound tenderness is noted. Examination findings are otherwise normal. Initial laboratory evaluation shows a white blood cell count of 12,900/μL (12.9×109/L), and the remainder of the blood cell count and metabolic panel are normal. The results of the antigen test for influenza, the heterophile antibody test for infectious mononucleosis, and the rapid streptococcal antigen test are negative. His CRP level is elevated to 12 mg/dL (120 mg/L). A computed tomographic scan …

Risk factors for peritonsillar abscess in streptococcus A-negative tonsillitis: a case control study.

The Centor criteria and the FeverPAIN score are recommended for guiding antibiotic prescription for tonsillitis, but they are not validated for this purpose. We aimed to identify risk factors for peritonsillar abscess in group A haemolytic streptococcus-negative tonsillitis and to test the performance of clinical scores and laboratory tests. In a retrospective case-control study at two regional hospitals from January 2015 to June 2018, we identified all cases of peritonsillar abscess and used propensity score matching utilising age and gender to select two controls per case from all patients who had a rapid group A haemolytic streptococcus antigen test in the emergency department. Exclusion criteria were age &lt;18 years, documented refusal and a positive antigen test. We abstracted patient history, physical examination and results of laboratory testing. Logistic regression analysis was used to identify risk factors. We included 141 cases of peritonsillar abscess, matched with 282 controls. Higher Centor score, C-reactive protein and white blood cell count were significantly associated with peritonsillar abscess, but had a low performance for predicting the latter (area under the receiver operator characteristic curve [ROC AUC] 0.76). The FeverPAIN score was not associated with peritonsillar abscess (ROC AUC 0.51). In the multivariable analysis, difficulty swallowing (odds ratio [OR] 18.4, 95% confidence interval [CI] 6.58&ndash;51.2), dyspnoea (OR 10.2, 95% CI 1.18&ndash;89.0), tonsillar swelling (OR 4.21, 95% CI 1.39&ndash;12.7) and unilateral signs and symptoms (OR 146, 95% CI 40.9&ndash;522) were risk factors of peritonsillar abscess. The Centor criteria, as well as C-reactive protein and white blood cell count, have a low discriminatory performance, and the FeverPAIN score is not useful in identifying patients at risk for peritonsillar abscess in group A haemolytic streptococcus-negative tonsillitis. To guide a rational antibiotic prescription, new decision tools need to be developed. These might include items such as difficulty swallowing, dyspnoea, tonsillar swelling and unilaterality.

A Young Child with Subacute Onset of Behavioral Changes.

1. Sarah Pradhan, MD* 2. Jessica Goldstein, MD† 3. Erin Frank, MD* 4. Allayne Stephans, MD* 1. *Department of Pediatric Hospital Medicine, 2. †Department of Pediatric Neurology, Rainbow Babies and Children’s Hospital, Cleveland, OH 1. Address Correspondence to Sarah Pradhan, MD; E-mail: sarah.pradhan6{at}gmail.com A 5-year-old healthy boy presents with a 3-week history of new onset aggression, obsessive-compulsive behavior, and nocturnal enuresis. One month ago he sustained a minor head trauma when he was sliding down the slide at a local playground. He was initially diagnosed with a mild concussion. His symptoms have now progressed and include frequent night waking, hand wringing, and behavioral outbursts. This prompts his pediatrician to refer him to the emergency department for evaluation. He undergoes computed tomography scan of the head, which is unremarkable. Laboratory evaluations include electrolytes, liver enzymes, complete blood cell count, rapid group A streptococcal antigen, thyroids studies, and heterophile antibody test, which are unremarkable. Urine and blood toxicology screens are negative. He is admitted to the inpatient unit. Vital signs are appropriate for age. He has difficulty answering questions and following commands. He is restless and disoriented. He intermittently gets up to run around the room and occasionally bangs his head on the wall. His cranial nerve, motor, reflexes, sensory, coordination, and gait examinations are normal. Brain magnetic resonance imaging is unremarkable. On video electroencephalogram he has bilateral fronto-temporal spikes that correspond with his abnormal movements and subclinical seizures arising from the right and left frontotemporal areas independently (arrows in Fig 1). Fosphenytoin is started, which controls his seizures, but he continues to have abnormal behavioral outbursts. Over the course of the week, he develops dysarthria, oral-facial …

126. Implementation of the core elements of an outpatient antimicrobial stewardship program in pediatric emergency departments and urgent care clinics

BackgroundWe used the Center for Disease Control and Prevention’s 4 core elements (commitment, action for policy and practice, tracking and reporting, education and expertise) to establish an outpatient antibiotic stewardship program (ASP) in 2 pediatric emergency departments (EDs) and 3 urgent care clinics (UCCs) of a healthcare system.MethodsThe outpatient ASP team consists of infectious diseases (ID) physicians, a pharmacist, and data analyst collaborating with ED and UCC providers. We placed a commitment letter in every exam room. We coach and support frontline providers to lead and sustain quality improvement (QI) projects. A monthly report evaluates rates of antibiotic use for viral infections and first-line antibiotic use for bacterial infections. We also compare rates of respiratory diagnoses and overall antibiotic use for all respiratory infections among the different sites. We developed an outpatient antibiotic handbook summarizing diagnosis and treatment recommendations for commonly encountered infections. Progress on prescribing trends and positive reinforcement are shared with providers during cookie rounds at bi-annual division meetings. We provide lectures, workshops, and newsletter articles on wise use of antibiotics.ResultsPre-implementation data showed < 5% antibiotic use for common pediatric viral infections and >85% use of first-line antibiotics for common bacterial infections. Trends in the report help us identify site-specific improvement opportunities we are working with frontline providers on addressing. In 2 years, our QI efforts have resulted in an increase in safety-net antibiotic prescriptions for acute otitis media in the EDs from 0.4% to over 7.5%, and a decrease in the percentage of rapid streptococcal testing performed in children < 3years old from 13% to 5% in one UCC (Figure 1). We have completed 15 cookie rounds attended by all ED/UCC core providers. In a survey completed by 61 providers, 85% found the handbook to be very beneficial, and 97% report it impacts their daily practice (Table 1).Figure 1: Annotated control charts of 2 quality improvement projects. A. Increase in safety-net antibiotic prescriptions offered to children diagnosed with acute otitis media in the emergency department. B. decrease in the percentage of streptococcal rapid antigen detection tests performed on children younger than 3 years of age in one urgent care clinic ConclusionSeeking leadership support and most importantly engaging frontline providers allowed us to be successful in implementing the suggested core elements of an outpatient ASP and maximize existing resources.Disclosures Brian R. Lee, MPH, PhD, Merck (Grant/Research Support)

Efficacy of Rapid Antigen Test and McIsaac / Modified Centor Scores for Diagnosis of Streptococcal Tonsillopharyngitis in Children

Objective: We aimed to determine the efficacy of rapid antigen tests, clinical signs, and McIsaac / modified Centor clinical scoring systems in the diagnosis of Group A streptococcus (GAS) at children. Materials and Methods: Subjects aged 3-14 years who presented with acute tonsillopharyngitis were questioned about their sociodemographic properties and symptoms. Their clinical signs and McIsaac / modified Centor scores were recorded. They underwent a rapid streptococcal antigen test and throat culture sampling. Results: GAS proliferated in culture %11 of cases. The risk of culture positivity was 4.8 times greater in children aged 6 years or older. There was a significant correlation between culture positivity and muscle pain, tonsillar edema. Rapid strep test had a sensitivity of 75% and a specifity of 100% for the diagnosis of streptococcal tonsillopharyngitis. Rapid strep test showed a sensitivity of 80% and a specifity of 100% in children with a McIsaac / modified Centor score of 4-5. Conclusions: Unnecessary antibiotic use for tonsillopharyngitis is an important problem. Therefore, it is ideal to order throat culture and act accordingly in every case suggesting GAS infection. However, when culture is not possible, rapid strep testing and McIsaac / modified Centor scoring are effective in guiding diagnosis and treatment.

The Multifaceted Nature of Streptococcal Antigen I/II Proteins in Colonization and Disease Pathogenesis.

Streptococci are Gram-positive bacteria that belong to the natural microbiota of humans and animals. Certain streptococcal species are known as opportunistic pathogens with the potential to cause severe invasive disease. Antigen I/II (AgI/II) family proteins are sortase anchored cell surface adhesins that are nearly ubiquitous across streptococci and contribute to many streptococcal diseases, including dental caries, respiratory tract infections, and meningitis. They appear to be multifunctional adhesins with affinities to various host substrata, acting to mediate attachment to host surfaces and stimulate immune responses from the colonized host. Here we will review the literature including recent work that has demonstrated the multifaceted nature of AgI/II family proteins, focusing on their overlapping and distinct functions and their important contribution to streptococcal colonization and disease.

Identification of Small-Molecule Inhibitors Targeting Porphyromonas gingivalis Interspecies Adherence and Determination of Their In Vitro and In Vivo Efficacies.

Porphyromonas gingivalis is one of the primary causative agents of periodontal disease and initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of a minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (AgI/II). Our previous work identified an AgI/II peptide that potently inhibited adherence and significantly reduced P. gingivalis virulence in vivo, suggesting that this interaction represents a potential target for drug discovery. To develop targeted small-molecule inhibitors of this protein-protein interaction, we performed a virtual screen of the ZINC databases to identify compounds that exhibit structural similarity with the two functional motifs (NITVK and VQDLL) of the AgI/II peptide. Thirty three compounds were tested for in vitro inhibition of P. gingivalis adherence and the three most potent compounds, namely, N7, N17, and V8, were selected for further analysis. The in vivo efficacy of these compounds was evaluated in a murine model of periodontitis. Treatment of mice with each of the compounds significantly reduced maxillary alveolar bone resorption in infected animals. Finally, a series of cytotoxicity tests were performed against human and murine cell lines. Compounds N17 and V8 exhibited no significant cytotoxic activity toward any of the cell lines, whereas compound N7 was cytotoxic at the highest concentrations that were tested (20 and 40 μM). These results identify compounds N17 and V8 as potential lead compounds that will facilitate the design of more potent therapeutic agents that may function to limit or prevent P. gingivalis colonization of the oral cavity.

Isolating Pathogen-Specific Human Monoclonal Antibodies (hmAbs) Using Bacterial Whole Cells as Molecular Probes.

The immunoglobulin capture assay (ICA) enables the enrichment for pathogen-specific plasmablasts from individuals with a confirmed adaptive immune response to vaccination or disseminated infection. Only single recombinant antigens have been used previously as probes in this ICA and it was unclear whether the method was applicable to complex probes such as whole bacterial cells. Here, we describe the enrichment of plasmablasts specific for polysaccharide and protein antigens of both Streptococcus pneumoniae and Neisseria meningitidis using whole formalin-fixed bacterial cells as probes. The modified ICA protocol described here allowed for a pathogen-specific hmAb cloning efficiency of >80%.

Group A Streptococcal Pharyngitis Testing Appropriateness in Pediatric Acute Care Settings.

Acute pharyngitis is one of the most common causes of ambulatory clinic visits; however, group A Streptococcus accounts for less than a third. National guidelines recommend against streptococcal testing in patients with viral features. This study aims to assess the rate of inappropriate streptococcal rapid antigen detection tests (RADT)s in children evaluated in urgent care clinics (UCC)s and emergency department (ED)s at a children's hospital. We retrospectively reviewed charts of 10% of children 3 years or older with RADTs ordered between April and September 2018 at EDs and UCCs. The test was determined to be inappropriate if the patient had no sore throat and/or had 2 or more viral symptoms: rhinorrhea/congestion, cough, diarrhea, hoarseness, conjunctivitis, or viral exanthem. Over the study period, 7678 RADTs were performed, of which 7024 (91.2%) were in children 3 years or older. We evaluated 708 charts and found 44% of RADTs were inappropriate. The predicted probability of inappropriate RADT was highest among patients with a triaged reason for visit for respiratory complaints (70.5%), viral upper respiratory tract infection (69.7%), and rash (61.3%). Of the inappropriate RADTs, 20.1% were positive, whereas 32.2% of the appropriate RADTs were positive. Quality improvement initiatives are needed to decrease the rate of inappropriate RADTs in pediatric UCC and ED settings.

Abstract CT241: Trial in progress: IFx-Hu2.0 (plasmid DNA coding for Emm55 streptococcal antigen in a cationic polymer) phase I first in human study for unresectable stage III or stage IV cutaneous melanoma

Abstract Background: Anti-PD-1 and anti-CTLA4 immune-based therapeutics have vastly improved melanoma survival rates, but many patients still do not benefit from these therapies. IFx-Hu2.0 is a plasmid DNA encoding the streptococcal membrane protein, Emm55, contained within a cationic polymer. Preliminary correlative laboratory data from the first in human IFx-Hu2.0 phase I feasibility study for use as an intralesional melanoma therapy is reported. No clinical data will be presented. The melanoma tumor microenvironment, pre- and post-treatment, was analyzed on FFPE tissues collected from the first three patients with a panel consisting of CD3, CD8, FOXP3, PD1, PDL1, SOX10 and DAPI. The numbers of SOX10+ melanoma cells tended to decrease with treatment (Patient 1: 16.7% SOX10+ cells pre-treatment, 0.3% SOX10+ cells post treatment; Patient 2: 47.1% pre/6.0% post; Patient 3: 49.0% pre/52.7% post). Multi-parameter analysis revealed that when the numbers of SOX10+ cells decreased, there were an increased number of T cells in the tumor environment. This observation also held true for the whole section for patient 2. In this patient, there were 0.3% CD3+CD8+ T cells prior to treatment but this number increased to 15.2% after treatment. Interestingly, the numbers of FOXP3 regulatory T cells also increased in this patient suggesting the formation of an immune response. Taken together, IFx-Hu2.0 is proposed to create an immune response in melanoma patients and is being tested in a first in human trial. Methods: Up to six patients (&amp;gt;18 years) with unresectable stage III or IV cutaneous melanoma will have cutaneous melanoma lesions injected with IFx-Hu2.0 to test the safety, tolerability, and feasibility of intralesional IFx-Hu2.0 injection. The subjects must have at least one lesion available for injection and another biopsiable lesion. This trial is unique as a cutaneous lesion as small as 3 mm may be injected. To be eligible, subjects should have been considered for anti-PD-1 therapy, TVEC and/or BRAF inhibition as indicated in the FDA labels for those agents. Small brain metastases (1 cm) are permitted assuming the subjects receive concurrent radiation at a site distant from intralesional injection with a greater than 3-month life expectancy. These patients may not be receiving any other systemic therapies, may not have uncontrolled hepatitis/HIV infection, and may not have a history of immunosuppression as is seen in patients who have undergone organ transplantation. For correlative studies, 4 tubes of peripheral blood will be collected at the beginning of the study and at the dose limiting toxicity (DLT) assessment visit 28 days later. Trial subjects will have the option of continued dosing every 3 weeks if they have a response to therapy. Success of the study is defined as being able to treat 5/6 subjects without DLT at 28 days. Three of the six planned trial subjects have been enrolled as of January 2020 (Clinical trial registry number: NCT03655756). Citation Format: Joseph Markowitz, Andrew Brohl, Amod A. Sarnaik, Zeynep Eroglu, Deanryan B. De Aquino, Nikhil Khushalani, Ahmad Tarhini, Vernon K. Sondak, Shari Pilon-Thomas. Trial in progress: IFx-Hu2.0 (plasmid DNA coding for Emm55 streptococcal antigen in a cationic polymer) phase I first in human study for unresectable stage III or stage IV cutaneous melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT241.

Increased vulnerability to impulsive behavior after streptococcal antigen exposure and antibiotic treatment in rats

RationaleThe inflammation induced by Group A Streptococcus (GAS) infection has been viewed as a vulnerability factor in mental disorders characterized by inhibitory control deficits, such as attention-deficit/hyperactivity disorder or obsessive–compulsive disorder. Antibiotic treatment reduces GAS symptoms; however, its effects on impulsivity have not been fully assessed. ObjectivesWe investigated whether GAS exposure during early adolescence might be a vulnerability factor for adult impulsivity, if antibiotic treatment acts as a protective factor, and whether these differences are accompanied by changes in the inflammatory cytokine frontostriatal regions. MethodsMale Wistar rats were exposed to the GAS antigen or to vehicle plus adjuvants at postnatal day (PND) 35 (with two boosts), and they received either ampicillin (supplemented in the drinking water) or water alone from PND35 to PND70. Adult impulsivity was assessed using two different models, the 5-choice serial reaction time task (5-CSRT task) and the delay discounting task (DDT). The levels of interleukin-6 (IL-6) and IL-17 were measured in the prefrontal cortex (PFc), and the tumor necrosis factor α levels (TNFα) were measured in the PFc and nucleus accumbens (NAcc). ResultsGAS exposure and ampicillin treatment increased the waiting impulsivity by a higher number of premature responses when the animals were challenged by a long intertrial interval during the 5-CSRT task. The GAS exposure revealed higher impulsive choices at the highest delay (40 s) when tested by DDT, while coadministration with ampicillin prevented the impulsive choice. GAS exposure and ampicillin reduced the IL-6 and IL-17 levels in the PFc, and ampicillin treatment increased the TNFα levels in the NAcc. A regression analysis revealed a significant contribution of GAS exposure and TNFα levels to the observed effects. ConclusionsGAS exposure and ampicillin treatment induced an inhibitory control deficit in a different manner depending on the form of impulsivity measured here, with inflammatory long-term changes in the PFc and NAcc that might increase the vulnerability to impulsivity-related neuropsychiatric disorders.

An audit of community-acquired pneumonia antimicrobial compliance using an intervention bundle in an Irish hospital

ObjectivesHospitalisations with community-acquired pneumonia (CAP) are often not managed in accordance with antimicrobial guidelines. This study aimed to assess whether guideline-driven antimicrobial prescribing for CAP can be improved using an intervention bundle. Secondary measures assessed were hospital length of stay (LOS), mortality, duration of intravenous antibiotics and total antibiotics, improved uptake of appropriate investigations, and documentation of CURB-65 score. MethodsA retrospective cohort of hospitalised CAP patients from August–September 2018 was compared with a post-intervention prospective cohort from May–June 2019. The intervention bundle included a mobile audience response system, promotion of the antimicrobial app, development of a physical card with local guidelines, and incorporating CURB-65 into the unscheduled admission proforma. Local guidelines are in keeping with British Thoracic Society CAP guidelines. ResultsA total of 69 adult patients (aged >18 years) were included in the study (37 retrospective, 32 prospective). Overall compliance with local CAP guidelines improved from 21.6% to 62.5% (P < 0.001). No difference in initial intravenous antibiotic duration was seen (median 4 days vs. 4 days; P = 0.70) and total antibiotic duration was significantly shorter in the post-intervention group (median 9 days vs. 7 days; P = 0.01). No difference in LOS or mortality was seen between the groups. Documentation of CURB-65 improved from 5.4% to 46.9% (P < 0.001). Uptake of streptococcal urinary antigen testing improved from 18.9% to 40.6% (P = 0.024). ConclusionsA simple, low-cost quality improvement bundle can significantly increase appropriate antimicrobial prescribing and shorten the total antibiotic duration.

Microbiome analysis of contact lens care solutions and tear fluids of contact lens wearers: Possible involvement of streptococcal antigens in allergic symptoms related to contact lens wear.

The present study elucidated the pathogenesis of allergic symptoms (AS) related to contact lens (CL) wear by assaying CL care solutions in lens storage cases and tears from subjects with AS using molecular biology techniques. A total of 15 CL storage cases were collected from subjects with AS (n=9) and healthy, asymptomatic control CL wearers (n=6). Bacterial populations in CL care solutions and tears were assayed by culture and 16S rDNA sequencing. Histamine levels in tears were measured by high-performance liquid chromatography. Western blot analysis was performed to identify the bacteria recognized by tear IgE from subjects with AS. No significant differences were found in the culture results between the subjects with AS and asymptomatic subjects. Histamine was detected in 2 subjects with AS. Meta-16S rDNA sequencing identified a cluster of 4 subjects with AS that were distinguished from others by principal coordinate analysis. Detailed population analysis revealed that the abundance of Gram-positive bacteria in the microbiomes of CL care solutions used by the subjects with AS were higher than those of asymptomatic subjects (42.24±9.47 vs. 16.85±22.76% abundance). Among these, Streptococcus was the dominant genus (12.1-18.3% abundance). Tear microbiome analysis revealed that the abundance of Streptococcus in the subjects with AS was significantly higher than that in other subjects (19.02±5.50 vs. 3.08±3.35%, P<0.01). Western blot analysis demonstrated that the tear IgE in all subjects with AS reacted with Streptococcus (100%), but not with Staphylococcus. On the whole, these results provide novel insight into the pathogenesis of AS and identify Streptococcus as an important factor in AS associated with CL wear.

The antibiotic prescribing behaviors of physicians are changed via rapid antigen test practice in the context of rational drug use

Background/aimRapid antigen test (RAT) is a practical test to detect the presence of Group A beta hemolytic streptococcus antigens in throat swab samples. The aim of this study is to investigate the changes in the empiric antibiotic prescribing behavior of 10 family physicians in Kırıkkale Province after using RAT in 2017. Materials and methods RAT test practice started in Family Medicine in February 2017. Family Medicine Information System (FMIS) includes clinical and prescription records of 10 family physicians, providing health service to approximately 35,000 residents in Kırıkkale. The numbers of antibiotics prescribed by the physicians according to the ICD-10 codes (including upper respiratory tract infections) in February, March, and April of 2015, 2016, 2017 were determined. The number and group of antibiotics prescribed by the family physicians with the determined diagnosis and time periods were specified in the FMIS and recorded.Results Antibiotic prescription behaviors of family physicians do not show a significant difference between 2015 and 2016. There was a dramatic and significant decrease in the number of prescribed antibiotics in 2017 compared to 2015 and 2016 (P < 0.05).Conclusion This study shows that there has been a significant decrease in antibiotic prescription in 10 Family Medicine departments in 2017 in comparison to February, March, and April 2015 and 2016. The use of RAT resulted in a decrease in antibiotic prescription rates in 2017.

You Say that You Want a Molecular Revolution? Changing from the Group A Streptococcus Antigen and Culture Paradigm to Molecular Testing

Group A Streptococcus (GAS) (Streptococcus pyogenes) is the most common bacterial cause of acute pharyngitis. Diagnosed cases of GAS pharyngitis should be treated with antibiotics to prevent primary and secondary complications. Commonly, testing for GAS pharyngitis can be done rapidly (in minutes) using rapid antigen detection tests (RADTs), which generally have relatively high specificity (>90%) but lower sensitivity (70 to 90%). The low sensitivity of GAS RADTs requires that culture be performed to maximize sensitivity, which delays the final result by 24 to 48 hours. New molecular GAS assays are on the market and offer relatively rapid (i.e., minutes to tens of minutes) and highly sensitive results so that culture is not required for negative results. We describe our experience with moving from RADT and culture testing for GAS to solely molecular testing, providing quicker results for improved patient care.

Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study

BackgroundStreptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore.MethodsRetrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design.ResultsWe identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson’s score 1 (IQR 0–4), vs 3 (1–5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8–17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06–0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson’s score > 3.ConclusionPatients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.

Update on group A streptococcal vaccine development.

There is a global need for well tolerated, effective, and affordable vaccines to prevent group A streptococcal infections and their most serious complications. The aim of this review is to highlight the recent progress in the identification of promising vaccine antigens and new approaches to vaccine design that address the complexities of group A streptococcal pathogenesis and epidemiology. Combination vaccines containing multiple shared, cross-protective antigens have proven efficacious in mouse and nonhuman primate models of infection. The development of complex multivalent M protein-based vaccines is continuing and several have progressed through early-stage human clinical trials. Formulations of vaccines containing universal T-cell epitopes, toll-like receptor agonists, and other adjuvants more potent than alum have been shown to enhance protective immunogenicity. Although the group A streptococcal vaccine antigen landscape is populated with a number of potential candidates, the clinical development of vaccines has been impeded by a number of factors. There are now concerted global efforts to raise awareness about the need for group A streptococcal vaccines and to support progress toward eventual commercialization and licensure. Preclinical antigen discovery, vaccine formulation, and efficacy studies in animal models have progressed significantly in recent years. There is now a need to move promising candidates through the clinical development pathway to establish their efficacy in preventing group A streptococcal infections and their complications.

A 45-year-old Female with an Atypical Presentation of Pharyngitis.

IntroductionEmergency physicians are trained to treat a variety of ailments in the emergency department (ED), some of which are emergent, while others are not. A common complaint seen in the ED is a sore throat. While most sore throats are easily diagnosed and treated, less common causes are often not considered in the differential diagnoses. Therefore, the purpose of this case study was to present an atypical case of sore throat and discuss differential diagnoses.Case PresentationThe patient was a 45-year-old female who presented to the ED with a three-day history of sore throat that was exacerbated by eating and drinking. The patient was not on any prescription medications, but tried over-the-counter medications for the sore throat without any improvement in symptoms. Review of systems was positive for sore throat, fevers, and chills. Physical examination of her oropharynx revealed mildly dry mucous membranes with confluent plaques and white patchy ulcerative appearance involving the tongue, tonsils, hard palate, and soft palate. Rapid streptococcal antigen, mononucleosis spot test, and KOH test were performed and found to be negative.DiscussionAfter initial testing was negative, a follow-up complete blood count with differential and complete metabolic profile were ordered. The patient was found to have decreased lymphocytes and platelets. Based upon those results, a diagnosis was made in the ED, the patient was started on medication, and further laboratory workup was ordered to confirm the diagnosis. ED providers should consider non-infectious as well as infectious causes for a sore throat, as this might lead to a diagnosis of an underlying condition.