Evidence-Based Management and Optimizing Antibiotic Therapy
Authors: Lynn P. Roppolo, MD, Assistant Professor, Division of Emergency Medicine, University of Texas Southwestern, Parkland Memorial Hospital, Dallas; and Riva L. Rahl, MD, Division of Emergency Medicine, University of Texas Southwestern, Parkland Memorial Hospital, Dallas.
Peer Reviewers: Albert C. Weihl, MD, Assistant Professor of Medicine and Surgery, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine, New Haven, CT; and Ralph Riviello, MD, FACEP, FAAEM, Assistant Professor of Emergency Medicine, Director of Clinical Research, Department of Emergency Medicine, Jefferson Medical College, Philadelphia, PA.
Approximately 20 million cases of acute bacterial rhinosinusitis (ABRS) are managed annually in the United States. According to National Ambulatory Medical Care Survey (NAMCS) data, sinusitis is the fifth most common diagnosis for which an antibiotic is prescribed, and accounted for 7-12% of all antibiotic prescriptions written from 1992 to 1999. In 1996, the primary diagnosis of sinusitis lead to expenditures of approximately $3.39 billion in the United States.
Acute bacterial sinusitis is one of the 10 most common diagnoses encountered in ambulatory practice. Primary care physicians frequently approach sinusitis as the manifestation of acute bacterial infection and prescribe an antibiotic in 85-98% of cases. However, sinusitis commonly is caused by viral infection, and often will resolve without antibiotic treatment, even if it is bacterial in origin.
Acute rhinosinusitis is defined by symptom duration of fewer than four weeks. Acute bacterial sinusitis usually is a secondary infection resulting from sinus ostia obstruction, impaired mucus clearance mechanisms caused by an acute viral upper respiratory tract infection, or both. According to epidemiologic estimates, only 0.2-2% of viral upper respiratory tract infections in adults are complicated by bacterial rhinosinusitis. The accepted standard for the definitive diagnosis of bacterial sinusitis is sinus puncture, with Streptococcus pneumoniae and Haemophilus influenzae bacteria most commonly isolated from infected maxillary sinuses. However, sinus puncture is an invasive procedure seldom performed in the primary care setting, and as a result, other criteria must be evaluated as triggers for antimicrobial therapy.
Because no simple and accurate office-based test for acute bacterial sinusitis currently is available, emergency clinicians must rely on clinical findings and historical features to confirm the diagnosis. This may be problematic, since signs and symptoms of acute bacterial sinusitis and those of prolonged viral upper respiratory tract infections are very similar, resulting in frequent misclassification of viral cases.
As expected, the diagnosis and management of acute bacterial sinusitis is a fiercely debated topic, with expert opinion varying as to when antibiotic therapy is appropriate and which specific antibiotics should be employed as first-line therapy. A recent set of recommendations published by the American College of Physicians (ACP) concluded that most cases of acute rhinosinusitis diagnosed in ambulatory care are caused by uncomplicated viral upper respiratory tract infections, and that specific clinical triggers should be utilized to initiate antibiotic-centered management.
Given the importance of this commonly encountered outpatient infection, this issue of Emergency Medicine Reports attempts to outline in evidence-based detail what the authors conclude to be optimal, risk-stratified, empiric treatment recommendations for this patient population. In addition, this review identifies key clinical findings, resistance patterns, risk factors, coexisting conditions, and other clinical triggers supporting referral of patients with ABRS to an otolaryngologist for more invasivei.e., multimodal surgical and more intensive antimicrobialmanagement strategies.
The ultimate goal is to provide a concise, practical, and clinically relevant schemata for day-to-day patient management in which evidence can be put into practice to optimize clinical outcomes in patients with ABRS.—The Editor
Definition of the Problem
The term sinusitis refers to inflammation of the mucosa lining one or more of the paranasal sinuses. The condition is invariably associated with contiguous inflammation of the nasal mucosa. Viral or allergic rhinitis typically precedes sinusitis, and sinusitis without rhinitis is rare. Thus, rhinosinusitis may be the more appropriate term to describe this disease process and will be used throughout this review. Sinus inflammation occurs in 90% of individuals with the common cold.1 Acute bacterial rhinosinusitis (ABRS) results when this sinus inflammation is complicated by bacterial infection and occurs in up to 2% of cases of patients with colds.2 Most cases of rhinosinusitis affect the maxillary and ethmoid sinuses. Isolated infection of the sphenoid and frontal sinus is rare, more serious, and usually is bacterial in origin.3-5
Emergency physicians should be aware of several challenges associated with the diagnosis and management of ABRS. Although most cases of ABRS are caused by viral upper respiratory infections, bacterial and viral causes are difficult to differentiate on clinical grounds. The diagnosis often is presumptive, and the treatment is empirical.6 The problem that arises is that many patients receive antibiotics for rhinosinusitis, which is not only ineffective against the more likely viral pathogen, but contributes to resistance of various bacteria to these drugs. Furthermore, the antibiotics that are prescribed frequently are used indiscriminately.7 The purpose of this paper is to review rhinosinusitis, particularly acute bacterial rhinosinusitis in the adult population, and to provide simple guidelines for the emergency physician in the diagnosis and management of this common disease.
Classification
Rhinosinusitis is classified as acute, subacute, or chronic based on the duration of symptoms. Acute rhinosinusitis may last as long as 4 weeks. Symptoms of subacute rhinosinusitis may persist for 4-12 weeks. Chronic rhinosinusitis is defined by symptom duration of greater than 12 weeks. Recurrent acute rhinosinusitis requires four or more episodes of acute rhinosinusitis lasting at least seven days each in any one-year period.8 Patients can have recurrent acute attacks or an acute exacerbation of chronic rhinosinusitis.
Epidemiology
The symptoms attributable to sinusitis are one of the most common reasons for visits in the acute care setting. Sinus disease affects more than 10% of the population.9 Approximately one billion cases of viral rhinosinusitis can be expected to occur annually in the United States alone, which can be complicated by 20 million cases of ABRS, assuming a 2% complication rate and an estimated 3-4 acute respiratory illnesses a year.10 The prevalence of acute rhinosinusitis is increasing according to data from the National Ambulatory Medical Care Survey, up from 0.2% of diagnoses at office visits in 1990 to 0.4% of diagnoses at office visits in 1995.11 Respiratory infections such as rhinosinusitis are a leading cause of morbidity and a significant financial burden to society.12 There is considerable cost associated with the symptoms, diagnosis, treatment, and complications of acute bacterial rhinosinusitis. In addition to the direct costs of office visits, diagnostic tests, and treatment drugs and modalities, the spectrum of the financial impact also includes cost of time lost from work for illness and office visits, the injudicious use of antibiotics, and inpatient costs for complications or morbid infections. In 1992, Americans spent $200 million on prescription medications for rhinosinusitis and more than $2 billion on over-the counter medications.11 Fortunately, patients with uncomplicated ABRS rarely need to be hospitalized. However, complications due to spread of infection into the periorbital space or central nervous system often require urgent hospitalization and aggressive treatment.
Pathophysiology
The paranasal sinuses are comprised of four paired air-filled cavities within the skull: maxillary, ethmoid, frontal, and sphenoid. The frontal sinuses are not present in young children and become fully developed around 12 years of age. The sphenoid sinuses are the last to develop and first appear around 7 years of age. The frontal and sphenoid sinuses become clinically important in the teenage years when they become infected in pansinusitis.4 The frontal, anterior ethmoid, and maxillary sinuses drain into the ostiomeatal complex located in the middle meatus, lateral to the middle turbinate. The sphenoidal sinus and posterior ethmoidal cells drain into the sphenoethmoidal recess.
The sinuses and nasal cavity are lined with ciliated pseudostratified columnar epithelium that serves both a functional and protective role. This area is rich in goblet cells that secrete mucus onto the surface epithelium. This blanket of mucus acts as a lubricant for the cilia and helps to trap inhaled particles. Mucus and debris are transported toward the ostia by the beating of the cilia and are expelled into the nasal airway. The sinuses are normally sterile, even though the sinus epithelium is contiguous with the nasal passages which are colonized with bacteria. This sterility is maintained by mucociliary clearance and immunologic host defense mechanisms. If the sinus ostia are obstructed, mucociliary flow is impaired. Obstruction of these ostia results in an anaerobic, high-carbon dioxide, and stagnant environment that can facilitate bacterial growth.13
Sinus infection usually occurs when predisposing events (see Table 1) result in inflammation and obstruction of drainage into the ostiomeatal complex. Obstruction of these ostia appears to be a critical factor in precipitating infection.14 The presence of bacteria in the absence of obstruction appears to be insufficient to cause disease.15 The most common predisposing factor is mucosal inflammation from viral upper respiratory infection or allergic rhinitis.16 Predisposing conditions may contribute to the increased incidence of ABRS as the inflammation impedes mucus flow and drainage.17,18 This relationship is at least as strong in the pediatric population.19
Table 1. Predisposing Events for Sinusitis
Certain anatomic variants may decrease the mucus drainage from the sinuses, thus increasing pooling and the possibility of bacterial overgrowth. Nasal polyps are thought to predispose to rhinosinusitis in two ways. In addition to impeding sinus drainage, their association with asthma and the associated mucociliary inflammation both increase the incidence of infection and inflammation.20-22 Immunodeficiency also is a risk factor for the development of ABRS.23 Previous trauma, intranasal cocaine use, and swimming all can lead to rhinosinusitis, as they upset the natural anatomy and pH of the turbinates, meatus, and sinuses.24
Rhinosinusitis should not be viewed simply as an infection treated only with antibiotics, but rather a complex process involving inflammatory processes that may include bacterial, viral infection, and obstructive phenomena.25
Etiology
Episodes of ABRS almost always appear as complications of viral upper respiratory infections, and less frequently with allergic rhinitis. The most common pathogens isolated from sinus drainage cultures in acute rhinosinusitis are Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarhallis, and Staphlyococcus aureus.26-29 The infection is polymicrobial in about one-third of the cases.30 Enteric bacteria are recovered less commonly.30 If resolution of the acute phase of rhinosinusitis does not take place, anaerobic bacteria of oral flora origin become predominant over time.6 Anaerobic infections typically also occur in association with dental disease.31 Although the organisms responsible for ABRS have remained unchanged, their susceptibility to a variety of antibiotics has changed significantly.32
Certain populations are more susceptible to developing complicated sinus infections based on anatomic variants or co-morbid conditions. Loss of immunocompetence related to HIV infection, chemotherapy, posttransplant immunosuppression, insulin-dependent diabetes mellitus, or some connective tissue disorders predisposes patients to rhinosinusitis and increases the likelihood of its persistence.4 Pseudomonas aeruginosa and other aerobic gram-negative rods are common in rhinosinusitis of nosocomial origin (e.g., nasogastric tubes or nasotracheal intubation), in immunocompromised individuals, and in patients with cystic fibrosis.30 Fungal rhinosinusitis is uncommon and is found in either atopic individuals who develop an allergic reaction to certain fungal pathogens or in immunocompromised patients, including diabetics who develop a much more invasive form of this disease.33
Differential Diagnosis
The differential diagnosis for ABRS includes viral or allergic rhinosinusitis, chronic rhinosinusitis, and other head and neck infections. Because the clinical spectrum of these other etiologies overlaps, many practitioners treat empirically with antibiotics.
The etiology most commonly mistaken for ABRS is viral rhinosinusitis. This fact alone likely contributes to the overuse of antibiotics prescribed in the ambulatory, urgent care, and emergency services population. Viral infections frequently are bilateral and have concomitant upper respiratory infection symptoms, and are suggested by more clear mucus secretions. In making a distinction between viral and bacterial sources of sinus infection, one often has to treat empirically using adjunctive therapies (without antibiotics) based on signs and symptoms. If after seven days the patient has persistent or worsening symptoms, the diagnosis of bacterial infection is suggested. Chronic rhinosinusitis also is in the differential, and may be difficult to distinguish from both allergic and bacterial rhinosinusitis. Other infections of the head and neck initially may present in a similar fashion to that of acute ABRS, but a thorough history and physical exam (and occasionally necessary ancillary studies) usually can delineate the location of infection.
Helpful features in differentiating bacterial from allergic causes include unilaterality of the pain and secretions, acute onset, fever, and preceding upper respiratory infection symptoms in patients with ABRS. Patients suffering from allergic rhinosinusitis often are misdiagnosed with a bacterial infection. There are common features, in addition to the fact that patients prone to allergic rhinosinusitis have risk factors for developing bacterial rhinosinusitis. These include inflammation and mucosal thickening as well as subsequent impedance of meatal mucus flow. Finally, other causes for headache pain also should be in the differential. Migraine headaches may be associated with nasal symptoms and should be considered.34
Clinical Features
Rhinosinusitis is an inflammatory disease of the paranasal sinuses and nasal cavity that can be characterized by a variety of presentations. An upper respiratory infection or a history of one may be present.35 The diagnosis often is based on symptoms indicating maxillary or frontal sinus involvement. Headache is the most prevalent symptom of bacterial rhinosinusitis.36 However, all rhinosinusitis pain is not the same. Maxillary rhinosinusitis pain most typically is located in the cheek, the gums, and the teeth of the upper jaw. Ethmoid rhinosinusitis pain is felt between the eyes. The eyeball may be tender, and pain may be aggravated by eye movement. Frontal rhinosinusitis pain is felt mainly in the forehead. Sphenoid rhinosinusitis pain is felt in the vertex, but has a more general localization.4 According to the Task Force on Rhinosinusitis of the American Academy of Otolaryngology-Head and Neck Surgery, diagnosis of acute bacterial rhinosinusitis depends on the presence of at least two major or one major and two minor criteria.8 (See Table 2.) Headache, fever, facial pain, and typical upper respiratory infection symptoms are the most common, although there are many different presentations. Unilateral facial pain suggests actual sinus infection because usually a single sinus is involved. On the other hand, bilateral facial pain and congestion would be seen more commonly with a straightforward viral upper respiratory infection. Blockage of sinuses often leads to other symptoms such as anosmia and halitosis, and the purulent rhinorrhea often may lead to a persistent cough.23 Often, a patient presents with typical upper respiratory infection symptoms that have worsened over several days, and obstruction of secretions in the sinuses causes pain, especially upon bending forward.37
Table 2. Diagnostic Criteria for
Acute
Bacterial Rhinosinusitis (ABRS)
The physical examination may not be helpful, particularly in sphenoid rhinosinusitis in which the diagnosis often is missed.4 Visualization of purulent nasal discharge on examination may be a strong indicator of ABRS;38 however, pus is not always seen in sphenoid rhinosinusitis.39 Sinus tenderness on physical examination is suggestive but not specific for rhinosinusitis.40 Transillumination of the sinuses has low sensitivity and specificity,35 and routine anterior rhinoscopy performed with a headlight and nasal speculum allows only limited inspection of the anterior nasal cavity.4
Diagnostic Studies
The diagnosis of acute bacterial rhinosinusitis can be made in several different ways. These include symptom complex, physical exam, endoscopy, sinus puncture and culture, and radiologically with computed tomography (CT), magnetic resonance imaging (MRI), plain films, or ultrasonography.
Many studies have been performed to try to identify diagnostic criteria for ABRS to determine the need for antibiotic treatment or further care. Predictors for bacterial infection include: purulent nasal discharge, unilaterality of pain on exam, maxillary toothache, and poor responsiveness to over-the-counter treatments.41-46 A randomized double-blind trial found that history of purulent nasal discharge and signs of pus in the nasal cavity and throat were the most predictive of responsiveness to antibiotics. These criteria were better than radiography, which was even better than c-reactive protein or CRP in this study.38 However, there is limited evidence to suggest that clinical criteria have better diagnostic accuracy than sinus radiography.11
Often, however, clinical exam cannot definitely detect a sinus infection. CT has become the most widely used diagnostic radiography for acute bacterial rhinosinusitis. Imaging must be performed in the coronal plane to adequately demonstrate the ethmoid complex. The mucosa of the normal, noninfected sinus approximates the bone so closely that it cannot be visualized on CT. Therefore, any soft tissue seen within a sinus is abnormal.47 Findings consistent with sinus inflammation include air-fluid levels, sinus opacification, sinus wall displacement, and mucosal thickening of 4 mm or greater. (See Figure 1.) IV contrast may be required to evaluate central nervous system or orbital complications.48 Unfortunately, CT findings of sinus inflammation are not diagnostic of ABRS. In a study by Gwaltney et al, 87% of patients who presented with the "common cold" and no previous history of rhinosinusitis had maxillary sinus abnormalities; 65% had ethmoid sinus abnormalities; and 30-40% had frontal or sphenoid sinus abnormalities on CT. This same study reported that up to 40% of asymptomatic adults have abnormalities on sinus CT scans.1 Sinus CT is helpful in persistent disease, treatment failures, or for guidance of therapy when done preoperatively.49 CT has not been shown to be cost-effective for the diagnosis of rhinosinusitis.50 Otolaryngologists order far more CTs, as they see patients in referral who already have been treated and perhaps have a higher prevalence of complicated rhinosinusitis.51
Figure 1. Coronal CT Scan Showing
Right Maxillary Sinus Opacification
Plain films of the sinuses are not sufficient to evaluate drainage patterns in all sinuses and thus are used infrequently. Standard radiography is inadequate for the clinical evaluation of rhinosinusitis because it does not evaluate the anterior ethmoid air cells, the upper two-thirds of the nasal cavity, or the infundibular, middle meatus, or frontal recess air passages.52 Visualization of the sphenoid sinus also is limited.4 Although such studies can disclose sinus opacification or reveal air fluid levels in the sinuses, one of the most commonly infected areas, the anterior ethmoid region, is poorly visualized on plain film radiographs.53 (See Figure 2.) MRI also has been occasionally used, although its use has been limited more to evaluating complications of acute and chronic rhinosinusitis.54 (See Figure 3.) Ultrasonography rarely is used in the evaluation of sinus disease. Studies evaluating its use in the diagnosis of rhinosinusitis reveal substantial variation in test performance.55
Figure 2.
Waters’ View of the Sinuses
Showing Partial Opacification
of the Right Maxillary Sinus, with an Air-Fluid Level
Figure 3.
Coronal MRI Scan Showing
Opacification
of the Left Maxillary
and Ethmoid Sinuses
Although not routinely performed in the emergency department, examination of nasal secretions also has been used to establish a diagnosis as well as to tailor therapy. While nasal cytology has been used to establish a diagnosis through neutrophil counts,56 culture of secretions is employed more commonly. Traditionally, sinus puncture has been used. Maxillary sinus puncture is performed through the lateral wall of the interior mental meatus.57 Because of the invasive nature of this procedure, newer endoscopic sampling, which is much less painful, has been established as a reasonable alternative.58 Nasal endoscopic sampling has been advocated as an adjunct to diagnosis and guidance in cases of treatment failure.53 Culture diagnosis often takes 2-3 days to obtain a specific etiology and antibiotic sensitivities. Other laboratory studies are unnecessary in the evaluation and management of most patients with uncomplicated rhinosinusitis.
Management
The first and most important question to ask in treatment is whether to use antibiotics. It is extremely important to limit use of antibiotics to those infections requiring antimicrobials for recovery and clinical benefit. This is due to the very real phenomena of antibiotic overuse, increasing antibiotic resistance, and subsequent development of difficult-to-treat complications. Appropriate antibiotic therapy is of paramount importance, even though it is estimated that spontaneous recovery occurs in 48% of patients.10 Most importantly, antibiotics are beneficial and effective in the prevention of the infectious complications of rhinosinusitis.
Most studies regarding antibiotic therapy in acute bacterial rhinosinusitis have been conducted in otolaryngology, non-emergency department settings. Some trials failed to find a difference between various antibiotics and placebo.59-62 This is probably because antibiotics are unlikely to make a therapeutic difference in most cases of viral rhinosinusitis, which is most of the remainder of cases. After conducting its own systematic review, the Agency for Health Care Policy and Research (AHCPR) concluded that in patients with ABRS, more patients are cured and cured earlier, when treated with antibiotics rather than placebo.11 Within the past several years, panels of experts have presented thorough reviews and made recommendations regarding the management of ABRS.32,63-70 These consensus statements and systematic reviews support similar management guidelines for ABRS. They suggest that patients with rhinosinusitis symptoms lasting fewer than seven days are unlikely to have a bacterial infection. Treatment of ABRS should begin with the most narrow-spectrum agents active against the most likely pathogens, S. pneumoniae and H. influenzae. The currently recommended first line agents include amoxicillin or TMP-SMX. In areas in which resistance to S. pneumoniae is high, the dose of amoxicillin should be doubled (up to 80-90 mg/kg/day, maximum of 3 g/d).32 Although the Sinus and Allergy Health Partnership recommends TMP-SMX only as an alternative in beta-lactam-allergic patients for the treatment of mild ABRS in adults and children who have not received antibiotics in the previous 4-6 weeks,65 its use requires consideration of local resistance patterns and individual patient factors.71 Prescribing physicians should consider factors that predispose patients to antibiotic-resistant bacteria, such as contact with children in daycare centers and recent antibiotic use. Despite these recommendations and consensus statements, some physicians still prescribe first-generation cephalo-sporins, such as cephalexin and doxycycline, for ABRS.
One study looked at antibiotic susceptibility for nasal swab samples of 16,213 cases of ABRS seen in outpatient primary care settings.29 Of the four most common pathogens (S. pneumoniae, H. influenzae, M. catarrhalis, and S. aureus), only the fluoroquinolones had greater than 95% coverage of these pathogens. While the macrolides had decent coverage for S. pneumoniae isolates (64-68%), they did not fare so well against S. aureus (31-69%). Only 64% of S. pneumoniae isolates were susceptible to penicillin.29 It is important to keep in mind that this study evaluated in vitro susceptibility of nasal swab isolates and did not measure clinical response. Because most of the studies evaluating clinical response of rhinosinusitis looked at penicillins (penicillin, amoxicillin or amoxicillin-clavulanate) or TMP-SMX, recommendations have been made based on these findings. Amoxicillin and TMP/SMX are recommended for first-line therapy for ABRS. Second-line agents include a variety of cephalosporins, fluoroquinolones, and macrolides. If symptoms do not improve in 72 hours, second-line antibiotic agents should be prescribed. For patients who fail to respond to initial therapy, sinus CT should be considered to confirm the diagnosis and assess for complications. In addition, referral to an ear, nose, and throat (ENT) specialist may be required. An algorithm for treatment of ABRS is found in Figure 4.
While the consensus statements would suggest only a small proportion of patients with upper respiratory infection symptoms presenting to an acute care setting would benefit from antibiotic treatment, the reality is that many more are prescribed antibiotics. Although the prescription rate is improved somewhat from earlier studies showing between 85% and 98% prescription rates,72,73 a more discriminate approach to antibiotic use is needed. Because many of the antibiotic vs. placebo trials have shown high cure rates without antimicrobials, it is important to limit antibiotic use. Recently, topical delivery of antibiotics has received attention as a method of decreasing systemic effects of antibiotic abuse. Nebulized solutions of locally delivered fosfomycin (Monurol) and tobramycin (TOBI) both have shown promise in treating ABRS. (The inhaled versions of both of these drugs are not FDA approved.)74,75
A multi-disciplinary panel consisting of emergency physicians, otolaryngologists, infectious disease experts, and primary care physicians have issued a set of guidelines based on evidentiary trials and other convenience, resistance, and patient toleration factors. (See Table 3.)
Other modalities useful in treating ABRS include nasal steroids, nasal saline, decongestants, and analgesics. Although most of these supportive therapies are unproven, these measures are inexpensive, uncomplicated, and do not have major side effects.32 These work by eliminating causative factors and controlling inflammatory components. Steroids studied include beclomethasone diproprionate (Beconase AQ, Beconase, Beclovent, Vancenase AQ, Vanceril), mometasone furoate (Elocon, Nasonex), and fluticasone propionate (Flovent, Flonase).76-81 A randomized trial compared intranasal steroids to placebo and found that the addition of intranasal steroid to antibiotics significantly reduces symptoms of acute rhinosinusitis compared with antibiotic treatment alone.76 Steroids also may be beneficial in prophylaxing against future episodes of rhinosinusitis by preventing impedance to mucus flow.78 An interesting feature of macrolides is their anti-inflammatory properties, explaining a reason in addition to the antimicrobial spectrum, that they are successful in treating ABRS.82,83 Decongestant nasal sprays (e.g., oxymetazoline [Afrin] and phenylephrine hydrochloride [Neo-Synephrine]) relieve acute symptoms by reducing mucosal edema. Their use should be limited to three days as they may cause rebound vasodilatation and inflammation (rhinitis medicamentosa). Oral decongestants such as pseudoephedrine also are effective, reasonable supportive alternatives. Mucolytic agents (e.g., guaifenesin) may facilitate mucociliary clearance by decreasing viscosity but there is no evidence that these may be useful. Saline spray or irrigation has a mild decongestant effect, liquifies viscous secretions, and is an important, often neglected adjunct to management.80 (See Table 4.) Antihistamines should not be used routinely because they may dry nasal and sinus secretions. Even in allergic rhinitis, the traditional indication for antihistamine therapy, intranasal corticosteroids are the recommended first-line therapy.84 Lastly, systemic analgesia, such as non-steroidal anti-inflammatory agents, can provide relief from associated discomfort. Surgery also is an option for patients in more complicated cases of rhinosinusitis and requires referral to an ENT specialist. Surgery may help to facilitate drainage of the involved sinus and to remove diseased mucosa.
Table 4. Adjunctive Therapy in ABRS63
Potential Complications
Acute bacterial rhinosinusitis can cause both intra- and extra-cranial complications such as meningitis, epidural or subdural empyema, cavernous sinus thrombosis, osteomyelitis, orbital cellulitis, or abscess.85 Untreated or undertreated ABRS also can evolve into chronic rhinosinusitis, which carries significant morbidity.29
Patients treated both with and without antibiotics may suffer complications from ABRS. These range from infectious to anatomic. Because strict diagnostic criteria for ABRS are used so infrequently, it is difficult to quantify the rate of complications. One study found a 3.7% complication rate, but this was in patients hospitalized for rhinosinusitis, which was more common several years ago but is unusual today.86 Patients who tend to suffer more complications, and thus usually would warrant otolaryngology referral, include those with immunocompromise, nasal polyps, or suggestion of chronic or repeated bacterial rhinosinusitis.80
One of the most common extra-nasal sites of infectious complications is the orbit, especially in the pediatric population. Untreated or inadequately treated rhinosinusitis often is the event leading to the development of orbital cellulitis in children. Other central nervous infectious complications, such as brain abscess or meningitis, are less common in the era of high antibiotic utilization, but still account for half of all infectious complications of ABRS.5 Infection may gain access to the intracranial space by direct extension through a defect in the posterior wall of the frontal sinus caused by the infection itself. Retrograde thrombophlebitis of the valveless ophthalmic vessels also may offer a route of transmission for infected material into the intracranial cavity.85 While antibiotics may have some impact on infectious complications, a review found that their use does not decrease the overall complication rate.87 Osteomyelitis can be diagnosed with the use of head CT or culture/biopsy of paranasal bones. Pott’s puffy tumor is osteomyelitis of the frontal bone, which causes a subperiosteal abscess. This usually is caused by S. aureus and its incidence also has dropped with the use of antibiotics.5
Anatomic complications from ABRS result from the changes that occur as the inflammation and tissue destruction change the structure and composition of the paranasal sinuses and surrounding area. The floor of the frontal sinus sits above the orbit, so disruption of the architecture predisposes to superior ophthalmic vein, dural vein, or cavernous sinus thrombosis or thrombophlebitis. Inflammation and scarring can contribute to the development of a mucocele, an expanded mucoid-filled sinus, or mucus retention cyst.
Complications of ABRS are not limited to individual instances, but can be expanded to include the impact on society that antibiotic overuse presents. The pharmacologic cost consideration is apparent, but increasing antibiotic resistance raises costs by the need for stronger, more expensive drugs and more resistant infections—including not only rhinosinusitis but also other infections. Penicillin-resistant S. pneumoniae is an increasing problem of variable magnitude in different communities, but will not retreat without extremely judicious use of narrow-spectrum drugs.
Disposition
The vast majority of patients with ABRS are treated successfully on an outpatient basis. The natural history of uncomplicated ABRS is resolution of symptoms in 4-10 days.88 It is difficult to prove that antibiotics change the clinical course for many reasons, including: 1) many people presumptively diagnosed with ABRS in reality have viral or allergic rhinosinusitis; 2) antibiotics often used to treat ABRS are effective against some but not all pathogens and isolates; and, thus 3) studies looking at efficacy are in fact diluted by many cases that would not respond to antibiotics regardless.
A proportion of patients do not respond to conventional therapy, including antibiotics and adjuncts. After a confirmation of the diagnosis with CT scan, these patients usually are referred to otolaryngologists for further care. One option is endoscopic sinus surgery. This procedure removes nasal polyps and thus the anatomic risk factor for mucous flow impedance. This newer procedure improves sinus drainage instead of just removing diseased mucosa.89 Another procedure, called the endoscopic modified Lothrop procedure, promotes patency in the frontal ostium. Symptomatic relief occurs in more than 90% of patients.90 Most patients who do not respond adequately to medical therapy eventually receive some sort of endoscopic sinus surgery.91
Special Populations
Immunocompromised patients, diabetics, those with cystic fibrosis, and children deserve special attention. The immunodeficient patient should be managed in consultation with an otolaryngologist, as sinus aspirate culture should be considered early in the course to guide therapy.
Cystic fibrosis patients are more prone to sinus infections by virtue of the ciliary defect. Staphylococcus aureus and Pseudomonas are particularly common causes of recurrent infection and should be treated accordingly with the appropriate antibiotic therapy.92 A culture diagnosis should be considered, owing to the frequent need for long-term antibiotics and chronicity of infections.
Although rhinosinusitis generally is more common in children than adults, frontal and sphenoid rhinosinusitis are rare in children. In the primary care setting, between 6% and 18% of children presenting with upper respiratory infections may have acute bacterial rhinosinusitis.11 Children are infected more frequently with M. catarrhalis than adults, and this should direct therapy effective against this pathogen. The American Academy of Pediatrics recommends a clinical diagnosis alone in children 6 years and younger. These symptoms should last more than 10 days but fewer than 30 days and include a fever of 39°C or higher, nasal or postnasal discharge, a daytime cough, and purulent nasal discharge present for at least 3-4 consecutive days.93 Adjuvant therapies are not recommended except for saline spray. Imaging is recommended only for complications or persistent symptoms. First-line therapy is high-dose amoxicillin (90 mg/kg/day in two divided doses). Amoxicillin/clavulanate or cefuroxime is recommended in cases that do not improve with amoxicillin. The Sinus and Allergy Health Partnership added cefpodoxime to the guidelines for treatment, and recommend a macrolide for patients who cannot tolerate penicillins due to allergy.66
Summary
Most patients with ABRS typically present with a multitude of symptoms, including headache, unilateral face or tooth pain, fever, and purulent nasal drainage. Although the gold standard for diagnosis includes sinus CT scan and culture of sinus aspirates, this is needed only in cases of diagnostic dilemma, lack of response to treatment, or complication. Empiric antibiotic therapy consists of amoxicillin, but only after symptoms have persisted at least seven days—making the diagnosis of viral rhinosinusitis less likely. Adjuvant treatment to antibiotics includes nasal decongestants, analgesics, intranasal saline, and steroid sprays. Referral to an otolaryngologist should be made for treatment failures, complications, or in special populations at high risk for the aforementioned. Surgical techniques can treat and prevent complications. Antibiotic overuse has become a problem in large part due to the massive abuse of antibiotics for simple upper respiratory infections incorrectly diagnosed as ABRS.
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Given the importance of acute bacterial rhinosinusitis (ABRS), a commonly encountered outpatient infection, this article attempts to outline in evidence-based detail what the authors conclude to be optimal, risk-stratified, empiric treatment recommendations. In addition, this review identifies key clinical findings, resistance patterns, risk factors, coexisting conditions, and other clinical triggers supporting referral of patients with ABRS to an otolaryngologist for more invasive i.e., multimodal surgical and more intensive antimicrobial management strategies.
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