Acute Bacterial Rhinosinusitis in Children

8/14/2019 Acute Bacterial Rhinosinusitis in Children

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Acute bacterial rhinosinusitis in children: Clinical features and diagnosis

INTRODUCTION — Acute rhinosinusitis is an illness that results from infection of one ormore of the paranasal sinuses. A viral infection associated with the common cold is themost frequent etiology of acute rhinosinusitis, more properly called viral rhinosinusitis.

(See "The common cold in children: Clinical features and diagnosis" and "The commoncold in children: Treatment and prevention" .)

Uncomplicated viral rhinosinusitis usually resolves without treatment in 7 to 10 days.Although acute bacterial rhinosinusitis (ABRS) also may resolve without treatment,treatment with antibiotics hastens recovery [1,2]. It is important to distinguish betweenuncomplicated viral rhinosinusitis and ABRS to prevent unnecessary use of antibiotics(table 1 ).

The clinical features and diagnosis of ABRS in children will be discussed here. Themicrobiology and treatment of ABRS in children and acute sinusitis and rhinosinusitis in

adults are discussed separately. (See "Acute bacterial rhinosinusitis in children:Microbiology and treatment" and "Acute sinusitis and rhinosinusitis in adults: Clinicalmanifestations and diagnosis" and "Acute sinusitis and rhinosinusitis in adults:Treatment" .)

ANATOMY — The paranasal sinuses develop as outpouchings of the nasal cavity (figure1) [3]. The onset and duration of development of the paranasal sinuses vary dependingupon the location, as described below. Development of the paranasal sinuses may not befully completed until 20 years of age; however, by 12 years of age, the nasal cavity and

paranasal sinuses in most individuals have nearly reached adult proportions [4].

The maxillary sinuses are present at birth and expand rapidly by four years of age[4]. Ciliary activity is necessary for drainage of secretions from the maxillary sinusinto the nose because the ostia are located high on the medial walls of the maxillarysinus [5].

The ethmoid sinuses are present at birth; they are comprised of a collection of tinyair cells, each with its own opening into the nose [4].

The sphenoid sinuses, which begin to develop during the first two years of life, aretypically pneumatized by five years of age, and attain their permanent size by 12years [4].

Development of the frontal sinuses is variable [3]. By six to eight years of age, thefrontal sinuses can be distinguished radiographically from the ethmoid sinuses [5],

but they do not complete their development for another 8 to 10 years. Between 1and 4 percent of adults have agenesis of the frontal sinuses, 80 percent have

bilateral frontal sinuses, and the remainder has unilateral frontal sinus hypoplasia[3].

DEFINITIONS — Sinusitis is inflammation of the mucosal lining of one or more of the paranasal sinuses [3]. The terms ―sinusitis‖ and ―rhinosinusitis‖ often are usedinterchangeably because inflammation of the paranasal sinuses is almost alwaysaccompanied by inflammation of the nasal mucosa [6].

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Inflammation of the sinuses is common during upper respiratory infection (URI) butusually resolves spontaneously. Acute bacterial rhinosinusitis (ABRS) occurs when there issecondary bacterial infection of the sinuses [3].

ABRS has been classified according to duration and recurrence as follows [7]:

Acute – symptoms completely resolve in <30 days Subacute – symptoms completely resolve in ≥30 and <90 days Recurrent acute – at least three episodes of <30 days’ duration separated by

intervals of ≥10 days without symptoms in a six -month period, or at least four suchepisodes in a 12-month period; individual episodes respond briskly to antibiotictherapy

Chronic sinusitis is defined by episodes of inflammation of the paranasal sinuses that last>90 days, during which patients have persistent symptoms (cough, rhinorrhea, nasalobstruction). Chronic rhinosinusitis may be related to noninfectious conditions such asallergy, cystic fibrosis, ciliary dyskinesia, gastroesophageal reflux, or exposure toenvironmental pollutants [8,9]. Chronic rhinosinusitis is discussed separately. (See"Clinical manifestations, pathophysiology, and diagnosis of chronic rhinosinusitis" and"Management of chronic rhinosinusitis" and "Microbiology and antibiotic management ofchronic rhinosinusitis" .)

EPIDEMIOLOGY — Acute bacterial rhinosinusitis (ABRS) is a common problem inchildren. It is estimated that approximately 5 to 7 percent of viral upper respiratoryinfections (URI) in children are complicated by the development of a secondary bacterialrhinosinusitis [2,10 ]. These proportions translate into a large number of infected individualsand substantial medical expenditures.

PATHOGENESIS — The paranasal sinuses are usually sterile [11-13 ]. However, becausethe membranes that line the nose are continuous with the membranes that line the sinuscavities, the paranasal sinuses may be contaminated with bacteria that colonize the nasalmucosa and nasopharynx. The contaminating bacteria are typically removed by mucociliaryclearance [3]. When mucociliary clearance is altered (eg, by conditions that damage theciliary epithelium or affect the number or function of cilia, the production or viscosity ofmucous, or the patency of the ostia), the sinuses may be inoculated with large numbers ofmicroorganisms, and infection may develop.

PREDISPOSING FACTORS — Viral upper respiratory infection (URI) is the mostimportant risk factor for the development of acute bacterial rhinosinusitis (ABRS) [14]. Therisk of viral URI is increased in children who attend day care [15]. Allergic rhinitis isanother important risk factor for ABRS [16-18 ]. URI and allergic rhinitis contribute to thedevelopment of ABRS through mucosal congestion and possibly by depressing the localand systemic immune response [19-21 ]. The epidemiology and clinical manifestations ofviral URI and allergic rhinitis are discussed separately. (See "The common cold in children:Clinical features and diagnosis" and "Allergic rhinitis: Clinical manifestations,epidemiology, and diagnosis" and "Epidemiology, clinical manifestations, and pathogenesisof rhinovirus infections" .)










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Less common predisposing factors to ABRS include [3]:

Anatomic obstruction (eg, nasal septal deformities; craniofacial anomalies;adenoidal hypertrophy; or nasal foreign bodies, masses, or polyps. The presence ofnasal polyps should prompt evaluation for possible cystic fibrosis and allergic

diatheses) [8]. (See "Etiologies of nasal symptoms: An overview" and "Cysticfibrosis: Clinical manifestations and diagnosis", section on 'Sinus disease' and"Clinical manifestations, pathophysiology, and diagnosis of chronic rhinosinusitis",section on 'CRS with nasal polyposis' .)

Mucosal irritants (eg, dry air, tobacco smoke, chlorinated water). Sudden changes in atmospheric pressure (eg, descent in an airplane) [20].

CLINICAL FEATURES

Symptoms and signs — The clinical and radiographic manifestations of acute bacterialrhinosinusitis (ABRS) in children are similar to those of viral upper respiratory infection(URI) [22]. The clinical course, particularly the persistence and severity of symptoms,helps to differentiate between uncomplicated viral URI and ABRS [6,7,23 ]. (See 'Clinicalcourse' below.)

In a small study in which the diagnosis of ABRS was confirmed by culture of the sinusaspirate, the frequency of clinical findings was as follows [23]:

Cough – 24 of 30 (chief complaint in 8) Nasal symptoms – 23 of 30 (chief complaint in 10) Fever – 19 of 30 children (not a chief complaint) Headache – 10 of 30 children (chief complaint in 8) Facial pain and swelling – 9 of 30 children (chief complaint in 2) Sore throat - 7 of 30 children (chief complaint in 1) Halitosis – 15 of 30 children (not a chief complaint)

Cough – Cough (wet or dry) is an important symptom in ABRS. The cough must be present during the day, but is often described as worse at night [6,7 ]. Nocturnal cough as asingle persistent symptom is nonspecific, and more suggestive of postnasal drip or reactiveairways disease [24]. The cough becomes more prominent with increasing duration ofillness [3].

Nasal symptoms – Nasal symptoms of ABRS include anterior or postnasal discharge,obstruction, and/or congestion. The nasal discharge may be of any quality: watery, serous,or purulent. Postnasal discharge may cause vomiting.

On examination, there may be mild erythema and swelling of the nasal turbinates withmucopurulent anterior nasal discharge. Drainage from the posterior ethmoids may lead to

purulent material in the posterior pharynx.







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Fever – Fever is a variable symptom of ABRS and may occur in association withcomplications. Temperature ≥39ºC (102.2ºF) for at least three consecutive days is acomponent of the severe presentation of ABRS. Fever that occurs in uncomplicated viralURI usually resolves after two days (figure 2 ) [25]. (See 'Acute bacterial rhinosinusitis'

below.)

Other findings – Complaints of headache and facial pain are also variable; they are lesscommon in young children [23,26 ]. Sinus tenderness (rare in young children) may beelicited with percussion of the upper molars or percussion or application of direct pressureover the body of the frontal or maxillary sinuses [27,28 ].

Some children may complain of sore throat or have bad breath, but these are not usually thesymptoms that lead to clinical presentation [23]. Postnasal discharge may cause vomiting.

Clinical course — Cough, nasal symptoms, and sore throat may occur with bothuncomplicated viral upper respiratory infection (URI) and acute bacterial rhinosinusitis(ABRS). The clinical course helps to differentiate the two clinical syndromes [6,7,23 ].

Uncomplicated URI — The course of most uncomplicated viral URIs is 7 to 10 days(figure 2 ) [25]. The patient may continue to have symptoms on the 10 th day, but almostalways the respiratory symptoms have begun to improve after peaking in severity on daysthree to six.

Most patients with uncomplicated viral URIs are afebrile. When fever occurs, it tends to doso early in the illness, with other constitutional symptoms (eg, headache, myalgias) [25,29 ].The fever and constitutional symptoms typically resolve in the first 24 to 48 hours when therespiratory symptoms become more prominent.

The nasal discharge generally begins as clear and watery, but the quality may changeduring the course of illness. Most typically, the nasal discharge becomes thicker and moremucoid and may become purulent (thick, colored, and opaque) for several days, after whichthe changes reverse — the purulent discharge becomes more mucoid, and then clear orsimply dries. The transition from clear to purulent to clear again occurs withoutantimicrobial therapy.

It is important to help parents of a child who has had URI symptoms for less than 10 daysor has thick, opaque nasal discharge to understand the difference between an URI and acute

bacterial sinusitis (table 1 ). It may be helpful to explain to them:

Most children with an uncomplicated viral URI get better on their own (only 5 to 7 percent of URIs are complicated by ABRS) (see 'Epidemiology' above)

Antibiotics will provide no benefit for a child with an uncomplicated viral URI andmay be associated with adverse effects (eg, the development of resistant pathogens,diarrhea, etc)



















































Acute bacterial rhinosinusitis — When viral URI is complicated by ABRS, there are three potential clinical presentations [6,7,23,30-32 ]:

Persistent symptoms – The most common clinical presentation is onset with persistent symptoms [6,7,33 ]. The cardinal clinical features are nasal symptoms

(anterior or posterior nasal discharge, obstruction, and/or congestion), cough, or both that persist for more than 10 but less than 30 days and are not improving [7].This last qualifier is extremely important. Some individuals with uncomplicatedviral URI have residual respiratory symptoms at the 10-day mark. To be considereda sign of ABRS, these respiratory symptoms must be persistent withoutimprovement .

The nasal discharge in patients with persistent symptoms may be of any quality:thick or thin, serous, mucoid, or purulent. The cough, which may be wet or dry,must be present during the daytime, although it is often described to be worse atnight [6,7 ].

Severe symptoms – ABRS can manifest with severe symptoms at onset. Inchildren, this presentation is defined by a combination of temperature ≥39ºC(102.2ºF), concurrent purulent nasal discharge for at least three to four consecutivedays, and ill-appearance [6,7 ]. Persistent high fever for at least three to four daysdistinguishes this presentation from an uncomplicated viral URI (in which fever isusually low-grade and present for less than 48 hours (figure 2 ) [25]).

Worsening symptoms – ABRS also can present with worsening symptoms (ie, a biphasic illness or "double sickening") [30,34 ]. In this presentation, the initialillness is similar to an uncomplicated viral URI from which the patient seems to berecovering. However, on the sixth or seventh day, the patient becomes acutely andsubstantially worse with an increase in respiratory symptoms (exacerbation of nasaldischarge or nasal congestion or daytime cough), a new onset of severe headache orfever, or a recurrence of fever if it had been present at the onset of illness.

Complications — Children with untreated bacterial rhinosinusitis are at risk for seriouscomplications, which may be the presenting manifestation. Complications may result fromorbital or intracranial extension. The exact rate of complications of ABRS is unknown, butthey are estimated to occur in approximately 5 percent of patients hospitalized forrhinosinusitis [35,36 ].

Findings that should prompt consideration of intracranial extension include [37,38 ]:

The combination of periorbital/orbital swelling with persistent headache andvomiting

Vomiting and headache that requires hospital admission, particularly in olderchildren

Altered level of consciousness Focal neurologic deficits Signs of meningeal irritation (eg, stiff neck)

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Clinical manifestations specific to orbital and intracranial complications of rhinosinusitisare listed below (table 2 ) [3,39-43 ]:

Preseptal (periorbital) cellulitis – Mild complication characterized by swelling anderythema of the lids and periorbital area; there is no proptosis or limitation of eye

movement (see "Preseptal cellulitis" ) Orbital cellulitis – Pain with eye movement, conjunctival swelling (chemosis), proptosis, limitation of eye movements (ophthalmoplegia), diplopia, vision loss (see"Orbital cellulitis" )

Septic cavernous sinus thrombosis – Bilateral ptosis, proptosis, ophthalmoplegia, periorbital edema, headache, change in mental status (see "Septic dural sinusthrombosis" )

Meningitis – Fever, headache, nuchal rigidity, change in mental status (see "Clinicalfeatures and diagnosis of acute bacterial meningitis in children older than one monthof age", section on 'Clinical features' )

Osteomyelitis of the frontal bone associated with a subperiosteal abscess (Pott puffytumor) – Forehead or scalp swelling and tenderness, headache, photophobia, fever,vomiting, lethargy [44]

Epidural abscess – Papilledema, focal neurologic signs, headache, lethargy, nausea,vomiting (see "Epidural abscess", section on 'Intracranial epidural abscess' )

Subdural abscess – Fever, severe headache, meningeal irritation, progressiveneurologic deficits, seizures, signs of increased intracranial pressure (papilledema,vomiting) [45]

Brain abscess – Headache, neck stiffness, changes in mental status, vomiting, focalneurologic deficits, seizures, third and sixth cranial nerve deficits, papilledema (see"Pathogenesis, clinical manifestations, and diagnosis of brain abscess" )

RADIOLOGIC FEATURES — Plain radiographic or computed tomography (CT) findingsthat are compatible with sinus inflammation include (image 1 ) [8,46 ]:

Complete opacification Mucosal thickening of at least 4 mm Air-fluid level

However, abnormal imaging studies cannot distinguish between bacterial, viral, or othercauses of sinus inflammation [6,47 ]. Observational studies performed with plainradiographs, CT, and magnetic resonance imaging have demonstrated frequentabnormalities in the paranasal sinuses of children [48-51 ] and adults with uncomplicatedviral upper respiratory infection [52].

Imaging studies are not usually necessary in the evaluation of children with uncomplicatedacute bacterial rhinosinusitis. When imaging studies are obtained, abnormal findings should

be interpreted in the context of clinical findings [48,53 ]. Normal imaging studies (CT or plain film) of the paranasal sinuses in children with respiratory symptoms excludesrhinosinusitis.

DIAGNOSIS




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Uncomplicated ABRS — The diagnosis of uncomplicated acute bacterial rhinosinusitis(ABRS) in children is usually made clinically. Imaging studies are not recommended forthe diagnosis of uncomplicated ABRS [7].

We suggest that both of the following criteria be met for diagnosis [6,7,23,30-32 ]:

Symptoms and signs compatible with sinus inflammation (daytime cough, nasalsymptoms, or both) (see 'Symptoms and signs' above), and

Clinical course suggestive of bacterial rather than viral infection, including (see'Acute bacterial rhinosinusitis' above):

Symptoms present without improvement for >10 and <30 days, or Severe symptoms (ill appearance, temperature ≥39ºC (102.2°F), and purulent nasa l

discharge for ≥3 consecutive days), or Worsening symptoms (increase in respiratory symptoms, new onset of severe

headache or fever, or recurrence of fever after initial improvement)

We have chosen these relatively strict criteria to limit the diagnosis to patients most likelyto benefit from antimicrobial therapy [6]. These criteria agree with those of amultidisciplinary consensus panel and clinical guidelines developed by the AmericanAcademy of Pediatrics and the Infectious Diseases Society of America [6,7,31,32 ]. Theyare supported by a study in which 77 percent of sinus aspirate cultures in children with

persistent or severe symptoms grew ≥10 4 colony forming units of pathogenic bacteria [23].

Complicated ABRS — Imaging studies are usually performed in children suspected to haveorbital and intracranial complications of ABRS [7,24 ]. (See 'Complications' above.)

It is recommended that children with potential orbital or intracranial complications ofABRS undergo contrast-enhanced computed tomography (CT) imaging of the orbits,sinuses, and brain [6,7,47 ]. Magnetic resonance imaging (MRI) is an alternative.Advantages of CT include increased availability, lack of need for sedation, and betterdemonstration of the sinus anatomy including the ostiomeatal complex and bony structures[6]. Advantages of MRI include improved ability to detect intracranial complicationswithout exposure to radiation [54-56 ].

Microbiologic studies — Microbiologic studies usually are not necessary for children withuncomplicated ABRS who improve as expected with antimicrobial therapy. (See "Acute

bacterial rhinosinusitis in children: Microbiology and treatment", section on 'Response totherapy' .)

However, attempts should be made to identify the pathogen in children who are toxic-appearing (eg, lethargic, poorly perfused, cardiorespiratory compromise), those with orbitalor intracranial complications, immunocompromised children, children with recurrentABRS, and children who fail to respond to antimicrobial therapy [6]. Isolation of a

pathogen and antimicrobial susceptibilities permit better targeting of antimicrobial therapy.















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When identification of a pathogen is necessary in children, sinus aspiration is the preferredmethod for obtaining samples [6,57 ]. Sinus aspiration should be performed by a specialist[6]. Appropriate sterilization of the area of the nose through which the trocar will pass isessential to avoid contamination from the nasal cavity [58]. Aspirated fluid should be sentfor Gram stain, aerobic and anaerobic culture, and antimicrobial susceptibility testing.

Sinus aspiration with a culture that yields ≥104

colony-forming units/mL of a significant pathogen is the gold standard for diagnosis of ABRS [6,30,59,60 ].

Nasopharyngeal and/or throat cultures should not be used as a surrogate for sinus aspirationin children with suspected ABRS [8]. There is a poor correlation between nasopharyngealand throat cultures and bacteria isolated from sinus aspirates [23].

Endoscopically obtained cultures of the middle meatus are of no use in children suspectedto have ABRS because the meatus is colonized with Streptococcus pneumoniae ,

Haemophilus influenzae , and Moraxella catarrhalis , even when children are asymptomatic[61].

DIFFERENTIAL DIAGNOSIS — The main consideration in the differential diagnosis ofacute bacterial rhinosinusitis is the distinction between viral upper respiratory infection orallergic inflammation and secondary bacterial infection of the paranasal sinuses. Theclinical course, particularly the persistence and severity of illness, is helpful in making thisdistinction. (See 'Clinical course' above.)

Other possible diagnoses in children with persistent nasal symptoms and/or cough include[3,8]:

Allergic rhinitis with or without reactive airways disease. (See "Allergic rhinitis:Clinical manifestations, epidemiology, and diagnosis", section on 'Clinicalmanifestations' .)

Nasal foreign body (usually suspected on basis of foul odor and serosanguineousnasal drainage; may be apparent by direct observation). (See "Diagnosis andmanagement of intranasal foreign bodies", section on 'Clinical manifestations' .)

Enlarged or infected adenoids (associated symptoms and signs include enlargedadenoids, mouth breathing and snoring). (See "Etiologies of nasal symptoms: Anoverview", section on 'Enlarged adenoids' .)

Structural abnormalities (eg, mucosal cyst of the maxillary antrum) may requireimaging (computed tomography or magnetic resonance imaging) for diagnosis.

Pertussis, particularly in the catarrhal stage. In pertussis, nasal symptoms usuallyresolve after one to two weeks, after which the severity of cough increases. Thecough is typically paroxysmal and sometimes followed by an inspiratory whoop.(See "Clinical features and diagnosis of Bordetella pertussis infection in infants andchildren", section on 'Catarrhal' .)

SUMMARY AND RECOMMENDATIONS

Rhinosinusitis is inflammation of the mucosal lining of one or more of the paranasalsinuses. Such inflammation is common during viral upper respiratory infections




























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(URI), but usually resolves spontaneously. Acute bacterial rhinosinusitis (ABRS)occurs when there is secondary bacterial infection of the sinuses. (See 'Definitions' above.)

Viral URI and allergic rhinitis are the most frequent predisposing factors for ABRSin children. Less common predisposing factors include anatomic obstruction,

mucosal irritants, and sudden changes in atmospheric pressure. (See 'Predisposingfactors' above.) The clinical features of ABRS include cough, nasal symptoms, fever, headache,

facial pain and swelling, sore throat, and halitosis. (See 'Symptoms and signs' above.)

The clinical course, particularly the persistence and severity of symptoms, helps todifferentiate between the ABRS and viral URI. (See 'Clinical course' above.)

Complications of ABRS, which may be the presenting manifestation, include preseptal (periorbital) and orbital cellulitis; septic cavernous sinus thrombosis;meningitis; osteomyelitis of the frontal bone; and epidural, subdural, or brainabscess (table 2 ). (See 'Complications' above.)

The diagnosis of uncomplicated ABRS can be made clinically in children withsymptoms and signs of sinus inflammation (ie, daytime cough, nasal symptoms, or

both) and one of the following presentations (see 'Uncomplicated ABRS' above):

Symptoms present without improvement for >10 and <30 days, or Severe symptoms (ie, ill appearance, temperature ≥39ºC [102.2°F], and purulent

nasal discharge for ≥3 consecutive days), or Worsening symptoms (ie, increase in respiratory symptoms, new onset of severe

headache or fever, or recurrence of fever after initial improvement)

Imaging studies are not necessary for children with uncomplicated ABRS. It isrecommended that children with potential orbital or intracranial complications ofABRS undergo contrast-enhanced computed tomography (CT) imaging of theorbits, sinuses, and brain. Magnetic resonance imaging is an alternative. (See'Complications' above and 'Radiologic features' above.)

The differential diagnosis of ABRS includes uncomplicated viral URI, allergic ornon-allergic rhinitis, nasal foreign body, enlarged or infected adenoids, mucosalcyst of the maxillary antrum, and the catarrhal stage of pertussis. These conditionscan usually be distinguished from ABRS with history and examination, but imagingmay be necessary to exclude structural abnormalities. (See 'Differential diagnosis' above.)












































Pathogenesis of allergic rhinitis (rhinosinusitis)

INTRODUCTION — Allergic rhinitis is associated with a symptom complex characterized by paroxysms of sneezing, rhinorrhea, nasal obstruction, and itching of the eyes, nose, and palate. It is also frequently associated with postnasal drip, cough, irritability, and fatigue [1-

3].The pathogenesis of allergic rhinitis is presented in this topic review. The clinicalmanifestations, diagnosis, and treatment of this condition are discussed separately. (See"Clinical manifestations, pathophysiology, and diagnosis of chronic rhinosinusitis" and"Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis" and"Pharmacotherapy of allergic rhinitis" .)

MECHANISMS OF UPPER AIRWAY ALLERGIC REACTIONS — Upon exposure to anallergen, atopic individuals respond by producing allergen-specific IgE. These IgEantibodies bind to IgE receptors on mast cells in the respiratory mucosa and to basophils inthe peripheral blood. When the same allergen is subsequently inhaled, the IgE antibodiesare bridged on the cell surface by allergen, resulting in activation of the cell. Mast cells inthe nasal tissues release preformed and granule-associated chemical mediators, which causethe symptoms of allergic rhinitis.

Models of nasal allergen challenge in patients with allergic rhinitis have providedinformation about the pathogenesis of allergic rhinitis [4,5]. In this model study system,individuals known to have allergic rhinitis on exposure to a particular allergen are exposedto incremental doses of that allergen placed in the nose. The subsequent reaction is thenmonitored over time with nasal biopsies or washes. This allows direct quantitation of celltypes by stains and surface markers and assessment of message for transcription or directmeasurement of cellular cytokines and other mediators of inflammation [6].Rhinomanometry, the measurement of nasal airway resistance, permits measurement of

both resistance and airflow following allergen provocative challenge [7]. (See"Occupational rhinitis", section on 'Rhinomanometry techniques' .)

Immunogenetics — The expression of allergic diseases of the upper airways reflects anautosomal dominant pattern of inheritance with incomplete penetrance. This inheritance

pattern is manifested as a propensity to respond to inhalant allergen exposure by producinghigh levels of allergen specific immunoglobulin E (IgE). The IgE response appears to becontrolled by immune response genes located within the major histocompatibility complex(MHC) on chromosome 6. (See "Major histocompatibility complex (MHC) structure andfunction" .)

The immunologic mechanisms of atopy have been studied in murine models and inhumans. These mechanisms involve the expression of a repertoire of responses associatedwith the Th2 type of T-helper lymphocyte. There are probably multiple genetic andenvironmental influences that lead to overexpression of Th2 type T cell responses relativeto Th1 responses (figure 1 ). (See "The adaptive cellular immune response" .)

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Th2 lymphocytes and IgE production — Sensitization to allergen is necessary to elicit anIgE response (figure 2 ). After inhalation, the allergen must first be internalized by antigen

presenting cells, which include macrophages, CD1+ dendritic cells, B-lymphocytes, and possibly epithelial cells [8]. After allergen processing, peptide fragments of the allergen areexteriorized and presented with class II (MHC) molecules of host antigen presenting cells

to CD4+ T lymphocytes. (See "The adaptive cellular immune response" .) Nasal provocation with allergen has been associated with increases of such HLA-DR andHLA-DQ positive cells in the lamina propria and epithelium in allergic subjects [9]. Theselymphocytes have receptors specific for the particular MHC peptide complex and thisinteraction results in the release of cytokines by the CD4+ cell.

The switch from the Th1 phenotype to the Th2 phenotype is the crucial early event inallergic sensitization and is key to the development of allergic inflammation. Allergicinflammation conceptually derives from two major Th2 mediated pathways:

One involves the secretion of interleukin-4 (IL-4) and IL-13 that results in isotypicswitching of B-lymphocytes to secrete IgE [10].

The second pathway involves the secretion of the eosinophil growth factor, IL-5[11 ].

Thus, the release of IL-4, IL-5, and IL-13 are cardinal features of allergic inflammation.

B-lymphocytes require two signals for isotypic switch to IgE. (See "Immunoglobulingenetics" and "Normal B and T lymphocyte development" .) In the first signal, IL-4 or IL-13 stimulate transcription at the Ce locus, the site of exons that encode the constant regionof the IgE heavy chain [10,12 ]. (See "The biology of IgE" .) Interaction of CD40 on the Bcell membrane with CD40 ligand on the surface of T lymphocytes provides the secondsignal that activates genetic recombination in the functional IgE heavy chain [13]. IL-4 andIL-13 also up-regulate vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells

promoting adhesion of inflammatory cell populations and facilitate their migration intoareas of allergic inflammation. (See "Leukocyte-endothelial adhesion in the pathogenesis ofinflammation" .)

In situ hybridization and/or antibody studies have demonstrated increased numbers of cellswith messenger RNA for and/or expression of IL-3, IL-4, IL-5, IL-13, eotaxin, and GM-CSF within the nasal mucosa after allergen provocation ( picture 1 ) [4,6]. Interferon-gamma(IFN-gamma), a Th1 type cytokine that inhibits B-lymphocyte activation and IgE synthesisis absent. Il-12 and IL-18, major inducers of IFN-gamma, are also absent.

Thus, atopy appears to be the result of a predisposition toward Th2 type responses, whichresults in the formation of large quantities of allergen specific IgE [4].

Mast cell activation — After IgE antibodies specific for a certain allergen are synthesizedand secreted, they bind to high-affinity receptors on mast cells (and basophils). Whenallergen is inhaled into the nose, it cross links these allergen specific cell bound IgEantibodies on the mast cell surface in a calcium dependent process, resulting in rapid



















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degranulation and mediator release. The mediators stimulate blood vessels, nerves, andglands to cause the clinical manifestations of allergic rhinitis and feed back to otherelements of the immune system to perpetuate the process.

The superficial nasal epithelium in patients with allergic rhinitis has 50-fold more

basophilic cells (mast cells and basophils) per specimen than does epithelium fromnonallergic subjects. Increased concentrations of mast cells are found near post capillaryvenules, where they increase vascular permeability; near sensory nerves, where they initiatethe sneeze reflex; and near glands, where they facilitate secretion. Nasal mast cells are

predominately located in the nasal lamina propria as connective tissue mast cells, although15 percent are epithelial and called mucosal mast cells. Mucosal mast cells express tryptasewithout chymase and proliferate in allergic rhinitis under the influence of Th2 cytokines.(See "Mast cells: Development, identification, and physiologic roles" .)

Mast cell mediators are either preformed, associated with granules, formed duringdegranulation, or generated after transcription [14]. (See "Mast cell derived mediators" .)

Histamine — Histamine is the most important preformed mediator in allergic rhinitis.Histamine reproduces all of the acute symptoms of allergic rhinitis when sprayed into thenoses of normal volunteers. Histamine causes mucus secretion, vasodilatation leading tonasal congestion, increased vascular permeability leading to tissue edema, and sneezingthrough stimulation of sensory nerve fibers.

Prostaglandins and leukotrienes — The cross linking of IgE antibody on mast cellsactivates phospholipase A2 and releases arachidonic acid from the A2 position of cellmembrane phospholipids. Mast cells then metabolize arachidonic acid either via thecyclooxygenase pathway to form prostaglandin and thromboxane mediators or via thelipoxygenase pathway to form leukotrienes. Prostaglandin D2 (PGD2), the sulfidopeptideleukotrienes LTC4, LTD4, and LTE4 are thus formed during degranulation. PGD2 issynthesized by mast cells, but not basophils, and appears to be more potent than histaminein causing nasal congestion. LTB4 is the most potent chemotactic factor yet described inhumans [15].

Other mediators — Platelet activating factor (PAF) and bradykinin (generated by the actionof tryptase) are also formed during degranulation. PAF is a potent chemotactic factor, andthe bradykinins are vasoactive.

Cellular infiltration — Once allergic reactions begin, mast cells amplify such reactions byreleasing not only vasoactive agents, but also cytokines, including GM-CSF, tumornecrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), IL-1 to IL-6, and IL-13 [16-18 ].

Tissue eosinophilia is characteristic of allergic rhinitis [19]. It appears that mast cell derivedcytokines promote further IgE production, mast cell and eosinophil growth, chemotaxis,and survival. As an example, IL-5, TNF-alpha, and IL-1 promote eosinophil movement byincreasing the expression of adhesion receptors on endothelium. In turn, eosinophils secretea plethora of cytokines including IL-3, IL-4, IL-5, IL-10, and GM-CSF which favor, among

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others, Th2 cell proliferation and mast cell growth. Eosinophils also serve an autocrinefunction in these reactions by producing the cytokines IL-3, IL-5, and GM-CSF, which areimportant in hematopoiesis, differentiation, and survival of eosinophils themselves [20,21 ].

Eosinophils release oxygen radicals and proteins including eosinophil major basic protein,

eosinophil cationic protein, and eosinophil peroxidases; these have been shown to beassociated with nasal epithelial injury and desquamation, subepithelial fibrosis, andhyperresponsiveness [6,22 ]. As a result of mast cell and eosinophil activation in the allergicresponse, the following events occur in succession:

Vascular endothelial cell expression of adhesion molecules Adhesion of leukocytes to vascular endothelium Transendothelial migration

Chemotaxis and increased survival of eosinophils occur within areas of allergicinflammation. In addition to the families of adhesion molecules, chemokine molecules thataffect the expression and function of adhesion molecules on endothelium and leukocytesare also expressed in these reactions. Increased numbers of cells positive for chemokines,such as RANTES, eotaxins, MCP-3, and MCP-4 are present in the mucosa after allergenchallenge [4,23 ]. These chemokines further enhance the recruitment and activation ofinflammatory cells possessing their cell surface receptors in allergic reactions [6]. Nitricoxide (NO), a vasodilator, is also produced in the nasal mucosa of patients with allergicrhinitis and may play a role in the production of nasal obstruction [24]. Nitric oxidesynthetase is expressed by mast cells, neutrophils, and endothelial cells, among others.

IMMEDIATE AND LATE NASAL REACTIONS — Exposing the nasal mucosa toragweed in ragweed sensitive subjects (nasal challenge) provokes the immediate onset ofsneezing and nasal itching associated with significantly increased concentrations ofinflammatory mediators. The time course of histamine concentration, symptoms (sneezing),and increases in nasal airway resistance are closely correlated (figure 3 ) [25,26 ].

Immediate — Within seconds to minutes of allergen exposure, an immediate allergicresponse is observed, which peaks in 15 to 30 minutes [19]. Sneezing correlates with theappearance of measurable histamine, the kininogen product tosyl-L-arginine methyl ester(TAME esterase), and PGD2 in nasal washes. Increased levels of sulfidopeptideleukotrienes C4 and B4, tryptase, kinins, albumin, eosinophil major basic protein, and

platelet activating factor are also present in nasal washes after allergen challenges [27]. The presence of histamine, tryptase, and prostaglandin D2 indicate the central role of the mastcell in the early response to allergen [26].

After about 30 minutes, PGD2 and histamine levels return to baseline, whereas TAMEesterase concentrations remain elevated. Biopsy specimens of the nasal mucosa at this timeshow an increased number of degranulated mast cells.

Late — A late phase nasal allergic reaction develops in approximately 50 percent of patients with seasonal rhinitis, which peaks at 6 to 12 hours after nasal allergen challenge[19]. This secondary inflammatory response is thought to be important in establishing the
















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chronicity of the disorder [20]. During this later phase, symptoms may recur after a secondrelease of mast cell mediators coincident with maximum mast cell cytokine production[26].

The late phase allergic reaction is associated with elevated levels of the same mediators

noted in the immediate reaction, except that PGD2 is not detected. Thus, basophils appearto be partly responsible for such late phase reactions because histamine is generated by bothmast cells and basophils, whereas only mast cells can produce PGD2. In support of thisconcept, marked basophil influx into the nasal mucosa has been noted 3 to 11 hours afterallergen challenge [28]. Large numbers of neutrophils, mononuclear cells, and eosinophilsalso migrate into the nasal mucosa at this time. Increases in eosinophil cationic protein andother eosinophil products also become detectable in nasal secretions. After allergenchallenge, lymphocytes remain the predominant cells in the nasal mucosa. These cellsactively transcribe messages for IL-3, IL-4, IL-5, and GM-CSF and have increasedexpression of the IL-2 receptor. IL-1 through IL-5 and GM-CSF, among others, have beenrecovered from nasal washes after allergen challenge.

ALTERATIONS OF NASAL PHYSIOLOGY — Under normal conditions, the noseaccounts for one-half to two-thirds of the resistance to airflow in the airway. It is lined by

pseudostratified epithelium resting upon a basement membrane that separates it fromdeeper submucosal layers [19]. The submucosa contains mucous, seromucous, and serousglands. The small arteries, arterioles, and arteriovenous anastomoses determine regional

blood flow. Capacitance vessels consisting of veins and cavernous sinusoids determinenasal patency. The cavernous sinusoids lie beneath the capillaries and venules, are mostdense in the inferior and middle turbinates, and contain smooth muscle cells controlled bythe sympathetic nervous system. Withdrawal of sympathetic tone, or to a lesser degree,cholinergic stimulation, causes this sinusoidal erectile tissue to become engorged.Cholinergic stimulation causes arterial dilation and promotes the passive diffusion of

plasma protein into glands and active secretion by mucous glands in cells.

The role of neurotransmitters may be important in the pathogenesis of allergic rhinitis. Novel neurotransmitters, including substance P, a chemical that increases vascular permeability, calcitonin gene related peptide, and vasointestinal peptide, have been detectedin nasal secretions after nasal allergen challenge of patients with allergic rhinitis [11 ].Capsaicin , which depletes sensory nerves of SP and CGRP, reduces symptoms induced bynasal allergen challenge [29]. Antidromic stimulation of sensory nerve fibers in the nosecan release a variety of neurotransmitters, including substance P. Neurotransmitters also

produce changes in regional blood flow and glandular secretion.

INVOLVEMENT OF THE PARANASAL SINUSES — There are data indicating that theinflammatory response noted in the mucosa of patients with allergic rhinitis is often presentin the paranasal sinuses as well [6]. There is concomitant epithelial denudation,extracellular matrix deposition, and basement membrane disruption.
















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Acute bacterial rhinosinusitis in children: Microbiology and treatmentAuthor Ellen R Wald, MD Section Editors Sheldon L Kaplan, MD

Glenn C Isaacson, MD, FAAP Robert A Wood, MD Deputy Editor Mary M Torchia, MD Disclosures All topics are updated as new evidence becomes available and our peer review process iscomplete.Literature review current through: Aug 2013. | This topic last updated: Jul 24, 2013.

INTRODUCTION — Acute rhinosinusitis is a disease that results from infection of one ormore of the paranasal sinuses. A viral infection associated with the common cold is themost frequent etiology of acute rhinosinusitis, more properly called viral rhinosinusitis.(See "The common cold in children: Clinical features and diagnosis" and "The commoncold in children: Treatment and prevention" .)

Uncomplicated viral rhinosinusitis usually resolves without treatment in 7 to 10 days.Although untreated acute bacterial rhinosinusitis (ABRS) also may resolve withouttreatment, treatment with antibiotics hastens recovery [1,2 ]. It is important to distinguish

between uncomplicated viral rhinosinusitis and ABRS to prevent unnecessary use ofantibiotics (table 1 ).

The microbiology and treatment of ABRS in children will be discussed here. The clinicalfeatures and diagnosis of ABRS in children and acute sinusitis and rhinosinusitis in adultsare discussed separately. (See "Acute bacterial rhinosinusitis in children: Clinical featuresand diagnosis" and "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations anddiagnosis" and "Acute sinusitis and rhinosinusitis in adults: Treatment" .)

CLINICAL PRESENTATIONS — The clinical presentation of acute bacterialrhinosinusitis in children is characterized by [3-8 ]:

Persistent symptoms (nasal discharge or cough or both) for >10 days withoutimprovement, or

Severe symptoms (onset with temperature of ≥39ºC [102.2ºF] and purulent nas aldischarge for ≥3 consecutive days), or

Worsening symptoms (respiratory symptoms that worsen after initial improvement)or onset of new fever or severe headache

(See "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on'Acute bacterial rhinosinusitis' .)

MICROBIOLOGY

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Common pathogens — Streptococcus pneumoniae , Haemophilus influenzae (nontypeable),and Moraxella catarrhalis are the predominant causes of acute bacterial rhinosinusitis(ABRS) [9-11 ].

Culture of material aspirated from the sinus yielding ≥10 4 colony-forming units/mL of

bacteria is the standard for determining the etiology of ABRS [12]. However, sinusaspiration is an invasive procedure that is not routinely performed in children withuncomplicated ABRS. Studies of the microbiology of ABRS in which sinus aspirates wereobtained from children with uncomplicated ABRS were performed before the widespreaddevelopment of antibiotic resistant S. pneumoniae [5]. However, because acute otitis media(AOM) and ABRS have similar pathogenesis and microbiology, data generated fromcultures of middle-ear fluid obtained by tympanocentesis from children with AOM can beused as a surrogate for cultures of the paranasal sinuses [13,14 ].

Before the availability of pneumococcal conjugate vaccines (2000), the relative proportionof middle ear isolates in cases of AOM was 55:35:10 for S. pneumoniae, H. influenzae and

M. catarrhalis , respectively. Studies of the microbiology of pediatric AOM after the pneumococcal conjugate vaccine was introduced into the childhood immunization scheduleindicate that S. pneumoniae is isolated in approximately 45 percent of episodes in which anorganism is cultured, H. influenzae (predominantly nontypeable H. influenzae ) in about thesame, and M. catarrhalis in the remainder [15,16 ]. There was a brief resurgence in therecovery of S. pneumoniae when penicillin-resistant serotype 19A emerged. However, thishas resolved since initiation of immunization with the 13-valent pneumococcal conjugatevaccine (in 2010), which includes serotype 19A. A study in which tympanocentesis was

performed in children with AOM during 2010 and 2011 indicates that nontypeable H.influenzae is currently the most frequent isolate in cases of AOM [17]. (See "Acute otitismedia in children: Epidemiology, microbiology, clinical manifestations, andcomplications", section on 'Microbiology' .)

Several studies have reported isolation of S. aureus from sinus aspirates (obtainedendoscopically) or from cultures of the middle meatus in children (most of whom hadchronic sinusitis) [18-20 ]. However, these studies must be interpreted with caution becauseof methodologic limitations (eg, unknown indication for obtaining culture, lack ofquantification, and possibility of contamination from the nasal cavity) and because culturesof the middle meatus have not been established as a reliable surrogate for maxillary sinusaspirates in children [21].

Antimicrobial susceptibility — The proportion of isolates of S. pneumoniae that arenonsusceptible to penicillin varies from community to community. Isolates obtained fromsurveillance centers nationwide indicate that 10 to 15 percent of upper respiratory tractisolates of S. pneumoniae are nonsusceptible to penicillin [22,23 ]. However, values as highas 50 to 60 percent have been reported in some areas [24,25 ]. Of the organisms that areresistant, approximately one-half are highly resistant to penicillin and the remaining one-half are intermediate in resistance [22,23,25-28 ]. Between 10 and 42 percent of H.influenzae [25-28 ] and close to 100 percent of M. catarrhalis are likely to be beta-lactamase positive and nonsusceptible to amoxicillin . A study of middle ear isolatesobtained from children with AOM during 2010-2011 found a decreasing recovery of S.




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pneumoniae (including penicillin-resistant S. pneumoniae ) and increasing recovery of beta-lactamase producing H. influenzae [17]. Unfortunately, there are scant data, even fromtympanocentesis, upon which to estimate the relative prevalence of S. pneumoniae and

beta-lactamase producing H. influenzae in cases of either acute otitis media or acute bacterial sinusitis [29]. (See "Resistance of Streptococcus pneumoniae to beta-lactam

antibiotics" .)Risks for antimicrobial resistance — Risks for resistant pathogens include [4,30-33 ]:

Living in an area with high endemic rates (ie, ≥10 percent) of invasive penicillinnon-susceptible S. pneumoniae

Age <2 years Daycare attendance Antibiotic therapy within the past month Hospitalization within the past five days

INDICATIONS FOR REFERRAL — Children with uncomplicated acute bacterialrhinosinusitis (ABRS) can usually be managed by their primary care provider. Consultationwith a specialist (eg, infectious disease, otolaryngology, immunology) may be warranted inthe following circumstances [4,34,35 ]:

Intracranial or orbital complications (see "Acute bacterial rhinosinusitis in children:Clinical features and diagnosis", section on 'Complications' )

Need for sinus aspiration (see "Acute bacterial rhinosinusitis in children: Clinicalfeatures and diagnosis", section on 'Microbiologic studies' )

Isolation of resistant or rare pathogens from sinus aspirate Diagnosed or suspected immunodeficiency Recurrent ABRS, particularly if it exacerbates underlying pulmonary conditions

(eg, asthma)

EMPIRIC ANTIBIOTIC THERAPY

General principles — We suggest that children with a clinical presentation that iscompatible with acute bacterial rhinosinusitis (ABRS) be treated with antimicrobial therapy(see 'Clinical presentations' above) [4]. In general, empiric antibiotic therapy should beinitiated promptly; prompt initiation of therapy may shorten the duration of illness.However, for children with ten days of persistent symptoms that are neither severe norworsening, some experts suggest observation for two to three days, with initiation ofantimicrobial therapy for clinical worsening or failure to improve, as an option [3]. Ourrecommendations for treatment are largely consistent with those of the Infectious DiseasesSociety of America (2012) and the American Academy of Pediatrics (2013) [3,4].

Unfortunately, there have been no randomized, placebo-controlled trials of antibiotictreatment for ABRS that have used pre- and post-treatment quantitative sinus aspirateculture as the standard for diagnosis and cure. Studies that use clinical and/or radiologiccriteria for diagnosis and outcome may underestimate the benefit of antibiotic therapy







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because they are likely to include at least some patients with self-limited uncomplicatedviral upper respiratory tract infection.

Randomized trials evaluating antibiotics versus placebo for the treatment of ABRS inchildren have conflicting results [1,2,36 ]. In a meta-analysis of three trials including a total

of 310 children [1,2,36 ], the rate of improvement or cure was greater among childrentreated with antibiotics than placebo (78.5 versus 59.7 percent, odds ratio 2.52, 95% CI1.52-4.18) [4]. In the only study that was performed after the development of widespreadantibiotic-resistant S. pneumoniae , treatment with amoxicillin-clavulanate was associatedwith increased rates of cure (50 versus 14 percent) and decreased rates of treatment failure(14 versus 68 percent) compared with placebo [2]. Adverse events, predominantly self-limited diarrhea, were more common in the treatment group (44 versus 14 percent), butonly three patients in the treatment group discontinued therapy because of adverse effects.

Outpatient therapy — Most children with ABRS can be treated as outpatients. Those whoare toxic-appearing (eg, lethargic, poorly perfused, with cardiorespiratory compromise) orhave complications or suspected complications should be admitted for parenteral therapy[11 ]. (See 'Inpatient therapy' below.)

Antibiotics that are used to treat ABRS must provide antibacterial coverage for S. pneumoniae , H. influenzae , and M. catarrhalis (see 'Microbiology' above). Additionalfactors in the choice of therapy include the severity of illness, risk of complications,likelihood of infection with a resistant organism, antimicrobial spectrum, acceptability,dosing convenience, and adverse effects [4,11 ].

We suggest amoxicillin-clavulanate as the first-line agent for the treatment of ABRS inchildren because of its spectrum of activity, effectiveness, and safety [2,4,29,37 ]. Lesscomprehensive alternatives include third-generation cephalosporins (eg, cefpodoxime andcefdinir ) [38]. Levofloxacin may be used when there is no other safe and effectivealternative (eg, in patients who have anaphylaxis with or are intolerant of beta-lactams)[39]. Levofloxacin typically remains active against multi-drug resistant pneumococci withhigh level resistance to penicillin or third-generation cephalosporins and is an option fortreatment when patients have failed first-line therapy.

Mild/moderate disease — Mild/moderate ABRS is characterized by temperature <39°C(102.2°F) and lack of systemic signs or a clinical severity score <8 (table 2 ).

For children with uncomplicated mild/moderate ABRS who have no risks for antibioticresistance, we suggest empiric antimicrobial therapy with standard dose amoxicillin-clavulanate rather than other oral antibiotics (eg, amoxicillin , fluoroquinolones, macrolides,trimethoprim-sulfamethoxazole , doxycycline , or second- or third-generationcephalosporins) (table 3 ) (see 'Risks for antimicrobial resistance' above) [4]:

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For children with uncomplicated mild/moderate ABRS who have one or more risks forantibiotic resistance, we suggest treatment with high-dose rather than standard-doseamoxicillin-clavulanate (table 3 ) (see 'Risks for antimicrobial resistance' above)

Amoxicillin-clavulanate 90 mg/kg per day of the amoxicillin component orally in

two divided doses (maximum daily dose 4 g)We suggest amoxicillin-clavulanate rather than amoxicillin because the addition ofclavulanate improves coverage for ampicillin -resistant H. influenzae and M. catarrhalis .Beta-lactamase producing nontypeable H. influenzae is an increasingly important cause ofrespiratory tract infection, particularly in children with acute otitis media (the microbiologyof which is similar to ABRS) since introduction of immunization the 13-valent

pneumococcal conjugate vaccine) [4,15,24,26,29,40-42 ]. However, some experts suggestthat amoxicillin may be used as initial therapy for mild/moderate disease [3]. Theyrecommend amoxicillin 45 mg/kg per day orally divided in two doses for children withoutrisk factors for antimicrobial resistance and amoxicillin 90 mg/kg per day orally divided intwo doses for children with risk factors for antimicrobial resistance. (See 'Risks forantimicrobial resistance' above.)

High-dose amoxicillin-clavulanate provides better coverage for penicillin nonsusceptible S. pneumoniae and ampicillin -resistant non-beta-lactamase producing H. influenzae thanstandard dose amoxicillin -clavulanate [24]. However, because of the slight increase in costand side effects, we suggest that high-dose amoxicillin-clavulanate be reserved for childrenwith severe disease or increased or unknown risk of antibiotic resistance (either penicillin-nonsusceptible S. pneumoniae or beta-lactamase producing H. influenzae ) [4]. (See 'Risksfor antimicrobial resistance' above.)

In a meta-analysis of randomized trials, fluoroquinolones provided no advantage over beta-lactam antibiotics in the treatment of ABRS in adults [43]. Although fluoroquinolones havea wider spectrum of activity, they are associated with more severe side effects thanamoxicillin-clavulanate . In vitro studies have demonstrated high rates of resistance amongthe most common ABRS pathogens to macrolides, trimethoprim-sulfamethoxazole , andvariable rates of resistance (especially penicillin non-susceptible S. pneumoniae ) to second-and third-generation cephalosporins [24,40,41,44-46 ].

Severe disease or risk for severe disease — Severe disease is characterized by temperature≥39°C (102.2°F) and other systemic signs or a clinical severity score ≥8 (table 2 ). Childrenwith immune compromising conditions (eg, human immunodeficiency virus) are atincreased risk for severe disease [4].

For children with severe ABRS or risk for severe ABRS who are treated as outpatients, wesuggest treatment with high-dose amoxicillin-clavulanate (table 3 ) [4].

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We suggest high-dose rather than standard-dose amoxicillin-clavulanate for children withsevere ABRS to provide coverage for penicillin-nonsusceptible S. pneumoniae in additionto ampicillin -resistant H. influenzae and M. catarrhalis [4]. (See 'Microbiology' above.)

Less comprehensive alternative regimens include a third-generation cephalosporin such as

cefpodoxime or cefdinir . The advanced generation cephalosporins have been consideredless comprehensive because they fall short in covering penicillin-resistant S. pneumoniae .However, if penicillin-resistant S. pneumoniae are diminishing as causes of acute otitismedia and acute bacterial sinusitis (since the introduction of immunization with the 13-valent pneumococcal conjugate vaccine) this may be less of an issue [17]. Levofloxacin , which has a comprehensive spectrum, should be reserved for cases in which there are noalternative choices:

Cefpodoxime 10 mg/kg per day orally divided every 12 hours or Cefdinir 14 mg/kg per day orally divided every 12 or 24 hours, or Levofloxacin 10 to 20 mg/kg per day orally divided every 12 to 24 hours;

levofloxacin should be reserved for cases in which there is no other safe andeffective alternative [39].

Penicillin allergy — Alternatives to amoxicillin-clavulanate for children with an allergy to penicillin depend upon the type of allergy (table 3 ). (See "Allergy to penicillins" and"Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams" .)

For children with uncomplicated ABRS who have a severe type I allergy to penicillin, we suggest levofloxacin 10 to 20 mg/kg per day orally divided every 12or 24 hours [4,39 ].

For children with uncomplicated ABRS who have a non-type I allergy to penicillin,we suggest therapy with a third-generation cephalosporin (eg, cefpodoxime orcefdinir ):

Cefpodoxime 10 mg/kg per day orally divided every 12 hours, or Cefdinir 14 mg/kg per day orally divided every 12 or 24 hours

Vomiting — A single dose of ceftriaxone 50 mg/kg per day (maximum dose 2 g/day)intravenously or intramuscularly can be used in children with uncomplicated ABRS andvomiting that precludes administration of oral antibiotics [3,4]. Therapy with an oralantibiotic should be initiated 24 hours later, provided the vomiting has resolved.

Inpatient therapy — Indications for hospitalization and parenteral antibiotics include toxic-appearance (eg, lethargic, poorly perfused, cardiorespiratory compromise), complicationsor suspected complications, and treatment failure with outpatient therapy (ie, high-doseamoxicillin-clavulanate , third-generation cephalosporin, or levofloxacin ) [11 ]. (See "Acute

bacterial rhinosinusitis in children: Clinical features and diagnosis", section on'Complications' and 'Treatment failure' below.)

Sinus imaging with contrast-enhanced computed tomography should be performed in patients with symptoms or signs of intracranial or orbital complications. (See "Acute







































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bacterial rhinosinusitis in children: Clinical features and diagnosis", section on'Complications' .)

Sinus aspiration (performed by a specialist) for Gram stain, aerobic and anaerobic culture,and antimicrobial susceptibility testing should be obtained in hospitalized children with

complications or outpatient failure [4,47 ]. Isolation of a pathogen and antimicrobialsusceptibilities enable better targeting of antimicrobial therapy. For children who wereinitially hospitalized for toxic appearance without complications or suspectedcomplications, sinus aspiration may be deferred pending response to intravenous therapy[3]. (See "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis",section on 'Microbiologic studies' .)

Empiric therapy for children hospitalized with ABRS should provide coverage for highlyresistant S. pneumoniae and ampicillin -resistant H. influenzae and M. catarrhalis . Theregimen should be adjusted based upon clinical response and culture results.

For children hospitalized with ABRS, we suggest empiric antibiotic therapy with one of thefollowing regimens (table 3 ) [4]:

Ampicillin-sulbactam 200 to 400 mg/kg per day intravenously (IV) divided everysix hours (maximum 8 g ampicillin component per day), or

Cefotaxime 100 to 200 mg/kg per day IV divided every six hours (maximum 8 g perday), or

Ceftriaxone 100 mg/kg per day IV divided every 12 hours (maximum 2 g per day),or

Levofloxacin 10 to 20 mg/kg per day IV divided every 12 to 24 hours (maximum500 mg per day); levofloxacin should be reserved for cases in which there is noother safe and effective alternative [39].

These suggestions are based on in vitro susceptibilities. There are no studies comparingintravenous antibiotic regimens for the treatment of ABRS in children.

RESPONSE TO THERAPY

Improvement — Most patients with acute bacterial rhinosinusitis (ABRS) who are treatedwith an appropriate antimicrobial agent respond within 48 to 72 hours with improvement ofsymptoms and general well-being [1,2]. We usually continue antimicrobial therapy for totalof 10 days in children whose symptoms improve within three days of initial therapy [48].(See 'Duration' below.)

Treatment failure — Treatment failure is defined by worsening within three days or failureto improve after three days of antimicrobial therapy [1,2]. Causes of treatment failure mayinclude [3,4]:

Resistant pathogen (see 'Microbiology' above)























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Complication (see "Acute bacterial rhinosinusitis in children: Clinical features anddiagnosis", section on 'Complications' )

Noninfectious etiology (eg, foreign body, structural abnormality) (see "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on'Differential diagnosis' )

Initial presentation of immune deficiency [49] (see "Approach to the child withrecurrent infections" )

MANAGEMENT OF TREATMENT FAILURE

In outpatients — For children with uncomplicated acute bacterial rhinosinusitis (ABRS)who are initially treated as outpatients and whose symptoms worsen after two to three daysor fail to improve after three days of initial antimicrobial treatment, we suggest broadeningantimicrobial coverage or switching to a different class of antibiotic. Potential regimensdepend on what was used initially and might include:

Amoxicillin-clavulanate 90 mg/kg per day of the amoxicillin component orally intwo divided doses (maximum daily dose 4 g) (for patients initially treated with low-dose amoxicillin or amoxicillin-clavulanate)

Ceftriaxone 50 mg/kg per day intramuscularly for one to three days, followed byamoxicillin-clavulanate 90 mg/kg per day of the amoxicillin component to complete10 to 14 days, or

Cefpodoxime 10 mg/kg per day orally divided every 12 hours or Cefdinir 14 mg/kg per day orally divided every 12 or 24 hours, or Levofloxacin 10 to 20 mg/kg per day orally divided every 12 or 24 hours;

levofloxacin should be reserved for cases in which there is no other safe andeffective alternative [39].

Imaging and/or sinus aspiration may be indicated to confirm the diagnosis, evaluatecomplications, and tailor therapy, particularly for children whose symptoms have notimproved or have worsened after three days of initial antibiotics and another three days of

broadened coverage. (See "Acute bacterial rhinosinusitis in children: Clinical features anddiagnosis", section on 'Complicated ABRS' and "Acute bacterial rhinosinusitis in children:Clinical features and diagnosis", section on 'Microbiologic studies' .)

Hospital admission for a trial of intravenous therapy and/or consultation with a specialist(eg, infectious disease, otolaryngology) may be warranted for children with ABRS who failto improve after second-line therapy. (See 'Inpatient therapy' above and 'Indications forreferral' above.)

In hospitalized patients — Failure to improve or worsening in hospitalized children who arereceiving empiric antibiotic therapy warrants additional evaluation, including [4]:

Contrast-enhanced computed tomography imaging (or magnetic resonance imaging)to exclude orbital and intracranial complications (if not performed previously).

Quantitative sinus aspirate cultures if they were not obtained at the time ofadmission.













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Antimicrobial therapy should be modified according to results of sinus aspirate cultures assoon as the results are available.

If sinus aspirate cultures are unavailable or if no pathogens are isolated in an ill child whohas not improved despite therapy with a third-generation cephalosporin, ampicillin-

sulbactam , or levofloxacin , the addition of vancomycin (to cover highly resistant S. pneumoniae and S. aureus ) with or without metronidazole (to cover anaerobes) may bewarranted [50].

Vancomycin 60 mg/kg per day IV divided every six hours (maximum 4 g/day) Metronidazole 30 mg/kg per day IV divided every six hours (maximum 4 g/day)

Consultation with an infectious disease specialist and/or otolaryngologist is suggested.

DURATION — The optimal duration of therapy for patients with acute bacterialrhinosinusitis (ABRS) has not been studied systematically. We consider 10 days adequate

for children whose symptoms improve within three days of initial therapy [48]. For thosewho improve more slowly or who have required escalation of therapy, we continueantibiotic therapy for seven days after the patient becomes free of symptoms (ie, aminimum of 10 days) [3,51 ]. (See 'Response to therapy' above.)

Guidelines from the Infectious Diseases Society of America suggest a 10- to 14-day coursefor the treatment of ABRS in children [4].

SYMPTOMATIC TREATMENT — Theoretic therapies to improve sinus drainage in patients with acute bacterial rhinosinusitis (ABRS), include [3,52,53 ]:

Saline nasal irrigation Decongestants (topical or systemic) Antihistamines Intranasal corticosteroids Sinus aspiration

There are limited data regarding the efficacy of these therapies in children with ABRS [53-55].

Topical saline — We suggest topical saline as an adjunctive therapy for children withABRS. Saline nose drops, saline nasal sprays, and/or saline nasal irrigation may help in

preventing crust formation and liquefying sinus secretions. In a small randomized trial,nasal saline irrigation improved symptoms, quality of life scores, and peak expiratory flowrates in children with acute sinusitis [56]. Although the potential benefits for children arenot well established by this single trial, topical saline is inexpensive and unlikely to beharmful or impede recovery.








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Decongestants and antihistamines — We do not suggest the use of decongestants orantihistamines in children with ABRS who do not have an underlying allergic component[3,52 ].

Although decongestants may reduce tissue edema, improve ostial drainage, and provide

symptomatic relief [52], these benefits may be offset by increased viscosity of secretions,decreased blood flow to the nasal mucosa (potentially impeding delivery of antibiotics tothe sinuses), and increased irritability in children. Antihistamines also can dry secretionsand impair sinus drainage. In a randomized trial in which children with presumed ABRSwere treated with amoxicillin and a combination decongestant-antihistamine or amoxicillinand placebo, symptoms improved in all children within three days of initiation ofantibiotics [57].

Intranasal corticosteroids — We do not suggest the use of intranasal corticosteroids inchildren with ABRS who do not have an underlying allergic component. Although nasalcorticosteroids theoretically may decrease inflammation of the mucous membranes, whichcontributes to obstruction of the ostia and impaired mucociliary clearance [58], the benefitsin randomized trials have been marginal and the trials have methodologic limitations (eg,varying inclusion criteria, inclusion of patients with and without allergies, varying outcomecriteria) [3,59-61 ].

Sinus aspiration — Sinus aspiration may be warranted for relief of intense headache orfacial pain [47]. Sinus aspiration should be performed by a specialist.

SUMMARY AND RECOMMENDATIONS

Clinical presentations compatible with a diagnosis of acute bacterial rhinosinusitis(ABRS) include (see 'Clinical presentations' above):

Persistent symptoms (nasal discharge or cough or both) for >10 days withoutimprovement, or

Severe symptoms (onset with temperature of ≥39ºC [102.2ºF] and purulent nasaldischarge for ≥3 consecutive days), or

Worsening symptoms (respiratory symptoms that worsen or onset of fever or severeheadache after initial improvement)

Streptococcus pneumoniae , Haemophilus influenzae (nontypeable), and Moraxellacatarrhalis are the predominant causes of uncomplicated ABRS in otherwisehealthy children. The proportion of S. pneumoniae isolates nonsusceptible to

penicillin varies from community to community. Approximately 10 to 42 percent of H. influenzae and more than 90 percent of M. catarrhalis respiratory tract isolatesare beta-lactamase producing (ie, resistant to ampicillin ). (See 'Microbiology' above.)

We suggest that children with a clinical presentation compatible with ABRS betreated with antimicrobial therapy (Grade 2B ). Empiric antibiotic therapy should beinitiated as soon as possible. (See 'General principles' above.)































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Most children with ABRS can be treated as outpatients. Those who are toxic-appearing (eg, lethargic, poorly perfused, with cardiorespiratory compromise) orhave complications or suspected complications should be admitted for parenteraltherapy. (See 'Outpatient therapy' above and 'Inpatient therapy' above.)

The choice of antibiotic is based upon the degree of severity of illness, recent

exposure to antibiotics, and the likelihood of infection with resistant bacteria (table3). We suggest amoxicillin-clavulanate rather than other oral antibiotics as theinitial treatment for uncomplicated ABRS in children (Grade 2B ). (See 'Outpatienttherapy' above.)

Treatment failure is defined by worsening after two to three days or failure toimprove after three days of antimicrobial therapy. Causes of treatment failure mayinclude a resistant pathogen, complication, noninfectious etiology (eg, foreign

body), or immune deficiency. (See 'Treatment failure' above.) For children with uncomplicated ABRS who are initially treated as outpatients and

whose symptoms worsen after two to three days or fail to improve after three days,we broaden antimicrobial coverage or switch to a different class of antibiotic (table3). (See 'In outpatients' above.)

We continue antibiotics for 10 days in children whose symptoms improve withinthree days of initial therapy. For children who respond more slowly, we continueantibiotics for seven days after symptoms resolve (a minimum of 10 days). (See'Duration' above.)

We suggest saline nose drops and/or saline nasal sprays for children with ABRS(Grade 2C ). We suggest not using decongestants, antihistamines, or nasalcorticosteroids (Grade 2B ). (See 'Symptomatic treatment' above

































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Acute Bacterial Rhinosinusitis in Children

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