Machine Learning for Clinical Decision Support of Acute Streptococcal Pharyngitis: A Pilot Study.

BACKGROUND: Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance. OBJECTIVES: To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children. METHODS: We assessed 54 children aged 2-17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification. RESULTS: The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36). CONCLUSIONS: Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.

Streptococcal Pharyngitis: Rapid Evidence Review.

Group A beta-hemolytic streptococcal pharyngitis is a common infection responsible for more than 6 million office visits in the United States annually. Only 10% of adults seeking care for a sore throat have group A beta-hemolytic streptococcal pharyngitis; however, 60% or more are prescribed antibiotics. Guidelines recommend using clinical decision rules to assess the risk of group A beta-hemolytic streptococcal infection, followed by rapid antigen testing if a diagnosis is unclear, before prescribing antibiotics. Fever, tonsillar exudate, cervical lymphadenitis, and patient ages of 3 to 15 years increase clinical suspicion. A cough is more suggestive of a viral etiology. The limited history used in these decision rules is amenable to virtual visits. After a negative rapid antigen test result, a throat culture is recommended in children and adolescents. Penicillin and amoxicillin are first-line antibiotics, with a recommended course of 10 days; first-generation cephalosporins are recommended for patients with nonanaphylactic allergies to penicillin. There is significant resistance to azithromycin and clarithromycin in some parts of the United States. Steroids are not recommended for symptomatic treatment. Patients with worsening symptoms after appropriate antibiotic initiation or with symptoms lasting 5 days after the start of treatment should be reevaluated. Tonsillectomy is rarely recommended as a preventive measure: seven episodes of streptococcal pharyngitis in 1 year, five episodes in each of the past 2 years, or three episodes in each of the past 3 years are commonly used thresholds for considering surgery.

Group A Streptococcus pharyngitis in Children: New Perspectives on Rapid Diagnostic Testing and Antimicrobial Stewardship.

The most common cause of bacterial pharyngitis is Group A Streptococcus (GAS). Accurate diagnosis of GAS pharyngitis is crucial to identify children who would benefit from antibiotic treatment. Rapid diagnosis has the potential to reduce antibiotic overuse. Current national guidelines differ in their recommendations for GAS testing. While rapid antigen detection tests (RADTs) are widely used, their sensitivity is considered too low for stand-alone testing by several expert bodies. Newer molecular tests using nucleic acid amplification show higher accuracy and fast results, but their cost, complexity, and very high sensitivity may limit widespread adoption. This review provides up-to-date evidence regarding rapid diagnostic testing and antimicrobial stewardship in children with sore throat. We discuss discrepancies across GAS testing guidelines at the international level, patient selection for testing for GAS, rapid test accuracy, and the potential role of rapid GAS tests to promote antibiotic stewardship, with emphasis on emerging rapid molecular tests.

Group A Streptococcus Infections.

Group A Streptococcus causes a variety of clinical manifestations, including pharyngitis and skin and soft tissue infections as well as more invasive disease. There are also multiple nonsuppurative complications of group A Streptococcus infection, including acute rheumatic fever and poststreptococcal glomerulonephritis. Pediatricians should be able to diagnose and treat the various presentations of the infection.

The effect of different endotracheal tube cuff pressure monitoring systems on postoperative sore throat in patients undergoing tracheal intubation: a randomized clinical trial.

BACKGROUND: Postoperative sore throat (POST) is an unpleasant outcome that can occur as a result of tracheal intubation in adults. Increased pressure from the endotracheal tube (ETT) cuff often leads to local mucosal injury, resulting in sore throat. The purpose of this study was to compare the effect of two different ETT cuff pressure monitoring systems vs. no cuff pressure monitoring on the incidence and severity of POST in adults. METHODS: One hundred and fourteen ASA I-III patients of either gender, aged 18-65 years, and undergoing surgery requiring endotracheal intubation were included in this study. Patients were randomized into three groups: control (C), cuff pressure gauge (G), and automated cuff controller (A). The ETT cuff pressure was not monitored intraoperatively in group C but was monitored using a cuff pressure gauge and an automated cuff controller in groups G and A, respectively. Postoperatively, patients were assessed at 2, 24, and 48 h for the presence and severity of POST, hoarseness and cough. RESULTS: One hundred and eleven patients completed the study. POST occurred in 40.5% of the patients in group G (n = 37) (p = 0.013) and 23.7% of the patients in group A (n = 38) (p < 0.001) within 48 h after surgery, compared to 69.4% in group C (n = 36). There were no significant differences in hoarseness, coughing, and dysphagia across the groups at any time. When comparing groups A and C, individuals in group A exhibited a lower occurrence of significant (grade ≥ 2) POST and hoarseness (10.5% vs. 41.7%, p = 0.002; 26.3% vs. 58.3%, p = 0.005). The incidence of significant cough and dysphagia did not differ substantially across the patient groups within 48 h after surgery. POST scores in group A at 2, 24 h postoperatively were both 0 (0-0), which was significantly lower than those in group C (1 (0-2) at 2 h, p < 0.001 ; 1 (0-1) at 24 h, p = 0.001). POST in group G at 2 h postoperatively was graded as 0 (0-1.5) which was milder than group C (P = 0.024). The severity of hoarseness in group A with scores of 0 (0-2) was superior to that in group C (2 (0-2), p = 0.006) at 2 h postoperatively. CONCLUSIONS: In conclusion, the findings of this study indicated that the occurrence of POST can be reduced by using either the cuff pressure gauge approach or the automated cuff controller method. The automated cuff controller monitoring can potentially decrease the severity of POST and hoarseness. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100054089, Date: 08/12/2021.

Systematic review and meta-analysis of the accuracy of McIsaac and Centor score in patients presenting to secondary care with pharyngitis.

BACKGROUND: Centor and McIsaac scores are clinical prediction rules for diagnosing group A streptococcus (GAS) infection in patients with pharyngitis. Their recommended thresholds vary between guidelines. OBJECTIVES: To estimate the sensitivity and specificity of the McIsaac and Centor scores to diagnose GAS pharyngitis and evaluate their impact on antibiotic prescribing at each threshold in patients presenting to secondary care. DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: Studies of patients presenting with acute pharyngitis to emergency or outpatient clinics that estimated the accuracy of McIsaac or Centor scores against throat cultures and/or rapid antigen detection tests (RADT) as reference standards. TESTS: Centor or McIsaac score. REFERENCE STANDARD: Throat cultures and/or RADT. ASSESSMENT OF RISK OF BIAS: Quality Assessment of Diagnostic Accuracy Studies. METHODS OF DATA SYNTHESIS: The sensitivities and specificities of the McIsaac and Centor scores were pooled at each threshold using bivariate random effects meta-analysis. RESULTS: Fourteen studies were included (eight McIsaac and six Centor scores). Eight studies had unclear and six had a high risk of bias. The McIsaac score had higher estimated sensitivity and lower specificity relative to Centor scores at equivalent thresholds but with wide and overlapping confidence regions. Using either score as a triage to RADT to decide antibiotic treatment would reduce antibiotic prescription to patients with non-GAS pharyngitis relative to RADT test for everyone, but also reduce antibiotic prescription to patients with GAS. DISCUSSION: Centor and McIsaac scores are equally ineffective at triaging patients who need antibiotics presenting with pharyngitis at hospitals. At high thresholds, too many true positive cases are missed, whereas at low thresholds, too many false positives are treated, leading to the over prescription of antibiotics. The former may be compensated by adequate safety netting by clinicians, ensuring that patients can seek help if symptoms worsen.

Use of saliva-based qPCR diagnostics for the accurate, rapid, and inexpensive detection of strep throat.

OBJECTIVES: Outpatient health care facilities are essential for quickly diagnosing common infectious diseases such as bacterial and viral pharyngitis. The only form of pharyngitis requiring antibiotics is strep throat (ST); however, antibiotic prescription rates are much higher than ST prevalence, suggesting antibiotics are being inappropriately prescribed. Current rapid ST diagnostics may be contributing to this problem due to the low sensitivity and variable specificity of these tests. It is best practice to verify a negative ST diagnosis with a group A Streptococcus (GAS) culture, but many clinics do not perform this test due to the additional cost and 24-72 h required to obtain results. This indicates there is great need for more accurate rapid diagnostic tools in outpatient facilities. We hypothesized that next generation qPCR technology could be adapted to detect GAS DNA from saliva samples (instead of the traditional throat swab) by creating a simple, fast, and inexpensive protocol. METHODS: Saliva specimens collected from patients at James Madison University Health Center were used to test the effectiveness of our Chelex 100-based rapid DNA extraction method, followed by a fast protocol developed for the Open qPCR machine to accurately detect ST. RESULTS: Our final saliva processing and qPCR protocol required no specialized training to perform and was able to detect ST with 100 % sensitivity and 100 % specificity (n=102) in 22-26 min, costing only $1.12 per sample. CONCLUSIONS: Saliva can be rapidly analyzed via qPCR for the accurate and inexpensive detection of ST.

Diagnostic performance of clinical prediction rules to detect group A beta-haemolytic streptococci in people with acute pharyngitis: a systematic review.

OBJECTIVE: To assess and compare the diagnostic performance of Clinical Prediction Rules (CPRs) developed to detect group A Beta-haemolytic streptococci in people with acute pharyngitis (or sore throat). STUDY DESIGN: A systematic review. METHODS: We searched PubMed, Embase and Web of Science (inception-September 2022) for studies deriving and/or validating CPRs comprised of ≥2 predictors from an individual's history or physical examination. Two authors independently screened articles, extracted data and assessed risk of bias in included studies. A meta-analysis was not possible due to heterogeneity. Instead we compared the performance of CPRs when they were validated in the same study population (head-to-head comparisons). We used a modified grading of recommendations, assessment, development, and evaluations (GRADE) approach to assess certainty of the evidence. RESULTS: We included 63 studies, all judged at high risk of bias. Of 24 derived CPRs, 7 were externally validated (in 46 external validations). Five validation studies provided data for head-to-head comparison of four pairs of CPRs. Very low certainty evidence favoured the Centor CPR over the McIsaac (2 studies) and FeverPain CPRs (1 study) and found the Centor CPR was equivalent to the Walsh CPR (1 study). The AbuReesh and Steinhoff 2005 CPRs had a similar poor discriminative ability (1 study). Within and between study comparisons suggested the performance of the Centor CPR may be better in adults (>18 years). CONCLUSION: Very low certainty evidence suggests a better performance of the Centor CPR. When deciding about antibiotic prescribing for pharyngitis patients, involving patients in a shared decision making discussion about the likely benefits and harms, including antibiotic resistance, is recommended. Further research of higher rigour, which compares CPRs across multiple settings, is needed.

Presentation Rates for Acute Pharyngitis in the Emergency Room Are Influenced by Extreme Weather Events.

OBJECTIVE: Extreme weather events are becoming more prevalent with the increasing pace of climate change. These events negatively impact human health and put considerable strain on health care resources, including emergency departments. Within otolaryngology, acute pharyngitis is a common reason for emergency room visits (ERV). Therefore, we aimed to investigate the impact of extreme meteorological conditions on ERV rates related to acute pharyngitis. STUDY DESIGN: Retrospective time-series study. SETTING: ERVs related to acute pharyngitis (n = 1511) were identified at a tertiary care hospital in Vienna, Austria, between 2015 and 2018. METHODS: The effects of single-day and prolonged (3-day) extreme weather events on ERVs were analyzed using a distributed lag nonlinear model. Relative risk (RR) and cumulative relative risk (cRR) were calculated over a lag period of 14 days. RR refers to the risk for pharyngitis-related ERV at extreme conditions (1st, 5th, 95th, or 99th percentile) compared to the risk at median conditions. RESULTS: Same-day RR (lag0) was elevated more than 3-fold after prolonged extremely low mean temperatures (P = .028). Furthermore, same-day RR after single-day and prolonged extremely high relative humidity was elevated by 51% (P = .024) and 46% (P = .036), respectively. Significant delayed effects on cRR were observed for extreme mean temperatures, relative humidity, and mean wind speeds within 8 days and for extreme atmospheric pressure within 14 days. CONCLUSION: Extreme weather events impact ERV rates for acute pharyngitis. Extremely low temperatures, high relative humidity, high atmospheric pressure, and low and high wind speeds were risk-promoting factors.

A pharmacy-led sore throat test and treat (STTT) service: antigen testing and antibiotic supply rates during the period of heightened public awareness of Group A Streptococcus infections.

BACKGROUND: Community pharmacies in Wales delivered an NHS-funded sore throat test and treat (STTT) service during the period of increased invasive Group A Streptococcus (iGAS) incidents in winter 2022-23. Service users were screened using FeverPAIN/CENTOR scores, offered GAS rapid antigen detection tests (RADT) if appropriate, and antibiotics if indicated. OBJECTIVES: To evaluate the service's response to a substantial rise in sore throat presentations during a period of heightened public anxiety. METHODS: Cross-sectional study with anonymized individual-level data from electronic pharmacy records of all eligible STTT service users, between January 2022 and March 2023. RESULTS: Antibiotics were supplied to 24% (95% CI: 23-24) of people who used the STTT service and 31% (95% CI: 31-32) of those who met the threshold for an RADT. Of 27 441 STTT consultations, 9308 (33.9%) occurred during December 2022. In the week commencing 2 December 2022, following the announcements of increased iGAS incidents, we observed a statistically significant increase of 1700 consultations (95% CI: 924-2476) and a statistically significant decrease in supply rate of 13.9 antibiotics per 100 RADT (95% CI: -18.40 to -9.40). Antibiotic supply rates increased thereafter to those observed before the announcements of iGAS incidents. Referral rates to other primary care or emergency settings remained below 10% throughout the study period. CONCLUSIONS: Our findings suggest that, despite a dramatic increase in sore throat consultation rates in response to media reports, the pre-specified pathway followed by pharmacists ensured appropriate use of antibiotics, and absorbed a substantial workload that would otherwise end up in other healthcare settings.

Internet Tool to Support Self-Assessment and Self-Swabbing of Sore Throat: Development and Feasibility Study.

BACKGROUND: Sore throat is a common problem and a common reason for the overuse of antibiotics. A web-based tool that helps people assess their sore throat, through the use of clinical prediction rules, taking throat swabs or saliva samples, and taking throat photographs, has the potential to improve self-management and help identify those who are the most and least likely to benefit from antibiotics. OBJECTIVE: We aimed to develop a web-based tool to help patients and parents or carers self-assess sore throat symptoms and take throat photographs, swabs, and saliva samples for diagnostic testing. We then explored the acceptability and feasibility of using the tool in adults and children with sore throats. METHODS: We used the Person-Based Approach to develop a web-based tool and then recruited adults and children with sore throats who participated in this study by attending general practices or through social media advertising. Participants self-assessed the presence of FeverPAIN and Centor score criteria and attempted to photograph their throat and take throat swabs and saliva tests. Study processes were observed via video call, and participants were interviewed about their views on using the web-based tool. Self-assessed throat inflammation and pus were compared to clinician evaluation of patients' throat photographs. RESULTS: A total of 45 participants (33 adults and 12 children) were recruited. Of these, 35 (78%) and 32 (71%) participants completed all scoring elements for FeverPAIN and Centor scores, respectively, and most (30/45, 67%) of them reported finding self-assessment relatively easy. No valid response was provided for swollen lymph nodes, throat inflammation, and pus on the throat by 11 (24%), 9 (20%), and 13 (29%) participants respectively. A total of 18 (40%) participants provided a throat photograph of adequate quality for clinical assessment. Patient assessment of inflammation had a sensitivity of 100% (3/3) and specificity of 47% (7/15) compared with the clinician-assessed photographs. For pus on the throat, the sensitivity was 100% (3/3) and the specificity was 71% (10/14). A total of 89% (40/45), 93% (42/45), 89% (40/45), and 80% (30/45) of participants provided analyzable bacterial swabs, viral swabs, saliva sponges, and saliva drool samples, respectively. Participants were generally happy and confident in providing samples, with saliva samples rated as slightly more acceptable than swab samples. CONCLUSIONS: Most adult and parent participants were able to use a web-based intervention to assess the clinical features of throat infections and generate scores using clinical prediction rules. However, some had difficulties assessing clinical signs, such as lymph nodes, throat pus, and inflammation, and scores were assessed as sensitive but not specific. Many participants had problems taking photographs of adequate quality, but most were able to take throat swabs and saliva samples.

Faringoamigdalitis y estreptococo, ¿enemigo o colonizador? / Tonsillopharyngitis and streptococcus, enemy or colonizer?

Introducción: la principal etiología de la faringoamigdalitis aguda (FAA) es vírica, y entre la bacteriana, Streptococcus pyogenes constituye un colonizador no despreciable de la población pediátrica sana. El objetivo del estudio es conocer el modo de utilización del test de diagnóstico rápido estreptocócico (TDR) en los servicios de urgencias pediátricas para poder optimizar su uso, reducir el sobrediagnóstico de las FAA estreptocócicas (FAAE) y la prescripción de antibióticos. Material y métodos: se recoge la información retrospectiva del número de TDR realizados a los pacientes atendidos en el servicio de urgencias pediátricas de un hospital terciario, desde enero de 2022 a enero de 2023 (ambos inclusive). También se ha recogido información acerca de a cuántos se les había practicado más de un TDR y el tiempo transcurrido. Resultados: durante los 13 meses estudiados se realizaron un total de 1610 TDR (43% en <5 años). Se realizó más de un TDR a 89 pacientes (53% en <5 años) y el 40% de estos se llevaron a cabo en los primeros 40 días. Discusión: las pruebas microbiológicas para detectar Streptococcus pyogenes no son capaces de diferenciar entre infección activa y estado de portador sano. Según los resultados de nuestro estudio parece existir un uso inadecuado de los TDR; la mayoría de las pruebas se realizan en <5 años, donde la etiología estreptocócica es menos frecuente y el estado de portador sano predominante. Esto conlleva un sobrediagnóstico de la FAAE, sobretratamiento antibiótico, aparición de efectos adversos y resistencias bacterianas. (AU)

Introduction: the most frequent aetiology of acute pharyngitis (AP) is viral, and among the bacterial causes, Streptococcus pyogenes is a colonizer that cannot be overlooked in the healthy paediatric population. The aim of the study was to determine how the rapid streptococcal diagnostic test (RST) is used in paediatric emergency departments in order to optimize its use and reduce the overdiagnosis of acute streptococcal pharyngitis (SP) and antibiotic prescribing. Material and methods: we collected retrospective data on the number of RSTs performed on patients managed in the paediatric emergency department of a tertiary care hospital between January 2022 and January 2023 (both included). We also collected data on the number of patients who underwent more than one RST and the time elapsed between tests. Results: during the 13-month study period, a total of 1610 RSTs were performed (43% in children < 5 years). More than one RST was performed in 89 patients (53% in children < 5 years), and 40% of additional tests were performed within 40 days of the previous one. Discussion: microbiological tests for S. pyogenes cannot differentiate between active infection and healthy carriage. Based on the findings of our study, there seems to be an inadequate use of RDTs; most tests are performed in children aged less than 5 years, in whom a streptococcal aetiology is less frequent and healthy carrier status predominates. This leads to overdiagnosis of acute SP, antibiotic overuse, adverse events and bacterial resistance. (AU)

Knowledge, attitudes and practices of patients with chronic pharyngitis toward laryngopharyngeal reflux in Suzhou, China.

BACKGROUND: This study aimed to investigate the knowledge, attitudes and practices (KAP) of patients with chronic pharyngitis in Suzhou, China toward laryngopharyngeal reflux (LPR). METHODS: This cross-sectional study was conducted in patients with chronic pharyngitis in Suzhou, China at the otolaryngology outpatient clinic of the First Affiliated Hospital of Soochow University between November, 2022, and May, 2023. Data was collected through a self-designed online questionnaire encompassing the sociodemographic characteristics and three dimensions of KAP. The questionnaire was administered using SoJump, and data were exported from this platform. Subsequently, statistical analysis, including Structural Equation Modeling, was performed using SPSS 22 software to evaluate the KAP scores. RESULTS: A total of 487 valid questionnaires were collected, with 275 (56.35%) female patients. The mean score of KAP were 4.76 ± 2.93 (possible range: 0-11), 33.10 ± 4.46 (possible range: 8-40), 31.29 ± 6.04 (possible range: 8-40), respectively. Pearson's correlation analysis showed significant positive correlations between knowledge and attitude dimensions (r = 0.413, P < 0.001), knowledge and practice dimensions (r = 0.355, P < 0.001), and attitude and practice dimensions (r = 0.481, P < 0.001). Structural equation modeling revealed that education exhibited positive effect on knowledge (ß = 0.476, P < 0.001) and attitude (ß = 0.600, P < 0.001), and having family history of chronic pharyngitis showed positive effect on knowledge (ß = 0.580, P = 0.047), experienced with reflux symptoms showed positive effect on knowledge (ß = 0.838, P = 0.001) and attitude (ß = 0.631, P = 0.085). Moreover, knowledge showed positive effect on attitude (ß = 0.555, P < 0.001) and practice (ß = 0.351, P < 0.001). Attitude, in turn, showed positive effect on practice (ß = 0.511, P < 0.001). CONCLUSION: Patients with chronic pharyngitis had inadequate knowledge, positive attitudes and suboptimal practices toward LPR. Education, family history of chronic pharyngitis, experienced with reflux symptoms might have effect on their KAP.

Evaluation of the Levels of Blood Cells, Vitamin D, and Inflammatory Factors in Children with PFAPA Syndrome.

BACKGROUND: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome) is the most common type of recurrent fever in childhood. The aim of this study was evaluation of the levels of blood cells, vitamin D, and inflammatory factors in children with PFAPA syndrome. METHODS: This retrospective descriptive study was conducted on the recorded information of children with PFAPA syndrome referred to the children's specialty clinic of Imam Khomeini Hospital in Ilam city from March 2021 to February 2022. Complete demographic information, presence of underlying disease, changes in blood cells, vitamin D level and inflammatory factors were obtained from the patients' records. Diagnosis of PFAPA syndrome was performed according to Thomas' criteria. RESULTS: This study was conducted on 40 children with PFAPA syndrome. The majority of patients were male and in the age range of 3 - 4 years. The results show that the average percentage of neutrophil and lymphocyte cells in the blood of patients was 54.45% and 40.62%, respectively. Also, 6 (15%), 3 (7.5%), and 31 (77.5%) patients had normal neutrophil levels, neutropenia, and neutrophilia, respectively. Regarding lymphocyte cells, 26 (65%), 8 (20%), and 6 (15%) people had normal lymphocyte level, lymphocytosis and lymphopenia, respectively. ESR levels increased in all patients (average percentage: 16.72). CRP level was negative in 9 (22.5%) and +1 in 19 (47.5%) patients, respectively. The results showed that 33 (82.5%) patients were deficient in vitamin D level. CONCLUSIONS: The etiology and pathogenesis of PFAPA is still unknown; however, the rapid response to corticosteroid therapy is the indication of an immune deregulation. Treatment guidelines for PFAPA syndrome based on controlled studies are needed, as well as a better understanding of the disease itself.

Volatile profiling distinguishes Streptococcus pyogenes from other respiratory streptococcal species.

Sore throat is one of the most common complaints encountered in the ambulatory clinical setting. Rapid, culture-independent diagnostic techniques that do not rely on pharyngeal swabs would be highly valuable as a point-of-care strategy to guide outpatient antibiotic treatment. Despite the promise of this approach, efforts to detect volatiles during oropharyngeal infection have yet been limited. In our research study, we sought to evaluate for specific bacterial volatile organic compounds (VOC) biomarkers in isolated cultures in vitro, in order to establish proof-of-concept prior to initial clinical studies of breath biomarkers. A particular challenge for the diagnosis of pharyngitis due to Streptococcus pyogenes is the likelihood that many metabolites may be shared by S. pyogenes and other related oropharyngeal colonizing bacterial species. Therefore, we evaluated whether sufficient metabolic differences are present, which distinguish the volatile metabolome of Group A streptococci from other streptococcal species that also colonize the respiratory mucosa, such as Streptococcus pneumoniae and Streptococcus intermedius. In this work, we identified 27 discriminatory VOCs (q-values < 0.05), composed of aldehydes, alcohols, nitrogen-containing compounds, hydrocarbons, ketones, aromatic compounds, esters, ethers, and carboxylic acid. From this group of volatiles, we identify candidate biomarkers that distinguish S. pyogenes from other species and establish highly produced VOCs that indicate the presence of S. pyogenes in vitro, supporting future breath-based diagnostic testing for streptococcal pharyngitis. IMPORTANCE Acute pharyngitis accounts for approximately 15 million ambulatory care visits in the United States. The most common and important bacterial cause of pharyngitis is Streptococcus pyogenesis, accounting for 15%-30% of pediatric pharyngitis. Distinguishing between bacterial and viral pharyngitis is key to management in US practice. The culture of a specimen obtained by a throat swab is the standard laboratory procedure for the microbiologic confirmation of pharyngitis; however, this method is time-consuming, which delays appropriate treatment. If left untreated, S. pyogenes pharyngitis may lead to local and distant complications. In this study, we characterized the volatile metabolomes of S. pyogenes and other related oropharyngeal colonizing bacterial species. We identify candidate biomarkers that distinguish S. pyogenes from other species and provide evidence to support future breath-based diagnostic testing for streptococcal pharyngitis.

Acute pharyngitis in children and adults: descriptive comparison of current recommendations from national and international guidelines and future perspectives.

This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A ß-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates.    Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.

PFAPA syndrome in children.

ABSTRACT: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is, as the name implies, characterized by an extremely regular cycle of fevers that is accompanied by one or more other symptoms such as oral ulcers, pharyngitis, adenitis, tonsillitis, sore throat, cervical adenopathy, and headache. Originally known as Marshall syndrome, PFAPA is most commonly identified in children younger than age 5 years; however, adults may also present with the disease, though they may report additional symptoms. PFAPA is now understood to be a diagnosis of exclusion. Laboratory studies are typically unremarkable except for increases in acute phase reactants such as C-reactive protein. Treatment is primarily supportive and most frequently uses systemic steroids to suppress the inflammatory response. Acute flares are self-limited, and the syndrome typically resolves on its own as the child reaches age 7 or 8 years.

A Longitudinal Study of Group A Streptococcal Colonization and Pharyngitis in US Children.

BACKGROUND: Group A streptococci (GAS) are a major cause of pharyngitis in children. Recently, there were severe GAS outbreaks. The aims of this study were to assess pharyngeal colonization prevalence in healthy children, to assess different diagnostic definitions for GAS pharyngitis and to estimate incidence rates for these infections. METHODS: A 2-year longitudinal study was conducted in healthy children in the United States. Pharyngeal swabs were cultured every 3 months for GAS colonization. Serum antistreptolysin O, antideoxyribonuclease B (DNaseB) and antistreptococcal C5a peptidase (SCP) antibody titers were assessed at baseline. When participants developed a sore throat, pharyngeal swabs were collected for rapid antigen detection test (RADT) and culture, and antibody titers were determined in serum samples. A range of case definitions were used for GAS pharyngitis. RESULTS: A total of 422 children 3-12 years old were enrolled (140, 141 and 141 were 3-5, 6-9 and 10-12 years of age, respectively). The overall prevalence of GAS colonization during the study was 48%. Baseline antistreptolysin O, anti-DNaseB and anti-SCP antibody titers were higher for children older than 5 years. The incidence of GAS pharyngitis per 100 person-years was 15.9 for RADT/culture-proven and 4.6 for serologically confirmed pharyngitis. CONCLUSIONS: GAS throat colonization and pharyngitis were frequent in children 3-12 years old. The case definition employed impacted the measured incidence of GAS pharyngitis, with higher rates detected using RADT/culture-based definitions. These data suggest that case definition is important and that young children are exposed to GAS, which may inform plans for vaccine development and implementation.

Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.

Despite the advanced knowledge concerning autoinflammatory diseases (AID), more data regarding the optimal treatment options and outcomes of the children who met the criteria of more than one AID are required. This study aimed to describe the demographic and clinical characteristics of children from familial Mediterranean fever (FMF)-endemic countries who meet both the FMF and the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome criteria. Moreover, we aimed to measure the response rates to colchicine and tonsillectomy and evaluate the factors affecting the colchicine response in these patients. The study was conducted at pediatric rheumatology tertiary centre. A total of 131 patients (58 females; 73 males) who met both the modified Marshall and pediatric FMF criteria were included. The median age at onset was 18 months (1-77 months), and the mean age at diagnosis was 47 ± 21.88 months. The median interval between episodes was 21 (7-90) days. The median disease duration was 46 (6-128) months. Consanguineous marriage was detected in 17 (13%) of the patients. The most common clinical finding was fever (100%), followed by exudative pharyngitis (88.5%), abdominal pain (86.3%), arthralgia (61.8%), stomatitis (51.1%), adenitis (42%), myalgia (28.7%), chest pain (16%), maculopapular rash (12.2%), arthritis (8.4%), and erysipelas-like rash (4.6%). MEFV gene variants were identified in 106 (80.9%) patients. The most common variants were M694V heterozygous (29%). We found that patients with tonsillopharyngitis, aphthous stomatitis, and PFAPA family history were more likely to be colchicine-resistant and tonsillectomy responsive, while those with exon 10 MEFV gene mutations were more prone to have a favorable response to colchicine.     Conclusion: PFAPA syndrome patients with exon 10 MEFV gene mutation, showing typical FMF symptoms, should be treated with colchicine, even after tonsillectomy. In multivariate analysis, PFAPA family history and lack of exon 10 MEFV gene mutations were independent risk factors for colchicine resistance. Thus, tonsillectomy may be recommended as a possible treatment option for these patients. It has yet to be clarified when colchicine treatment will be discontinued in patients whose attacks ceased after tonsillectomy that was performed due to colchicine unresponsiveness. What is Known: • A certain number of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome concomitantly fulfill the familial Mediterranean fever (FMF) criteria. • While colchicine is proposed as a first treatment choice in familial Mediterranean fever (FMF), corticosteroids are recommended as a first-line treatment in PFAPA syndrome patients. What is New: • In patients with concomitant PFAPA syndrome and FMF, PFAPA family history and lack of exon 10 MEFV gene mutation are predictive factors of colchicine resistance. • The presence of exon 10 MEFV gene mutations in patients with concomitant FMF and PFAPA syndrome has a favourable effect on response to colchicine treatment.

Knowledge, attitudes and practices of general practitioners and paediatricians towards Group A beta-haemolytic streptococcal tonsillopharyngitis: A cross-sectional study from Türkiye.

BACKGROUND AND OBJECTIVES: General practitioners (GPs) and paediatricians are very important in the management of sore throat in terms of providing correct diagnosis and treatment. The aim of this study was to evaluate the knowledge, attitudes and practices of GPs and paediatricians towards Group A beta-haemolytic streptococcal (GABHS) tonsillopharyngitis. METHOD: Three vignettes/case studies, in which the causative agents were GABHS, Epstein-Barr virus (EBV) and non-EBV viral infection, were presented as part of a questionnaire sent to paediatricians and GPs to elicit information regarding their diagnosis and treatment of tonsillopharyngitis. RESULTS: In all, 236 physicians responded to the questionnaire (126 paediatricians, 106 GPs). GPs registered more accurate diagnoses of GABHS tonsillopharyngitis and tended to administer more symptomatic treatment in the case of non-EBV tonsillopharyngitis than paediatricians. Paediatricians requested more tests in the diagnosis of GABHS tonsillopharyngitis than GPs. DISCUSSION: Most GPs and paediatricians possess adequate knowledge regarding GABHS diagnosis and the differential diagnosis of patients. Differences between the hospital and general practice settings may have affected the approach to symptomatic treatment and requesting tests.