Delayed Prescribing—A Sensible Approach to the Management of Acute Otitis Media

Based on experience in Holland,¹ evidence from systematic reviews,² and recent evidence in the United Kingdom,³ many northern European countries, including the United Kingdom, have developed guidelines to advise physicians to delay for a short time before prescribing antibiotics for children with acute otitis media (AOM).⁴ The Dutch developed a policy of no prescription for AOM unless the patient has significant otalgia, fever, or both 72 hours after seeing the physician, or if a prolonged otic discharge develops.⁵ One study showed that if this watchful-waiting approach is used, there are likely to be few cases of complications (only 1 case of mastoiditis occurred in a 5000-patient cohort, and this patient had waited nearly a week).¹ Patients and their families should be given clear advice about returning to see their physician if signs of complications occur, ie, worsening systemic features such as fever or vomiting.

The study by Spiro and colleagues⁶ in this issue of JAMA is a welcome addition to the literature, suggesting that a “wait-and-see” approach in the management of AOM is effective in the emergency department setting. Children randomized to the wait-and-see approach used fewer antibiotics (38% compared with 87%), and there was no difference in subsequent fever, otalgia, or unscheduled visits for medical care. The study provides evidence that there is probably little to be gained in terms of symptom resolution by immediate prescription of antibiotics for most children. Compared with previous trials of delayed antibiotic prescribing, the effect sizes are smaller than a Canadian study⁷ and similar to a United Kingdom study³ that used similar exclusion criteria. Further evidence of the limited utility of providing immediate antibiotics comes from a Cochrane review that suggests more than 15 children have to be treated for 1 child to benefit.²

The study by Spiro at al⁶ demonstrates that the wait-and-see approach is acceptable to parents in the United States, a finding that could have a substantial influence on the traditionally high rate of prescribing antibiotics for AOM in the United States. It also demonstrates that a wait-and-see approach works in the emergency department setting, where patients have no ongoing relationship with a physician. That children in such a setting might have worse outcomes had been a concern.

However, several notes of caution are required. Both this study and previous studies excluded children whom clinicians considered to be toxic, and thus it would be unwise to extrapolate these results to very sick children. Furthermore, most children with AOM present within 24 hours after symptom onset.³ It would be unwise to suggest a further delay of 72 hours if the child already has a high fever and severe otalgia for 72 hours or longer, so the delaying times should be adjusted for the length of prior severe otalgia and fever. Especially in an emergency department setting, it would be advisable for physicians to emphasize the importance of repeat assessment if symptoms do not improve following the delayed prescription.

There are several potential advantages of delayed prescribing. First, delayed prescribing rationalizes antibiotic use. Evidence from a systematic review of delayed prescribing trials for a variety of respiratory infections⁸ supports findings from the current study that delayed prescribing is likely to reduce antibiotic use. The study by Spiro et al⁶ suggests that a waiting period of 48 hours is likely to result in 62% of patients not using antibiotics; advising a wait of 72 hours is likely to result in even fewer antibiotic prescriptions being used.³ When patients are asked to return to collect their delayed antibiotic prescription from the physician's office, antibiotic use is likely to be little greater than using a policy of no initial offer of antibiotics.^{9 - 10} Second, delayed prescribing changes patient and family beliefs about antibiotics. Prescribing antibiotics probably fuels a cycle of belief in antibiotics, subsequent reattendance, and further antibiotic request and use.^{11 - 12} Delayed prescribing appears to be as effective as not prescribing antibiotics in changing beliefs, and it also changes subsequent consultation behavior. Delayed prescribing has similar or lower rates of reattendance when compared with not prescribing.^{10 - 11} Third, delayed prescribing achieves acceptable symptom control. Previous systematic reviews of delayed prescribing have called for more evidence on this point. Most trials, including the trial by Spiro et al,⁶ do not report the severity of symptoms in the first few days.¹³ However, a trial reporting severity of symptoms suggested good control of symptom severity.³ Although patients with AOM have considerable pain in the first 24 to 48 hours after the consultation—hence, the importance of advice about use of systemic analgesics, topical analgesics, or both—antibiotics make little difference at this stage.³ And fourth, delayed prescribing provides a backup plan and rapid access to antibiotics when there is uncertainty about which children will do poorly if antibiotics are not provided and thus may be preferable to not prescribing initially.

An important consideration is whether the wait-and-see approach has clinical dangers. Evidence from the United Kingdom and European studies suggests that localities or countries that have lower prescribing of antibiotics have higher admission rates for mastoiditis.^{13 - 14} Furthermore, time trends have suggested that increased use of delayed prescription by clinicians for upper respiratory tract infection may be associated with an increase in mastoiditis in children.¹⁴ However, these data are based on ecological observations and have well-known limitations. Even assuming such ecological data do provide evidence of genuine harm, the data suggest that several thousand prescriptions would be required to prevent 1 case of mastoiditis in developed countries.^{14 - 15} Furthermore, the increased use of delayed prescriptions by clinicians in the United Kingdom study¹⁴ followed a trial in upper respiratory tract infection (acute sore throat),¹⁵ and it seems possible that clinicians used guidance for upper respiratory tract infections (which is longer than for AOM) inappropriately for AOM. Parents of children with AOM should be advised to wait no longer than 72 hours after the consultation if significant fever or otalgia persists,^{1 ,3} whereas for sore throat, the wait-and-see time can be longer.⁹

There may be several alternatives to delayed antibiotic prescribing, including the following: (1) not to prescribe at all, which is probably a less safe option¹ ; (2) to prescribe in all cases, which is likely to lead to adverse effects, antibiotic resistance,¹⁶ and possibly more complications associated with antibiotic resistance³ ; (3) not to prescribe but to advise patients to return if the child is worsening or not improving, which provides the clinician with more control but may result in higher reconsultation rates for no clear benefit¹⁰ ; or (4) to prescribe antibiotics for those likely to develop prolonged illness or adverse events; unfortunately, there are few good prospective clinical studies to define such at-risk groups and the benefit of antibiotics in such groups. Meanwhile, every clinician uses his/her own criteria to target antibiotics in respiratory infections.¹⁷

Further evidence is needed to inform clinicians about when to use delayed prescribing. Studies are needed to define children at risk of adverse outcomes. For instance, most severely ill children and children about whom the physician was concerned for other reasons will not have entered the trial by Spiro et al⁶ or other trials. Further studies also are needed to determine the most effective alternatives to antibiotics. However, given the current evidence base, a reasonable approach would be as follows. When the child is not systemically ill and the physician has no major concerns, delayed prescribing can be used. If the physician has concerns about sicker or at-risk patients (eg, those with systemic symptoms or comorbidity, infants younger than 6 months), then antibiotics should be prescribed.

If parents are given clear information about the timing of antibiotic use and specific guidelines for signs and symptoms that should trigger reassessment, delayed prescribing probably has its place, should be acceptable to parents, appears reasonably safe, and provides a significant step in the battle against antibiotic resistance.