Pneumonia

BY

Dr. Mohamed Samy Atta

Professor of Chest diseases Alexandria University

Definition
Inflammation

parenchyma An acute lower respiratory infection associated with recently developed Radiological signs.

of the lung

Classification
Aetiological I- Bacterial : gram +ve, gram ve, anaerobic, Intra cellular, T.B, Nocardia, Actinomyces, Typhoid. II- Viral : RSV CMV Influenza Herpes III- Fungal IV- Protozoal : Pneumocystic Carinii Toxoplasma

Aetiological
V- Rickettsial :Typhus Q Fever VI- Collagen diseases : Rheumatoid SLE - Rheumatic Fever VII- Chemical : Mendelsons syndrome Lipoid Pneumonia

VIII- Radiation Pneumonia

Classification
Radiological

Lobar : Lobar or segmental consolidation

Bronchopneumonia : Bilateral patchy or lobular consolidation

Recurrent Pneumonia
I- Local Bronchial obstruction :

intra luminal e.g. Foreign body intramural e.g Adenoma - Carcinoma stenosis
II- Local Bronchopulmonary disease : Congenital e.g sequestration, Localized Bronchiectasis, Carnified lung from chronic pneumonia

Recurrent Pneumonia
III. Generalized Broncho-pulmonary disease :

Bronchiectasis Cystic Fibrosis COPD Chronic sinusitis with postnasal drip

Recurrent Pneumonia
(IV) Non-respiratory Causes : Recurrent aspiration : Neuromuscular Esophageal Alcoholics Epileptics Gingival disease Immune deficiency states CHF

Classification
I) Community-Acquired Pneumonia (CAP) II) Hospital Acquired Pneumonia (Nosocomial)
i.e Pneumonia occurring 48 hr after admission and excluding any infection incubating at the time of admission VAP HCAP

Community Acquired Pneumonia

CAP

Community Acquired Pneumonia (CAP)

I)

Gram +ve bacteria

Streptococcus Pneumonia 30 40 % St. pyogened, Staph. Aureus

II) Gram ve bacteria

Haemophilus influenzae
11 %

2-

Moraxella catarrhalis 2% Klebsiella Pseudomonas E coli

Community Acquired Pneumonia (CAP)

III) Anaerobic bacteria

IV) Atypical (Intracellular) organisms : Legionella pneumophilia 1-16 % Mycoplasma Pneumoniae 11-17 % Chlamydia Pneumoniae 6-15 %

Typical symptoms and signs of Pneumonia

Symptom

General : malaise fever rigors myalgia Specific : dyspnea chest pain (either central or dull periferal pleuritis) cough sputum production wheezes Signs cyanosis herpes labialis cough sputum production

Symptoms and signs of atypical Pneumonia

Symptoms Headache Confusion Diarrhea Incontinence Signs Cyanosis Tachycardia Tachypnoea Rash (skin, mucous, membrane)
Chest signs are usually widespread but may correlate poorly with the chest X-ray appearance

Complication of Pneumonia
Empyema (2) Lung abscess (3) Septic extrathoracic complications arthritis cellulitis pericarditis endocarditis - meningitis brain abscess (4) Abnormal liver function tests
(1)

Complication of Pneumonia
(5) Haemolytic anaemia (6) Circulatory failure (7) Renal failure (8) Thrombo phlebitis (9) Glomerulonephritis (10) Herpes labialis

Features associated with increased mortality in CAP

( Hospital Admission )

CURB 65

Age 60 years Respiratory rate > 30 /min Diastolic BP < 60 mmHg New AF Confusion

Hospital Admission

High blood urea

WBC < 4000 or > 30000

Serum albumin < 3.5 gm

Low PaO2

Multiple lobes involved in Xray

ICU Admission

Need for mechanical ventilation

Septic Shock

Diagnosis
1- Chest X Ray :
Confirm Diagnosis Rule out complications

2- Gram stain, C. S. of sputum if :

Drug resistant pathogen is suspected Organism not covered by empiric therapy is suspected

Diagnosis
Routine Blood Chemistry CBC ESR ABG Blood Culture Serologic testing Bronchoscopy Urinary antigen for legionella pneumophila and streptococcus pneumoniae

Diagnosis of pneumonia
Examination of respiratory tract specimens

How to get ?

Sputum induction Nasotracheal suction Trans laryngeal aspiration Trans thoracic needle aspiration Fiber optic bronchoscopy :wash, brush, BAL, BX. protect specimen brush, Pro-BAL Open lung biopsy

Diagnosis of pneumonia
Criteria of satisfactory sputum sample
1) 2) 3)

4)

Squamous epithelial cells < 25 / LPF Leukocytes > 25/ LPF Presence of Alveolar macrophages Presence of columnar ciliated bronchial epithelial cells

Diagnosis of pneumonia
Examination of respiratory specimens How to test for ?
1) 2)

3) 4)

Gram and special stains if needed Appropriate culture (quantitative) > 107 bacterial /ml PSB > 103 bacterial /ml BAL > 104 bacterial /ml PCR Specific markers in BAL : Endotoxin elastin fiber poly morphonuclear cell containing bacteria

Diagnosis
Even with intensive diagnostic testing, most investigators can not identify a specific etiology for Community Acquired Pneumonia in up to half or more

CAP Management

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of patients individual circumstances

I. Empirical Therapy II. All patients should be treated for the possibility of Atypical infection

One

large medicine study showed that 30-d CAP mortality was increased when administration of the first dose of antibiotic was delayed > 8h from time of arrival to the hospital

Patient stratification
Place

of therapy - out patient - Inpatient word - ICU Presence of cardiopulmonary disease or comorbidity Presence of modifying factors

However, determination of the initial site of care remains an Art of medicine decision that can not be easily made by any of the existing prediction models.

Modifying factors that increase the risk of infection with specific pathogens

Penicillin resistant and drug-resistant pneumococci

Age > 65 years. -Lactam therapy within past 3 months Alcoholism Immune Suppressive illness (including therapy with corticosteroids) Multiple medical comorbidities Exposure to a child in a day care center

Modifying factors that increase the risk of infection with specific pathogens
Pseudomonas aeruginosa Structural lung disease (bronchiectasis) Corticosteroid therapy ( > 10 mg of prednisolone per day) Broad spectrum antibiotic therapy For > 7 day in the past month Malnutrition

Modifying factors that increase the risk of infection with specific pathogens
Enteric gram ve Residence in a nursing home. Underlying cardiopulmonary disease. Multiple medical comorbidities. Recent antibiotic therapy.

Group I : Outpatients, no cardiopulmonary

disease, no modifying factors

Organisms

Therapy
Advanced generation Macrolide : Azithromycin Or Clarithromycin Or Doxcycline

Streptococcus pneumoniae Mycoplasma pneumoniae Chlamydia Pneumoniae (alone or as mixed infection) Haemophilus influenzae Respiratory viruses Miscellaneous Legionella Spp. Mycobacterium tuberculosis Endemic fungi

Group II: Out patients, cardiopulmonary

disease and/or modifying factors

Organisms
Streptococcus pneumoniae (Including DRSP) Mycoplasma pneumoniae Chlamydia Pneumoniae Mixed infection (bacteria plus Atypical pathogen or virus) Haemophilus influenzae Enteric G -ve Respiratory viruses Miscellaneous Motexella catarrhalis Legionella Spp., Aspiration (anaerobes) Mycobacterium tuberculosis Endemic fungi
Anti

Therapy
pneumococcal fluoro quinolone (used alone moxifloxacin,gemifloxacin or 750 mg levofloxacin) OR

-Lactam + macrolide
(high dose Amoxicillin /clavulante 2gm 2 times daily + azithromycin)

Group III:Inpatient,non ICU

Respiratory fluroqinolone (moxifloxacin,gemifloxacin,or levofloxacin750mg) B lactam (cefotaxime, ceftriaxone, ertapenem) + macrolid

GroupIV:Inpatient ICU

B lactam ( cefotaxime , ceftriaxone,ampicillin-sulbactam ) + Azithromycin or flroqinolone

Group IV: ICU Admitted patients

(B)

risk for Pseudomonas aeruginosa

Organisms Therapy
Selected I.V. Antipseudomonal

Streptococcus pneumoniae

(Including DRSP) Legionella Spp . Haemophilus influenzae Enteric G-ve bacilli Staphylococcus aureus Mycoplasma pneumoniae Risperatory viruses Miscellaneous C. pneumoniae Mycobacterium tuberculosis Endemic fungi

-Lactam (Cefepime, Impenem,

meropenem piperacillin / tazobactam) Plus I.V. Antipseudomonal fluoroquinolone (Ciprofloxacine or 750mg levofloxacin)

Or
Selected I.V. Antipseudomonal

-Lactam (Cefepime, Impenem,

meropenem piperacillin / tazobactam) Plus I.V. Aminoglycosides Plus ethier I.V. Macrolid

Azlthromycin or I.V. Anti pneumococcal quinolone .

 For

community acquired MRSA infection add vancomycin or linezolid.

Once the aetiology of CAP has been identified on the basis of reliable microbiological methods antimicrobial therapy shoud be directed at the pathogen.

Duration of therapy

Minimum 5 days Afebrile for 48 72 Clinically stable : Temp < 37.8 HR < 100 beats/m RR < 24 breath/m sys BP > 90 mmHg O2 sat > 90% Ability to maintain oral intake normal mental status

Switch to oral therapy and discharge

Improvement in Cough and dyspnea A febrile on two occasions 8 h a part Decreasing WBC Functionating GIT Hemodynamically stable Use same drug orally or same drug class

Patients with CAP who have persistent septic shock despite fluid resuscitation should be considered for treatment with drotrecogin alfa activated within 24 h of admission.

Hypotensive, fluid-resucitaed patients with sever CAP should be screened for occult adrenal insufficiency

Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation (NIV) unless they require immediate intubation because of severe hypoxemia (arterial oxygen pressure/ fraction of inspired oxygen [PaO2/FiO2] ratio, <150)and bilateral alveolar infiltrates.

Low-tidal-volume ventilation (6 Cm3/kg of ideal body weight) should be used for patients undergoing ventilation who have diffuse bilateral pneumonia or ARDS.

Non Responding Pneumonia

Absence of or delay in achieving clinical stability ( 3 days )

Patterns and etiologies of types of failure to respond.

1. Failure to improve Early (<72 h of treatment) normal response Delayed Resistant microorganism Uncovered pathogen Inappropriate by sensitivity

Parapneumonic effusion/empyema Nosocomial superinfection Nosocomial pneumonia Extrapulmonary Noninfectious Complicationof pneumonia (e.g , BOOP) Misdiagnosis: PE, CHF, vasculities Drug fever

2. Deterioration or progression Early (<72 of treatment) Severity of illness at presentaion Resistant microorganism Uncovered pathogen Inappropriate by sensitivity Metastatic infection Empyema/ parapneumonic Endocarditis, meningitis, arthritis

Inaccurate diagnosis PE, aspiration, ARDS Vasulitis (e.g., SLE) Delayed Nosocomial superinfection Extrapulmonary Exacerbation of comorbid illness Intercurrent noninfectious disease PE Myocardial infarction Renal faliure

Management of non responding CAP

1- transfer of the patient to a higher level of care. 2- Further diagnostic testing 3- escalation in treatment

Response to therapy
Fever Leucocytosis Crackles X ray

2- 4 days 4 days 7 days weeks

Response to therapy
Early clinical response Switch to oral therapy and discharge 2) Lack of clinical response day 3 (Re-evaluation) 3) Clinical deterioration day 1 or 2 (Re-evaluation)
1)

Failure to respond to therapy in CAP

1) 2) 3) 4) 5) 6)

7)

Is your diagnosis of CAP in error ? Are you failing to treat invasive pathogens ? Is the organism resistant to antibiotic ? Do you need to exclude bronchial obstruction ? Is there empyema or lung abscess ? Is there metastatic infections ? Heart ? Meningitis ? Bone ? Drug fever ?

Hospital Acquired Pneumonia HAP (Nosocomial Pneumonia)

Nosocomial Pneumonia
Definition : Pneumonia occurring 2 days or more after admission and excluding any infection incubating at time of admission. Incidence : 13 18 % of Noso-comial infections 10 25 % of ICU patients Mortality up to 70 %

HCAP
Any patient who : 1- hospitalized in an acute care hospital for two or more days within last 90 days 2- resided in a nursing home or long term care facility 3- received recent IV antibiotic, chemotherapy or wound care within the past 30 days

VAP

Pneumonia that arises more than 48-72 hours after endotracheal intubation

Nosocomial Pneumonia
Pathogens :
1)

G-ve Bacilli

60 %

P. aerugeinosa Klebsiella Proteus - E. coli H. influenzae M. catarrhalis Legionella

2)

G +ve Cocci 20 - 40 %

Staph. aureus S. pneumoniae

Nosocomial Pneumonia
Pathogens : Anaerobic bacteria Mycobacterium tuberculosis Viruses Fungi and protozoa

Pathogenesis

1- Bacterial colonisation of the aerodigestive tract 2- Aspiration of the contaminated secretions into the normally sterile lower repiratory tract

Hospital Acquired pneumonia

Bacteriology Core pathogen : Non pseudomonal G ve enteric organisms H. Influenzae Pneumococcus methicillin sensitive staph. Others (according to risk factor) : Staph. aureus (methicillin resistance)

Pseudomonas

- Anaerobes

Ventilator associated pneumonia

New and persistent X-ray infiltrates + one of the following :1)

2)
3) 4) 5)

Positive culture of pleura, blood or tracheal aspirates X-ray cavitations Histo-pathologic evidence New fever and leukocytosis Incidence 6 30 %

Nosocomial Pneumonia Diagnosis

Alveolar

infiltrates on chest X Ray plus two or more of

1- Hypo / hyperthermia (< 36 or > 38 C) 2- Leucopenia or leukocytosis 3- Purulent tracheal secretions 4PaO2

Nosocomial Pneumonia Diagnosis

Blood

culture (low sensitivity, specificity) Qualitative culture of endotracheal tubes or aspiration material Quantitative culture using invasive methods (PSB BAL Pro BAL)

Controversies in the diagnosis of Nosocomial Pneumonia and VAP

The

role of invasive bronchoscope approach is still not universally accepted due to lack of definitive favorable outcome data.

Controversies in the diagnosis of Nosocomial Pneumonia and VAP

It

takes several days for culture results to be available which may be too late to impact on outcome. With false ve results, there is a risk of holding treatment.

Risk Factors

Recent abdominal surgery Witnessed aspiration D. M. Prolonged ICU stay Coma

Risk Factors

Corticosteroides Head trauma Prior antibiotics Renal failure Structure lung disease

Severe pneumonia
Respiratory Hypoxemia There

rate > 35/min

is need for M. V. Rapid X- ray worsening Shock Oligurea Renal failure

Onset
Early Late

before 5 days on or after 5 days

Risk factors for multidrug-resistant VAP pathogens

1. 2. 3. 4. 5. 6.

7. 8.

Duration of current hospitalization 5days or longer Recent antimicrobial therapy (in the preceding 90 days) Recent hospitalization (For 2 days or more in the preceding 90 days High frequency of antibiotic resistance in the community or in the specific unit Resistance in a nursing home or extent care facility Home infusion therapy Chronic dialysis Home wound care

Hospital Acquired pneumonia

Category I

Early onset No risk factor for MDR pathogens

All disease severity

Hospital Acquired pneumonia

Category I
Recomended antibiotic therapy: ceftriaxone Or Levofloxacin, moxifloxacin or ciprofloxacin (levofloxacin, moxifloxacin, gatifloxacin and gemifloxacin are prefered to ciprofloxacin) Or ampicillin/ sulbactam Or Ertapenem Vancomycin remains an acceptable empiric choise for those with a compatible Gram stain result while awaiting sensitivity testing .

Hospital Acquired pneumonia

Category II
Late onset Or risk for MDR pathogen Any disease severity

Hospital Acquired pneumonia Category II

Antipseudomonal cephalosporin (cefepime or ceftazidime) OR Antipseudomonal carbapenem (imipenem meropenem) OR Beta-lactam/beta-lactamase inhibitor(piperacillintazobactam) Plus Antipseudomonal flouroquinolone(ciprofloxacin or levofloxacin) OR Aminoglycoside(amikacin, gentamycin, tobramycin) Plus Linezolid or vancomycin

Cefipime Ceftazidime Imipenem Meropenem Ertapenem Ampicillin-sulbactam Pipracillin-Tazobactam Gentamycin Tobramycin Amikacin

Recommended dosage of antibiotics used for treatment of HAP every 24h Ceftriaxone 1-2g
1-2g every 8-12h 2g every 8h 1/2g/6h or 1g/8h 1g/8h 1g/24h 3g/6h 4.5 g every 6h 7 mg/kg every 24h 7mg/kg every 24h 20 mg/kg every 24h

Moxifloxacin Ciprofloxacin Levofloxacin Vancomycin 12h Linezolid Azithromycin Minocycline Colistin

400 mg every 24h 400 mg every 8h 750 mg every 24h 15 mg/kg every 600 mg every 12h 500 mg every 24h 100 mg every 12h 2.5-5 mg/kg/d

Assessment of Nonresponders
Wrong organism Drug-resistant pathogen: (bacteria, mycobaceria, virus, fungus Inadequate Antimicrobal Therapy
Wrong Diagnosis Atelectasis pulmonaryEmbolus ARDS Pulmonary Hemorrhage Underlying Disease Neoplasm

Complication Empyema or lung Abcess Clostridium difficile Colitis Occult Infection Drug Fever

Highlights
Although a lower respiratory tract culture should be collected from all patients before starting antibiotics, culture collection sholud not delay the intitiation of therapy in critically ill patients Either semiquantitative or quantitative culture data are appropriate for the management of patients of HAP

Lower respiratory tract cultures can be obtained by bronchoscopy or by other means and can be cultured semiquantitatively or quantitatively. Qantitative cultures increase specifity of the diagnosis of HAP without harmful consequences . Local expertise and experience should influence the choice of specific quantitative technique.

Negative lower respiratory tract cultures in a patient who has not changed antibiotics in the past 72 hours can be used to stop antibiotic therapy Early, appropriate ,broad-spectrum antibiotic therapy should be prescribed in sufficient doses to optimise antimicrobial efficacy

Empiric therapy should include agents from a different antibiotic class than the patient has received recently When treating HAP , combination therapy for a specific pathogen should be used judiciously. Consideration should be given to short-duration (five days) aminoglycoside therapy when used in combination with a B-lactam to treat P.aeruginosa pneumonia

Linezolid is an alternative to vancomycin. Unconfirmed, preliminary data suggest that linzolid may be better than vancomycin for proven VAP caused by methicillin-resistant S.aureus Colistin should be considered in patients with VAP caused by a carbapenemresistant Acinetobacter species

Aerosolized antibiotics may be helpful as ajunctive therapy in patients with VAP caused by some MDR pathogens Based on the patients clinical response and the results of lower respiratory tract cultures, deescalation of antibiotics should be considered

A shorter duration of antibiotic therapy (seven to eight days) is recommended for patients with uncomplicated HAP, VAP ,or HCAP who have received initially appropriate therapy and have had a good clinical response provided they have no evidence of infection with nonfermenting Grem-negative bacilli

As supine position has been identified as a risk factor for VAP , especially during feeding , intubated patients should be kept in a semirecumbent position Neither selective decontaminations of the digestive tract nor prophylactic systematic antibiotics following intubation is recommended for routine use

HAP, VAP or HCAP Suspected

Obtain lower respiratory tract (lRT) sample for culture (quantitative or semiquantitative) &Microscopy

Unless there is both a low clinical suspicion for Pneumonia & Negative microscopy of LRT sample, begin empiric antimicrobial Therapy using algorithm in figure 2 & local microbiologic data

Days 2&3: check cultures &asses clinical response : (temperature, WBC, chest X-ray, oxygenation, purulent sputum, Hemodynamic changes & organ function)

Clinical improvement at 48-72 Hours

NO
Cultures -

YES
Cultures + Cultures Cultures +
De-escalate Antibiotics If possible. Treat selected Patients for 7-8 days & reassess

Adjust antibiotic therapy Search for other pathogens, Search for other pathogens Consider stopping complications other Antibiotics diagnosis or other sites or Complications, other diagnosis Or other sites of infection infection