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PNEUMONIA

Dr. A.Torossian, M.D., Ph. D.Department of Respiratory Diseases

Definition

l Pneumonia is an inflammation of the lungs caused by bacteria, viruses, fungi, rickettsiae and other microorganisms.

l Sometimes they may also be due to the inhalation of chemicals or trauma to the chest wall.

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Classifications

Based on various characteristics of the illness, such as:

l Anatomic or radiologic distributionLobar pneumonia

Segmental pneumonia

Bronchopneumonia (multifocal or lobular pneumonia)

Interstitial pneumonia

l The pathogen responsiblel The setting or mechanism of acquisition

Setting of Infection

l Community-acquired pneumonia

Community-acquired pneumonia (CAP) is defined as pneumonia that develops in the outpatient setting or within 48 hours of admission to a hospital.

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Hospital-acquired pneumonia(HAP)

Pneumonia that develops at least 48 hours after admission to a hospital and is characterized by increased risk of exposure to multidrug-resistant (MDR) organisms, as well as gram-negative organisms.Risk factors for exposure to such organisms in HAP include the following :

l Antibiotic therapy within 90 days of the hospital-acquired infection

l Current length of hospitalization of 5 days or morel High frequency of antibiotic resistance in the local

community or within the specific hospital unitl Immunosuppressive disease or therapy

l Nursing home patients with pneumonia are less likely to present with classic signs and symptoms of the typical pneumonia presentation, such as fever, chills, chest pain, and productive cough, but instead often have delirium and altered mental status.

l VAP may occur in as many as 10-20% of patients who are on ventilators for more than 48 hours.

Healthcare-associated pneumonia Nursing home-associated pneumoniaVentilator-associated pneumonia

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Aspiration Pneumonia

Caused by the aspiration of oropharyngeal secretions into the lung

Patients with increased risk of aspiration and/or the development of aspiration pneumonia :

l Decreased ability to clear oropharyngeal secretions - Poor cough or gag reflex, impaired swallowing mechanism (eg. dysphagia in stroke patients), impaired ciliary transport (eg. from smoking)

l unconsciousness- seizures, coma, anesthesial Increased volume of secretionsl Increased bacterial burden of secretionsl Presence of other comorbidities - Anatomic abnormalities,

gastroesophageal reflux l Intubation/extubation

l Because the episode of aspiration is usually not witnessed, the diagnosis is inferred when a patient at risk of aspiration develops evidence of a radiographic infiltrate in characteristic anatomic pulmonary locations or bronchopulmonary segments.

l The classic findings are in the right lower lobe.

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Causes: Community Acquired Pneumonia

Bacteria: Typical l Streptococcus Pneumoniael Staphylococcus aureusl Haemophilus Influenzae l Moraxella catarrhalis

Hospital-acquired pneumonia

Typical :Gram-negative bacteria

l Pseudomonas aeruginosal Klebsiella pneumoniael Haemophilus influenzael Escherichia colil Acinetobacter baumannii and others

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Atypical organisms

Atypical organisms are generally associated with a milder form of pneumonia, the so-called "walking pneumonia." A feature that makes these organisms atypical is the inability to detect them on Gram stain or to cultivate them in standard bacteriologic media.

l Mycoplasma pneumoniae: Mycoplasmas are the smallest known free-living organisms in existence; they lack cell walls (and therefore are not apparent after Gram stain) but have protective 3-layered cell membranes.

l Chlamydophila species (Chlamydophila psittaci, Chlamydophila pneumoniae): Psittacosis, also known as “parrot disease” or “parrot fever”, is caused by C psittaci and is associated with the handling of various types of birds.

l Legionella species: Legionella species are gram-negative bacteria found in freshwater; they are known to grow in complex water distribution systems; institutional water contamination is frequently noted in endemic outbreaks. Legionella species are the causative agent of Legionnaires disease.

l Coxiella burnetii: C burnetii is the causative agent of Q fever. It is spread from animals to humans; person-to-person transmission is unusual. Animal reservoirs typically include cats, sheep, and cattle.

Anaerobic organisms

l Pneumonia due to anaerobes typically results from aspiration of oropharyngeal contents. These infections tend to be polymicrobial and may consist of the following anaerobic species: Peptostreptococcus, Bacteroides, Fusobacterium, and Prevotella.

l They are often combined with aerobic species.

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Viruses

Common causes of viral pneumonia are:l Influenza virus A and B l Respiratory syncytial virus (RSV)l Human parainfluenza viruses (in children) Rarer viruses that commonly result in pneumonia include:l Adenoviruses (in military recruits)l Metapneumovirusl Severe acute respiratory syndrome virus (SARS coronavirus)

Viruses that primarily cause other diseases, but sometimes causepneumonia include:

l Herpes simplex virus (HSV), mainly in newborns l Varicella-zoster virus (VZV) l Cytomegalovirus (CMV), mainly in people with immune system problems

Fungal pneumonia

l Endemic fungal pathogens (eg, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis) cause infection in both healthy and immunocompromised hosts in defined geographic locations of the Americas and around the world.

l Opportunistic fungal organisms (eg, Candidaspecies, Aspergillus species, Mucor species, Cryptococcus neoformans) tend to cause pneumonia in patients with congenital or acquired defects in their host defenses.

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Parasitic pneumonia

The most common parasites involved:l Ascariasisl Schistosomal Toxoplasma gondii

l The most common bacterial pathogens that cause CAP include Streptococcus pneumoniae (both penicillin-sensitive and -resistant strains), H influenzae (both ampicillin-sensitive and -resistant strains), and Moraxella catarrhalis (all strains penicillin-resistant).

l These 3 pathogens account for approximately 85% of CAP cases.

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l Staphylococcus aureus, Klebsiella pneumoniae,and Pseudomonas aeruginosa are not causes of CAP in typical hosts.

l S aureus causes CAP in the setting of postviral influenza.

l K pneumoniae CAP occurs primarily in persons with chronic alcoholism.

l Ps. aeruginosa is a cause of CAP in patients with bronchiectasis or cystic fibrosis.

l Other gram-negative pathogens rarely cause CAP.

l Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa are the most common bacterial causes of HAP

l HAP can also be caused by viruses, fungi, anaerobic bacteria and combinations of these

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Ethiology of CAP (European region)

0-10Pneumocystis carinii

2-15Viral agents

5-25Others

30-60Unknown pathogen

0-10Mycobacterium tuberculosis

0-15Legionella pneumophila

5-15Chlamydophila pneumoniae

1-10Mycoplasma pneumoniae

10-30Atypical pathogens

0-5Moraxella catarrhalis

2-10Haemophillus inflienzae

15-25Streptococcus pneumoniae

40-60Typical pathogens

percentage (%)cause

l CAP is usually acquired via inhalation or aspiration of pulmonary pathogenic organisms into a lung segment or lobe.

l Less commonly, CAP results from secondary bacteremia from a distant source, such as Escherichia coli urinary tract infection

l CAP due to aspiration of oropharyngeal contents involves multiple pathogens.

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Anamnesis

l Determining the presence of pneumonial Assessing disease severity at the time of

presentationl Identifying the causative agent

Anamnesis

Symptomsl The presence of cough, particularly cough productive of sputum,

is the most consistent presenting symptom. The character of the sputum may suggest a particular pathogen, for example:Rust-colored sputum - Frequently associated with infection by S. pneumoniaeFoul-smelling or bad-tasting sputum - Often produced by anaerobic infections

l Chest pain, dyspnea, hemoptysis, are also highly indicative of a pulmonary process

l Nonspecific symptoms such as fever, rigors or shaking chills, and malaise are common.

l Other nonspecific symptoms - myalgia, arthralgia, headache-often seen in cases with atypical pneumonia

l sometimes nausea, vomiting, diarrhea, and altered sensorium.

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Anamnesis

Potential exposuresl Exposure to contaminated air-conditioning or

water systems -Legionella speciesl Exposure to overcrowded institutions (eg. jails,

homeless shelters) –S pneumoniae, Mycoplasmal Exposure to various types of animals - cats,

cattle, sheep, goats (C burnetii, B anthracis)turkeys, chickens, ducks, or other birds (C psittaci), etc.

Anamnesis

Patients at increased risk of aspiration are also at increased risk of developing pneumonia secondarily

Aspiration risksl Alcoholisml Altered mental statusl Anatomic abnormalities, congenital or acquiredl Dysphagial GERD (gastro-esophageal reflux disease)l Seizure disorder,unconsciousness

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Additional host factorsl Comorbid conditionsl Previous surgeriesl Possibility of immunosuppressionl Social historyl Family historyl Medication historyl Allergy history

Anamnesis

Risk Factors for severe disease

l Age over 65 years l Recent antibiotics l Immune compromised (e.g. HIV Infection) l Respiratory illness (COPD, Asthma) l Diabetes Mellitusl Chronic Liver Diseasel Chronic Kidney Diseasel Cancer

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Physicalexamination

l Physical examination findings may vary depending on the type of organism, severity of infection, coexisting host factors, and the presence of complications.

Signs:l Hyperthermia (fever, typically >38°C) or hypothermia

(<35°C)l Tachypnea (>18 respirations/min)l Use of accessory respiratory musclesl Tachycardia (>100 bpm) or bradycardia (<60 bpm)l Central cyanosisl Altered mental status

Physicalexamination

l Adventitious breath sounds, such as rales/crackles, rhonchi or wheezes

l Decreased intensity of breath soundsl Whispering pectoriloquyl Dullness to percussion

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HOW TO DIFFERENTIATE BETWEEN PNEUMONIA AND OTHER RESPIRATORY TRACT INFECTIONS?

A patient should be suspected of having pneumonia when the following signs and symptoms are present:

an acute cough and one of the following: l new focal chest signs, l dyspnoea, l tachypnoea, l fever > 4 days.

l If pneumonia is suspected, a chest X-ray should be performed to confirm the diagnosis.

Imaging methods

Chest X-ray

l Radiology is generally helpful in detecting suspected pneumonia and identifying the presence of complications

l only occasionally can imaging suggest specific pathogens

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Computed tomographyCT scanning may identify pulmonary infections earlier than plainradiography. In most cases, it can be helpful in the analysis ofmore complex lung findings and evaluation of other intrathoracicstructures.

UltrasonographyUltrasonography is useful in evaluating suspected parapneumonic effusions, especially if septations are present within the fluid collection that may not be visible on CT scans.Ultrasonography also has great utility for direct operation by physicians at the patient bed

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Labs

The amount of laboratory and microbiological work-up should be determined by the severity of pneumonia

l Complete Blood Countl Sputum Gram stainl Sputum Culturel C-reactive proteinl Consider urine antigen testing for pneumococcus

and Legionella pneumophila

Tests

The following initial tests are indicated in more severe cases:

l Blood culture, prior to antibiotic therapyl Endotracheal aspirate for culture in

intubated patientsl Culture and study of pleural fluid if

effusion is present

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Procedures

l Bronchoscopy with or without bronchoalveolar lavage (BAL): Lung tissue can be visually evaluated and bronchial washing specimens can be obtained with the aid of a fiberoptic bronchoscope. Protected brushings and BAL can be performed for fluid analysis and cultures.

l Thoracocentesis: This is an essential procedure in patients with a parapneumonic pleural effusion. Obtaining fluid from the pleural space for laboratory analysis allows for the differentiation between simple and complicated effusions. The fluid can also be sent for Gram stain and culture.

Treatment

l Almost all major decisions regarding management of pneumonia address the initial assessment of severity.

l Perhaps the most important initial determination is that of the need for hospitalization.

l In determining site or level of care, options include outpatient, medical ward care, or medical ICU care.

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Various systems to assess the severity of disease and risk of death exist and are in wide use, including the PSI/PORT (ie, Pneumonia Severity Index/Patient Outcomes Research Team score), CURB-65 and others

mild moderate severe

Out-patient hospital ICU

Gr.1 Gr. 2 Gr. 3 Gr. 4 Gr. 5

Ramirez, Dis Manage Heart Outcomes 2003; 11 (1) 33-43

Place of treatment

Severity

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CURB-65

CURB-65One point is given for the presence of each of the

following:l Confusion of new onset - Altered mental statusl Uremia - BUN greater than 7 mmol/ll Respiratory rate - Greater than or equal to 30

breaths per minutel Blood pressure - Systolic less than 90 mm Hg or

diastolic less than 60 mm Hgl Age older than 65 years

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009BTS guidelines

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Criteria of acute respiratory failure, severe sepsis or septic shock and radiographic extension of infiltrates should prompt consideration of the admission to the ICU or an intermediate care unit.

The presence of at least two of

l systolic blood pressure < 90 mmHg, l severe respiratory failure (PaO2/FIO2 < 250), l Involvement of > 2 lobes on chest radiograph (multilobar involvement)

or one of l requirement for mechanical ventilation or l requirement of vasopressors > 4 hours (septic shock)

indicates severe CAP and can be used to guide ICU referral.

lWHO SHOULD BE CONSIDERED FOR ICU ADMISSION?

l Differentiation between community-acquired pneumonia (CAP), healthcare-associated pneumonia (HCAP), hospital-acquired pneumonia (HAP), and other pulmonary pathology at presentation is important for several reasons, but primarily because the varying pathogens implicated in each category dictate the empiric therapy likely to be most useful.

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Management

l Determine if hospitalization needed l Be aware of Antibiotic Resistancel Start antibiotic within 4 hours of

hospitalization – Decreases mortality – Decreases length of stay

Review of patients in the community with CAP isrecommended after 48 h or earlier if clinically

indicated.Disease severity assessment should form part ofthe clinical review. Those who fail to improve after 48 h of treatmentshould be considered for hospital admission or

chest radiography.

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Medication

l The goals of pharmacotherapy for bacteria pneumonia are to eradicate the infection, reduce morbidity, and prevent complications.

Treatment of pneumonia depends largely on the empiric use of antibiotic regimens directed against potential pathogens as determined by the setting in which the infection took place and potential for exposure to multidrug-resistant (MDR) organisms and other more virulent pathogens (ie, CAP, healthcare-acquired pneumonia (HCAP), hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP).

Duration of medication

l Usually 7-10 days

l Atypical pathogens-min 14 days

l Clinical improvement is expected during the first 2-3 days

l The patients should be instructed to contact the physician if there is no improvement

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AMOXICILLIN CLAVULANATEMOXIFLOXACINLEVOFLOXACIN

NO RISK ACTORS FOR Ps aeruginosa

BRONCHIECTASIS

ACYLUREIDOPENICILLIN/β-LACTAMASE INHIBITOR + CIPROFLOXACIN orCARBAPENEM + CIPROFLOXACIN

ANTI-PSEUDOMONALCEPHALOSPORIN + CIPROFLOXACIN

SEVERE +RISK FACTORS FOR Ps aeruginosa

CAP

3rd CEPHALOSPORIN + (LEVOFLOXACIN OR MOXIFLOXACIN)

3rd CEPHALOSPORIN + MACROLIDE***

SEVERE CAP

LEVOFLOXACINMOXIFLOXACIN

PENICILLIN G ±MACROLIDE***•AMINOPENICILLIN ±MACROLIDE***•CO-AMOXICLAV ±MACROLIDE***•2nd OR 3rd

CEPHALOSPORIN ±MACROLIDE***

NON-SEVERECAP

CIPROFLOXACIN+ RISK FACTORS FOR Ps aeruginosa

COPD

LEVOFLOXACINMOXIFLOXACIN

CO-AMOXICLAVMODERATE / SEVERECOPD

CO-AMOXICLAVMACROLIDE***LEVOFLOXACINMOXIFLOXACIN

AMOXICILLIN orTETRACYCLINE**

MILDCOPD@HOSPITAL

CO-AMOXICLAVMACROLIDE***LEVOFLOXACINMOXIFLOXACIN

AMOXICILLIN orTETRACYCLINE**

ALLLRTI@COMMUNITY

ALTERNATIVE*PREFERREDSEVERITY/SUB-GROUPLRTI TYPESETTING

Oral therapy with amoxicillin and a macrolide ispreferred for patients with moderate severity CAPwho require hospital admission.Monotherapy with a macrolide may be suitable forpatients who have failed to respond to an adequatecourse of amoxicillin prior to admission.

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When oral therapy is contraindicated, the preferredparenteral choices include intravenous amoxicillin

or benzylpenicillin, together with clarithromycin.

For those intolerant of penicillins or macrolides, oral doxycyline is the main alternative agent.

Oral levofloxacin and oral moxifloxacin are otheralternative choices.

Patients with high severity pneumonia should betreated immediately after diagnosis with parenteralantibiotics. An intravenous combination of a broad-spectrum beta-

lactamase stable antibiotic such as co-amoxiclavtogether with a macrolide such as clarithromycin ispreferred. In patients allergic to penicillin, a second-generation(eg, cefuroxime) or third-generation (eg, cefotaxime orceftriaxone) cephalosporin can be used instead of

coamoxiclav, together with clarithromycin.

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Aspiration pneumonia empiric therapy

l Although the causative organisms in aspiration pneumonia have been noted to be similar to those of CAP or HCAP, patients with severe periodontal disease, putrid sputum, or a history of alcoholism with suspected aspiration pneumonia may be at greater risk of anaerobic infection. One of the following antibiotic regimens is suggested for such patients:

l Piperacillin-tazobactaml Imipeneml Clindamycin or metronidazole plus a respiratory

fluoroquinolone plus ceftriaxone

Additional supportive care measures :

l Analgesia and antipyreticsl Intravenous fluids (and, conversely, diuretics) if

indicatedl Oxygen supplementationl Respiratory therapy, including treatment with

bronchodilators and N –acetylcysteinel Chest physiotherapy, early mobilization

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l Low molecular heparin is indicated in patients with acute respiratory failure.

l Steroids have no place in the treatment of pneumonia unless septic shock is present

l Suctioning and bronchial hygiene

l mechanical ventilation

l Clinical response to antibiotic therapy should be evaluated within 48-72 hours of initiation. With appropriate antibiotic therapy, improvement in the clinical manifestations of pneumonia should be observed in 48-72 hours.

l Because of the time required for antibiotics to act, antibiotics should not be changed within the first 72 hours unless marked clinical deterioration occurs.

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WHEN SHOULD IV BE USED AND WHEN SHOULD THE SWITCH

TO ORAL OCCUR?

l In mild pneumonia, treatment can be applied orally from the beginning.

l In patients with moderate pneumonia, sequential treatment should be considered in all patients except the most severely ill.

l The optimal time to switch to oral treatment is also unknown; it seems reasonable to target this decision according to the resolution of the most prominent clinical features at admission.

l The timing of radiologic resolution of pneumonia varies with patient age and the presence or absence of an underlying lung disease. The chest radiograph usually clears within 4 weeks in patients younger than 50 years without underlying pulmonary disease.

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l If patients do not improve within 72 hours, an organism that is not susceptible or is resistant to the initial empiric antibiotic regimen should be considered. Lack of response may also be secondary to a complication such as empyema or abscess formation.

l Also consider broadening the differential diagnosis to include noninfectious etiologies such as malignancies, congestive heart failure, etc., or other pathogens -M.Tuberculosis

l Diagnostic testing may require more complex studies when the cause of disease is less apparent.

Further Outpatient Care

l When treated in an outpatient setting, arranging adequate follow-up evaluations for the patient is mandatory. Patients also should be instructed to return if their condition deteriorates.

l Patients should have a follow-up chest radiograph to ensure resolution of consolidation.

l Chest radiograph findings indicating nonresolution should raise the consideration of an endobronchial obstruction as a cause of postobstructive pneumonia. A CT scan may be of benefit in these cases.

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Complications

Potential complications include the following:

l Destruction and fibrosis/organization of lung parenchymal Necrotizing pneumonia/Pulmonary abscessl Bronchiectasisl Empyemal Respiratory failurel Acute respiratory distress syndromel Death

Differential diagnosis

l Lung cancerl Other malignancyl Tuberculosisl Fibrosisl Collagenosisl PTl others

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Prognosis

l Generally, the prognosis is good in otherwise healthy patients with uncomplicated pneumonia

l Advanced age, aggressive organisms (eg, Klebsiella, Legionella, resistant S.pneumoniae), comorbidity, respiratory failure, neutropenia, and features of sepsis, alone or in combination, increase morbidity and mortality