Jennifer Cortes, PharmD Candidate

Dr. Kyle is an assistant professor ofpharmacy practice at the McWhorterSchool of Pharmacy at SamfordUniversity, Birmingham, Alabama.Ms. Cortes is a 2009 PharmD Candidateat Palm Beach Atlantic University,Gregory School of Pharmacy, West PalmBeach, Florida.

Approximately 20 million casesof acute bacterial rhinosinusitis(ABRS) occur every yearin the United States.

 According toNational Ambulatory Medical CareSurvey data, ABRS is the fifth mostcommon reason physicians prescribeantibiotics.

 ABRS results in >1.5 millionambulatory care visits and anexpenditure of $5.3 billion yearly inthe cost of office visits, procedures,and antibiotics.

ABRS usually follows a viral upperrespiratory tract infection, which canbe caused by human rhinovirus, respiratorysyncytial virus, adenovirus,parainfluenza, and enterovirus.

 ABRSalso can develop as a result of nose andparanasal sinus inflammation, whichcan be caused by dental infection, allergies,or trauma.

The most prevalent risk factor forABRS is having a recent viral upperrespiratory tract infection. Other riskfactors include allergic or nonallergicrhinitis, anatomical abnormalities (eg,a deviated septum or hypertrophic middleturbinates), diving and swimming,exposure to cigarette smoke, cysticfibrosis, and asthma.

The most common signs and symptomsof ABRS tend to overlap withthose of viral upper respiratory tractinfections. These begin after an initialblockage of the maxillary sinus ostium,located beneath the middle turbinate.This blockage, along with mucus retentionand bacteria accumulation, bringabout such symptoms as nasal drainageand congestion; facial pain or pressure,especially when concentrated in 1 areaof the sinuses; postnasal drip; hyposmiaand, in some cases, anosmia; fever;cough; fatigue; and possible dental andear pain.

According to a position paper ofthe Centers for Disease Control andPrevention, the American Academyof Family Physicians,the AmericanCollege of Physicians-American Societyof Internal Medicine, and the InfectiousDiseases Society of America, 4 signsand symptoms are the most beneficialin predicting ABRS4: purulent nasal discharge;maxillary tooth or facial pain,especially when it is unilateral; unilateralmaxillary sinus tenderness; andworsening symptoms after an initialimprovement.

Due to overlapping symptoms, it oftencan be hard to properly diagnoseABRS. Physical examination providesvery little information. Computed axialtomography scans and magnetic resonanceimaging can be helpful at timesin the diagnosis, but are not necessaryfor ABRS.

 The ideal way to confirma diagnosis of ABRS is to aspirate thefluid from the affected sinuses andperform a culture.

 In the diagnosisof ABRS, the culture of the purulentsinus mucus should reveal at least 10

 This method isinvasive, time-consuming, and painfuland therefore not routinely performed.

In general, a diagnosis of ABRS is madein children and adults when signs andsymptoms have not improved after 10days or when the symptoms worsenover 5 to 7 days.

The question of whether or not totreat ABRS is not easy to answer for anumber of reasons. Roughly 97.8% to99.5% of rhinosinusitis cases are due toa viral infection and therefore do notrequire treatment with an antibiotic.More often than not, however, antibioticsare still prescribed despite increasingantibiotic resistance.

analyzed patient data from 9 randomizedtrials. The patient population included2500 intention-to-treat patients diagnosedwith ABRS who were randomizedto receive an antibiotic or placebo.

The outcome of interest was the proportionof patients cured.

 The resultsrevealed the calculated number neededto treat (NNT) was 15.6 In patients witha purulent discharge, the NNT droppedto 8, revealing that 8 patients need tobe treated before 1 additional patientis cured with antibiotics.

 The authorsconcluded that their results further validatedthat patients presenting with rhinosinusitisshould not receive an antibiotic,unless a diagnosis is confirmedby imaging or culture.

 Additionally,they emphasized their results are notevidence against prescribers wantingto wait and watch the symptoms beforetreating with an antibiotic.

Should treatment be warranted, antibioticregimens are targeted to adult andpediatric patient populations and aredependent on severity of symptoms,b-lactam allergy status, and recent antibioticuse (Tables 1 and 2). In patientswho are at high risk for drug-resistant

 (DRSP),high-dose amoxicillin/clavulanate shouldbe used. Patients who are consideredhigh risk for DRSP include those whorecently have used antimicrobials(past 4-6 weeks), as well as those whoare immunodeficient, have recurrentsinusitis, or are a day care worker orattendee.

Those patients who do not respondto their prescribed antibiotic within 72hours and their symptoms are persistentor worsening should be reevaluated andan alternate agent be selected.

 Overall,the duration of treatment has not beenwell established. Most evidence-basedmedicine concludes that treatment durationshould last anywhere from 10 to 14days.

 Ancillary therapies that are sometimessuggested to patients who haveABRS may include oral decongestants,topical decongestants, antihistamines,and normal saline nasal spray. Theseancillary therapies for ABRS lack soundevidence, however.

 Whereas some trialshave shown an improvement in symptoms,no clinical trials have shown thatancillary therapy decreases the durationof the infection.

Pharmacists have a duty to accuratelycounsel patients on ABRS and be awarethat the majority of sinus infectionsare viral in nature, and therefore donot require antibiotic therapy. Patientsshould be counseled on the signs andsymptoms, even if the watch-and-waitapproach is used. Pharmacists are animportant source of information forpatients on the use of antibiotics inABRS, while working closely with physicians.

Anon JB, Jacobs MR, Poole MD, et al. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis.

Brook I. Current issues in the management of acute bacterial sinusitis in children. 

Ah-See KW, Evans AS. Sinusitis and its management. 

Scheid DC, Hamm RM. Acute bacterial rhinosinusitis in adults: part I evaluation. 

Wald ER, Bordley WC, Darrow DH, et al. Clinical practice guideline: management of sinusitis. 

Young J, De Sutter A, Merenstein D, et al. Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data. 

Scheid DC, Hamm RM. Acute bacterial rhinosinusitis in adults: part II treatment. 

Articles

A majority of sinus infections are viral in nature, and a thorough understanding of risk factors and symptoms will help clinicians know when antibiotics are needed.

Acute Bacterial Rhinosinusitis: Knowing the Signs

Dr. Kyle is an assistant professor ofpharmacy practice at the GregorySchool of Pharmacy at Palm BeachAtlantic University,West Palm Beach,Florida. Ms. Cortes is a 2009 PharmDcandidate at the Gregory School ofPharmacy at Palm Beach AtlanticUniversity,West Palm Beach, Florida.

, commonlyreferred to as a boxedwarning, is a notification to practitionersfrom the FDA that 1 of 3 situations hasoccurred: (1) "There is an adverse reactionso serious in proportion to thepotential benefit from the drug that it isessential that it be considered in assessingthe risks and benefits of using adrug"; (2) "There is a serious adverseevent reaction that can be prevented orreduced in frequency or severity byappropriate use of the drug"; or (3) "FDAapproved the drug with restrictions toassure safe use because FDA concludedthat the drug can be safely used only ifdistribution or use is restricted."

Does this mean that a drug with ablack box warning should not be used?No, it does not. The FDA requires thewarning to be placed in the packageinsert so that practitioners can heed thewarnings. Medications with a black boxwarning have either shown or areexpected to have a serious adverseevent or death. Therefore, patients whoare on these medications should becarefully monitored on a regular basis.

Based on a number of both publishedand unpublished trials, the FDA voted 18to 5 on September 14, 2004, to issue ablack box warning for all selective serotoninreuptake inhibitors (SSRIs) stating:"Antidepressants increased the risk ofsuicidal thinking and behavior (suicidality)in short-term studies in childrenand adolescentswith manic depressive disorder (MDD) andother psychiatric disorders."

 Additionally,it was observed that the increased risk of suicide was higherduring the first few months of treatment withan SSRI.

 The initial concern overthe increased risk of suicide inchildren stemmed from reports of suicidal behavioroccurring in some paroxetine (Paxil) trials,as well as recommendations fromthe United Kingdom Medicines andHealthcare Products Regulatory Agencyurging that paroxetine not be used inindividuals younger than 18 years old.

The FDA then began an investigationreviewing some 23 trials funded byindustry, as well as the Treatment forAdolescents with Depression Study(TADS). The analysis from these 24 trials,which included approximately 4000patients, overall found that suicidalbehavior occurred in 109 patients; inaddition, 47 patients were hospitalizedand 66 committed harm to themselves,but an actual incidence of suicide wasnever reported.

Some of the data collected by the FDAfrom the 23 unpublished industry-fundedtrials included the following medications:fluoxetine (Prozac), sertraline (Zoloft),paroxetine, citalopram (Celexa), and venlafaxine(Effexor). Fluoxetine did not showa "suicide/self-harm risk" in 2 trials thatwere analyzed.5 Another with sertralinehad a 4.1% "possibly suicide-related" riskversus 0% in placebo.

 A paroxetine trialrevealed a "possibly suicide-related" risk of6.5% versus 1.1% in placebo; in addition,the trial found 5.4% suicide attempts versus0% in placebo.5 One citalopram studyshowed a 13% "possibly suicide-related"risk and suicide attempts versus 8% inplacebo.

 Venlafaxine is not considered anSSRI, but it also revealed an increase in"possibly suicide-related" risk and suicideattempts, when compared with placebo.

Although FDA officials knew of thesefindings, they contracted experts fromColumbia University to review the narrativesof adverse events reports and toreport the incidence of suicidality from theindustry-funded unpublished trials.

 TheFDA researchers then compiled all theinformation into a meta-analysis, and theresults revealed that suicide behavior inchildren was 2 times greater than withplacebo.

The TADS study was a 12-week randomized,placebo-controlled trial thatincluded 439 patients aged 12 to 17years old with an MDD diagnosis.7 Theparticipants were randomized to one of4 treatment arms: cognitive-behavioraltherapy (CBT) alone, fluoxetine alone(FLX), combination of fluoxetine withCBT, or placebo.

 The study authors concludedthat the combination therapy(fluoxetine with CBT) had greater effectivenessin reducing the symptoms ofdepression.

 In the December 2006TADS study, safety results were published,and the authors compared the"rates of physical, psychiatric, and suicide-related events in adolescents withMDD treated with [FLX], CBT, combinationtreatment, or placebo."

 Althoughthe article reported 24 suicide-relatedevents, only 23 cases were documented:5 in the CBT arm, 10 in the fluoxetinearm, 5 in the combination arm, and 3with placebo.

The authors revealed that only 5 actualsuicide attempts occurred: 1 in theCBT arm, 2 in the fluoxetine arm, 2 in thecombination arm, and 0 in the placeboarm.

 The study concluded that a combinationof fluoxetine and CBT is saferthan using a medication alone, because,although suicidal ideation improved inall treatment arms, the greatest improvementwas seen in the combinationtreatment arm.

In trying to assess the risk of suicidalthoughts and behavior in adults, the FDAcollected data from 295 trials thatincluded approximately 77,000 patientswith MDD and other psychiatric disorders.

 Then in December 2006, after theinformation was compiled and interpreted,the FDA?s PsychopharmacologicDrugs Advisory Committee agreed thatlabeling changes should be made inorder to increase awareness of the riskof suicide in young adults.

 The committeealso stated that practitioners shouldbe reminded that the use of antidepressantsis beneficial in older adults andthat underlying psychiatric disordersalso can cause an increase in suicidality.

On May 2, 2007, the FDA proposedthat all manufacturers update and add astatement of an increased risk of suicidalbehavior for individuals aged 18through 24 years to the black box warningon all antidepressant medications?labeling.

 In addition to the inclusion of ablack box warning to the labeling, theFDA recommended that cliniciansassess the risk of suicide prior to prescribingan antidepressant in childrenand adolescents.

At the time an antidepressant is dispensed,the FDA requires that a medicationguide be given to each patient. Themedication guide includes symptomsthat the patient?s family/caregiver shouldwatch for, major counseling points concerningantidepressant medications, andthe most important information regardingantidepressants and suicidal behavior.During this time, pharmacists shouldtake the opportunity to review the medicationguide with the patient and/orcaregiver. Pharmacists also shouldencourage families to be very observantof their children?s behavior or any unusualchange in behavior that may lend itselfto suicide, especially during the initial fewmonths of a course of drug therapy, or attimes of dose changes. Symptoms suchas anxiety, agitation, panic attacks, irritability,hostility, impulsivity, and maniamay represent warning signs of suicidalideation. Patients should be aware ofalternative forms of treatment such asCBT. CBT is a "relatively short-term focusedpsychotherapy for a wide range of psychologicalproblems."

 In children andadolescents, CBT often is used to treatdepression, anxiety, obsessive?compulsivedisorder, and attention-deficit/hyperactivitydisorder, with the ultimate goal ofimproving one?s quality of life.

Currently, the only FDA-approvedSSRIs for use in pediatrics include fluoxetinefor MDD and sertraline, fluoxetine,paroxetine, and fluvoxamine (Luvox) forobsessive?compulsive disorder.

 Despitethe fact that SSRIs have a black boxwarning of suicidality for use in childrenand adolescents, these medicationshave been proven safe and effective andare still frequently prescribed. Patientswith a prior history of suicidal ideation orbehavior, however, should have considerationof other options such as CBTbefore an SSRI is initiated.

FDA/CBER resources page. Food and Drug Administration Web site. Available at: 

Black Box Warnings from Drug Facts & Comparisons page. Facts & Comparisons Web site. Available at: 

Revisions to Product Labeling. FDA Web site. Available at: 

www.fda.gov/cder/drug/antidepressants/antidepressants_label_change_2007.pdf

Leslie LK, Newman TB, Chesney PM, Perrin JM. The Food and Drug Administration's deliberation on antidepressant use in pediatric patients. 

FDA Antidepressant Suicide Warning. McMan's Depression and Bipolar Web site. Available at: 

Newman TB. A black box warning for antidepressants in children? 

March J, Silva S, Petrycki S, et al. Fluoxetine, a cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents with depression study (TADS) randomized controlled trial. 

Emslie G, Kratochvil C, Vitiello B, et al. Treatment for Adolescents with Depression Study (TADS): safety results. 

FDA News page. Food and Drug Administration Web site. Available at: 

www.fda.gov/bbs/topics/news/2007/new01624.html

What is cognitive therapy?. The American Institute for Cognitive Therapy Web site. Available at: 

www.cognitivetherapynyc.com/default.asp?sid=768

Child and Adolescent Treatment page. The American Institute for Cognitive Therapy Web site. Available at: 

Prozac [package insert]. Indianapolis, IN: Eli Lilly and Co; 2008.

Zoloft [package insert]. New York, NY: Roerig, a division of Pfizer, Inc., 2008.

Paxil [package insert]. Research Triangle Park, NC: GlaxoSmithKline, 2008.

Luvox [package insert]. Marietta, GA: Solvay Pharmaceuticals, Inc. 2000.

The FDA directs that all SSRIs contain a black box warning. Patients taking these medications may continue therapy, but they should be monitored carefully on a regular basis.