Thompson KM, Sterkel AK, McBride JA, Corliss RF.
The Shock of Strep: Rapid Deaths Due to Group a Streptococcus.
Acad Forensic Pathol. 2018 Mar;8(1):136-149. doi: 10.23907/2018.010. Epub 2018 Mar 7.
Abstract/Text
Streptococcus pyogenes, also known as group A beta-hemolytic strep, is a Gram positive coccus responsible for several million infections every year. The types of infections vary widely from pharyngitis to myositis, but all can advance to severe life threatening invasive disease. Of those infected, approximately 1100 to 1600 people die each year due to invasive disease. Why certain individuals contract severe infections is not known, but many strains of Streptococcus pyogenes are known to produce toxins and superantigens. Invasive Streptococcus pyogenes infections have been shown to cause significant morbidity and rapid mortality. In many cases, patients expire before full antemortem testing can be performed, causing physicians and families to look to forensic pathologists for answers. Understanding the pathogenesis of invasive group A strep infections, relevant gross and microscopic findings, and proper culturing techniques is critical for forensic pathologists to diagnosis this condition and assist in the education and protection of the communities they serve.
市田蕗子,佐地勉,梶野浩樹,小川俊一, 中西敏雄:平成21年度 稀少疾患サーベイランス調査結果．日本小児循環器学会誌 2007;26(4):348-50.
2016年CHD・希少疾患サーベイランス調査結果.日本小児循環器学会. Available from: http://jspccs.jp/wp-content/uploads/rare_disease_surveillance_2016_rev181201.pdf
Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK.
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases.
Am J Psychiatry. 1998 Feb;155(2):264-71. doi: 10.1176/ajp.155.2.264.
Abstract/Text
OBJECTIVE: The purpose of this study was to describe the clinical characteristics of a novel group of patients with obsessive-compulsive disorder (OCD) and tic disorders, designated as pediatric autoimmune neuropsychiatric disorders associated with streptococcal (group A beta-hemolytic streptococcal [GABHS]) infections (PANDAS).
METHOD: The authors conducted a systematic clinical evaluation of 50 children who met all of the following five working diagnostic criteria: presence of OCD and/or a tic disorder, prepubertal symptom onset, episodic course of symptom severity, association with GABHS infections, and association with neurological abnormalities.
RESULTS: The children's symptom onset was acute and dramatic, typically triggered by GABHS infections at a very early age (mean = 6.3 years, SD = 2.7, for tics; mean = 7.4 years, SD = 2.7, for OCD). The PANDAS clinical course was characterized by a relapsing-remitting symptom pattern with significant psychiatric comorbidity accompanying the exacerbations; emotional lability, separation anxiety, nighttime fears and bedtime rituals, cognitive deficits, oppositional behaviors, and motoric hyperactivity were particularly common. Symptom onset was triggered by GABHS infection for 22 (44%) of the children and by pharyngitis (no throat culture obtained) for 14 others (28%). Among the 50 children; there were 144 separate episodes of symptom exacerbation; 45 (31%) were associated with documented GABHS infection, 60 (42%) with symptoms of pharyngitis or upper respiratory infection (no throat culture obtained), and six (4%) with GABHS exposure.
CONCLUSIONS: The working diagnostic criteria appear to accurately characterize a homogeneous patient group in which symptom exacerbations are triggered by GABHS infections. The identification of such a subgroup will allow for testing of models of pathogenesis, as well as the development of novel treatment and prevention strategies.
国立感染症研究所. 国内における劇症型溶血性レンサ球菌感染症の増加について（2024年6月時点）. https://www.niid.go.jp/niid/ja/tsls-m/2655-cepr/12718-stss-2024-06.html（2024年11月閲覧）.
Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH; Infectious Diseases Society of America.
Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Infectious Diseases Society of America.
Clin Infect Dis. 2002 Jul 15;35(2):113-25. doi: 10.1086/340949.
Abstract/Text
Shaikh N, Leonard E, Martin JM.
Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a meta-analysis.
Pediatrics. 2010 Sep;126(3):e557-64. doi: 10.1542/peds.2009-2648. Epub 2010 Aug 9.
Abstract/Text
OBJECTIVES: Prevalence estimates can help clinicians make informed decisions regarding diagnostic testing of children who present with symptoms of pharyngitis. We conducted a meta-analysis to determine the (1) prevalence of streptococcal infection among children who presented with sore throat and (2) prevalence of streptococcal carriage among asymptomatic children.
METHODS: We searched Medline for articles on pediatric streptococcal pharyngitis. We included articles in our review when they contained data on the prevalence of group A Streptococcus (GAS) from pharyngeal specimens in children who were younger than 18 years. Two evaluators independently reviewed, rated, and abstracted data from each article. Prevalence estimates were pooled in a meta-analysis and stratified according to age group.
RESULTS: Of the 266 articles retrieved, 29 met all inclusion criteria. Among children of all ages who present with sore throat, the pooled prevalence of GAS was 37% (95% confidence interval [CI]: 32%-43%). Children who were younger than 5 years had a lower prevalence of GAS (24% [95% CI: 21%-26%]). The prevalence of GAS carriage among well children with no signs or symptoms of pharyngitis was 12% (95% CI: 9%-14%).
CONCLUSIONS: Prevalence rates of GAS disease and carriage varied by age; children who were younger than 5 years had lower rates of throat cultures that were positive for GAS.
厚生労働省健康・生活衛生局 感染症対策部 感染症対策課. 抗微生物薬適正使用の手引き 第三版. 2023.
忠義池辺. 溶血性レンサ球菌感染症の疫学. 日本食品微生物学会雑誌. 2019;36(2):85–88.
Yoder EL, Mendez J, Khatib R.
Spontaneous gangrenous myositis induced by Streptococcus pyogenes: case report and review of the literature.
Rev Infect Dis. 1987 Mar-Apr;9(2):382-5. doi: 10.1093/clinids/9.2.382.
Abstract/Text
A 54-year-old man presented with gangrenous myositis caused by Streptococcus pyogenes. A review of the literature disclosed 10 similar cases. Their presenting manifestations were spontaneously occurring, localized, excruciating pain; mottling suggestive of ischemic changes; and signs of sepsis. The duration of illness ranged from two to six days, and the outcome was uniformly fatal. This rare but distinct entity resembles clostridial myonecrosis except that it lasts slightly longer and does not involve gaseous crepitus. A definitive diagnosis of myonecrosi scan be established by surgical exploration; early, radical debridement plus penicillin therapy should be undertaken after diagnosis in an attempt to alter the usual devastating outcome.
Shaikh N, Swaminathan N, Hooper EG.
Accuracy and precision of the signs and symptoms of streptococcal pharyngitis in children: a systematic review.
J Pediatr. 2012 Mar;160(3):487-493.e3. doi: 10.1016/j.jpeds.2011.09.011. Epub 2011 Nov 1.
Abstract/Text
OBJECTIVE: To conduct a systematic review to determine whether clinical findings can be used to rule in or to rule out streptococcal pharyngitis in children.
STUDY DESIGN: Two authors independently searched MEDLINE and EMBASE. We included articles if they contained data on the accuracy of symptoms or signs of streptococcal pharyngitis, individually or combined into prediction rules, in children 3-18 years of age.
RESULTS: Thirty-eight articles with data on individual symptoms and signs and 15 articles with data on prediction rules met all inclusion criteria. In children with sore throat, the presence of a scarlatiniform rash (likelihood ratio [LR], 3.91; 95% CI, 2.00-7.62), palatal petechiae (LR, 2.69; CI, 1.92-3.77), pharyngeal exudates (LR, 1.85; CI, 1.58-2.16), vomiting (LR, 1.79; CI, 1.58-2.16), and tender cervical nodes (LR, 1.72; CI, 1.54-1.93) were moderately useful in identifying those with streptococcal pharyngitis. Nevertheless, no individual symptoms or signs were effective in ruling in or ruling out streptococcal pharyngitis.
CONCLUSIONS: Symptoms and signs, either individually or combined into prediction rules, cannot be used to definitively diagnose or rule out streptococcal pharyngitis.
Copyright © 2012 Mosby, Inc. All rights reserved.
Ebell MH, Smith MA, Barry HC, Ives K, Carey M.
The rational clinical examination. Does this patient have strep throat?
JAMA. 2000 Dec 13;284(22):2912-8. doi: 10.1001/jama.284.22.2912.
Abstract/Text
CONTEXT: Sore throat is a common complaint, and identifying patients with group A beta-hemolytic streptococcal pharyngitis (strep throat) is an important task for clinicians. Previous reviews have not systematically reviewed and synthesized the evidence.
OBJECTIVE: To review the precision and accuracy of the clinical examination in diagnosing strep throat.
DATA SOURCE: MEDLINE search for articles about diagnosis of strep throat using history-taking and physical examination.
STUDY SELECTION: Large blinded, prospective studies (having > or =300 patients with sore throat) reporting history and physical examination data and using throat culture as the reference standard were included. Of 917 articles identified by the search, 9 met all inclusion criteria.
DATA EXTRACTION: Pairs of authors independently reviewed each article and used consensus to resolve discrepancies.
DATA SYNTHESIS: The most useful findings for evaluating the likelihood of strep throat are presence of tonsillar exudate, pharyngeal exudate, or exposure to strep throat infection in the previous 2 weeks (positive likelihood ratios, 3.4, 2.1, and 1.9, respectively) and the absence of tender anterior cervical nodes, tonsillar enlargement, or exudate (negative likelihood ratios, 0.60, 0.63, and 0.74, respectively). No individual element of history-taking or physical examination is accurate enough by itself to rule in or rule out strep throat. Three validated clinical prediction rules are described for adult and pediatric populations.
CONCLUSIONS: While no single element of history-taking or physical examination is sufficiently accurate to exclude or diagnose strep throat, a well-validated clinical prediction rule can be useful and can help physicians make more informed use of rapid antigen tests and throat cultures.
Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K.
The diagnosis of strep throat in adults in the emergency room.
Med Decis Making. 1981;1(3):239-46. doi: 10.1177/0272989X8100100304.
Abstract/Text
Adult patients who presented to an urban emergency room complaining of a sore throat had cultures and clinical information recorded. Models were constructed, using logistic regression analysis, of both a positive culture for Group A beta streptococcus and a positive guess by a resident. The model of a positive culture consisted of four variables--tonsillar exudates, swollen tender anterior cervical nodes, lack of a cough, and history of fever. Patients with all 4 variables had a 56% probability of a positive culture; 3 variables, 32%; 2 variables, 15%; 1 variable, 6.5%; and 0 variables, 2.5%. The model of a positive guess by a resident demonstrated an over-reliance on physical exam and an underuse of history. The model of a positive culture allows stratification of patients to assist clinicians in the management strategies.
McIsaac WJ, Goel V, To T, Low DE.
The validity of a sore throat score in family practice.
CMAJ. 2000 Oct 3;163(7):811-5.
Abstract/Text
BACKGROUND: Reducing the number of antibiotic prescriptions given for common respiratory infections has been recommended as a way to limit bacterial resistance. This study assessed the validity of a previously published clinical score for the management of infections of the upper respiratory tract accompanied by sore throat. The study also examined the potential impact of this clinical score on the prescribing of antibiotics in community-based family practice.
METHODS: A total of 97 family physicians in 49 Ontario communities assessed 621 children and adults with a new infection of the upper respiratory tract accompanied by sore throat and recorded their prescribing decisions. A throat swab was obtained for culture. The sensitivity and specificity of the score approach in this population were compared with previously published results for patients seen at an academic family medicine centre. In addition, physicians' prescribing practices and their recommendations for obtaining throat swabs were compared with score-based recommendations.
RESULTS: Of the 621 cases of new upper respiratory tract infection and sore throat, information about prescriptions given was available for only 619; physicians prescribed antibiotics in 173 (27.9%) of these cases. Of the 173 prescriptions, 109 (63.0%) were given to patients with culture-negative results for group A Streptococcus. Using the score to determine management would have reduced prescriptions to culture-negative patients by 63.7% and overall antibiotic prescriptions by 52.3% (both p < 0.01). Culturing of throat samples would have been reduced by 35.8% (p < 0.01). There was no statistically significant difference in the sensitivity or specificity of the score approach between this community-based population (sensitivity 85.0%, specificity 92.1%) and an academic family medicine centre (sensitivity 83.1%, specificity 94.3%).
INTERPRETATION: An explicit clinical score approach to the management of patients presenting with an upper respiratory tract infection and sore throat is valid in community-based family practice and could substantially reduce the unnecessary prescribing of antibiotics for these conditions.
Woods WA, Carter CT, Schlager TA.
Detection of group A streptococci in children under 3 years of age with pharyngitis.
Pediatr Emerg Care. 1999 Oct;15(5):338-40. doi: 10.1097/00006565-199910000-00011.
Abstract/Text
OBJECTIVE: To determine the frequency of group A streptococcal pharyngitis in young preschool children presenting to the emergency department with upper respiratory tract infection.
METHODS: A prospective, observational study performed between September 1995 and September 1997. Throat swabs were obtained on young children less than 3 years old with pharyngeal erythema as well as age- and time-matched controls without pharyngeal erythema or exudate. Signs and symptoms that were recorded included: age, temperature, pharyngeal erythema, tonsillar exudate, cervical adenopathy, scarlatini-form rash, rhinorrhea, school-aged child in the home, day care attendance. Swabs were inoculated on 5% sheep blood agar and incubated for 48 hours. Beta-hemolytic colonies were sero-grouped by latex agglutination.
RESULTS: Seventy-eight children with pharyngeal erythema, and 152 controls had pharyngeal specimens obtained and signs or symptoms recorded. Under 2 years of age, the detection of group A streptococci was similar to controls. Detection of group A streptococci was significantly different from controls in children over 2 years of age. Ten (29%) of 35 children over 2 years were positive for group A streptococci compared to 2 (7%) of 29 controls of the same age group (P = 0.03, odds ratio 5, 95% CI: 1.2-24). Findings on clinical examination in children with pharyngeal erythema did not distinguish those that would be culture-positive for group A streptococci.
CONCLUSION: In our emergency department, group A streptococci caused 30% of pharyngitis seen in children between 2 and 3 years of age. Diagnostic testing is recommended because physical examination may not accurately distinguish etiology in this age group.
石和田稔彦, 新庄正宜監修. 小児呼吸器感染症診療ガイドライン2022. 協和企画. 2022.
David W. Kimberlin, MD, FAAP, et al. Red Book®2024-2027 Report of the Committee on Infectious Diseases, 33rd Edition. American Academy of Pediatrics, 2024.
砂押克彦,中山栄一,小林玲子,他：小児急性気道感染症より分離されたA群溶血レンサ球菌の薬剤感受性とT型別．日化療会誌 2004;52:401-407．.
河邉慎司,西村直子,後藤研誠,宮川恵子,山口千絵,矢崎雄彦,尾崎隆男:A群レンサ球菌感染症の臨床的及び細菌学的検討.小児感染免疫2003;15(3）:297-303.
松原茂規:鼻腔・咽頭のA群溶血性連鎖球菌感染症.日本耳鼻咽喉科感染症研究会会誌 2003 21(1）:74‐79.
舟橋恵二,中根一匡, 牛垣眞由美, 田中克己, 西村直子, 尾崎隆男:当院小児科におけるA群溶連菌の細菌学的検討.医学検査 2003 52(1):26-30.
Funahashi K, Nakane K, Yasuda N, Suzuki M, Narita A, Arai N, Ahn J, Koyama N, Ushida H, Nishimura N, Ozaki T.
T serotypes and antimicrobial susceptibilities of group A streptococcus isolates from pediatric pharyngotonsillitis.
Jpn J Infect Dis. 2008 Nov;61(6):454-6.
Abstract/Text
Group A streptococcus (GAS) is a major cause of pediatric pharyngotonsillitis. In this study we determined the T serotype and antimicrobial susceptibility of GAS isolates from Japanese children. From January to December 2006, a total of 438 isolates of GAS were obtained from pharyngeal swabs of 438 children with pharyngotonsillitis. The commonest T serotype was type 1 (110 strains, 25.1%), followed by type 12 (107, 24.4%) and type 4 (77, 17.6%). All GAS isolated from pharyngeal swabs were susceptible to beta-lactams (benzylpenicillin, amoxicillin, cefotaxime, ceftriaxone, imipenem, panipenem, and cefditoren) and vancomycin, but 19.6, 19.6, 3.2, 11.6, and 27.6% were resistant to erythromycin, clarithromycin, clindamycin, minocycline, and norfloxacin, respectively. Resistance varied considerably with the T serotype. In particular, type 4 isolates had the highest resistance (67.5, 67.5, 26.0, and 53.2% were resistant to erythromycin, clarithromycin, minocycline, and norfloxacin, respectively).
国立感染症研究所感染症情報センター:IASR 病原微生物検出情報Vol.36 No.8(No.426).2015:152.
Bergman M, Huikko S, Pihlajamäki M, Laippala P, Palva E, Huovinen P, Seppälä H; Finnish Study Group for Antimicrobial Resistance (FiRe Network).
Effect of macrolide consumption on erythromycin resistance in Streptococcus pyogenes in Finland in 1997-2001.
Clin Infect Dis. 2004 May 1;38(9):1251-6. doi: 10.1086/383309. Epub 2004 Apr 14.
Abstract/Text
The aim of this study was to investigate the association between regional macrolide resistance in Streptococcus pyogenes and macrolide use in Finland. During 1997-2001, a total of 50,875 S. pyogenes isolates were tested for erythromycin susceptibility in clinical microbiology laboratories throughout Finland. The local erythromycin resistance levels were compared with the regional consumption data of all macrolides pooled and, separately, with the use of azithromycin. The regional resistance rates of 1 year were compared with the regional consumption of the previous year and with the average rates of use for the 2 previous years. A linear mixed model for repeated measures was used in modeling the association. A statistically significant association existed between regional erythromycin resistance in S. pyogenes and consumption of macrolides; association with azithromycin use alone was not found.
舟橋恵二,大岩加奈,河内誠,岩田泰,野田由美子,中根一匡,西村直子,尾崎隆男:2013年に気道感染症小児から分離されたA群溶血性レンサ球菌の細菌学的検討―過去4回の調査成績と比較して―.医学検査2016;65(2):229-234.
Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention.
Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention.
Ann Intern Med. 2016 Mar 15;164(6):425-34. doi: 10.7326/M15-1840. Epub 2016 Jan 19.
Abstract/Text
BACKGROUND: Acute respiratory tract infection (ARTI) is the most common reason for antibiotic prescription in adults. Antibiotics are often inappropriately prescribed for patients with ARTI. This article presents best practices for antibiotic use in healthy adults (those without chronic lung disease or immunocompromising conditions) presenting with ARTI.
METHODS: A narrative literature review of evidence about appropriate antibiotic use for ARTI in adults was conducted. The most recent clinical guidelines from professional societies were complemented by meta-analyses, systematic reviews, and randomized clinical trials. To identify evidence-based articles, the Cochrane Library, PubMed, MEDLINE, and EMBASE were searched through September 2015 using the following Medical Subject Headings terms: "acute bronchitis," "respiratory tract infection," "pharyngitis," "rhinosinusitis," and "the common cold."
HIGH-VALUE CARE ADVICE 1: Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected.
HIGH-VALUE CARE ADVICE 2: Clinicians should test patients with symptoms suggestive of group A streptococcal pharyngitis (for example, persistent fevers, anterior cervical adenitis, and tonsillopharyngeal exudates or other appropriate combination of symptoms) by rapid antigen detection test and/or culture for group A Streptococcus. Clinicians should treat patients with antibiotics only if they have confirmed streptococcal pharyngitis.
HIGH-VALUE CARE ADVICE 3: Clinicians should reserve antibiotic treatment for acute rhinosinusitis for patients with persistent symptoms for more than 10 days, onset of severe symptoms or signs of high fever (>39 °C) and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or onset of worsening symptoms following a typical viral illness that lasted 5 days that was initially improving (double sickening).
HIGH-VALUE CARE ADVICE 4: Clinicians should not prescribe antibiotics for patients with the common cold.
ESCMID Sore Throat Guideline Group; Pelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, Little P, Verheij T.
Guideline for the management of acute sore throat.
Clin Microbiol Infect. 2012 Apr;18 Suppl 1:1-28. doi: 10.1111/j.1469-0691.2012.03766.x.
Abstract/Text
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.
© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.
Casey JR, Pichichero ME.
Meta-analysis of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis in children.
Pediatrics. 2004 Apr;113(4):866-82. doi: 10.1542/peds.113.4.866.
Abstract/Text
OBJECTIVE: To conduct a meta-analysis of randomized, controlled trials of cephalosporin versus penicillin treatment of group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis in children.
METHODOLOGY: Medline, Embase, reference lists, and abstract searches were conducted to identify randomized, controlled trials of cephalosporin versus penicillin treatment of GABHS tonsillopharyngitis in children. Trials were included if they met the following criteria: patients <18 years old, bacteriologic confirmation of GABHS tonsillopharyngitis, random assignment to antibiotic therapy of an orally administered cephalosporin or penicillin for 10 days of treatment, and assessment of bacteriologic outcome using a throat culture after therapy. Primary outcomes of interest were bacteriologic and clinical cure rates. Sensitivity analyses were performed to assess the impact of careful clinical illness descriptions, compliance monitoring, GABHS serotyping, exclusion of GABHS carriers, and timing of the test-of-cure visit.
RESULTS: Thirty-five trials involving 7125 patients were included in the meta-analysis. The overall summary odds ratio (OR) for the bacteriologic cure rate significantly favored cephalosporins compared with penicillin (OR: 3.02; 95% confidence interval [CI]: 2.49-3.67, with the individual cephalosporins [cephalexin, cefadroxil, cefuroxime, cefpodoxime, cefprozil, cefixime, ceftibuten, and cefdinir] showing superior bacteriologic cure rates). The overall summary OR for clinical cure rate was 2.33 (95% CI: 1.84-2.97), significantly favoring the same individual cephalosporins. There was a trend for diminishing bacterial cure with penicillin over time, comparing the trials published in the 1970s, 1980s, and 1990s. Sensitivity analyses for bacterial cure significantly favored cephalosporin treatment over penicillin treatment when trials were grouped as double-blind (OR: 2.31; 95% CI: 1.39-3.85), high-quality (OR: 2.50; 95% CI: 1.85-3.36) trials with well-defined clinical status (OR: 2.12; 95% CI: 1.54-2.90), with detailed compliance monitoring (OR: 2.85; 95% CI: 2.33-3.47), with GABHS serotyping (OR: 3.10; 95% CI: 2.42-3.98), with carriers eliminated (OR: 2.51; 95% CI: 1.55-4.08), and with test of cure 3 to 14 days posttreatment (OR: 3.53; 95% CI: 2.75-4.54). Analysis of comparative bacteriologic cure rates for the 3 generations of cephalosporins did not show a difference.
CONCLUSIONS: This meta-analysis indicates that the likelihood of bacteriologic and clinical failure of GABHS tonsillopharyngitis is significantly less if an oral cephalosporin is prescribed, compared with oral penicillin.
Casey JR, Pichichero ME.
Metaanalysis of short course antibiotic treatment for group a streptococcal tonsillopharyngitis.
Pediatr Infect Dis J. 2005 Oct;24(10):909-17. doi: 10.1097/01.inf.0000180573.21718.36.
Abstract/Text
OBJECTIVE: To compare bacterial and clinical cure rates in patients with group A streptococcal (GAS) tonsillopharyngitis treated with oral beta-lactam or macrolide antibiotics for 4-5 days versus 10-day comparators.
METHODS: Medline, Embase, reference lists and abstract searches were used to identify available publications. Trials were included if there was bacteriologic confirmation of GAS tonsillopharyngitis, random assignment to antibiotic therapy for a beta-lactam or macrolide antibiotic of a shortened course versus a 10-day comparator and assessment of bacteriologic outcome using a throat culture.
RESULTS: Twenty-two trials involving 7470 patients were included in 4 separate analyses. Trials were grouped by a short course of cephalosporins (n = 14), macrolides (other than azithromycin) (n = 6) and penicillin (n = 2). Cephalosporin trials were further grouped by the comparator, penicillin or the same cephalosporin. Short course cephalosporin treatment was superior for bacterial cure rate compared with 10 days of penicillin [odds ratio (OR), 1.47; 95% confidence interval (CI), 1.06-2.03]. For trials with short course macrolide therapy, OR = 0.79 (95% CI 0.59-1.06) neither the macrolides nor the 10-day comparators. Short course penicillin therapy was inferior in achieving bacterial cure versus 10 days of penicillin, OR = 0.29 (95% CI 0.13-0.63). Clinical cure rates mirrored bacteriologic cure rates.
CONCLUSION: Superior cure rates can be achieved with shortened courses of cephalosporin therapy, but 5 days is inferior to 10 days of penicillin treatment.
Sakata H.
Comparative study of 5-day cefcapene-pivoxil and 10-day amoxicillin or cefcapene-pivoxil for treatment of group A streptococcal pharyngitis in children.
J Infect Chemother. 2008 Jun;14(3):208-12. doi: 10.1007/s10156-008-0597-0. Epub 2008 Jun 24.
Abstract/Text
In order to compare the bacteriological and clinical efficacy and safety of cefcapene-pivoxil (CFPN-PI) for 5 days, CFPN-PI for 10 days, and amoxicillin (AMPC) for 10 days for the treatment of pharyngitis due to group A beta-hemolytic streptococcus (GAS) in children, a prospective multicenter randomized open-label comparative study was performed with 12 pediatric clinics in Asahikawa between June 2006 and February 2007. Two hundred and fifty children (age range 6 months to 12 years) with signs and symptoms of acute pharyngitis were enrolled. All had a positive throat culture for GAS and were fully evaluable. Eighty-two patients received CFPN-PI 9-10 mg/kg/day three times a day for 5 days, 88 received CFPN-PI three times a day for 10 days, and 80 received AMPC three times a day for 10 days. The CFPN-PI for 5 days regimen, the CFPN-PI for 10 days regimen, and the AMPC for 10 days regimen produced bacteriological eradication at the end of treatment in 93.8%, 96.2%, and 91.7% of the patients, respectively. The clinical cure rate observed at the end of therapy was 100% of the patients in the three groups. Relapse rates were 1.3% in CFPN-PI for 5 days, 4.0% in CFPN-PI for 10 days, and 2.9% in AMPC for 10 days. There were no significant differences in eradication rate, clinical cure rate, and relapse rate between the three treatment groups. The only adverse effects were infrequent diarrhea in all three groups, and a rash which occurred in 6 patients (8.0%) of the AMPC treatment group. Five days of treatment with CFPN-PI was as efficacious in bacteriological eradication and clinical response as 10 days of CFPN-PI or AMPC treatment.
Ozaki T, Nishimura N, Suzuki M, Narita A, Watanabe N, Ahn J, Koyama N, Ushida H, Nakane K, Yasuda N, Funahashi K.
Five-day oral cefditoren pivoxil versus 10-day oral amoxicillin for pediatric group A streptococcal pharyngotonsillitis.
J Infect Chemother. 2008 Jun;14(3):213-8. doi: 10.1007/s10156-008-0602-7. Epub 2008 Jun 24.
Abstract/Text
We prospectively compared the efficacy of oral cefditoren-pivoxil and conventional oral amoxicillin for pharyngotonsillitis caused by group A streptococcus in children. Either oral cefditoren-pivoxil (3 mg/kg t.i.d. for 5 days) or amoxicillin (10 mg/kg t.i.d. for 10 days) was administered to patients with group A streptococcal pharyngotonsillitis attending the pediatric outpatient clinic of Showa Hospital (Konan, Japan) between January and December 2006. Diagnosis was based on isolation of bacteria from a pharyngeal swab. Culture was always done to confirm eradication, and urinalysis and follow-up were performed at least once weekly for 4 weeks. Among 258 patients, 103 (aged 5.5 +/- 2.3 years) received cefditoren-pivoxil and 155 (aged 5.2 +/- 2.0 years) received amoxicillin. There were no significant between-group differences in age, sex, or symptoms. Eradication was confirmed in 99% (102/103) of the cefditoren-pivoxil group and 100% of the amoxicillin group. Recurrence within 4 weeks occurred in 8 and 15 patients in the cefditoren-pivoxil and amoxicillin groups, respectively, showing no significant difference in the recurrence rate, and all isolates had the same serotypes as before. There were no clinically significant adverse reactions or complications. The 50%/90% minimum inhibitory concentrations (microg/ml) of cefditoren-pivoxil and amoxicillin for the 258 isolates were < or =0.03/< or =0.03 and < or =0.03/0.06, respectively, so all isolates were susceptible to both agents. Because the efficacy for pediatric group A streptococcus pharyngotonsillitis was similar between oral cefditoren-pivoxil for 5 days and amoxicillin for 10 days, the shorter treatment period may make the former regimen preferable.
Tsumura N, Nagai K, Hidaka H, Otsu Y, Tanaka Y, Ikezawa S, Honma S, Shindo S, Ubukata K.
[Antibiotic therapy against acute tonsillopharyngitis in children due to group A beta-hemolytic streptococci: comparison of clinical efficacy, the bactericidal effects, and effects on oral flora between cefditoren pivoxil for 5 days and amoxicillin for 10 days].
Jpn J Antibiot. 2011 Jun;64(3):179-90.
Abstract/Text
We compared the clinical efficacy, the bactericidal effects, effect on the oral microbial flora, and adverse reactions between cefditoren pivoxil (CDTR-PI) for 5 days and amoxicillin (AMPC) for 10 days in children with acute group A beta-hemolytic streptococci (GAS) tonsillopharyngitis, and simultaneously examined the emm genotype and drug susceptibility of the isolated GAS. The results showed that the clinical efficacy was 100% for CDTR-PI and 97.9% for AMPC, with no difference between the two groups, and the bacterial elimination rate was 100% in both groups. No serious adverse event was noted in either group. On the other hand, concerning changes in the oral microbial flora between before and after treatment, the amount of bacteria showed no change in the CDTR-PI group (p = 0.5761) but clearly decreased in the AMPC group (p = 0.0049). This indicates that CDTR-PI does not disturb the oral microbial flora compared with AMPC. Also, the emm types determined in the 112 GAS strains isolated in this study were similar to those that have recently been isolated frequently in Japan. Concerning the drug resistance, none of the isolates showed resistance to beta-lactam antibiotics, but 45% of them were resistant to macrolides. The advantages of short-term treatment are considered to include a lower cost, improvement in drug compliance, decrease in the frequency of the occurrence of adverse reactions, decrease in the frequency of the appearance of drug-resistant strains, and alleviation of the psychological burden of patients and their parents. For these reasons, we conclude that CDTR-PI for 5 days is a useful option for the treatment of acute GAS tonsillopharyngitis in children.
Altamimi S, Khalil A, Khalaiwi KA, Milner RA, Pusic MV, Al Othman MA.
Short-term late-generation antibiotics versus longer term penicillin for acute streptococcal pharyngitis in children.
Cochrane Database Syst Rev. 2012 Aug 15;(8):CD004872. doi: 10.1002/14651858.CD004872.pub3. Epub 2012 Aug 15.
Abstract/Text
BACKGROUND: The standard duration of treatment for children with acute group A beta hemolytic streptococcus (GABHS) pharyngitis with oral penicillin is 10 days. Shorter duration antibiotics may have comparable efficacy.
OBJECTIVES: To summarize the evidence regarding the efficacy of two to six days of newer oral antibiotics (short duration) compared to 10 days of oral penicillin (standard duration) in treating children with acute GABHS pharyngitis.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 3) which contains the Cochrane Acute Respiratory Infections Group's Specialized Register, MEDLINE (January 1966 to March week 3, 2012) and EMBASE (January 1990 to April 2012).
SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing short duration oral antibiotics to standard duration oral penicillin in children aged 1 to 18 years with acute GABHS pharyngitis.
DATA COLLECTION AND ANALYSIS: Two review authors scanned the titles and abstracts of retrieved citations and applied the inclusion criteria. We retrieved included studies in full, and extracted data. Two review authors independently assessed trial quality.
MAIN RESULTS: We included 20 studies with 13,102 cases of acute GABHS pharyngitis. The updated search did not identify any new eligible studies; the majority of studies were at high risk of bias. However, the majority of the results were consistent. Compared to standard duration treatment, the short duration treatment studies had shorter periods of fever (mean difference (MD) -0.30 days, 95% confidence interval (CI) -0.45 to -0.14) and throat soreness (MD -0.50 days, 95% CI -0.78 to -0.22); lower risk of early clinical treatment failure (odds ratio (OR) 0.80, 95% CI 0.67 to 0.94); no significant difference in early bacteriological treatment failure (OR 1.08, 95% CI 0.97 to 1.20) or late clinical recurrence (OR 0.95, 95% CI 0.83 to 1.08). However, the overall risk of late bacteriological recurrence was worse in the short duration treatment studies (OR 1.31, 95% CI 1.16 to 1.48), although no significant differences were found when studies of low dose azithromycin (10 mg/kg) were eliminated (OR 1.06, 95% CI 0.92 to 1.22). Three studies reported long duration complications. Out of 8135 cases of acute GABHS pharyngitis, only six cases in the short duration treatment versus eight in the standard duration treatment developed long-term complications in the form of glomerulonephritis and acute rheumatic fever, with no statistically significant difference (OR 0.53, 95% CI 0.17 to 1.64).
AUTHORS' CONCLUSIONS: Three to six days of oral antibiotics had comparable efficacy compared to the standard duration 10-day course of oral penicillin in treating children with acute GABHS pharyngitis. . In areas where the prevalence of rheumatic heart disease is still high, our results must be interpreted with caution.
Adam D, Scholz H, Helmerking M.
Short-course antibiotic treatment of 4782 culture-proven cases of group A streptococcal tonsillopharyngitis and incidence of poststreptococcal sequelae.
J Infect Dis. 2000 Aug;182(2):509-16. doi: 10.1086/315709. Epub 2000 Jul 28.
Abstract/Text
A large-scale study with a 1-year follow-up was performed to compare 10 days of penicillin V with a short-course treatment (5 days) of other oral antibiotics in the treatment of group A beta-hemolytic streptococcus (GABHS) tonsillopharyngitis, to evaluate the efficacy and the incidence of poststreptococcal sequelae. The clinical response rates after completion of therapy were 94.5% in the 5-day group and 93.4% in the penicillin group (P<.001, equivalence test). The GABHS eradication rates were 83.3% in the 5-day group and 84.4% in the penicillin group (P=.022, equivalence test). Poststreptococcal sequelae were rare (5 patients) and did not occur in the context of this study. The efficacy of 5-day antibiotic regimens was equivalent to 10 days of penicillin V, but resolution of clinical symptoms was faster in the 5-day group (P<.001, Fisher's exact test). Recurrent tonsillopharyngitis occurs more frequently after treatment with penicillin (P=.03, Fisher's exact test).
公益社団法人日本小児科学会 薬事委員会:ピボキシル基含有抗菌薬の服用に関連した低カルニチン血症に係る注意喚起;2019年7月.
Adams EM, Gudmundsson S, Yocum DE, Haselby RC, Craig WA, Sundstrom WR.
Streptococcal myositis.
Arch Intern Med. 1985 Jun;145(6):1020-3.
Abstract/Text
Two patients had streptococcal myositis. Both patients developed extensive muscle necrosis and overwhelming sepsis after trivial skin trauma. Death occurred within 48 hours of hospital admission despite aggressive surgical and medical treatment. Review of the literature is included to highlight the fulminant nature of this unusual infection and to contrast streptococcal myositis with other soft-tissue streptococcal infections.
Bisno AL, Stevens DL.
Streptococcal infections of skin and soft tissues.
N Engl J Med. 1996 Jan 25;334(4):240-5. doi: 10.1056/NEJM199601253340407.
Abstract/Text
Gemmell CG, Peterson PK, Schmeling D, Kim Y, Mathews J, Wannamaker L, Quie PG.
Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin.
J Clin Invest. 1981 May;67(5):1249-56. doi: 10.1172/jci110152.
Abstract/Text
Streptococcus pyogenes, bearing M-protein on its surface, resists opsonization by normal human serum and subsequent phagocytosis by human polymorphonuclear leukocytes. Previous studies have shown that M-protein positive organisms are poorly opsonized by the alternate pathway of complement. In an attempt to define further the role of the surface components of S. pyogenes in this process, we examined the ability of clindamycin, an antibiotic that inhibits protein biosynthesis, to alter bacterial opsonization. An M-protein positive strain of S. pyogenes was grown in varying concentrations of clindamycin at levels lower than those which inhibited growth, i.e., at levels less than the minimal inhibitory concentration. These bacteria were incubated with purified human polymorphonuclear leukocytes and peripheral blood monocytes. Significant enhancement of bacterial opsonization, phagocytosis, and killing resulted. Measurement of complement consumption and binding of the third component of complement (C3) onto the bacterial surface demonstrated that organisms grown in the presence of clindamycin activated complement more readily and fixed more C3 on their surface. Electron microscopy revealed the probable basis for these findings. Streptococci exposed to clindamycin during growth were largely denuded of surface "fuzz," the hairlike structures bearing M-protein. We conclude that the incorporation of clindamycin at concentrations that fail to inhibit growth of S. pyogenes nevertheless causes significant changes in the capacity of these bacteria to resist opsonization by serum complement. These findings support the hypothesis that M-protein inhibits bacterial opsonization by interfering with effective complement activation on the bacterial surface.
Stevens DL.
Streptococcal toxic-shock syndrome: spectrum of disease, pathogenesis, and new concepts in treatment.
Emerg Infect Dis. 1995 Jul-Sep;1(3):69-78. doi: 10.3201/eid0103.950301.
Abstract/Text
Since the 1980s there has been a marked increase in the recognition and reporting of highly invasive group A streptococcal infections with or without necrotizing fasciitis associated with shock and organ failure. Such dramatic cases have been defined as streptococcal toxic-shock syndrome. Strains of group A streptococci isolated from patients with invasive disease have been predominantly M types 1 and 3 that produce pyrogenic exotoxin A or B or both. In this paper, the clinical and demographic features of streptococcal bacteremia, myositis, and necrotizing fasciitis are presented and compared to those of streptococcal toxic-shock syndrome. Current concepts in the pathogenesis of invasive streptococcal infection are also presented, with emphasis on the interaction between group A Streptococcus virulence factors and host defense mechanisms. Finally, new concepts in the treatment of streptococcal toxic-shock syndrome are discussed.
Zimbelman J, Palmer A, Todd J.
Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection.
Pediatr Infect Dis J. 1999 Dec;18(12):1096-100. doi: 10.1097/00006454-199912000-00014.
Abstract/Text
CONTEXT: Animal model studies have demonstrated the failure of penicillin to cure Streptococcus pyogenes myositis and have suggested that clindamycin is a more effective treatment.
OBJECTIVE: To determine the most effective antibiotic treatment for invasive S. pyogenes infection in humans.
DESIGN AND SETTING: We conducted a retrospective review of the outcomes of all inpatients from 1983 to 1997 treated for invasive S. pyogenes infection at Children's Hospital.
PATIENTS: Fifty-six children were included, 37 with initially superficial disease and 19 with deep or multiple tissue infections.
MAIN OUTCOME MEASURE: Lack of progression of disease (or improvement) after at least 24 h of treatment.
RESULTS: The median number of antibiotic exposures was 3 per patient (range 1 to 6) with clindamycin predominating in 39 of 45 courses of protein synthesis-inhibiting antibiotics and beta-lactams predominating amongst the cell wall-inhibiting antibiotics in 123 of 126 of the remainder. Clindamycin was often used in combination with a beta-lactam antibiotic. Overall there was a 68% failure rate of cell wall-inhibiting antibiotics when used alone. Patients with deep infection were more likely to have a favorable outcome if initial treatment included a protein synthesis-inhibiting antibiotic as compared with exclusive treatment with cell wall-inhibiting antibiotics (83% vs. 14%, P = 0.006) with a similar trend in those with superficial disease (83% vs. 48%, P = 0.07). For those children initially treated with cell wall-inhibiting antibiotics alone, surgical drainage or debridement increased the probability of favorable outcome in patients with superficial disease (100% vs. 41%, P = 0.04) with a similar trend in a smaller number of deep infections (100% vs. 0%, P = 0.14).
CONCLUSIONS: This retrospective study suggests that clindamycin in combination with a beta-lactam antibiotic (with surgery if indicated) might be the most effective treatment for invasive S. pyogenes infection.
Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan EL, Montoya JG, Wade JC; Infectious Diseases Society of America.
Practice guidelines for the diagnosis and management of skin and soft-tissue infections.
Clin Infect Dis. 2005 Nov 15;41(10):1373-406. doi: 10.1086/497143. Epub 2005 Oct 14.
Abstract/Text
国立国際医療研究センター 国際感染症センター. 劇症型溶血性レンサ球菌感染症（STSS）. https://dcc-irs.ncgm.go.jp/material/manual/stss.html（2024年11月閲覧）.
Ikebe T, Wada A, Oguro Y, Ogata K, Katsukawa C, Isobe J, Shima T, Suzuki R, Ohya H, Tominaga K, Okuno R, Uchitani Y, Watanabe H; Working Group for Beta-hemolytic Streptococci in Japan.
Emergence of clindamycin-resistant Streptococcus pyogenes isolates obtained from patients with severe invasive infections in Japan.
Jpn J Infect Dis. 2010 Jul;63(4):304-5.
Abstract/Text
Nakamura S, Yanagihara K, Kaneko Y, Ohno H, Higashiyama Y, Miyazaki Y, Hirakata Y, Tomono K, Tashiro T, Kohno S.
[A case of invasive group A Streptococcus infection which was successfully treated with linezolid].
Kansenshogaku Zasshi. 2004 May;78(5):446-50. doi: 10.11150/kansenshogakuzasshi1970.78.446.
Abstract/Text
A 53-year-old male was admitted to our hospital with a high fever and pain in the right arm. He was diagnosed as toxic shock-like syndrome by Streptococcus pyogenes. His arm was amputated because of necrotizing myositis and his renal damage was severe, he was treated in the intensive care unit with continuous hemodiafiltration. Bacteria were isolated from blood, ascites, pleural effusion, skin, and muscle. He was treated with a large amount of ampicillin, clindamycin, and gammaglobulin. However, his general status became worse. His illness improved after linezolid was administered. The reason for the success in treatment with linezolid, which was the inhibitory effect on bacterial toxin and its excellent penetration into the tissue.
尾内一信,黒崎知道,岡田賢司 監修:5章 上気道炎 2．咽頭・扁桃炎.小児呼吸器感染症診療ガイドライン2011, 協和企画 2011;16-19.
武田修明,桑門克治,藤原充弘,新垣義夫,本郷俊治:溶連菌感染後急性糸球体腎炎の最近の動向と発症予防の可能性.小児科臨床 2007;60(5):31-36.
市田蕗子,佐地勉,梶野浩樹,小川俊一,中澤誠:平成20年度稀少疾患サーベイランス調査結果.日本小児循環器学会誌 2007;25(5）:746-748.
坂田宏:近年の小児の溶連菌感染後急性糸球体腎炎の実態調査.日児誌 2009;113(12):1809-1813.
金井宏明,武井義親,東田耕輔,杉田完爾:溶連菌感染後の定期尿検査の必要性についての検討.小児科臨床 2010;63(10）:2151-2155.
Kikuta H, Shibata M, Nakata S, Yamanaka T, Sakata H, Fujita K, Kobayashi K.
Efficacy of antibiotic prophylaxis for intrafamilial transmission of group A beta-hemolytic streptococci.
Pediatr Infect Dis J. 2007 Feb;26(2):139-41. doi: 10.1097/01.inf.0000253060.72953.9d.
Abstract/Text
BACKGROUND: The role of chemoprophylaxis for household contacts of patients with acute streptococcal disease is uncertain.
METHODS: The subjects were 1440 sibling contacts of 1181 index patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis. Instances of subsequent GABHS pharyngitis in sibling contacts who received chemoprophylaxis and in a control group without prophylaxis were compared.
RESULTS: Of the 948 siblings in the prophylaxis group, 507 were treated with cephalosporins and 441 were treated with penicillins for 3 to 5 days. Subsequent GABHS pharyngitis occurred within 30 days in 28 (3.0%) of the 948 siblings in the prophylaxis group and in 26 (5.3%) of the 492 siblings in the control group. Among siblings in the prophylaxis group, subsequent GABHS pharyngitis occurred in 9 (1.8%) of the 507 siblings in the cephalosporin prophylaxis group and in 19 (4.3%) of the 441 siblings in the penicillin prophylaxis group. When these data were each compared with that in the control group (5.3%), a significant statistical difference was seen in the cephalosporin prophylaxis group (P = 0.003) but not in the penicillin prophylaxis group (P = 0.542). Only 5-day cephalosporin prophylaxis showed significant reduction in the rate of subsequent GABHS pharyngitis compared with that in the control group (P = 0.002).
CONCLUSIONS: In view of the low incidence of subsequent GABHS pharyngitis in the nonprophylaxis group, the usual self-limited nature of GABHS pharyngitis, the cost of prophylaxis and the risk for selecting resistant flora, routine chemoprophylaxis against GABHS pharyngitis for sibling contacts is not recommended.
国立感染症研究所. 感染症発生動向調査で届け出られた劇症型溶血性レンサ球菌感染症（STSS）症例の概要. https://www.niid.go.jp/niid/ja/tsls-m/tsls-idwrs/12806-stss-20240802.html（2024年11月閲覧）.
