Respiratory Tract Infections In the Emergency Department

Lecture Objectives

Review presentation and diagnosis of respiratory tract infections seen in the emergency department (E.D.)

Discuss and compare different antibiotic treatment regimens for respiratory tract infections

Respiratory Tract Infections

> 200 million cases per year in U.S.A.10 % of office visits to primary care M.D.'sRx uses 1/2 of outpt. & 1/3 of inpt. antibioticsDirect Rx costs $15 billion per year Indirect Rx costs $9 billion per year

Upper tract infections:–Rhinitis, pharyngitis, sinusitis, otitis, epiglottitis, croup

Lower tract infections:–Tracheitis, bronchitis (acute & chronic), pneumonia

Lower Respiratory Tract Infections

Incidence–2.5 to 3 million cases per year in U.S.–25 % require hospitalization–? 50,000 deaths per year in U.S.–Account for 28 % of E.D. patients with respiratory symptoms

Acute Bronchial Infections

Most common etiologic agents:–Hemophilus influenzae (24 %) –H. parainfluenzae (17 %) –Streptococcus pneumoniae (20 %)–Branhamella catarrhalis (11 %)–Neisseria species

Note the top 4 account for 74 %

Acute Bronchial Infections

Less common etiologic agents:–Klebsiella –Pseudomonas–Staphylococcus aureus–Serratia marcescens–Other streptococci–? % role for mycoplasma & chlamydia

General Etiologies of Non-Viral Community- Acquired

Pneumonias

Strep. pneumoniae 60 to 75 %Legionella sp. 5 to 15 %Mycoplasma pneumoniae 5 to 18 %Hemophilus influenzae 2 to 5 %Chlamydia pneumoniae 2 to 5 %Staph. aureus 1 to 5 %Branhamella catarrhalis 1 to 5 %

Risk Factors for Additional Pathogens

(besides Strep. pneumoniae)

COPDAlcoholismDiabetesInstitutionalized"Active cancer"Bronchiectasis

Conditions Predisposing to Anerobic Lung Infections

Aspiration–Esophageal dysfunction–Suppressed consciousness

ƒ EtOH, drug OD, CVA, Seizure, AnesthesiaGingival infectionsUnderlying lung conditions

–Bronchiectasis, pulmonary infarction, neoplasms, other obstructive lesions

Subphrenic abscessPenetrating chest traumaThoracotomy

Classical aspiration pneumonia infiltrate (apical posterior segment of the right upper lobe)

Infiltrates six hours after aspiration

Causes of Pneumonia Associated with Hilar Adenopathy

AnthraxBlastomycosisCoccidiomycosisHistoplasmosisMycoplasmaPertussisEchovirus

PlaguePsittacosisTularemiaTuberculosisSporotrichosisRubeolaVaricella

Histoplasmosis with 2 to 5 mm nodules

Varicella pneumonia in a 24 year old female renal transplant patient

Bilateral upper lobe cavitary tuber-culosis

Miliary tuberculosis

Exudative right upper lobe infiltrate from tuber-culosis

Tuberculous pneumonia in the left upper lobe with consolidation and cavitation

Implanted Lucite plastic balls to collapse the upper lobes (old treatment for tuberculosis prior to antibiotics)

Viruses Causing Pneumonia

Most common:–Influenza–Adenovirus–RSV–CMV–Varicella-Zoster–Measles

Less common:–Parainfluenza–Rhinovirus–Coxsackie–Echovirus–Herpes simplex–Rubella

Pneumocystis carinii pneumonia

Pneumocystis carinii pneumonia

Pneumocystis pneumonia 4 days after a normal chest film

Sputum silver stain of Pneumocystis carinii

Pulmonary Kaposi’s sarcoma in an A.I.D.S. patient

Differential diagnosis of focal infiltrates in immuno-compromised patients

AG

L

S

S

Malignancy

AP

C

C

D

P

Differential diagnosis of diffuse interstitial infiltrates in immuno-compromised patients

Clinical Features of Pneumonia in the Elderly

Main symptoms may be malaise, weakness, stupor, "failure to thrive"

Cough may not be present Fever may not be presentTachypnea/tachycardia may be only signsLeucocytosis may not be presentX-ray findings may be obscured by CHF, COPD, old

TuberculosisResolution often prolongedSepsis and death more frequent

Indications for Pulse Oximetry when Pneumonia Suspected

Just about everybody !

Indications for Getting Arterial Blood Gases if Pneumonia

Suspected

O2 saturation < 90 % on O2Pulse oximeter unable to trackAltered mental statusPatient appears to be tiringIntubatedSubjective respiratory distress

Pneumococcal Pneumonia

Sudden onsetSx: chills, rigors, fever, pleuritic chest

painCough may be initially absentLung consolidation occurs early25 % of patients develop bacteremia5 % overall mortality

Left upper lobe infiltrate and CHF from Pneumococcal pneumonia

Sputum gram stain showing Streptococcus pneumoniae

Sputum gram stain of Streptococcus pyogenes

Complications of Pneumococcal Pneumonia

ARDSEmpyemaPurulent pericarditisPurulent arthritisMeningitis Endocarditis

Legionnaire's DiseaseGeneral Risk Factors

Ususally summer to early fallOccurs in all age groupsMiddle-aged males : most frequent1/2 of patients have underlying illness

–Immunosuppression (renal transplants)–Diabetes mellitus–COPD–Renal disease–Neoplasms

Legionella outbreak at Chambersburg Hospital in Pennsylvania

Legionnaire's DiseaseSocial and Occupational Risk Factors

SmokingEtOH useConstruction workExcavation of soil nearbyOvernight travel during incubation periodPerson to person transmission very rare ;

resp. isolation of case not needed

Legionella Pneumonia

Incidence–0.5 to 15 % of community-acquired pneumonias–Up to 30 % of nosocomial pneumonias ( if present in water supply)

If identified in hospital water supply, should attempt to eradicate organism :–Use superheated (> 70 degrees C) water to flush distal outlets–Hyperchlorination of hospital water to 4 to 6 ppm

Legionnaire's Disease(Legionella pneumophila)

Associated clinical findings:–Fever (continuous, not spiking; > 39.4 C in 80 %)–Malaise (100 %)–Weakness (100 %) : may be chief complaint–Anorexia (100 %)–Cough (92 %) : initially non-productive–Shaking chills (78 %) : usually begin on day 2 to 3–Bradycardia (60 %) : relative to temperature–Diarrhea (50 %) : watery, non-bloody, no abd. pain–Confusion, lethargy (33 %) : may be other CNS sx–Pleuritic chest pain (33 %)

O

Legionnaire's Disease

Less common clinical findings:–Hemoptysis (25 %) : usually minor–Headache–Myalgias–Arthralgias

Rhinitis & pharyngitis usually absent

Legionnaire's Disease

Lab and CXR findings:–Few to moderate polys on sputum gram stain–No bacteria on sputum gram stain–Leucocytosis–Elevated SGOT, LDH, Alk phos, bili (50 %)–Hyponatremia (50 %)–Hypophosphatemia–Proteinuria (50 %)–CXR: early patchy infiltrate, later lobar infiltrate

Legionella pneumonia in left upper and mid lung fields

Legionnaire's DiseaseConfirmation of Diagnosis

Culture–Charcoal yeast extract agar–Growth evident in 48 to 72 hours

Stains–Direct flourescent antibody (DFA) : best–Gimenez & Dieterla stains : not specific

Serologic–Indirect flourescent antibody (IFA)–Takes 3 to 6 weeks for IFA titer to increase–Dx by 4X increase in titer

Mycoplasma Pneumonia

Incidence greatest in 10 to 30 year oldsIncubation period 2 to 3 weeksHeadache, malaise, low fever,

nonproductive coughErythema multiforme may occur :

confirms diagnosisBullous myringitis : diagnosticMay also have otitis or non-exudative pharyngitisElevated cold agglutinin titers in second week

Complications of Mycoplasma Pneumonia

Hemolytic anemiaThrombocytopeniaDICStevens Johnson SyndromeMyocarditis / pericarditisMeningoencephalitisPolyneuritis / myelitisPancreatitisGlomerulonephritisAsthma

Chlamydia Pneumonia

Fever, cough, mucoid sputumPharyngitis commonMay have laryngitisChest pain / hemoptysis unusualDiagnosis by serology

(microimmunofluorescence)

Branhamella (Moraxella) catarrhalis Respiratory

Infections

Gram negative diplococciProduce beta-lactamaseCommonly cause COPD exacerbationsFever & leucocytosis in 50 %CXR infiltrates in 40 %

Staphylococcus aureus Pneumonia

1 to 5 % of all bacterial pneumonias30 % of bacterial pneumonias during

influenza outbreaksOverall mortality 20 %Postinfluenza mortality 50 %

Sputum gram stain of Staph. aureus

Conditions Associated with Aerogenous Staph. aureus

Pneumonia

InfluenzaNosocomialInstitutionalizedHIV infectionNeurosurgery

Right upper lobe infiltrate which progressed to an abscess (note air-fluid level) ; can occur from Staph. or Klebsiella

General Indications for Admission for Acute Lower Respiratory Tract

Infections

Persistent subjective respiratory distressHypoxemia (O2 sat. < 92 % on room air)Multilobar involvementHypercapnia or acidosisPersistent vomitingFailure of outpatient treatment"Toxic appearance" (altered mental status,

hemodynamic compromise)WBC count < 3000 (?)Comorbid diseases

Comorbid States Usually Mandating Admission for Treatment of Lower

Respiratory Tract Infections

Age > 65 years (?)Immunosuppressive illness (AIDS, etc.)"Active" cancerCHF exacerbationWheezing exacerbation (COPD)IDDMPoor clearance of secretions

–Neuromuscular disease–NG tube or feeding tube

Individual Factors NOT Necessarily Mandating Admission for Lower Resp. Tract Infections

FeverLeucocytosisWheezing on presentationPregnancyHemoptysis (if only represents blood -

streaked sputum)

Requirements for Outpatient Treatment of Pneumonia

Mild clinical findingsNo evident systemic toxicityNo respiratory distressNo hypoxemiaNo underlying diseasesAdequate home support systemAvailability of early followup care

General Antibiotic Choices for Pneumonia

Aspiration–Cefuroxime / Cefoxitin + aminoglycoside

Community acquired–Azithromycin / erythromycin

Gram negative rods–Same as aspiration +/- quinolone

Staphylococcal–Semisynthetic PCN* / 1st generation cephalosporin

Pneumococcal– PCN*

* May substitute azithromycin / erythromycin if PCN allergic

Azithromycin Dosing Regimens

Pathogen–Strep. pneumoniae–Hemophilus influ.–Staph. aureus–Gram neg. bacilli–Legionella pneu.–Agent unknown

Duration (days)–7 to 10–14–14 to 21 (42 ?)–14 to 21–14 to 21–At least 14

Treatment Durations with "Standard" Antibiotics for

Pneumonia

Relative Contraindications to Use of Quinolones for Pneumonia

Anerobes are suspected main pathogen (aspiration)

Uncomplicated Strep. pneumo. infectionChildren or Pregnancy (? cartilage

growth interference)Suspected chlamydia or mycoplasma

infections

Medications Causing Reduced Absorption of Quinolones

Aluminum antacidsMagnesium antacidsZinc (in multivitamins)Iron (ferrous sulfate)High dose calcium supplementsSucralfate

Comparative Advantages of Azithromycin Over Quinolones

No effect on fetal or pediatric cartilageBetter activity against Strep. pneumo.,

Legionella, Chlamydia, & MycoplasmaLesser discontinuance rate (0.2 to 0.7 % vs.

3.5 %)Lesser incidence of side effects (11 % vs. 16

%)No effect on theophylline levels (which are

elevated by quinolones)

Comparative Advantages of Azithromycin Over Doxycycline

Better activity against Strep. pneumo.Lesser incidence of GI side effectsNo sun exposure sensitivity / dermatitisNo effect on dentitionBetter compliance (less frequent dosing)

Comparative Advantages of Azithromycin Over Clarithromycin

More reliable / extensive Hemophilus influenzae coverage

Improved compliance–5 day duration vs. 7 to 10 day–Once daily dose vs. bid dose

Less drug interactions (safer)–No prolonged QT / arrhythmia with Seldane or Hismanal–No increased theophylline levels–No increased warfarin levels / effect

Additional Comparative Advantages of Azithromycin Over Clarithromycin

Longer elimination half life –68 hours vs. 3 to 5 hours

No adverse effects demonstrated on pregnancy outcome and fetal development in animal models (monkeys, rats, mice, rabbits show problems with clarithromycin)

Lesser discontinuance rate –0.2 to 0.7 % vs. 4 %

No metallic taste or aftertasteCost

–$36.00 vs. $56.45 (for standard regimen)

Study on Cost Efficacy of Azithromycin

Magid DJ, Douglas J, Schwartz JS : "Doxycycline versus Azithromycin in the Treatment of Women with Chlamydia Infections : A Cost-Effectiveness Analysis". Denver General Emergency Medicine Residency and Univ. of Pennsylvania, Presented at SAEM mtg. May 1993. Results: Azithromycin cost $49 per case &

doxycycline cost $55 per case when complications considered

Goals of Alteration of the Erythromycin Macrolide Ring in Developing New

Macrolides Like Azithromycin

Increased bioavailabilityStability in gastric acidGastrointestinal toleranceBroader antibacterial activityIncreased serum and tissue levelsLonger serum half life

Other Macrolides Currently Under Study

RoxithromycinMidecamycinJosamycinSpiramycin

Resolution of Common Pneumonias

Infection

Initial CXR pathology

Radiologic Clearing

Residual CXR Abnor-malities

Strep. pneu. usual 3 to 5 mo. 25 to 35 %

Legionella majority 2 to 6 mo. 10 to 25 %

Mycoplasma unusual 2 to 8 wks. rare

Chlamydia rare 1 to 3 mo. 10 to 20 %

Viral variable variable variable*

* Common with measles, varicella, adenovirus

Noninfectious Causes of Persistent CXR Infiltrates

Obstructing cancersAdenomasPapillomasLymphomaWegener's GranulomatosisBronchocentric GranulomatosisEosinophilic pneumoniaThromboembolismForeign body aspirationLipoid pneumonia

Efficacy of Pneumococcal Vaccine Butler et al. JAMA 1993; 270(15): 1826-

31.Condition

–Diabetes–Asplenia–CAD–CHF–COPD–Age > 65

% Efficacy–84–77–73–69–65–75

Conditions Identified in Butler's JAMA Study for Which Pneumococcal Vaccine

NOT Efficacious

Alcoholism / cirrhosisSickle cell diseaseChronic renal failureLymphoma / leukemiaMultiple myeloma

Dirithromicin : A Newly Released Oral Macrolide

F.D.A. approved for :–Bronchitis due to Strep. pneumo., Branhamella–Community acquired pneumoniaƒ Pneumococciƒ Mycoplasmaƒ Legionella–Skin & soft tissue infections due to Staph. aureus–Pharyngitis due to group A Strep.

Pharmacology of Dirithromycin

Hydrolyzed to active erythromycylaminePeak serum concentration in 4 to 5 hoursHalf life 30 hours, permitting once daily dosing

Allergy cross-reactivity with erythromicinHemophilus influenzae is resistantLower serum concentrations than other macrolides

Same GI side effects rate as erythromycin

Dosage & Cost of the Macrolides

DRUG DOSAGE COST*

Azithromycin 500 mg day 1, 250 mg q d X4

$ 36.23

Clarithromycin 250 to 500 mg bid x 7 days

$ 43.23

Dirithromycin 500 mg q day x 7 days

$ 26.25

Erythromycin(enteric generic)

250 mg qid x 7 days

$ 7.53

Ery-Tab (Abbott)

250 mg qid x 7 days

$ 6.65

ERYC (Parke-Davis)

250 mg qid x 7 days

$ 12.00

*1995