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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