Strep throat, the common bacterial infection of the throat, is caused by the Streptococcus bacteria. Rheumatic fever is one of the sequelae of this infection and is discussed below.
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EPIDEMIOLOGY CHARACTERIZATION AGE RANGE-MEDIAN
Group A streptococcal pharyngitis in adults 30 to 65 years of age.
Woods WA, Carter CT, Stack M, Connors AF Jr, Schlager TA.
Department of Emergency Medicine, University of Virginia Health Sciences Center, Charlottesville, USA.
South Med J 1999 May;92(5):491-2 Abstract quote
BACKGROUND: Although the frequency of group A streptococcal pharyngitis in adults is assumed to be low, there is little information on frequency other than in military populations.
METHODS: A prospective, observational study was done to determine the frequency of group A streptococcal pharyngitis in adults seen in the emergency department. Throat swabs were obtained on adults (30 to 65 years of age) with sore throat and pharyngitis on examination. Swabs were also obtained in a group of control subjects.
RESULTS: Of the 148 adults with pharyngitis, 65 (44%) had throat specimens positive for group A streptococci. In the 50 control subjects, all throat cultures were negative for group A streptococci. A significant number of patients with group A streptococcal pharyngitis had school-aged children at home.
CONCLUSION: The high rate of detection of group A streptococci in adults outside the military has not been previously reported.
Incidence of invasive pneumococcal disease in Scotland, 1988-99.
Kyaw MH, Clarke S, Jones IG, Campbell H.
University of Edinburgh, Public Health Sciences.
Epidemiol Infect 2002 Apr;128(2):139-47 Abstract quote
A review of the epidemiology of invasive pneumococcal disease in Scotland was carried out using data from laboratory-based systems during the period 1988-99. This comprised 5456 (90.8%) isolates of Streptococcus pneumoniae from blood, 467 (7.8%) from cerebrospinal fluid (CSF) and 84 (1.4%) from other sterile sites.
The mean annual incidence of invasive disease was 9.8/10(5) population (9.0/10(5) for bacteraemia and 0.8/10(5) for meningitis). Invasive disease was highest in children < 2 years of age and in the elderly > or = 65 years (44.9/10(5) and 28.4/10(5) population in these age groups respectively). The highest incidence of pneumococcal meningitis, 11.8/10(5) persons occurred in children < 2 years of age. Males had a higher incidence of pneumococcal bacteraemia and meningitis than females (male:female = 1.2:1 for bacteraemia (RR = 1.17, 95 % CI 1.11, 1.24) and 1.5:1 for meningitis (RR = 1.41, 95 % CI 1.18, 1.70)). Pneumococcal disease was highest in winter periods and coincided with influenza activity.
The proportion of penicillin and erythromycin non-susceptible isolates increased from 4.2% in 1992 to 12.6% in 1999 and from 5.6% in 1994 to 16.3% in 1999 respectively. Our data confirm the substantial and increasing disease burden from pneumococcal disease and rise in prevalence of antibiotic non-susceptibility among pneumococci in Scotland. Continued surveillance of groups at increased risk for pneumococcal disease and the antibiotic susceptibility and serotype distribution of isolates are important to develop appropriate policies for the prevention of pneumococcal disease in Scotland.
DISEASE ASSOCIATIONS CHARACTERIZATION FOOD CONTAMINATION
Streptococcal contamination of food: an unusual cause of epidemic pharyngitis.
Katzenell U, Shemer J, Bar-Dayan Y.
Department of Otolaryngology, Wolfson Medical Center, Holon, Israel.
Epidemiol Infect 2001 Oct;127(2):179-84 Abstract quote
The purpose of this article is to define the distinguishing characteristics of food-borne streptococcal pharyngitis by reviewing the literature. The main cause of this infection lies in poor handling and preservation of cold salads, usually those which contain eggs and are prepared some hours before serving. A shorter incubation period and a higher attack rate (51-90%) than in transmission by droplets was noted.
The epidemics tend to occur in warm climates and in the hottest months of the year. Streptococcus pyogenes seems to originate from the pharynx or hand lesions of a food handler. In comparison to airborne transmission symptoms such as sore throat, pharyngeal erythema, and enlarged tonsils, submandibular lymphadenopathy are more frequent than coughing and coryza. Seven out of 17 reports revealed an M-untypeable serotype, which may possess virulent characteristics. Penicillin prophylaxis was shown to limit additional spread of the infection. There were no non-suppurative sequels, and suppurative sequels were very rare.
We assume that the guidelines for the prevention of food poisoning would apply to food-borne streptococcal pharyngitis. Food handlers should be supervised to ensure they comply with strict rules of preparation and storage of food. Cold salads, especially those containing eggs, should not be left overnight before serving.
STEM CELL TRANSPLANTATION
Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey.
Engelhard D, Cordonnier C, Shaw PJ, Parkalli T, Guenther C, Martino R, Dekker AW, Prentice HG, Gustavsson A, Nurnberger W, Ljungman P; The Infectious Disease Working Party of the European Bone Marrow Transplantation (IDWP-EBMT).
Department of Pediatrics, Hadassah University Hospital and Hebrew University Hadassah Medical School, Ein Karem, Jerusalem, Israel.
Br J Haematol 2002 May;117(2):444-50 Abstract quote
Streptococcus pneumoniae (S. pneumoniae) may cause severe and lethal infections months and years following stem cell transplantation (SCT).
In a prospective survey over a 3.5-year period, we assessed the incidence, risk factors and outcome for invasive pneumococcal infection (IPI) following SCT. Fifty-one episodes of IPI were reported: 43 episodes after bone marrow transplantation (BMT) and 8 after peripheral blood stem cell transplantation (PBSCT); 35 after allogeneic SCT and 16 after autologous SCT. Seven IPI episodes, all bacteraemias, were defined as early, occurring 1-35 d (median 3 d) post transplantation. Forty-four episodes were defined as late (> or = 100 d post SCT), occurring 4 months to 10 years (median 17 months) post transplantation. The incidences of early and late IPI were 2.03/1000 and 8.63/1000 transplantations respectively (P = 0.001). A higher incidence of late IPI was observed after BMT than after PBSCT (10.99 versus 3.23/1000; P < 0.01) and after allogeneic versus autologous SCT (12.20 versus 4.60/1000; P < 0.01). There was a higher estimated incidence of IPI in allogeneic patients with than in those without graft-versus-host disease (GVHD) (18.85 versus 8.25/1000; P = 0.015). The mortality rate was 20%, including 2/7 of early and 8/44 of late IPI. S. pneumoniae is a rare but important complication during the aplastic phase after SCT.
In conclusion, S. pneumoniae is a significant cause of morbidity late post-transplantation, especially in allogeneic patients, and particularly those with GVHD. The high IPI mortality rate, both early and late post-transplantation, requires preventive approaches, mainly effective immunization.
PATHOGENESIS CHARACTERIZATION GROUP A
A comparison of group A streptococci from invasive and uncomplicated infections: are virulent clones responsible for serious streptococcal infections?
Johnson DR, Wotton JT, Shet A, Kaplan EL.
Department of Pediatrics, World Health Organization Collaborating Center for Reference and Research on Streptococci, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
J Infect Dis 2002 Jun 1;185(11):1586-95 Abstract quote
From the mid-1980s, numerous reports of invasive group A streptococcal infections suggested that "highly virulent clones" were responsible. However, there have been virtually no extensive reports and comparisons of diverse temporal and geographic community isolates from uncomplicated throat infections to confirm the hypothesis.
A unique collection of such "control" strains allowed in-depth assessment of association of M serotypes 1, 3, and 28 "clones" with invasive infections. Clones were defined by using small-fragment chromosomal restriction-enzyme analysis, pulsed-field gel electrophoresis, and M protein gene (emm) sequencing. After comparison with controls, no clone within these M serotypes had statistically increased association with invasive infections. The prevalence of specific virulence-associated clones appeared to essentially reflect their normal population prevalence.
Although this does exclude other potential streptococcal factors, these findings suggest that host factors including individual and population-based immunity must also be significant in influencing infection potential.
CHARACTERIZATION RADIOLOGIC LABORATORY MARKERS PCR
Polymerase chain reaction for Streptococcus pyogenes used to evaluate an optical immunoassay for the detection of group A streptococci in children with pharyngitis.
Kaltwasser G, Diego J, Welby-Sellenriek PL, Ferrett R, Caparon M, Storch GA.
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Pediatr Infect Dis J 1997 Aug;16(8):748-53 Abstract quote
BACKGROUND: In evaluations of sensitive rapid tests for group A streptococci such as the optical immunoassay (OIA), some samples are positive by the antigen test but negative by culture. A method is needed for resolving these discrepant results.
OBJECTIVE: To develop a PCR-based assay to detect group A streptococci and to use it to establish a reference standard for evaluating an OIA for group A streptococcal antigen.
METHODS: A PCR assay that detects a segment of the MF gene of Streptococcus pyogenes was developed for the detection of group A streptococci in throat swabs. Paired swabs were obtained from 200 children with symptomatic pharyngitis and used to perform OIA, agar culture, broth-enhanced culture and PCR. As a reference standard any patient with group A streptococci detected by either culture or PCR was considered to be truly positive.
RESULTS: In comparison to agar and broth-enhanced culture procedures, OIA had sensitivities of 82 and 80% and specificities of 87 and 89%, respectively. Eight (44%) of 18 samples that were positive by OIA but negative by culture were positive for group A streptococci by PCR. Compared with the reference standard, sensitivities were OIA 76%, agar culture 79%, broth-enhanced culture 86% and PCR 96%. The specificity of OIA was 92%.
CONCLUSIONS: PCR can be used to establish a reference standard for evaluating rapid tests for group A streptococci. With this reference standard OIA was nearly as sensitive as but less specific than agar culture for detection of group A streptococci. Maximum detection requires use of both tests.
RAPID STREPTOCOCCAL TESTING
Streptococcal pharyngitis: impact of a high-sensitivity antigen test on physician outcome.
Needham CA, McPherson KA, Webb KH.
Department of Laboratory Medicine, Lahey Clinic, Burlington, Massachusetts, USA.
J Clin Microbiol 1998 Dec;36(12):3468-73 Abstract quote
The purpose of the present study was to determine whether the availability of results from a high-sensitivity, rapid test for group A streptococci (Strep A OIA; BioStar, Inc., Boulder, Colo.) improves physician outcome.
The study population included 465 consecutive patients with symptoms of acute pharyngitis seen in two outpatient clinics in a large suburban medical center; one clinic, a walk-in clinic (WIC), primarily saw adult patients, and one clinic, a pediatric and adolescent medicine clinic (PED), primarily saw pediatric patients.
We measured improvement in physician outcome by comparing physician intent for prescribing an antibiotic based on clinical impression with physician practice once the results of the Strep A OIA were known. Based upon intent, the physicians seeing WIC patients (WIC physicians) would have prescribed an appropriate antibiotic course for 42% of patients with cultures positive for group A beta-hemolytic streptococci (GABHS) and 61% of patients with cultures negative for GABHS. After receiving the results of the Strep A OIA, WIC physicians prescribed an appropriate antibiotic course for 81% of patients with positive cultures and 72% of patients with negative cultures. Based upon intent, the physicians seeing PED patients (PED physicians) would have prescribed an appropriate antibiotic course for 35% of patients with positive cultures and 77% of patients with negative cultures. After receiving the results of the Strep A OIA, PED physicians prescribed an appropriate antibiotic course for 90% of patients with positive cultures and 81% of patients with negative cultures. Based on a 14.5% prevalence of GABHS among WIC patients, Strep A OIA improved the overall WIC physician outcome from 58 to 74%. Based on a 31.5% prevalence of GABHS among PED patients, Strep A OIA improved the PED physician outcome from 64 to 84%.
Had Strep A OIA alone guided therapeutic choice, physicians would have prescribed an appropriate antibiotic course for 95% of the patients at the time of the initial encounter. We conclude that the use of Strep A OIA improves physician outcome.
Evaluation of the Strep A OIA assay versus culture methods: ability to detect different quantities of group A Streptococcus.
Kuhn S, Davies HD, Katzko G, Jadavji T, Church DL.
Department of Pediatrics, University of Calgary, Alberta, Canada.
Diagn Microbiol Infect Dis 1999 Aug;34(4):275-80 Abstract quote
The Strep A OIA assay by Biostar (Boulder, Co., USA) is a unique optical immunoassay system for the rapid detection of Group A streptococcal carbohydrate. As part of a community-based pediatric cohort study of Group A Streptococcus (GAS) persistence following antibiotic therapy of pharyngitis, the performance of the Strep A OIA assay was compared with the amount of growth from standard throat swab culture methods.
A total of 363 throat swabs taken over the course of the study was evaluated from 248 children between 2 and 18 years of age. Two culture methods were performed: an agar plate with the throat swab using Columbia agar base with 5% sheep blood incubated under an anaerobic environment for 48 h and Todd-Hewitt broth (THB) enhancement. The Strep A OIA was then performed. A total of 144 of 363 (39.7%) samples was positive for GAS by one or more of the laboratory tests across study visits: agar culture detected 132 of 144 (91.7%), THB culture detected 128 of 144 (88.9%), and the Strep A OIA assay detected 129 of 144 (89.6%). Complete agreement among all three laboratory tests was found for 333 of 363 (91.7%) of the samples. Agar culture results were comparable to THB cultures with a sensitivity of 96.9%, specificity of 96.6%, a positive predictive value of 93.9%, and a negative predictive value of 98.3%. Although the performance of the Strep A OIA assay had similar specificity (96.5%) and positive predictive value (93.8%) compared with the combined results of the two culture methods, the sensitivity (89.0%) and negative predictive value (93.6%) were lower.
A significant difference (p < 0.001) was found in the ability of the Strep A OIA assay to detect agar culture-positive swabs that had a light growth (1+ or 2+) (63.0%) versus a moderate (3+) or heavy (4+) growth (98.1%) of GAS. Although the Strep A OIA assay allows GAS throat swab results to be reported an average of 24 h sooner than either of the cultures, the rapid assay was not as sensitive in detecting light growth GAS-positive cultures.
Importance of inoculum size and sampling effect in rapid antigen detection for diagnosis of Streptococcus pyogenes pharyngitis.
Kurtz B, Kurtz M, Roe M, Todd J.
Texas College of Osteopathic Medicine, Fort Worth, Texas, USA.
J Clin Microbiol 2000 Jan;38(1):279-81 Abstract quote
Current recommendations suggest that negative rapid Streptococcus pyogenes antigen tests be backed up with a culture, reflecting evidence that culture may have a higher sensitivity and also that testing of a second swab may yield a different (i.e., a positive) result because of variation in sample size or distribution. If the latter is common, the sensitivities of current antigen detection tests might be improved by simply increasing the amount of sample tested.
The present study assessed the effect of antigen testing of two swabs extracted together compared to independent testing of each swab extracted separately for children with clinical pharyngitis. S. pyogenes grew from one or both swabs for 198 (37%) of 537 children. The combined culture was significantly (P < 0.05) more sensitive than culture of either swab alone. Compared to combined culture, antigen testing of two swabs extracted and tested together was significantly more sensitive than two single swab extractions (94.1 versus 80%; P = 0.03); however, the specificity was decreased (81.5 versus 89.8 to 92.7%; P < 0.05).
This study suggests that sample size and/or uneven sample distribution may have influenced the apparent sensitivities of prior studies that compared antigen tests to a single plate culture. A strategy, such as the one used in the present study, that increases the sample size available for antigen testing (i.e., extraction of samples from both swabs) may improve detection rates to a level that will better approximate true disease status and obviate the need for backup cultures if specificity can be improved.
CHARACTERIZATION GENERAL GROUP B PERINATAL INFECTIONS
Group B streptococci during pregnancy and infancy.
Department of Pediatrics, University Hospital Freiburg, Freiburg, Germany.
Curr Opin Infect Dis 2002 Jun;15(3):307-13 Abstract quote
Group B streptococcus (Streptococcus agalactiae) is still of great relevance in the perinatal period, although maternal antimicrobial prophylaxis has significantly reduced the rate of culture-confirmed invasive infection in neonates.
This strategy, however, raises considerable concern because preterm delivery or late-onset sepsis cannot be prevented, and antibiotic resistance is increasing worldwide. Several advances in the development of conjugate vaccines and in research on virulence factors and pathways involved in the immune response to group B streptococcus have been accomplished, some of which might reach clinical practice in the near future.
Diagnosis of strep throat in adults: are clinical criteria really good enough?
Bisno AL, Peter GS, Kaplan EL.
Department of Medicine, University of Miami School of Medicine and Veterans Affairs Medical Center, Miami, FL, 33125, USA.
Clin Infect Dis 2002 Jul 15;35(2):126-9 Abstract quote
The clinical manifestations of group A streptococcal and nonstreptococcal pharyngitis overlap quite broadly. For this reason, the updated Infectious Diseases Society of America practice guideline for group A streptococcal pharyngitis, published in this issue of Clinical Infectious Diseases, recommends laboratory confirmation of the clinical diagnosis by means of either throat culture or a rapid antigen detection test.
However, a recently published guideline, developed by a subcommittee of the American College of Physicians-American Society of Internal Medicine (ACP-ASIM) in collaboration with the Centers for Disease Control and Prevention, advocates use of a clinical algorithm alone, in lieu of microbiologic testing, for confirmation of the diagnosis in adults for whom the suspicion of streptococcal infection is high.
In this discussion, we examine the assumptions of the ACP-ASIM guideline, question whether its recommendations will achieve the stated objective of dramatically decreasing excess antibiotic use, and suggest that its recommendations be confirmed by clinical trials before clinicians abandon long-held teachings regarding diagnosis and management of group A streptococcal pharyngitis.
PUSTULOSIS ACUTA GENERALISATA
Pustulosis acuta generalisata is a post-streptococcal disease and is distinct from acute generalized exanthematous pustulosis.
Auer-Grumbach P, Pfaffenthaler E, Soyer HP.
Department of Dermatology, University of Graz, Austria.
Br J Dermatol 1995 Jul;133(1):135-9 Abstract quote
Generalized pustular eruptions with fever present a diagnostic and therapeutic problem. Based on a case of pustulosis acuta generalisata and a review of the literature, this entity can be regarded as an exclusively post-streptococcal disorder with an elevated antistreptolysin titre. It has a distinct clinical presentation of isolated pustules on normal skin, predominantly in an acral location.
We propose criteria for the clear separation of this disease from acute generalized exanthematous pustulosis and from pustular psoriasis.
Resurgence of rheumatic fever in the United States. The changing picture of a preventable illness.
Department of Pediatrics, University of Florida College of Medicine, Gainesville.
Postgrad Med 1992 Sep 1;92(3):133-6, 139-42 Abstract quote
The recent resurgence of rheumatic fever reported in eight locations in the United States after years of decline has several noteworthy characteristics.
Most patients were children of families in high- to middle-income brackets with ready access to medical care. In four of the outbreaks, the majority of patients were adults, who were more likely than children to have arthritis and less likely to have Sydenham's chorea. Many patients had no clinical history of streptococcal pharyngitis. Rheumatic fever developed in some patients despite antibiotic treatment for streptococcal pharyngitis. Analysis of the outbreaks supports the following conclusions: No population is exempt from rheumatic fever.
Physicians should be diligent in performing throat cultures in cases of suspected streptococcal pharyngitis. The efficacy of orally administered penicillin in preventing rheumatic fever should be reexamined, and oral antibiotics that are potentially more effective should be sought.
Rullan E, Sigal LH.
Department of Medicine, Division of Rheumatology, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place, PO Box 19, MEB-484, New Brunswick, NJ 08903-0019, USA.
Curr Rheumatol Rep 2001 Oct;3(5):445-52 Abstract quote
Rheumatic fever is a multisystem inflammatory disease that occurs as a delayed sequel to group A streptococcal pharyngitis. It is less common than it was 50 years ago but is still a major cause of heart disease in developing areas of the world. The relationship between the site of infection, the type of causative organism, and susceptibility of the host is essential in the development of the disease.
Its major clinical manifestations include carditis, migratory polyarthritis, chorea, erythema marginatum, and subcutaneous nodules. It can manifest as an acute febrile illness consisting of migratory polyarthritis involving the large joints, as carditis and valvulitis, or as Sydenham's chorea with involvement of the central nervous system. The disorder in its milder form resolves itself without sequelae. Carditis is the condition most associated with increased mortality and morbidity and may be fatal in its severe forms.
Penicillin is the most appropriate primary and secondary prophylaxis. Anti- inflammatory agents provide symptomatic relief but do not prevent rheumatic heart disease.
TOXIC SHOCK SYNDROME
Streptococcal toxic shock syndrome: a description of 14 cases from North Yorkshire, UK.
Barnham MR, Weightman NC, Anderson AW, Tanna A.
Department of Microbiology, Harrogate District Hospital, North Yorkshire, UK.
Clin Microbiol Infect 2002 Mar;8(3):174-81 Abstract quote
OBJECTIVE: To analyze the clinical and laboratory features of patients diagnosed with streptococcal toxic shock syndrome (TSS) in North Yorkshire from 1986 to 1999.
METHODS: Records of patients with features satisfying the published criteria for streptococcal TSS were reviewed from laboratory and clinical records made at the time and from the hospital case notes. Isolates of streptococci were analyzed for serotype and genes encoding for the production of streptococcal pyrogenic exotoxins.
RESULTS: Fourteen patients satisfied the entry criteria. In one district, where the data were complete, the annual incidence of detected streptococcal TSS rose from 1.1 to 9.5 cases per million population in the 1990s. TSS was associated with various M serotypes of group A streptococci and various exotoxin genotypes. Two cases (14% of the series) were associated with severe group G streptococcal infection. The fatality rate was 64%, and the mode of time to death was 4 days. Local tissue necrosis occurred in 71% of cases, including necrotizing fasciitis, intrathoracic and intra-abdominal forms. Non-steroidal anti-inflammatory drugs (NSAIDs) had been taken around the time of onset of disease by 92% of the patients with TSS.
CONCLUSIONS: There has been a dramatic increase in the number of detected cases of streptococcal TSS over the 14 years since the first case was recognized here. There was a wide range of invasive forms of infection, a high fatality rate even in fit young adults, and a rapid course from onset to death. There was a high association of TSS with aggressive streptococcal infection producing local tissue necrosis.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS TREATMENT ANTIBIOTICS
Macrolide therapy of group A streptococcal pharyngitis: 10 days of macrolide therapy (clarithromycin) is more effective in streptococcal eradication than 5 days (azithromycin).
Kaplan EL, Gooch III WM, Notario GF, Craft JC.
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
Clin Infect Dis 2001 Jun 15;32(12):1798-802 Abstract quote
We compared recommended doses of 2 oral macrolide antibiotics (10 days of clarithromycin, 5 days of azithromycin) for eradicating group A streptococci from the throats of individuals aged > or = 12 years with symptomatic pharyngitis and a positive throat culture.
Patients received either clarithromycin (250 mg b.i.d. for 10 days [n=260]) or azythromycin (500 mg on day 1, followed by 250 mg q.d. for 4 days [n=265]). Follow-up throat cultures were obtained both at 13--19 days and at 28--38 days. We evaluated 392 patients (median age, 26 years; clarithromycin, 194 patients; azyithromycin, 198 patients). Ten days of clarithromycin therapy was more effective than 5 days of azithromycin therapy in eradicating the organism (91% [176/194] vs. 82% [162/198]; P=.012). More than 97% of all streptococcal isolates were macrolide-sensitive.
Whether these bacteriologic eradication rates were the result of the 2 macrolides compared or were due to differences in duration of therapy could not be determined, but the statistically significant difference in eradication of group A streptococci does raise additional questions about shortened courses of macrolide therapy for this common infection.
Bacteriological and clinical efficacy of various antibiotics used in the treatment of streptococcal pharyngitis in Italy. An epidemiological study.
Rondini G, Cocuzza CE, Cianflone M, Lanzafame A, Santini L, Mattina R.
Div. Pat. Neonatale OSM IRCCS, University of Pavia, Pavia, Italy.
Int J Antimicrob Agents 2001 Jul;18(1):9-17 Abstract quote
A total of 123 community paediatricians and 23 microbiology laboratories studied the clinical and bacteriological efficacy of treatment of group A streptococcal pharyngitis in Italy. Of 1065 patients, from whom Streptococcus pyogenes was isolated, 723 returned to follow up and of these 138 (19%) still had a positive throat culture.
The erythromycin resistance (ER) rate was 23.7% with resistance phenotype distribution of: 31.7% constitutive (CR), 26.6% inducible (IR) and 41.7% efflux pump (M) resistance phenotype. All strains were susceptible to the beta-lactam agents tested. CR strains were highly resistant to all 14, 15 and 16 membered macrolides with the exception of rokitamycin which showed activity against 37.8% of isolates. All phenotype M and some IR isolates were susceptible to clindamycin, rokitamycin, josamycin and spiramycin; clarithromycin was active against a small percentage of strains belonging to the IR and M phenotype. Bacterial eradication was found in 85.5, 78.7 and 75.8% of the penicillin, macrolide and cephalosporin treated groups. Genotyping of strains showed that 8.7% of the 19% of cases classified as 'failed bacterial eradication' were due to recolonization with a different isolate, observed exclusively among beta-lactams treated patients.
Clinical cure was achieved in a high percentage of cases, irrespective of the antibiotic prescribed, with the best clinical efficacy being found following therapy with amoxycillin and clarithromycin (90.9%).
Open-Label, parallel-group, multicenter, randomized study of cefprozil versus erythromycin in children with group A streptococcal pharyngitis/tonsillitis.
Brook I, Aronovitz GH, Pichichero ME.
Department of Pediatrics, Georgetown University School of Medicine, Washington, DC 20016, USA.
Clin Ther 2001 Nov;23(11):1889-900 Abstract quote
BACKGROUND: Cefprozil and erythromycin are acceptable alternatives to penicillin in the treatment of pharyngitis/tonsillitis due to group A beta-hemolytic streptococcus (GABHS).
OBJECTIVE: The purpose of this trial was to determine the relative efficacy and tolerability of cefprozil and erythromycin in the treatment of pediatric pharyngitis/tonsillitis due to GABHS.
METHODS: This trial compared the bacteriologic and clinical efficacy of erythromycin and cefprozil in children 2 to 12 years of age with culture-documented GABHS pharyngitis/ tonsillitis. Children who were allergic to penicillin, cefprozil, or erythromycin were excluded. Patients were prospectively randomly assigned to receive 10 days of oral therapy with either cefprozil suspension 15 mg/kg per day in 2 divided doses or erythromycin ethylsuccinate suspension 30 mg/kg per day in 3 divided doses. Primary efficacy end points were bacteriologic and clinical response 2 to 8 days after treatment ended. The frequency and severity of adverse events and their relationship to treatment were also assessed.
RESULTS: A total of 199 patients were enrolled and treated (cefprozil, 99; erythromycin, 100); 12 patients in the cefprozil group and 15 in the erythromycin group were not evaluable. The GABHS eradication rate was significantly higher with cefprozil (95%) than with erythromycin (74%) (P = 0.001). The posttreatment carrier rate was lower in the cefprozil group (5%) than in the erythromycin group (18%) (95% CI, -22.3 to -3.8). Clinical cure rate was 90% (78/87) with cefprozil and 91% (77/85) with erythromycin (P = 0.95) (treatment group difference, -0.93; 95% CI, -9.9% to 8.0%). The overall incidence of drug-related adverse events was not significantly different in the 2 groups (11% with cef- prozil, 18% with erythromycin). The most common adverse events were diarrhea and vomiting. Two patients in the erythromycin group discontinued therapy because of adverse events.
CONCLUSIONS: The bacteriologic eradication rate was significantly greater with cefprozil compared with erythromycin in children with pharyngitis/tonsillitis. Both cefprozil and erythromycin produced a clinical cure in >90% of patients.
Five day clarithromycin modified release versus 10 day penicillin V for group A streptococcal pharyngitis: a multi-centre, open-label, randomized study.
Portier H, Filipecki J, Weber P, Goldfarb G, Lethuaire D, Chauvin JP.
Dijon University Hospital, Hopital du Bocage, Service des Maladies Infectieuses, 2 boulevard de Lattre de Tassigny, 21034, Dijon, France.
J Antimicrob Chemother 2002 Feb;49(2):337-44 Abstract quote
OBJECTIVE: A multicentre, comparative, randomized, open-label, Phase III trial evaluated the efficacy and tolerability of clarithromycin modified release (MR) versus penicillin V for pharyngitis due to group A beta-haemolytic streptococci (GABHS).
METHODS: Three hundred and forty-nine patients (12-40 years) with acute pharyngotonsillitis and a positive Streptococcus A antigen immunoassay test were randomized to receive clarithromycin MR 500 mg od for 5 days or penicillin 590 mg tds for 10 days. Patients were clinically evaluated and a throat swab for culture obtained before treatment, after treatment (day 8 or 13 depending on the treatment arm) and at the follow-up visit (day 30). The main criterion for efficacy was the bacteriological cure rate after treatment.
RESULTS: Three hundred and forty-nine patients were considered for the intent-to-treat analysis. After treatment, clinical cure rates were 88.1% in the clarithromycin group and 92.4% in the penicillin group, and eradication rates were 82.8% and 83.6%, respectively. There were no statistically significant differences between the two treatments. Three hundred and three (87%) patients had a positive culture before treatment, among which 29 (9.7%) were found to be clarithromycin resistant. Two hundred and thirty-nine patients were clinically and bacteriologically evaluable for per protocol analysis. After treatment, clinical cure rates were 95.2% in the clarithromycin group and 97.3% in the penicillin group, and eradication rates were 94.4% and 92%, respectively. No statistically significant difference was shown. Adverse events occurred in 46 patients of the clarithromycin group and 31 of the penicillin group (with no statistical difference). Most of them were of mild or moderate severity.
CONCLUSION: Clarithromycin MR administered once daily for 5 days is as safe and effective as penicillin V administered three times a day for 10 days in the treatment of GABHS pharyngitis.
Azithromycin versus penicillin V for treatment of acute group A streptococcal pharyngitis.
Schaad UB, Kellerhals P, Altwegg M; THe Swiss Pharyngitis Study Group.
University Children's Hospital of Basel, Zurich, Switzerland.
Pediatr Infect Dis J 2002 Apr;21(4):304-8 Abstract quote
OBJECTIVE: To compare a 3-day azithromycin vs. a 10-day penicillin V regimen for treatment of acute group A streptococcal (GAS) pharyngitis in children and to determine whether viral infection and/or pharyngeal GAS carriage in patients and adult contacts affect clinical and bacteriologic efficacy.
METHODS: This multicenter, randomized, comparative, open label study compared 3-day, once daily 10 mg/kg azithromycin oral suspension with a 10-day regimen of 100,000 IU/kg/day penicillin V oral suspension in three divided doses in children with acute GAS pharyngitis. Clinical and bacteriologic efficacy and tolerability of the antibiotics were evaluated. Recurrence of symptoms and infection was monitored for 6 months.
RESULTS: In total, 292 children (age range, 2 to 12 years) received at least one dose of study medication. Clinical success (cure/improvement) with either antibiotic was similar at the end of therapy (Day 14; azithromycin, 95%; penicillin V, 97%) and at Day 28 (azithromycin, 94%; penicillin V, 95%). Bacteriologic eradication was significantly less with azithromycin than with penicillin V at Day 14 (azithromycin, 38%; penicillin V, 81%; P < 0.001) and at Day 28 (azithromycin, 31%; penicillin V, 68%; P < 0.001). There was no associated increase in GAS-related sequelae. The lower incidence of bacteriologic eradication with azithromycin was not the result of possible concomitant viral infections in the patients, GAS carriage in one parent/guardian or any reduced susceptibility in pretreatment GAS isolates. Both antibiotics were equally well-tolerated.
CONCLUSIONS: Treatment with 3-day, once daily 10 mg/kg azithromycin for GAS pharyngitis is associated with similar high levels of clinical efficacy, but lower levels of bacteriologic eradication, than with 10-day 100,000 IU/kg/day penicillin V.
Narrow Versus Broad Spectrum Antibacterials: Factors in the Selection of Pneumococcal Resistance to beta-Lactams.
Carbon C, Isturiz R.
Division of Infectious Diseases, CHUV, Lausanne, Switzerland.
Drugs 2002;62(9):1289-94 Abstract quote
Streptococus pneumoniae represents an interesting model to discuss the relative impact of broad versus narrow spectrum antibacterials as potential selectors for resistance. Indeed, this pathogen is responsible for potentially severe infections in the community, and has a great capacity for acquisition of resistance to antibacterial agents. It has been the focus of many studies to elucidate some unique aspects of molecular biology, including the adaptive mechanisms responsible for emergence and spread of multiresistance. In the past, the use of narrow spectrum agents was recommended in order to try to reduce the risk of selection of resistance. This concept is nowadays somewhat obsolete for several reasons. S. pneumoniae is able to acquire resistance to antibacterials belonging to different families of drugs through different molecular mechanisms.
Thus, selection of multiresistant pneumococci can result from exposure to very different agents, including narrow spectrum as well as broad spectrum agents. In vitro studies have shown a different potential for selection of resistance among the beta-lactam agents. Furthermore, several studies have more or less directly established a close relationship between the level of antibacterial use and the rate of selection of resistance. In addition to the overall amount of antibacterials prescribed in the community, several other factors have been shown to influence the rate of selection of resistance, including the use of doses that are too low, the length of therapy and the duration of bacterial exposure to long-acting agents compared to drugs with short half-lives.
Therefore, there are three main ways to control selection and spread of resistant strains: by (i) reducing the amount of antibacterials used; (ii) using optimal dosages (avoiding underdosing) and treatments of short duration; and (iii) reducing the risk of transmission among young children attending daycare centres or kindergartens. In order to help physicians reduce the number of unnecessary prescriptions, it is important to develop rapid tests to recognise the bacterial origin of a febrile illness and even more important to detect resistance to antibacterials. However, apart from rapid diagnostic tests for streptococcal pharyngitis, those tests are not currently available. As a consequence, currently, the debate around narrow versus broad spectrum antibacterials remains a false debate. Physicians should use broad spectrum agents in many instances of upper or lower respiratory tract infection, taking into consideration the probable pathogens and the risk of (multi)resistance to antibacterials. Once rapid diagnostic are available in community practice, allowing a precise diagnosis of the offending agent and its susceptibility profile, physicians will be able to add to their current criteria the selective potential for resistance of the antibacterials that appear to be active in vitro.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
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