A Discussion On The Killer Infectious Disease Of Lungs:

PneumoniaPresented By:

Dr. Pravin Prasad Dr. Rabin Babu PaudyalInterns, Medicine Unit III

PNEUMONIA: INTRODUCTION• Pneumonia is an infection of the pulmonary parenchyma.

(Harrison- 18th Ed)• Pneumonia is defined as an acute respiratory illness

associated with recently developed radiological pulmonary shadowing which may be segmental, lobar or multilobar. (Davidson- 21st Ed)

• Pneumonia was typically classified as community-acquired (CAP), hospital-acquired (HAP), or ventilator-associated (VAP).

• Over the past two decades, however, some persons presenting as outpatients with onset of pneumonia have been found to be infected with the multidrug-resistant (MDR) pathogens previously associated with HAP: - thus development of the term Health Care–associated Pneumonia (HCAP).

Pneumonia: Classification I

A. Classification By Site

Lobar Pneumonia

Bronchopneumonia

Interstitial Pneumonia

Pneumonia: Classification IIB. Classification By Aetiology

• Primary Pneumonia• Secondary Pneumonia (including Aspiration

Pneumonia)• Suppurative Pneumonia (necrotizing pneumonia)

Common Organisms Less Common OrganismsStreptococcous pneumoniae Klebsiella pneumoniae

Haemophilus influenza Streptococcus pneumonia

Moraxella catarrhalis Pseudomonas aeruginosa

Staphylococcus aureus Coxiella burnetii

Legionella pneumophilia Chlamydia pneumoniae

Mycoplasma pneumoniae Chlamydia psittaci

Actinomyces israeli Viruses (including SARS)Table 1: Organisms responsible for primary pneumonia

Pneumonia: Classification III

C. Classification by mode of acquiring pneumonia• Community-acquired Pneumonia• Hospital acquired pneumonia, or Ventilator associated

pneumonia)• Health Care Associated Pneumonia• Pneumonia in immuno-compromised host

Pneumonia: Pathophysiology• Pneumonia results from the proliferation of

microbial pathogens at the alveolar level and the host's response to those pathogens.

• Microorganisms gain access to the lower respiratory tract in several ways.• Aspiration from the oropharynx; (most

common)• Inhalation of contaminated droplets; • Hematogenous spread• Contiguous extension.

Pneumonia: Pathophysiology (contd.)• Defense Mechanisms against Pneumonia

• Hairs and turbinates of the nares • Branching architecture of the

tracheobronchial tree• Muco-ciliary clearance and local

antibacterial factors• Gag reflex and the cough mechanism • the normal flora adhering to mucosal

cells of the oropharynx• Alveolar Macrophages, local proteins

(e.g., surfactant proteins A and D)

Pneumonia: Pathophysiology (contd.)• Only when the capacity of the alveolar macrophages to

ingest or kill the microorganisms is exceeded does clinical pneumonia become manifest.

• The alveolar macrophages initiate the inflammatory response to bolster lower respiratory tract defenses.

Mediators Responsible Effects

IL-1 and TNF Fever

IL – 8 , GCSF stimulates release & attraction of neutrophils to the lungs

Causes peripheral leucocytosis, increased purulent secretions

Inflammatory mediators (macrophages) & neutrophils

Localised alveolar capillary leak

Table 2: Mediators responsible in patho-physiology of Pneumonia

Pneumonia: Pathophysiology (contd.)

Mechanism Clinical Features

Leaky alveolar capillaries

Hemoptysis

Radiologic infiltrates

Rales on auscultation

Alveolar filling and action of bacterial pathogens

Hypoxemia

Decreased compliance of lungs Dyspnoea

Reduction in lung volume and complianceIntra-pulmonary shunting of blood

Death

Stages/Phases of Pneumonia Characteristic FeaturesOedematous Phase Alveoli filled with proteinaceous

exudate and bacteria Rapidly followed by Red hepatization

phaseStage of Red hepatization Presence of erythrocytes in the cellular

intraalveolar exudate Neutrophil influx Bacteria can be seen in specimens

Stage of Gray hepatization(successful containment of the infection & improvement in gas exchange)

Erythrocytes extravasation ceases, extravasated ones get lysed and degraded

Neutrophils predominant Abundant fibrin deposition Disappearance of bacteria

Stage of Resolution Macrophages reappear Debris (PMN, Bacteria, fibrin) cleared Inflammatory response cleared

Pneumonia: Pathology

Table 3: Different Pathologic Phases of Pneumonia*Has been described best for lobar pneumococcal pneumonia.

CAP & HAP: A ComparisonCommunity Acquired Hospital Acquired

Definition It indicates pneumonia occuring in a person in a community (outside hospital)

Refers to a new episode of pneumonia occurring at least 2 days after admission to hospital.

Predisposing Factors

Cigarette smokingUpper respiratory tract infectionsAlcoholCorticosteroid therapyOld ageRecent influenza infectionIndoor air pollution

Reduced host defences against bacteriaAspiration of nasopharyngeal/gastric secretionsBacteria introduced into lower respiratory tractBacteraemia

Mode of Spread

Droplet Infection

Infecting Agent

S. Pneumoniae, S. aureus, H. influenzaViruses (influenza, parainfluenza, measles, Herpes simplex, Varicella, CMV)

Early-Onset: similar to CAPLate-Onset: Escherichia, Pseudomonas, Klebsiella, MRSA, anaerobes

CAP & HAP: Presentation(contd.)Community Acquired Hospital Acquired

Can vary from indolent to fulminating presentation

Pulmonary Symptoms : breathlessness, cough,-non-productive or productive (mucoid, purulent , blood stained) haemoptysis, plueritic chest pain, may able to speak sentences/ short of breath

Systemic Features : fever a/w chills n rigors, tachycardia, vomiting, decreased appetite, headache, fatigue, myalgias, arthralgia

Elderly: New-onset/ progressive confusion Severely ill: septic shock or organ-failure Tachypnoea, use of accessory muscles,

increased/decreased vocal fremitus, Percussion note: dull to flat Bronchial Breathing, Crackles Whispering pectoriloquy, pleural friction rub

Universally agreed diagnostic criteria lacking

Should be considered in any hospitalised /ventilated patient who develops: purulent sputum (or

endotracheal secretions), new radiological infiltrates, an otherwise unexplained

increase in oxygen requirement,

a core temperature > 38.3°C, and

leucocytosis or leucopenia.

CAP & HAP: InvestigationCommunity Acquired Hospital Acquired

Chest Radiology: to confirm the diagnosis and to exclude complications

Pulse oximetry to monitor response to oxygen therapy, if SaO2 < 93%, features of severe pneumonia, identify ventilatory failure or acidosis

Cell count: neutrophil leucocytosisMicrobiologic Studies: for severe CAP

and for those that do not respond to initial therapy (Gram stain, sputum culture, blood culture, Polymerase Chain Reaction, Serology, Antigen Detection)

Renal Function Tests: Urea & electrolytes

Liver Function TestsElevated C-Reactive Protein

Circulating biomarkers may assist with the diagnosis but are currently non-specific.

Appropriate investigations are similar to CAP, microbiological confirmation preferrable.

In mechanically ventilated patients, bronchoscopy-directed protected brush specimens or bronchoalveolar lavage (BAL) may be performed.

Endotracheal aspirates are easy to obtain but less reliable.

Chest Radiology In Pneumonia

Left Lobar Pneumonia with pleural effusion

Right Middle LobarPneumonia

Right Upper LobarPneumonia

Right Upper Lobe Pneumonia with air bronchograms

Hospital Care Associated Pneumonia

• HCAP represents a transition between classic CAP and typical HAP• Refers to the development of pneumonia in a person who has spent at least

2 days in hospital within the last 90 days, attended a haemodialysis unit, received intravenous antibiotics, or been resident in a nursing home or other long-term care facility. (Davidson-21st Ed.)

• MRSA in particular is more common in HCAP than in traditional HAP/VAP.• Patients at greatest risk for HCAP are not well defined.

• Patients from nursing homes are not always at elevated risk for infection with MDR pathogens.

• Low risk of MDR infection if they have not recently received antibiotics and are independent in most activities of daily living.

• Patients receiving home infusion therapy or undergoing chronic dialysis are probably at particular risk for MRSA pneumonia

• In general, management of HCAP due to MDR pathogens is similar to that of MDR HAP/VAP.

Pneumonia: Severity Assessment• There are currently two sets of criteria:

• Pneumonia Severity Index (PSI), a prognostic model used to identify patients at low risk of dying; and

• CURB-65 criteria, a severity-of-illness score.Assessment for need for ICU care provided by severity criteria proposed by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS)

≥≥

≤ ≤≥

CAP TREATMENT: GENERAL CONSIDERATION

• Adequate hydration, oxygen therapy for hypoxemia, and assisted ventilation

• Patients with severe CAP who remain hypotensive despite fluid resuscitation may have adrenal insufficiency and may respond to glucocorticoid treatment.

• Immunomodulatory therapy in the form of drotrecogin alfa (activated) should be considered for CAP patients with persistent septic shock and APACHE II scores of 25, particularly if the infection is caused by S. pneumoniae.

• Once the etiologic agent(s) and susceptibilities are known, therapy may be altered to target the specific pathogen(s).

• Switch to oral treatment is appropriate as long as the patient can ingest and absorb the drugs, is hemodynamically stable, and is showing clinical improvement.

• The duration of treatment for CAP has generated considerable interest

CAP: Empirical Treatment for Out-Patients

Modality RegimenPreviously healthy and no antibiotics in past 3 months:

A macrolide [clarithromycin (500 mg PO bid) or azithromycin (500 mg PO once, then 250 mg qd)] orDoxycycline (100 mg PO bid)

Comorbidities or antibiotics in past 3 months: select an alternative from a different class

A respiratory fluoroquinolone [moxifloxacin (400 mg PO qd), gemifloxacin (320 mg PO qd), levofloxacin (750 mg PO qd)] or A β-lactam [preferred: high-dose amoxicillin (1 g tid) or amoxicillin/clavulanate (2 g bid); alternatives: ceftriaxone (1–2 g IV qd), cefpodoxime (200 mg PO bid), cefuroxime (500 mg PO bid)] plus a macrolide

In regions with a high rate of "high-level" pneumococcal macrolide resistance,

consider alternatives listed above for patients with comorbidities.

CAP: Empirical Treatment for In-Patients

Modality Regimen

Non ICU Patients A respiratory fluoroquinolone [moxifloxacin (400 mg PO or IV qd), gemifloxacin (320 mg PO qd), levofloxacin (750 mg PO or IV qd)]

A β-lactam [cefotaxime (1–2 g IV q8h), ceftriaxone (1–2 g IV qd), ampicillin (1–2 g IV q4–6h), ertapenem (1 g IV qd in selected patients)] plus a macrolide [oral clarithromycin or azithromycin or IV azithromycin (1 g once, then 500 mg qd)]

ICU Patients A β-lactam [cefotaxime (1–2 g IV q8h), ceftriaxone (2 g IV qd), ampicillin-sulbactam (2 g IV q8h)] plus 

Azithromycin or a fluoroquinolone

CAP: Empirical Treatment Special Concerns

Organism being considered

Treatment Regimen

Pseudomonas An antipneumococcal, antipseudomonal β-lactam [piperacillin/tazobactam (4.5 g IV q6h), cefepime (1–2 g IV q12h), imipenem (500 mg IV q6h), meropenem (1 g IV q8h)] plus either ciprofloxacin (400 mg IV q12h) or levofloxacin (750 mg IV qd)

The above β-lactams plus an aminoglycoside [amikacin (15 mg/kg qd) or tobramycin (1.7 mg/kg qd) and azithromycin]

The above β–lactams plus an aminoglycoside plus an antipneumococcal fluoroquinolone

CA-MRSA Add linezolid (600 mg IV q12h) or vancomycin (1 g IV q12h).

CAP TREATMENT: FAILURE TO RESPOND

• Patients who are slow to respond to therapy should be reevaluated at about day 3 (sooner if their condition is worsening rather than simply not improving)

• Check the drug, dose of the correct drug• Pathogen resistant to the drug selected, or a sequestered

focus (e.g., a lung abscess or empyema). • Consider possibility of an unsuspected pathogen (e.g., CA-

MRSA, M. tuberculosis, or a fungus).• Re-consider your Diagnosis: tuberculosis, pulmonary edema,

pulmonary embolism, lung carcinoma, radiation and hypersensitivity pneumonitis, and connective tissue disease involving the lungs.

• Nosocomial superinfections—both pulmonary and extrapulmonary

HAP: Emperical Treatment

Categories Treatment Patients without Risk Factors for MDR Pathogens 

Ceftriaxone (2 g IV q24h) or  Moxifloxacin (400 mg IV q24h), ciprofloxacin (400 mg IV

q8h), or levofloxacin (750 mg IV q24h) or  Ampicillin/sulbactam (3 g IV q6h) or Ertapenem (1 g IV q24h)

Patients with Risk Factors for MDR Pathogens 

 1. A β-lactam:Ceftazidime (2 g IV q8h) or cefepime (2 g IV q8–12h) orPiperacillin/tazobactam (4.5 g IV q6h), imipenem (500 mg

IV q6h or 1 g IV q8h), or meropenem (1 g IV q8h) plus2. A second agent active against gram-negative bacterial pathogens:

Gentamicin or tobramycin (7 mg/kg IV q24h) or amikacin (20 mg/kg IV q24h) or

Ciprofloxacin (400 mg IV q8h) or levofloxacin (750 mg IV q24h) plus

3. An agent active against gram-positive bacterial pathogens:Linezolid (600 mg IV q12h) orVancomycin (15 mg/kg, up to 1 g IV, q12h)

PNEUMONIA: COMPLICATIONS• Para-pneumonic effusion• Empyema• Retention of sputum causing lobar collapse• Pulmonary embolism and DVT• Pneumothorax (S. aureus)• Suppurative pneumonia/ lung abscess• ARDS, renal failure, multi-organ failure• Ectopic abscess formation (S. aureus), Metastatic infection• Pericarditis, hepatitits, myocarditis, meningoencephalitis• Pyrexia due to drug hypersensitivity• Exacerbation of comorbid illnesses.• Complicated pleural effusion: diagnostic/therapeutic tapping required• If the fluid has a pH of <7, a glucose level of <2.2 mmol/L, and a lactate

dehydrogenase concentration of >1000 U/L or if bacteria are seen or cultured, then the fluid should be drained; a chest tube is usually required.

PNEUMONIA: FOLLOW UP• Fever and leukocytosis usually resolve within 2–4 days in

otherwise healthy patients with CAP, but physical findings may persist longer.

• Chest radiographic abnormalities are slowest to resolve and may require 4–12 weeks to clear

• Patients may be discharged from the hospital once their clinical conditions are stable, with no active medical problems requiring hospital care.

• For a patient whose condition is improving and who (if hospitalized) has been discharged, a follow-up radiograph can be done ~4–6 weeks later.

• If relapse or recurrence is documented, particularly in the same lung segment, the possibility of an underlying neoplasm must be considered.

PNEUMONIA: PROGNOSIS• Depends on

• Patient's age, • Comorbidities, and • Site of treatment (inpatient or outpatient).

• Young patients without comorbidity do well and usually recover fully after ~2 weeks.

• Older patients and those with comorbid conditions can take several weeks longer to recover fully.

• Overall mortality rate for the outpatient group is <1%. • Overall mortality rate for Inpatient group is estimated at 10%,

with ~50% of deaths directly attributable to pneumonia.

PNEUMONIA: PREVENTION• The main preventive measure is vaccination. • In the event of an influenza outbreak, unprotected patients at

risk from complications should be vaccinated immediately and given chemoprophylaxis with either oseltamivir or zanamivir for 2 weeks—i.e., until vaccine-induced antibody levels are sufficiently high.

• Because of an increased risk of pneumococcal infection, even among patients without obstructive lung disease, smokers should be strongly encouraged to stop smoking.

• 7-valent pneumococcal conjugate vaccine: produces T cell–dependent antigens that result in long-term immunologic memory.

From our Department….

• Sama Prasad, 55 years Male, non smoker, non alcohol consumer, resident of Bara, working as labour in cement factory for 15 yrs, married, Hindu, came to ED 6 days back with:• Cough-productive, scanty, yellowish for 3 days• Fever- a/w chills & rigors, not documented for 2 days• Loss of appetite for 2 days

• No significant past medical, surgical, personal, family history

From our Department….• General Examination:

• Ill looking, conscious, oriented to time, place & person• No signs of pallor, icterus, cyanosis, clubbing, koilonychiya,

lymphadenopathy, edema, dehydration• Febrile (100oF), tachypnoeic (30 breaths/min), pulse 100 b/miin,

BP 110/60 mm of Hg• Chest Examination:

• Inspection- B/L symmetrical & elliptical, use of accessory muscle present

• Palpation- no mediastinal shift, increased vocal fremitus over right infra-mammary region, reduced chest expansion on right side

• Percussion- dull note over same area• Auscultation- decreased air entry & coarse crepitations over

same area, wheeze over right subscapular area as well• Other Systems Examination: No Significant Findings

From our Department….

• Provisional Diagnosis: Right Middle Zone Pneumonia• Investigations requested:

• Hb% - 10.25%• TLC – 24,700, neutrophilic predominance• RBC & Platelet count – Within normal limit• Chest X-ray, Postero-Anterior View

CURB-65 Score: 2/5; Hospital Supervised Treatment (Short stay Inpatient )

From our Department….• Pt. treated on Non-ICU Inpatient basis.• Coverage for Pseudomonas & CA-MRSA considered• Emperical Treatment Started with:

• Tab. Levoflox 500 mg PO OD• Inj. Durataz (Tazobactam & Piperacillin) 4.5gm IV TDS

(Pseudomonas coverage)• Tab. Linez (Linezolid) 600 mg PO BD (CA-MRSA coverage)

• Supportive Treatment:• Tab. Nacfil 600 mg PO BD• Syp. Bronchosolvin 10 PO TDS• Tab. Pantium 40mg PO OD• O2 inhalation if SpO2 < 90%• Nebulization with I:NS 6 hourly

REFERENCES• Douglas, G; Nicol, F; Robertson, C; Macleod’s Clinical

Examination, 12th Ed. 2009

• Davidson’s Principles and Practice of Medicine, 21st Ed. 2010

• Mathew, K. G. Aggarwal, P. Medicine Prep Manual for Undergraduates, 3rd Ed. 2010

• Harrison’s Principle of Internal Medicine- 18th Ed. 2012• http://laboratorysciencereview.tumblr.com/post/61505647877

• http://emedicine.medscape.com/article/360090-overview#a19

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