Current approaches to the treatment of URTIs in children

Current approaches to the treatment of URTIs in children SPL Ed Clarke PhD, MRCPCH and Adam Finn MA, PhD, FRCP, FRCPCH Our series Prescribing in children gives practical advice on the management of childhood problems in general practice. Here, the authors discuss the management of upper respiratory tract infections. Figure 1. URTIs are extremely common in childhood; clinical assessment should be made by an appropriately trained individual, particularly as other serious infections are less easily distinguished in younger children Upper respiratory tract infections (URTIs), including the common cold, acute pharyngitis and tonsillitis, acute sinusitis and acute otitis media (AOM) are extremely common in childhood. Over the winter months preschool children can expect to suffer with a common cold on an approximately monthly basis. The incidence peaks between one and five years of age, being a little lower in infancy and in older children. 1 Bacterial sinusitis is said to complicate between 5 and 10 per cent of common colds in childhood and is therefore also a frequent complaint. 2 By the age of two the vast majority of children will have suffered an episode of AOM, which may also follow an initial viral infection, although it is said to have a purely viral aetiology in as few as 20 per cent of cases. 3 The incidence of phar yngitis and tonsillitis is also high in childhood, though the result of a group A streptococcal (GAS) infection in only between 15 and 30 per cent of cases, typically between the ages of 5 and 15 years. 4 Aetiology The majority of URTIs in children are associated with viral infections 5 and as such symptoms may respond to analgesic/antipyretic medications but will not require antibiotics. However, certain clinical syndromes are more commonly associated with a bacterial aetiology. Table 1 lists some of the agents commonly associated with URTIs in childhood. Diagnosis Decisions regarding therapy should only be made after an appropriate clinical assessment by an appropriately trained and skilled individual. This is particularly important in younger children in whom the clinical presentations may be less clear and other serious infections less easily distinguished. The aims of the assessment are: to ensure that an accurate diagnosis is made to assess illness severity to identify complications to confirm the absence of other more serious conditions (eg lower respirator y tract infections or, more rarely, invasive bacterial infections including sepsis and meningitis). The symptoms and signs, complications and normal clinical course of URTIs in children, which will guide treatment decisions, are outlined in Table 2. 40 Prescriber December 2010

General management The treatments available for URTIs in childhood are include non prescription medications for symptomatic relief and anti - biotics. Dosage and formulation Except where specifically relevant, dosages and formulations available will not be further discussed and readers are strongly encouraged to refer to the annually updated BNF for Children (BNFc). For many of the medications both proprietary and generic formulations will be available with nothing to specifically recommend one particular formulation over any other. Nonprescription medications A number of medications available without prescription have been used for the symptomatic relief of URTIs in children. These include: analgesics/antipyretics (paracetamol and ibuprofen) other nonprescription medications: decongestants (antihistamine and nonantihistamine based) cough suppressants expectorants. Analgesics/antipyretics If pain or fever is making a child unwell or distressed, the use of paracetamol or ibuprofen for symptomatic relief is appropriate. However, there is a lack of evidence to support the use of antipyretics with the sole aim of reducing fever in a child who is not distressed by it. 6 Both agents are effective in reducing fever, have comparable safety profiles and are well tolerated in otherwise healthy children. Many health professionals continue to use paracetamol as first-line therapy due to longer clinical experience with the drug. However, evidence suggests that ibuprofen is the more effective of the two antipyretics in initial fever reduction and the drug may therefore be recommended as first-line therapy. 7,8 The combination of paracetamol and ibuprofen is more effective than either medication alone in reducing fever and should be Common cold Pharyngitis and tonsillitis Acute bacterial sinusitis Acute otitis media Viruses rhinoviruses rhinoviruses RSV influenza influenza influenza parainfluenza parainfluenza parainfluenza RSV coronaviruses enteroviruses coronaviruses adenoviruses rhinoviruses adenoviruses HSV types 1 and 2 CMV EBV adenovirus CMV HSV coxsackievirus Bacteria group A streptococcus pneumococcus pneumococcus groups C and nontypeable Haemophilus nontypeable G streptococci group A Streptococcus Haemophilus anaerobes Moraxella group A Streptococcus diphtheria anaerobes Moraxella Other Mycoplasma and Chlamydia species Notes exclusively viral considered to be bacterial the isolated role of infections but in origin but typically viruses in otitis media predispose to the follows a viral URTI is unclear although development of both many episodes of acute bacterial bacterial otitis media sinusitis and acute will follow viral URTIs otitis media RSV respiratory syncytial virus; EBV Epstein-Barr virus; CMV cytomegalovirus; HSV herpes simplex virus Table 1. Infectious agents commonly associated with URTIs in children Prescriber December 2010 41

Common cold Pharyngitis and tonsillitis Acute bacterial sinusitis Acute otitis media Symptoms rhinorrhoea clear, sore throat persistent or worsening unilateral or bilateral and may become nausea or vomiting nasal discharge or cough earaches history discoloured before abdominal pain beyond 10 days following otorrhoea drying headache the onset of a common nasal obstruction cough cold sneezing myalgia purulent nasal discharge irritated throat history of GAS exposure (unusual) Signs fever more common tender LN enlargement and persistent fever unilateral or bilateral in young children lymphadenitis purulent nasal discharge erythematous bulging and usually only fever facial tenderness and tympanic membranes short lived (2 or 3 conjunctivitis periorbital oedema may fever days) at the start scarlet fever rash or viral be present but neither are purulent aural discharge of the illness exanthema sensitive or specific signs (unusual) persistent fever is oral ulceration or perioral unusual and should vesicles prompt reassessment and consideration of secondary bacterial complications (see below) mild-to-moderate cervical LN enlargement Typical 10 14 days 7 10 days 14 21 days 4 5 days duration in childhood Compli- results in acute suppurative peritonsillar intracranial extension with mastoiditis cations bacterial sinusitis or abscess formation, abscess formation meningitis acute otitis media in lymphadenitis, mastoiditis 5 10% of cases poststreptococcal (immune mediated) glomerulonephritis, arthritis, rheumatic fever LN lymph node; GAS group A Streptococcus Table 2. Clinical presentation and complications of URTIs in children considered when persistent fever is associated with ongoing distress. Attention should be paid to ensuring that parents have a clear understanding regarding the dosage and frequency, particularly when they are being used in combination, to minimise the risk of medication errors. 6 8 Aspirin should not be used in children due to the risks of Reye s syndrome. 9 Decongestants, cough suppressants and expectorants Despite their widespread availability and high cost, there is no evidence to support the use of any other nonprescription medication in children with URTIs. Accidental overdose, either due to misinterpretation of labelling or failure to secure medicines appropriately is an additional concern. Furthermore, neither the appropriate dosing schedules nor the safety of such medications have been reliably established; indeed a 42 Prescriber December 2010

AOM and acute sinusitis First-line oral agents: amoxicillin a macrolide antibiotic (if clearly documented history of penicillin allergy); clarithromycin or azithromycin is likely to be better tolerated than erythromycin Second line: a failure to respond to first-line oral antibiotics warrants review, firstly to consider whether an isolated viral infection is more likely, the duration of which may be prolonged (see Table 2), and secondly to ensure that other diagnoses and complications are not missed if a bacterial infection continues to be considered to be clinically likely and a clear failure to respond to initial therapy is confirmed, co-amoxiclav represents an appropriate second-line agent to cover both anaerobic bacteria and beta-lactamase producing organisms due to the documented increase in beta-lactamase producing organisms in the months following a course of a beta-lactam antibiotic, co-amoxiclav may be considered as a first-line agent in children who have received such therapy in the preceding 2 or 3 months 22 5 (AOM) to 7 (sinusitis) days treatment will generally be sufficient but should be guided by clinical response; 10 days may be required in some cases Pharyngitis and tonsillitis phenoxymethylpenicillin if GAS infection is proven, amoxicillin may be used as it is likely to be better tolerated, and compliance with the 3-times-daily regimen, as opposed to the 4-times-daily regimen for phenoxymethylpenicillin, is likely to be higher amoxicillin is generally avoided initially due to the risk of developing a significant rash in the case of an EBV-associated pharyngitis or tonsillitis a macrolide antibiotic (as previously) 10-days therapy remains standard; however, in the UK where nonsuppurative complications of GAS infection are rare, 6 days therapy has comparable efficacy to 10 days, even including only children with proven GAS throat infections, and may therefore be considered 29 Table 3. Choice of antibiotic for URTIs number of deaths have been attributed to the use or misuse of such medications in children. As such, they should not be recommended for symptomatic relief of URTIs in childhood. 10 12 Antibiotics The potential aims of antibiotic therapy in the management of URTIs in children are twofold: to prevent the development of serious complications to reduce the duration of an illness which will nonetheless be selflimiting. Issues surrounding antibiotic use Reducing serious complications Antibiotic prescribing for URTIs has fallen in the UK and some other parts of Europe over the past two decades, having peaked in the early part of the 1990s. 13 15 Further - more, in the UK the practice has generally been discouraged by the National Institute for Health and Clinical Excellence (NICE) in recent guidance. 6,16 Retrospective studies indicate that a large number of children need to be treated with antibiotics in order to prevent the development of rare suppurative complications, eg peritonsillar abscesses or mastoiditis. 15 For example, it has been calculated than between 5000 and 14 000 children need to receive antibiotics for AOM in order to prevent a single case of mastoiditis. 17,18 Furthermore, the majority of children who nevertheless go on to develop complications will have received antibiotics at their initial assessment, presumably on the basis of a more severe clinical presentation. 15 In line with these findings, the rate of serious suppurative complications appears to have increased little, if at all, as a result of the reduced rates of antibiotic prescribing. 13,14 The rarity of nonsuppurative complications (glomerulonephritis, rheumatic fever, arthritis) after GAS infection in current UK general practice means that any risk reduction as a result of presumptive antibiotic treatment for pharyngitis and tonsillitis is difficult to assess but is likely to be very low. 16 Therefore, the indiscriminate prescribing of antibiotics in an attempt to prevent complications is not justified. Nonetheless, it is important to recognise that antibiotics will be warranted for this purpose on rare occasions based on a clinical assessment of disease severity or a failure to follow the expected clinical course. Reducing illness duration The use of antibiotics with the sole purpose of reducing the duration of an illness must be weighed against the risk of antibiotic-associated sideeffects, the risk of driving clinically significant resistance in the individual and the population at large (see below) and the cost. While a modest decrease in pain between days 2 and 7 is associated with the prescription of antibiotics for AOM, 15 children need to be treated to prevent one suffering with some earache at two days. 19 44 Prescriber December 2010

Furthermore, 1 in 24 children will develop diarrhoea, vomiting or rash following antibiotic treatment leaving the risk/benefit analysis finely balanced. 19 To date, even guidelines that appear to discourage the routine use of antibiotics for AOM leave the onus on the managing clinician to use their judgement, particularly in young children. 16 Driving bacterial resistance Aside from the inevitable increase in the occurrence of antibiotic-associated side-effects and the unwarranted expense resulting from the injudicious prescribing of antibiotics, the risks of driving bacterial resistance is a further reason to discourage antibiotic use in the community. The rates of penicillin resistance in pneumococcal isolates across Europe strongly correlate with the levels of community penicillin use. 20,21 In individual children, a number of studies have confirmed the expected increase in the rate with which resistant bacteria are isolated from the throat following antibiotic treatment. 22 Furthermore, a significant association between antibiotic prescribing in general practice and Prescriber December 2010 45

levels of resistance has been demonstrated, although this is at a level whereby, for ever y 20 per cent reduction in ampicillin or amoxicillin prescriptions that is achieved, only a 1 per cent reduction in resistant isolates can be expected. 23 Guidelines regarding antibiotic use The following guidance is based predominantly on NICE clinical guidelines 16 and readers are referred to these for further details. When considering the use of anti - biotics, three distinct strategies may be employed: no antibiotics delayed antibiotics either following review at 48 72 hours or through the provision of a prescription for use at the same 48 72 hour time-point if a child is not judged by their care-giver to be clinically improving at that time immediate antibiotics. For the vast majority of children with URTIs, either no antibiotics or a delayed antibiotic prescribing strategy is recommended. Providing delayed antibiotics has been shown to reduce the levels of community antibiotic use without any increase in disease-associated morbidity in the majority of patients. 24,25 However, depending on a clinical assessment of severity, immediate antibiotics may also be considered, particularly in the following scenarios in which the likelihood of significant bacterial illness is at its highest: bilateral acute otitis media in children younger than two years acute otitis media with otorrhoea phar yngitis and tonsillitis with three or more of the following Centor criteria: 26,27 tonsillar exudates tender anterior cervical lympha - denopathy/lymphadenitis history of fever absence of cough. Care should be taken when using the Centor criteria in children, particularly young children. The criteria were developed in adults to predict the likelihood of GAS infection. The use of three Centor criteria has not been demonstrated to reliably predict a group of children who will benefit from antibiotic treatment. The threshold for prescribing antibiotics should also be reduced in children with underlying health problems, which may put them at an increased risk of complications. This would include children with significant respiratory or cardiac disease (eg cystic fibrosis, poorly controlled asthma, cyanotic congenital heart disease), congenital or acquired disorders of their immune system (eg primar y immunodeficiency syndromes, HIV, children receiving chemotherapy or other immunosuppressive agents) and other children judged to be at particular risk of developing complications (eg neuromuscular disorders). The strategy of antibiotic prescribing chosen should depend primarily on the clinical presentation and the identification of additional risk factors. However, it should also take the parent s expectations into account and must engage them with the final treatment decision. The provision of written information has been shown to reduce antibiotic prescribing and intention to reconsult in the future without reducing parental satisfaction and should therefore be considered. 16,28 Parents should be made aware of the expected clinical course and duration of the illness (see Table 2) not only to avoid further unnecessary consultations but also to highlight when seeking review is important. The choice of antibiotic is outlined in Table 3. Conclusion URTIs are common in childhood and the majority will be the result of viral infections. As such, they will be self-limiting, although symptomatic relief may be provided with ibuprofen and/or paracetamol. Other nonprescription medications should not be recommended and may have deleterious effects. Certain clinical presentations are more likely to be associated with a bacterial infection. Antibiotics may be prescribed to reduce symptom duration in a child who will nonetheless recover, in which case the likely benefit must be weighed against the chances of antibioticassociated side-effects, the development of antimicrobial resistance and the cost of treatment. A delayed prescription or reassessment in 48 72 hours may be appropriate in this situation. However, on certain occasions antibiotics will be Forum If you have any issues you would like to air with your colleagues or comments on articles published in Prescriber, the Editor would be pleased to receive them and, if appropriate, publish them on our Forum page. Please send your comments to: The Editor, Prescriber, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, or e-mail to prescriber@wiley.com 46 Prescriber December 2010

required on the basis of the initial clinical assessment due to the judged risks of developing serious complications. Although certain clinical presentations pose higher risk in this regard, thorough clinical assessment remains central to this judgement. All decisions regarding treatment must be made in conjunction with a child s primary care-giver and the provision of written information is also likely to be helpful. The importance of seeking reassessment for any child who is failing to follow the expected clinical course, as set out at the initial consultation, cannot be highlighted enough. References 1. Rosenstein N, et al. Pediatrics 1988;1001:181 4. 2. Wald ER, et al. Pediatrics 2009;124:9 15. 3. Vergison A, et al. Vaccine 2008;26 Suppl 7:G5 10. 4. Danchin MH, et al. Pediatrics 2007;120:950 7. 5. Harnden A, et al. Arch Dis Child 2007;92:594 7. 6. NICE. Feverish illness in children. Assessment and initial management in children younger than 5 years. CG47. May 2007. 7. Hay AD, et al. BMJ 2008;337:a1302. 8. Hay AD, et al. Health Technol Assess 2009;13:iii iv, ix x, 1 163. 9. Glasgow JF, et al. Arch Dis Child 2001;85:351 3. 10. Bell EA, et al. Otolaryngol Head Neck Surg 2010;142:647 50. 11. Lokker N, et al. Pediatrics 2009; 123:1464 71. 12. Shefrin AE, et al. Can Fam Physician 2009;55:1081 3. 13. Molstad S, et al. Lancet Infect Dis 2008;8:125 32. 14. Sharland M, et al. BMJ 2005;331: 328 9. 15. Keith T, et al. Curr Opin Infect Dis 2010;23:242 8. 16. NICE. Respiratory tract infections antibiotic prescribing. Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children. CG69. July 2008. 17. Petersen I, et al. BMJ 2007;335:982. 18. Thompson PL, et al. Pediatrics 2009;123:424 30. 19. Glasziou PP, et al. Cochrane Database Syst Rev 2004(1): CD000219. 20. Goossens H, et al. Lancet 2005;365:579 87. 21. Riedel S, et al. Eur J Clin Microbiol Infect Dis 2007;26:485 90. 22. Chung A, et al. BMJ 2007;335:429. 23. Priest P, et al. BMJ 2001;323:1037 41. 24. Spiro DM, et al. Jama 2006;296:1235 41. 25. Spurling GK, et al. Cochrane Database Syst Rev 2007(3): CD004417. 26. Centor RM, et al. Med Decis Making 1981;1:239 46. 27. Zwart S, et al. BMJ 2003;327:1324. 28. Francis NA, et al. BMJ 2009;339:b2885. 29. Altamimi S, et al. Cochrane Database Syst Rev 2009(1): CD004872. Dr Clarke is National Institute for Health Research clinical lecturer, School of Clinical Sciences, University of Bristol, and Professor Finn is head of the Academic Unit of Child Health at Bristol Medical School and an honorary consultant in paediatric infectious diseases and immunology at Bristol Royal Hospital for Children 48 Prescriber December 2010