Diagnosis and Treatment of Community-Acquired Pneumonia

Diagnosis and Treatmentof Community-Acquired PneumoniaM. NAWAL LUTFIYYA, PH.D., ERIC HENLEY, M.D., M.P.H., and LINDA F. CHANG, PHARM.D., M.P.H., B.C.P.S.University of Illinois College of Medicine at Rockford, Rockford, IllinoisSTEPHANIE WESSEL REYBURN, M.D., M.P.H., Mayo School of Graduate Medical Education, Rochester, MinnesotaPatients with community-acquired pneumonia often present withcough, fever, chills, fatigue, dyspnea, rigors, and pleuritic chest pain.When a patient presents with suspected community-acquired pneumonia,the physician should first assess the need for hospitalizationusing a mortality prediction tool, such as the Pneumonia SeverityIndex, combined with clinical judgment. Consensus guidelines fromseveral organizations recommend empiric therapy with macrolides,fluoroquinolones, or doxycycline. Patients who are hospitalized shouldbe switched from parenteral antibiotics to oral antibiotics after theirsymptoms improve, they are afebrile, and they are able to tolerate oralmedications. Clinical pathways are important tools to improve careand maximize cost-effectiveness in hospitalized patients. (Am FamPhysician 2006;73:442-50. Copyright © 2006 American Academy ofFamily Physicians.)ILLUSTRATION BY MARK E. SCHULERMembers of variousfamily medicine departmentsdevelop articles for“Practical Therapeutics.”This article is one in aseries coordinated by theDepartment of FamilyMedicine at the Universityof Illinois at ChicagoCollege of Medicine,Chicago, Ill. Guest editorof the series is Eric Henley,M.D., M.P.H.Community-acquired pneumonia(CAP) is defined as pneumonianot acquired in a hospital or along-term care facility. Despite theavailability of potent new antimicrobials andeffective vaccines, 1 an estimated 5.6 millioncases of CAP occur annually in the UnitedStates. 2 The estimated total annual cost ofhealth care for CAP in the United States is$8.4 billion. 2 Table 1 presents an overview ofCAP including definition, signs and symptoms,etiology, and risk factors.EpidemiologyThe epidemiology of CAP is unclear becausefew population-based statistics on the conditionalone are available. The Centers forDisease Control and Prevention (CDC) combinespneumonia with influenza when collectingdata on morbidity and mortality,although they do not combine them whencollecting hospital discharge data. In 2001,influenza and pneumonia combined werethe seventh leading causes of death in theUnited States, 3,4 down from sixth in previousyears, and represented an age-adjusted deathrate of 21.8 per 100,000 patients. 3 Deathrates from CAP increase with the presenceof comorbidity and increased age; the conditionaffects persons of any race or sex equally.The decrease in death rates from pneumoniaand influenza are largely attributed to vaccinesfor vulnerable populations (e.g., olderand immunocompromised persons).Clinical PresentationPneumonia is an inflammation or infectionof the lungs that causes them to functionabnormally. Pneumonia can be classifiedas typical or atypical, although the clinicalpresentations are often similar. Severalsymptoms commonly present in patientswith pneumonia.types of capTypical pneumonia usually is caused bybacteria such as Streptococcus pneumoniae.Atypical pneumonia usually is caused by theinfluenza virus, mycoplasma, chlamydia,legionella, adenovirus, or other unidentifiedmicroorganism. The patient’s age is themain differentiating factor between typicaland atypical pneumonia; young adults aremore prone to atypical causes, 5,6 and veryDownloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2006 American Academy of Family Physicians. For the private, noncommercialuse of one individual user of the Web site. All other rights reserved. Contact copyrights@aafp.org for copyright questions and/or permission requests.

SORT: KEY RECOMMENDATIONS FOR PRACTICEClinical recommendationEvidenceratingReferencesPatients with suspected community-acquired pneumonia (CAP) shouldreceive chest radiography.The Pneumonia Severity Index should be used to assist in decisionsregarding hospitalization of patients with CAP.The initial treatment of CAP is empiric, and macrolides or doxycycline(Vibramycin) should be used in most patients.Respiratory fluoroquinolones should be used when patients have failedfirst-line regimens, have significant comorbidities, havehad recent antibiotic therapy, are allergic to alternative agents, or havea documented infection with highly drug-resistant pneumococci.C 8A 8, 9, 15, 16C 8, 9, 29C 8, 9, 28, 29A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence;C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For informationabout the SORT evidence rating system, see page 374 or http://www.aafp.org/afpsort.xml.young and older persons are more predisposedto typical causes.symptomsCommon clinical symptoms of CAP includecough, fever, chills, fatigue, dyspnea, rigors,and pleuritic chest pain. Depending on thepathogen, a patient’s cough may be persistentand dry, or it may produce sputum. Other presentationsmay include headache and myalgia.Certain etiologies, such as legionella, also mayproduce gastrointestinal symptoms.Diagnosisphysical examinationPhysical examination may reveal dullnessto percussion of the chest, crackles or raleson auscultation, bronchial breath sounds,table 1Overview of Community-Acquired PneumoniaDefinitionLower respiratory tract infection in anonhospitalized person that is associated withsymptoms of acute infection with or withoutnew infiltrate on chest radiographsClinical presentationTemperature greater than 38˚C (100.4˚F)Cough with or without sputum, hemoptysisPleuritic chest painMyalgiaGastrointestinal symptomsDyspneaMalaise, fatigueRales, rhonchi, wheezingEgophony, bronchial breath soundsDullness to percussionAtypical symptoms in older patientsEtiologyBacterialChlamydia speciesHaemophilus influenzaeLegionella speciesMoraxella catarrhalisMycoplasma pneumoniaeStaphylococcus aureusStreptococcus pneumoniaeViralAdenovirusInfluenza A and BParainfluenzaRespiratory syncytial virusEndemic fungiBlastomycosisCoccidioidomycosisHistoplasmosisRisk factorsAge older than 65 yearsHuman immunodeficiency virus orimmunocompromisedRecent antibiotic therapy or resistanceto antibioticsComorbiditiesAsthmaCerebrovascular diseaseChronic obstructive pulmonarydiseaseChronic renal failureCongestive heart failureDiabetesLiver diseaseNeoplastic diseaseFebruary 1, 2006 ◆ Volume 73, Number 3 www.aafp.org/afp American Family Physician 443

Community-Acquired Pneumoniatactile fremitus, and egophony (“E” to “A”changes). The patient also may be tachypneic.A prospective study 7 showed thatpatients with typical pneumonia were morelikely than not to present with dyspnea andbronchial breath sounds on auscultation.radiographyChest radiography (posteroanterior and lateralviews) has been shown to be a critical componentin diagnosing pneumonia. 8 According totable 2Sensitivity and Specificity of Diagnostic Tests for CAPDiagnostic tests by pathogen Sensitivity (%) Specificity (%)ChlamydiaRapid PCR (sputum, BAL fluid) 30 to 95 > 95Serology (fourfold rise in serumand convalescent titers)10 to 100 —Sputum culture 10 to 80 > 95Gram-negative rodsSputum Gram stain 15 to 100 11 to 100Haemophilus influenzae,Moraxella catarrhalis,PneumoniaeSputum cultureInfluenzaDiagnostic yield20 to 79*Rapid DFA (sputum, BAL fluid) 22 to 75 90Legionella pneumophilaDFA (sputum, BAL fluid) 22 to 75 90PCR (sputum, BAL fluid) 83 to 100 > 95Serum acute titer 10 to 27 > 85Urinary antigen 55 to 90 > 95Mycoplasma pneumoniaeAntibiotic titers 75 to 95 > 90Cold agglutinins 50 to 60 —PCR (sputum, BAL fluid) 30 to 95 > 95Pneumococcal pneumoniaeChest radiography (lobar infiltrate) 40† —Sputum cultureDiagnostic yield20 to 79*Diagnostic yield20 to 79*Diagnostic yield20 to 79*Sputum Gram stain 15 to 100 11 to 100CAP = community-acquired pneumonia; PCR = polymerase chain reaction; BAL =bronchoalveolar lavage; DFA = direct fluorescence antibody.*—Overgrowth of oral flora, isolation of atypical agents requires special media.†—Acute symptoms.Information from references 2, 8, 11, and 13.the latest American Thoracic Society (ATS)guidelines for the diagnosis and treatment ofadults with CAP, “all patients with suspectedCAP should have a chest radiograph to establishthe diagnosis and identify complications(pleural effusion, multilobar disease).” 8 Chestradiography may reveal a lobar consolidation,which is common in typical pneumonia; orit could show bilateral, more diffuse infiltratesthan those commonly seen in atypicalpneumonia. However, chest radiographyperformed early in the course of the diseasecould be negative.laboratory testsHistorically, common laboratory tests forpneumonia have included leukocyte count,sputum Gram stain, two sets of blood cultures,and urine antigens. However, thevalidity of these tests has recently beenquestioned after low positive culture rateswere found (e.g., culture isolates of S. pneumoniaewere present in only 40 to 50 percentof cases). 9 Such low positive culture ratesare likely due to problems with retrievingsamples from the lower respiratory tract,previous administration of antibiotics, contaminationfrom the upper airways, faultyseparation of sputum from saliva whenstreaking slides or plates, 9 or viral etiology.Furthermore, sputum samples are adequatein only 52.3 percent of patients with CAP,and only 44 percent of those samples containpathogens. 10 Nonetheless, initial therapyoften is guided by the assumption that thepresenting disease is caused by a commonbacterial pathogen.Findings 11 also cast doubt on the clinicalutility of obtaining blood cultures frompatients with suspected CAP. In a study 12 ofCAP cases in 19 Canadian hospitals over asix-month period, positive blood cultureswere obtained in only 5.2 to 6.2 percentof patients, including those with the mostsevere disease. Based on these findings,other researchers 13 concluded that a positiveblood culture had no correlation with theseverity of the illness or outcome. Anotherprospective study 10 showed that blood cultureswere positive in only 10.5 percent ofpatients with pneumonia. Despite these and444 American Family Physician www.aafp.org/afp Volume 73, Number 3 ◆ February 1, 2006

Community-Acquired Pneumoniaother research findings, current ATS guidelines8 recommend that patients hospitalizedfor suspected CAP receive two sets of bloodcultures. Blood cultures, however, are notnecessary for outpatient diagnosis. 8Legionella antigens were found in theurine of 48 percent of patients with suspectedLegionella pneumophila serogroup 1 infection.14 Table 2 2,8,11,13 includes the sensitivityand specificity of diagnostic tests for CAP.TreatmentInitial treatment of CAP is based on physicalexamination findings, laboratory results,and patient characteristics (e.g., age, chronicillnesses, history of smoking, history of theillness). 15 Physicians should begin theirtreatment decisions by assessing the need forhospitalization using a prediction tool forincreased mortality, such as the PneumoniaSeverity Index (Table 3 15 ), combined withclinical judgment. 9outpatient vs. inpatient treatmentChoosing between outpatient and inpatienttreatment is a crucial decision because ofthe possible risk of death. 9,15,16 This decisionnot only influences diagnostic testing andmedication choices, it can have a psychologicalimpact on patients and their families. Onaverage, the estimated cost for inpatient careof patients with CAP is $7,500. Outpatientcare can cost as little as $150 to $350. 17-19Hospitalization of a patient should dependon patient age, comorbidities, and the severityof the presenting disease. 9,20Physicians tend to overestimate a patient’srisk of death 14 ; therefore, many low-riskpatients who could be safely treated as outpatientsare admitted for more costly inpatientcare. The Pneumonia Severity Index(Table 3 15 ) was developed to assist physiciansin identifying patients at a higherrisk of complications and who are morelikely to benefit from hospitalization. 9,15,16Investigators developed a risk model basedon a prospective cohort study 16 of 2,287patients with CAP in Pittsburgh, Boston,and Halifax, Nova Scotia. By usingthe model, the authors found that 26 to31 percent of the hospitalized patients weregood outpatient candidates, and an additional13 to 19 percent only needed briefhospital observation. They validated thismodel using data 17 from more than 50,000patients with CAP in 275 U.S. and Canadianhospitals. 15-17,21,22TABLE 3Pneumonia Severity IndexPatient CharacteristicsPointsDemographicsMaleAge (years)Female Age (years) − 10Nursing home resident + 10Comorbid illnessNeoplastic disease + 30Liver disease + 20Congestive heart failure + 10Cerebrovascular disease + 10Renal disease + 10Physical examination findingsAltered mental status + 20Respiratory rate > 30 breaths per minute + 20Systolic blood pressure < 90 mm Hg + 20Temperature < 35˚C (95˚F) or > 40˚C (104˚F) + 15Pulse rate > 125 beats per minute + 10Laboratory and radiographic findingsArterial pH < 7.35 + 30Blood urea nitrogen > 64 mg per dL+ 20(22.85 mmol per L)Sodium < 130 mEq per L (130 mmol per L) + 20Glucose > 250 mg per dL (13.87 mmol per L) + 10Hematocrit < 30 percent + 10Partial pressure of arterial oxygen < 60 mm Hg or + 10oxygen percent saturation < 90 percentPleural effusion + 10Total points:Point totalRiskRiskclassMortality %(No. of patients)Recommendedsite of careNo predictors Low I 0.1 (3,034) Outpatient≤ 70 Low II 0.6 (5,778) Outpatient71 to 90 Low III 2.8 (6,790) Inpatient(briefly)91 to 130 Moderate IV 8.2 (13,104) Inpatient> 130 High V 29.2 (9,333) InpatientInformation from reference 15.February 1, 2006 ◆ Volume 73, Number 3 www.aafp.org/afp American Family Physician 445

Community-Acquired PneumoniaManagement of CAPNoTreat as outpatientPreferred antibioticsMacrolides (level A)Fluoroquinolones (level A)Doxycycline (Vibramycin)Alternative antibioticsAmoxicillin/clavulanate(Augmentin) (level A)Beta-lactam (cefpodoxime[Vantin], cefprozil [Cefzil],cefuroxime [Ceftin]) (level A)Although the Pneumonia Severity Indexcan serve as a general guideline for management,clinical judgment should alwayssupersede the prognostic score. 9pharmacotherapyThe primary goals of pharmacotherapy forpatients with CAP include eradicating thecausative pathogens, resolving the clinicalsigns and symptoms, minimizing hospitalization,and preventing reinfection. 23-27 Physiciansshould choose a medication based on thepharmacokinetic profile, adverse reactions,drug interactions, and cost-effectiveness. 23-27Further, patient evaluation should focus onseverity of illness, patient age, comorbidities,clinical presentation, epidemiologic setting,and previous exposure. 9 The majorityof patients with CAP are treated empiricallybased on the most common pathogen(s)associated with the condition. 23-27CAP diagnosisComorbidities presentAssign a risk class (see Table 3)Low risk classII and IIIFigure 1. Algorithm for the management of CAP. (CAP = communityacquiredpneumonia.)Adapted with permission from Fish D. Pneumonia. PSAP, Pharmacotherapy Self-AssessmentProgram. Kansas City, Mo.: American College of Clinical Pharmacy, 2002:202.YesModerate risk class IVand high-risk class VTreat as inpatientPreferred antibioticsIntravenous beta-lactam(cefotaxime [Claforan] orceftriaxone [Rocephin]) plusa macrolide (level A) or afluoroquinolone alone (level A)Consensus guidelines from ATS, 8 InfectiousDiseases Society of America, 9 andCanadian Guidelines for the Initial Managementof Community-Acquired Pneumonia 28(Figure 1 6 ) recommend initial empiric therapywith macrolides, fluoroquinolones, ordoxycycline (Vibramycin). A fourth guideline29 developed by the Therapeutic WorkingGroup of the CDC, however, recommendsusing fluoroquinolones sparingly because ofresistance concerns.Although data are limited on durationof CAP therapy, current research 30 recommendsseven to 10 days of therapy forS. pneumoniae and 10 to 14 days of therapyfor Mycoplasma pneumoniae and Chlamydiapneumoniae. After a hospitalized patient isclinically stable (i.e., temperature less than37.8° C [100.0° F], pulse under 100 beats perminute, respiratory rate below 24 breathsper minute, systolic blood pressure above90 mm Hg, and blood oxygen saturationover 90 percent) and able to tolerate oralintake, the patient may be treated with oralantibiotics for the remainder of the therapycourse. This can save money and allow forearlier hospital discharge, which minimizes apatient’s risk of hospital-acquired infection.Pneumococcal ResistanceS. pneumoniae, which accounts for 60 to70 percent of all bacterial CAP cases, canaffect all patient groups and can cause a fatalform of CAP. The alarming rate of resistanceto many commonly used antibiotics raisesgreat concern. Penicillin-resistant S. pneumoniaewas uncommon in the early 1990s buthas since become increasingly prevalent. 29,31Resistant strains are classified as havingintermediate or high-level resistance. Surveillancedata in the United States 30 revealedthat, overall, pneumococcal strains had a28 percent immediate resistance rate and a16 percent high-level resistance rate. Decreasedsusceptibility to other commonlyused antibiotics has also been observed(Table 4 32 ). 29-31 The clinical importance ofthese data is questionable because recruitingpatients infected with resistant pathogensfor clinical trials is difficult. Furthermore,available outcomes on the treatment of446 American Family Physician www.aafp.org/afp Volume 73, Number 3 ◆ February 1, 2006

Table 4Patterns of Resistance to Antibioticsin North America*AntibioticPenicillinsAmoxicillin/clavulanate(Augmentin)Resistance(%)†4.1Penicillin 21.3CephalosporinsCefepime (Maxipime) 0.4Cefprozil (Cefzil) 23.9Ceftriaxone (Rocephin) 1.9Cefuroxime (Ceftin) 24.7MacrolidesAzithromycin (Zithromax) 23.0Clarithromycin (Biaxin) 26.6Erythromycin 28.3FluoroquinolonesGatifloxacin (Tequin) 0.7Levofloxacin (Levaquin) 0.7Moxifloxacin (Avelox) 0.4MiscellaneousClindamycin (Cleocin) 9.2Tetracycline 18.8Trimethoprim/sulfamethoxazole(Bactrim, Septra)29.9Vancomycin (Vancocin) 0.0*—Antibiotics tested against Streptococcus pneumoniaeisolates.†—Resistance rates averaged across all patient agegroups.Information from reference 32.pneumonia caused by resistant pneumococcalstrains are conflicting. 30The CDC and others recommend outpatientoral empirical antibiotics with a macrolide,doxycycline, or an oral beta-lactam(amoxicillin, cefuroxime [Ceftin], or amoxicillin/clavulanate[Augmentin]) or inpatienttreatment with an intravenous beta-lactam(cefuroxime, ceftriaxone [Rocephin], cefotaxime[Claforan]) or a combination ofampicillin/sulbactam (Unasyn) with a macrolide(Figure 1 6 ). 28,29 Conservative use ofnew fluoroquinolones (levofloxacin [Levaquin],gatifloxacin [Tequin], moxifloxacin[Avelox]) also is recommended to minimizeresistance patterns. 28,29 The new fluoroquinolones(minimum inhibitory concentration:4 mcg per mL or greater) should be usedonly when patients have failed recommendedfirst-line regimens, are allergic to alternativeagents, or have a documented infection withhighly drug-resistant pneumococci such asthose resistant to penicillin. 28,29Cost of Antimicrobial TherapyEconomic pressures have accentuated thefocus on reducing health care costs andutilizing resources while maintaining orimproving quality of care. 31 These pressuresare exacerbated by the growing resistanceof S. pneumoniae to penicillin. 31,32 This patternof resistance increases the cost of treatmentbecause of prolonged hospitalization,relapses, and the use of more expensiveantibacterial agents. 33-37reducing costsNumerous methods for reducing costs whentreating patients with bacterial infectionscan be applied to CAP (Table 5). Choosingmonotherapy instead of combination therapyTable 5Strategies for Reducing the Costof Antibiotic TherapyAdministrationUse the shortest appropriate course possible.Switch from parenteral to oral antibiotics assoon as clinically appropriate.Adverse eventsAvoid agents with serious or costly adverseeffects.Avoid agents known to induce resistance.Drug costCompare low impact with total hospital costs(but significant to pharmacy costs).HospitalizationUse knowledge of local resistance to initiateearly therapy with appropriate spectrumagent (few data available).Consider availability and cost-effectivenessof intravenous versus oral administration.MonitoringAvoid agents that require therapeuticmonitoring or laboratory safety tests.PharmacotherapyUse long-acting antibiotics.Use potent bactericides.Avoid antibiotics with poor tissue penetration.Community-Acquired PneumoniaFebruary 1, 2006 ◆ Volume 73, Number 3 www.aafp.org/afp American Family Physician 447

Table 6Antimicrobial Therapies for CAPAgent Dosage* Cost per course† (generic) Common adverse reactions‡CephalosporinsCefotaxime (Claforan)Cefpodoxime (Vantin)Cefprozil (Cefzil)Ceftriaxone (Rocephin)Cefuroxime (Ceftin)1 g IV every six to eight hours200 mg orally twice per day500 mg orally twice per day1 g IV every 24 hours500 mg orally twice per day0.75 to 1.5 g IV every eight hours$355 (330)124 (110)192392219 oral250 to 358 IVMild diarrheaRashClindamycinsClindamycin (Cleocin)300 mg orally every six hours600 mg IV every eight hours238 (148 to 168) oral250 IVMild diarrheaAbdominal painPseudomembranous colitisRashFluoroquinolonesGatifloxacin (Tequin)Levofloxacin (Levaquin)Moxifloxacin (Avelox)400 mg orally or IV once per day500 mg orally or IV once per day400 mg orally once per day98 oral, 382 IV56 oral, 438 IV107Mild diarrheaNauseaVomitingConstipationDizzinessHeadacheMacrolidesAzithromycin (Zithromax)Clarithromycin (Biaxin)Erythromycin500 mg orally for one dose, then250 mg once per day for four doses500 mg IV every 24 hours500 mg orally twice per day500 mg orally every six hours500 to 1,000 mg IV every six hours49 to 60 oral295 IV9617 (8 to 10) oral(167) IVMild diarrheaNauseaVomitingAbdominal painRashPenicillinsAmoxicillinAmoxicillin/clavulanate(Augmentin)Penicillin GPenicillin V500 mg orally every eight hours875 mg orally every 12 hours875 mg/125mg orally every 12 hours1 to 3 mU IV every four hours500 mg orally four times per day4 (4 to 8)20 (18 to 19)166 (110 to 115)(273)15 (9 to 15)Mild diarrheaNauseaVomitingRashTetracyclinesDoxycycline (Vibramycin) 100 mg orally twice per day 102 (16 to 21)Mild diarrheaNauseaVomitingPhototoxicityCAP = community-acquired pneumonia; IV = intravenously.*—Usual duration for adults with CAP and normal renal function is 10 to 14 days.†—Estimated cost to the pharmacist based on average wholesale prices in Red Book. Montvale, N.J.: Medical Economics Data, 2005. Cost to thepatient will be higher, depending on prescription filling fee.‡—Adverse events occurring at a rate of approximately 1 to 10 percent.Adapted with permission from Fish D. Pneumonia. Pharmacotherapy Self-Assessment Program. 4th ed. Kansas City, Mo.: American College of ClinicalPharmacy 2002:198.reduces costs associated with administeringan antibacterial. 33-37 Using agents with longerhalf-lives allows for once-daily administration,which in turn leads to improvedcompliance and outcomes and decreasedcosts. 33-37 In addition, transitioning patientsto oral therapy as soon as they are clinicallystable can significantly reduce the lengthof hospitalization—the major contributingfactor to health care costs. 33-37448 American Family Physician www.aafp.org/afp Volume 73, Number 3 ◆ February 1, 2006

Community-Acquired Pneumoniacost-effective careWhen choosing a treatment, it is essential tocompare costs and outcomes of all recommendeddrug therapies. 31 Table 6 6 includesthe costs of and common adverse reactionsto antimicrobial therapies for CAP.The goal of a formal pharmacoeconomicassessment is to enhance overall patient careusing available resources. The evaluationshould lead to a decision that will maximizethe value of health care services, not simplyreduce the costs of drug therapy. For instance,a particular drug may be more expensive, butit may also be more effective, thus loweringoverall costs. Another drug may have a higherrate of treatment failures, creating addedcosts associated with managing the failures.The overall cost of each therapy should beobtained by comparing the end cost with theprobability of achieving a positive outcome.Depending on the relative costs associatedwith treatment failures compared with thecosts of cures, the decision to choose oneagent over another may change.The best way to apply cost-savingapproaches to the treatment of patients withCAP is by using a clinical pathway. 38 Thisis a method of facilitating multidisciplinarypatient care by moving processes of caresequentially through various stages, withinspecified time frames, toward a desired outcome.These pathways should be specific toeach institution, taking into account resistancerates in the community and encouraging theuse of the most active, cost-effective agents toproduce rapid, positive clinical outcomes. 31,39The authors thank Joel Emery McCullough, M.D., M.S.,M.P.H., and Adam Reyburn, M.D., for their assistance inthe preparation of the manuscript.The AuthorsM. NAWAL LUTFIYYA, PH.D., is assistant professor anddirector of research in the Department of Family andCommunity Medicine at the University of Illinois College ofMedicine at Rockford. She also is adjunct assistant professorin the University of Illinois at Chicago (UIC) School of PublicHealth. Dr. Lutfiyya earned her doctorate at the University ofMassachusetts at Amherst after completing other graduateleveltraining at the University of Iowa, Iowa City.ERIC HENLEY, M.D., M.P.H., is associate professor and headof the Department of Family and Community Medicine atthe University of Illinois College of Medicine at Rockford.He is an adjunct faculty member in the UIC School ofPublic Health. Dr. Henley received his medical degree fromGeorgetown University, Washington, D.C., and completed afamily medicine residency at the University of ConnecticutSchool of Medicine, Hartford. He earned his master’s inpublic health at Harvard Medical School, Boston, Mass.LINDA F. CHANG, PHARM.D., M.P.H., B.C.P.S., is clinicalassistant professor in the Department of Family andCommunity Medicine and the Department of PharmacyPractice at the University of Illinois College of Medicineat Rockford. She received a doctorate in pharmacy at UICand completed a general practice pharmacy residency atthe Chicago Veterans Administration Hospital.STEPHANIE WESSEL REYBURN, M.D., M.P.H., is a familypractice resident at the Mayo School of Graduate MedicalEducation, Rochester, Minn. She received her medical degreeat the University of Illinois College of Medicine at Rockfordand her master’s at the UIC School of Public Health.Address correspondence to M. Nawal Lutfiyya, Ph.D.,University of Illinois College of Medicine at Rockford,Department of Family and Community Medicine, 1601Parkview Ave., Rockford, IL 61107 (email: lutfiyya@uic.edu). Reprints are not available from the authors.Author disclosure: Nothing to disclose.REFERENCES1. Andrews J, Nadjm B, Gant V, Shetty N. 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