Optimal management of adults with pharyngitis – a multi-criteria decision analysis

BACKGROUND: Current practice guidelines offer different management recommendations for adults presenting with a sore throat. The key issue is the extent to which the clinical likelihood of a Group A streptococcal infection should affect patient management decisions. To help resolve this issue, we conducted a multi-criteria decision analysis using the Analytic Hierarchy Process. METHODS: We defined optimal patient management using four criteria: 1) reduce symptom duration; 2) prevent infectious complications, local and systemic; 3) minimize antibiotic side effects, minor and anaphylaxis; and 4) achieve prudent use of antibiotics, avoiding both over-use and under-use. In our baseline analysis we assumed that all criteria and sub-criteria were equally important except minimizing anaphylactic side effects, which was judged very strongly more important than minimizing minor side effects. Management strategies included: a) No test, No treatment; b) Perform a rapid strep test and treat if positive; c) Perform a throat culture and treat if positive; d) Perform a rapid strep test and treat if positive; if negative obtain a throat culture and treat if positive; and e) treat without further tests. We defined four scenarios based on the likelihood of group A streptococcal infection using the Centor score, a well-validated clinical index. Published data were used to estimate the likelihoods of clinical outcomes and the test operating characteristics of the rapid strep test and throat culture for identifying group A streptococcal infections. RESULTS: Using the baseline assumptions, no testing and no treatment is preferred for patients with Centor scores of 1; two strategies – culture and treat if positive and rapid strep with culture of negative results – are equally preferable for patients with Centor scores of 2; and rapid strep with culture of negative results is the best management strategy for patients with Centor scores 3 or 4. These results are sensitive to the priorities assigned to the decision criteria, especially avoiding over-use versus under-use of antibiotics, and the population prevalence of Group A streptococcal pharyngitis. CONCLUSION: The optimal clinical management of adults with sore throat depends on both the clinical probability of a group A streptococcal infection and clinical judgments that incorporate individual patient and practice circumstances

Pharyngitis Management: Defining the Controversy

Despite numerous controlled trials, clinical practice guidelines and cost-effective analyses, controversy persists regarding the appropriate management strategy for adult pharyngitis. In this perspective, we explore this controversy by comparing two competing clinical guidelines. Although the guidelines appear to make widely diverging recommendations, we show that the controversy centers on only a small proportion of patients: those presenting with severe pharyngitis. We examine recently published data to illustrate that this seemingly simple problem of strep throat remains a philosophical issue: should we give primacy to relieving acute time-limited symptoms, or should we emphasize the potential societal risk of antibiotic resistance? We accept potentially over treating a minority of adult pharyngitis patients with the most severe presentations to reduce suffering in an approximately equal number of patients who will have false negative test results if the test-and-treat strategy were used

The utility of rapid antigen detection testing for the diagnosis of streptococcal pharyngitis in low-resource settings

Funding Information: This study was supported by USAID. The Croatian and Latvian sites were funded by the Department of Child and Adolescent Health and Development, World Health Organization, Geneva. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or the stated policy of the World Health Organization. Thermo Biostar donated the STREP A OIA MAX rapid test kits for use in this study free of charge.Objectives: To evaluate the utility of rapid antigen detection testing (RADT) for the diagnosis of group A streptococcal (GAS) pharyngitis in pediatric outpatient clinics in four countries with varied socio-economic and geographic profiles. Methods: We prospectively evaluated the utility of a commercial RADT in children aged 2-12 years presenting with symptoms of pharyngitis to urban outpatient clinics in Brazil, Croatia, Egypt, and Latvia between August 2001 and December 2005. We compared the performance of the RADT to culture using diagnostic and agreement statistics, including sensitivity, specificity, and positive and negative predictive values. The Centor scores for GAS diagnosis were used to assess the potential effect of spectrum bias on RADT results. Results: Two thousand four hundred and seventy-two children were enrolled at four sites. The prevalence of GAS by throat culture varied by country (range 24.5-39.4%) and by RADT (range 23.9-41.8%). Compared to culture, RADT sensitivity ranged from 72.4% to 91.8% and specificity ranged from 85.7% to 96.4%. The positive predictive value ranged from 67.9% to 88.6% and negative predictive value ranged from 88.1% to 95.7%. Conclusions: In limited-resource regions where microbiological diagnosis is not feasible or practical, RADTs should be considered an option that can be performed in a clinic and provide timely results.publishersversionPeer reviewe

Antibiotic Stewardship Among Primary Care Providers In Mississippi

The World Health Organization states antimicrobial resistance is the ability of a microorganism to stop an antimicrobial from working which results in ineffective treatment and persistent infections. The Center for Disease Control and Prevention (CDC, 2017) reported that in the year 2015, 269.4 million antibiotic prescriptions were written in the outpatient setting, and approximately 30% of antibiotics written are unwarranted. Of those cases, most patients receive an antibiotic related to acute uncomplicated bronchitis, pharyngitis, or rhinosinusitis. The CDC reported that Americans spend nearly $11 billion yearly on antibiotics alone. However, up to 50% of all antibiotics prescribed are not indicated or optimally effective which eventually leads to resistance. Antibiotic resistant infections are associated with loss of productivity, poorer health outcomes, and greater healthcare costs. The CDC launched The Get Smart: Know When Antibiotics Work campaign in 2003 which aimed to direct appropriate antibiotic use (CDC, 2017). Within this campaign, the CDC provides outpatient regarding condition, epidemiology, diagnosis, and management for providers to follow for appropriate prescription. The purpose of this study was to determine if primary care providers in Mississippi are following the CDC Adult Treatment Recommendations for antibiotic use in the treatment of acute uncomplicated bronchitis, streptococcal pharyngitis, and acute unspecified pharyngitis (CDC, 2016). The researchers collected data in six rural clinics across Mississippi. This study consisted of a quantitative, retrospective chart review with descriptive statistics. A convenience sampling of 582 charts were obtained for the retrospective review. For data collection, the researchers used a data collection tool which included information related to age, gender, insurance, title o f provider, and diagnoses related to the current research and CDC Adult Treatment Recommendations. Prior to conducting the study, consent was obtained from the Institutional Review Board (IRB) at the Mississippi University for Women. After data collection, data were subjected to analyses using descriptive statistics including, but not limited to, frequency, distributions, and percentages. The findings suggested that primary care providers in Mississippi are not consistently following the CDC Adult Treatment Recommendations for acute pharyngitis and uncomplicated bronchitis

Time to negative throat culture following initiation of antibiotics for pharyngeal group A Streptococcus: a systematic review and meta-analysis up to October 2021 to inform public health control measures

Background: Public health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12–24 h from antibiotic initiation to prevent onward transmission requires a strong evidence base. Aim: To estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics through a systematic literature review (PROSPERO CRD42021290364) and meta-analysis. Methods: We searched Ovid MEDLINE (1946–), EMBASE (1974–) and Cochrane library. We included interventional or observational studies with ≥ 10 participants reporting rates of GAS throat culture positivity during antibiotic treatment for culture-confirmed GAS pharyngitis, scarlet fever and asymptomatic pharyngeal GAS carriage. We did not apply age, language or geographical restrictions. Results: Of 5,058 unique records, 43 were included (37 randomised controlled studies, three non-randomised controlled trials and three before-and-after studies). The proportion of individuals remaining culture-positive on day 1, day 2 and days 3–9 were 6.9% (95% CI: 2.7–16.8%), 5.4% (95% CI: 2.1–13.3%) and 2.6% (95% CI: 1.6–4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI: 2.5–16.1%) and 1.6% (95% CI: 0.04–42.9%), respectively. Overall, for 9.1% (95% CI: 7.3–11.3), throat swabs collected after completion of therapy were GAS culture-positive. Only six studies had low risk of bias. Conclusions: Our review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 h but highlights the need for further research given methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and asymptomatic individuals

Diagnostic studies in children with acute infections : Microbes and biomarkers

We did four distinct clinical studies, mainly in the emergency department (ED) setting, to pragmatically evaluate the accuracy, feasibility and characteristics of different diagnostic tests in children with acute infections, and documented the etiology of febrile pharyngitis. The results of this study show that point-of-care tests (POCTs) for white blood cell count and C-reactive protein (CRP) were feasible and relatively accurate in comparison with standard laboratory methods. The occurrence of discrepant plasma procalcitonin (PCT) and CRP levels in acutely ill children was 29%. We confirmed an earlier finding that PCT rises more rapidly than CRP in bacteremic patients and made a new observation that PCT increases also in patients with acute diabetic ketoacidosis. In addition, a multianalyte antigen detection POCT for respiratory viruses was proven user-friendly and specific. It gave an overall sensitivity of 83% for influenza viruses, 89% for respiratory syncytial virus but only 25% for adenovirus in comparison with the polymerase chain reaction method. Finally, we found that febrile pharyngitis was caused solely by viruses in 59%, by viruses together with group A streptococcus (GAS) in 13% and solely by GAS in 10% of the children. Blood myxovirus resistance protein A (MxA) levels were increased in most of the pharyngitis patients with virus detection further supporting the causative role of viruses. These results highlight the usefulness of POCTs in ED setting. In addition, we completed the etiological picture of febrile pharyngitis.Tutkimuksia lasten äkillisten infektioiden diagnostiikasta: mikrobeja ja merkkiaineita Kuumeisen lapsen lääketieteellinen arvio perustuu ensisijaisesti potilaan kliiniseen tutkimiseen. Arvion apuna voidaan tarvittaessa käyttää laboratoriotutkimuksia. Teimme neljä erillistä kliinistä tutkimusta selvittääksemme tiettyjen laboratoriokokeiden käytettävyyttä, tarkkuutta ja ominaisuuksia äkillisiä infektioita sairastavien lapsien diagnostiikassa. Tutkimukset tehtiin käytännönläheisesti ja ne toteutettiin pääsääntöisesti päivystyspoliklinikalla. Lisäksi selvitimme kuumeisen nielutulehduksen aiheuttajat. Tutkimuksen tulokset osoittavat, että valkosolujen ja C-reaktiivisen proteiinin (CRP) nopeat vieritestit olivat käytettävyydeltään hyviä ja suhteellisen tarkkoja laboratorion vakiomenetelmiin verrattuna. Totesimme myös, että 29 %:lla äkillisesti sairastuneista lapsista prokalsitoniinin (PCT) ja CRP:n pitoisuudet plasmassa ovat keskenään ristiriidassa. Vahvistimme samalla aiemmat havainnot siitä, että PCT-pitoisuus suurenee CRP:tä nopeammin baktereemisilla potilailla. Teimme uuden havainnon PCT:n noususta akuuttia ketoasidoosia sairastavilla lapsilla. Antigeenin osoitukseen perustuva monianalyyttinen hengitystievirusten pikatesti osoittautui käyttäjäystävälliseksi ja tarkaksi. Vertailussa nukleiinihapon osoitukseen perustuvaan menetelmään testin herkkyys influenssaviruksille oli 83 %, RS-virukselle 89 % mutta adenovirukselle vain 25 %. Nielutulehduksen aiheuttajaksi todettiin 59 %:lla lapsista virus, 13 %:lla virus ja A-ryhmän streptokokki (GAS) yhdessä ja 10 %:lla GAS yksinään. Veren myxovirus resistance protein A (MxA) -pitoisuus oli suurentunut suurimmalla osalla viruspositiivisista potilaista tukien ajatusta viruksesta kyseisen taudin aiheuttajana. Tuloksemme korostavat vieritestien käyttökelpoisuutta päivystyspoliklinikalla. Lisäksi täydensimme tietämystä lasten nielutulehduksen etiologiasta.Siirretty Doriast

Economic Analyses of Respiratory Tract Infection Diagnostics:A Systematic Review

BACKGROUND: Diagnostic testing for respiratory tract infections is a tool to manage the current COVID-19 pandemic, as well as the rising incidence of antimicrobial resistance. At the same time, new European regulations for market entry of in vitro diagnostics, in the form of the in vitro diagnostic regulation, may lead to more clinical evidence supporting health-economic analyses. OBJECTIVE: The objective of this systematic review was to review the methods used in economic evaluations of applied diagnostic techniques, for all patients seeking care for infectious diseases of the respiratory tract (such as pneumonia, pulmonary tuberculosis, influenza, sinusitis, pharyngitis, sore throats and general respiratory tract infections). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles from three large databases of scientific literature were included (Scopus, Web of Science and PubMed) for the period January 2000 to May 2020. RESULTS: A total of 70 economic analyses are included, most of which use decision tree modelling for diagnostic testing for respiratory tract infections in the community-care setting. Many studies do not incorporate a generally comparable clinical outcome in their cost-effectiveness analysis: fewer than half the studies (33/70) used generalisable outcomes such as quality-adjusted life-years. Other papers consider outcomes related to the accuracy of the test or outcomes related to the prescribed treatment. The time horizons of the studies generally are limited. CONCLUSIONS: The methods to economically assess diagnostic tests for respiratory tract infections vary and would benefit from clear recommendations from policy makers on the assessed time horizon and outcomes used. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40273-021-01054-1

PRImary care Streptococcal Management (PRISM) study:In vitro study, diagnostic cohorts and a pragmatic adaptive randomised controlled trial with nested qualitative study and cost-effectiveness study

Background: Antibiotics are still prescribed to most patients attending primary care with acute sore throat, despite evidence that there is modest benefit overall from antibiotics. Targeting antibiotics using either clinical scoring methods or rapid antigen detection tests (RADTs) could help. However, there is debate about which groups of streptococci are important (particularly Lancefield groups C and G), and uncertainty about the variables that most clearly predict the presence of streptococci. Objective: This study aimed to compare clinical scores or RADTs with delayed antibiotic prescribing. Design: The study comprised a RADT in vitro study; two diagnostic cohorts to develop streptococcal scores (score 1; score 2); and, finally, an open pragmatic randomised controlled trial with nested qualitative and cost-effectiveness studies. Setting: The setting was UK primary care general practices. Participants: Participants were patients aged ≥ 3 years with acute sore throat. Interventions: An internet program randomised patients to targeted antibiotic use according to (1) delayed antibiotics (control group), (2) clinical score or (3) RADT used according to clinical score. Main outcome measures: The main outcome measures were self-reported antibiotic use and symptom duration and severity on seven-point Likert scales (primary outcome: mean sore throat/difficulty swallowing score in the first 2-4 days). Results: The IMI TestPack Plus Strep A (Inverness Medical, Bedford, UK) was sensitive, specific and easy to use. Lancefield group A/C/G streptococci were found in 40% of cohort 2 and 34% of cohort 1. A five-point score predicting the presence of A/C/G streptococci [FeverPAIN: Fever; Purulence; Attend rapidly (≤ 3 days); severe Inflammation; and No cough or coryza] had moderate predictive value (bootstrapped estimates of area under receiver operating characteristic curve: 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection. In total, 38% of cohort 1 and 36% of cohort 2 scored ≤ 1 for FeverPAIN, associated with streptococcal percentages of 13% and 18%, respectively. In an adaptive trial design, the preliminary score (score 1; n = 1129) was replaced by FeverPAIN (n = 631). For score 1, there were no significant differences between groups. For FeverPAIN, symptom severity was documented in 80% of patients, and was lower in the clinical score group than in the delayed prescribing group (-0.33; 95% confidence interval -0.64 to -0.02; p = 0.039; equivalent to one in three rating sore throat a slight rather than moderately bad problem), and a similar reduction was observed for the RADT group (-0.30; -0.61 to 0.00; p = 0.053). Moderately bad or worse symptoms resolved significantly faster (30%) in the clinical score group (hazard ratio 1.30; 1.03 to 1.63) but not the RADT group (1.11; 0.88 to 1.40). In the delayed group, 75/164 (46%) used antibiotics, and 29% fewer used antibiotics in the clinical score group (risk ratio 0.71; 0.50 to 0.95; p = 0.018) and 27% fewer in the RADT group (0.73; 0.52 to 0.98; p = 0.033). No significant differences in complications or reconsultations were found. The clinical score group dominated both other groups for both the cost/quality-adjusted life-years and cost/change in symptom severity analyses, being both less costly and more effective, and cost-effectiveness acceptability curves indicated the clinical score to be the most likely to be cost-effective from an NHS perspective. Patients were positive about RADTs. Health professionals' concerns about test validity, the time the test took and medicalising self-limiting illness lessened after using the tests. For both RADTs and clinical scores, there were tensions with established clinical experience. Conclusions: Targeting antibiotics using a clinical score (FeverPAIN) efficiently improves symptoms and reduces antibiotic use. RADTs used in combination with FeverPAIN provide no clear advantages over FeverPAIN alone, and RADTs are unlikely to be incorporated into practice until health professionals' concerns are met and they have experience of using them. Clinical scores also face barriers related to clinicians' perceptions of their utility in the face of experience. This study has demonstrated the limitation of using one data set to develop a clinical score. FeverPAIN, derived from two data sets, appears to be valid and its use improves outcomes, but diagnostic studies to confirm the validity of FeverPAIN in other data sets and settings are needed. Experienced clinicians need to identify barriers to the use of clinical scoring methods. Implementation studies that address perceived barriers in the use of FeverPAIN are needed

Diagnostic stewardship : the impact of rapid diagnostic testing for paediatric respiratory presentations in the emergency setting : a systematic review

Antimicrobial resistance is a growing public health crisis, propelled by inappropriate antibiotic prescription, in particular the over-prescription of antibiotics, prolonged duration of antibiotic therapy and the overuse of broad-spectrum antibiotics. The paediatric population, in particular, those presenting to emergency settings with respiratory symptoms, have been associated with a high rate of antibiotic prescription rates. Further research has now shown that many of these antibiotic prescriptions may have been avoided, with more targeted diagnostic methods to identify underlying aetiologies. The purpose of this systematic review was to assess the impact of rapid diagnostic testing, for paediatric respiratory presentations in the emergency setting, on antibiotic prescription rates. To review the relevant history, a comprehensive search of Medline, EMBASE and Cochrane Database of Systematic Reviews was performed. Eighteen studies were included in the review, and these studies assessed a variety of rapid diagnostic testing tools and outcome measures. Overall, rapid diagnostic testing was found to be an effective method of diagnostic antibiotic stewardship with great promise in improving antibiotic prescribing behaviours. Further studies are required to evaluate the use of rapid diagnostic testing with other methods of antibiotics stewardship, including clinical decisions aids and to increase the specificity of interventions following diagnosis to further reduce rates of antibiotic prescriptio

Antibiotic Resistance: Use of Delayed Prescriptions for Viral Syndromes in Urgent Care

Purpose: Widespread use of antibiotics leads to a development of antimicrobial resistance, an increasing global problem. The rise of antibiotic-resistant bacterial strains represents a serious threat to the public. The Centers for Disease Control and Prevention (CDC) estimates at least two million illnesses and 23,000 deaths are caused by antibiotic resistant bacteriain the United States (CDC, 2014). The strategy of delayed antibiotic prescribing, sometimes called “wait and see” prescriptions, may reduce antibiotic use for viral syndromes in primary care settings. The overall purpose of this scholarly project is to explore delayed prescriptions used by providers in two urgent care settings, with a potential to reduce the amount of antibiotics consumed by patients for viral syndromes. These diagnoses include influenza, upper respiratory infection (URI), pharyngitis, sinusitis, acute bronchitis, acute otitis media (AOM). Significance of the Project: There have been numerous studies in the past addressing the importance of reducing antibiotic use. The need to slow the emergence of resistant bacteria by judicious use of antibiotics in healthcare and agricultural settings will require the cooperation and engagement of healthcare providers, healthcare leaders, pharmaceutical companies, and patients. Providers are well aware of the dangers of prescribingantibiotics for viral syndromes and have strict requirements as to which patients they will issue delayed prescriptions. According to the American College of Emergency Physicians (ACEP), antibiotics are given to patients with acute bronchitis 65% to 80% of the time, acute pharyngitis visits receive antibiotics 60% of the time, and acute sinusitis receives antibiotics 80% of the time out of 4 million annual outpatient visits (Radecky, 2014). Using antibiotics for conditions that have only a marginal, self-limiting or no clinical effect has been labelled unnecessary or inappropriate antibiotic use or antibiotic overuse or misuse (Hoye, Gjelstad, & Lindbaek, 2013). Factors contributing to overuse of antibiotics could include patient demand, lack of information on viruses and antibiotics, perceived ideas of duration of illness, uncertainty of diagnosis and inability to spend time with patients due to volume. According the Journal of Urgent Care Medicine (JUCM), 52.9% of visits to urgent care centers in 2014 were for viral syndromes, otitis media, URI, coughs, and 1.6% influenza visits (JUCM, 2015). There is evidence that the majority of patients believe that antibiotics are an appropriate treatment for these diagnoses. Methods: Urgent care centers have been around for about a decade and considered new models of healthcare in the niche between primary care offices and emergency departments. Urgent care centers have extended hours and envisioned as functioning as low-acuity emergency departments with extended services such as Radiology, and Lab testing. They mainly have emergency board certified physicians, but some may have primary care providers on duty. Generally urgent care centers are open selected hours seven days a week. This project was conducted in two urgent care centers in two different counties, with a combined patient volume of 16,000 yearly. The urgent care centers used in this project are affiliated with a major hospital system in central New Jersey. The providers currently work at both urgent care centers on a rotational basis, as well as the emergency department of the main hospital. The physicians were asked to participate and welcomed the project. With the diagnosis of viral syndrome, the provider would recommend a delayed prescription for an antibiotic. At discharge, the nurse would explain the dangers of antibiotic resistance using patient handouts from the CDC’s “Get Smart about Antibiotics” (CDC, 2014). The patient wasasked to wait four days and if the symptoms were not better, they would be able to begin their antibiotic instead of returning for another visit. A phone survey was conducted on day five -post visit to determine if the patient filled or did not fill the prescription. Project Outcomes: Through patient education and the use of handouts, this project proved that educating patients at time of discharge could increase the likelihood of the patient’s decision not to fill their delayed prescription. Of sixty-eight patients surveyed by phone, thirty-four did not fill their antibiotic prescriptions and thirty-four patients did fill their antibiotics within the five-day range. There was a significant difference in who filled their prescriptions and who did not, by whether the provider or the nurse handed out the education packet to the patient. The nurse given the education packet had a better response to patients not filling their antibiotic. Though the cumulative percentage of patients who did not fill their prescriptions was slightly greater than 50%, the outcome has the potential to decrease the amount of antibiotics the public consumes with delayed prescriptions and education at discharge. Clinical Significance: The practice of overprescribing of antibiotics has contributed to an increase in resistance and treatment failures for bacterial illnesses. Patient satisfaction has become a large part of the healthcare system and was taken into consideration in this project. Patients are requesting antibiotics for diagnosed viral infections due to theirlack of education, the proper use for antibiotics, and dangers from misuse such as allergic reactions, abdominal pain and most common, diarrhea and vomiting. Healthcare providers can help lower the prescription rates of antibiotics with educational information as well as using delayed prescriptions. Increasing knowledge about antibiotic misuse can be statistically significant in demonstrating that adding education can decrease the use of antibiotics when not needed. Time with the patient at discharge and patient education proved to be significant therefore beneficial to not filling the delayed antibiotic prescription