0071448802_chap69

KEY CONCEPTS

Antibiotic resistance patterns affect treatment options forbacterial upper respiratory tract infections.

The majority of uncomplicated acute otitis media infectionsresolve spontaneously without significant morbidity.

Antibiotic therapy for acute otitis media should be reservedfor children who are most likely to benefit from therapy: thoseunder 2 years of age and those with severe disease.

Proper diagnosis of bacterial upper respiratory tract infectionsis crucial to identify patients who require antibiotics to avoidunnecessary antibiotic use.

Amoxicillin and amoxicillin-clavulanate are first-line antibi-otics for acute otitis media.

Antibiotic therapy for sinusitis should be reserved for patientswith moderate persistent symptoms, clinical decompensation,or severe symptoms.

Empirical antibiotic selection for acute bacterial rhinosinusitisshould incorporate patient risk factors for bacterial resistance.

Amoxicillin and amoxicillin-clavulanate are first-line antibi-otics for acute bacterial rhinosinusitis.

The goals of therapy for streptococcal pharyngitis are to erad-icate infection, reduce symptoms and infectivity, and preventcomplications.

Penicillin is the drug of choice for streptococcal pharyngitis,but cephalosporins may be appropriate alternative first-lineagents owing to increasing failure rates after penicillin therapy.

Upper respiratory tract infection (URI) is a term that refers tovarious upper airway infections, including otitis media, sinusi-tis, pharyngitis, and rhinitis. Most URIs are viral and often self-limited. Over 1 billion viral URIs occur annually in the UnitedStates, resulting in millions of physician office visits each year.1

Excessive antibiotic use for URIs has contributed to the signifi-cant development of bacterial resistance. Guidelines have beenestablished to reduce inappropriate antibiotic use for viralURIs.2 This chapter will focus on acute otitis media, sinusitis,and pharyngitis because they are frequently caused by bacte-ria and require appropriate antibiotic therapy to minimizecomplications.

OTITIS MEDIA

Otitis media, or inflammation of the middle ear, is the mostcommon reason for prescribing antibiotics in children. Itusually occurs after a viral infection of the nasopharynx andcan be subclassified as acute otitis media or otitis media with

69 UPPER RESPIRATORY TRACT INFECTIONSHeather L. VandenBussche

LEARNING OBJECTIVES

UPON COMPLETION OF THE CHAPTER, THE READER WILL BE ABLE TO:

1. List the most common bacterial pathogens that cause acute otitis media, acute bacterialrhinosinusitis, and acute pharyngitis.

2. Explain the pathophysiologic causes of and risk factors for acute otitis media, bacterialrhinosinusitis, and acute pharyngitis.

3. Identify clinical signs and symptoms associated with acute otitis media, bacterialrhinosinusitis, and streptococcal pharyngitis.

4. List treatment goals for acute otitis media, bacterial rhinosinusitis, and streptococcal pharyngitis.

5. Develop an appropriate antibiotic regimen for each infection based on patient-specific data.

6. Recommend appropriate adjunctive therapy for a patient with acute otitis media, acutebacterial rhinosinusitis, or streptococcal pharyngitis.

7. Create a monitoring plan for a patient being treated for each infection using patient-specificinformation and prescribed therapy.

8. Educate patients about upper respiratory tract infections and proper use of antibiotic therapy.

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effusion. Acute otitis media (AOM) is a symptomatic middleear infection that occurs rapidly along with effusion, or pres-ence of fluid. Otitis media with effusion (OME) is the presenceof fluid in the middle ear without symptoms of acute illness. Itis important to distinguish between AOM and OME becauseantibiotics are only useful for treatment of AOM. Effusions canbe present for up to 6 months after an acute episode.

Epidemiology and Etiology

Otitis media is most common in children between 6 months and2 years of age but can occur in all age groups, including adults. By12 months of age, 75% of children have had at least one episodeof otitis media, and up to 20% have recurrent infections.3,4 Atleast 13 million antibiotic prescriptions are written annually inthe United States for otitis media, resulting in $2 billion in directcosts.5 Many risk factors (Table 691) predispose children to oti-tis media and can be associated with microbial resistance, such asday-care attendance, prior antibiotic exposure, and age youngerthan 2 years.3,4,6

Bacteria frequently are isolated from middle ear fluid inchildren with AOM, but viruses also play a predominant role.Streptococcus pneumoniae traditionally has been the most

common organism, responsible for 25% to 50% of cases.5,7

Nontypeable Hemophilus influenzae and Moraxella catarrhaliscause 15% to 30% and 3% to 20% of cases, respectively.Recent data suggest that the microbiology of AOM is shiftingtoward a prevalence of H. influenzae owing to routine child-hood immunization with pneumococcal conjugate vaccine.8

Bacteria that are less frequently associated with AOM includeS. pyogenes, Staphylococcus aureus, and Pseudomonas aerugi-nosa. Viruses such as respiratory syncytial virus, influenzavirus, rhinovirus, and adenovirus are isolated from middle earfluid with or without concomitant bacteria in over half ofAOM cases.9,10 Lack of improvement with antibiotic therapy isoften a result of viral infection and subsequent inflammationrather than antibiotic resistance.

Bacterial resistance has significantly affected treatmentguidelines for AOM. Penicillin-resistant S. pneumoniae (PRSP)encompasses both intermediate resistance (minimum inhibitoryconcentrations between 0.1 and 1.0 mcg/mL) and high-levelresistance (minimum inhibitory concentration of 2.0 mcg/mLand higher). Approximately 35% of respiratory pneumococcalisolates are penicillin-resistant owing to altered penicillin-binding proteins, and almost half are highly penicillin-resistant.11

PRSP are also commonly resistant to other drug classes,including sulfonamides, macrolides, and clindamycin, andincreasingly resistant to fluoroquinolones. Although inappro-priate use of antibiotics for URIs has led to increased resistancerates, treatment for pneumococcal AOM is necessary becauseinfection caused by S. pneumoniae is unlikely to resolve spon-taneously. -Lactamase production occurs in 30% and nearly100% of H. influenzae and M. catarrhalis, respectively.12

Although infections caused by these organisms are more likelyto resolve without treatment, they must be considered in casesof treatment failure.

Pathophysiology

Multiple factors play a role in the development of AOM. Viralinfection of the nasopharynx impairs eustachian tube functionand causes mucosal inflammation, impairing mucociliary clear-ance and promoting bacterial proliferation and infection.Children are predisposed to AOM because their eustachiantubes are shorter, more flaccid, and more horizontal than adults,which make them less functional for drainage and protection ofthe middle ear from bacterial entry. Clinical signs and symptomsof AOM are the result of host immune response and damage tocells caused by inflammatory mediators such as tumor necrosisfactor and interleukins that are released from bacteria.4

The majority of uncomplicated AOM cases resolve sponta-neously without significant morbidity. Untreated AOMimproves by day 2 or 3 of illness in 80% of children withoutincreasing the risk of complications.13 Antibiotics improve earpain in only 7% of children between days 2 and 7 of therapyand significantly improve recovery in children younger than

Patient Encounter 1, Part 1

A 15-month-old girl presents to the pediatricclinic with 2 days of fever (38.9C), runny nose,

and fussiness. Her mother states that she is more irritablethan usual and cries many times throughout the night. She isnot as interested in eating today. She attends day care andhas a 5-year-old brother who recently had a cold. Physicalexamination reveals erythema and bulging of the right tym-panic membrane and the presence of middle ear fluid. Theleft tympanic membrane is obscured with cerumen.

What information is suggestive of AOM?Does the child have risk factors for AOM?Is there any additional information you need to know

before recommending a treatment plan?

TABLE 691. Risk Factors for Otitis Media3,4,6

Viral respiratory tract infection/ Native American or Inuitwinter season ethnicity

Day-care attendancea Low socioeconomic statusSiblings Pacifier useMale gender Lack of breastfeedingTobacco smoke exposure Young age at first diagnosisa

Allergies ImmunodeficiencyAnatomic defects such as Gastroesophageal reflux

cleft palatePositive family history/genetic

predisposition

aRisk factors for infection with a resistant pathogen (day-care attendee,age under 2 years, recent antibiotic use in previous 3 months).


CHAPTER 69 / UPPER RESPIRATORY TRACT INFECTIONS 1063

2 years of age and in those with severe AOM symptoms.5,14,15

Therefore, antibiotics should be reserved for children mostlikely to benefit from therapy. Delayed antibiotic therapy in olderchildren and those with less severe disease does not result inmore infectious complications, such as mastoiditis or meningi-tis, when compared with routine initial antibiotic treatment.14

Use of this approach or use of a safety-net antibiotic prescrip-tion that parents fill 2 days later only if the child is not bettercan reduce antibiotic use for AOM dramatically withoutincreasing complications.16

Viscous middle ear effusions caused by allergy or irritantexposure may contribute to impaired mucociliary clearanceand AOM in susceptible individuals.4 OME occurs chronicallyin atopic children, and effusion can persist for months after anepisode of AOM. Children with chronic OME usually requiretympanostomy tube placement to reduce complications suchas hearing and speech impairment and recurrent otitis media.

Treatment

Desired OutcomesTherapy for AOM focuses on symptom relief and preventionof complications. The goals of treatment are to alleviate earpain and fever, if present; eradicate infection; prevent seque-lae; and minimize unnecessary antibiotic use.

General Approach to Treatment Treatment of AOM depends on patient age, illness

severity, and the certainty of diagnosis. Children younger than2 years of age have a higher incidence of penicillin-resistantpneumococcal infections and have higher clinical and bacteri-ologic failure rates and complications when not treated ini-tially with antibiotics as compared with older children.5,15

Patients with severe illness, defined by degree of fever andpain severity, have lower spontaneous recovery rates thanthose with nonsevere disease.14,15 Current guidelines recom-mend stratifying patients based on these criteria, along withcertainty of diagnosis, in order to identify those most likely tobenefit from antibiotic therapy.5

Clinical Presentation and Diagnosis

It is important to differentiate AOM from OMEbecause they are treated dramatically differently.

Patients with AOM usually have cold symptoms, including rhinorrhea, cough, or nasal congestion before or at diagnosis.

Symptoms Young children: ear tugging, irritable, poor sleeping and

eating habits Older patients: ear pain (mild, moderate, or severe), ear

fullness, hearing impairment

Signs5,7

Fever: present in less than 25% of patients; often inyounger children

Middle ear effusion Otorrhea (middle ear perforation with fluid drainage):

uncommon Bulging tympanic membrane Limited or absent mobility of tympanic membrane

Distinct erythema of tympanic membrane Opaque or cloudy tympanic membrane obscuring or

reducing visibility of middle ear

Laboratory TestsGram stain, culture, and sensitivities of ear fluid if drainingspontaneously or obtained via tympanocentesis (not per-formed routinely in practice)

Complications Infectious: mastoiditis, meningitis, osteomyelitis, intracranial

abscess Structural: perforated eardrum, cholesteatoma Hearing and/or speech impairment

Diagnosis5

Certain AOM: Requires all the following: Rapid onset of signs and symptoms Middle ear effusion findings with pneumatic otoscopy

(as above) Inflammation indicated by either otoscopic evidence

(distinct erythema) or otalgia Uncertain AOM: Not all three criteria are present. Severe AOM: Moderate to severe ear pain or fever of

39C or greater. Nonsevere AOM: Mild ear pain and fever of less than

39C in past 24 hours.

Patient Encounter 1, Part 2

On further questioning, you discover that thechild is allergic to penicillin. She developed a

nonurticarial rash last year during treatment for pharyngitis.She has not received antibiotics since that time, and this isher first ear infection.

Immunizations: Up to date

Meds: Acetaminophen drops 120 mg PO every 4 to 6 hoursas needed for fever or pain

ROS: (+) nasal congestion and rhinorrhea, () vomiting,diarrhea, or cough

PE: Gen: Irritable child but consolable VS: Blood pressure 100/60 mm Hg, pulse 120 beats per

minute, respiratory rate 18 breaths per minute, tempera-ture 38.6C

HEENT: As noted before

Identify your treatment goals for this child.Given this information, what nonpharmacologic and phar-

macologic therapy do you recommend?



Nonpharmacologic TherapyWatchful waiting and safety-net antibiotic prescriptions areapproaches being used more frequently to attenuate microbialresistance and avoid unnecessary adverse events and costs ofantibiotics. Observation is practiced extensively in Europe andinvolves monitoring for 48 to 72 hours after diagnosing AOMto see if spontaneous resolution will occur. Observation ordelayed antibiotic therapy should be considered only in other-wise healthy children without recurrent disease (Fig. 691) andonly if proper follow-up and good communication exist betweenclinicians and the parent/caregiver.4,5,16

Other nondrug approaches include the use of external heat orcold to reduce postauricular pain and surgery. Tympanostomytubes are most useful for patients with recurrent disease orchronic OME with impaired hearing or speech. Adenoidectomymay be necessary for children with chronic nasal obstruction, buttonsillectomy is rarely indicated.

Pharmacologic Therapy

Antibiotic TherapyWhen antibiotic therapy is needed, many factors influence ini-tial drug selection. Clinicians must consider drug factors such as

antimicrobial spectrum, likelihood of clinical response, inci-dence of side effects, drug interactions, and cost, as well aspatient factors, including risk factors for bacterial resistance,allergies, ease of dosing regimen, medication palatability, andpresence of other medical conditions. Studies in uncomplicatedAOM have not revealed significant differences between antibi-otics in clinical response rates that can be confounded by spon-taneous resolution. Bacteriologic response varies among antibi-otics and does not always correlate with clinical response. Tworecent well-designed trials that performed tympanocentesis atbaseline and at days 4 to 6 of treatment found significantly lessclinical improvement with azithromycin than with amoxicillin-clavulanate (p < 0.05) with even larger differences in bacterio-logic eradication (p < 0.01).17,18 These studies are importantbecause they only included patients with bacteriologicallyproven AOM and assessed bacteriologic cure separately fromclinical resolution, highlighting that clinical success does notequal bacteriologic success.

Guidelines from the American Academy of Pediatrics andthe American Academy of Family Physicians are available forchildren between 2 months and 12 years of age with uncom-plicated AOM (Fig. 692) and are based on published trialsand expert opinion.5 Amoxicillin remains the drug of choice

Age

Under 6 months 6 months to 2 years 2 years and older

Diagnosis certain?

Severe illness?

Yes

Yes

Antibiotic therapy Observation option

Failure

No Yes No

No

FIGURE 691. Treatment algo-rithm for initial antibiotics orobservation in children with sus-pected or certain uncomplicatedAOM.5



in most patients because of its proven effectiveness in AOM whenused in sufficient doses for PRSP, as well as its excellent safety pro-file, low cost, good-tasting suspension, and relatively narrow spec-trum of activity (Table 692). High-dose amoxicillin (8090mg/kg per day) is preferred over conventional doses becausehigher drug levels are achieved in middle ear fluid to overcomepneumococcal resistance without substantially increasingadverse effects.19 In cases of severe illness or when coveragefor b-lactamase-producing organisms is desired, high-doseamoxicillin-clavulanate is the preferred agent. Pneumococcalresistance to trimethoprim-sulfamethoxazole andmacrolides is problematic and strikingly common in PRSP,making these agents less desirable for most patients.6,20,21

Patients with penicillin allergies require alternative first-linetherapy (see Fig. 692). Children who have received an antibi-otic in the previous month are more likely to harbor resistantorganisms and also should receive alternative therapy.6 A sin-gle dose of intramuscular ceftriaxone is effective for childrenwho cannot tolerate oral medications, but a 3-day course maybe preferred because of increasing pneumococcal resistance andfailure of single doses.22 Ototopic antibiotics are an alternative

to systemic agents for AOM in patients with tympanostomytubes.23

If there is a lack of improvement or worsening with initialtherapy during the first 48 to 72 hours, antibiotic selectionmust be reassessed, and other contributing diseases must beexcluded5,6 (see Fig. 692). Tympanocentesis can help to guidetherapy in difficult cases.

Duration of therapy, like drug selection, depends on patientage and disease severity. Standard 10-day oral therapy is moreeffective than shorter courses for uncomplicated AOM in chil-dren younger than 2 years of age and those with recurrent infec-tions, as well as in older patients with severe illness.5,24

Exceptions to the 10-day regimen are for azithromycin and cef-triaxone. In older children with mild or moderate illness, antibi-otic therapy is needed only for 5 to 7 days.

Adjunctive TherapyPain is a central feature of AOM but is often overlooked in diseasemanagement. If pain is present on presentation, analgesics or top-ical anesthetics can be used to alleviate otalgia. Acetaminophenand ibuprofen are commonly used over-the-counter agents

FIGURE 692. Treatmentalgorithm for uncomplicatedAOM in children 2 months to12 years of age.5,6



TABLE 692. Antibioticsa for the Treatment of AOM5,7

Drug Usual Dose and Schedule Common Adverse Effects Relative Costb Comments

Amoxicillin 8090 mg/kg per day in 23 doses Nausea, vomiting, diarrhea, $ Drug of choice for AOM;(adult: 875 mg twice daily) rash experts recommended

high-dose overconventional doses(4045 mg/kg per day)

Amoxicillin- 8090 mg/kg per day in 23 doses Nausea, vomiting, diarrhea, $$$$$$$ More diarrhea thanclavulanate (adult: 875 mg twice daily) rash, diaper rash amoxicillin, Augmentin

ES formulationpreferred owing tolower daily clavulanatecomponent

Cefuroxime axetil 30 mg/kg per day in 2 doses (max Nausea, vomiting, diarrhea, $$$ Suspension gritty and bitter1 g/d with suspension; rash, diaper rash tasting, not adult: 250 mg twice daily) interchangeable with

tablets (less bioavailable)Cefdinir 14 mg/kg per day in 12 doses Diarrhea, rash, vomiting, diaper $$$ Preferred oral

(adult: 300 mg twice daily rash, yeast infections cephalosporin (goodor 600 mg once daily) taste); separate from Al

or Mg antacids and Fesupplements by 2 hours

Cefpodoxime 10 mg/kg per day in 2 doses Diarrhea, diaper rash, vomiting, $$$ Suspension is bitter tastingproxetil (adult: 200 mg twice daily) rash, yeast infections

Ceftriaxone 50 mg/kg IM or IV for 13 days Injection site pain, swelling, or $$$$$$$ 3-day regimen preferred(max 1 g/dose) erythema, diarrhea, rash for PRSP; avoid in

children under 2 monthsAzithromycin 10 mg/kg 1 day, 5 mg/kg per Nausea, vomiting, diarrhea, $$ Separate from Al or Mg

day 4 days; 10 mg/kg per abdominal pain antacids by 2 hours; day 3 days; or 30 mg/kg diarrhea/vomiting moresingle dose (adult dose common with single-500 mg 1,250 mg 4 days; dose regimen; 3- or 5-day 500 mg/d 3 days) courses preferred;

increasing pneumococcalresistance; many failureswith H. influenzaeinfection

Clarithromycin 15 mg/kg per day in 2 doses Diarrhea, vomiting, rash, $$ Many drug interactions(adult: 250 mg twice daily) abnormal taste, abdominal (inhibits cytochrome

pain P-450 3A4); suspensioncannot be refrigerated and has metallic taste;same microbiologicissues as azithromycin

Erythromycin- 50 mg/kg per day of erythromycin Nausea, vomiting, abdominal $$ Many drug interactions (likesulfisoxazole component in 34 doses pain, diarrhea, rash clarithromycin),

contraindicated inchildren under 2 months;increasing pneumococcalresistance

Trimethoprim- 810 mg/kg per day of trimethoprim Nausea, vomiting, anorexia, $ Increasing pneumococcalsulfamethoxazole component in 2 doses rash, urticaria resistance;

contraindicated in children under 2 months

Clindamycin 2030 mg/kg per day in 34 doses Nausea, diarrhea, C. difficile $ Oral liquid has very poor(adult: 300 mg four times daily colitis, anorexia taste; only for or 450 mg three times daily) pneumococcal infection

aOther FDA-approved antibiotics for AOM not included in AAP/AAFP guidelines: cefaclor, cephalexin, cefprozil, cefixime, loracarbef, and ceftibuten.bApproximate cost per course: $ (under $25), $$ ($25$50), $$$ ($50$100), $$$$ (over $100).



for mild to moderate pain. While studies have not demon-strated superior therapeutic advantages of one agent over theother,25 ibuprofen has a longer duration of effect but is notused routinely in children younger than 6 months of agebecause of increased toxicity concerns. Alternating ibuprofenwith acetaminophen is not recommended owing to a lack ofsafety and efficacy data on combination therapy and thepotential for dosing confusion and error. Topical anestheticdrops such as benzocaine (Auralgan) provide pain reliefwithin 30 minutes of administration and may be preferredover systemic analgesics when fever is absent. Myringotomyprovides immediate relief but is performed rarely. Other med-ications such as decongestants, antihistamines, and corticos-teroids have no role in the treatment of AOM and can, insome cases, prolong effusion duration.26,27 Data are lacking onthe safety and efficacy of complementary and alternativetreatments.

PreventionImmunizations may prevent AOM in certain patients, but data areconflicting. Influenza vaccine is more effective in preventingAOM in children older than 2 years of age than in youngerpatients perhaps owing to impaired immune response and imma-ture host defense in infants and toddlers.28,29 Pneumococcal con-jugate vaccine is protective against infection by vaccine serotypesonly with a limited overall benefit for AOM.30 Antibiotic prophy-laxis is no longer recommended for otitis-prone children becauseof increasing resistance. Avoidance or minimization of risk factorsassociated with otitis media, such as tobacco smoke and bottlefeeding, is advised, but the effects of these interventions remainunproven.

Outcome Evaluation

Improvement of signs and symptoms (i.e., pain, fever, andtympanic membrane inflammation) should be evident by 72hours of therapy. Children can appear clinically worse duringthe first 24 hours of treatment but often stabilize during thesecond day with defervescence and improved eating and sleep-ing patterns. If clinical improvement is not seen, or if thepatient worsens, reevaluation must occur to determine theproper diagnosis and treatment. Counsel patients and care-givers regarding common antibiotic adverse events such asrash, diarrhea, and vomiting that may prompt additional med-ical attention.

Presence of middle ear effusion in the absence of symp-toms is not an indicator of treatment failure. Children whocomplete therapy and are otherwise healthy should be reeval-uated after 3 months for the presence of effusion that requiresa hearing evaluation. Preschool-aged and younger childrenmay need reexamination 3 to 6 weeks after therapy becausespeech and hearing impairment is more difficult to assess inthis age group.

SINUSITIS

Sinusitis, or inflammation of the paranasal sinuses, is betterdescribed as rhinosinusitis that also involves inflammation ofcontiguous nasal mucosa, which occurs in virtually all cases ofviral respiratory infections. Acute rhinosinusitis is character-ized by symptoms that resolve completely in less than 4 weeks,whereas chronic rhinosinusitis typically persists as cough, rhi-norrhea, or nasal obstruction for more than 90 days. Acutebacterial rhinosinusitis (ABRS) refers to an acute bacterialinfection of the sinuses that can occur independently or besuperimposed on chronic sinusitis. The focus of this sectionwill be on ABRS and appropriate treatment.


Rhinosinusitis is one of the most common medical conditionsin the United States, affecting about 1 billion people annually.1

It is caused mainly by respiratory viruses such as rhinovirus,influenza virus, and respiratory syncytial virus but also can be

Patient Care and Monitoring

1. Assess the patients signs and symptoms. Arethey consistent with acute otitis media?

2. Review diagnostic information to determine if acute infec-tion is present. Are all three diagnostic criteria present?Was the proper method used for diagnosis (pneumaticotoscopy)?

3. Does the patient require antibiotic therapy, or is obser-vation an appropriate option?

4. Obtain a complete medication history, including pre-scription drugs, nonprescription drugs, and natural prod-uct use, as well as allergies and adverse effects.

5. Determine what medication should be used for pain, ifpresent.

6. If applicable, determine which antibiotic to use and theduration of therapy.

7. Develop a plan to assess effectiveness of the chosentherapy and course of action to take if the patient doesnot improve or worsens.

8. Provide patient education on What to expect from prescribed medication, including

potential adverse effects Avoidance of antihistamines and decongestants Signs of treatment failure

9. Stress the importance of adherence to therapy, includingantibiotic resistance concerns.

10. Determine the need for influenza and pneumococcalvaccinations.

11. Educate the family regarding risk factors for otitis media.



due to allergies or environmental irritants. Only 0.5% to 2% ofviral rhinosinusitis in adults is complicated by secondary bacte-rial infection, but this occurs in 5% to 13% of children.31,32

Upper respiratory infections of less than 7 days duration usuallyare of viral etiology, whereas more prolonged disease or diseasewith severe symptoms often is caused by bacteria. Risk factorsfor ABRS include prior viral respiratory infection, allergicrhinitis, anatomic defects, and certain medical conditions31,33

(Table 693). Clinicians often inappropriately prescribe antibi-otics for clinically suspected rhinosinusitis that usually is self-limiting and infrequently is complicated by bacterial disease.Antibiotics are useful only in shortening the course of ABRS.

Bacterial pathogens that cause sinusitis are similar to thosethat cause acute otitis media. S. pneumoniae and H. influenzaeare responsible for 50% to 60% of cases in all patients, with anadditional 20% of cases caused by M. catarrhalis in children.31,33

Risk factors for drug-resistant pathogens are also similar tothose in AOM.1 Other pathogens that cause sinusitis includeStreptococcus pyogenes (up to 5%), anaerobic bacteria such asBacteroides and Peptostreptococcus spp. (up to 9% of adults),and Staphylococcus aureus (up to 5% of adults).31 Chronicinfections are commonly polymicrobial with a higher incidenceof anaerobes, gram-negative bacilli, and fungi.

Pathophysiology

Rhinosinusitis is caused by mucosal inflammation and localdamage to mucociliary clearance mechanisms usually as a resultof viral infection or allergy. Increased mucus production andreduced clearance of secretions can lead to blockage of the sinusostia, or the opening of the sinuses to the upper airway. Thisenvironment is ideal for bacterial growth and promotes a cycleof local inflammatory response and mucosal injury character-ized by increased concentrations of interleukins, histamine, andtumor necrosis factor.31,33 Factors that contribute to bacterialinvasion include nose blowing, reduced local immunity, viralvirulence, and nasopharyngeal colonization with bacteria.31

Damage to the host defense system perpetuates bacterial over-growth and persistence of infection. Despite bacterial illness,there is a 50% to 70% spontaneous resolution rate forABRS.3436

Treatment

Desired OutcomesThe goals of treatment for ABRS are to eradicate bacteria andprevent serious sequelae. Specific aims are to relieve symptoms,normalize the nasal environment, use antibiotics when appro-priate, select effective antibiotics that minimize resistance, andprevent development of chronic disease or complications.

General Approach to TreatmentInitial management of rhinosinusitis focuses on symptom relieffor patients with mild disease lasting less than 10 days. Routineantibiotic use is not recommended for all patients because viralsinusitis is self-limiting and bacterial infection resolves sponta-neously in many cases. Antibiotic therapy should be reservedfor persistent, worsening, or severe ABRS: patients with mild tomoderately severe symptoms based on clinical judgment that havepersisted for greater than 10 days or worsened after 5 to 7 days andpatients with severe disease regardless of duration.31,34 Empiricalselection is often employed and should target likely pathogensbecause sinus cultures are rarely obtained.

TABLE 693. Risk Factors for Acute BacterialRhinosinusitis31,33

Viral respiratory tract infection/winter Anatomic defects (e.g.,season septal deviation)

Allergic or nonallergic rhinitis Intranasal medications orillicit drugs

Tobacco smoke exposure ImmunodeficiencyDental infections or procedures Swimming/divingCystic fibrosis or ciliary dyskinesia Mechanical ventilationNasogastric tubes Traumatic head injuryAspirin allergy, nasal polyps, and Female gender

asthma


Sinusitis symptoms typically last 7 to 10 days aftera viral infection and are caused by activation of

the immune system and parasympathetic nervous system.

Acute Signs and Symptoms31,32

Adults: Nasal congestion or obstruction, nasal/postnasaldischarge or purulence, facial pain or pressure (especiallyunilateral in a sinus area), diminished sense of smell, fever,cough, maxillary dental pain, fatigue, ear fullness or pain

Children: Nasal/postnasal drainage, congestion, persistentcough (particularly at night), fever, pharyngitis, ear dis-comfort, halitosis, morning periorbital edema or facialswelling, fatigue, facial or tooth pain

ComplicationsOrbital cellulitis or abscess, periorbital cellulitis, meningitis,cavernous sinus thrombosis, ethmoid or frontal sinus erosion,chronic sinusitis, and exacerbation of asthma or bronchitis

Diagnosis31,34 Clinical diagnosis: Most common method; a viral URI that

has not resolved after 10 days or worsens after 5 to 7 days and with signs and symptoms of acute infection(as above).

Radiographic studies: Useful for assessing presence ofabscess or intracranial complication.

Paranasal sinus puncture: Gold standard; not performedroutinely but can be useful in complicated or chronic cases.

Laboratory studies/nasopharyngeal cultures: Not recom-mended for routine diagnosis.



Nonpharmacologic TherapyAncillary treatments such as humidifiers, vaporizers, andsaline nasal sprays or drops are used to moisturize the nasalcanal and impair crusting of secretions along with promotingciliary function. Although many patients report benefit fromsuch therapies, there are no controlled studies that supporttheir use.32,34,36

Pharmacologic Therapy

Adjunctive TherapySupportive medications that target symptoms of viral URIs areused widely in patients with rhinosinusitis, particularly in theearly stage of infection. There is a lack of evidence supportingtheir use in ABRS, but they may provide temporary relief in cer-tain patients.32,36,37 Analgesics can be used to treat fever andpain from sinus pressure. Oral decongestants relieve congestednasal passages but should be avoided in children younger than2 years of age and patients with ischemic heart disease oruncontrolled hypertension. Intranasal decongestants can beused for severe congestion in most patients 6 years of age orolder, but use should be limited to 3 days or less to avoidrebound nasal congestion. Antihistamines should be avoidedbecause they thicken mucus and impair its clearance, but theymay be useful in patients with predisposing allergic rhinitis orchronic sinusitis. Similarly, intranasal corticosteroids usually

are reserved for patients with allergies or chronic sinusitis, butthey may be beneficial as monotherapy or with antibiotics inABRS.38,39

Antibiotic TherapyAlthough many clinical studies have been performed evaluat-ing antibiotics for ABRS, no randomized, double-blind, placebo-controlled studies have used pre- and posttreatment sinus aspi-rate cultures as an outcome measure. Despite this, antibioticsappear to resolve symptoms more quickly and reduce failurerates and complications compared with no treatment.3537 Sincediagnosis usually is based on clinical presentation and notsinus aspirate cultures, clinicians must attempt to differentiateABRS from viral rhinosinusitis. Therefore, it is important tolimit antibiotic use to cases where infection is unlikely to resolvewithout causing prolonged disease: patients with mild to moder-ate symptoms that persist for 10 days or worsen over 5 to 7 daysand patients with severe symptoms.31,34

Treatment guidelines developed by the Sinus and AllergyHealth Partnership reflect antibiotic choices that are likely toresult in favorable clinical and bacteriologic outcomes basedon pathogen distribution, spontaneous resolution rates, andnationwide resistance patterns.31 These guidelines (Figs. 693and 694) stratify therapy based on severity of disease and riskof infection with resistant organisms, defined as mild disease inpatients with prior antibiotic use within 4 to 6 weeks. Other riskfactors for resistance include day-care attendance or frequent

FIGURE 693. Treatment algorithm for acute bacterial rhinosinusitis in patients with mild disease with-out recent antibiotic exposure.31 aAntibiotics are listed in order of predicted efficacy based on predictedclinical and bacteriologic efficacy rates, clinical studies, safety, and tolerability. Doses can be found inTable 694. bCephalosporins should be considered for patients with non-type I hypersensitivity to peni-cillins; they are more likely to be effective than the alternative agents. cHigh doses (90 mg/kg per day)are recommended for most children, especially those with day-care contacts or frequent infections.



exposure to children in day care and recurrent disease. Severedisease requires evaluation and treatment in conjunction withspecialized physicians such as otolaryngologists.

Antibiotic therapy (Table 694) is targeted against S. pneu-moniae, but consideration must be given to other pathogenssuch as H. influenzae, M. catarrhalis, and PRSP. Patients withmild disease and no prior antibiotic exposure should receive initialtherapy with amoxicillin or amoxicillin-clavulanate. Amoxicillinis effective for most mild infections and can be used in highdoses to cover PRSP. It is less expensive and better toleratedthan amoxicillin-clavulanate, which provides expanded cover-age against -lactamase-producing bacteria. Patients who areallergic to penicillins can be treated with an appropriatecephalosporin; severe penicillin allergies require treatment withalternative agents that may be less effective based solely onmicrobial resistance trends and not clinical data11,20,31,36 (seeFig. 693). Initial therapy for patients with moderate symptomsor those with recent antibiotic exposure includes high-doseamoxicillin-clavulanate or a respiratory fluoroquinolone31,32

(see Fig. 694).Failure to respond to initial therapy after 3 days requires

patient reevaluation to consider changing therapy to coverpathogens not treated with the initial choice. Antibiotics tradi-tionally have been given for at least 10 to 14 days, with up to21 days needed for resolution in some patients.31 Recent datasuggest that 5-day treatment courses of some fluoroquinolonesand telithromycin are as effective as longer courses in adults with

uncomplicated acute maxillary sinusitis.40 Treatment success isinfluenced by medication adherence to the prescribed regimen,where once- or twice-daily agents are preferred over multipledaily doses.

Outcome Evaluation

Clinical improvement should be evident by 72 hours of ther-apy, as demonstrated by defervescence, reduction in nasalcongestion and discharge, and improvements in facial pain orpressure and other symptoms. Patients should be monitoredfor common adverse events and referred to a specialist if clin-ical response is not obtained with first- or second-line ther-apy. Referral is also important for recurrent or chronic sinusi-tis or acute disease in immunocompromised patients. Surgerymay be indicated in complicated cases.

PHARYNGITIS

Pharyngitis is an acute throat infection caused by viruses orbacteria. Other conditions, such as gastroesophageal reflux,postnasal drip, or allergies, also can cause sore throat andmust be distinguished from infectious causes. Acute pharyn-gitis is responsible for 1% to 2% of adult physician visits and6% to 8% of pediatric visits but generally is self-limited with-out serious sequelae.41,42 Antibiotics are prescribed in 50% to70% of cases in adults and children because of the inability to

FIGURE 694. Treatment algorithmfor acute bacterial rhinosinusitis inpatients with mild disease andrecent antibiotic exposure or moder-ate disease.31 aAntibiotics are listed inorder of predicted efficacy based onpredicted clinical and bacteriologicefficacy rates, clinical studies, safety,and tolerability. Doses can be foundin Table 694. bCephalosporinsshould be considered for patientswith non-type I hypersensitivity topenicillins; they are more likely tobe effective than the alternativeagents. cRespiratory fluoroquinolone =gatifloxacin, levofloxacin, moxi-floxacin. dCombination therapyshould provide gram-positive andgram-negative coverage. Examplesare high-dose amoxicillin or clin-damycin plus rifampin or cefixime.There are no published clinical stud-ies to support such combinations.



TABLE 694. Antibioticsa,b for the Treatment of Acute Bacterial Rhinosinusitis31,32

Drug Adult Dose Pediatric Dosec Comments

Amoxicillin 1.54 g/d in 23 doses 90 mg/kg per day in 2 doses Lacks coverage against -lactamase producersAmoxicillin-clavulanate 1.754 g/d in 23 doses 90 mg/kg per day in 2 doses Broad coverage particularly with high doses;

Augmentin XR (2 g every 12 hours) targeted toward PRSP

Cefdinir 600 mg/d in 12 doses 14 mg/kg per day in 12 doses Preferred oral liquid cephalosporin owingto palatability

Cefpodoxime proxetil 200 mg twice daily 10 mg/kg per day in 2 dosesCefuroxime axetil 250500 mg twice daily 1530 mg/kg per day in 2 dosesCeftriaxone 1 g IM/IV every 24 hours 50 mg/kg IM/IV every 24 hours Experts recommend a 5-day treatment courseTrimethoprim- 160/800 mg (1 DS tablet) 810 mg/kg per day of Considerable pneumococcal resistance

sulfamethoxazole twice daily trimethoprim component limits use of this agentin 2 doses

Azithromycin 500 mg 1 day, 250 10 mg/kg 1 day, 5 mg/kg per Increasing pneumococcal resistance and limitedmg/day 4 days; day 4 days; 10 mg/kg per H. influenzae activity; single-dose regimen500 mg/day 3 days; day 3 days has high incidence of nausea, vomiting, and2 g 1 dose diarrhea

Clarithromycin 500 mg twice daily or 1 g 15 mg/kg per day in 2 doses XL tablets reported to have fewer gastrointestinalonce daily (XL only) problems and taste disturbances than

twice-daily preparationTelithromycin 800 mg once daily 5 days Not available Improved pneumococcal coverage over

macrolides; can cause blurred or double vision and difficulty focusing; cost and otherside effects similar to clarithromycin-azithromycin

Doxycycline 100 mg twice daily Avoid in children under 8 years Can cause photosensitivity, gastrointestinal problems, tooth staining in young children;many drug-drug interactions (antacids, iron, calcium)

Gatifloxacin 400 mg once daily Not available Common fluoroquinolone side effects are Levofloxacin 500750 mg once daily Not available nausea, vaginitis, diarrhea, dizziness; many

(750 mg ( 5 days) drug-drug interactions (antacids, iron, Moxifloxacin 400 mg once daily Not available calcium); tendon rupture, photosensitivity,

QT prolongation possible; cost similar to amoxicillin/clavulanate

Clindamycin 150450 mg 34 times 2040 mg/kg per day in No gram-negative coverage; use indaily 34 doses combination

aRefer to Table 692 for more information on antibiotics.bOther FDA-approved antibiotics for ABRS not included in the Sinus and Allergy Health Partnership or AAP guidelines: cefaclor, cefprozil, cefixime,ciprofloxacin, erythromycin, loracarbef.cMaximum dose not to exceed adult dose.


1. Assess the patients signs and symptoms. Arethey consistent with ABRS?

2. How long have the patients symptoms been present? Ifsymptoms are mild and present for fewer than 10 days,viral sinusitis is likely. Persistent moderate or acute severesymptoms are more indicative of bacterial infection.

3. Does the patient require antibiotic therapy? Avoid antibi-otic use in viral disease.

4. Obtain a complete medication history, including prescrip-tion drugs, nonprescription drugs, and natural product use,as well as allergies and adverse effects.

5. Determine what adjunctive therapies should be used forsymptoms, such as pain and congestion.

6. If applicable, determine which antibiotic to use and theduration of therapy.

7. Develop a plan to assess effectiveness of the chosen ther-apy and course of action to take if the patient does notimprove or worsens.

8. Provide patient education on What to expect from the antibiotic and other medica-

tions, including potential adverse effects Avoidance of antihistamines, if appropriate Signs of treatment failure Role of viral infections in sinusitis and how to prevent

disease transmission9. Stress the importance of adherence to therapy, including

antibiotic resistance concerns.



easily distinguish between viral and bacterial pathogens andfear of untreated streptococcal illness.42,43


Viruses most commonly cause pharyngitis, usually as partof an upper respiratory infection, and include rhinovirus,coronavirus, adenovirus, influenza virus, parainfluenza, andEpstein-Barr virus. S. pyogenes, or group A Streptococcus, is themost common bacterial cause of acute pharyngitis, responsi-ble for 15% to 30% of cases in children and 5% to 10% ofadult infections.41,44 Infection is most common in late winterand early spring and is spread easily through direct contactwith contaminated secretions. Clusters of infection are com-mon within families, classrooms, and other crowded areas. Lesscommon causes of bacterial pharyngitis are Corynebacteriumdiphtheriae, groups C and G streptococci, and Neisseria gonor-rhoeae. This section will focus on group A streptococcal dis-ease in which antibiotic therapy is indicated.

Pathophysiology

Pharyngeal colonization with group A streptococci occurs in upto 20% of children and is a risk factor for developing streptococ-cal pharyngitis after a break in mucosal integrity.45 Cliniciansshould recognize that the symptoms of streptococcal pharyngitisusually are self-limited and resolve within 2 to 4 days of onsetwithout treatment.44 Historically, untreated or inappropri-ately treated disease caused acute rheumatic fever, potentialpermanent heart valve damage, and complications such as peri-tonsillar abscesses. Delayed antibiotic therapy given up to 9 daysafter symptom onset can prevent these sequelae, so properdiagnosis is important to minimize unnecessary antibiotic usefor viral disease and complications of untreated streptococcalinfection.44,45

Treatment

Desired Outcomes The goals of therapy for streptococcal pharyngitis are to

eradicate infection in order to prevent complications, shorten thedisease course, and reduce infectivity and spread to close con-tacts. Sequelae that can be prevented by antibiotic use are peri-tonsillar or retropharyngeal abscess, cervical lymphadenitis,and rheumatic fever. There is no evidence that antibiotic usehas an impact on the incidence of poststreptococcalglomerulonephritis.

Pharmacologic Therapy Antibiotics should be used only in cases of laboratory-

documented streptococcal pharyngitis associated with clinicalsymptoms in order to avoid overtreatment45,46 (Fig. 695).Effective therapy (Table 695) reduces the infectious periodfrom approximately 10 days to 24 hours and shortens symptomduration by 1 to 2 days.41 Treatment guidelines recommendpenicillin as the drug of choice owing to its narrow antimicrobialspectrum, documented safety and efficacy in eradicating strepto-cocci from the nasopharynx, and low cost.41,45 Historical studiesproving that antibiotics prevent rheumatic fever used intramus-cular procaine penicillin, but other antibiotics can eradicatenasopharyngeal streptococci and presumably are effective for

Patient Encounter 2

A 7-year-old boy presents to the pediatrician witha sore throat and fever of 39.2C for 24 hours.

His mother reports that other children in his class have hadstrep throat recently. He also complains of pain on swal-lowing and is not eating or drinking very much. He does nothave any other symptoms and has no known drug allergies.Physical examination reveals pharyngeal and tonsillar ery-thema with exudates and painful cervical lymphadenopathy.

Does this child have streptococcal pharyngitis?Is antibiotic therapy indicated? If so, what agent should be

initiated and for how long?What education should be provided to his mother regarding

treatment?


Children between 5 and 15 years of age havethe highest incidence of streptococcal

pharyngitis. Parents and adults with significant pediatriccontact are also at increased risk.

Signs and Symptoms of Streptococcal Pharyngitis44.45

Sudden onset of sore throat with severe pain on swallowing

Fever Headache, abdominal pain, nausea, or vomiting (espe-

cially in children) Pharyngeal and tonsillar erythema with possible patchy

exudates Tender, enlarged anterior cervical lymph nodes Swollen and red uvula Soft palate petechiae Scarlatiniform rash General absence of conjunctivitis, hoarseness, cough, rhi-

norrhea, discrete ulcerations, and diarrhea (suggestive ofviral etiology)

Diagnosis41,45

Throat swab and culture: Gold standard; results within 24 to 48 hours

Rapid antigen detection test: 80% to 90% sensitivity;results within minutes

These tests should be performed only if there is a clinicalsuspicion of streptococcal pharyngitis.



preventing rheumatic heart disease.45 Recent data suggest thatcephalosporins are more effective than penicillin in producing bacteri-ologic and clinical cure and can be considered as first-line therapyalternatives in children and adults.47,48 Possible reasons for improvedcephalosporin efficacy include the copresence of -lactamase-producing organisms that inactivate penicillin, improvederadication of commensal streptococci by penicillin that areprotective against group A streptococcal disease, and improvedpharyngeal tissue penetration of cephalosporins. Usual dura-tion of therapy is 10 days, but evidence is mounting that 5-daycourses of certain cephalosporins are just as effective for bacter-ial eradication as 10 days of penicillin.49,50

Antibiotic resistance plays a smaller role in pharyngitistherapy compared with other URIs. Penicillin resistance hasnot yet been documented in group A streptococci, but resistance

and clinical failures occur more frequently with tetracyclines,trimethoprim-sulfamethoxazole, and to a lesser degree macrolides.As such, patients with penicillin allergies should be treatedwith a first-generation cephalosporin (if non-type I allergy), amacrolide/azalide, or clindamycin. Recurrent infections causedby reinfection, poor adherence to therapy, or true penicillin fail-ure can be treated with amoxicillin-clavulanate, clindamycin, orpenicillin G benzathine.45

Outcome Evaluation

Antibiotics relieve symptoms over 3 to 5 days, and after thefirst 24 hours of therapy, patients can return to work or schoolif improved clinically. Follow-up cultures are not recom-mended to test for bacterial eradication. Lack of improvement

TABLE 695. Antibioticsa for the Treatment of Streptococcal Pharyngitis44,45

Drug Adult Dose Pediatric Dose Duration Comments

Penicillin V 250 mg 34 times daily 250 mg 23 times daily 10 days Drug of choice but increasing reportsor 500 mg twice daily 500 mg twice daily of treatment failures

(over 12 years)Penicillin G benzathine 1.2 million units 600,000 units (if under 1 IM dose Useful for nonadherence or emesis;

27 kg) painful injectionAmoxicillin 250500 mg 3 times daily 4050 mg/kg per day in 10 days Preferred over penicillin V for young

750 mg daily being studied 3 doses children (more palatable)Cephalexin 250500 mg 4 times daily 2550 mg/kg per day in 10 days Consider in penicillin allergy (if

4 doses non-type I reaction)Cefadroxil 500 mg twice daily 30 mg/kg per day in 2 doses 10 daysCefuroxime axetil 250 mg twice daily 20 mg/kg per day in 2 doses 10 daysCefdinir 300 mg twice daily or 14 mg/kg per day in 12 doses 510 days Broad spectrum; expensive

600 mg once dailyAzithromycin 500 mg once daily 12 mg/kg once daily 5 days Increasing resistanceClindamycin 150 mg 4 times daily 2030 mg/kg per day in 10 days Useful for recurrent infections

3 doses

aOther FDA-approved agents include amoxicillin-clavulanate, cefixime, cefaclor, cefprozil, cefpodoxime, erythromycin, clarithromycin, and others.

FIGURE 695. Treatment algorithmfor management of pharyngitis inchildren and adults.45,46 aRapidantigen detection tests (RADTs) arepreferred if the test sensitivityexceeds 80%.



or worsening of symptoms after 72 hours of therapy requiresreevaluation. Recurrent symptoms following an appropriatetreatment course should prompt reevaluation for possibleretreatment.

ABBREVIATIONS

ABRS: acute bacterial rhinosinusitisAOM: acute otitis media

OME: otitis media with effusionPRSP: penicillin-resistant Streptococcus pneumoniaeURI: upper respiratory tract infection

Reference lists and self-assessment questions and answers areavailable at .

KEY REFERENCES AND READINGS

American Academy of Pediatrics Subcommittee on Management ofAcute Otitis Media. Diagnosis and management of acute otitismedia. Pediatrics 2004;113(5):14511465.

Bisno AL, Gerber MA, Gwaltney JM, et al. Practice guidelines for thediagnosis and management of group A streptococcal pharyngi-tis. Clin Infect Dis 2002;35:113125.

Casey JR, Pichichero ME. Meta-analysis of cephalosporin versuspenicillin treatment of group A streptococcal tonsillopharyngi-tis in children. Pediatrics 2004;113(4):866882.

Cooper RJ, Hoffman JR, Bartlett JG, et al. Principles of appropriateantibiotic use for acute pharyngitis in adults: Background. AnnIntern Med 2001;134:509517.

Dowell SF, Butler JC, Giebink GS, et al. Acute otitis media: Managementand surveillance in an era of pneumococcal resistanceA reportfrom the Drug-resistant Streptococcus pneumoniae TherapeuticWorking Group. Pediatr Infect Dis J 1999;18:19.

Glasziou PP, Del Mar CB, Sanders SL, Hayem M. Antibiotics for acuteotitis media in children. Cochrane Database Syst Rev 2004;1:CD000219.

Ioannidis JPA, Lau J. Technical report: Evidence for the diagnosis andtreatment of acute uncomplicated sinusitis in childrenA sys-tematic overview. Pediatrics 2001;108(3):e57.

Lau J, Zucker D, Engels EA, et al. Agency for Health Care Policyand Research Publication No. 99-E016. Evidence report:Diagnosis and treatment of acute bacterial rhinosinuitis.Rockville, MD: Agency for Health Care Policy and Research;March 1999.

Sinus and Allergy Health Partnership. Antimicrobial treatmentguidelines for acute bacterial rhinosinusitis. Otolaryngol HeadNeck Surg 2004;130(suppl):S145.


1. Assess the patients signs and symptoms. Arethey consistent with streptococcal pharyngitis?

Are symptoms of viral infection present?2. Perform laboratory testing to confirm the presence of

group A streptococci.3. Does the patient require antibiotic therapy? Avoid antibi-

otic use in viral disease.4. Obtain a complete medication history, including pre-

scription drugs, nonprescription drugs, and natural prod-uct use, as well as allergies and adverse effects.

5. Recommend antipyretic or analgesic therapy, if needed.6. If applicable, determine which antibiotic to use and the

duration of therapy.7. Develop a plan to assess effectiveness of chosen therapy

and course of action to take if the patient does notimprove or worsens.

8. Provide patient education on What to expect from the antibiotic, including potential

adverse effects Avoidance of close contacts for 24 hours Signs of treatment failure

9. Stress the importance of adherence to therapy, includingantibiotic resistance concerns.


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