Therapeutic Management of Bronchitis

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Pharmacy Times, Volume 0, 0

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

Behavioral Objectives

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

1. Review the epidemiology and pathogenesis of acutebronchitis, including a discussion of the bacteriologicetiology.

2. Discuss clinical features that are diagnostic of acutebronchitis and acute exacerbation of chronic bronchitis.

3. Discuss the therapeutic options in the treatment ofbronchitis.

4. Understand the importance of judicious use of antibiotics inthe treatment of bronchitis and the impact of resistance inthe development of new drugs and dosage formulations.

5. Formulate a therapeutic plan for a given case study of apatient with acute bronchitis or acute exacerbation ofchronic bronchitis.

Acute bacterial bronchitis and acuteexacerbation of chronic bronchitis(AECB) are among the most commondiseases encountered in clinical practice.Successful treatment can be achallenge, however, especially with theemergence of antibiotic resistance.New agents have been approved by theFDA that address the problem, butsociety guidelines have yet to catch upwith clinical practice. This article willcover therapeutic management ofacute bacterial bronchitis and AECB. Italso will discuss the challenges of bacterialresistance and ongoing efforts tocircumvent this problem.

Acute Bacterial Bronchitis

Acute bronchitis is one of the mostcommon diseases encountered in clinicalpractice. It is estimated that 30 millionambulatory visits for cough leadingto approximately 12 milliondiagnoses of bronchitis were made inthe United States in 1997.1 Althoughviruses are responsible for most cases ofacute bronchitis, 70% to 80% ofpatients with acute bronchitis whoseek medical attention are prescribedantibiotics.2

Pathogenesis

Acute bronchitis is defined as inflammationof the bronchi in the presenceof cough and associated symptoms ofan upper respiratory infection. Somepatients may experience dyspnea,purulent sputum production, chestpain, and fever. At least 60% of thetime, microbiologic studies are unableto identify a pathogen associated withacute bronchitis.3 As stated above,most identifiable cases of uncomplicatedacute bronchitis (³90%)are caused by viruses (Table 1).4,5 Theinfluenza viruses are most frequentlyassociated with acute bronchitis.

Bacterial pathogens account for 5%to 10% of all cases of uncomplicatedacute bronchitis.5 Bordetella pertussis,Mycoplasma pneumoniae, and Chlamydiapneumoniae are the only bacteriathat have been associated with acutebronchitis. Although the pertussis vaccineis approximately 90% efficacious,its protective effect in children decreasesto 46% in the seventh year afterimmunization.6,7 This decrease createsa large pool of adolescents and adultssusceptible to B pertussis.

Other bacteria—including Streptococcuspneumoniae, Haemophilus influenzae,and Moraxella catarrhalis—donot appear to cause acute bronchitis inadults who do not have underlyinglung disease. These bacteria, however,may play a role in secondary infectionafter an acute viral respiratory illness,or in patients with underlying lungabnormalities (eg, AECBs, tracheostomy,or endotracheal intubation).8

Clinical Presentation and Diagnosis

The primary symptom of acute bronchitisis cough (with or without sputumproduction) lasting less than 3weeks.9 Approximately 20% ofpatients, however, may continue toexperience cough after 4 weeks.10 B pertussisinfection should be considered inpatients with persistent paroxysmalcough (usually lasting 4-6 weeks) andwith close contact with an infectedindividual.5 Approximately 20% ofpatients with cough lasting longerthan 2 to 3 weeks have pertussis.11 Thepresence of purulent sputum is notexclusive to bacterial causes of acutebronchitis. Purulence can result fromeither a bacterial or a viral infection.

Diagnosis of acute bronchitis isbased on clinical findings and requiresexcluding the possibility of pneumonia.The absence of abnormal vitalsigns (heart rate ³100 beats/min, respiratoryrate ³24 breaths/min, or oraltemperature ³38̊C) and a normalchest examination significantly decreasethe possibility of pneumonia.12Chest radiography is recommendedfor patients with abnormal vital signsor abnormal findings on lung examination,patients with underlying lungdisease, and patients with suspectedsevere acute respiratory syndrome.2,3Postnasal drip syndrome, asthma(especially when the patient isexposed to cold or exercise), gastroesophagealreflux disease, or a combinationof these conditions is the mostlikely diagnosis in immunocompetentadult patients with persistent coughlasting more than 3 weeks and a negativechest radiograph.9,13 In fact, theseconditions account for 90% of diagnosesin patients with persistentcough.14 Because sputum Gram stainand culture do not consistently identifyB pertussis, M pneumoniae, and Cpneumoniae, these diagnostic tests arenot recommended.3

Treatment

The overuse of antibiotics in thetreatment of acute bronchitis has beena public health issue over the pastdecades. Since most cases of uncomplicatedacute bronchitis are caused byviruses (Table 1), the routine use ofantibiotics—including erythromycin,doxycycline, or trimethoprim/sulfamethoxazole(TMP/SMX)—providesonly a marginal benefit and is highlydiscouraged.2,15,16 Hence, antibiotictreatment should not be initiated inpatients with acute bronchitis causedby viruses. Despite this caution, physiciansprescribe antibiotics for acutebronchitis up to 80% of the time.16 Inaddition, the identification of M pneumoniaeand C pneumoniae on culture isdifficult. Currently, there is a lack ofclinical studies with adequate samplesize to support antibiotic treatment forthese pathogens.

Guidelines from the American Collegeof Physicians and the Centers forDisease Control and Prevention supportthe use of antibacterial agentsonly for bronchitis that is caused by Bpertussis.3,14 Therapy with erythromycin250 to 500 mg 4 times a day inpatients with pertussis helps to resolvesymptoms.17 Other macrolides, includingclarithromycin and azithromycin,are therapeutic options for pertussis.

Initiation of treatment early in thecourse of illness (within 7-14 days afterthe onset of symptoms) is necessary tomaximize the clinical benefit. Patientswith pertussis, however, frequently donot seek medical care within this timeframe. With these patients, the purposeof recommending antibiotic treatmentis to prevent transmission of thedisease rather than resolution of symptoms.Antibiotic treatment should bereserved for patients in whom pertussisis highly probable (ie, prolonged coughand recent exposure to a person withpertussis), as well as for their close contacts.Close contacts should be treatedwith the same dose and duration oferythromycin. Compared with ethylsuccinateand stearate formulations,the estolate formulation of erythromycinhas been associated with the fewestbacteriologic and clinical relapses.18Hence, estolate is the recommendeddosage formulation for the treatmentof pertussis. Therapy should continuefor 14 days, although a 7-day coursehas been shown to be equally effective.18,19

Acute bacterial bronchitis caused byatypical pathogens, including M pneumoniaeor C pneumoniae, occurs in aminority of patients. It should be suspectedin patients with prolongedcough and bronchial symptoms. Tetracyclines,macrolides, and fluoroquinolonesprovide excellent activityagainst these bacteria. Routine use ofantibiotics to direct therapy againstthese pathogens is highly discouraged,however, because there has been a lackof clinical trials to support this practice.

Since patients may present withupper respiratory or common coldsymptoms, the use of nasal decongestants,nonsteroidal anti-inflammatorydrugs, aspirin, acetaminophen, and/ornasal ipratropium may provide symptomaticrelief. Because most cases ofacute bronchitis present with cough,antitussives, such as dextromethorphanand codeine, to reduce cough areoften prescribed, although the evidencesupporting their benefit issmall.5 A recent meta-analysis concludedthat the use of oral or inhaled beta-2 agonists was not effective in reducingacute cough in adults and childrenwho did not have airflow obstruction.20

Acute Exacerbation of ChronicBronchitis

Chronic bronchitis, particularly duringacute exacerbation, contributes tosignificant disability, morbidity, andmortality in people with chronicobstructive pulmonary disease(COPD). In the United States, approximately16 million people are affectedby COPD.21 Evidence indicates thatCOPD, particularly its mild form, isunderdiagnosed.22

AECB has been shown to impair thequality of life of people with COPD.23An estimated 500,000 hospitalizationsand 110,000 deaths occur annually inpatients with COPD exacerbations.21,22

The World Health Organization in2002 reported that COPD was thefifth leading cause of death in theworld, and its prevalence and mortalityare predicted to increase.24,25 Becausethe prevalence is high, the economicand social impact of COPD isconsiderable. The annual expenditurefor COPD is $23.9 billion, with anestimated direct cost of $1500 perpatient per year.26,27

Pathogenesis

Chronic bronchitis is characterizedby increased mucosal inflammationand mucus hypersecretion of thebronchi, and it usually is accompaniedby airflow obstruction. Smoking isassociated with most cases of COPD.Air pollution, allergens, occupationalexposure, airway infection, and geneticfactors (eg, deficiency in alpha1-antitrypsin) are also risk factors forCOPD.27 AECB is characterized by anincrease in the quantity and purulenceof sputum, increased dyspnea, andfever. Although inhaled irritants, pollution,and allergies can trigger anacute exacerbation, infections causedby viruses and bacteria account for50% to 80% of AECB cases.28,29 Viruses—including influenza, rhinovirus,parainfluenza, respiratory syncytialvirus, coronavirus, and adenovirus—contribute to the majority (33%-56%)of AECB cases.29-32

The most common bacterial pathogensisolated in patients with AECBare S pneumoniae, H influenzae, and Mcatarrhalis.33 C pneumoniae, M pneumoniae,Staphylococcus aureus, Klebsiella,and Pseudomonas aeruginosa also maycause AECB.28,30,34 Interestingly, bacteriathat are isolated in patients withstable chronic bronchitis are similar toones that are cultured during acuteexacerbations.29 Patients with chronicbronchitis usually are colonized withbacteria, which may cause and lead toairway inflammation.35,36

Clinical Presentation and Diagnosis

Chronic bronchitis is characterizedby persistent cough and sputum productionfor 3 months per year for atleast 2 consecutive years. Patients withAECB present with more frequentand/or severe symptoms of COPD, aswell as other features (Table 2).

Chest radiography remains unchangedduring AECB and is useful todifferentiate AECB from pneumonia,because the clinical presentations maybe similar. Expectorated sputum samplesof patients with COPD contain ahigh concentration of polymorphonuclearleukocytes (PMNs), both duringstable chronic bronchitis and AECB.37As noted earlier, pathogens culturedduring stable chronic bronchitis aresimilar to those of AECB. The indistinctpattern of bacteria and PMNsbetween stable bronchitis and AECBmakes sputum cultures of little valuein diagnosing AECB. In fact, the AmericanCollege of Physicians does notrecommend performing sputum culturesduring exacerbations.21 Sputumcultures should be reserved forpatients not responding to empiricalantibiotic therapy.

Treatment

Clinically significant AECB is morelikely to occur in patients with bacterialcolonization and severe underlyingpulmonary disease. In this patientpopulation, AECB may lead to hospitalizationand respiratory failure.Hence, antibiotic treatment should beoffered for eradication of bacteria andresolution of airway inflammation.36Mild episodes of AECB, especially inpatients with less severe underlyinglung disease (forced expiratory volumein 1 sec >50% of predicted value), mayresolve spontaneously, and judicioususe of antibiotics in this population ismerited to prevent bacterial resistance.

Studies evaluating the use of antibioticsin patients with AECB, identifiedby worsening dyspnea and increasedpurulence and volume of phlegm,demonstrated clinical benefit.38-40Antibiotics were beneficial in patientswith 2 of these 3 symptoms, butappeared to offer minimal or no benefitin patients with mild exacerbations(ie, when only 1 or none of thesesymptoms were present). Based on recommendationsfrom the AmericanCollege of Chest Physicians, theNational Institutes of Health, and theAmerican Thoracic Society, empiricalantibiotic therapy directed against thecommon bacterial pathogens of AECBis recommended for patients withAECB, especially if infection issevere.21,41,42 The choice of antibioticshould reflect local susceptibility patterns of S pneumoniae, H influenzae, andM catarrhalis. A narrow-spectrum antibiotic(eg, amoxicillin 500 mg 3 timesdaily, doxycycline 100 mg twice daily,or TMP/SMX 160/800 mg twice daily)for 3 to 14 days generally is used.21,41,43The optimal duration of therapy hasnot been well-studied. Unfortunately,the increasing prevalence of resistanceamong the common bacterialpathogens of AECB, particularly inpatients with severe underlying COPDor those with recent antibiotic usage,limits the effectiveness of these narrow-spectrum agents.

New Approaches to Treatment ofAECB

New or extended-spectrum antibioticshave been studied or FDAapprovedfor the treatment of AECB(Table 3).33,44 These antibiotics mayplay a major role in the treatment ofAECB. In fact, studies have demonstratedthat the use of these new orextended-spectrum antibiotics, comparedwith the use of the traditionalnarrow-spectrum agents, was associatedwith fewer relapses.44,45 For the past3 years, however, there have been noupdates of guidelines from majorauthorities to help direct physicians onthe appropriate use of these newantimicrobials as first-line agents.

High-dose amoxicillin with clavulanateis now available in formulationsintended to enhance compliance andeffectiveness against drug-resistant Spneumoniae (1000 mg amoxicillin and62.5 mg clavulanate per extendedreleasetablet; 14:1 ratio of amoxicillinto clavulanate in powder for oral suspension).Amoxicillin (+ clavulanate),which exerts its bactericidal activity byinhibiting cell-wall synthesis, remainsas a first-line therapeutic option fortreating AECB. The clavulanate componentprovides additional activityagainst beta-lactamase producers, Hinfluenzae and M catarrhalis.

Pharmacokinetic and pharmacodynamicstudies demonstrate that high-doseamoxicillin (+ clavulanate), definedas 4 g per day in adults, providesenhanced activity against resistantpneumococci.46,47 The most commonadverse effects are gastrointestinal-related,including nausea and diarrhea.The incidence of adverse effects associatedwith high-dose amoxicillin iscomparable to that with standard-doseamoxicillin.47,48 Compared with twicedailydosing, however, 3-times-dailydosing of high-dose amoxicillin wasassociated with a significantly higherincidence of diarrhea.46

Fluoroquinolones bind to enzymes,including DNA gyrase and topoisomeraseIV to inhibit bacterial DNA synthesis.Major advantages of this class ofantibiotics are their excellent penetrationinto respiratory secretions andinfrequent dosing. In addition, the fluoroquinolonesprovide excellent coverageagainst most respiratory pathogens,including atypical bacteria (eg, Cpneumoniae and M pneumoniae). Only aminute number of cases of AECB andacute bronchitis are caused by atypicalbacteria, however. Levofloxacin, gatifloxacin,moxifloxacin, and gemifloxacin,which have been available fora number of years, provide excellentactivity against S pneumoniae, H influenzae,M catarrhalis, and S aureus and areFDA-approved for the treatment ofAECB.49 Ciprofloxacin, although activeagainst H influenzae and M catarrhalis,has limited activity against pneumococci.Although fluoroquinolones areincreasingly used for treating AECB,the recent emergence of pneumococciwith reduced susceptibility to fluoroquinoloneshas created concern abouttheir widespread usage.50-52

The newer macrolides, includingclarithromycin and azithromycin, alsoprovide excellent activity against Spneumoniae, H influenzae, and Mcatarrhalis as well as against atypicalrespiratory pathogens. Macrolidesexert their bacteriostatic activity bybinding to the 50S ribosomal subunitto inhibit protein synthesis. The FDArecently approved the extended-releaseformulation of clarithromycin foronce-daily dosing to enhance compliance.Fluoroquinolones and macrolidesare therapeutic options forpatients with true hypersensitivity topenicillin. They have been associatedwith emerging resistance, however,particularly among penicillin-nonsusceptiblepneumococcal isolates in theUnited States.51,53,54

A new class of antibiotics called theketolides was developed to addressmacrolide-resistant bacteria.55 In thepresence of the ermB gene (and, in thecase of telithromycin, ermB and mefAgenes), ketolides remain active againstmacrolide-resistant pathogens.56 Althoughsimilar to the macrolides,ketolides bind more tightly to the 50Sribosomal subunit to enhance theiractivity against respiratory pathogensresistant to macrolides.57 Telithromycin,the first ketolide, recentlyreceived FDA approval for the treatmentof AECB, acute bacterial rhinosinusitis,and mild-to-moderate community-acquired pneumonia. Thespectrum of activity of telithromycinin the treatment of AECB includes Hinfluenzae, M catarrhalis, S pneumoniae,S aureus, C pneumoniae, and M pneumoniae.58 Telithromycin 800 mg once dailyfor 5 days provided a clinical curerate of 78% to 86%, which is comparableto comparators cefuroxime andamoxicillin/clavulanate.59,60 The 5-dayregimen also offers improved ease ofadministration as compared with thestandard 10-day regimens of amoxicillin/clavulanate, cefuroxime, andclarithromycin. Telithromycin servesas an alternative in the treatment ofAECB. The most common adverseeffects reported were gastrointestinal-related,including nausea and diarrhea.

Other treatment considerations forpatients with AECB and COPD areantibiotic prophylaxis, mucolyticagents, and vaccines. Antibiotics,specifically tetracycline or TMP/SMX,for patients with chronic bronchitisshould not be routinely used prophylactically,because the benefit is limitedto a minor reduction in the number ofdays of illness from AECB.59 If used,antibiotic prophylaxis, particularlyduring the winter months, should beconsidered only for patients with multiplerelapses of AECB within a year.In a recent meta-analysis, treatmentwith mucolytics has been shown toreduce acute exacerbations and thetotal number of days of disability.61Influenza and pneumococcal vaccinesare recommended for patients withCOPD and other chronic lung diseases.Annual administration of the influenzavaccine reduces the rate and severity ofillness, lost workdays, and physicianvisits.62 The polysaccharide pneumococcalvaccine appears to reduce invasivepneumococcal disease.63

Challenges of BacterialResistance

Bacterial resistance among respiratorypathogens occurs through multiplemechanisms (Table 4). Over the pastfew decades, antibiotic resistance hasincreased dramatically. To addressresistance, the most recent guidelinesfor the treatment of acute bronchitisand AECB focus on judicious use ofantibiotics. Under the selective pressureof antibiotic use, susceptible bacteriasuccumb, and, with less competition,resistant bacteria flourish.William Osler once wrote that thedesire to take medicine is perhaps thegreatest feature that distinguisheshumans from animals. This desireappears to be especially true for antibiotics.Their overuse greatly contributesto the increasing trend of resistanceamong respiratory bacterial pathogens.For example, multidrug-resistant pneumococci,defined as strains resistant toat least 3 classes of antibiotics, wererecovered in 26% of all isolates.51

The most common bacterial pathogensassociated with AECB are S pneumoniae,H influenzae, and M catarrhalis.Alteration of the penicillin-bindingproteins, a resistance mechanism acquiredby pneumococci, renders theorganisms resistant to penicillins,cephalosporins, and other beta-lactamantibiotics. In the United States, theprevalence of penicillin-nonsusceptible(include resistant and intermediatelysusceptible) strains of S pneumoniaereached a peak of 36% in 2001.64 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%).53 Most isolates of S pneumoniaeremain susceptible to respiratory fluoroquinolones(including gatifloxacin,gemifloxacin, levofloxacin, and moxifloxacin).Concern about the developmentof resistance is arising, however,from the extensive use of fluoroquinolonesin the treatment of community-acquired respiratory tractinfections.50

Cross-resistance between erythromycinand clindamycin occurred inapproximately 32% of S pneumoniaeisolates in the United States.53 Resistanceto both erythromycin and clindamycinis mediated by the ermB ribosomalmethylation mechanism (MLSB-phenotype), which inhibits binding ofthe antibiotic to the target site.64,65Most erythromycin-resistant S pneumoniae strains (68%) remain susceptibleto clindamycin, however.66 In theseisolates, resistance occurs by the mefAefflux pump (M-phenotype), whichdecreases antibiotic accumulation inthe bacteria.66,67

H influenzae (30%) and M catarrhalis(92%) confer resistance to penicillinsby producing beta-lactamases.53 Betalactamase-inhibitor combinations (eg,amoxicillin with clavulanate) andcephalosporins (specifically, ceftriaxone,cefixime, and cefdinir) retainexcellent activity against these pathogens.Both H influenzae and M catarrhalisare highly susceptible to the fluoroquinolones.Resistance of Hinfluenzae to TMP/SMX (22%) has beenobserved.55

Many studies strongly suggest thatjudicious use of antibiotics reducesresistance. In Finland, for example, acampaign to restrict antibiotic use ledto a decrease in erythromycin resistanceamong Group A streptococci.68This outcome supports the conceptthat a thoughtful approach to the useof antibiotics and restricting their useto appropriate situations will be beneficial.Table 5 provides some strategiesto reduce antibiotic use.

Conclusion

To optimize the treatment of acutebronchitis and AECB, the clinicianmust understand the pathogenesis andclinical features of these infections.Viruses are responsible for most casesof acute bronchitis and AECB. In thesescenarios, routine use of antibiotics isinappropriate and highly discouraged,because it may contribute to theincreasing prevalence of bacterialresistance. To encourage judicious useof antibiotics, the clinician must determinewhen bacterial infection is highlyprobable. Furthermore, although itis critical to consider guidelines whenselecting the optimal therapy, newresearch demonstrates improved treatmentin cases of bacterial resistance,and the society guidelines have yet tocatch up with clinical practice.

Case Study

A 65-year-old man presents to a primarycare clinic with a marked increase incough and purulent sputum production forthe past 4 days. He reports experiencing afever of 38.5ºC and worsening dyspneasince 2 days ago. He has a history of diabetesmellitus, chronic bronchitis, andsevere COPD. The patient is currently takingseveral medications for his lung diseaseand has been compliant with his regimen.Two weeks ago, he received TMP/SMX forthe treatment of a urinary tract infection.The result of a chest x-ray, which was doneto exclude pneumonia, indicates chroniclung changes with no acute infiltrate.What are treatment considerations for thispatient diagnosed with severe AECB?

AECB is characterized by anincrease in the frequency and/orseverity of symptoms associated withCOPD, including cough, dyspnea, andsputum production and purulence.These symptoms, accompanied byfever, are present in this patient.Because symptoms of AECB may overlapwith those associated with pneumonia,pneumonia must be consideredin the differential diagnosis,particularly in this patient withchronic lung disease. The chest x-rayrevealed no acute changes; hence, thispatient was diagnosed with AECB.

Although viruses contribute to themajority of cases of AECB, bacterialpathogens—most commonly S pneumoniae,H influenzae, and M catarrhalis—also can cause AECB. Antibiotictreatment should be reserved forpatients with clinically significantAECB, which is more likely to occurwhen multiple symptoms associatedwith AECB and severe underlying pulmonarydisease are present. Therefore,antibiotic therapy is recommendedfor the case patient with severe underlyingCOPD who is experiencingincreased and worsening symptoms.The goals of therapy are to (1) resolvesymptoms associated with airwayinflammation, (2) eradicate bacteria,(3) prevent hospitalization, and (4)prevent complications, including respiratorydistress and/or failure.

Therapeutic options for the treatmentof AECB include a narrow-spectrumantibiotic (eg, amoxicillin, doxycycline,or TMP/SMX). With therecent exposure to TMP/SMX, however,there is a higher likelihood of infectioncaused by a resistant pathogen,specifically S pneumoniae or H influenzae.In addition, the increasing prevalenceof bacterial resistance in patientswith severe underlying COPD limitsthe effectiveness of these narrow-spectrumagents.

New or extended-spectrum antibioticsthat have been studied or FDA-approvedfor the treatment of AECBare amoxicillin with clavulanate,cephalosporins, respiratory fluoroquinolones(levofloxacin, moxifloxacin,gatifloxacin, and gemifloxacin),macrolides (clarithromycinand azithromycin), and telithromycin.Although these antimicrobialagents, as compared with the narrow-spectrumantibiotics, have been associatedwith fewer relapses, there havebeen no updates of guidelines frommajor authorities to help direct physicianson the appropriateness of theiruse as first-line agents. Nonetheless,these are therapeutic options in thecase patient. One major advantage offluoroquinolones, macrolides, andtelithromycin is that they provideexcellent activity against atypical bacteria(eg, C pneumoniae and M pneumoniae),which are less common causesof AECB. In addition to antibiotictherapy, treatment for the casepatient's COPD should be optimized.He also should receive a mucolyticagent and influenza and pneumococcalvaccines. 

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.

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(Based on the article starting on page 55.) Choose the 1 most correct answer.

1. What percentage of uncomplicatedacute bronchitis is caused by bacterialpathogens?

  • 5% to 10%
  • 10% to 15%
  • 15% to 20%
  • 20% to 25%

2. What is the primary symptompresented by a patient with acutebronchitis?

  • Fever lasting less than 3 weeks
  • Fever lasting more than 3 weeks
  • Cough lasting less than 3 weeks
  • Cough lasting more than 3 weeks

3. A 22-year-old college student presentsshortly after Christmas vacation with a4-day history of a productive cough,myalgias, and a low-grade fever. Severalof her classmates have similar symptoms.The most likely cause of her infection is:

  • Mycoplasma pneumoniae.
  • Chlamydia pneumoniae.
  • Coronavirus.
  • Influenza virus.

4. Diagnosis of acute bronchitis is basedon clinical findings and requires theexclusion of pneumonia. Chest radiographymay help exclude pneumonia. Inwhich of the following scenarios is theuse of chest radiography appropriate?

  • In a patient with the following vitalsigns: heart rate 80 beats/min,respiratory rate 20 breaths/min,and oral temperature <38&#778;C
  • In a patient with suspectedpertussis
  • In a patient with underlying lungdisease
  • In a patient with a history of persistentcough and purulent sputumproduction for 2 weeks

5. The routine use of antibiotics in thetreatment of acute bronchitis is not recommended,because viruses account forthe majority of cases. Which of the followingpathogens is most likely to causeyou to consider using an antibiotic forthe treatment of acute bronchitis in apatient without underlying lung disease?

  • Streptococcus pneumoniae
  • C pneumoniae
  • M pneumoniae
  • Bordetella pertussis

6. Patients with pertussis generally seekmedical care later in the course of infection.What is the primary purpose forrecommending antibiotic treatment inthese patients?

  • Antibiotic therapy can preventtransmission.
  • Antibiotic therapy can preventcomplications.
  • Antibiotic therapy can resolvesymptoms.
  • Antibiotic therapy is not indicated,because pertussis is a self-limitinginfection.

7. What is the oral formulation of erythromycinrecommended for the treatmentof acute bronchitis caused by B pertussis?

  • Ethylsuccinate
  • Estolate
  • Stearate
  • Lactobionate

8. Which of the following antibiotics isactive against atypical bacterial pathogensincluding M pneumoniae andC pneumoniae?

  • High-dose amoxicillin
  • Amoxicillin with clavulanate
  • Levofloxacin
  • Clindamycin

9. Which of the following infectionscontributes to significant disability, morbidity,and mortality in people withchronic obstructive pulmonary disease?

  • Acute bacterial rhinosinusitis
  • Chronic rhinosinusitis
  • Acute bronchitis
  • Chronic bronchitis

10. Chronic bronchitis is characterizedby increased mucosal inflammation andmucus hypersecretion. What is the mostcommon cause of acute exacerbation ofchronic bronchitis (AECB)?

  • Smoking
  • Virus
  • Bacteria
  • Air pollution or allergen

11. An AECB is characterized by all ofthe following except:

  • An increase in sputum production.
  • Increasing cough.
  • An abnormal chest x-ray.
  • Dyspnea.

12. A 70-year-old woman presents to thehospital with increased cough andsputum production. She also complainsof worsening dyspnea and laboredbreathing (respiratory rate, 26). Gramstaining of her sputum sample revealsmany polymorphonuclear leukocytes(PMNs). Which of the following clinicalfeatures is least consistent with AECB?

  • Expectorated sputum containingmany PMNs
  • Increased frequency and severity ofcough and sputum production
  • Increased respiratory rate(>25 breaths/min)
  • Worsening dyspnea

13. For which of the following patientswould you recommend collecting a sputumsample for Gram stain and culture?

  • A patient with AECB who is notresponding to empirical antibiotictherapy
  • A patient with acute bronchitiscaused by M pneumoniae
  • A patient with persistent andparoxysmal cough lasting 3 weeks
  • A patient with purulent cough for3 months in 2 consecutive years

14. Which of the following antibiotics isconsidered a narrow-spectrum antibioticused in the treatment of acute exacerbationsof chronic bronchitis?

  • Levofloxacin
  • Amoxicillin
  • Azithromycin
  • Clarithromycin

15. High-dose amoxicillin withclavulanate has enhanced activityagainst which of the following bacterialpathogens?

  • M pneumoniae
  • Drug-resistant S pneumoniae
  • Moraxella catarrhalis
  • b and c only

16. Twice-daily dosing of high-doseamoxicillin, compared with 3-times-dailydosing, has been associated with a significantlylower incidence of ___________.

  • Nausea
  • Diarrhea
  • Rash
  • Hypersensitivity reaction

17. What is the primary concern withthe use of fluoroquinolones in thetreatment of AECB?

  • Poor penetration into respiratorysecretions
  • Frequent dosing
  • Emergence of resistance
  • Inadequate coverage againstatypical bacterial pathogens

18. Which of the following antibioticsexerts its effect by binding tightly to the50S ribosomal subunit to enhanceactivity against respiratory pathogens,including drug-resistant S pneumoniae?

  • Amoxicillin
  • Clarithromycin
  • Moxifloxacin
  • Telithromycin

19. Isolates of S pneumoniae may harborantibiotic resistance mediated by theermB ribosomal methylation mechanism.To what antibiotics are these strainsresistant?

  • Erythromycin and clindamycin
  • Amoxicillin and doxycycline
  • Fluoroquinolones andcephalosporins
  • Trimethoprim/sulfamethoxazole

20. How does Haemophilus influenzaeconfer resistance to penicillins?

  • Ribosomal methylation mechanism
  • Production of beta-lactamases
  • Alteration of penicillin-bindingprotein
  • Efflux pump