Management of Bacterial Rhinosinusitis

Brought to you through an unrestricted educational grant from Aventis-Sanofi

Behavioral ObjectivesAfter completing this continuing education article, the pharmacist should be able to:

• Review the epidemiology and pathogenesis of rhinosinusitis,including a discussion of the bacteriologic etiology of rhinosinusitis.
• Compare and contrast the clinical features of acute (bacterialversus viral) and chronic rhinosinusitis.
• Understand the importance of judicious use of antibiotics inthe treatment of acute and chronic rhinosinusitis.
• Formulate a therapeutic plan for a given case study of apatient with acute or chronic rhinosinusitis.
• Describe the impact of resistance in the development of newdrugs and dosage formulations.

Acute Bacterial Rhinosinusitis

Acute bacterial rhinosinusitis (ABRS)occurs in approximately 0.5% to 2% ofall cases of viral upper respiratory tractinfections (URI).¹ It is estimated that20 million people acquire ABRS eachyear in the United States.² Sinusitis isthe 5th most common diagnosis forwhich an antibiotic is prescribed in theUnited States.³ In fact, 9% and 21% ofall antibiotic prescriptions in 2002were written for pediatric and adultpatients, respectively, with a diagnosisof sinusitis.⁴ Antibiotic prescriptionsfor acute sinusitis accounted for approximately$400 million to $600 millionin health care expenditures in2002.⁴ The estimated total expendituresassociated with sinusitis were$3.5 billion in 1996.⁵

Pathogenesis

The 4 pairs of sinuses include themaxillary, ethmoid, frontal, and sphenoidsinuses. Most cases of sinusitisinvolve the maxillary and/or ethmoidsinuses. Far less common is an isolatedinfection of the frontal or sphenoidsinus. Sinusitis is more properly termedrhinosinusitis because it is an inflammatoryprocess that involves the mucousmembranes of the nose and paranasalsinuses. Rhinosinusitis is classified asacute (sudden onset of symptoms withduration of <4 weeks), subacute (duration4 to 12 weeks), or chronic (duration>12 consecutive weeks).

Viruses are responsible for the majorityof acute rhinosinusitis.⁶ The humanrhinovirus accounts for almost 50% ofall viral URIs. Other viruses that cancause acute rhinosinusitis includeinfluenza A and B viruses, parainfluenzavirus, respiratory syncytial virus, adenovirus,and enterovirus. Most cases ofacute viral rhinosinusitis are self-limitingand resolve within 7 to 10 days.

Viruses inhibit macrophage andlymphocyte function, increasing susceptibilityto secondary bacterial infection.In addition, viruses cause inflammatorychanges which can block thesinus ostia, impair mucous drainage,and cause poor aeration, which createsan environment conducive for developinga bacterial infection.⁷ Therefore,ABRS is generally considered as asuperinfection that can occur any timeduring a viral URI. Although infrequent,ABRS may complicate 0.5% to2% of viral URIs.¹ The incidence ofABRS parallels the pattern of viral URIsand increases during early fall to earlyspring. Fungi, on rare occasions, cancause rhinosinusitis. Nasal allergy,trauma, swimming, local irritants, andnasal obstruction from polyps or foreignbodies may also precipitate ABRS.

ABRS occurs when bacteria that colonizethe nasopharynx invade the normallysterile paranasal sinuses. By earlychildhood, most children are colonizedby at least 1 of 3 respiratory tractpathogens, including Streptococcuspneumoniae, Haemophilus influenzae,and Moraxella catarrhalis.^8-10 Colonizationmay persist for up to 12 monthsand increases during the winter seasonwhen the incidence of viral URI rises.⁸S pneumoniae and H influenzae are themost common bacteria isolated fromadult patients with communityacquiredABRS (Table 1).^6,11-13 M catarrhalis,anaerobic bacteria, Staphylococcusaureus, and Streptococcus pyogenescan also cause ABRS. The distributionof bacterial pathogens in adults is similarin children, except M catarrhalis ismore prevalent in children thanadults.^11,12 Rhinosinusitis caused byanaerobic bacteria usually occurs aftera dental root infection.¹² The clinicalsignificance of atypical pathogens,including Chlamydia pneumoniae andMycoplasma pneumoniae, in the pathogenesisof community-acquired ABRSremains unclear.

Nosocomial ABRS may occur duringhospitalization, especially in patientswith nasal colonization by entericgram-negative bacilli, patients beingfed by nasogastric tubes, patientsundergoing sedation, and those scoring7 on the Glasgow coma score.¹⁴ Thecommon pathogens associated withnosocomial rhinosinusitis in adultsand children include S aureus,Pseudomonas aeruginosa, Escherichiacoli, Klebsiella pneumoniae, and otherEnterobacteriaceae organisms.^15,16 Anaerobicbacteria, Candida species (especiallyCandida albicans), and fungi mayalso cause nosocomial ABRS. Polymicrobialinfection may occur in the hospitalsetting.^15,16

Clinical Presentation and Diagnosis

No single sign or symptom clinicallydistinguishes a viral rhinosinusitis("common cold") from ABRS, presentinga challenge to primary care physicians.Most patients with ABRS initiallyreport symptoms of the commoncold, including sneezing, rhinorrhea,nasal congestion, postnasal drip, sorethroat, cough, fever, and myalgia.ABRS is a secondary infection thatoccurs after the onset of a viral URI,especially if symptoms persist after 7 to10 days or symptoms worsen after 5 to7 days of illness.^6,13 Double sickening,which occurs when a patient clinicallyworsens after initial improvement, isalso suggestive of ABRS. In patientswith rhinorrhea, nose blowing maycreate enough pressure to introducebacteria from the middle meatus to thesinus cavity and thereby cause infection.¹⁷ Inflammation of the nose andparanasal sinuses may persist for 2months.

Predictors for ABRS consist of maxillarydental pain, facial erythema/swelling/pain (especially when unilateral),purulent (thick, colored, andopaque) nasal secretions, history ofcolored nasal discharge, poor responseto decongestants, and fever.^6,13,18 It isimportant to note that purulent nasalsecretions and a change in the color ofnasal discharge are not specific indicatorsof bacterial infection. Purulent dischargecan also occur in patients withviral rhinosinusitis. Localization offacial pain or tenderness may assist indetermining the affected sinus (ie,cheek or upper teeth pain for maxillaryinfection, forehead pain for frontal,tenderness over the medial canthalregion for ethmoid, or retro-orbitalpain for sphenoid). Symptoms of ABRSmay persist for 4 weeks.

Community-acquired ABRS shouldbe highly considered in patients withpersistent symptoms of the commoncold?lasting more than 7 to 10 days?or in patients with worsening symptomsafter 5 to 7 days. Persistent orworsening symptoms are highlyindicative of a secondary bacterialinfection, especially in the presence offacial erythema/swelling/pain, fever,and poor response to decongestants.Some patients may present withoutinitial symptoms of viral URI. In thesepatients, tooth pain or other signs of adental infection, a history of allergy,swimming, and/or persistent nasalobstruction are usually present. NosocomialABRS should be considered inpatients with nasal intubation orimpaired sinus drainage.

Complications of acute rhinosinusitisthat involve the central nervous system,orbit of the eye, and periorbitaltissues rarely occur.^6,11 In the presenceof these complications, immediatemedical attention is necessary. Abnormalvision, altered mental status, andperiorbital edema may signify the presenceof complications. Patients presentingwith these symptoms shouldbe closely monitored.

The gold standard for diagnosingABRS is sinus puncture with subsequentaspirate culture.^6,12 Sinus punctureis rarely performed in the ambulatorysetting for immunocompetentpatients, however, because it is aninvasive and painful procedure. As aresult, the diagnosis of ABRS is almostalways a clinical diagnosis. Althoughno single sign or symptom is highlysensitive or specific, the presumptivediagnosis of ABRS based on the overallconstellation of clinical findings isgenerally sufficient for treatment. Theuse of imaging studies (radiography,computerized tomography [CT], ormagnetic resonance imaging) is notnecessary to confirm diagnosisbecause abnormal findings indicatepresence of inflammation withoutproviding the cause (ie, virus, bacteria,or allergy). Imaging studies should,however, be considered in patientswith suspected acute complications(eg, orbital cellulitis) or in those individualswith persistent or recurrentinfection who are unresponsive totherapy.¹¹ CT scanning is the imagingstudy of choice because it is more sensitiveand specific than plain radiographs.

Treatment

Symptomatic relief is the primarygoal in the treatment of viral rhinosinusitis.Initial therapy with decongestants,humidifiers, nonsteroidal antiinflammatorydrugs (NSAIDsincluding ibuprofen and naproxen),acetaminophen, and/or possiblymucolytics may help suppress symptomsin patients with viral rhinosinusitis.In the presence of cough, acough suppressant (dextromethorphan)may be added. Although commonlyused, there is lack of evidencesupporting the benefits of first-generationantihistamines (eg, chlorpheniramine,brompheniramine, and clemastine),mucolytic agents, andtopical intranasal steroids for symptomatictreatment.^1,11 Saline nasal dropsor spray, however, may be beneficialby serving as a mild vasoconstrictor,dissolving secretions, and preventingcrust formation.11 Treatment shouldcontinue for several days. If symptomspersist after 7 to 10 days or worsenafter 5 to 7 days, initiation of antibiotictherapy to treat a potential secondarybacterial infection should be considered.

Because the clinical features of viralrhinosinusitis and ABRS are similar, itis not surprising to observe excessiveuse of antibiotics. Overuse of antibioticshas contributed to emergenceand increasing prevalence of resistancein the United States, particularlyS pneumoniae to penicillin, trimethoprim/sulfamethoxazole (TMP/SMX),macrolides, doxycycline, and ofloxacin.19 In addition, H influenzae and Mcatarrhalis produce &#946;-lactamases,which render resistance to all &#946;-lactamantibiotics except &#946;-lactamase inhibitorcombinations and cephalosporins.^19-21

ABRS may spontaneously resolvewithout antibiotic treatment in bothadults and children.^6,22 In fact, theresults of 2 meta-analyses indicate thatthe benefit of using antibiotics inpatients with ABRS is minimal andthat 69% of patients receiving placeboimprove by 14 days.^23,24 If initiated,antibiotic treatment of ABRS shouldtarget the common pathogens, particularlyS pneumoniae, H influenzae, andM catarrhalis. Although ABRS is usuallya self-limited infection, eradicationof bacterial pathogens may lead todecreased duration of illness and preventcomplications associated withABRS. Bacterial resistance is an importantconcern when considering therapeuticoptions. The risk of acquiringinfection caused by resistant pathogensincreases with recent antibioticuse.²⁵

Treatment recommended by theSinus and Allergy Health Partnershipfor adult patients with mild community-acquired ABRS and no recent antibioticexposure are listed in Table 2.¹³The recommended first-line agents areamoxicillin (&#177; clavulanate) and second-and third-generation cephalosporins(specifically, cefuroxime, cefpodoxime,and cefdinir). High-doseamoxicillin (&#177; clavulanate) should beused in patients with suspected drug-resistantpneumococci (eg, recentantibiotic use, immunodeficiency, andcontact with children attending daycare). When M catarrhalis is highly suspected,the use of amoxicillin alone isineffective because most isolates produce&#946;-lactamases. Treatment optionsfor M catarrhalis include amoxicillinwith clavulanate and cephalosporins.Because failure rates can reach 25%,TMP/SMX, doxycycline, macrolides,and telithromycin should be reservedfor patients with true allergy or intoleranceto &#946;-lactam antibiotics. Patientsgenerally respond to appropriate treatmentwithin 48 to 72 hours. Recommendationfor initial antibiotic treatmentprovided by the Centers forDisease Control and Prevention andthe Infectious Diseases Society ofAmerica is similar to the Sinus andAllergy Health Partnership. Initialtherapy should include narrow-spectrumagents including amoxicillin,doxycycline, and TMP/SMX.⁶

Patients with mild disease who areunresponsive after 72 hours of antibiotictherapy, patients with mild ABRSand recent exposure to antibiotics(within the previous 4 to 6 months),and patients with moderate diseaseshould be treated with respiratory fluoroquinolones(levofloxacin, gatifloxacin,and moxifloxacin), highdoseamoxicillin/clavulanate (4 g/250 mg per day), or ceftriaxone.¹³Clinical response is predicted in 90%to 92% of patients receiving respiratoryfluoroquinolones, ceftriaxone, oramoxicillin/clavulanate, and 83% to88% with amoxicillin, cefpodoxime,cefixime, cefuroxime, and cefdinir.The recommended duration of therapyfor all patients with ABRS is 10 to14 days, although a 7-day course ofamoxicillin (&#177; clavulanate) has beenevaluated.¹³ Studies indicate that 5days of ceftriaxone or telithromycinand 3 days of azithromycin are alsoeffective.^13,26,27

Treatment options for ABRS in children(Table 2) are similar to adults,except doxycycline is contraindicatedin children <8 years of age because ofthe risk for permanent teeth discoloration.^11,13 In addition, telithromycinhas not been approved by the FDA forpediatric use.²⁶ Because of its safety,palatability, and low cost, the AmericanAcademy of Pediatrics recommendsamoxicillin as first-line therapyin children with mild to moderatesymptoms. High-dose amoxicillinshould be used in patients with suspecteddrug-resistant pneumococci.High-dose amoxicillin with clavulanateis recommended for childrenwith moderate to severe symptoms(fever &#8805;39°C with concurrent purulentnasal discharge for at least 3 to 4 consecutivedays or persistent symptomsexceeding 10 days), recent antibioticexposure, or in those who attend daycare.¹¹ When using high-dose amoxicillinwith clavulanate, the recommendeddose of clavulanate is 6.4mg/kg/day to limit the incidence ofdiarrhea. Other therapeutic optionsinclude cefpodoxime, cefuroxime, cefdinir,and ceftriaxone. Except for a historyof immediate Type I hypersensitivityreaction to &#946;-lactams, childrenwith other types of reactions to onespecific &#946;-lactam antibiotic may tolerateanother &#946;-lactam. Therapy shouldcontinue for 10 to 14 days, or 7 days

after the beginning of clinical improvement.The bacterial pathogens associatedwith nosocomial rhinosinusitis differfrom those in community-acquiredrhinosinusitis. Empiric antimicrobialtherapy for nosocomial rhinosinusitisshould provide adequate coverage for Saureus and gram-negative bacteria. Ifsinus aspirate culture and sensitivityinformation are available, treatmentshould be tailored toward the specificpathogen. Polymicrobial infectionmay occur in patients with nosocomialbacterial rhinosinusitis.

Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is acommonly diagnosed illness thataffected almost 30 million people inthe United States in 2002.²⁸ The socioeconomicimpact of CRS is significant.CRS results in an estimated 18 millionto 22 million physician office visitsannually and $200 million in expenditureson medications.^29,30 Furthermore,this chronic disease may lead to functionaland emotional impairmentsthat affect quality of life.³¹

Pathogenesis

The pathogenesis of CRS is an ongoingarea of research. The cause of CRSis believed to be multifactorial. Potentialcauses or predisposing factorsinclude microorganisms (bacteria, fungi),inflammatory agents (eg, allergens,pollutants, smoke), asthma, cysticfibrosis, immunodeficiency, nasalpolyposis, and autoimmune diseases(eg, systemic lupus erythematosus,Wegener's granulomatosis).³⁰ Thesefactors may appear concurrently tocause persistent inflammation of thenose and paranasal sinuses.

The microbiology and role of bacteriain the pathogenesis of CRS are notas well established as for ABRS. Thepresence of bacteria may provide adirect insult to the nose and paranasalsinuses to cause CRS. Alternatively, thebacteria can indirectly cause CRS byaggravating a noninfectious inflammatoryprocess. The predominant bacteriaassociated with CRS are coagulase-negativestaphylococci (24% to 36%),S aureus (22% to 25%), Streptococcusspecies (20% to 27%), and anaerobes(6% to 10%).^32-34 The clinical significanceof coagulase-negative Staphylococcusis uncertain. Some studies reporta high incidence (19% to 48%) ofanaerobic bacteria isolated in patientswith CRS.^35,36 The most commonanaerobes are Prevotella species, anaerobicstreptococci, and Fusobacteriumspecies. Polymicrobial infections occurmore often in CRS than ABRS.³⁷

The clinical significance of fungiremains controversial. Some studiesdemonstrate a role of fungi in thepathogenesis of CRS.³⁰ Disease occurseither by formation of fungal balls orinflammatory response to the presenceof the fungus. A clinically distinctform of CRS is allergic fungal rhinosinusitis.Patients with allergicfungal rhinosinusitis present withnasal polyposis, allergy, production ofeosinophilic mucin, and unilateralpredominance.³⁸

Clinical Presentation and Diagnosis

The clinical features of CRS are comparableto acute sinusitis, making diagnosisof CRS very difficult. The maindistinction between chronic and acutedisease is duration of symptoms.Patients with CRS present with persistentinflammation of the mucosa ofthe nose and paranasal sinuses lasting>12 weeks.³⁰ The most common andproblematic symptoms experienced bypatients with chronic infection includenasal obstruction or congestion, headache,and fatigue.³⁹ The presence ofnasal polyps, crusts, and turbinate edemaor hypertrophy are also commonfindings in patients with CRS. In contrastto ABRS, purulent nasal dischargeis highly suggestive of a bacterial etiologyin patients with CRS. A diagnosisof CRS should be confirmed by physicalevidence of mucosal inflammation.³⁰

Patients with CRS who are unresponsiveto treatment are candidatesfor sinus cultures and/or imaging studies.A standard sinus CT scan is the preferredmethod to locate, confirm, anddetermine severity of disease.^40,41 Itshould be used to evaluate patientsbefore undergoing sinus surgery.

Treatment

Because the pathogenesis mayinvolve multiple factors, which currentlyremain largely unknown, theoptimal treatment of CRS is uncertain.In fact, there are currently no antimicrobialsapproved by the FDA for treatmentof CRS. Antibiotics that havebeen studied in patients with bacterialCRS or acute exacerbation of CRS areamoxicillin/clavulanate and cefuroxime.⁴² The use of clarithromycin, clindamycin,or a respiratory fluoroquinolonecan be considered inpatients with allergy to pencillin.⁴³ Therecommended duration of therapy is 3to 6 weeks; however a 14-day coursehas been shown to produce a 90% clinicalresponse.⁴²

Other treatment modalities thatshow benefit in providing symptomaticrelief are nasal lavage and topicalsteroids. Nasal irrigation with a warmsaline solution (isotonic or hypertonic)twice daily has been shown to reducenasal congestion.^44,45 In patients withallergic disease, steroidal intranasalsprays (fluticasone) may help reducemucosal inflammation and swelling.⁴⁶Nebulized antibiotics, decongestants,mucolytic agents, and antihistaminesmay serve as adjunctive therapies; theevidence for their value in treatment ofCRS, however, is either inconclusive ordeficient. Sinus surgery may be consideredin patients who fail aggressivepharmacologic therapy.

Challenges of BacterialResistance

Over the past few decades, antibioticresistance has increased dramatically.To address resistance, the most recentguidelines for treatment of acute rhinosinusitisfocus on judicious use ofantibiotics.^6,11,13,47 Improper diagnosisof ABRS leading to overuse of antibioticsmay have contributed to theincreasing trend of resistance amongrespiratory bacterial pathogens. Multidrugresistant pneumococci, defined asstrains resistant to at least 3 classes ofantibiotics, were recovered in 26% ofall isolates.¹⁹

The most common bacterial pathogensassociated with ABRS are S pneumoniae,H influenzae, and M catarrhalis.Alteration of the penicillin-bindingproteins, a resistance mechanismacquired by pneumococci, renders theorganism resistant to penicillins,cephalosporins, and other &#946;-lactamantibiotics. In the United States, theprevalence of penicillin-nonsusceptible(include resistant and intermediatelysusceptible) strains of S pneumoniaereached a peak of 36% in 2001.⁴⁸ Inaddition, penicillin-nonsusceptiblestrains of S pneumoniae are associatedwith cross-resistance to other classes ofantibiotics; thus these isolates aretermed drug-resistant S pneumoniae(DRSP). Resistance of DRSP to otherantibiotics includes TMP/SMX (37%),macrolides (29%), doxycycline (21%),clindamycin (10%), and ofloxacin(7%).¹⁹ Most isolates of S pneumoniaeremain susceptible to respiratory fluoroquinolones(including gatifloxacin,gemifloxacin, levofloxacin and moxifloxacin).However, concern for developmentof resistance is arising fromextensive use of fluoroquinolones inthe treatment of community-acquiredrespiratory tract infections, however.⁴⁹

Cross-resistance between erythromycinand clindamycin occurred inapproximately 32% of S pneumoniaeisolates in the United States.¹⁹ Resistanceto both erythromycin and clindamycinis mediated by the ermB ribosomalmethylation mechanism (MLSBphenotype),which inhibits binding ofthe antibiotic to the target site.^50,51Most erythromycin-resistant S pneumoniaestrains (68%) remain susceptibleto clindamycin, however.⁵² In theseisolates, resistance occurs by the mefAefflux pump (M-phenotype), whichdecreases antibiotic accumulation inthe bacteria.^50,53

H influenzae (30%) and M catarrhalis(92%) confer resistance to penicillinsby producing &#946;-lactamases.¹⁹ &#946;-lactamase-inhibitor combinations (eg,amoxicillin with clavulanate) andcephalosporins (specifically, ceftriaxone,cefixime, and cefdinir) retainexcellent activity against thesepathogens. Both H influenzae andM catarrhalis are highly susceptible tothe fluoroquinolones. Resistance ofH influenzae to TMP/SMX (22%) hasbeen observed.¹⁹

Recently Available Agents

Newer antibiotics and dosage formulationsprovide treatment options forinfections caused by resistant respiratorypathogens. High-dose amoxicillinwith clavulanate is now available informulations intended to enhancecompliance and effectiveness againstDRSP (1000 mg amoxicillin and 62.5mg clavulanate per extended-releasetablet; 14:1 ratio of amoxicillin toclavulanate in powder for oral suspension).Amoxicillin (&#177; clavulanate),which exerts its bactericidal activity byinhibiting cell-wall synthesis, remainsa first-line agent in the treatment ofABRS. In addition, the clavulanatecomponent provides activity against&#946;-lactamase producers, H influenzaeand M catarrhalis.

Pharmacokinetic and pharmacodynamicstudies demonstrate that highdoseamoxicillin (&#177; clavulanate),defined as 4 g/day in adults and 80mg/kg/day to 90 mg/kg/day in children,provides enhanced activityagainst DRSP.^54,55 The most commonadverse effects are gastrointestinal-related,including nausea and diarrhea.The incidence of adverse effects associatedwith high-dose amoxicillin iscomparable to standard-dose amoxicillin.^55,56 Compared with twice dailydosing, however, 3-times-daily dosingof high-dose amoxicillin was associatedwith significantly higher incidenceof diarrhea.⁵⁴

Fluoroquinolones bind to DNAgyrase and topoisomerase IV to inhibitbacterial DNA synthesis. The respiratoryfluoroquinolones provide excellentcoverage against respiratory pathogens,including atypical bacteria. Therole of atypical bacteria in rhinosinusitisis uncertain, however. Levofloxacin,gatifloxacin, and moxifloxacin, whichhave been available for a number ofyears, provide excellent activity againstS pneumoniae, H influenzae, M catarrhalis,and S aureus⁵⁷ and are FDA-approvedfor treatment of ABRS. Anewer agent, gemifloxacin, also providesexcellent activity against respiratorypathogens, but this agent has yetto gain FDA approval for use in ABRS.Ciprofloxacin, while active againstH influenzae and M catarrhalis, has limitedactivity against pneumococci. Theprimary concern with the use of fluoroquinolonesis the recent emergence ofpneumococci with reduced susceptibilityto fluoroquinolones.^47,49,58

The more recent macrolides, includingclarithromycin and azithromycin,also possess excellent activity againstS pneumoniae, H influenzae, M catarrhalis,and atypical respiratory pathogens. Bybinding to the 50S ribosomal subunit,macrolides inhibit protein synthesis toexert their bacteriostatic activity. FDArecently approved the extended-releaseformulation of clarithromycin foronce-daily dosing to enhance compliance.Fluoroquinolones and macrolidesare therapeutic options inpatients with true hypersensitivity topenicillin. They have been associatedwith emerging resistance, however,particularly among penicillin-nonsusceptiblepneumococcal isolates in theUnited States.^19,47,59

A new class of antibiotics called theketolides was developed to addressmacrolide-resistant bacteria.⁶⁰ In thepresence of the ermB gene (and in thecase of telithromycin, ermB and mefAgenes), ketolides remain active againstmacrolide-resistant pathogens.⁶¹ Althoughsimilar to the macrolides,ketolides bind more tightly to the 50Sribosomal subunit to enhance activityagainst respiratory pathogens.⁶² Telithromycin,the first ketolide, recentlyreceived FDA approval for the treatmentof acute bacterial rhinosinusitis.The spectrum of activity of telithromycinin acute bacterial sinusitisincludes S pneumoniae, H influenzae,M catarrhalis, and S aureus.⁶³ Telithromycin800 mg once daily for 5 daysprovided a clinical cure rate of 75% to91%.^26,64,65 The most common adverseeffects reported were gastrointestinal-related,including nausea and diarrhea.

Conclusion

To optimize treatment of acute andchronic rhinosinusitis, the clinicianmust understand the pathogenesis anddistinct clinical features of these infections.Viruses are responsible for mostcases of acute rhinosinusitis. The causeof chronic rhinosinusitis is multifactorial,and the role of bacteria in its pathogenesisis not well established. The useof antibiotics in viral acute rhinosinusitisis inappropriate and contributes tothe increasing prevalence of bacterialresistance. Antibiotic resistance is alimitation in the management of ABRS,thereby necessitating appropriate useof antibiotics. To encourage judicioususe of antibiotics, the clinician mustdetermine when bacterial infection ishighly probable and subsequently considerguidelines when selecting theoptimal therapy.

Jennifer Le, PharmD: Assistant Professor of Pharmacy Practice, College of Pharmacy, Western University of Health Sciences. Martin S. Lipsky, MD: Dean and Professor of Family Medicine, University of Illinois, College of Medicine, Rockford

For a list of references, send a stamped,self-addressed envelope to: ReferencesDepartment, Attn. A. Stahl, Pharmacy Times,241 Forsgate Drive, Jamesburg, NJ 08831;or send an e-mail request to: astahl@mwc.com.

CE REVIEW QUESTIONS

(Based on the article starting on page 63.) Choose the 1 most correct answer.

1. Rhinosinusitis is classified as acute,subacute, and chronic based on the durationof symptoms. What is the durationof symptoms in a patient with acute rhinosinusitis?

• Less than 2 weeks
• Less than 4 weeks
• 4 - 8 weeks
• 8 - 12 weeks

2. What is the most common cause ofacute rhinosinusitis?

• Fungi
• Yeasts
• Bacteria
• Viruses

3. What are the most common causes ofacute community-acquired bacterial rhinosinusitisin adults?in descending order of prevalence?

• Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis
• Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis
• Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis
• Haemophilus influenzae, Moraxella catarrhalis, and Chlamydia pneumoniae

4. It is difficult to clinically distinguish a viral upper respiratory infection ("commoncold") from acute bacterial rhinosinusitis (ABRS). Which of the followingclinical features is a predictive factor specifically for ABRS?

• Maxillary dental pain
• Unilateral facial swelling
• Poor response to decongestants
• A, B, and C

5. Select the patient who most likely hasacute bacterial rhinosinusitis.

• 25-year-old man with sneezing, rhinorrhea,and nasal congestion for 2 days
• 29-year-old woman with fever, rhinorrhea,sore throat, and cough for 5 days
• 22-year-old man with sneezing,nasal congestion, and a history ofcolored nasal discharge for 5 days
• 35-year-old man with fever, rhinorrhea,cough, and toothache for 6 days

6. Which of the following characteristicsis a risk factor for developing nosocomialbacterial rhinosinusitis?

• Glasgow coma score greater than 8
• History of allergy
• Nasal intubation
• Increasing age

7. Diagnosis of acute bacterial rhinosinusitisin immunocompetent patients isgenerally based on:

• Computerized tomography (CT)
• Magnetic resonance imaging
• Sinus puncture and aspirate culture
• Clinical presentation

8. A 40-year-old man presents to thephysician office with a 7-day history ofnasal congestion and purulent rhinorrheaand a 3-day history of fever. When wouldCT scanning be appropriate for thispatient with acute bacterial rhinosinusitis?

• To confirm diagnosis
• To differentiate between viral andbacterial cause of his infection
• To differentiate between acute andchronic rhinosinusitis
• To determine presence ofcomplication

9. A 45-year-old man presents to theambulatory clinic with complaints offatigue, nasal congestion, and headachefor the past 3 months. Patient does nothave any allergies. Which of the followingadjunctive therapy has been shownto reduce nasal congestion and should berecommended for this patient?

• Nasal irrigation with a warm salinesolution
• Steroidal intranasal sprays
• Nebulized antibiotics
• Nasal decongestants

10. Bacterial resistance is an importantconcern when considering therapeuticoptions for ABRS. Which of the followingcharacteristics is a risk factor fordeveloping ABRS caused by a resistantpathogen?

• Recent antibiotic use
• Contact with children attendingday care
• Moderate to severe infection
• A and B

11. A 32-year-old woman presents to anambulatory clinic with a 10-day history of nasal congestion, rhinorrhea, andpostnasal drip. She has tried OTC medications including a nasal decongestant,ibuprofen, and guaifenesin for the past 5 days without any improvement in symptoms.During the past 2 days, the patient began to experience facial pain andcough. She does not have any known allergies. In addition to the use of nasalsaline therapy, what would you recommend for this patient?

• Amoxicillin for 5 days
• Doxycyline for 5 days
• Amoxicillin for 10 days
• Doxycyline for 10 days

12. The recommended duration of therapy for acute community-acquired bacterialrhinosinusitis is 10 to 14 days. However, a 5-day course is also effective. Whichof the following antibiotic(s) would you consider using for 5 days in an adult patient?

• High-dose amoxicillin with clavulanate
• Cefpodoxime
• Telithromycin
• Doxycycline

13. A 7-year-old girl has a fever of 38.5°C and purulent nasal discharge for the past3 days. The patient does not attend day care and was not exposed to an antibioticrecently. She experiences a nonpruritic rash when using amoxicillin. What is themost appropriate therapy for her diagnosis with acute bacterial rhinosinusitis?

• Cefuroxime
• Telithromycin
• Clindamycin
• Doxycycline

14. The bacterial pathogens associated with acute nosocomial rhinosinusitis differfrom acute community-acquired rhinosinusitis. What bacterial pathogenshould be empirically covered when treating nosocomial rhinosinusitis?

• Enterococcus faecalis
• Staphylococcus aureus
• Chlamydia pneumoniae
• Streptococcus pyogenes

15. Polymicrobial infection is most likely to occur in patients with:

• Acute community-acquired bacterial rhinosinusitis.
• Acute viral rhinosinusitis.
• Acute nosocomial rhinosinusitis.
• Chronic rhinosinusitis.

16. All of the following factors have been associated as potential etiologies forchronic rhinosinusitis except:

• Bacteria.
• Allergens.
• Cystic fibrosis.
• Chronic obstructive pulmonary disease.

17. What is the main distinction between acute and chronic rhinosinusitiscaused by bacterial pathogens?

• Duration of nasal inflammation
• High fever
• Headache
• Nasal congestion

18. A 39-year-old woman complains of fatigue, headache, fever, and purulentnasal discharge. Physical evidence of nasal mucosal inflammation and durationof symptoms for more than 12 weeks indicate that the patient haschronic rhinosinusitis. Which symptom or factor suggests that the patient has abacterial infection?

• Purulent nasal discharge
• Fatigue
• Headache
• Fever

19. An aspirate culture of a patient with acute bacterial rhinosinusitis was positivefor Streptococcus pneumoniae. Susceptibility testing indicated that the isolate wasresistant to both erythromycin and clindamycin.What is the mechanism of resistance displayed by this isolate of S pneumoniae?

• Alteration of penicillin-binding protein
• Production of &#946;-lactamase
• ermB ribosomal methylation
• mefA efflux pump

20. Why is twice-daily dosing preferred over 3-times-daily dosing of high-doseamoxicillin with clavulanate?

• Limit true hypersensitivity reactions
• Limit the incidence of diarrhea
• Increase effectiveness against drug-resistant Streptococcus pneumoniae
• Increase effectiveness against Moraxella catarrhalis

CE ANSWER FORM INSTRUCTIONS

TESTING AND GRADING PROCEDURES

• Each participant achieving a passing grade of 70% or higher onany examination will receive a statement of credit giving thenumber of CE credits earned. This form should be safeguardedand may be used as documentation of credits earned.
• Participants receiving a failing grade on any exam will be notifiedand permitted to take 1 reexamination at no extra cost.
• All answers should be recorded on the answer form attached.For each question, decide which choice is the best answer, andcircle the letter of the response representing your choice.
• Mail your completed exam form to the following address: PharmacyTimes, 405 Glenn Drive, Suite 4, Sterling, VA 20164-4432.

NEW SCORING OPTIONS

• Mail
• Fax: 703-404-1801
• This lesson is FREE on-line; receive instant grading, as wellas download your certificate?www.pharmacytimes.com

Please print clearly?certificate will be issued frominformation given.Please mail completed forms to:Pharmacy Times CE Department, 405 Glenn Drive,Suite 4, Sterling, VA 20164-4432