Guideline for the management of acute sore throat.

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.

Related papers:

title: Effect on antibiotic prescribing of repeated clinical prompts to use a sore throat score: lessons from a failed community intervention study.
abstract: Infections with group A streptococcus (GAS) occur in 10% to 20% of patients with sore throats, whereas antibiotics are prescribed 50% of the time. Clinical scoring rules can more accurately predict the likelihood of GAS infection, but whether family physicians will adopt such approaches is unclear. This study sought to determine whether repeated clinical prompts to use a scoring approach could help family physicians lower antibiotic use in patients with a sore throat.



Randomized trial in which physicians were assigned to use either (1) chart stickers that prompted them to calculate a score based on clinical findings and provided management recommendations linked to score totals or (2) a clinical checklist.



Ninety-seven family physicians in Ontario, Canada, assessed 621 children and adults with sore throat and obtained a throat swab for culture.



(1) Unnecessary antibiotic prescriptions given to patients with a negative throat culture and (2) overall antibiotic use.



There were no differences between the control and intervention group in unnecessary antibiotic prescriptions (16.1% vs 20.4%, respectively, P =.29) or overall antibiotic use (27.9% vs 28.1%, P =.97). However, a number of physicians dropped out of the study; as a result, the characteristics of the physicians in the 2 groups were dissimilar in factors related to prescribing. After adjusting for these differences and patient clustering by physician, the odds ratio for the effect of the intervention on unnecessary antibiotic prescriptions was 0.76 (95% confidence interval [CI] = 0.42, 1.40) and 0.57 for overall antibiotic use (95% CI = 0.27, 1.17).



Chart prompts during clinical encounters to use a clinical score in the assessment of patients with a sore throat did not reduce unnecessary antibiotic prescribing by family physicians. The problems encountered in conducting this community-based intervention trial are discussed in relation to the negative result.

title: Diagnosing streptococcal pharyngitis in the emergency department: Is a sore throat score approach better than rapid streptococcal antigen testing?
abstract: Reducing the number of unnecessary antibiotic prescriptions given for common respiratory infections has been recommended as a way to limit bacterial resistance. This study assessed the validity of a clinical sore throat score in 2 community emergency departments (EDs) and its impact on antibiotic prescribing. We also attempted to improve on this approach by using a rapid streptococcal antigen test.



A total of 126 patients with new upper respiratory tract infections accompanied by sore throat were assessed by a physician. Pharyngeal swabs were obtained for a rapid test and throat culture, and information was gathered to determine the sore throat score. The sensitivity and specificity of the score approach were compared with usual physician care based on the rapid test results.



Of the 126 cases of new upper respiratory infections with sore throat, physicians who followed their usual care routine, guided by the rapid test results, prescribed antibiotics for 46 patients. Of the 46 prescriptions, 18 were given to patients with culture-negative results for group A streptococcal (GAS) pharyngitis. Use of the sore throat score would not have reduced the number of prescriptions but would have missed only 1 patient with a positive culture result (p < 0.05). The rapid test was not as sensitive as throat culture.



An explicit clinical score approach to the management of GAS pharyngitis is valid in a community ED setting and could improve the pattern of antibiotic prescribing. While the addition of a rapid streptococcal antigen test significantly decreased the sensitivity of detecting GAS infections, a combined approach consisting of the clinical score and throat culture for patients with negative results on the rapid test would decrease antibiotic prescribing and telephone follow-up without decreasing the sensitivity of detecting GAS infection.

title: How effective are treatments other than antibiotics for acute sore throat?
abstract: To estimate the benefits of treatments other than antibiotics for acute sore throat, and the differences between non-antibiotic interventions and controls in patient-perceived pain of sore throat, a systematic review of controlled trials in Medline and the Cochrane Library was carried out. Sixty-six randomised controlled trials (with or without additional antibiotics) were identified and 17 met the selection criteria. Twenty-two non-antibiotic managements for sore throat were compared. Their efficacy relative to placebo ranged from no effect to 93%. Some non-antibiotic treatments may be more effective than antibiotics; however, publication bias may have exaggerated the benefits. These treatments should be investigated further with respect to efficacy, safety, and side-effects as potential firstline management options for acute sore throat.

title: Efficacy and Tolerability of the Anti-inflammatory Throat Lozenge Flurbiprofen 8.75mg in the Treatment of Sore Throat
abstract: ObjectiveThis randomised, double-blind, parallel group study compared the efficacy and tolerability of flurbiprofen lozenges (8.75mg or 12.5mg) with demulcent placebo lozenges in the treatment of patients with sore throat due to upper respiratory tract infection. total of 320 patients with objective and subjective evidence of sore throat were randomised to treatment with flurbiprofen 8.75mg (n = 128), flurbiprofen 12.5mg (n = 64) or placebo (n = 128) lozenges.Main Outcome MeasuresEfficacy was assessed by changes in subjective ratings scales measuring pain relief, throat soreness and swollen throat at specified intervals over a 6-hour period following administration of a single dose. Tolerability was assessed over a 5-day multiple-dose regimen.ResultsFlurbiprofen 8.75mg lozenge was significantly superior to placebo for the primary efficacy variable, total pain relief summed over 15 to 120 minutes (TOTPAR15–120min), and for reducing throat soreness over 2 hours and swollen throat over 2 and 6 hours (p < 0.05). Flurbiprofen 12.5mg treatment was not significantly better than flurbiprofen 8.75mg. There were no significant differences between treatment groups in the incidence of adverse events when reports of taste perversion, which reflects an aspect of patient acceptability rather than tolerability, were removed from the analysis (p = 0.776).ConclusionsThe efficacy and tolerability profile of flurbiprofen 8.75mg lozenges indicated that they provide a convenient treatment for patients with sore throat. Symptomatic relief was rapid, occurring within 15 minutes of administration due to lozenge demulcency, and statistically significant differences between active and placebo lozenges were detected within 30 minutes and sustained over 4 hours.

title: Onset of analgesia of a paracetamol tablet containing sodium bicarbonate: A double-blind, placebo-controlled study in adult patients with acute sore throat.
abstract: The aim of this study was to determine the time to onset of pain relief from a single dose of a tablet formulation of paracetamol (acetaminophen) containing sodium bicarbonate (PSC).



A single oral dose of PSC or placebo was randomly administered to patients with acute sore throat under double-blind conditions. Patients rated their pain relief using a conventional categorical relief scale every 5 minutes during the first hour postdose to determine the time to onset of pain relief. They continued evaluations of pain relief at less frequent intervals to 6 hours postdose to confirm the overall analgesia of PSC compared with placebo. To determine if food had any effect on the onset of action of PSC, time to onset of analgesia by PSC was compared between patients in the fed and fasted states. Patients were randomized 3:1 to PSC:placebo based on whether they had eaten food within 2 hours of baseline. Adverse events were recorded by questioning throughout the study period.



A total of 241 patients were enrolled. Both treatment groups were well matched for age (mean, 20 years), sex (male:female ratio, approximately 1:1.5), sore throat duration (mean, 3 days) and severity (mean score, 8). PSC separated significantly from placebo beginning at 15 minutes postdose (P < or = 0.03). There was no difference for onset of analgesia between PSC in the fed and fasted states. PSC showed significantly greater total pain relief over 30 minutes, 1 hour, and 6 hours compared with placebo (all, P < 0.05). Both treatments were well tolerated and there were no serious adverse events.



PSC was effective beginning 15 minutes postdose and well tolerated compared with placebo in this population of adults with acute onset of sore throat pain.

title: Effects of acetylsalicylic acid on sore throat pain and other pain symptoms associated with acute upper respiratory tract infection.
abstract: Acetylsalicylic acid (ASA) has been widely used for over a century to treat pain and fever associated with acute upper respiratory tract infection (URTI), but there is a lack of clinical data to support the efficacy of ASA in this disease state. The objective of this study was to investigate the efficacy and safety of ASA for the treatment of sore throat pain associated with URTI.



A double-blinded, placebo-controlled, parallel group design. Two hundred seventy-two patients (mean age: 25 years) with sore throat pain associated with URTI were recruited at two centers. Pain scores were made during a 2-hour laboratory phase and continued for secondary objectives during a 4-hour home phase. Patients were treated with either two effervescent tablets of ASA 400 mg in water or matched placebo tablets. Patients took medication as required over a 3-day home phase.



ASA was found to be superior to placebo for: The primary efficacy parameter predefined in the protocol, reduction in sore throat pain intensity over 2 hours (P < 0.001), and for secondary efficacy parameters, reduction in sore throat pain intensity over 4 and 6 hours, relief of sore throat pain over 2, 4, and 6 hours, reduction in intensity of pain associated with headache, and reduction in muscle aches and pains over a 2-hour time period (P < 0.01). No safety problems were encountered.



Treatment with ASA was shown to provide relief from sore throat pain, headache, and muscle aches and pains associated with URTI.

title: Lowest Effective Single Dose of Diclofenac for Antipyretic and Analgesic Effects in Acute Febrile Sore Throat
abstract: ObjectiveTo compare the antipyretic and analgesic effects of a single oral dose of diclofenac potassium 6.25, 12.5 or 25mg with paracetamol l000mg and placebo in patients with fever resulting from acute febrile sore throat.Design and settingThis was a multicentre, double-blind, double-dummy, randomised, placebo-controlled, parallel group study conducted at 21 primary-care centres throughout France.PatientsIn total, 343 adult patients with acute febrile sore throat (fever ≥38.0°C) were randomised to the five treatment groups.InterventionsPatients received one oral dose of medication. Fever, spontaneous throat pain and pain on swallowing were recorded over 6 hours. If acute symptoms persisted 2 hours after study drug administration, the patient was allowed to take rescue medication and discontinue the trial.ResultsThe antipyretic effects of diclofenac potassium 6.25, 12.5 and 25mg and paracetamol l000mg were significantly greater than placebo. The antipyretic effects of diclofenac potassium 12.5 and 25mg were numerically greater than paracetamol l000mg, which was comparable to the effect of diclofenac potassium 6.25mg. The analgesic effects of the higher doses, diclofenac potassium 12.5 and 25mg, and of paracetamol l000mg were significantly better than placebo. Summary efficacy measures over the first 4 hours post-dose showed a dose-response relationship among the diclofenac doses, with statistically significant differences on some outcomes between the 25mg and the 6.25mg doses. On the global efficacy evaluation for relief of fever and throat pain, patients rated both diclofenac potassium 12.5 and 25mg significantly higher than paracetamol lOOOmg (p ≤ 0.01). In contrast, paracetamol l000mg and diclofenac 6.25mg were not rated significantly higher than placebo. Diclofenac potassium was well tolerated, with a safety profile comparable to that of placebo, and slightly favourable compared with that of paracetamol.ConclusionsDiclofenac potassium administered as single doses of 12.5 and 25mg significantly reduced fever and throat pain in patients with acute febrile sore throat. The overall efficacy of these doses was rated significantly higher than that of paracetamol l000mg or placebo. A dose-response relationship was seen between placebo and the three diclofenac doses. On most outcomes, paracetamol l000mg was similar to or only slightly better than the diclofenac potassium 6.25mg dose. Diclofenac potassium 12.5mg is the lowest unit dose that could be recommended to provide reliable reduction of oral temperature and relief of throat pain.

title: Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model
abstract: The dose response of flurbiprofen lozenges (2.5, 5.0, and 12.5 mg) was evaluated in the treatment of sore throat. A refined version of the sore throat pain model showed that 12.5 mg flurbiprofen was significantly more effective than placebo at providing total pain relief and reducing throat soreness (p < .05). Flurbiprofen, 5.0 mg, was more effective than placebo for the reduction of throat soreness and the sensation of throat swelling (P < .05). The 2.5‐mg flurbiprofen lozenge was indistinguishable from placebo. For every milligram of increase in the dose of flurbiprofen, there was an approximately 0.3‐unit increase in total pain relief (P < .05). Flurbiprofen lozenges in all 3 dosages were well tolerated. Flurbiprofen lozenges are effective for sore throat at a dose between 5.0 mg and 12.5 mg; the sore throat pain model is a sensitive assay for demonstration of the dose‐response relationship of an analgesic agent.

title: Tolerability of ibuprofen, aspirin and paracetamol for the treatment of cold and flu symptoms and sore throat pain.
abstract: This double-blind randomised study compared the tolerability of ibuprofen (up to 1.2 g daily), aspirin and paracetamol (both up to 3 g daily) for up to seven days, in patients with mild to moderate pain resulting from cold/flu symptoms or sore throat (CF/ST) (n = 2,815). The main outcome was the rate of significant adverse events (SGAE). Rates of SGAE for ibuprofen, aspirin and paracetamol were respectively 12.0%, 15.7% and 12.3%. Ibuprofen was significantly better tolerated than aspirin (p = 0.02) and had comparable tolerability with paracetamol. The latter was also true for total digestive system events and for abdominal pain and dyspepsia. In conclusion, in patients with CF/ST, ibuprofen used at over-the-counter doses is as well tolerated as paracetamol and much better tolerated than aspirin.

title: Pelargonium sidoides extract for acute respiratory tract infections.
abstract: Pelargonium sidoides (P. sidoides), also known as Umckaloabo, is a herbal remedy thought to be effective in the treatment of acute respiratory infections (ARIs).



To assess the efficacy and safety of P. sidoides for the treatment of ARIs in children and adults.


SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 4) which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1966 to November 2007); EMBASE (1974 to December 2007); and other electronic databases.



Randomized controlled trials (RCTs) examining the efficacy of P. sidoides preparations in ARIs compared to placebo, no treatment or any other treatment. Complete resolution of all symptoms was defined as a primary outcome.



Three review authors (AT, JG, WK) independently extracted and quality scored the data. Separate analyses were performed by age group and disease entity. Heterogeneity was examined using the I-square (I(2)) statistic. Pooled relative risks (RR) were calculated using a fixed-effect model if heterogeneity was absent (I(2) < 5%; P > 0.1), or a random-effects model in the presence of heterogeneity. If heterogeneity was substantial (I(2) > 50%; P < 0.10), a pooled effect was not calculated.



Three trials (746 patients) of efficacy in acute bronchitis in adults showed substantial heterogeneity for all relevant outcomes. and three trials (819 children) were similarly inconsistent for acute bronchitis in children. Type of preparation was a potential cause of heterogeneity (not effective in tablet form). One unpublished study in patients with sinusitis (n = 103 adults) showed significant treatment effects (complete resolution at day 21; RR 0.43, 95% CI 0.30, 0.62). One study in the common cold demonstrating efficacy after 10 days, but not five days. Four trials were excluded because of excessive risk of bias. There were no valid data for the treatment of other acute respiratory tract infections. Adverse events were more common with P. sidoides, but none were serious.



P. sidoides may be effective in alleviating symptoms of acute rhinosinusitis and the common cold in adults, but doubt exists. It may be effective in relieving symptoms in acute bronchitis in adults and children, and sinusitis in adults. Reliable data on treatment for other ARIs were not identified.

title: Chinese medicinal herbs for sore throat.
abstract: Chinese herbal medicines are commonly used to treat sore throat in China and among Chinese people worldwide. Their efficacy in treating sore throat has not previously been systematically reviewed.



To assess the efficacy and safety of Chinese herbal medicines for patients with sore throat.


SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2006) which contains the Acute Respiratory Infections Group's specialised register; MEDLINE (1966 to August 2006); EMBASE (1980 to August 2006); AMED (1985 to August 2006); the Chinese Biomedical Database (CBM) (1975 to August 2006), and China National Knowledge Infrastructure (CNKI) (1994 to August 2006).



We only included randomised controlled trials (RCTs) assessing Chinese herbal medicines for the treatment of sore throat with the outcomes of recovery, inefficacy, and adverse events.



One review author contacted the trial authors of claimed RCTs. Three review authors extracted and analysed the data.



Seven trials involving 1253 participants were included. All trials were identified as being of methodologically poor quality (C category). All of the Chinese herbal preparations in this review were inadequately characterised and were assessed in one trial only. It is highly likely that there was selection bias or detection bias, or both, in all of the included trials. Conflict of interest may have been another factor in producing a positive result in three studies as the prepared drugs were made in the trial author's hospital. We did not perform a meta-analysis and the results of the studies are reported separately. Three formulations were shown to be superior to the control in improving recovery: Ertong Qingyan Jiere Koufuye was more effective than Fufang Shuanghua Koufuye for acute pharyngitis (OR 1.54, 95% Cl 1.11 to 5.74); Yanhouling mixture was more effective than the gentamicin atomised inhalation for acute pharyngitis (OR 5.39, 95% CI 2.69 to 10.81) for acute pharyngitis; and Qinganlan Liyan Hanpian was more effective than Fufang Caoshanhu Hanpian for chronic pharyngitis (OR 2.25, 95% CI 1.08 to 4.67). Four four formulations were shown to be equal in efficacy to the control.



Based on the existing evidence included in this review, the efficacy of Chinese herbal medicine for treating sore throat is controversial and questionable. We cannot recommend any kind of Chinese medical herbal formulation as an effective remedy for sore throat, due to the lack of high quality clinical trials.

title: Safety and efficacy of a traditional herbal medicine (Throat Coat) in symptomatic temporary relief of pain in patients with acute pharyngitis: a multicenter, prospective, randomized, double-blinded, placebo-controlled study.
abstract: To investigate the safety and efficacy of Throat Coat) (Traditional Medicinals,) Sebastopol, CA), a traditional demulcent herbal tea, in comparison with a placebo tea in the symptomatic treatment of acute pharyngitis.



Multicenter, prospective, randomized, double-blinded, placebo-controlled, two-armed, parallel-group clinical trial.



Three primary care clinics in Duluth, MN, Madison, WI, and Middleton, WI.



Patients of both genders (>or=18 years of age) with clinical diagnoses of acute pharyngitis.



Patients (n = 60) were randomly assigned to receive 5-8 oz of Throat Coat (n = 30) or a placebo (n = 30), four to six times daily. The study period was 2 to 7 days with a window for the follow-up visit of 2-10 days accounting for the variable duration of sore throat symptoms.



Primary efficacy parameter: sum of pain intensity differences (SPID) for pain in throat on swallowing, calculated as the area under the curve (AUC) of pain intensity difference scores (assessed at 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, and 30 minutes after treatment). Secondary efficacy parameter: total pain relief (TOTPAR), calculated as the AUC from time 0 (baseline) to 30 minutes of pain relief (assessed at 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, and 30 minutes).



Compared to placebo, intensity of throat pain when swallowing was significantly reduced by Throat Coat in intention to treat and valid for efficacy analysis (VEA). Significant differences in change from baseline pain were observed at 5 min (p = 0.007), 10 min (p = 0.005), 15 minutes (p = 0.01), 20 minutes (p = 0.05), and 30 minutes (p = 0.04) after completion of the first dose (VEA analysis). There was a statistically significant improvement of SPID in the Throat Coat-treated group: Least square means +/- standard error of the means (SEM) of SPID were -16.5 +/- 13.9 in the placebo group and -43.8 +/- 11.9 in the Throat Coat-treated group (p = 0.012). TOTPAR was also significantly higher in the Throat Coat-treated group: Least square means +/- SEM of TOTPAR were 32.4 +/- 12.8 in the placebo group and 53.6 +/- 10.9 in the Throat Coat-treated group (p = 0.031). This study shows that Throat Coat is significantly superior to placebo and provided a rapid, temporary relief of sore throat pain in patients with pharyngitis.

title: Efficacy and tolerability of a spray with Salvia officinalis in the treatment of acute pharyngitis - a randomised, double-blind, placebo-controlled study with adaptive design and interim analysis.
abstract: This randomised, double-blind, parallel group phase II/III study with adaptive two-stage design and interim analysis compared the efficacy and tolerability of spray (containing a Salvia officinalis fluid extract) against placebo in the treatment of patients with acute viral pharyngitis. -



in two study parts, a total of 286 patients with subjective and objective evidence of pharyngitis were randomized. In the first study part 122 patients were enrolled. In the second study part 164 patients were included. The treatment duration per patient was 3 days, including one baseline visit and one final visit. -



Area under Curve for change of throat pain intensity (spontaneous pain), documented every 15 minutes within the first 2 hours after the first application as compared to baseline using a visual analog scale (VAS 100 mm). -



Following the interim analyses of the first study part the 15 % spray containing 140 microl sage extract per dose was the most promising preparation for the second study part (main study) whereas for the 30% and the 5% preparation results made superiority over placebo unlikely in the final analysis. Overall, the 15 % spray was significantly superior to placebo for the primary efficacy variable with regard to a reduction of the throat pain intensity score. Only minor side effects such as dry pharynx or burning of mild intensity were seen. -



The efficacy and tolerability profile of a 15 % sage spray indicated that this preparation provides a convenient and safe treatment for patients with acute pharyngitis. A symptomatic relief occurred within the first two hours after first administration and was statistically significantly superior to placebo.

title: Treatment of acute tonsillitis with a fixed-combination herbal preparation
abstract: In an observational study involving 10 non-hospital-affiliated physicians, 48 patients between 6 and 73 years of age with symptoms of acute tonsillitis were treated with either a liquid or tablet formulation of a herbal compound ofPhytolacca,Guajacum, andCapsicum. More than half of the patients reported marked alleviation of the principal symptom, moderate or severe difficulty in swallowing, within the first 5 days of treatment. Comparable improvements occurred in other outcome measures, including earache, headache, and fatigue. No adverse side effects were reported.

title: Comparison of solid and liquid forms of homeopathic remedies for tonsillitis.
abstract: The efficacy of three plants used in homeopathy to treat acute tonsillitis was evaluated. A fixed combination of three plant substances (Phytolacca americana, Guajacum officinale, Capsicum annuum) was used in either solid (tablet) or liquid (drop) formulation: 107 patients were treated and no antibiotics were used. The objective and subjective symptoms of acute tonsillitis were noted. A significant decrease in symptoms was observed as early as 2.5 days after treatment startup; no serious adverse effects were reported. It was concluded that acute tonsillitis can be treated with a homeopathic remedy characterized by its immunomodulatory, analgesic, and anti-inflammatory properties.

title: Evaluation of Ibuprofen vs Paracetamol Analgesic Activity Using a Sore Throat Pain Model
abstract: To validate a slightly modified sore throat pain model by comparing the analgesic efficacy of ibuprofen with that of paracetamol.
 Design: A double-blind, double-dummy study was conducted.
 Setting: Nineteen primary care centres in France.
 Patients: Adults consulting their general practitioner with acute sore throat of a maximum of two days’ duration.
 Interventions: Patients (n = 113) with acute pain associated with tonsillo-pharyngitis randomly received either 400mg ibuprofen or 1000mg paracetamol. The study design included repeated administration up to 48 hours to assess tolerability.
 Main Outcome Measures: At hourly intervals for 6 hours after the first dose of treatment, the patients evaluated pain intensity on swallowing, difficulty in swallowing and global pain relief according to visual analogue scales.
  Ibuprofen 400mg was significantly more effective than paracetamol 1000mg in all three ratings, at all time-points for pain intensity and difficulty in swallowing, and from two hours onwards for pain relief. There were no serious adverse effects and no statistically significant difference in the incidence of adverse events in the two treatment groups.
  Sore throat pain provided a sensitive model to assess the analgesic efficacy of class I analgesics and discriminated between the analgesic efficacy of ibuprofen and paracetamol. Sore throat is a very common complaint and practising physicians should consider ibuprofen as an effective alternative to paracetamol in the treatment of sore throat pain. The sore throat model should be considered by researchers as a sensitive assay of analgesic activity.

title: Zinc Gluconate Lozenges for Treating the Common Cold in Children A Randomized Controlled Trial
abstract: Context.—The common cold is one of the most frequently occurring illnesses and
is responsible for substantial morbidity and economic loss. Biochemical evidence
suggests that zinc may be an effective treatment, and zinc gluconate glycine
(ZGG) lozenges have been shown to reduce the duration of cold symptoms in
adults.Objective.—To determine the efficacy of ZGG treatment of colds in children and
adolescents.Design.—A randomized, double-masked, placebo-controlled study.Setting.—Two suburban school districts in Cleveland, Ohio.Patients.—A total of 249 students in grades 1 through 12 were enrolled within
the first 24 hours of experiencing at least 2 of 9 symptoms of the common
cold.Intervention.—Zinc lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6)
or 6 times a day (in grades 7-12).Main Outcome Measures.—Time to resolution of cold symptoms based on subjective daily symptom
scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal
drainage, scratchy throat, sore throat, and sneezing.Results.—Time to resolution of all cold symptoms did not differ significantly
between students receiving zinc (n=124) and those receiving placebo (n=125)
(median, 9 days; 95% confidence interval [CI], 8-9 days; median, 9 days, 95%
CI, 7-10 days, respectively; P=.71). There were no
significant differences in the time to resolution of any of the 9 symptoms
studied. Compared with controls, more students in the zinc group reported
adverse effects (88.6% vs 79.8%; P=.06); bad taste
(60.2% vs 37.9%; P=.001); nausea (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%; P=.03); and diarrhea (10.6% vs 4.0%; P=.05).Conclusions.—In this community-based, randomized controlled trial, ZGG lozenges were
not effective in treating cold symptoms in children and adolescents. Further
studies with virologic testing are needed to clarify what role, if any, zinc
may play in treating cold symptoms.

title: Antibiotics for sore throat.
abstract: Sore throat is a very common reason for people to seek medical care. It is a disease that remits spontaneously, that is, 'cure' is not dependent on treatment. Nonetheless primary care doctors commonly prescribe antibiotics for sore throat and other upper respiratory tract infections.



To assess the benefits of antibiotics in the management of sore throat.


SEARCH STRATEGY
Systematic search of the literature from 1945 to 2003, using electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, issue 2, 2003); MEDLINE (January 1966 to May 2003); EMBASE (January 1990 to March 2003), and the reference sections of the articles identified. We applied no language restrictions. We used abstracts of identified articles to identify trials.



Trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache or fever), or suppurative complications (meaning: forming pus) and non-suppurative complications of sore throat.



Two reviewers independently screened potential studies for inclusion and resolved differences in opinion by discussion. The reviewers then independently extracted the data from the selected studies. We contacted the authors of three studies to acquire additional information not available in published articles. Potential studies were screened independently by two reviewers for inclusion, with differences in opinion resolved by discussion. Data was then independently extracted from studies selected by inclusion by two reviewers. Authors of three studies were contacted to acquire additional information not available in published articles.



We included twenty-six studies, covering 12,669 cases of sore throat in the review.1. Non-suppurative complications There was a trend for protection against acute glomerulonephritis by antibiotics, but insufficient cases were recorded to be sure of this effect. Several studies found that antibiotics reduced acute rheumatic fever, to less than one third (odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.20 to 0.45). 2. Suppurative complications Antibiotics reduced the incidence of acute otitis media to about one quarter of that in the placebo group (OR = 0.22; 95% CI 0.11 to 0.43) and reduced the incidence of acute sinusitis to about one half of that in the placebo group (OR = 0.46; 95% CI 0.10 to 2.05). The incidence of quinsy was also reduced in relation to placebo group (OR = 0.16; 95% CI 0.07 to 0.35). 3. Symptoms Symptoms of headache, throat soreness and fever were reduced by antibiotics to about one half. The greatest time for this to be evident was at about three and a half days (when the symptoms of about 50% of untreated patients had settled). About 90% of treated and untreated patients were free of symptoms by one week. The overall number needed to treat to prevent one sore throat at day three was about 5.0 (95% CI 4.5 to 5.8); and at one week was 14.2 (95% CI 11.5 to 20.6). 4. Subgroup analyses of symptom reduction Subgroup analysis by age; blind versus unblinded; or use of antipyretics yielded no significant differences. The results of swabs of the throat for Streptococcus influenced the effect of antibiotics. If the swab was positive, antibiotics were more effective (the OR reduced to 0.16, 95% CI 0.09 to 0.26) than if it was negative (OR 0.65; 95% CI 0.38 to 1.12).



Antibiotics confer relative benefits in the treatment of sore throat. However, the absolute benefits are modest. Protecting sore throat sufferers against suppurative and non-suppurative complications in modern Western society can be achieved only by treating with antibiotics many who will derive no benefit. In emerging economies where rates of for example acute rheumatic fever are high, the number needed to treat may be much lower. Antibiotics shorten the duration of symptoms by a mean of one day about half way through the illness (the time of maximal effect), and by about sixteen hours overall.

title: Principles of appropriate antibiotic use for acute pharyngitis in adults: background.
abstract: The following principles of appropriate antibiotic use for adults with acute pharyngitis apply to immunocompetent adults without complicated comorbid conditions, such as chronic lung or heart disease, and history of rheumatic fever. They do not apply during known outbreaks of group A streptococcus.1. Group A beta-hemolytic streptococcus (GABHS) is the causal agent in approximately 10% of adult cases of pharyngitis. The large majority of adults with acute pharyngitis have a self-limited illness, for which supportive care only is . Antibiotic treatment of adult pharyngitis benefits only those patients with GABHS infection. All patients with pharyngitis should be offered appropriate doses of analgesics and antipyretics, as well as other supportive care.3. Limit antibiotic prescriptions to patients who are most likely to have GABHS infection. Clinically screen all adult patients with pharyngitis for the presence of the four Centor criteria: history of fever, tonsillar exudates, no cough, and tender anterior cervical lymphadenopathy (lymphadenitis). Do not test or treat patients with none or only one of these criteria, since these patients are unlikely to have GABHS infection. For patients with two or more criteria the following strategies are appropriate: a) Test patients with two, three, or four criteria by using a rapid antigen test, and limit antibiotic therapy to patients with positive test results; b) test patients with two or three criteria by using a rapid antigen test, and limit antibiotic therapy to patients with positive test results or patients with four criteria; or c) do not use any diagnostic tests, and limit antibiotic therapy to patients with three or four criteria. 4. Throat cultures are not recommended for the routine primary evaluation of adults with pharyngitis or for confirmation of negative results on rapid antigen tests when the test sensitivity exceeds 80%. Throat cultures may be indicated as part of investigations of outbreaks of GABHS disease, for monitoring the development and spread of antibiotic resistance, or when such pathogens as gonococcus are being considered.5. The preferred antibiotic for treatment of acute GABHS pharyngitis is penicillin, or erythromycin in a penicillin-allergic patient.

title: Delayed antibiotics for respiratory infections.
abstract: Modest benefits of antibiotics for acute upper respiratory tract infections have to be weighed against common adverse reactions, cost and antibacterial resistance. There has been interest in ways to reduce antibiotic prescribing. One strategy is to provide the prescription, but advise delay of more than 48 hours before use, in the hope symptoms resolve first. Advocates suggest this will preserve patient satisfaction. This review asks what effect delayed antibiotics have on clinical outcomes of respiratory infections, antibiotic use and patient satisfaction.



To evaluate the prescribing strategy of delayed antibiotics for acute respiratory tract infections compared to immediate or no antibiotics for clinical outcomes, antibiotic use and patient satisfaction.


SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2006); MEDLINE (January 1966 to January Week 2, 2007), EMBASE (1990 to Week 2, 2007) and Current Contents - ISI Web of Knowledge (1998 to January 2007).



Randomised controlled trials (RCTs) involving patients of all ages defined as having an acute respiratory infection were included in which delayed antibiotics were compared to antibiotics used immediately or no antibiotics. Outcomes measured included clinical outcomes, antibiotic use and patient satisfaction.



Data were collected and analysed by three review authors.



Nine trials were eligible on the basis of design and relevant outcomes. For most clinical outcomes there was no difference between delayed, immediate and no antibiotics. Antibiotics prescribed immediately were more effective than delayed for fever, pain and malaise in some studies of patients with acute otitis media and sore throat but for other studies there was no difference. There was no difference for the common cold and bronchitis. Delaying antibiotic prescriptions reduced antibiotic use, and in three studies, reduced patient satisfaction compared to immediate antibiotics. In the other two studies comparing delayed and immediate antibiotics measuring satisfaction, there was no difference. Two studies also included a 'no antibiotics' arm for bronchitis and sore throat: there was no difference in symptom resolution nor patient satisfaction from antibiotic delay. In one study, but not the other, antibiotic use was significantly decreased with no, rather than delayed, antibiotics.



For most clinical outcomes there is no difference between the strategies. Immediate antibiotics was the strategy most likely to provide the best clinical outcomes in patients with sore throat and otitis media. Delaying or avoiding antibiotics, rather than providing them immediately, reduces antibiotic use for acute respiratory infections. Delay also reduced patient satisfaction in three trials, compared to immediate antibiotics with no difference in two other trials. Delaying antibiotics seems to have little advantage over avoiding them altogether where it is safe to do so.

title: Short versus standard duration antibiotic therapy for acute streptococcal pharyngitis in children.
abstract: The standard duration of treatment for acute group A beta hemolytic streptococcus (GABHS) pharyngitis with oral penicillin is 10 days. Shorter duration antibiotics may have comparable efficacy.



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 STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 4), which contains the Acute Respiratory Infections Group's Specialized Register; the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (1966 to October 2007); OLDMEDLINE (1950 to December 1965); and EMBASE (January 1990 to November 2007).



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.



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.



Twenty studies were included with 13,102 cases of acute GABHS pharyngitis. Compared to standard duration treatment, the short duration treatment had shorter periods of fever (mean difference (MD) -0.30 days, 95% 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 (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 (OR 1.31, 95% CI 1.16 to 1.48), although no significant differences were found when studies of low dose azithromycin (10mg/kg) were eliminated (OR 1.06, 95% CI 0.92 to 1.22). Three studies reported long duration complications with no statistically significant difference (OR 0.53, 95% CI 0.17 to 1.64).



Three to six days of oral antibiotics had comparable efficacy compared to the standard duration 10 day oral penicillin in treating children with acute GABHS pharyngitis. In countries with low rates of rheumatic fever, it appears safe and efficacious to treat children with acute GABHS pharyngitis with short duration antibiotics. In areas where the prevalence of rheumatic heart disease is still high, our results must be interpreted with caution.

title: Meta-analysis of cephalosporins versus penicillin for treatment of group A streptococcal tonsillopharyngitis in adults.
abstract: We conducted a meta-analysis of 9 randomized controlled trials (involving 2113 patients) comparing cephalosporins with penicillin for treatment of group A beta -hemolytic streptococcal (GABHS) tonsillopharyngitis in adults. The summary odds ratio (OR) for bacteriologic cure rate significantly favored cephalosporins, compared with penicillin (OR,1.83; 95% confidence interval [CI], 1.37-2.44); the bacteriologic failure rate was nearly 2 times higher for penicillin therapy than it was for cephalosporin therapy (P=.00004). The summary OR for clinical cure rate was 2.29 (95% CI, 1.61-3.28), significantly favoring cephalosporins (P<.00001). Sensitivity analyses for bacterial cure significantly favored cephalosporins over penicillin in trials that were double-blinded and of high quality, trials that had a well-defined clinical status, trials that performed GABHS serotyping, trials that eliminated carriers from analysis, and trials that had a test-of-cure culture performed 3-14 days after treatment. This meta-analysis indicates that the likelihood of bacteriologic and clinical failure in the treatment of GABHS tonsillopharyngitis is 2 times higher for oral penicillin than for oral cephalosporins.

title: Meta-analysis of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis in children.
abstract: To conduct a meta-analysis of randomized, controlled trials of cephalosporin versus penicillin treatment of group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis in children.



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.



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.



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.

title: Metaanalysis of Short Course Antibiotic Treatment for Group A Streptococcal Tonsillopharyngitis
abstract: To compare bacterial and clinical cure rates in patients with group A streptococcal (GAS) tonsillopharyngitis treated with oral β-lactam or macrolide antibiotics for 4–5 days versus 10-day comparators.  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 β-lactam or macrolide antibiotic of a shortened course versus a 10-day comparator and assessment of bacteriologic outcome using a throat culture.  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.  Superior cure rates can be achieved with shortened courses of cephalosporin therapy, but 5 days is inferior to 10 days of penicillin treatment.

title: Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for upper respiratory tract infections.
abstract: We carried out a meta-analysis of randomized controlled trials comparing 3-5 days of azithromycin with other antibiotics that are typically given in longer courses for the treatment of upper respiratory tract infections. For acute otitis media (19 comparisons including 3421 patients), acute sinusitis (11 comparisons including 1742 patients) and acute pharyngitis (16 comparisons including 2447 patients), azithromycin had similar clinical failure rates to the other antibiotics [random effects odds ratios 1.12, 95% confidence interval (CI) 0.81-1.54; 0.91, 95% CI 0.60-1.39; and 1.07, 95% CI 0.59-1.94, respectively]. The difference in clinical failures was <0.5%, and no 95% CIs exceeded 2.0%. There was no heterogeneity between studies. Subtle differences between comparators could have been due to chance. There were no significant differences in bacteriological outcomes. Azithromycin was discontinued because of adverse events in only 37 of 4870 (0.8%) patients. Short courses of azithromycin are as effective as longer courses of other antibiotics for upper respiratory tract infections. Convenience of dosing should be balanced against the increased cost of this regimen for the treatment of these common infections, where often no antibiotic may be indicated at all.

title: Comparative efficacy and safety of 5-day cefaclor and 10-day amoxycillin treatment of group A streptococcal pharyngitis in children.
abstract: A total of 384 children with group A beta-haemolytic streptococcal (GABHS) pharyngitis were randomized to receive either 40 mg/kg/day of cefaclor in two doses for 5 days (192 patients), or 40 mg/kg/day of amoxycillin in three doses for 10 days (192 patients). The signs and symptoms of pharyngitis were recorded and throat cultures were obtained at presentation and on days 6-7, 11-15, 16-20 and 28-35. Patient compliance was significantly higher in the children treated with cefaclor (100 vs. 95.1%; P = 0.003). At the end of follow-up, the percentage of clinical success was 91.4% for cefaclor and 91.9% for amoxycillin (P = 0.974); bacteriological success was obtained in 85.7 and 89.6% children (P = 0.348), respectively. Both treatments were well-tolerated with adverse event rates of 8.3% in the cefaclor group and 9.4% in the amoxcillin group (P = 0.857). Our study shows that five days' treatment with cefaclor is as effective and safe as the conventional 10-day course of amoxycillin in the treatment of GABHS pharyngitis, but compliance seems to be significantly greater.

title: Comparative study of 5-day cefcapene-pivoxil and 10-day amoxicillin or cefcapene-pivoxil for treatment of group A streptococcal pharyngitis in children
abstract: 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 β-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.

title: Pharmacodynamic Analysis and Clinical Trial of Amoxicillin Sprinkle Administered Once Daily for 7 Days Compared to Penicillin V Potassium Administered Four Times Daily for 10 Days in the Treatment of Tonsillopharyngitis Due to Streptococcus pyogenes in Children
abstract: An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC90 of 0.06 μg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, −12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of ≥85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, −11.6% to −0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC90 more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer treatment courses and maximal bacterial eradication rates reported in the literature, an alternative composite PK/PD target taking into consideration the duration of therapy, or total T >MIC, was considered and provides an alternative explanation for the observed failure rate of amoxicillin sprinkle.

title: Five vs ten days of penicillin V therapy for streptococcal pharyngitis.
abstract: To determine the effectiveness of a short (five-day) course of penicillin V potassium therapy, 172 patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis were randomly assigned to receive 250 mg of penicillin V potassium three times daily for either five or ten days. The patients in the two treatment groups were comparable with respect to clinical findings, compliance, and serologic response to GABHS. A bacteriologic treatment failure was defined as the presence of the same serotype of GABHS in the follow-up as in the initial throat culture and occurred in 13 (18%) of the 73 patients in the five-day treatment group and in six (6%) of the 99 patients in the ten-day treatment group. These findings support the current recommendation for a full ten days of oral penicillin V therapy for the treatment of GABHS pharyngitis.

title: Penicillin V for group A streptococcal pharyngotonsillitis. A randomized trial of seven vs ten days' therapy.
abstract: The effect of duration of orally administered penicillin V potassium on the bacteriologic and clinical cure of group A streptococcal pharyngitis was evaluated. One hundred ninety-one middle-class patients received either seven days (96 patients) or ten days (95 patients) of therapy. Compliance with taking penicillin was assessed by multiple methods, including penicillinuria. Throat cultures were obtained during therapy and three times in the three weeks after therapy. M-precipitin and T-agglutinin typing were done on paired isolates of group A streptococci from patients who had recurrences. Patients treated for seven days had a significantly greater failure rate (30/96 [31%]) compared with patients receiving ten days of penicillin (17/95 [18%]). Compliance rates were high; 66% to 81% of patients showed penicillinuria throughout the study period. Treatment failure was not a function of poor compliance in either treatment group. The data support the current recommendation for ten full days of penicillin therapy and suggest that persistence of streptococci in the throat after adequate therapy may be common.

title: Penicillin for acute sore throat: randomised double blind trial of seven days versus three days treatment or placebo in adults
abstract: To assess whether treatment with penicillin for three days and the traditional treatment for seven days were equally as effective at accelerating resolution of symptoms in patients with sore throat compared with placebo.  Randomised double blind placebo controlled trial.  43 family practices in the Netherlands.  561 patients, aged 15-60 years, with sore throat for less than seven days and at least three of the four Centor criteria—that is, history of fever, absence of cough, swollen tender anterior cervical lymph nodes, and tonsillar exudate. 142 patients were excluded for medical reasons and 73 needed penicillin.  Patients were randomly assigned to penicillin V for seven days, penicillin V for three days followed by placebo for four days, or placebo for seven days.  Resolution of symptoms in the first week, eradication of bacteria after two weeks, and recurrences of sore throat after two, four, and six months.  Symptoms resolved 1.9 and 1.7 days earlier in patients taking penicillin for seven days than in those taking penicillin for three days or placebo respectively. Symptoms resolved 2.5 days earlier in patients with group A streptococci and 1.3 days earlier in patients with high colony counts of non-group A streptococci. 23 (13%) of the placebo group had to be given antibiotics later in the week because of clinical deterioration; three developed a peritonsillar abscess. The eradication rate for group A streptococci was 72% in the seven day penicillin group, 41% in the three day penicillin group, and 7% in the placebo group. Sore throat recurred more often in the three day penicillin group than in the seven day penicillin or placebo groups.  Penicillin treatment for seven days was superior to treatment for three days or placebo in resolving symptoms of sore throat in patients with group A streptococcal pharyngitis and, possibly, in those with non-group A streptococcal pharyngitis.

title: Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics
abstract: To assess the medicalising effect of prescribing antibiotics for sore throat.  11 general practices in England.  Randomised trial of three approaches to sore throat: a 10 day prescription of antibiotics, no antibiotics, or a delayed prescription if the sore throat had not started to settle after three days.  716 patients aged 4 and over with sore throat and an abnormal physical sign: 84% had tonsillitis or pharyngitis.  Number and rate of patients making a first return with sore throat, pharyngitis, or tonsillitis. Early returns (within two weeks) and complications (otitis media, sinusitis, quinsy). Outcomes were documented in 675 subjects (94%).  Mean follow up time was similar (antibiotic group 1.07 years, other two groups 1.03 years). More of those initially prescribed antibiotics initially returned to the surgery with sore throat (38% v 27%, adjusted hazard ratio for return 1.39, 95% confidence interval 1.03 to 1.89). Antibiotics prescribed for sore throat during the previous year had an additional effect (hazard ratio 1.69, 1.20 to 2.37). Longer duration of illness (> 5 days) was associated with increased return within six weeks (hazard ratio 2.90, 1.70 to 4.92). Prior attendance with upper respiratory conditions was also associated with increased reattendance. There was no difference between groups in early return (13/238 (5.5%) v 27/437 (6%)), or complications (2/236 (0.8%) v3/434 (0.7%)).  Complications and early return resulting from no or delayed prescribing of antibiotics for sore throat are rare. Both current and previous prescribing for sore throat increase reattendance. To avoid medicalising a self limiting illness doctors should avoid antibiotics or offer a delayed prescription for most patients with sore throat.  Sore throat is one of the commonest presentations of upper respiratory illness in primary care and attendence is increasing Complications are rare with no, or delayed, antibiotic prescription Prescribing antibiotics increases reattendance for future episodes Unless patients are very ill general practitioners should consider exploring concerns, explain the natural history, and avoid or delay prescribing antibiotics

title: Zinc for the common cold.
abstract: The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted in high-income countries since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results.



To assess whether zinc (irrespective of the zinc salt or formulation used) is efficacious in reducing the incidence, severity and duration of common cold symptoms. In addition, we aimed to identify potential sources of heterogeneity in results obtained and to assess their clinical significance.



In this updated review, we searched CENTRAL (2012, Issue 12), MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013), Web of Science (1985 to January 2013), LILACS (1982 to January 2013), WHO ICTRP and clinicaltrials.gov.



Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold.



Two review authors independently extracted data and assessed trial quality.



Five trials were identified in the updated searches in January 2013 and two of them did not meet our inclusion criteria. We included 16 therapeutic trials (1387 participants) and two preventive trials (394 participants). Intake of zinc was associated with a significant reduction in the duration (days) (mean difference (MD) -1.03, 95% confidence interval (CI) -1.72 to -0.34) (P = 0.003) (I(2) statistic = 89%) but not the severity of common cold symptoms (MD -1.06, 95% CI -2.36 to 0.23) (P = 0.11) (I(2) statistic = 84%). The proportion of participants who were symptomatic after seven days of treatment was significantly smaller (odds ratio (OR) 0.45, 95% CI 0.20 to 1.00) (P = 0.05) than those in the control, (I(2 )statistic = 75%). The incidence rate ratio (IRR) of developing a cold (IRR 0.64, 95% CI 0.47 to 0.88) (P = 0.006) (I(2) statistic = 88%), school absence (P = 0.0003) and prescription of antibiotics (P < 0.00001) was lower in the zinc group. Overall adverse events (OR 1.58, 95% CI 1.19 to 2.09) (P = 0.002), bad taste (OR 2.31, 95% CI 1.71 to 3.11) (P < 0.00001) and nausea (OR 2.15, 95% CI 1.44 to 3.23) (P = 0.002) were higher in the zinc group. The very high heterogeneity means that the averaged estimates must be viewed with caution.



Zinc administered within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people but some caution is needed due to the heterogeneity of the data. As the zinc lozenges formulation has been widely studied and there is a significant reduction in the duration of cold at a dose of ≥ 75 mg/day, for those considering using zinc it would be best to use it at this dose throughout the cold. Regarding prophylactic zinc supplementation, currently no firm recommendation can be made because of insufficient data. When using zinc lozenges (not as syrup or tablets) the likely benefit has to be balanced against side effects, notably a bad taste and nausea.

title: Susceptibility of group A beta-hemolytic streptococci to thirteen antibiotics: examination of 301 strains isolated in the United States between 1994 and 1997.
abstract: Because of continuing reports from many countries of increasing resistance of group A streptococci to macrolide antibiotics, we determined the antibiotic susceptibility of recent group A streptococcal isolates from the United States.



We evaluated 301 Streptococcus pyogenes isolates (245 from patients with uncomplicated pharyngitis and 56 isolates from patients with invasive systemic infections) for susceptibility using the Etest technique. The isolates came from 24 states and the District of Columbia during the years 1994 through 1997. Thirteen antibiotics (azithromycin, ceftriaxone, cephalothin, chloramphenicol, ciprofloxacin, clindamycin, erythromycin, imipenem, levofloxacin, oxacillin, penicillin G, tetracycline and trimethoprim-sulfamethoxazole) were studied.



The MIC90 for penicillin was 0.016 microg/ml, which is not significantly different from previous reports. Of the 301 isolates only 2.6% were resistant to a macrolide antibiotic and only 4% were resistant to tetracycline.



These data indicate that antibiotic resistance among recent isolates of group A streptococci (including those from patients with severe infections) currently is not a clinically significant problem in the United States.

title: So what's wrong with penicillin for strep throat?
abstract: “Change is one thing, progress is another.” Bertrand Russell (1872–1970) 

Group A β-hemolytic streptococcal (GABHS) pharyngitis is one of the most common infections of children. For 5 decades, penicillin has been the treatment of choice for this infection, and it is currently recommended by the American Academy of Pediatrics,1 the American Heart Association,2 the World Health Organization,3 and the Infectious Diseases Society of America.4 Amoxicillin is often utilized in young children in place of penicillin V because of taste considerations. Although the problem of increasing antimicrobial resistance among bacteria is one of the most important infectious disease issues of our time,5 GABHS remarkably have never developed resistance to any of the penicillins or cephalosporins or shown any increase in penicillin minimal inhibitory concentrations over at least 5  However, it is appropriate to reconsider periodically whether penicillin should remain the treatment of choice or whether a compelling argument can be made to change the recommendation to a different agent such as a cephalosporin. In the April issue of Pediatrics , Casey and Pichichero7 presented a meta-analysis of 35 clinical trials performed between 1970 and 1999 in which a cephalosporin was compared with penicillin for the treatment of GABHS pharyngitis.7 Based on this analysis, they concluded that cephalosporins should be added as a “treatment of choice for GABHS tonsillopharyngitis.” However, their report has several major flaws that make it impossible to accept the validity of their conclusion.

Meta-analysis is “a statistical analysis which combines or integrates the results of several clinical trials considered by the analyst to be ‘combinable.’”8 Over time, meta-analysis research is thought to have led to improved conduct and reporting of clinical trials, including the removal of major sources of bias that, for example, occur in studies that are … 

Address correspondence to Stanford T. Shulman, MD, Division of Infectious Diseases, Children’s Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614.

title: Are cephalosporins superior to penicillin for treatment of acute streptococcal pharyngitis?
abstract: Penicillin has been the " gold standard " for treatment of acute pharyngitis due to group A streptococci (GAS) (i.e., " strep throat ") for 5 decades. It is effective not only for treating acute infection but also for preventing acute rheumatic fever. GAS have remained exquisitely and uniformly susceptible to penicillin in vitro, and the drug is notable for its safety, narrow spectrum , and low cost. For these reasons, it is considered to be the agent of choice in guidelines published by the American Heart Association, the Infectious Diseases Society of America (IDSA), the American College of Physicians, and the American Academy of Pediatrics. Starting in the 1980s, there have been reports of increased bacteriologic and clinical failure rates associated with penicillin. In this issue of Clinical Infectious Diseases, Casey and Pichichero  present a meta-analysis of treatment of GAS tonsillo-pharyngitis in adults and conclude that the likelihood of bacteriologic and clinical failure associated with oral penicillin therapy is 2 times higher than that for oral ceph-alosporin therapy. Pichichero  previously published a similar meta-analysis in a study involving pediatric populations, but that analysis was severely criticized in some quarters because of methodological flaws . Moreover, a careful analysis of older and more recent articles published during 1953–1979 and 1980–1993, respectively , that met scrupulous design criteria failed to find evidence of an increase in penicillin failures among patients with GAS pharyngitis . Although Casey and Pichichero  have attempted to address many of the flaws criticized in the pediatric study, their efforts are inevitably deterred by the quality of the trials available for review. Although they excluded most of the published trials on methodological grounds, many of the 9 trials eventually included for analysis had appreciable deficiencies. For example, as they point out, 3 trials did not provide detailed descriptions of signs and symptoms required for enrollment, 3 did not provide adequate methods for monitoring treatment compliance, 2 did not perform follow-up cultures early enough to avoid confusion introduced by reacquisition, 3 did not specifically attempt to define and eliminate GAS carriers from the study, and 5 did not include typing of GAS strains recovered from patients in whom treatment apparently failed. The latter 2 deficiencies leave open the possibility that the patient groups under study may either have contained an increased number of patients with chronic strepto-coccal carriage or that the strains recovered during convalescence were …