APPROACH TO A PATIENT WITH ACUTE RESPIRATORY INFECTION

Learning Objectives

• Spectrum• Pathophysiology• Classification• Approach • Clinical syndromes• Case discussion

Impact

• Sixth most common cause of death

• Second biggest cause of DALY(disability adjusted

life years)

• Most common infectious cause of death

• Most common cause of intravenous antibiotic

use in hospitals

ATS Global Scholars program, Pneumonia in children and adults, 2016

ATS Global Scholars program, Pneumonia , in children and adults, 2016

SpectrumRhinitis

Tonsillitis

Sinusitis

Otitis media

Pharyngitis

Epiglottitis

Laryngitis

Tracheitis

Bronchitis

Bronchiolitis

Pneumonia

Pleurisy

Upper respiratory tract infection

Etiology

Rhinovirus(45)Influenza(25)Coronavirus(10)Adenovirus(10)Metapneumovirus(5)Enterovirus(10)RSV(5)

Mandell 8th edition

Acute rhinosinusitis

• Inflammation of nasal cavity and sinuses• <4 weeks

Symptoms Suggesting Bacterial InfectionProlonged symptoms (> 10 days)Unilateral maxillary sinus tendernessUnilateral purulent nasal dischargeDouble sickening (symptoms improve then worsen)

Chow et al. Clin Infect Dis. 2012; 54(8):e72-112

Acute Pharyngitis

Sudden onset

High fever

Lymph nodes

Treatment: Penicillin V 500mg BD x 10 days or Amoxicillin 1000mg OD x 10 days

Influenza virus

Pneumonia

• Inflammation of the pulmonary parenchyma plus clinical evidence that the infiltrate is of an infectious origin, which include new onset of – Fever(< 7 days)– Purulent sputum– Leukocytosis – Decline in oxygenation

ATS 2005 HAP/VAP Guildelines

Classification

•Viral•Bacterial•FungalEtiological

•Lobar•Broncho•Interstitial

Morphological

•Community acquired•Hospital Acquired•Ventilator acquired

Clinical syndrome

Epidemiological triad

AgeNormal floraGlottis reflexImmunityEpithelial sheddingMucociliary clearance

Condition OrganismIn almost all cases Strep and H. influenzae are predisposed as they are most common.In Indian settings, most conditions also pre dispose to Tuberculosis

Bat exposures, Bird droppings Histoplasma, Cryptococcus

Paddy fields, farmers, rodent exposure Leptospira

Hilly areas(Himalyan belt) Scrub typhus

Birds Chlamydia psittaci

Farm animals Q fever(Coxiella)

North America travel

Aspiration risk/Alcohol Anaerobes

Structural lung disease Pseudomonas, Burkholderia, NTM, fungal

Injection drug users Staphylococcus, Anaerboes

Influenza outbreak Influenza, Staphylococcus

Air conditioners, cooling towers, pot water

Leigionella

COPD Moraxella, Pseudomonas

Fishmans Pulmonary Medicine 5th edition

Physical examination• Respiratory system examination– Respiratory rate– Bronchial sounds, dullness to percussion, crackles

• Additional exam– Cutaneous abscess– Skin lesions– Lymph nodes– Periodontal hygiene– Gag reflex– Ear examination

Investigations

NONINVASIVE

INVASIVE

Hematological

1. CBC with DLC

2. KFT3. LFT4. Biomarkers

Microbiology

1. Sputum2. Nasal Swab3. Blood

cultures4. ET aspirate5. Newer test

Radiology1. Chest X-ray2. CT scan

1. Bronchoscopy2. Lung Biopsy

Biomarkers

• Erythrocyte sedimentation rate(ESR)• C- Reactive Protein(CRP)• Procalcitonin(PCT)• Trigerring receptor expressed on Myeloid

cells(sTREM1)

Procalcitonin• Precursor of calcitonin – Thyroid and K cells of lung• CAP – Only role may be to differentiate from decompensated

heart failure and non infective causes• HAP/VAP – Not used for diagnosis and initiation of antibiotics

but clinical as well as Procalcitonin may be used to stop antibiotics

• Sequential use of Procalcitonin for levels maybe useful

Sensitivity Specificity False Positive False negative

67% 83% 33% 17%

Negative Positive Sepsis Severe sepsis<0.05ng/ml >0.5ng/ml >2 ng/ml > 5 ng/ml

Gilbert N. D. , Procalcitonin in Respiratory Tract Infections d CID 2011:52 S347

Kidney dysfunction??

Sputum examination

• Collection– Morning before breakfast– Induced or spontaneous– Deep breath– Direct into container

• Adequacy– <10 squamous ep. Cells/lpf– >25 or more PMNL/lpf

• ProcessingWashington Murray grading system

• Stains– Gram stain– Ziehl-Neelsen(AFB**)– Fungal wet mount(KOH)– Giemsa

• Culture (Agar)– Blood – Mac Conkey – Chocolate

Culture methods

Quantitative Semi- Quantitative

In terms of cfu/mlCut offs1. Sputum – 105-106

2. ET aspirate – 105-106

3. Mini Bal – 103-104

4. BAL – 103-104

5. PSB - >103

Types1. 1+ 2+ 3+ 4+ 2. Rare /Light /Mod

/Heavy

Moderate or 3+ areconsidered significant

Ref

Newer tests• Urinary Antigen – Streptococcus(X) and Gp 1 Legionella (Room 2079)– Sensitivity – 75%, Specificity - >95%– Early(<15 min), no effect with antibiotics

• Serological tests(Anaerobe lab)– IgM for Chlamydia and Mycoplasma

• Molecular diagnostics– Sensitive but no resistance pattern and costly(X)

Radiological tests

• Chest X ray – 75% sensitivity– Lateral view

• CT scan – Gold standard– Definite indications – fungal, unclear CXR, COPD

patient, non resolving pneumonia

Radiological classification

• Alveolar pneumonia• Bronchopneumonia• Interstitial pneumonia

Common X-rays

CT(Computed tomography) scan

Lung Ultrasound

• Sensitivity – 60-90%, Specificity – >90%• Advantages– Radiation free, bedside and quick – Pregnant women– Dynamic evaluation

• Appearence– Serrated margins with hepatization– Air bronchogram(dynamic)– Pleural shred sign

Chaves MA et al. , Lung ultrasound for the diagnosis of pneumonia in adults: Respir Res 2014; 15:50

Flexible Bronchoscopy• Endoscopic procedure to visualise

tracheobronchial tree• Various specimens:– Bronchial brush– Bronchial washing– Bronchoalveolar lavage(BAL)– Endobronchial biopsy– Transbronchial(TB) lung biopsy– TB needle aspiration– Endobronchial ultrasound

Other samples

ET aspirate**

•Non invasive•No special equipment required

Mini BAL(mBAL)

•Advantage: Possible bedside, cheaper •Disadv: Blind procedure

PSB•Newer technique•Less chances of contamination

ET- EndotrachealPSB – Protected specimen brush

Clinical syndromes

• Community Acquired pneumonia– Typical and atypical

• Hospital acquired pneumonia• Ventilator acquired pneumonia

• Health care associated pneumonia

Community Acquired Pneumonia

LRTI mortality Tuberculosis Infectious diseases0

50

100

150

200

250

Mortality per year /1,00,000 people

Etiology

Gupta D et al. Guidelines for diagnosis and management of community-and hospital-acquired pneumonia in adults: Joint ICS/NCCP(I) recommendations. Lung India. 2012

Streptoco

ccus(3

-51)

Mycoplas

ma(4-24)

Chlamyd

ia(2-23)

H. Influenzae

(5-21)

Viruses(1

0-36)

Leigi

onella(1-6)

Staphylo

coccu

s(1-2)

0

10

20

30

40

50

6040-71% had a microbiological diagnosis

B. A. Cunha et al. Clin Microbiol Infect 2006; 12 (Suppl. 3): 12–24

Atypical pneumonia

• Walking pneumonia• Difference: – Systemic manifestations**– Minimal sputum – Sub acute progression– Chest X ray pattern – Fever and leukocytosis less common

• Mycoplasma(25%), Chlamydia(12-21%), Legionella, Q fever

Admission decisionCURB 65(BTS)

Confusion

Urea(>20mg/dL)

Respiratory rate >30

Blood pressure <90 systolic ; or < 60 diastolicAge>65 years

Pneumonia Severity IndexGenderDemographyCo morbiditiesPhysical examinationLab and radiographic findingsScored in points I – 0-50II – 51-70 III – 71-90IV – 91-130V – 131-395

Fine MJ et al. N Engl J Med. 1997;336:243-250.Capelastegui A et al.  Eur Respir J. 2006;27:151-157

Each gets one point

BTS – British Thoracic society

Severity AssessmentPneumonia

Severity Index30 day mortality(%)

CURB-65 30 day mortality(%)

Where to manage?

I 0.1 0 0.7 Outpatient

II 0.6 1 2.1 Outpatient

III 0.9 2 9.2 Inpatient(Short observation)

IV 9.3 3 15 Inpatient

V 27 4 40 Inpatient-ICU

Fine MJ et al. N Engl J Med. 1997;336:243-250.Capelastegui A et al.  Eur Respir J. 2006;27:151-157

Physicians decision

IDSA 2007 severity assessment

1 MAJOROR

3 MINOR

ICU/HDU

IDSA/ATS Guidelines for CAP in Adults, Mandell A. L et al CID 2007:44 (Suppl 2)

TreatmentClinical Profile Antibiotic

Outpatient

Previously healthy and no antibiotic in last 90 days

Macrolide(Aithromycin/Clarithromycin/Erythromycin) OR Doxycycline

Comorbidity or antibiotic in 90 days Respiratory Fluoroquinolone(Gemifloxacin/Moxifloxacin/ Levofloacin)Or β-lactam + macrolide

Inpatient

Non ICU Same as above

ICU admission β-lactam + Fluoroquinolone/AzithromycinOr Aztreonam + Fluoroquinolone

ICU with ? Pseudomonas Antipneumococcal, antipseudomonal β-lactam plus Ciprofloxacin/LevofloxacinOr Aminoglycoside + Azithromycin

ATS/IDSA Guidelines 2007

Clinical response of pneumonia

Pneumonia

Tachycardia and hypotension

Fever, tachypnea and arterial oxygenation

Cough and fatigue

Radiological resolution

2 days

3 days

14 days

3-4 weeks

Highly variable1. Co morbidity2. Age3. Severity

Marrie TJ, et al. Resolution of symptoms in CAP on ambulatory basis, J Infect 2004; 49:302

Other considerations

• Role of steroids

• IV to oral shifting

• Duration of antibiotics

1.No role in non severe(2A)2. Role in severe CAP with severe inflammation(CRP>15mg/dL), septic shock or ARDS2. Mortality risk reduction3. Contraindications to be ruled out4. Dose regimen

5-7 days, if MRSA/Leigionella/ pneumococcal sepsis; may require for longer time, but clinical stability and 48-72 hours afebrile

Patient is cinically better

ATS 2007 Guidelines and 2012 Lung India guidelines

Non community acquired

Hospital acquired Ventilator associated

Non - ICU ICU Early Late(>4)

48 48-72

Healthcare associated pneumonia • Hospitalization for more than 48 hours in the last 90 days• residence in a nursing home or extended care facility• home infusion therapy• chronic dialysis within one month• home wound care• a family member with a multi-drug resistant organism.

Controversy

Next guidelines of CAP will likely include it

ATS /IDSA HAP/VAP Guidelines 2005

EtiologyIncidence of VAP is much higher in developing countries

Study at AIIMS, 478 BAL samples tested, 192(40%) showed isolates

Ritu Singhal, Srujana Mohanty. Profile of bacterial isolates from patients with VAP. Indian J Med Res 121, January 2005, pp 63-64Khilnani GC, Jain N. Ventilator-Associated pneumonia. Indian J Crit Care Med 2013;17:331-2.

Organism NumberAcinetobacter 86(44.8%)

Psudomonas 77(40.1%)

Others- E. Coli 8(4.2%) ; Citrobater 4(2.1%) ; Enterobacter – 3(1.6%)

Staph. Aureus 2 (1.1%)

Diagnosis of HAP/VAPRadiology Sign/Symptoms/Lab

2 or more serial X-rays with at least one of the following: 1. New or Progressive and persistent infiltrates2. Consolidation3. Cavitation

At least one :1. Fever2. Leukopenia or leucocytosis3. If age>70; altered mental statusAt least 2 of the following:1. Sputum ( new onset/ change in

character) or increased secretions increased suctioning requirement

2. Worsening gas exchange(desaturation/increased oxygen requirement/ increased ventilatory requirements)

3. New onset dyspnea/cough/tachypnea4. Rales or bronchial breath sounds

2013 CDC definitions for Healthcare associated infections

At least 2/3Persistent infiltrates

+1. Leucocytosis

2. Change in oxygen/ventilatory requirement

3. Secretions

Risk factors for MDR VAP 1. Prior antibiotic use in 90 days

2. Septic shock at time of VAP

3. ARDS preceding VAP

4. >5 days of admission before VAP

6. Dialysis before VAP

Risk factors for MDR HAP/MRSA or MDR Pseudomonas in HAP or VAP

Injectable antibiotic use in last 90 days

Risk of death in HAP1. Ventilatory support2. Septic shock

ATS Guidelines for HAP/VAP Management, 2016

ATS/IDSA Guidelines for HAP/VAP 2016

7

Prevention of VAP

Nancy Munro et al. Ventilator-Associated Pneumonia Bundle, AACN 2014 Vol 25 175-183

Changes in 2016 guidelines

• Removal of HCAP

• Equal efficacy of non invasive sampling(like endotracheal aspirate) and semiquantitative culture

• Systemic colistin used only with inhaled colistin

• Use dual antibiotics(for Pseudomonas) even after culture if patient has septic shock or high risk of death.

Fungal pneumonia• Mortality – 50-90%• Structural lung disease• Risk factors:

• Broad spectrum antibiotics• TPN, Central catheters• Prolonged ICU stay• Renal/hepatic dysfunction• Large BT requirements

• Leading causes –Aspergillus, Mucor, Candida• Endemic fungi(Cryptococcus, Histoplasma etc)

Pneumocystis jiroveci(PJP)

• Immunocompromised • (A-a) gradient• Induced sputum (Variable), BAL(90% yield)• Treatment needs to be started empirically• Treatment – 15-20mg/kg/day of

Cotrimoxazole QID (2tab DS TDS) x 21 days• Steroids-PaO2<70, A-a gradient>35, hypoxia

Aspergillus

ABPA

• Refractory asthma

• Mucus plugs

• NOT A TRUE INFECTION

Aspergilloma

• Patients withprior co morbidities

• Sub acute pneumonia with constitutional symptoms

CNPA

• History of disease suggestive of cavity ?TB

• Asymptomatic or hemoptysis

• Rarely fever

Invasive Aspergillosis

• Immunocompromised patients

• Rapidly progressive pneumonia

ABPA- Allergic bronchopulmonary aspergillosisCNPA- Chronic Necrotizing Pulmonary Aspergillosis

• Specific criteria

• Fleeting opacities, HAM

• Treat with steroids and if reuired Itraconazole

• Chest X ray and CT shows cavity with soft tissue density

• Itraconazole, inhaled KTZ

• Other antifungals

• Tissue and sputum needs to demonstrate Aspergillus (GMS stain)

• Serial Galactomannan monitoring

• CT signs – Halo sign • DOC- Voriconazole

ABPA Aspergilloma CNPA Invasive Aspergillosis

ParasiticFocal

Consolidation

Paragonimus

Cystic

Entamoeba

Coin lesion

Dirofilaria

Diffuse

Transient(Loeffler’s)

Hookworm

Roundworm

Alveolar

Schistosoma

Strongyloides

Tropical Pulmonary

eosinophilia

Mycobacteria

• As community acquired pneumonia 3-16% but even as high as 30%

• Fluoroquinolones – Do not use as earlly resistance(5-10 days)

• Clues – Endemic, co morbidities, pleural effusion, chronicity of symptoms, upper lobe, cavity, norrmal TLC

L.M. Pinto et al. / Respiratory Medicine (2011) 138e140R.F. Grossman et al. / International Journal of Infectious Diseases 18 (2014) 14–21

TAKE HOME MESSAGES

• Investigate in a planned way• Know the interpretation• Lung USG is a must

• “Pneumonia” or “LRTI” is not the complete diagnosis

• Evidence based management and de escalation

• Never forget “TB” and avoid Levofloxacin