Key points

Introduction

Acute rhinosinusitis is one of the most common health problems in children and has increased in prevalence and incidence. It causes significant physical symptoms, negatively affects quality of life, and can substantially impair daily functioning. Prospective longitudinal studies performed in young children (6–35 months of age) illustrated that viral upper respiratory tract infection (URTI) occurred with an incidence of 6 episodes per patient-year, and that 8% (0.5 episodes per patient-year) were complicated by acute rhinosinusitis. The pathophysiological cause of rhinosinusitis may be obstruction of sinus drainage pathways (sinus ostia), ciliary impairment, and altered mucus quantity and quality.

Acute rhinosinusitis is defined as an inflammation of the mucosal lining of the nasal passage and paranasal sinuses lasting up to 4 weeks, and can be caused by various factors, including environmental irritants, allergy, and viral infection, bacteria, or fungi.

Introduction

Acute rhinosinusitis is one of the most common health problems in children and has increased in prevalence and incidence. It causes significant physical symptoms, negatively affects quality of life, and can substantially impair daily functioning. Prospective longitudinal studies performed in young children (6–35 months of age) illustrated that viral upper respiratory tract infection (URTI) occurred with an incidence of 6 episodes per patient-year, and that 8% (0.5 episodes per patient-year) were complicated by acute rhinosinusitis. The pathophysiological cause of rhinosinusitis may be obstruction of sinus drainage pathways (sinus ostia), ciliary impairment, and altered mucus quantity and quality.

Acute rhinosinusitis is defined as an inflammation of the mucosal lining of the nasal passage and paranasal sinuses lasting up to 4 weeks, and can be caused by various factors, including environmental irritants, allergy, and viral infection, bacteria, or fungi.

History

Suspicion of acute bacterial rhinosinusitis (ABRS) is based on clinical symptoms and signs when at least 2 major or 1 major and 2 minor criteria are present ( Table 1 ). The most common presentation is a persistent (and nonimproved) nasal discharge or cough (or both) lasting more than 10 days. Typical clinical manifestations of ABRS in children are cough that worsens at night (80%), nasal symptoms (anterior or posterior discharge, obstruction, and/or congestion) (76%), and fever for more than 3 days (63%). Malodorous fetid breath is common, whereas facial pain and swelling, sore throat, and headache are rare in children. There is only one study of children that correlated the presence of respiratory signs and symptoms with the findings of sinus aspiration.

Differentiating viral URTI from ABRS is critical and remains difficult. The main feature of viral URTI is the presence of nasal symptoms (discharge and congestion/obstruction) or cough or both, and sometimes also a scratchy throat. Fever is absent in most patients and when present it occurs early in the illness. Fever and constitutional symptoms generally disappear within 24 to 48 hours, after which the respiratory symptoms predominate. Most with acute viral rhinosinusitis improved spontaneously after 7 to 12 days. Generally, the nasal discharge is clear and watery initially, but often its quality changes over time. In most individuals, the discharge turns thicker and more mucoid and purulent. After several days, these changes are reversed, with the purulent discharge turning mucoid and then clear, or dry. These changes occur in uncomplicated viral URTIs without the use of antimicrobials.

The characteristic presenting symptoms that are commonly associated with a bacterial rather than viral infection were evaluated by 5 consensus panels, created by 5 national societies. The panels highlighted 3 clinical presentations that should prompt consideration of ABRS rather than a viral URTI:

• 1.
  

  Onset with persistent symptoms (respiratory symptoms that are present for more than 10 but fewer than 30 days with no improvement). The criterion of duration of symptoms for 10 or more days or signs and worsening of symptoms within 10 days after initial improvement (double-sickening) is used to differentiate between bacterial versus viral acute rhinosinusitis. Patients manifest low-grade or nonresolving respiratory symptoms. Nasal discharge and daytime cough are common, whereas headache, facial pain, and fever are variable.

Confirmation of bacterial infection by sinus aspiration was possible in only about two-thirds of adults with symptoms lasting longer than 7 to 10 days. This suggests that additional qualifying clinical features are needed to differentiate viral from ABRS.

• 2.
  

  Onset with severe symptoms (an ill appearance with fever of at least 39°C [102°F] and purulent nasal discharge for at least 3–4 consecutive days at the beginning of illness) ( Table 2 ). The onset of fever, headache, and facial pain differs from an uncomplicated viral URTI, as the elevated temperature and purulent nasal discharge in ABRS occur at the beginning of the illness.

  
  
  
  

  Table 2

  
  

  Severity of symptoms and signs in acute bacterial sinusitis

  
  

  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

  Nonsevere	Severe
  Rhinorrhea (of any quality)	Purulent (thick, colored, opaque) rhinorrhea
  Nasal congestion	Nasal congestion
  Cough	Facial pain or headache
  Headache, facial pain, and irritability (variable)	Periorbital edema (variable)
  Low-grade or no fever	High fever (temperature ≥39°C)

  
  
  
  
• 3.
  

  Worsening symptoms after initial improvement with a new onset of fever, an increase in nasal discharge or cough, or the onset of severe headache (also called “double-sickening”).

The symptoms and signs of acute bacterial infection can be divided into nonsevere and severe (see Table 2 ). The severe form carries a higher risk of complications and mandates earlier use of antimicrobial therapy. The combination of high fever and purulent nasal discharge that lasts for at least 3 to 4 days suggests ABRS.

Individuals with ABRS often have edema of nasal mucous membranes, mucopurulent nasal discharge, persistent postnasal drip, fever, and malaise. The quality of the nasal discharge varies, and can be thin or thick, clear mucoid, or purulent. Tenderness and pain of the involved sinus can be induced by percussion of the affected sinus. Cellulitis can also be present overlying the affected sinus. Other findings, especially in acute ethmoiditis, are periorbital cellulitis, edema, and proptosis. Failure to transilluminate the sinus and the presence of nasal voice can be present in many patients. Direct smear of nasal secretions usually shows the predominance of neutrophils, and the observation of numerous eosinophils suggests allergy.

The symptoms are generally protracted and vary considerably in subacute or chronic bacterial sinusitis. Fever can be of low grade or absent. The patient may complain of malaise, easy fatigability, irregular nasal or postnasal discharge, frequent headaches, difficulty in mental concentration, anorexia, and pain or tenderness to palpation over the affected sinus. Cough and nasal congestion can persist, and a sore throat (because of mouth-breathing) is frequent.

Bacterial etiology

The most common bacteria recovered from pediatric and adult patients with community-acquired, ABRS are Streptococcus pneumoniae, nontypeable Haemophilus influenzae, Moraxella catarrhalis, Group A beta-hemolytic streptococci, and Staphylococcus aureus. The vaccination of children with the 7-valent pneumococcal vaccine, introduced in 2000 in the United States, brought about the decline in the recovery rate of S pneumoniae and an increase in H influenzae. S aureus is a common pathogen in sphenoid sinusitis. Recent data illustrate a significant increase in the rate of recovery of methicillin-resistant S aureus (MRSA) in patients with ABRS.

The infection is polymicrobial in about a third of the patients. Enteric bacteria are rarely isolated, and anaerobes account for about 8% of isolates and are usually recovered from ABRS associated with an odontogenic origin, mainly as an extension of the infection from the roots of the premolar or molar teeth. Pseudomonas aeruginosa and other aerobic and facultative gram-negative rods are mainly recovered from nosocomial rhinosinusitis (mostly in those with nasal tubes or catheters), the immunocompromised, and those with human immunodeficiency virus (HIV) infection or cystic fibrosis.

The dynamics of sinusitis, as well as otitis media, progress through several phases ( Fig. 1 ). The early phase is generally viral (mostly rhinovirus, adenovirus, influenza, and parainfluenza viruses) and lasts up to 10 days when complete recovery occurs in 99% of individuals. In a small number of patients, a secondary acute bacterial infection may emerge, generally caused by aerobic bacteria (ie, S pneumoniae , H influenzae, or M catarrhalis ). If resolution does not take place, anaerobic bacteria from the oropharyngeal flora become predominant over time. The mechanism by which viruses predispose to bacterial sinusitis may involve viral-bacterial synergy, induction of local inflammation that blocks the sinus ostia, increase of bacterial attachment to the epithelial cells, and disruption of the local immune defense.

The chronology of viral and bacterial causes of sinusitis.

Diagnosis

Treatment

The medical management of ABRS includes the use of antibiotics and adjuvants. The goals of therapy are to eliminate infection, decrease the severity and duration of symptoms, and prevent complications.

The management of sinusitis has become a challenging endeavor because the choice of appropriate antimicrobial agents has become more complex in recent years. This is because many of the predominant bacterial pathogens have developed resistance to commonly used antibiotics.

Culture obtained through direct aspiration or endoscopy can direct the selection of antimicrobials in the treatment of patients who fail to respond.

The emerging antimicrobial resistance among respiratory pathogens leads to the empiric overuse of broad-spectrum antibiotics, which generates selective pressure that promotes the emergence of greater antimicrobial resistance.

Several practice guidelines for the treatment of ABRS have been published in the United States within the past decade. These guidelines present varying opinions about the clinical criteria for initiation and choice of empiric antimicrobial regimens. The most recent guideline, developed by the IDSA, addresses some of the more controversial areas concerning initial choice of empiric management of ABRS in children and adults.

Empiric antimicrobial therapy should be started as soon as the clinical diagnosis of ABRS is made. Pharmacokinetic/pharmacodynamic principles should guide adequate dosing for respiratory tract infections. The utility of these diagnostic criteria for initiating antibiotic treatment has been validated by 3 randomized clinical trials in children. These studies demonstrated significantly higher cure rates in those treated with antibiotics compared with placebo. Some children with mild but persistent symptoms can be observed without giving antimicrobial therapy. These children need close observation and antimicrobials should be administered if improvement has not occurred within 3 days.

Amoxicillin is no longer considered to be adequate for the initial empiric treatment of ABRS in children. The addition of clavulanate improves the amoxicillin coverage against beta-lactamase–producing pathogens in ABRS, estimated to be present in about a quarter of patients. These include 25% to 35% of H influenzae and more than 90% of M catarrhalis.

The “standard-dose” of amoxicillin-clavulanate is 45 mg/kg/d orally 3 times a day or twice a day or 500 mg orally 3 times a day, and the “high-dose” amoxicillin-clavulanate is 90 mg/kg/d orally twice a day, or 2 g orally twice a day. The primary disadvantages of using the “high-dose” amoxicillin-clavulanate is the added cost and potentially higher incidence of adverse effects. “High-dose” amoxicillin-clavulanate is recommended for children with ABRS from locations with high rates of penicillin-nonsusceptible S pneumoniae , recent hospitalization, or antibiotic use within the past month; those with severe infection; those with evidence of systemic toxicity (eg, fever of 39°C [102°F] or higher); those with comorbidities; or those who are immunocompromised.

Studies determining S pneumoniae penicillin resistance using the revised Clinical Laboratory Standards Institute breakpoints defining penicillin-intermediate (minimal inhibitory concentration [MIC] 4 μg/mL; treatable with “high-dose” amoxicillin) and penicillin-resistant S pneumoniae (MIC ≥8 μg/mL; untreatable with amoxicillin), illustrated a higher rate of penicillin susceptibility (89%–93%) than those using earlier breakpoints. These studies suggest that unless the rate of penicillin-nonsusceptible S pneumoniae in the community is high (>10%), “standard-dose” amoxicillin-clavulanate should be adequate for the treatment of nonmeningitic S pneumoniae infections, including ABRS.

Oral cephalosporins are inactive against penicillin-resistant S pneumoniae . The activity of second-generation and third-generation oral cephalosporins (ie, cefaclor, cefuroxime axetil, cefpodoxime, cefprozil, cefdinir, and cefixime) is variable against penicillin-intermediate and resistant S pneumoniae . Cefpodoxime, cefuroxime axetil, and cefidnir are moderately active against this organism (<50% susceptible), and cefixime is less effective. The parenteral third-generation cephalosporins, cefotaxime and ceftriaxone, are active against all S pneumoniae, including penicillin-resistant ones and are the recommended second-line empiric therapy (in place of high-dose amoxicillin-clavulanate) for hospitalized children. The most active oral cephalosporin against both H influenzae and M catarrhalis (beta-lactamase positive and negative) is cefpodoxime, followed by cefixime, cefuroxime, and cefdinir. Cefaclor and cefprozil are least effective.

Because of the variable activity of second-generation and third-generation oral cephalosporins against S pneumoniae and H influenzae, they are no longer adequate as monotherapy for the initial empiric treatment of ABRS. If an oral cephalosporin is used, a third-generation cephalosporin (eg, cefpodoxime or cefixime) combined with clindamycin is recommended in regions with high isolation rates of penicillin-nonsusceptible S pneumoniae (≥10%).

The increased recovery of MRSA in ABRS requires consideration of the need for coverage against these organisms. A comparison of the rate of recovery of MRSA between 2001–2003 and 2004–2006 in 244 patients with ABRS illustrated a significant increase in the rate of recovery of this organism in patients (from 3% of patients to 10%, P <.01). This finding suggests the use of greater index of suspicion for the presence of MRSA in sinusitis and greater use of sinus cultures, especially in patients who do not improve or fail antimicrobial treatment after 48 hours of therapy. Because the nose can be a reservoir for S aureus , there is a concern that the recovery of S aureus could be attributable to contamination by the nasal flora during sinus aspiration or acquisition of middle meatus cultures. Accurate diagnosis of MRSA rhinosinusitis by microbiological cultures is essential for appropriate antimicrobial treatment.

Currently there is insufficient evidence to support the empiric coverage for MRSA in ABRS; however, in seriously ill individuals with suspected orbital or intracranial complication, and hospitalized patients with nosocomial sinusitis, empiric coverage for MRSA is helpful. Although vancomycin is considered the gold standard for therapy of MRSA, the increasing in vitro resistance to vancomycin and reports of clinical failures underscore the need for alternative therapies. Other agents with good in vitro activity include trimethoprim-sulfamethoxazole, clindamycin, linezolid, quinupristin-dalfopristin, daptomycin, and tigecycline.

For children with a history of immediate-type hypersensitivity response to penicillin, levofloxacin is recommended as an alternative to amoxicillin-clavulanate. In those with a history of non–type I hypersensitivity reaction to penicillin, a third-generation oral cephalosporin (eg, cefixime or cefpodoxime) in combination with clindamycin is recommended. Cefixime or cefpodoxime are active against most strains of H influenzae and M catarrhalis, whereas clindamycin is active against S pneumoniae, including penicillin-intermediate and penicillin-resistant strains.

The current treatment guidelines for ABRS that generally recommend a course of antimicrobial therapy for 10 to 14 days are derived from the length of therapy in many of the randomized controlled studies in adults. Some recommend treatment for 7 days beyond the time symptoms had resolved. Data in children, about the optimal duration of therapy, are nonconclusive because the efficacy of shorter courses has not been studied in a rigorous randomized manner. In children with ABRS, the longer treatment duration of 10 to 14 days is still recommended.

Clinically, improvement is expected within 3 to 5 days following initiation of effective antimicrobials. Complete resolution of symptoms occurred in 45% of children with ABRS on antibiotics compared with 11% of those on placebo. A study that compared “high-dose” amoxicillin-clavulanate to placebo illustrated that 19 (83%) of the 23 of children failed in the placebo group and 4 (17.4%) in the antibiotic group failed to improve or worsened within 3 days.

Most pathogens are eliminated from the maxillary sinuses by the third day of adequate antimicrobial therapy. A correlation was noted between time to bacterial eradication and time to clinical resolution. If symptoms and signs worsen despite 3 days of initial empiric antimicrobial therapy, the potential reasons for treatment failure must be evaluated. These include the presence of resistant pathogens, structural abnormalities, or a noninfectious etiology. Similarly, if there is no clinical improvement within 3 to 5 days despite initial empiric antimicrobial therapy, an alternate management strategy should be considered.

Consecutive endoscopic cultures from the maxillary sinus were performed of aspirates obtained from 20 patients with ABRS who failed initial empiric antimicrobial therapy. Increased level of resistance with MIC at least twofold higher than for the pretreatment isolate was identified in half of patients. These findings show that bacterial resistance should be considered in all patients who fail to respond to initial empiric antimicrobial therapy.

In choosing a second-line treatment in those who failed initial antimicrobial choice, an agent with a broader spectrum of activity and in a different antimicrobial class should be considered. Antimicrobials selected should be active against penicillin-nonsusceptible S pneumoniae and ampicillin-resistant H influenzae, as well as other beta-lactamase–producing respiratory pathogens.

The recommended second-line antimicrobial agents suitable for children with treatment failure to first-line agents are amoxicillin-clavulanate (90 mg/kg/d orally twice a day); clindamycin (30–40 mg/kg/d by mouth 3 times a day) plus cefixime (8 mg/kg/d orally twice a day) or cefpodoxime (10 mg/kg/d orally twice a day); or ceftriaxone (50 mg/kg/d intramuscularly).

It is advisable that cultures be obtained from the involved sinuses in those who have failed to respond to empiric antimicrobial therapy. Identification and susceptibility testing of the isolates can guide the choice of the second-line agent(s). Endoscopically guided middle meatus cultures can be considered as an alternative in older children ; however, their reliability in young children has not been established. Sinus puncture can be performed in children whose endoscopic cultures show no growth. Nasopharyngeal cultures are unreliable and are not recommended for the microbiologic diagnosis of ABRS.