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PNEUMONIA

PHARMACOTHERAPY
 Definition
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 Pneumonia is an infection of the pulmonary parenchyma

 To the pathologist, pneumonia is an infection of the alveoli, distal airways,
and interstitium of the lung that is manifested by:
 Increased weight of the lungs,

 Replacement of normal lung’s sponginess by consolidation, and

 Alveoli filled with white blood cells, red blood cells and fibrin.
 Definition
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 To the clinician, pneumonia is a constellation of symptoms and signs:

Fever, chills, cough, pleuritic chest pain,
Sputum production,
Increased respiratory rate,
Dullness to percussion, bronchial breathing,
Crackles, wheezes, pleural friction rub
 In combination with at least one opacity on chest radiography.
 Classification
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1. Etiologic
Infections I.e bacteria is the most common/, viruses, fungi
Inhalation of gastric contents
Immunological reactions
Inhalation of other toxic substances
2. Anatomic
 Lobar or segmental: process is confined to the division of the lung
 Bronchopneumonia: small areas of the lung alveoli and lobule around small
terminal bronchi are affected
 Classification
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 Revised Classification System

1. Community-acquired pneumonia (CAP):
 Cases of infectious pneumonia in patients living independently in the community
 Patients who have been hospitalized for other reasons for less than 48 hours
before the development of respiratory symptoms
2. Health care-associated pneumonia (HCAP)
a) Hospital-acquired pneumonia (HAP)
◼ Patients who have been hospitalized for at least 2 days
b) Ventilator-associated pneumonia (VAP)
◼ Patients contracting pneumonia >48 hours after the institution of endotracheal
intubation and mechanical ventilation
 Pathogenesis
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 Routes of Infection
 Gross aspiration: postoperative, seizure, stroke patients

 Microaspiration of oropharyngeal secretions colonized with pathogenic

microorganisms
 Hematogenous spread from a distant infected site
 Direct spread from a contiguous infected site

 Host Factors
 Hypogammaglobulinemia

 Defects in phagocytosis or ciliary function, neutropenia, functional or anatomical

asplenia, or a reduction in CD4+ T lymphocyte counts
 Anatomical defects such as obstructed bronchus, bronchiectasis
 Community-Acquired Pneumonia
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 Epidemiology: With an annual cost of $9.7 billion, CAP affects 4 million

adults per year in the United States.
 Rates of pneumonia are higher for men than for women and for black than
for white persons.
 Risk factors: Independent risk factors for CAP include
 Alcoholism [RR 9],
 Asthma (RR 4.2),
 Immunosuppression (RR 1.9), and
 Age of >70 years (RR 1.5 vs. age of 60 to 69 years).
 Etiology
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 Most cases of pneumonia are caused by a few common respiratory

pathogens, including
 S. pneumoniae, H. influenzae, S. aureus, M. pneumoniae, C. pneumoniae, Moraxella
catarrhalis, Legionella spp., aerobic gram-negative bacteria,
 Influenza viruses, adenoviruses, and respiratory syncytial virus.

 Overall, S. pneumoniae accounts for 50% of all cases of CAP requiring

admission to the hospital
 Microbial Causes of CAP, by Site of Care
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Outpatients Hospitalized Patients

Non-ICU ICU

S. pneumoniae S. pneumoniae S. pneumoniae

M. pneumoniae M. pneumoniae S. aureus
H. influenzae C. pneumoniae Legionella spp.
C. pneumoniae H. influenzae Gram-negative bacilli

Respiratory viruses Legionella spp. H. influenzae

Respiratory viruses
 Clinical Manifestations
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 Signs and symptoms

Abrupt onset of fever, chills, dyspnea, and productive cough
Rust-colored sputum or hemoptysis
Pleuritic chest pain
 Physical examination
Tachypnea and tachycardia
Dullness to percussion
Increased tactile fremitus
Chest wall retractions and grunting respirations
Diminished breath sounds over affected area
Inspiratory crackles during lung expansion
 Investigations
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 Chest radiograph
 Dense lobar or segmental infiltrate
 Etiologic diagnosis
 Gram stain of sputum
 Culture of sputum (≤50%)

 Blood culture (5–14%)

 Antigen tests

 PCR

 Serology

 Bronchoscopy
 Treatment
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 Goals of Therapy
 Eradication of the offending organism through selection of the appropriate
antibiotic
 Complete clinical cure
 General Approach to Treatment
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 Oxygen or, in severe cases, mechanical ventilation and fluid resuscitation

 Administration of bronchodilators (albuterol) when bronchospasm is
present,
 Chest physiotherapy with postural drainage if evidence of retained
secretions
 Adequate hydration (IV if necessary), optimal nutritional support, and
control of fever
 Pharmacologic Therapy
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 Selection of Antimicrobial Agents

Initially involves the empirical use of a relatively broad-spectrum antibiotic that is
effective against probable pathogens
Therapy should be narrowed to cover specific pathogens after the
results of cultures are known.
 Factors to define the potential pathogens:
Patient age,
Previous and current medication history,
Underlying disease(s),
Major organ function, and
Present clinical status.
 Severity-of-illness scoring: CURB-65 Scoring
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Symptom Points
Confusion 1
Urea > 19 mg/dL 1
Respiratory rate ≥ 30 breaths/minute 1
SBP < 90 mm Hg, DBP ≤ 60 mm Hg 1
Age ≥ 65 yr 1
Score Risk of Death at 30 Days (%) Location of Therapy

0 0.7 Treat as outpatient

1 2.1 Treat as outpatient
2 9.2 Outpatient or inpatient
3 14.5 Inpatient (± ICU)
4 40.0 Inpatient (± ICU)
5 57.0 Inpatient (± ICU)
 Empirical Antibiotic Treatment of CAP
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 Outpatients
 Previously 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)] or
◼ Doxycycline (100 mg PO bid)
 Comorbidities or antibiotics in past 3 months:
◼A respiratory fluoroquinolone (moxifloxacin [400 mg PO qd],
gemifloxacin [320 mg PO qd], levofloxacin [750 mg PO qd]) or
◼A β-lactam (high-dose amoxicillin [1 g tid] or amox/clavulanate [2 g
bid] or ceftriaxone [1–2 g IV qd] cefpodoxime [200 mg PO bid] or
 Empirical Antibiotic Treatment of CAP
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 Inpatients, non-ICU
A respiratory fluoroquinolone [moxifloxacin, gemifloxacin, levofloxacin]
OR
 A β-lactam [cefotaxime, ceftriaxone, ampicillin] plus a macrolide
[clarithromycin or azithromycin]
 Inpatients, ICU
A β-lactam [cefotaxime, ceftriaxone, ampicillin-sulbactam]
PLUS
 azithromycin or a fluoroquinolone
 Switch from IV to PO Antibiotics
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 Switching from IV to PO antibiotics can be done safely when:

The white blood cell count is returning toward normal,
There are two normal temperature readings (37.5 0C) 16 hr apart, and
There is improvement in cough and shortness of breath.
 Case study, Pneumonia
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 M.R. is a 33-year-old man presenting to the ED with fevers, chills, and chest
pain. His symptoms have persisted for 3 days, and he has a productive
cough with rusty-colored sputum and dyspnea with exertion. He has had
no recent illnesses and no known sick contacts, but he was recently
released from a 2-year period of incarceration. He has tried ibuprofen to
alleviate his fever and chest pain
 Past medical history is positive for asthma, for which he is prescribed
fluticasone and albuterol, and depression, for which he takes sertraline
 Case study, Pneumonia
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 Vital signs reveal a temperature of 40.1◦C, heart rate of 128 beats/minute,

blood pressure of 130/76 mm Hg, and respiratory rate of 32
breaths/minute with accompanying oxygen saturations of 85% on 5 L of
oxygen by nasal cannula. The remainder of the physical examination is
notable for orientation to person but not place or time and for diffuse
crackles bilaterally, which are most apparent on the right side.
 Laboratory results include: WBC, 15,500 cells/μL; Hematocrit, 29.3%;
Sodium, 133 mmol/L; Potassium, 3.8 mmol/L; BUN, 23 mg/dL; SCr, 0.8
mg/dL; Glucose 148, mg/dL; pH 7.42; PO2, 61 mm Hg; PCO2, 46 mm Hg;
HCO3, 28 mEq/L
 Case study, Pneumonia
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 A test for human immunodeficiency virus is negative. Chest radiograph

reveals a right lower lobe infiltrate.
1. What signs, symptoms, and tests are consistent with CAP in M.R.?
2. Which antimicrobial agent(s) should be chosen for the initial management
of M.R?
3. What is the appropriate length of therapy for M.R.?
4. What are the monitoring parameters for treatment outcome?
 Health Care-Associated Pneumonia (HCAP)
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 Hospital-acquired pneumonia (HAP)

 Patients who have been hospitalized for at least 2 days
 Ventilator-Associated Pneumonia (VAP)
 Patientscontracting pneumonia greater than 48 hours after the institution of
endotracheal intubation and mechanical ventilation
 HCAP
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 Endotracheal intubation increases the risk of pneumonia in several ways.

The tube serves as a direct conduit for bacterial introduction into the
lower respiratory tract,
Prevents effective coughing to clear lower respiratory secretions,
Damages the tracheal epithelium, and
Allows the accumulation of oropharyngeal secretions
 Microbiologic Causes of VAP
Non-MDR Pathogens MDR Pathogens
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Streptococcus pneumoniae Pseudomonas aeruginosa

Other Streptococcus spp. MRSA

Haemophilus influenzae Acinetobacter spp.

MSSA Antibiotic-resistant Enterobacteriaceae

Antibiotic-sensitive Enterobacteriaceae ✓ Enterobacter spp.

✓ Escherichia coli ✓ ESBL-positive strains

✓ Klebsiella pneumoniae ✓ Klebsiella spp.

✓ Proteus spp. ✓ Legionella pneumophila

✓ Enterobacter spp. ✓ Burkholderia cepacia

✓ Serratia marcescens ✓ Aspergillus spp.

 HCAP Treatment
Patients
25 without Risk Factors for MDR Pathogens Patients with Risk Factors for MDR Pathogens

1. A β-lactam:
Ceftriaxone or cefotaxime or
Ceftazidime (2 g IV q8h) or cefepime (2 g IV q8–12h) or
Moxifloxacin, ciprofloxacin, or levofloxacin or
Piperacillin/tazobactam, plus

2. A second agent active against gram-negative bacteria:

Ampicillin/sulbactam (3 g IV q6h) or

Gentamicin (7 mg/kg IV q24h) or

Ertapenem (1 g IV q24h) Ciprofloxacin or levofloxacin plus
3. An agent active against gram-positive bacteria:

Vancomycin (15 mg/kg q12h) or Linezolid (600 mg IV q12h)

 Duration of Antimicrobial Therapy
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 Adult outpatient CAP:

◼ 5-dayduration of therapy: levofloxacin (the 750-mg dose) and azithromycin
◼ 7 to 10 days for other therapies

 Admitted to the hospital: 7 to 10 days

 HCAP, HAP, or VAP: 10 to 21 days.
 PNEUMONIA IN PEDIATRICS
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Etiologies
AGE GROUP PATHOGENS
Neonates GBS, E coli, other Gram-negative bacilli, S pneumoniae, H inflenzae
( <3 wk)
3 wk-3 mo RSV, other respiratory viruses (rhinoviruses, parainflenza virus, inflenza virus,
adenovirus), S. pneumoniae, H. inflenzae;

4 mo-4 yr RSV, other respiratory viruses (rhinoviruses, parainflenza virus, inflenza virus,
adenovirus), S. pneumoniae, H. inflenzae, M. pneumoniae, group A streptococcus

≥5 yr M. pneumoniae, S. pneumoniae, C. pneumoniae, H. inflenzae, inflenza viruses, adenovirus,

Legionella pneumophila
 Pneumonia in Pediatrics
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 Pneumonia is classified as severe or non-severe on the basis of clinical

features,
 The management is based on the classification.
 Severe Pneumonia
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 Diagnosis: Cough or difficulty in breathing, plus at least one of the following:

 Central cyanosis or oxygen saturation < 90% on pulse oximetry
 Severe respiratory distress (e.g. grunting, very severe chest indrawing)
 Signs of pneumonia with a general danger sign:
◼ Inability to breastfeed or drink,
◼ Lethargy or unconscious,
◼ Convulsions.
 Treatment
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 Admit the child to hospital.

 Oxygen therapy
 Antibiotic therapy
 Give intravenous ampicillin (or benzylpenicillin) and gentamicin.
◼ Ampicillin 50 mg/kg IM or IV every 6 h for at least 5 days
◼ Gentamicin 7.5 mg/kg IM or IV once a day for at least 5 days
 If no improvement within 48 h and staphylococcal pneumonia is suspected, switch to
gentamicin 7.5 mg/kg IM or IV once a day and cloxacillin 50 mg/kg IM or IV every 6 h
 Use ceftriaxone (80 mg/kg IM or IV once daily) in cases of failure of first line treatment.
 Supportive Care
 If the child has fever (≥ 39 °C), give paracetamol.
 If wheeze is present, give a rapid-acting bronchodilator, and start
steroids when appropriate.
 Pneumonia
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Diagnosis
 Cough or difficult breathing plus at least one of the following signs:

 Fast breathing:
◼ age 2–11 months, ≥ 50/min
◼ age 1–5 years, ≥ 40/min

 Lower chest wall indrawing

 Crackles or pleural rub
 Pneumonia
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Treatment
 Treat child as outpatient.

 Advise parents to give normal fluid requirements plus extra breast milk or

fluids if there is a fever.

 Antibiotic therapy

 Oral amoxicillin 40 mg/kg per dose twice a day for 5 days

 No pneumonia: cough or cold
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 No signs of pneumonia or severe pneumonia

 Home care
 Soothe the throat and relieve cough with safe remedy.
 OUTCOME EVALUATION
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 Improvement of symptoms (within 24 to 72 hours)

 resolution of cough, sputum production, and presence of constitutional
symptoms (malaise, nausea or vomiting,
and lethargy)
 Assess WBC, chest radiograph, and blood gas determinations