All the following are used in the treatment of
Pneumocystis carinii except: (AIIMS Nov 2009)
Pneumocystis pneumonia (PCP)
Pneumocystis is an opportunistic fungal pulmonary organisms are commonly found in the lungs of healthy individuals. Most children are believed to have been exposed to the organism by age 3 or 4 years, and its occurrence is worldwide
Development of PCP
Disease occurs when both cellular immunity and humoral immunity are defective. Once inhaled, the trophic form of Pneumocystis organisms attach to the alveoli. Multiple host immune defects allow for uncontrolled replication of Pneumocystis organisms and development of illness. Activated alveolar macrophages without CD4+ cells are unable to eradicate Pneumocystis organisms.
1). It causes pneumonia in the immunosuppressed Q (HIV) as well as in COPD cases (Harrison, 18th edition, Page 1671).
2). The organism responsible was previously called pneumocystis carinii Q, and now called pneumocystis jiroveci
3). It presents with a dry cough, exertional dyspnoea & fever.
4). CXR may be normal or show bilateral perihilar interstitial shadowing.
5). Persons at risk for Pneumocystic disease (Pneumocystosis)
b. Patients Receiving immunosuppressive therapy.
c. Children with primary immunodeficiency diseases
d. Premature malnourished infants (immunodeficient)
Clinical features of pneumocystis Carinii pneumonia
1). 2-3 week history
2). Fever with dry cough
3). Disproportionate breathlessness
4). No response to standard antibiotics
5). Few signs on auscultation
6). Exercise – related desaturation
Pneumocystic Pneumonia: Diagnosis
Diagnosis of Pneumocystic Pneumonia is based on specific identification of organism in respiratory specimen with appropriate histological staining
1). Usually diagnosed by sputum examination
2). Sputum samples should always be obtained by induction (with hypertonic saline)
3). Routine sputum specimen is often inadequate
4). BAL forms the mainstay of diagnosis for Pneumocystic Pneumonia
Extra Edge: Sputum Induction
1). If P carinii pneumonia (PCP) is strongly suspected, obtain a sputum sample by sputum induction for histopathologic testing.
2). Pneumocystis organisms are frequently found in sputum induced by inhalation of a hypertonic saline solution. Sputum induction is the quickest and least-invasive method for definitively diagnosing PCP.
3). Expectorated sputum has a very low sensitivity and should not be submitted for diagnosis.
Extra Edge: Bronchoalveolar lavage (BAL)
1). BAL is the most common invasive procedure used to diagnose P carinii pneumonia (PCP). It has a diagnostic yield that exceeds 90% (and may be higher if multiple lobes are sampled).
2). Obtain BAL if PCP is strongly suspected and the induced sputum sample findings are negative
Pathogenesis and Pathology (Ref. Hari 18t ed., page 1671)
1). Pneumocystis commonly colonizes patients who are immunosuppressed or who have chronic obstructive pulmonary disease.
2). The host factors that predispose to the development of PcP include defects in cellular and humoral immunity. The risk of PcP among HIV-infected patients rises markedly when circulating CD4+ T cell counts fall below 200/µL.
3). The principal host effector cells against Pneumocystis are alveolar macrophages, which ingest and kill the organism, releasing a variety of inflammatory mediators. Proliferating organisms remain extracellular within the alveolus, attaching tightly to type I cells. Alveolar damage results in increased alveolar-capillary permeability and surfactant abnormalities, including a fall in phospholipids and an increase in surfactant proteins A and D.
4). The alveoli are filled with a typical foamy, vacuolated exudate. Severe disease may include interstitial edema, fibrosis, and hyaline membrane formation. The host inflammatory changes usually consist of hypertrophy of alveolar type II cells, a typical reparative response, and a mild mononuclear cell interstitial infiltrate.
5). Malnourished infants display an intense plasma cell infiltrate that gave the disease its early name: interstitial plasma cell pneumonia.
Differences between PCP infection in adult & infant
Pneumocystic pneumonia in Adults
Pneumocystis pneumonia in malnourished infants
In adults the disease appears to be predominantly alveolar
Air spaces (alveoli) are filled with a foamy, eosinophilic exudate and appear honey coombed The intra-alveolar exudate consists of organisms, surface glycoprotein exudate and debri of macrophages and inflammatory cells.
In infants the disease has a predominant interstitial component
The interstitium is filled with fluid plasma cells and lymphocytes.
These formed elements seem to overflow into air spaces which are filled with a frothy eosinophilic exudates.
Drugs used for treatment of pneumocystic carinii infection include:
First choice drug
Mild to moderate pneumonia
Trimethoprim – Dapsone
Clindamycin – Primaquine
Clindamycin – Primaquine
Indications for prophylaxis against Pneumocystic carinii
1). An absolute CD4 count <200/μL (CD4 percentage <20%) (Primary prophylaxis)
2). Oropharyngeal candidiasis (Primary prophylaxis)
3). Prior Pneumocystic carinii pneumonia (Secondary prophylaxis)
Extra Edge: Criteria for discontinue – CD4 count >200 for ≥ 3 months.
Chemoprophylaxis in patients with HIV Infection
Chemoprophylaxis is recommended for the following groups:
1). Adults, adolescents, and pregnant patients with a CD4 count < 200/µL,oropharyngeal candidiasis, unexplained fever exceeding 100°F (37.7° C) for more than 2 weeks, and a prior episode of PCP regardless of CD4 count should receive prophylaxis.
2). Children born to mothers with HIV infection should receive prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) beginning at age 4-6 weeks.
3). Children who are determined to be HIV positive through the first year of life, then as determined by age-specific CD4 levels, should receive prophylaxis.
4). Prophylaxis may be discontinued in patients with HIV infection whose CD4 count > 200/µL for 3 consecutive months while on highly active antiretroviral therapy (HAART). Prophylaxis should be restarted if the CD4 count drops below 200/µL. Prophylaxis should be continued for life in patients who developed PCP while their CD4 level exceeded 200/µL.
1). TMP-SMX is the agent of choice for PCP prophylaxis.
2). Dapsone is given with pyrimethamine
Extra Edge: Avian influenza
Avian-to-human transmission the H5N1 strain of influenza A causes serious infection in humans with a 50% mortality.
Treatment: OseltamivirQ (Tamiflu).