Guideline for the management of acute sore throat: ESCMID Sore Throat Guideline Group

The European Society for Clinical Microbiology and Infectious Diseases established the Sore Throat Guideline Group to write an updated guideline to diagnose and treat patients with acute sore throat. In diagnosis, Centor clinical scoring system or rapid antigen test can be helpful in targeting antibiotic use. The Centor scoring system can help to identify those patients who have higher likelihood of group A streptococcal infection. In patients with high likelihood of streptococcal infections (e.g. 3–4 Centor criteria) physicians can consider the use of rapid antigen test (RAT). If RAT is performed, throat culture is not necessary after a negative RAT for the diagnosis of group A streptococci. To treat sore throat, either ibuprofen or paracetamol are recommended for relief of acute sore throat symptoms. Zinc gluconate is not recommended to be used in sore throat. There is inconsistent evidence of herbal treatments and acupuncture as treatments for sore throat. Antibiotics should not be used in patients with less severe presentation of sore throat, e.g. 0–2 Centor criteria to relieve symptoms. Modest benefits of antibiotics, which have been observed in patients with 3–4 Centor criteria, have to be weighed against side effects, the effect of antibiotics on microbiota, increased antibacterial resistance, medicalisation and costs. The prevention of suppurative complications is not a specific indication for antibiotic therapy in sore throat. If antibiotics are indicated, penicillin V, twice or three times daily for 10 days is recommended. At the present, there is no evidence enough that indicates shorter treatment length.     

A six-month audit of the isolation of Fusobacterium necrophorum from patients with sore throat in a district general hospital

Fusobacterium necrophorum is an obligate anaerobe believed to be a member of the normal flora of the human oropharangeal and urogenital tract. It has been associated with deep-seated infections and was first described in 1936 by Lemierre, a French microbiologist. There is now strong evidence to suggest that it is also a cause of recurrent sore throat and persistent sore throat syndrome (PSTS) without leading to full systemic infection. It is considered to be the second most common cause of sore throat after group A beta-haemolytic streptococci. This study was performed over a six-month period (October 2004 to March 2005) at the Eastbourne District General Hospital. All throat swabs received in the laboratory are cultured routinely for haemolytic group A streptococci and pathogenic Corynebacteria spp. During the study period an extra fastidious anaerobic blood agar plate with neomycin was inoculated, with a 30 microg vancomycin disc placed at the junction of the second and third streaks. This was examined after 48 h for the presence of F. necrophorum. A total of 1157 swabs were processed during the study period: 156 were positive for haemolytic group A streptococci, 57 were positive for F. necrophorum, 47 for group C haemolytic streptococci, nine for group G haemolytic streptococci, and one was positive for C. ulcerans. Patient age ranged from less than a year old to 88. The majority of F. necrophorum isolates were from patients in the 11-25 age group, with an isolation rate of 9.48% (44/464). This age group accounted for 40% (464/1157) of the swabs received during the study period and 77% (44/57) of these were positive for F. necrophorum. Group A haemolytic streptococci showed an overall isolation rate of 13.5%, with peaks of 23% in the 0-10 and 26-35 age ranges. Together, these two organisms were responsible for 18.4% (213/1157) of all throat infections in this study. The results presented here indicate that F. necrophorum is second to group A haemolytic streptococci as a cause of sore throat, especially in the young adult, and introduction of routine culture should be considered.     

Incidence and clinical variables associated with streptococcal throat infections: a prospective diagnostic cohort study

Background

Management of pharyngitis is commonly based on features which are thought to be associated with Lancefield group A beta-haemolytic streptococci (GABHS) but it is debatable which features best predict GABHS. Non-group A strains share major virulence factors with group A, but it is unclear how commonly they present and whether their presentation differs.

Aim

To assess the incidence and clinical variables associated with streptococcal infections.

Design and setting

Prospective diagnostic cohort study in UK primary care.

Method

The presence of pathogenic streptococci from throat swabs was assessed among patients aged ≥5 years presenting with acute sore throat.

Results

Pathogenic streptococci were found in 204/597 patients (34%, 95% CI = 31 to 38%): 33% (68/204) were non-group A streptococci, mostly C (n = 29), G (n = 18) and B (n = 17); rarely D (n = 3) and Streptococcus pneumoniae (n = 1). Patients presented with similar features whether the streptococci were group A or non-group A. The features best predicting A, C or G beta-haemolytic streptococci were patient’s assessment of severity (odds ratio [OR] for a bad sore throat 3.31, 95% CI = 1.24 to 8.83); doctors’ assessment of severity (severely inflamed tonsils OR 2.28, 95% CI = 1.39 to 3.74); absence of a bad cough (OR 2.73, 95% CI = 1.56 to 4.76), absence of a coryza (OR 1.54, 95% CI = 0.99 to 2.41); and moderately bad or worse muscle aches (OR 2.20, 95% CI = 1.41 to 3.42).

Conclusion

Non-group A strains commonly cause streptococcal sore throats, and present with similar symptomatic clinical features to group A streptococci. The best features to predict streptococcal sore throat presenting in primary care deserve revisiting.     

High group A streptococcal carriage in the Orthodox Jewish community of north Hackney.

BACKGROUND: General practitioners and the microbiologist serving north Hackney in north east London formed the impression, that of throat swabs sent to the laboratory, a disproportionate number of those positive for group A streptococcus appeared to come from Orthodox Jewish patients. AIM: To confirm the clinical impression that the pharyngeal carriage of group A streptococci was higher in the Orthodox Jewish population than in other members of the population in the same locality. DESIGN OF STUDY: A general practice questionnaire survey of all patients aged three years or over attending two practices that are about one kilometre apart, over a five-week period. SETTING: Two general practices in north London, one of which had a significant Orthodox Jewish patient list. METHODS: Throat swabs were taken from eligible patients who were invited to participate by completing a questionnaire and having a throat swab taken. RESULTS: Swabs were taken from 1223 people. After correction for age (child or adult) and history of recent sore throat, the Orthodox Jewish community had a significantly higher carriage rate of group A streptococci than the rest of the population (odds ratio = 5.0 [2.1 to 11.9]). The proportion of adults with group A streptococci with and without sore throats was 6.4% and 2.4% respectively in the Orthodox Jewish group and 0.45% and 1% respectively in the 'others' group. The proportion of children with group A streptococci with and without sore throats was 17.4% and 5.9% respectively and 3.4% and 0% respectively in the others. These differences were not explained by the larger family size and domestic overcrowding in the Orthodox Jewish group. CONCLUSIONS: Orthodox Jews in north London have a higher pharyngeal carriage rate of group A streptococci than the neighbouring population. These results may have implications for the diagnosis and treatment of acute sore throat in Orthodox Jewish patients, especially children.     

Bacteraemia caused by beta-haemolytic streptococci in North Queensland: changing trends over a 14-year period

Group A streptococci (GAS) are usually the predominant species in cases of bacteraemia caused by β haemolytic streptococci (BHS). An increasing worldwide incidence of invasive disease from non-group A BHS has been reported. Little is known about the changing trends in invasive disease caused by BHS in Australia. North Queensland has a relatively large indigenous population, who experience significantly higher rates of group A-related disease than the non-indigenous population. This prospective study examined changing trends of disease from large colony BHS that group with A, B, C and G antisera over a 14-year period at the single large tertiary referral hospital in the area. We identified 392 bacteraemic episodes caused by BHS. GAS were most commonly isolated (49%), with adjusted rates remaining stable over the period. There was a significant increase in the incidence of non-neonatal bacteraemia caused by group B streptococci (GBS) over the study period (r = 0.58; p 0.030), largely driven by infection in older, non-indigenous women. Rates of bacteraemia caused by group C streptococci also experienced a modest, but significant, increase over time (r = 0.67; p 0.009). GAS, which had no predominant emm type, were seen most commonly in indigenous subjects (52%). Mortality rates ranged from 3.2% (group G) to 10.3% (group C), with a rate of 7.9% associated with group A disease. The marked rise in GBS disease has been noted worldwide, but the relatively low incidence in indigenous Australian patients has not been described before, despite the burden of wellrecognized risk factors for GBS disease within this group.     

Do patients with sore throat benefit from penicillin? A randomized double-blind placebo-controlled clinical trial with penicillin V in general practice.

BACKGROUND: The effect of antibiotic therapy in sore throat is questionable and this dilemma has been complicated by the emergence of multiple resistant strains of micro-organisms. AIM: A randomized double-blind placebo-controlled clinical trial was undertaken in patients aged 4-60 years to assess the efficacy of penicillin V on the clinical course and bacteriological response in patients with sore throat in general practice. METHOD: Two hundred and thirty-nine patients presenting with an acute sore throat to 37 general practices in the Netherlands who were clinically suspected of group A beta-haemolytic streptococci (GABHS) were randomized for treatment with penicillin V (n = 121) or placebo (n = 118). Resolution of sore throat, fever and return to daily activities were evaluated by the general practitioner 2 days after the start of treatment and by the patients keeping a diary for 7 days. The result of throat culture after 2 days was evaluated. RESULTS: A difference in resolution of sore throat was present after 2 days in all patients, but was a result of GABHS-positive patients (n = 111; 46%) in favour of those randomized for penicillin V (adjusted odds ratio 5.3; 95% CI 1.9-15.1). An effect in the course of fever was also seen in GABHS-positive patients (adjusted odds ratio 5.3; 95% CI 1.02-27.7). A difference of 1-2 days was seen in clinical recovery. No difference was found in daily activities between the treatment groups. After 2 days, 4% of the penicillin-treated patients harboured GABHS compared with 75% of the placebo group. CONCLUSION: Only GABHS-positive patients benefit from penicillin V in their clinical cure in the first few days. Therefore, rapid testing is necessary. Treatment may be beneficial with regard to the clinical course, but it is not necessary.     

Flurbiprofen microgranules for relief of sore throat: a randomised,double-blind trial

Background

Many people with sore throat seek, and are often inappropriately prescribed, antibiotics.

Aim

The objective of this study was to determine the analgesic efficacy of flurbiprofen 8.75 mg microgranules versus placebo. These microgranules are a possible alternative treatment for patients with sore throat due to upper respiratory tract infection (URTI).

Design and setting

Randomised, double-blind, placebo-controlled, multiple-dose study conducted at eight primary care sites in Australia.

Method

Participants with sore throat of onset within the past 4 days received either flurbiprofen 8.75 mg microgranules or non-medicated placebo microgranules. Throat soreness, difficulty in swallowing, sore throat pain intensity, sore throat relief, oral temperature, and treatment benefits were all assessed at regular intervals.

Result

Of 373 patients from eight centres, 186 received flurbiprofen 8.75 mg microgranules and 187 received placebo microgranules (intent-to-treat population). Throat soreness was significantly reduced over the first 2 hours after the first dose. Reductions in difficulty in swallowing were observed at all time points from 5 to 360 minutes after the first dose, after taking flurbiprofen microgranules versus placebo. Sore throat relief was also evident at 1 minute and lasted for at least 6 hours. The multiple-dose efficacy results showed reduction of difficulty in swallowing at the end of days 1–3 and sore throat relief at the end of day 1.

Conclusion

Microgranules containing flurbiprofen 8.75 mg provided fast and effective relief from sore throat due to URTI and represent an alternative treatment option to antibiotic therapy.     

The use of rapid test QuikRead go® Strep A in bacterial pharyngotonsillitis diagnosing and therapeutic decisions

Group A Streptococci (GAS) are the main causative agents of bacterial pharyngitis, which require antibiotic therapy. Rapid diagnostic tests detecting GAS combined with Centor/McIsaac score enable accurate differential diagnosis (viral vs. bacterial) and prompt commencement of targeted treatment. The aim of this study was to assess the specificity, sensitivity, PPV and NPV of QuikRead go® Strep A (Orion Diagnostica Oy, Finland) recommended for the detection of GAS in pharyngeal swabs. Quick diagnostic test results were compared with physical examination findings, Centor/McIsaac score and results of reference testing (conventional microbial cultures). The study group of 96 participants consisted of 44 women (46%) and 52 men (54%); children aged 3–14 years constituted 46% of the patients. S. pyogenes were cultured from 43 of 96 pharyngeal swabs. Almost half of all positive samples (47%, n = 20) were collected from children aged 3 to 14 years. Positive GAS cultures were confirmed in 33% of patients with Centor/McIsaac score of 2 points, 48% of patients with score of 3, and 50% of patients with score of 4–5. Microbial cultures confirmed the positive results of QuikRead go® Strep A test in 83% of cases. Test specificity and sensitivity were calculated for the entire study group, which were 85% and 91%, respectively. The PPV of the test was 83% and its NPV was 92%. Using quick tests to detect GAS antigens appears a good alternative to conventional microbial diagnosis of strep throat, as it enables making a diagnosis and deciding on treatment plan in one appointment.     

Differentiation of species in human beta-haemolytic group G streptococci using immunoglobulin Fc fragment receptor.

AIMS: To assess the ability of human immunoglobulin Fc fragment binding activity to differentiate human biotype large colony group G streptococci from the group G "Streptococcus milleri group". METHODS: Fifty two isolates of large colony group G streptococci and 30 group G "S milleri group" strains were tested for their ability to bind fluorescein conjugated human IgG Fc fragments after acetone fixation. Immunoblotting with peroxidase labelled human Fc fragments after resolution of bacterial polypeptides by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed for six large colony strains. RESULTS: All large colony group G streptococci showed positive Fc fragment binding whereas all "S milleri group" bacteria failed to bind Fc fragments when viewed by fluorescence microscopy. All six large colony strains showed similar immunoblot binding patterns. CONCLUSION: Immunoglobulin Fc fragment receptor content distinguishes the large colony group G streptococci from the group G "S milleri group" and mayhave a role in the rapid laboratory diagnosis of pharyngeal pathogens.     

Distribution of emm types and subtypes among noninvasive group A, C and G streptococcal isolates in western Norway

Characterization of the reservoir of beta-hemolytic streptococci in a community may shed light on the pathogenesis of severe infections caused by these bacteria. We used emm sequence typing to characterize group A streptococci (GAS), group C streptococci (GCS) and group G streptococci (GGS) in community isolates associated with noninvasive disease in western Norway. A total of 165 isolates during a 13-month period were examined. Skin and throat isolates accounted for 123 and 16, respectively, and the remaining 26 isolates were from other non-sterile sites. We identified 18 previously validated emm types and one novel subtype, emm11.7, among the 101 GAS isolates. The two predominant types, emm28 and 12, were found in 40.6% of the GAS isolates. Compared to other recent studies of noninvasive GAS infections from elsewhere in the world, we found a higher frequency of emm82 (5.9%) and emm87 (12.9%) and a lower frequency of emm1 (4.0%) and emm3 (4.0%). We found a different distribution of GAS emm types compared to a previous study from western Norway. Among the 64 isolates of GCS and GGS, 15 previously described emm types and four novel subtypes, stC1400.5, stCK401.3, stG6.3 and stG652.3, were found, stG6, stG643 and stG485 were the most prevalent types and accounted for 59.4% of the GCS and GGS isolates. The high proportion of skin isolates in the present study may indicate the existence of GAS, GCS and GGS strains with predominantly skin and soft tissue tropism in our community.     

Distribution of <Emphasis Type="Italic">emm</Emphasis> types in invasive and non-invasive group A and G streptococci

Our study describes the emm type distributions of invasive and non-invasive group A streptococci (GAS) and group G streptococci (GGS) strains in one of the biggest Health Districts in Finland. A total of 571 GAS or GGS were recovered from patients with invasive or non-invasive infections during a 1-year period in 2008–2009 in Pirkanmaa Health District in Finland. We describe here the emm type distributions of GAS and GGS collected from throat (n = 246), pus (n = 217), deep tissue (n = 56) and blood (n = 52). The most common emm types among GAS were emm77, emm1, emm28, emm89 and emm12. Among GGS, the most common emm types were stG480, stG643, stG6, stC6979 and stG485. Some emm types were found to associate with certain infection focus. In GAS, emm77 associated with pus isolates, whereas emm1 and emm12 were more frequent among throat isolates. In GGS, stG480 was more commonly found from throat isolates.     

A foodborne outbreak of a group A streptococcal infection in a Japanese university hospital

We describe an outbreak of foodborne tonsillopharyngitis caused by group A streptococcus (GAS), a rarely reported event that occurred during a campus orientation meeting in Japan. Of 461 students and staff members who had eaten boxed lunches during a meeting at Kitasato University, 298 developed sore throat and/or fever, and 285 underwent medical examination. Amoxicillin was prescribed when throat culture specimens yielded GAS. The attack rate was 64.6%. T-25 GAS was isolated from 150 examined persons. Of 65 patients who received amoxicillin for 3 days, GAS was eradicated before the first follow-up throat culture in 46 (70.8%) cases. Susceptibility was demonstrated to penicillins, cephalosporins, and macrolides in 86 GAS isolates obtained more than once from a given patient. GAS strains isolated at various time points were indistinguishable by pulsed-field gel electrophoresis (PFGE), and prtF1 was present. GAS strains were often difficult to eradicate because of a short initial treatment period, patient compliance problems, and the presence of prtF1.     

Direct detection of groups A,C and G streptococci in clinical specimens by a trivalent colour test

A simple trivalent colour test, developed for the rapid detection and identification of streptococci belonging to Lancefield groups A, C and G, was evaluated for sensitivity and specificity with cultures and when directly used with wound and throat swabs. In tests performed on cultures, all of 94 group A, 78 group C and 94 group G cultures were correctly identified. In direct tests on wound swabs, 49 of 52 group A, 17 of 19 group C and 48 of 51 group G streptococci were detected and correctly identified; no false positives were observed. With throat swabs from pharyngitis patients 34 of 36 group A, 3 of 6 group C and 5 of 8 group G streptococci gave positive results. Almost 10% of these swabs gave false positive reactions with the group C component of the test system. Samples taken from uninfected individuals indicated that the false positives were probably associated with blood group A. The test system gives rapid and reliable results with streptococcal cultures, but when directly applied to clinical samples the results must be interpreted with caution, particularly if the patient's blood group is not known.     

Pharyngeal carriage of group B streptococci: detection by three methods.

The prevalence of pharyngeal carriage of group B streptococci was evaluated in patients with and without the complaint of a sore throat by three methods (blood agar plates, Columbia CNA agar plates, and a selective enrichment broth containing gentamicin and nalidixic acid). The overall carriage rate of group B streptococci was 12%, and there was no significant difference between the two groups of patients. The selective broth medium was more sensitive than the two solid agar plate methods in detecting carriage, and 37% of all group B streptococci were recovered solely from the broth. Use of the broth alone would have permitted a 94% detection of the group B streptococcal carriers.     

Improving diagnostic accuracy of bacterial pharyngitis by near patient measurement of C-reactive protein (CRP)

BACKGROUND: Sore throat or pharyngitis is an extremely prevalent condition in primary care. There is a diagnostic dilemma in differentiating bacterial and non-bacterial infections for adequate use of antibiotics. Standard diagnostic procedures take too long for an immediate decision. AIM: To evaluate, if near patient C-reactive protein measurement in the general practice surgery improves diagnostic accuracy. METHOD: One hundred and seventy-nine consecutive patients with sore throat, from 15 general practitioners (GPs) in southern Germany (phase 1) and 161 consecutive patients from 14 GPs (phase 2), were examined physically and a throat-swab was taken and white blood-cell count (WBC) and CRP-measurement were performed. In phase 1, CRP was measured centrally to assess the method's diagnostic value and the adequate threshold. In the second phase, near patient CRP was measured and CRP values were used to make a diagnosis. RESULTS: Using relative operating characteristics (ROC) analysis, the diagnostic value of CRP measurement was much better than WBC count (area under curve = 0.85 versus 0.68). All diagnostic parameters improved when using the near patient CRP measurement. Sensitivity went up from 0.61 (95% confidence interval = 0.45-0.75) to 0.78 (0.61-0.90), specificity went up from 0.73 (0.65-0.81) to 0.82 (0.73-0.88). Positive and negative predictive value improved significantly as well. Diagnostic accuracy went up from 70.1% to 81.0%. Out of 1000 theoretical patients with sore throat, 109 more will be treated correctly when using CRP measurement as a diagnostic tool. CONCLUSIONS: Use of near patient CRP measurement can improve diagnostic accuracy in the differentiation of bacterial and non-bacterial pharyngitis in primary care, and potentially results in a more adequate use of antibiotics.     

Beta-D-glucuronidase activity assay for rapid differentiation of species within beta-haemolytic group C and G streptococci.

Methylumbelliferyl-conjugated enzyme substrates were assessed for their ability to differentiate beta haemolytic streptococci in Lancefield groups C and G. Both Streptococcus equisimilis (group C) and large colony human biotype group G strains were consistently differentiated from group C and G "Streptococcus milleri group" bacteria by their ability to hydrolyse the beta-D-glucuronide substrate. The test was completed in less than one hour.     

Illness behaviour and antibiotic prescription in patients with respiratory tract symptoms.

BACKGROUND: Although the vast majority of respiratory tract symptoms are self-limiting, many patients visit their GP for these symptoms and antibiotics are over-prescribed. AIM: To explore determinants of patients visiting GPs for recent cough, sore throat, or earache; for being prescribed antibiotics; and for patients' satisfaction with visiting the GP. Design of the study: Second Dutch National Survey of General Practice (DNSGP-2) with a health interview and an additional questionnaire. SETTING: A total of 7057 adult patients of 163 GPs in the Netherlands. METHOD: Characteristics of patients and GPs as well as morbidity data were derived from the DNSGP-2 and a health interview. Characteristics of the symptoms, GPs' management and patients' satisfaction were measured by an additional written questionnaire. Data were analysed by means of multivariate logistic regression. RESULTS: About 40% of the responders (n = 1083) reported cough, sore throat, or earache in the 2 weeks preceding the interview and, of them, 250 visited their GP. Of this latter group, 97 patients were prescribed antibiotics. Apart from non-medical reasons, relevant medical factors played an important role in deciding to visit the GP. Smokers and patients with cardiac disease or diabetes mellitus were not especially inclined to see their GP. Smoking behaviour, fever, and views on respiratory tract symptoms and antibiotics of patients and GPs were associated with being prescribed antibiotics. Patients' perception of having been carefully examined was associated with their satisfaction, while receiving antibiotics was not. CONCLUSION: GPs should inform patients with clear elevated risk when to visit their GP in cases of cough, sore throat, or earache. There is still a need for GPs and patients to be better informed about the limited significance of single inflammation signs (for example, fever and green phlegm) as an indication for antibiotics. Careful examination of the patient contributes to patient satisfaction.     

Rapid biochemical tests for the identification of groups A, B, C, F, and G streptococci from throat cultures.

A test employing three fluorogenic 4-methylumbelliferyl substrates and the lectin of Dolichos biflorus was developed for the identification of beta-hemolytic streptococcal colonies associated with throat cultures. This non-serological method is unique in that it permits the accurate identification of groups C, F, and G streptococci, as well as groups A and B streptococci. The method is rapid, simple, and specific and appears to be a useful means to identify groups A, B, C, F, and G streptococci.