Evidence based pediatrics - part 3 ppt

Nondrug Therapy: Inhalation Therapy Breathing in steam or warm mist has long been known to provide a measure of comfort for those suffering from nasal and sinus congestion. The physical benefit probably stems from the liquefaction of respiratory secretions, which enables more effective removal by either coughing or nose blowing. Additionally, warm, moist air is soothing to an irritated respira- tory epithelium. Aromatics have also been added to steam to provide a sensation of relief, although these have not been examined scientifically. Menthol tablets create a subjective sense of nasal decongestion but have not been shown to change nasal airflow when measured objectively 12 (level I). Studies on the effect of steam inhalation on the common cold have shown conflicting results. Two early studies lend support to the hypothesis that nasal hyperthermia reduced the symptoms of the common cold. The effects of steam inhalation on nasal patency and on nasal symptoms in 62 patients with the common cold were studied in a double-blind, random- ized, placebo-controlled clinical trial 13 (level I). Treatment consisted of two 20-minute ses- sions, during which one patient group inhaled saturated, hot (42 to 44°C) air through the nose. This was compared with a control group which received inhalations of room air (20 to 24°C) for similar time periods. During the week following treatment, the subjective response was recorded by each patient on a daily symptom score card. Nasal patency was determined before treatment, the following day, and 1 week later by measuring peak nasal expiratory and inspiratory airflow. Steam inhalation resulted in the alleviation of cold symptoms and increased nasal patency in a significantly higher percentage of patients in the actively treated group than in the placebo-treated group. In the second study, 87 subjects with simple colds breathed warm, humidified air at 43°C for 20 minutes per day and were compared with 84 subjects breathing air at 30°C 14 (level I). Patients recorded their symptoms, and observers recorded symptoms and signs, weight of nasal secretions, isolation of virus, and antibody responses in volunteers. Patients treated with the warm air had roughly half the score for symptoms of those treated at 30°C. The study concluded that nasal hyperthermia will pro- vide immediate relief of symptoms and improve the course of the common cold. Two more recent trials have attempted to examine the effect of inhaling warm, humidi- fied air.The first of these was a randomized double-blind trial performed on 68 volunteers with naturally occurring colds 15 (level I). The first part of the study indicated that in-vivo rhinovirus was greatly inhibited if exposed to temperatures higher than 43°C for 60 minutes. In the sec- ond part of the study, 32 individuals received a 1-hour treatment with steam (43°C) and were compared with 36 who received room air (20 to 24°C). A 7-day follow-up revealed no differ- ence in symptom scores or objective scores of nasal airflow. A second trial was performed on 20 volunteers who were experimentally infected with rhinovirus 16 (level II-1). Eight participants received two 30-minute treatments of (42 to 44°C) steam at 1 and 2 days after inoculation. Six received a similar regime of room temperature vapor (22 to 23°C). The outcomes were assessed over the following 4 days. There was no difference in rhinovirus titers in nasal washings and no difference in symptom scores. The authors commented on the low power of this trial and its inability to detect symptom improvement. Certainly, the steam had no antiviral effect. These studies (none of which included children) provide conflicting evidence for the effects of inhaled steam for the relief of nasal congestion (recommendation C). It should be noted that the steam was delivered by a specially designed ultrasonic heater that directs moist air to the nares, using a mask device. The practical issue of safely delivering this treatment to children will need to be addressed (Table 5–4). Pharmacotherapy The fact that there are so many widely differing therapies for the common cold suggests that none really work very well. Many parents understandably want to ease these minor but irri- tating symptoms in their children and often turn to OTC medications for help. Antihista- Acute Rhinitis and Pharyngitis 85 mines, decongestants, cough suppressants or expectorants, analgesics, and various combina- tions of these are available. The breadth of choice is all the more striking, given the limited scientific information demonstrating their effectiveness. 17 Commonly used cough and cold medications can be divided into the following groups: antihistamines, decongestants, cough medications, ipratropium, combination products, analgesics/nonsteroidal anti-inflammatory drugs, zinc gluconate, antibiotics, antiviral therapies, and vitamin C. Antipyretics (reviewed in detail in another chapter) are often combined with many of the cold medications. Antihistamines Antihistamines exert their effects via their anticholinergic activity designed to dry up the res- piratory secretions. The anticholinergic effect is often weak, given the dosages used in most OTC preparations. The antihistamine effect is also probably minimal due to the lack of his- tamine released during a viral nasopharyngitis. 18 The most common groups of antihista- mines include the ethanolamines (diphenhydramine and dimenhydrinate) alkylamines (chlorpheniramine and brompheniramine), and the piperidines (terfenadine and astemi- zole). In certain circumstances, such as in a child with allergic rhinitis, antihistamines may be effective in relieving some of the symptoms. In therapeutic doses, some antihistamines act as a sedative. Many parents wrongly attribute this to a relief of symptoms. Paradoxically, use of these medications may occasionally result in overstimulation in children. The literature has not supported the use of antihistamines for the common cold in chil- dren. In one systematic review of OTC cold medications, there was no evidence for antihis- tamines causing clinical improvement in children. 17 There was evidence for a beneficial effect brought about by chlorpheniramine in adolescents and adults. In addition, a few first-gen- eration antihistamines have recently been found to be useful in the common cold in adults. Doxylamine succinate 19 (level I), clemastine fumarate 20,21 (level I), and chlorpheniramine maleate 22 (level I) all reduce rhinorrhea, sneezing, and volume of nasal secretion. Terfena- dine has not been found to reduce symptoms, possibly because of its relative lack of anti- cholinergic activity. 18 Recently, the efficacy of brompheniramine maleate was tested in a randomized, controlled trial of volunteers with experimental rhinovirus colds 23 (level I). Brompheniramine (12 mg) or placebo was administered for 4 days after the onset of symp- toms. During the first 3 days of treatment, nasal secretion weights, rhinorrhea scores, sneeze counts, sneeze severity scores, and cough counts were lower in subjects receiving brompheni- ramine than in controls. Treatment with brompheniramine was associated with adverse effects such as somnolence and confusion in a small number of subjects. Overall, it was con- cluded that brompheniramine was efficacious treatment for the sneezing, rhinorrhea, and cough associated with rhinovirus colds. A recent systematic review examined whether studies on antihistamines showed clini- cally significant relief from the symptoms of the common cold in adults and children. 24 Three out of five studies reporting on sneezing found a statistically significant improvement in the antihistamine group; similarly, 3 of 7 studies reporting on nasal discharge found a statisti- cally significant improvement with therapy. No study reported improvement in total symp- tom score at the significance level of p=.05. The validity of the studies was weakened by several flaws, such as inattention to clinical significance and functional impact, inappropri- ate use of statistical tests, and poorly described methodology. The authors of this review con- cluded that the medical literature offered little support for the use of antihistamines in the treatment of the common cold. In summary, there is some evidence that antihistamines reduce nasal symptoms of the common cold in adolescents and adults, although the clinical significance of this benefit is questionable (recommendation C). There may be some benefit if there is a history of accom- panying allergic disease. Younger children do not appear to respond to these medications (recommendation E) (see Table 5–4). 86 Evidence-Based Pediatrics Decongestants (Alpha-Adrenergic Agents) These sympathomimetic substances produce a physiologic response similar to that of the cat- echolamines. Decongestants either directly stimulate the alpha and beta adrenergic recep- tors or release endogenous noradrenaline from presynaptic nerve terminals. The main beneficial action of these medications is the vasoconstriction of the nasal mucosa, which reduces edema and therefore improves nasal airflow and reduces sinus congestion. These medications are found in bronchodilators, stimulants, and appetite suppressants as well as cough and cold medications. In a systematic review of OTC cold medications, there was no evidence for decongestants causing clinical improvement in the common cold in children. 17 Oral alpha-adrenergic agents. Ephedrine and pseudoephedrine have a rapid onset of action, reaching a peak at 1 to 2 hours after ingestion. They can produce hypertension and tachycardia, which are more often a problem in adults than children. 25 Signs and symptoms of toxicity in the pediatric age group include headache, nausea, vomiting, diaphoresis, agitation, psychosis,hypertension, seizures,tremulousness, and rhabdomyolysis. 25 Phenylpropanolamine is another sympathomimetic compound with a similar action and side-effect profile to ephedrine and pseudoephedrine. This substance is used in combination with analgesics, anti- histamines, anticholinergic, and antitussive medications. The major problem caused by it is hypertension, especially when it is taken in combination with caffeine. 26 Norephedrine has also been shown to be mildly effective. 27 Side effects (particularly, CNS overstimulation and hyper- tension) have been reported both in therapeutic doses and in excessive ingestion. Topical alpha-adrenergic agents. The imidazolines (oxymetazoline, naphazoline, tetrahydrozoline, and xylometazoline) are used as topical agents for their vasoconstrictive action. Studies have reached different conclusions regarding their effectiveness: (level II-2), 28 (level I). 29,30 The imidazolines are used in sinusitis, allergic rhinitis, colds, and ocular irrita- tions. In short-term use, topical vasoconstrictors are promptly effective, although when used continuously (especially over 3 to 4 days), they can result in rebound nasal congestion and thus prolong the cold. As a result, these medications are not recommended for use in chil- dren (recommendation D). Signs of clinical toxicity cover a wide range of symptoms from lethargy, somnolence, pallor, and cool extremities to miosis, bradycardia, hypotension, loss of consciousness, and respiratory depression. 31 The evidence would suggest that these medications are effective in adolescents and adults, but the side effects may be significant in certain individuals (recommendation C) (see Table 5–4). Cough Suppressants/Expectorants Dextromethorphan is one of the most commonly used antitussive medications. It acts in a sim- ilar manner to codeine by suppressing the cough center in the medulla oblongata. Both codeine and dextromethorphan are frequently used for their antitussive effects, despite evidence to the contrary 32 (level I). Although generally considered safe, dextromethorphan has been shown to cause CNS side effects, including hyperexcitability, increased muscle tone, and ataxia. Expectorants reduce the viscosity of the secretion to promote more effective expectora- tion. Guaifenesin is the most widely used of these medications. In one clinical trial, young adults with a cold perceived a minor reduction in the quantity of sputum after using this medication 33 (level I) (recommendation D). In some formulations, this substance is com- bined with a cough suppressant, which makes little sense. There is no evidence, therefore, that dextromethorphan and guaifenesin are effective in relieving cold symptoms in children (recommendation E) (see Table 5–4). Ipratropium Ipratropium is a parasympatholytic medication with a highly topical action. It has been used successfully as a bronchodilator in asthma. One randomized trial looked at the effectiveness Acute Rhinitis and Pharyngitis 87 of intranasal ipratropium bromide (IB) for the treatment of symptoms of the common cold 34 (level I). Four hundred and eleven university students were randomized to either IB nasal spray, a nasal spray of salt solution, or no treatment. The treatments were self-administered three or four times daily for 4 days. Recipients of IB had 26 percent less nasal discharge, 31 percent less rhinorrhea and less sneezing on days 2 and 4. The medication was well tolerated but was associated with higher rates of blood-tinged mucus and nasal dryness than the con- trol spray. Patient assessments of the overall effectiveness of treatment were more favorable for IB than for the control spray. The study concluded that intranasal IB provides specific relief of rhinorrhea and sneezing associated with the common cold. In another study, three doses of IB nasal spray were compared with the vehicle alone and with no treatment, for the relief of rhinorrhea in patients with naturally acquired colds 35 (level I). Rhinorrhea severity was measured by determination of nasal discharge weights and a subjective symptom scale. Compared with either the vehicle or no treatment, IB nasal spray produced a significant decrease in the severity of rhinorrhea. A dose of 84 micrograms (two sprays of a 0.06 percent solution) in each nostril was more efficacious than a dose of 42 micrograms per nostril and only marginally less efficacious than a dose of 168 micrograms per nostril. The dose of 84 micrograms per nostril also was associated with fewer adverse events than the higher dose. None of the adverse events related to intranasal IB therapy were of a serious nature. This study indicates the pharmacologic benefits of differing doses of this medication. The study concluded that the use of IB nasal spray appears to be an effective and safe approach to relieving rhinorrhea associated with the common cold. Ipratropium bromide seems to be a promising therapy in alleviating rhinorrhea (recom- mendation B). Side effects may be a problem for some individuals.As the evidence is drawn from adult studies, it remains to be seen whether this treatment is effective in children (see Table 5–4). Combination Products Drug combinations are the most common form of treatment for simple viral upper respiratory infections and possess the theoretical advantage of treating the various symptoms that accom- pany a cold. However, this treatment is less desirable pharmacologically because of the fixed amounts and ratios of each of the component drugs. This makes it less than ideal for children with differing ages and weights. One systematic review identified a probable reduction in symp- toms with a decongestant and antihistamine preparation in adolescents and adults. 17 Benefits included a reduction in nasal symptoms (decrease in congestion, postnasal drip, and rhinor- rhea) as well as less cough and fewer ear symptoms. The inclusion of analgesics (acetaminophen or ibuprofen) in the preparation relieved headaches and generalized discomfort. In a more recent trial on preschool children, an antihistamine-decongestant combina- tion was compared with a placebo in temporarily relieving symptoms of upper respiratory tract infection (URI) 36 (level I). Preschool children with a cold were randomly assigned to receive brompheniramine maleate–phenylpropanolamine hydrochloride (ADC) or placebo, as needed for respiratory symptoms. Two hours after each dose of study medication, changes in the child’s nasal discharge, nasal congestion, cough, and sleep status were assessed by means of a standardized questionnaire. There were no statistically significant differences in symptom improvement between the ADC and the placebo groups. However, the proportion of children still asleep 2 hours after receiving ADC was significantly higher than the pro- portion receiving placebo. Results were unchanged after control for the correlated nature of repeated responses, age, symptom duration, use of acetaminophen, time that the medication was given, and parental desire for medication. The study concluded that ADC was equiva- lent to the placebo in providing temporary relief of URI symptoms in preschool children. However, ADC did have significantly greater sedative effects than did the placebo. There seems to be no evidence, therefore, that these medications are of benefit in preschool children, who arguably have the greatest need for symptom relief. Sedation may 88 Evidence-Based Pediatrics be a beneficial side effect, for both parents and child, but is not an acceptable reason to rec- ommend this as a therapy (recommendation E). Combination products may provide bene- fit in older children, adolescents, and adults (recommendation B) (see Table 5–4). Antipyretics, Analgesics, and Nonsteroidal Anti-inflammatory Drugs The fever which commonly accompanies viral upper respiratory infections generates con- siderable anxiety in parents, leading them to seek medical attention early and frequently. 37,38 Many families aggressively treat even a mild elevation of temperature (37 to 37.8°C) with antipyretics, a level which includes the normal range. There has been considerable debate whether pharmacologic reduction of fever is beneficial or hazardous to the host. 39 Fever is a reliable sign of illness, and reduction may mask the onset of a more serious disease. High fever may also be a useful mechanism for fighting bacterial infections. On the other hand, an elevated temperature is uncomfortable, and adverse events such as seizures, confusion, or dehydration are more likely. Common OTC medications used for fever are acetaminophen, acetylsalicylic acid, naproxen, and ibuprofen. Due to the association between aspirin and Reye’s syndrome, acetaminophen has virtually replaced all OTC analgesic preparations. Acetaminophen can be found in a variety of forms, either on its own or combined with a variety of substances, in cough and cold preparations. In a recent report, the use of aspirin and acetaminophen was associated with suppression of serum-neutralizing antibody response and increased nasal symptoms and signs in the common cold, compared with ibuprofen or placebo. 40 Naproxen sodium has been thought to increase nasal symptoms and virus shedding and decrease serum neutralising antibody response in patients infected with the rhinovirus. However, in a study of adults with experimental rhinovirus colds, naproxen treatment did not alter virus shedding or antibody responses 41 (level I). The medication had a beneficial effect on headache, mylagia, and cough. Overall, the consistent benefit from these medications seemed to be analgesia (recommendation B) (see Table 5–4). Zinc Gluconate There is suggestive evidence from the laboratory that zinc gluconate may be effective in the treatment of the common cold. Despite this evidence, there continues to be controversy regarding its effectiveness. Initially, it was thought to be effective, 42 but subsequent trials failed to confirm this when placebos were used (level I). 43–46 Two more recent trials demon- strated efficacy in adults (level I). 47,48 A recent randomized, placebo-controlled study examined 249 students in grades 1 through 12 49 (level I). Ten milligram zinc gluconate glycine lozenges were given either five or six times a day. The time to resolution of the symptoms was based on daily symptom scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and sneezing. The study showed that time to resolution of all cold symptoms did not differ significantly between students receiving zinc and those receiv- ing placebo. In addition, more students in the zinc group reported adverse effects such as bad taste, nausea, oral discomfort, and diarrhea. In this community-based trial, zinc lozenges were thus not effective in treating cold symptoms in children and adolescents (recommen- dation E). Overall, the published evidence demonstrates conflicting results with regard to the use of zinc in adults (recommendation C) (see Table 5–4). Antibiotics A well-designed study from Switzerland found co-amoxiclav to be beneficial in 20 percent of adults with the common cold whose nasopharyngeal secretions contained Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae 50 (level I). It is not clear how this information can be used in practice, as patients would have to wait for cultures, by which time the major symptoms of the cold would have passed. The benefit to those with positive Acute Rhinitis and Pharyngitis 89 cultures appears marginal, and the risks of excessive antibiotic use are too high to recom- mend its routine use (recommendation D) (see Table 5–4). Antiviral therapy Antiviral drugs for respiratory viruses generally bind to hydrophobic pockets in the virion capsid and inhibit virion attachment or uncoating. The main difficulties in the development of effective antiviral drugs for the common cold include the wide variety of viruses, mutant strains, and the development of resistance. Several studies have treated rhinovirus colds with no appreciable benefit 51,52 (level I). In Hayden’s trial, intranasal pirodavir was assessed in a ran- domized, double-blind manner. Adults with laboratory-documented rhinovirus colds were randomly assigned to intranasal sprays of pirodavir or placebo six times daily for 5 days. In this study, no significant differences in the resolution of respiratory symptoms were apparent between the treatment and control groups. The median duration of illness was 7 days in each group. Reduced frequencies of rhinovirus shedding were observed in the pirodavir group on days 3 and 5, but not after the cessation of treatment on day 7. No pirodavir-resistant viruses were recovered from treated individuals. The pirodavir group had higher rates of nasal dry- ness, blood in mucus, or unpleasant taste on several study days. In summary, intranasal sprays of pirodavir were associated with significant antiviral effects but no clinical benefit in treat- ing naturally occurring rhinovirus colds. Other antiviral agents have been tried similarly with successful reduction of the viral load but, again, with little clinical benefit. Interferon prevents viral invasion of the nasal mucosa. As with many common cold ther- apies, the results have been conflicting. Interferon alpha 2 has been tested in two studies. In both these studies, a nasal spray was administered once daily for 7 days when cold symptoms appeared in another family member. A decrease in colds due to rhinovirus as well as a decrease in all respiratory illnesses was observed. 53,54 This short-term prophylaxis of colds was not confirmed in another study. 55 Combination therapy with interferon alpha 2b, ipra- tropium bromide, and oral naproxen reduced cold symptoms (rhinorrhea, cough, malaise, and sore throat) effectively in a small study of adults 56 (level II-2). Overall, there has been no clear effective antiviral therapy for colds in adults (recommendation D).At the current time, there is no evidence supporting the use of antiviral medication in children for the preven- tion or treatment of the common cold (see Table 5–4). Vitamin C Vitamin C has long been felt to play both a preventive and therapeutic role in the common cold. There have been many studies of varying quality which have attempted to determine this issue. A recent review of 30 trials by the acute respiratory infection group of the Cochrane Collabo- ration has provided a useful contribution to this debate. 57 In this review, which was undertaken using strict criteria, the authors found that regular high-dose vitamin C had no important effect on the incidence of the common cold. However, there was a modest benefit in the treatment of the common cold by reducing its duration. The magnitude of this effect was a reduction of symptoms by 8 to 9 percent, or about a half symptom day per episode. The studies reviewed included both adult and children. The authors concluded that prophylaxis should be discour- aged but that higher-dose therapy (>8 g/day) should be studied for its therapeutic benefit. This is likely to be a topic of debate for many years. Further studies examining the therapy in high doses may reveal whether there is value in using this medication for the common cold. It is not currently recommended for use in children or adults (recommendation C) (see Table 5–4). PHARYNGITIS Disease Overview Group A beta-hemolytic streptococci (GABHS) are the most common bacterial cause for acute pharyngitis. Establishing the diagnosis of GABHS is particularly important because of 90 Evidence-Based Pediatrics the acute morbidity of the illness as well as the potentially severe nonsuppurative sequelae (acute rheumatic fever and acute glomerulonephritis). The bacteria are spread by person- to-person contact with infected nasal or oral secretions. Transmission is more common in crowded environments, such as schools or dormitories. Clinical Features and Diagnosis For the majority of children with a sore throat, diagnosis focuses on either a viral cause or GABHS pharyngitis. Pharyngitis caused by a virus requires no treatment. If the patient has respiratory difficulty, then pharyngeal or peritonsillar abscess or tonsillar hypertrophy from Epstein-Barr virus infection needs to be considered. Buccal or gingival inflammation, vesi- cles on the posterior pharynx, or diffuse cervical or posterior lymphadenopathy imply a viral cause. Scarlet fever is distinguished by a fine sandpaper-like rash seen in children older than 3 years. It is seen about 24 hours after the development of the illness, beginning on the chest and spreading all over, with accentuation in the flexural creases. The redness fades in several days and the skin begins to desquamate as in the case of a sunburn downwards from the face extending out to the peripheries. Children with GABHS infection present with sudden onset of a sore throat, painful swal- lowing, and fever (Table 5–2). These symptoms may also be accompanied by headache, nau- sea and vomiting, and abdominal pain. Examination shows tonsillopharyngeal erythema with or without exudate, a red swollen uvula, petechiae on the palate and large, tender, anterior cervical lymph nodes. The papillae on the tongue may be red and swollen giving the “straw- berry tongue” appearance. Younger children may have a more prolonged course of GABHS with chronic low grade fever, generalized lymphadenopathy and coryza with crusting below the nares with little or no pharyngitis. This condition is known as streptococcosis. Scoring Systems The clinical diagnosis of GABHS infection is difficult as many of the clinical features are also associated with other forms of pharyngitis or viral illnesses. Several attempts have been made to establish a predictive score for GABHS infection by incorporating clinical and epidemio- logic features. 59–61 One study looked specifically at the clinical features to determine whether these can suggest GABHS infection. 62 In 192 children presenting with acute pharyngitis, 89 percent had GABHS isolated by throat culture. Using otoscopic magnification, the pharynx was examined for the presence of nine clinical features. Children with GABHS pharyngitis were more likely to have one out of the following six features: (1)pharyngeal erythema, (2)palatal enanthem, (3)uvular erythema, (4)uvular edema, (5)tonsillar erythema, and Acute Rhinitis and Pharyngitis 91 Table 5–2 Features Suggestive of GABHS Pharyngitis Clinical findings Sudden onset of sore throat Fever Headache Marked inflammation of the pharynx and tonsils Tonsillar hypertrophy Patchy discrete exudate Tender enlarged cervical lymph nodes Nausea, vomiting, abdominal pain Absence of coryza, cough, conjunctivitis, or diarrhea Epidemiological findings 5 to 15 years Winter and early spring Exposure to others with infection With permission from Gerber MA. Diagnosis of group A streptococcal pharyngitis. Pediatr Ann 1998;27:269–73. (6)tonsillar exudate. The combinations of two or three of these findings produced a positive predictive value of greater than 90 percent. However, these combinations were never present in more than 30 to 40 percent of the patients studied. In a recent study, a score based on clinical symptoms and signs was developed to iden- tify, in general practice, GABHS infection in patients presenting with a new upper respira- tory tract infection. 61 The score ranged in value from 0 to 4. A total of 521 patients (with ages ranging from 3 to 76 years) were studied. The management and outcome of patients using the clinical score was compared with those of patients receiving the usual physician care. The sensitivity of the score for identifying GABHS infection was 83.1 percent, compared with 69.4 percent for usual physician care; the specificity values of the two approaches were similar. Among patients aged 3 to 14 years, the sensitivity of the score approach was higher than that of usual physician care (96.9 percent versus 70.6 percent). The authors calculated that if the score were implemented, the proportion of patients receiving initial antibiotic prescriptions would have been reduced by 48 percent compared with usual physician prescribing, without any increase in the use of throat culture. They concluded that an age-appropriate sore throat score identified GABHS infection in children and adults better than the usual care by fam- ily physicians. It had the additional benefit of significantly reducing unnecessary prescrip- tion of antibiotics (Recommendation B) (Table 5–5). Throat Culture Throat swab culture on sheep blood agar plate remains the gold standard for the diagnosis of GABHS infection. 63,64 Unfortunately, this method is not without potential problems. Firstly, the swab must pass over both the tonsils and the posterior pharyngeal wall. 65 If this is not done correctly, the swab will often be negative. Secondly, negative results can also be obtained if the patient has been on antibiotics prior to obtaining the sample. Thirdly, the length of incubation is important, as 24 to 48 hours of incubation will identify more strep- tococci than that of 18 to 24 hours. 66 Fourthly, the number of colonies of growth, anaerobic versus aerobic incubation, and the bacitracin disc to identify GABHS are also important determinants of microbiological yield. 58,66,67 Rapid Antigen Detection Kits Rapid diagnosis of GABHS pharyngitis results in significant advantages. The spread of the illness can be checked and the morbidity of the illness reduced. 58,68,69 Most of the rapid anti- gen detection tests have an excellent specificity of around 95 percent when compared with sheep blood agar plates. This means that positive results can usually be trusted. However, as the sensitivity is often less than the specificity (around 80 to 90 percent), negative results can- not always be trusted. It has been recommended, therefore, that a negative antigen detection test be confirmed with a throat culture 70,71 (Recommendation A) (see Table 5–5). Recently, newer antigen detection kits have been developed using enzyme immunoas- say techniques, which have more sharply defined endpoints and an increased sensitivity. The most recent tests are optical immunoassay (OIA) and chemiluminescent DNA probes. 72–74 One trial compared the accuracy of an OIA for the rapid diagnosis of group A streptococcal pharyngitis with the gold standard blood agar plate (BAP) culture. 74 The trial took place in six pediatricians’ offices in two cities. Over 2,000 patients with acute pharyngitis participated in it. In each office, the OIA was more sensitive than the BAP culture, with overall sensitiv- ities of the OIA and BAP culture of 84 percent and 78 percent, respectively, while the speci- ficities were 93 percent and 99 percent, respectively. The results of this office-based investigation suggest that, with adequately trained personnel, negative OIA test results need not always be routinely confirmed with BAP cultures. A 1998 decision analysis similarly con- cluded that confirmatory cultures do not have to be performed with the newer rapid diag- nostic testing. 75 92 Evidence-Based Pediatrics Repeat diagnostic testing after therapy is not indicated for routine patients. 76 A signifi- cant number of them will demonstrate streptococcal carriage, which often results in addi- tional antibiotic therapy. In addition, up to 25 percent of household contacts will harbor GABHS. As with carriers, it is not necessary to treat these individuals, unless they become symptomatic. It is only necessary to investigate and treat other asymptomatic individuals if there is an increased likelihood of nonsuppurative complications or if there is an outbreak of GABHS in a crowded community such as a school, day care, or long term care institution. Treatment of GABHS Infection The main benefits of correct treatment are the prevention of rheumatic fever and the relief of discomfort. Moreover, appropriate treatment will shorten the course of the illness, decrease the spread through the child’s community, and reduce the likelihood of both sup- purative and nonsuppurative complications. 77 Which treatment is most appropriate will depend on several factors such as clinical efficacy, likelihood of adherence, potential side effects, and cost to the patient. No medication or regimen provides 100 percent removal of GABHS from the pharynx. The various antibiotic treatment alternatives include penicillin, macrolides, cephalosporins, and others. Certain antibiotics should not be used. These treat- ment options are discussed below. Penicillin Penicillin is arguably the safest and most well known of all the antibiotics and is the stan- dard choice in the treatment of GABHS pharyngitis. The only exception to this is for those individuals with penicillin allergy. It can be given either orally or intramuscularly with equal effectiveness. It has a very narrow spectrum of activity, and there have been no documented cases of resistance. However, oral penicillin fails to remove GABHS from the pharynx in 15 percent of those treated. 78 The reasons for this are unclear, although some have proposed that it may be due to poor compliance, inclusion of carriers in clinical trials, suboptimal doses, low penicillin concentration, or presence of beta-lactamase bacteria in the pharynx. 79 The first-line therapy is oral penicillin V (phenoxymethyl penicillin) in the dose of 250 mg two or three times daily 77,80,81 (level III); or 25 to 30 mg/kg/day divided into two or three doses not exceeding 750 mg/day 82 (level III). Adolescents and adults probably need 500 mg three times daily 80 (level III). It is very important to remind patients to take the entire 10-day course, even though they will likely feel better in the first few days of treatment. This will improve the chance of GABHS eradication and prevent rheumatic fever. An injection of intramuscular penicillin G (Benzathine penicillin) can also be given in place of the 10-day course of the oral preparation. This is recommended when compliance is likely to be low or in cases of possible rheumatic fever. The injection is painful and should be given into a large muscle mass. The pain can be reduced by warming the injected solution or by using prepa- rations that include procaine penicillin. The recommended dose is 600,000 Units IM (<27 kg) or 1.2 million Units (>27 kg). Amoxicillin is often used in place of penicillin because of convenience or familiarity. 83 However, treatment with this broader-spectrum antibiotic is unnecessary and may increase antibiotic resistance. 84 One recent trial examined the use of this antibiotic as a once-daily therapy 85 (level I). One hundred and fifty children were randomly assigned to once-daily amoxicillin or three times daily penicillin V for 10 days. There was no significant difference in the clinical or bacteriologic outcome.Amoxicillin also requires a completed 10-day course of therapy. The major problem with penicillin therapy, as noted above, is the potential for allergic reactions. These are rare and occur more often in adults than in children. Penicillin reaction can produce urticaria, angioneurotic edema, serum sickness, or, rarely, anaphylaxis. Many children are diagnosed with penicillin allergy due to the appearance of a rash during a pre- Acute Rhinitis and Pharyngitis 93 vious antibiotic treatment. Although this rash may be due, in fact, to a viral agent, it is often mislabeled as an allergic reaction. Thus, many physicians opt to treat with a nonpenicillin antibiotic. Even though there is little level I evidence for the use of penicillin as a first-line therapy, most would argue that the long experience with this medication, its safety profile, and lack of bacterial resistance, have proved it to be the drug of choice in GABHS pharyngitis (rec- ommendation A) (Table 5–6). Macrolides The macrolide group of antibiotics provide an acceptable alternative to penicillin in the allergic patient. 86,87 Although rare in North America, there are some areas of the world where there is streptococcal resistance to macrolides 88 The major problems with the older versions of these drugs have been the gastrointestinal side effects such as abdominal dis- comfort. The most commonly prescribed macrolides are erythromycin estolate (20 to 40 mg/kg/day in two to four divided doses) or erythromycin ethylsuccinate (40 mg/kg/day in two to four divided doses) 79,82 (level III). Both these medications require a 10-day course. The newer macrolides are much better tolerated, being well absorbed orally and resulting in fewer gastrointestinal effects. Clarithromycin (15 mg/kg/day in two divided doses) can be given on a full or empty stomach but requires a 10-day course 89 (level I); 90,82,79 (level III). Azithromycin (12 mg/kg/day once daily, maximum 500 mg/day) must be given on an empty stomach but need only be given for 5 days. 91 (level I); 79 (level III). Both these newer med- ications compare favorably with oral penicillin in the treatment of GABHS pharyngitis. There is good evidence that the newer macrolides provide an equivalent, though expen- sive, alternative to penicillin in patients with GABHS pharyngitis (recommendation A) (Table 5–6). Cephalosporins Cephalosporins are effective in a variety of infections including GABHS pharyngitis. Broad- spectrum cephalosporins (such as cefaclor, cefixime, cefprozil. cefuroxime axetil, cefpo- doxime proxetil) should not be used as they provide a broader coverage than necessary. Antibiotics with a narrower spectrum (for example, cefadroxil or cephalexin) are preferable and require a 10-day course for the eradication of GABHS. It should be noted that approx- imately 20 percent of penicillin-allergic individuals are also allergic to cephalosporins. Some reports have concluded that a 10-day course of an oral cephalosporin is superior to penicillin in the eradication of GABHS from the pharynx. In one study, a 10-day course of ceftibuten oral suspension was compared to penicillin V in children (aged between 3 and 18 years) who were treated for pharyngitis and scarlet fever 92 (level I). Overall clinical suc- cess at the primary end point of treatment was achieved in 97 percent of ceftibuten-treated patients versus 89 percent of penicillin V-treated patients. Streptococci elimination after 5 to 7 days of therapy was achieved in 91 percent of ceftibuten-treated patients versus 80 per- cent of penicillin V-treated patients. No patient developed rheumatic fever or nephritis. These data suggest that once-daily ceftibuten is as safe as and more effective than penicillin V three times daily for the treatment of GABHS pharyngitis. In a similar study that compared cefuroxime axetil with penicillin V suspension, GABHS was eradicated from 94 percent of the cefuroxime patients and 84.1 percent of the penicillin- treated patients 93 (level I). In this study, cefuroxime axetil suspension given twice daily resulted in significantly greater bacteriologic and clinical efficacy than that of penicillin V suspension given three times daily to pediatric patients presenting with acute pharyngitis and a positive throat culture for GABHS. Another study reported similar results with cefpo- doxime proxetil with greater eradication of Streptococcus pyogenes when compared with peni- cillin 94 (level I). 94 Evidence-Based Pediatrics [...]... children JAMA 1994;272:1025 30 98 Evidence- Based Pediatrics 7 English JA, Bauman KA Evidence- based management of upper respiratory infection in a family practice teaching clinic Fam Med 1997;29 :38 –41 8 Mainous AG III, Hueston WJ, Clark JR Antibiotics and upper respiratory infection: do some folks think there is a cure for the common cold [see comments] J Fam Pract 1996;42 :35 7–61 9 Mainous AG III, Hueston... drug prescribing among office -based physicians in the United States JAMA 1995;2 73: 214–9 2 Dowell S, Marcy M, Phillips W, et al Otitis media—principles of judicious use of antimicrobial agents Pediatrics 1998;101:165–71 3 Berman S, Roark R, Luckey D Theoretical cost effectiveness of management options for children with persisting middle ear effusions Pediatrics 1994; 93: 3 53 63 4 Paradise JL, Rockette HE,... Europe J Antimicrob Chemother 1991;28 :31 –8 41 Arason V, Kristinsson K, Sigurdsson J, et al Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross-sectional prevalence study Br Med J 1996 ;31 3 :38 7–91 42 Hathaway TJ, Katz HP, Dershewitz RA, et al Acute otitis media: who needs post-treatment follow-up? Pediatrics 1994;1994:1 43 7 43 Cohen R, Levy C, Boucherat M, et... Media, Atlanta, GA, March 2 0-2 1, 1997 118 Evidence- Based Pediatrics 57 Drugs for treatment of acute otitis media in children Med Letter Drugs Ther 1994 ;36 :1 9-2 1 58 Poole MD Implications of drug-resistant Streptococcus pneumoniae for otitis media Ped Infect Dis J 1998;17:9 53 6 59 Neu HC Diagnosis and treatment: drugs five years later: amoxicillin Ann Intern Med 1979;90 :35 6–60 60 Berman S Otitis media... Pediatr Ann 1998;27:277–80 96 Evidence- Based Pediatrics Table 5–4 Summary of Therapy: Common Cold Intervention Age Group Level of Evidence Recommendation Steam inhalation therapy Adults Level I to II-1 C No evidence for children Antihistamines Children Adolescents and adults Level I Level I E C Decongestants Children Adolescents and adults Level I to II-2 Level I to II-2 D C Cough suppressants and... September 28 - October 1, 1997 76 Nelson CT, Mason EO, Kaplan SL Activity of oral antibiotics in middle ear and sinus infections caused by penicillin-resistant Streptococcus pneumoniae: implications for treatment Pediatr Infect Dis J 1994; 13: 585–9 77 Cetron M, Breiman R, Jorgensen J Multi-site population -based surveillance for drug-resistant Streptococcus pneumoniae (DRSP) [abstract C-2 83] , 97th General... Pediatr 19 93; 122:799–802 33 Kuhn JJ, Hendley JO, Adams KF, et al Antitussive effect of guaifenesin in young adults with natural colds Objective and subjective assessment Chest 1982;82:7 13 8 34 Hayden FG, Diamond L, Wood PB, et al Effectiveness and safety of intranasal ipratropium bromide in common colds A randomized, double-blind, placebo-controlled trial [see comments] Ann Intern Med 1996;125:89–97 35 Diamond... approach to the otitis prone child Contemp Pediatrics 1987;4 :30 –54 8 Hayden GF Acute suppurative otitis media in children Diversity of clinical diagnostic criteria Clin Pediatr 1981;20:99–104 9 Kaleida P, Stool SE Assessment of otoscopists’ accuracy regarding middle-ear effusion Am J Dis Child 1992;146: 433 –5 10 Klein JO Otitis media Clin Infect Dis 1994;19:8 23 33 11 Karma P, Sipila M, Kayaja M, et al... diagnosis Am Fam Phys 1996; 53: 1200–6 116 Evidence- Based Pediatrics 16 Stool SE, Berg AO Managing otitis media with effusion in young children Can J Pediatr 1995.2 .37 9–87 17 Babonis TR, Weir MR, Kelly PC Impedance tympanometry and acoustic reflectometry at myringotomy Pediatrics 1991;87:475–80 18 Belshe R, Mendelman P, Treanor J, et al The efficacy of live attenuated, cold-adapted, trivalent, intranasal... colds Antimicrob Agents Chemother 1987 ;31 :11 83 7 100 Evidence- Based Pediatrics 45 Farr BM, Gwaltney JM Jr The problems of taste in placebo matching: an evaluation of zinc gluconate for the common cold J Chronic Dis 1987;40:875–9 46 Weismann K, Jakobsen JP, Weismann JE, et al Zinc gluconate lozenges for common cold A double-blind clinical trial Dan Med Bull 1990 ;37 :279–81 47 Godfrey JC, Conant Sloan . than 43 C for 60 minutes. In the sec- ond part of the study, 32 individuals received a 1-hour treatment with steam ( 43 C) and were compared with 36 who received room air (20 to 24°C). A 7-day. cefpo- doxime proxetil with greater eradication of Streptococcus pyogenes when compared with peni- cillin 94 (level I). 94 Evidence- Based Pediatrics Results of these studies have been cited as evidence. treatment 96 Evidence- Based Pediatrics Table 5–4 Summary of Therapy: Common Cold Intervention Age Group Level of Evidence Recommendation Steam inhalation Adults Level I to II-1 C therapy No evidence