Wednesday, November 18, 2009
Monday, November 9, 2009
CLINDAMYCIN IN RESPIRATORY DISEASE
Clindamycin is a lincosamide antibiotic.
I found this drug really good perticularly in respiratory tract diseases.
Indications
Used primarily to treat infections caused by
· Susceptible anaerobic bacteria, including infections of the respiratory tract, skin and soft tissue infections, and peritonitis.
· In patients with hypersensitivity to penicillins, clindamycin may be used to treat infections caused by susceptible aerobic bacteria as well.
· It is also used to treat bone and joint infections, particularly those caused by Staphylococcus aureus.
· Topical application of clindamycin phosphate can be used to treat mild to moderate acne.[5]
Roale in Respiratory infections
Susceptible bacteria
It is most effective against infections involving the following types of organisms:
Aerobic Gram-positive cocci, including some members of the Staphylococcus and Streptococcus (e.g. pneumococcus) genera, but not enterococci.
Anaerobic, Gram-negative rod-shaped bacteria, including some Bacteroides, Fusobacterium, and Prevotella, although resistance is increasing in Bacteroides fragilis.
These are the common bactrias in aAc. Exacerbation of COPD,Community Acquired pneumonia, and Upper respiratory tract infection.
But one has to remember that most aerobic Gram-negative bacteria (such as Pseudomonas, Legionella, Haemophilus influenzae and Moraxella) are resistant to clindamycin, as are the facultative anaerobic Enterobacteriaceae.
Other
1.It can also be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA); many strains of MRSA are still susceptible to clindamycin.
Clindamycin is used in cases of suspected toxic shock syndrome, often in combination with a bactericidal agent such as vancomycin. The rationale for this approach is a presumed synergy between vancomycin, which causes the death of the bacteria by breakdown of the cell membrane, and clindamycin, which is a powerful inhibitor of toxin synthesis. Both in vitro and in vivo studies have shown that clindamycin reduces the production of exotoxins by staphylococci; it may also induce changes in the surface structure of bacteria that make them more sensitive to immune system attack (opsonization and phagocytosis)
Clindamycin has been proven to decrease the risk of premature births in women diagnosed with bacterial vaginosis during early pregnancy to about a third of the risk of untreated women.
Parasitic
Plasmodium falciparum malaria
Clindamycin is effective and well-tolerated in treating Plasmodium falciparum malaria. It is to be used along with Chloroquinine or quinine for this perpouse.Quinine plus clindamycin combination is particularly useful for children, and is the treatment of choice for pregnant women who become infected in areas where resistance to chloroquine is common.
Clindamycin should not be used as an antimalarial by itself, although it appears to be very effective as such, because of its slow action.
Other Parasitic infection
The combination of clindamycin and quinine is the standard treatment for severe babesiosis
Clindamycin may also be used to treat toxoplasmosis, in combination with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.
Adverse effects
Common adverse drug reactions (ADRs) associated with clindamycin therapy—found in over 1% of patients—
Diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal pain or cramps, rash, and/or itch. High doses (both intravenous and oral) may cause a metallic taste, and topical application may cause contact dermatitis
Pseudomembranous colitis is a potentially-lethal condition commonly associated with clindamycin, but which also occurs with other antibiotics. Overgrowth of Clostridium difficile, which is inherently resistant to clindamycin, results in the production of a toxin that causes a range of adverse effects, from diarrhea to colitis and toxic megacolon
Rarely—in less than 0.1% of patients—clindamycin therapy has been associated with anaphylaxis, blood dyscrasias, polyarthritis, jaundice, raised liver enzyme levels and/or hepatotoxicity.
Pharmacology
Pharmacokinetics
Approximately 90% of an oral dose of clindamycin is absorbed from the gastrointestinal tract, and it is widely distributed throughout the body, excluding the central nervous system. Adequate therapeutic concentrations can be achieved in bone. There is also active uptake into white blood cells, most importantly neutrophils.
Clindamycin is extensively metabolised in the liver, probably by CYP3A4; some of its metabolites are active, such as N-dimethyl clindamycin and clindamycin sulfoxide. The elimination half-life is 1.5 to 5 hours. Clindamycin is primarily eliminated by hepatic metabolism; after an intravenous dose of clindamycin phosphate, about 4.5% of the dose is excreted in urine as clindamycin and about 0.35% as the phosphate salt The metabolites are excreted primarily in the urine.
Mechanism of action
Clindamycin has a bacteriostatic effect. It is a bacterial Protein synthesis inhibitor by inhibiting ribosomal translocation, in a similar way to macrolides. It does so by binding preferentially to the 23S subunit of the bacterial ribosome.
Interactions
Clindamycin may prolong the effects of neuromuscular-blocking drugs. Its similarity to the mechanism of action of macrolides and chloramphenicol means they should not be given simultaneously, as this causes antagonism and possible cross-resistance.
I found this drug really good perticularly in respiratory tract diseases.
Indications
Used primarily to treat infections caused by
· Susceptible anaerobic bacteria, including infections of the respiratory tract, skin and soft tissue infections, and peritonitis.
· In patients with hypersensitivity to penicillins, clindamycin may be used to treat infections caused by susceptible aerobic bacteria as well.
· It is also used to treat bone and joint infections, particularly those caused by Staphylococcus aureus.
· Topical application of clindamycin phosphate can be used to treat mild to moderate acne.[5]
Roale in Respiratory infections
Susceptible bacteria
It is most effective against infections involving the following types of organisms:
Aerobic Gram-positive cocci, including some members of the Staphylococcus and Streptococcus (e.g. pneumococcus) genera, but not enterococci.
Anaerobic, Gram-negative rod-shaped bacteria, including some Bacteroides, Fusobacterium, and Prevotella, although resistance is increasing in Bacteroides fragilis.
These are the common bactrias in aAc. Exacerbation of COPD,Community Acquired pneumonia, and Upper respiratory tract infection.
But one has to remember that most aerobic Gram-negative bacteria (such as Pseudomonas, Legionella, Haemophilus influenzae and Moraxella) are resistant to clindamycin, as are the facultative anaerobic Enterobacteriaceae.
Other
1.It can also be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA); many strains of MRSA are still susceptible to clindamycin.
Clindamycin is used in cases of suspected toxic shock syndrome, often in combination with a bactericidal agent such as vancomycin. The rationale for this approach is a presumed synergy between vancomycin, which causes the death of the bacteria by breakdown of the cell membrane, and clindamycin, which is a powerful inhibitor of toxin synthesis. Both in vitro and in vivo studies have shown that clindamycin reduces the production of exotoxins by staphylococci; it may also induce changes in the surface structure of bacteria that make them more sensitive to immune system attack (opsonization and phagocytosis)
Clindamycin has been proven to decrease the risk of premature births in women diagnosed with bacterial vaginosis during early pregnancy to about a third of the risk of untreated women.
Parasitic
Plasmodium falciparum malaria
Clindamycin is effective and well-tolerated in treating Plasmodium falciparum malaria. It is to be used along with Chloroquinine or quinine for this perpouse.Quinine plus clindamycin combination is particularly useful for children, and is the treatment of choice for pregnant women who become infected in areas where resistance to chloroquine is common.
Clindamycin should not be used as an antimalarial by itself, although it appears to be very effective as such, because of its slow action.
Other Parasitic infection
The combination of clindamycin and quinine is the standard treatment for severe babesiosis
Clindamycin may also be used to treat toxoplasmosis, in combination with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.
Adverse effects
Common adverse drug reactions (ADRs) associated with clindamycin therapy—found in over 1% of patients—
Diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal pain or cramps, rash, and/or itch. High doses (both intravenous and oral) may cause a metallic taste, and topical application may cause contact dermatitis
Pseudomembranous colitis is a potentially-lethal condition commonly associated with clindamycin, but which also occurs with other antibiotics. Overgrowth of Clostridium difficile, which is inherently resistant to clindamycin, results in the production of a toxin that causes a range of adverse effects, from diarrhea to colitis and toxic megacolon
Rarely—in less than 0.1% of patients—clindamycin therapy has been associated with anaphylaxis, blood dyscrasias, polyarthritis, jaundice, raised liver enzyme levels and/or hepatotoxicity.
Pharmacology
Pharmacokinetics
Approximately 90% of an oral dose of clindamycin is absorbed from the gastrointestinal tract, and it is widely distributed throughout the body, excluding the central nervous system. Adequate therapeutic concentrations can be achieved in bone. There is also active uptake into white blood cells, most importantly neutrophils.
Clindamycin is extensively metabolised in the liver, probably by CYP3A4; some of its metabolites are active, such as N-dimethyl clindamycin and clindamycin sulfoxide. The elimination half-life is 1.5 to 5 hours. Clindamycin is primarily eliminated by hepatic metabolism; after an intravenous dose of clindamycin phosphate, about 4.5% of the dose is excreted in urine as clindamycin and about 0.35% as the phosphate salt The metabolites are excreted primarily in the urine.
Mechanism of action
Clindamycin has a bacteriostatic effect. It is a bacterial Protein synthesis inhibitor by inhibiting ribosomal translocation, in a similar way to macrolides. It does so by binding preferentially to the 23S subunit of the bacterial ribosome.
Interactions
Clindamycin may prolong the effects of neuromuscular-blocking drugs. Its similarity to the mechanism of action of macrolides and chloramphenicol means they should not be given simultaneously, as this causes antagonism and possible cross-resistance.
Now the most important thing is that it is less costly drug we are using these days for similar pathogenic spectrum. For Eg. Co-Amoxy Clavulanic Acid, Third gen. Cephalosporin.higher quinolones.
Be carful about Side efects.
Thursday, September 24, 2009
Saturday, September 19, 2009
ACEBROPHYLLINE
Acebrophylline (ambroxol-theophylline-7-acetate)
is an airway mucus regulator with antiinflammatory action. The drug's approach involves several points of attack in obstructive airway disease. The molecule contains ambroxol, which facilitates various steps in the biosynthesis of pulmonary surfactant, theophylline-7 acetic acid whose carrier function raises blood levels of ambroxol, thus rapidly and intensely stimulating surfactant production. The resulting reduction in the viscosity and adhesivity of the mucus greatly improves ciliary clearance. By deviating phosphatidylcholine towards surfactant synthesis, making it no longer available for the synthesis of inflammatory mediators such as the leukotrienes, acebrophylline also exerts an inflammatory effect. This is confirmed in vivo by the reduction in aspecific bronchial hyper-responsiveness in patients with stable bronchial asthma. On a clinical level, acebrophylline is therapeutically effective in patients with acute or chronic bronchitis, chronic obstructive or asthma-like bronchitis and recurrence of chronic bronchitis; it reduces the frequency of episodes of bronchial obstruction and reduces the need for beta2-agonists, and improves indexes of ventilatory function
is an airway mucus regulator with antiinflammatory action. The drug's approach involves several points of attack in obstructive airway disease. The molecule contains ambroxol, which facilitates various steps in the biosynthesis of pulmonary surfactant, theophylline-7 acetic acid whose carrier function raises blood levels of ambroxol, thus rapidly and intensely stimulating surfactant production. The resulting reduction in the viscosity and adhesivity of the mucus greatly improves ciliary clearance. By deviating phosphatidylcholine towards surfactant synthesis, making it no longer available for the synthesis of inflammatory mediators such as the leukotrienes, acebrophylline also exerts an inflammatory effect. This is confirmed in vivo by the reduction in aspecific bronchial hyper-responsiveness in patients with stable bronchial asthma. On a clinical level, acebrophylline is therapeutically effective in patients with acute or chronic bronchitis, chronic obstructive or asthma-like bronchitis and recurrence of chronic bronchitis; it reduces the frequency of episodes of bronchial obstruction and reduces the need for beta2-agonists, and improves indexes of ventilatory function
Friday, September 18, 2009
Community Acquired Pneumonia
Definition of community acquired pneumonia
• Symptoms and signs consistent with an acute lower respiratory tract infection associated with new radiographic shadowing for which there is no other explanation (e.g. not pulmonary edema or infarction); The illness is the primary reason for hospital admission and is managed as pneumonia.
• Pathologically : Pneumonia is an illness of the lungs and respiratory system in which the alveoli become inflamed and flooded with fluid
Incidence
• The annual incidence in the community is 5–11 per 1000 adult population.
• CAP accounts for 5–12% of all cases of adult lower respiratory tract infection managed by general practitioners in the community
• The incidence varies markedly with age, being much higher in the very young and the elderly.
• The incidence of CAP requiring admission to hospital varies between 1.1 and 4 per 1000 population.
• Between 22% and 42% of adults with CAP are admitted to hospital.
• Between 5% and 10% of adults admitted to hospital with CAP are managed on an ICU.
Sex: Incidence is greater in males than in females.
Age: Advanced age increases the incidence of pneumonia and the mortality from pneumonia.
• This is because elderly persons have weaker immune responses, higher risk of aspiration, and other co-morbidities.
• In a 20-year US study, the mortality rate from pneumococcal pneumonia with bacteremia was 20.3%, overall. However, a higher mortality rate (37.7%) occurred in elderly patients
The mortality
• The reported mortality rate of adults with CAP managed in the community in the UK is very low at less than 1% .
• The reported mortality rate of adults admitted to hospital with CAP in the UK has varied between 5.7% and 12% .
• BUT The mortality rate of patients with severe CAP requiring admission to an ICU in the UK is high at over 50%.
Economic consequences
• The direct costs associated with CAP are high and mostly associated with inpatient care costs.
• Substantial cost savings could probably be made by strategies to prevent CAP, reduce the requirement for hospital admission, and shorten the length of hospital stay for patients with non-severe CAP.
ETIOLOGY
o S pneumoniae
o M pneumoniae
o H influenzae
o Anaerobs
o Gram negative enteric bacilli
o S aureus
o M catarrhalis
o Legionella spp
o C pneumoniae
o C psittaci
o C burneti
o All viruses
o Influenza A & B
o Mixed
Diagnosis
Outpatients contact GPs with complaints like
• Coughing
• Chest pain:-central/dull peripheral/pleuritic
• Fever, and
• Difficulty in breathing
Patients may also have:-
General Symptoms
• Malaise
• Fever
• Rigors/ shaking chills
• Myalgia
Signs
• Cyanosis
• Herpes labialis
• Sputum production
Focal signs
• Tachypnoea/tachycardia
• Decrease movement
• Dullness
• Crepitation
• Bronchial breathing/ WP/ TVF/ Egophony
• Pleuritic rub
• Cyanosis
Atypical pneumonias may additionally have
Bloody or rust-colored : pneumococcal
Green: Pseudomonas, Haemophilus, and pneumococcal
Currant-jelly : Klebsiella or pneumococcal species.
Foul-smelling and bad-tasting : anaerobic infections
Can the aetiology of CAP be predicted from clinical features?
The likely aetiological agent causing CAP cannot be accurately predicted from clinical features.Some clinical features reported to be more common with specific pathogens
1.Streptococcus pneumoniae: Increasing age, cardiovascular, comorbidity, acute onset, high fever and pleuritic chest pain
2.Bacteraemic Streptococcus pneumoniae: Female sex, excess alcohol, diabetes mellitus, chronic obstructive pulmonary disease, dry cough
3.Legionella pneumophila :Younger patients, smokers, absence ofcomorbidity, diarrhoea, neurological symptoms, more severe infection, evidence of multisystem involvement (e.g. abnormal liver function tests, elevated serum creatine kinase.
4.Mycoplasma pneumoniae :Younger patients, prior antibiotics, lessmultisystem involvement
5.Chlamydia pneumoniae: Longer duration of symptoms beforehospital admission, headache
6.Coxiella burnetii: Male sex, dry cough, high fever
7.Klebsiella pneumoniae Men were more commonly affected and presented with a lower platelet count and leucopenia.Alcoholics were at particular risk of bacteraemic and fatal Klebsiella pneumoniaH/O Co morbid illness, Liver disease, Renal, Malignancy, DM, Cardiovascular, CCF, H/O Co morbid illness is important as it can lead to, Dose adjustment, Chronicity, Diagnostic problem
Predisposing factors:
Physical examination: - findings that may indicate the etiology of pneumonia are as follows:
Physical findings & Etiology of pneumonia:
1.Periodontal disease with foul-smelling sputum Anaerobes, possible mixed aerobic-anaerobic infection
2.Bullous myringitis Mycoplasma pneumoniae
3.Absent gag reflex, altered level of consciousness, recent seizure :Polymicrobial (aerobic and anaerobic), 4.Possible macroaspiration or microaspiration:Encephalitis M pneumoniae, C burnetii, L pneumophila
5.Cerebellar ataxia,: erythema multiforme, erythema nodosum Chlamydia pneumoniae, M tuberculosis
6.Erythema gangrenosum :Pseudomonas aeruginosa, Serratia marcescensCutaneous nodules (abscesses and CNS findings) Nocardia species,
A review of published studies reported that there were no individual clinical findings that reliably diagnosed CAP. • The problem is compounded by poor inter-observer reliability in eliciting respiratory signs.•
Although most patients with CAP can be managed successfully in the community by their general practitioner without investigations, distinguishing CAP from other causes of respiratory symptoms and signs can be difficult, particularly where the presence of co-morbidity such as LVF, chronic lung disease, or COPD complicate the clinical picture. The elderly can present a particularly difficult diagnostic challenge because they more frequently present with non-specific or absent symptoms and signs
Invstigation
Radiology
General
Microbiology
Chest X-ray
a. The diagnosis of CAP on the basis of history and physical findings is inaccurate without a chest radiograph
b. A chest X-ray is not always necessary to confirm a case of pneumonia, but it can help in several circumstances:• Determining whether or not pneumonia is actually present• Providing clues as to the kind of pneumonia• Showing the severity of the disease• Monitoring how the patient is doing over time, particularly if he is not improving as expected• Presence of complication (pleural effusion, multilob. disease)Chest radiography• Evidence of consolidation (lobar/ segmental)• Cavitation• Effusion• Pneumonia is not always seen on x-raysa. Initial stagesb. Involves a part of the lung not easily seenc. Dehydrated patientNo characteristic chest radiograph features allow a confidant prediction of likely pathogenChest radiography clue to Etiologyo Focal opacity (segment or lobar pneumonia - S pneumoniae, M pneumoniae, L pneumophila, S aureus, C pneumoniae, M tuberculosis, B dermatitidiso Interstitial pattern (diffuse process identified as reticulonodular or reticular process) - M pneumoniae, P carinii, C psittacio Interstitial pattern with hilar and/or mediastinal lymphadenopathy - M pneumoniae, Epstein-Barr virus, Francisella tularensis, C psittaci, fungio Cavitation or necrotizing pneumonia - Mixed aerobic-anaerobic infection (lung abscess), aerobic gram-negative bacilli, M tuberculosis, L pneumophila, C neoformans, Nocardia asteroides, Actinomyces israelii, C immitiso Bulging oblique or horizontal fissure - K pneumoniae, L pneumophilaMultifocal bilateral segment or lobar opacities - S aureus, C burnetii, L pneumophila, S pneumoniae, bacteraemic pneumococcal pneumonia Chest radiography clue to Etiology (conti……..o Miliary (diffuse micronodular) pattern - M tuberculosis, H capsulatum, C immitis, B dermatitidis, varicella zostero Pneumatoceles (thin-walled cavities) - S aureus, Streptococcus pyogenes, P cariniio "Round" pneumonia (often presents as solitary pulmonary nodule) - C burnetii, S pneumoniae, L pneumophila, S aureuso Pleural effusions -were more common in bacteraemic pneumococcal diseaseo Spontaneous pneumothorax- S aureus o Air bronchograms may be observed in the presence of S pneumoniae. Frank consolidation and air bronchograms have been associated with a higher incidence of bacteremia.o Cavitation and associated pleural effusions are observed in cases of S aureus infection, anaerobic infections, gram-negative infections, and tuberculosis.o Legionella has a predilection for the lower lung fields.o Klebsiella has a tendency to occur in the upper lobes.High-resolution CT• In unclear cases, high-resolution CT scanning of the lungs may aid in the diagnosisGeneral testNon-microbiological investigations Performed to • Assess severity • Detect the presence of any co-morbid disease• Assess the impact on co-morbid disease• Provide some pointer to the particular aetiological agent or group of pathogens• Identify complications• Monitor progress What general investigations should be done in a patient with suspected CAP in the community? • General investigations, including a CXR, not necessary for majority of pt.with CAP who are managed in community. • Out of hours & emergency GPs assessment centres should consider obtaining SpO2 for simple assessment of oxygn All patients should have the following tests performed on admission:+ Chest radiograph.+ Full blood count.+ Urea, electrolytes and liver function tests .+ CRP when locally available .+ Oxygenation assessment. • SaO2 should be measured on admission. Those with SaO2 <92%>25 neurophil /LPF leukocyte Sq.epi.cell Bacterial Pathogens Sputum Gram Stain Stre. pneumoniae Encapsulated lancet-shaped Gram-positive diplococci or short chains Quellung reaction positive H. influenzae Small Gram-negative pleomorphic encapsulated bacillus (Group B) Occasionally disease caused by nontypable strains S. aureus Gram-positive cocci in clusters S. pyogenes Gram-positive cocci in chains Quellung reaction negative K pneumoniae Gram-negative rod (encapsulated in patients with cystic fibrosis) Enteric bacilli Same as P. aeruginosa Variable -- Gram-negative rod P. aeruginosa Gram-negative rod (encapsulated in patients with cystic fibrosis) Enteric bacilli Same as P. aeruginosa Variable -- Gram-negative rod Enteric bacilli Variable -- Gram-negative rod Moraxella Intracellular Gram-negative diplococci Absence of large no. of organism in adequate sputum Legionella pneumophilia,mycoplasma,coxiella,viral Advantages • Quick and inexpensive. • Can assess quality of samples (cytological content) with rejection of poor quality samples. • Can aid the interpretation of culture results and occasionally give an early indication of possible aetiology. Disadvantages • Strict criteria for interpretation require appropriate operator training. • Validity of results is directly related to the experience of the interpreter. • Sputum Gram stain correlates poorly with culture results in conditions other than CAP. This poses practical difficulties for laboratories that frequently have to interpret results with little or no clinical information. Z-N staining for AFB & culture Sputum cultures Routine sputum cultures are, however, neither very sensitive nor specific, and often do not contribute to initial patient MM Problems include: (1) The inability of patients to produce good specimens. (2) Prior exposure to antibiotics. (3) Delays in transport and processing. (4) Difficulty in interpretation due to contamination of the sample by upper respiratory tract flora, which may include potential pathogens such as S pneumoniae and coliforms (especially in patients already given antibiotics) • Sputum samples should be sent for culture and sensitivity tests from patients admitted to hospital with non-severe CAP who are able to expectorate purulent sputum. • Samples and have not received prior antibiotic treatment. Specimens should be transported rapidly to the laboratory. • Sputum cultures should also be performed for patients with severe CAP or those who fail to improve. Sputum cultures may identify the causative agent in CAP including unexpected or antibiotic resistant pathogens such as S aureus orpenicillin resistant pneumococci. Blood cultures • Recommended for all patients admitted with CAP, preferably before antibiotic treatment is commenced. • Isolation of S pneumoniae, H influenzae, S aureus, &K pneumoniae is highly specific in determining microbial aetiology. • Bacteraemia is also a marker of illness severity. • In pneumococcal pneumonia the sensitivity of blood cultures is at most only 25%, and is even lower for patients given antibiotic treatment before admission. SEROLOGY FOR RESPIRATORY PATHOGENS Usually comprise antibody tests for the atypical pathogens Complement fixation tests: Many laboratories still rely but • Time consuming • Inconvenient to perform • Have poor sensitivity and specificity • Other tests are becoming increasingly available WHEN • Paired serological tests should be performed for all patients with severe CAP, those unresponsive to β-lactam antibiotics, & for selected patients with particular epidemiological risk factors or in whom a specific microbiological diagnosis is important for public health measures. • Serological tests should be extended to all patients admitted to hospital with CAP during outbreaks and when needed for the purposes of surveillance. • There is little value in testing single serum samples taken within 7 days of the onset of CAP. • Such samples can be stored until the follow up (convalescent) sample is taken 7–10 days later and the paired samples can be tested in parallel. • Serum samples taken more than 1 week into the illness can be tested immediately. As, raised antibody titres, particularly to L pneumophila or M pneumoniae, may be found in some patients on or soon after admission to hospital, particularly if the onset of symptoms is more than 7 days before admission. A suggested algorithm for performing serological investigations is NON-CULTURAL TESTS FOR S PNEUMONIAE Pneumococcal antigen detection • Can be detected in various body fluids during active pneumococcal infection including sputum, pleural fluid, serum, and urine. • Less affected by prior antibiotic treatment and the detection of antigenaemia is correlated with clinical severity. • There is currently insufficient evidence to recommend widespread use of pneumococcal antigen tests or serological tests in CAP. • Antigen tests should be used for patients with severe CAP, if available locally. Techniques Various techniques have been used to detect pneumococcal polysaccharide antigens or C-polysaccharide. Counterimmunoelectrophoresis Is the least sensitive technique but has been studied the most. Latex agglutination Latex agglutination has improved sensitivity but produces poor results with urine samples. Enzyme immunoassays (EIAs) Promising in terms of improved sensitivity and specificity But have not been rigorously evaluated SAMPLE Urine Detection of pneumococcal antigen in serum or urine is reasonably specific but less sensitive. Sputum Higher sensitivity is found with sputum, but specificity is compromised by cross reactions with “viridans” streptococci and false positive results due to oropharyngeal carriage of S pneumoniae Not been widely adopted • Due to cost • Lack of sensitivity • Lack of “robustness” in a routine diagnostic setting. • further work in this area is awaited. Pneumococcal serology • The detection of antibodies to the pneumococcal toxin pneumolysin. • Reported sensitivity and specificity (80–90%). • Reserved for epidemiological studies Pneumococcal polymerase chain reaction • Still under development for routine diagnosis. TESTS FOR LEGIONNAIRES’ DISEASE • Recommended for all patients with severe CAP • Patients with specific risk factors • For all patients with CAP during outbreaks. Rapid testing and reporting for legionella urine antigen should be available in at least one laboratory per region. Urine antigen detection by EIA • Highly specific (>95%) and sensitive (~80%) test. • Rapid results can be obtained at an early stage of the illness. • Principally L pneumophila serogroup 1 and do not detect antigen from other Legionella species. Legionella direct immunofluorescence (DIF) tests • L pneumophila can be detected by DIF on invasive respiratory samples such as bronchial aspirates. • L pneumophila specific reagents should be used and not hyperimmune rabbit antisera which are poorly specific. • The value of performing DIF on expectorated sputum samples is less well established. Culture Legionella • Every effort should be made to diagnose by culture of Legionella species from clinical samples (principally respiratory samples). • Culture is 100% specific. • The only method of detecting infection with Legionella species other than L pneumophila. • Culture is also valuable for epidemiological investigations. Problems with culture • The inability of many patients with legionella pneumonia to produce sputum samples • Prior antibiotic treatment • Laboratory time and cost in processing samples • Lack of rapid results (10 days). Determination of antibody levels • Commercial assays are currently under evaluation. PCR Detection of legionella DNA by PCR from respiratory samples, blood, and urine is still only available as a research tool. TESTS FOR M PNEUMONIAE The mainstay of diagnosis is by serological testing. Culture is generally not available in diagnostic lab. CFT • The most common serological assay used • “Gold standard” • Various alternative assays such as microparticle agglutination and EIAs are also available. • Raised titres are usually detected no earlier than 10–14 days after the onset of mycoplasma infection, but the insidious onset and slow progression of symptoms means that many patients admitted to hospital with mycoplasma CAP have raised titres on or shortly after admission. • Genomic detection of M pneumoniae in respiratory specimens by amplification techniques such as PCR is currently under development. TESTS FOR CHLAMYDIA SPECIES • Chlamydial antigen detection tests should be available for invasive respiratory samples from patients with severe CAP or where there is a strong suspicion of psittacosis. • The CFT remains the most suitable and practical serological assay for routine diagnosis of respiratory chlamydial infections. • There is no currently available serological test that can reliably detect infections due to C pneumoniae. Invsive methods for obtaining respiratory secretions o They are associated with morbidity o Reserve to patient who are severely ill o And in whom it is considered important to identify organism rather then rely on empirical antibiotic approch o Or in whom such approch already failed 1. Trans tracheal aspiration 2. FOB bal PSB 3. Percutaneous ultra thin needle lung aspiration Trans tracheal aspiration • Healthy adults have sterile tracheal specimens. • Was regarded gold standard. • Invasive procedure. • Cultures of secretions from the lower respiratory tract obtained by this method more accurately reflect the bacterial flora of an infection of the lower respiratory tract than expectorated sputum. • It also provides samples for anaerobic culture. • Isolated case reports have described life-threatening complications and death. • When TTA used for diagnosis, the incidance of false negative culture result in Pt. Not given previous anti biotic is about 1%. Indications TTA • No sputum or pleural fluid available for analysis. • Analysis of expectorated sputum unacceptable due to contamination. • Suspected anaerobic infection in severely ill patient. • Pneumonia not responding to therapy. Contra indications TTA (1) Inability to identify clearly the landmarks of a normal cricothyroid membrane (2) Potential disorders of bleeding, which could not be corrected before the procedure. (3) Hypoxemia that could not be improved with supplemental oxygen to an arterial oxygen pressure (PaO,) of at least 70 mm Hg. (4) Severe coughing (5) Inability of patient to cooperate Procedure • Position Supine with pillow under the shoulder. • Neck hyper extended. • Locate cricothyroid membrane. • Overlying skin sterilized & anasthesized. • 16 gauge needle with indwelling cathater inserted through skin and cricothyriod membrane. • After trachea entered the needle angled cauded and catheter advanced into trachea. • The covering needle is removed leaving catheter in place • Aspirate secretions with syringe. Assessment of possible contamination In order to help ensure that the specimen from TTA was not contaminated during procedure, 5 to 10 ml of a 0.5 percent soln of methylene blue was first nebulized into patient’s oropharynx and then swallowed. Absence of any bluish discoloration in the specimen from TTA ruled out obvious oropharyngeal contamination and also made it exceedingly unlikely that any contamination had occurred. False positive results may present in 1.chronic bronchitis 2.Bronchogenic carcinoma 3.Repeated aspirations Complications • Bleeding • Paratracheal and cutaneous infection • Subcutaneous or mediastinal emphycema • Hypoxemia • Vasovagel reactions Bronchoscpy with aspiration • Safe and can provide clues when other methods failed. • Even when picture is clouded by prior antibiotic use. • FOB picks up oropharyngeal contamination so PSB should be used. • PSB may be combined with BAL to obtain quantitative culture in order to discriminate between presence or absence of pneumonia. • Diagnostic threshold is 103 cfu/ml. • Infection with less common organism can be detected. • Anatomical defect may R/O Trans thoracic lung aspiration (TLA) • Specimen taken directly from lung paranchyma. • Can be done after X-ray, USG or CT localization • False + results are low (from skin) Contraindication • Bullous emphysema • Pulmonary hypertension • Bleeding disorder • Suspected vascular lesion • Uncontrolled coughing • Un cooperative patient Complications are more then TTA • Pneumothorax • Haemoptysis • Extension of infection • Air embolism Trans bronchial or open lung biopsy Rarely used D/D Atelectasis Bronchiectasis Chronic Bronchitis Chronic Obstructive Pulmonary Disease Foreign Body Aspiration Influenza Klebsiella Infections Lung Abscess Lung Cancer, Non-Small Cell Lung Cancer, Oat Cell (Small Cell) Mycobacterium Avium-Intracellulare Mycobacterium Kansasii Pneumococcal Infections Pneumocystis Carinii Pneumonia Pneumonia, Aspiration Pneumonia, Community-Acquired Pneumonia, Fungal Pneumonia, Viral Psittacosis Q Fever Respiratory Failure Sepsis, Bacterial Why etiology is important How to reach etiology Is the etiology different in specific population groups? THE ELDERLY • Most pathogens: frequency is same in young and elderly • Atypical pathogen: M pneumoniae and legionella infection are less frequent in elderly. • Gram-negative enteric bacilli were no more common in elderly patients. PATIENTS WITH COPD H influenzae and M catarrhalis may be more frequent. PATIENTS WITH DIABETES: may be more frequent are Bacteraemic pneumococcal pneumonia NURSING HOME RESIDENTS Aspiration Gram-negative enteric bacilli Anaerobes May occur more frequently than in matched elderly patients ALCOHOLIC PATIENTS: may be more frequent are. • Aspiration • Pneumococcal infection overall • Bacteraemic pneumococcal infection • Gram-negative enteric bacilli. • Legionella • Atypical pathogens • C pneumoniae • Anaerobes • Mixed infections PATIENTS ON ORAL STEROIDS Legionella species may be more frequent. ASPIRATION PNEUMONIA: may be more common • Anaerobic bacteria • Gram-negative enteric bacilli The frequency of radiographic deterioration after hospital admission and the rates of resolution of radiographic shadowing differed according to the underlying aetiolo • S aureus pneumonia is observed in those who abuse intravenous drugs. S aureus generally occurs in hospitalized patients and patients with prosthetic devices; it spreads hematogenously to the lungs from contaminated local sites. This pathogen also is an important cause of pneumonia following infection with influenza A. Treatment: Therapeutic recommendations are provided in AIDS Clinical Trials Unit, Baltimore, Maryland 21205. two categories. The first category includes the recommenda- Classification of pneumonia • Pathologists classification anatomic changes that were found in the lungs during autopsies. lobar pneumonia, Multilobar pneumonia, Interstitial pneumonia • Rradiological classification. • Microbiologic classification • Combined clinical classification : combines many factors Age Risk factors for certain microorganisms Presence of underlying lung disease Presence of underlying systemic disease Whether he or she has recently been hospitalized. Advantage of Combined clinical classification guide the selection of appropriate initial treatments even before the microbiologic cause of the pneumonia is known TYPES Community-acquired pneumonia Hospital-acquired pneumonia.
• Symptoms and signs consistent with an acute lower respiratory tract infection associated with new radiographic shadowing for which there is no other explanation (e.g. not pulmonary edema or infarction); The illness is the primary reason for hospital admission and is managed as pneumonia.
• Pathologically : Pneumonia is an illness of the lungs and respiratory system in which the alveoli become inflamed and flooded with fluid
Incidence
• The annual incidence in the community is 5–11 per 1000 adult population.
• CAP accounts for 5–12% of all cases of adult lower respiratory tract infection managed by general practitioners in the community
• The incidence varies markedly with age, being much higher in the very young and the elderly.
• The incidence of CAP requiring admission to hospital varies between 1.1 and 4 per 1000 population.
• Between 22% and 42% of adults with CAP are admitted to hospital.
• Between 5% and 10% of adults admitted to hospital with CAP are managed on an ICU.
Sex: Incidence is greater in males than in females.
Age: Advanced age increases the incidence of pneumonia and the mortality from pneumonia.
• This is because elderly persons have weaker immune responses, higher risk of aspiration, and other co-morbidities.
• In a 20-year US study, the mortality rate from pneumococcal pneumonia with bacteremia was 20.3%, overall. However, a higher mortality rate (37.7%) occurred in elderly patients
The mortality
• The reported mortality rate of adults with CAP managed in the community in the UK is very low at less than 1% .
• The reported mortality rate of adults admitted to hospital with CAP in the UK has varied between 5.7% and 12% .
• BUT The mortality rate of patients with severe CAP requiring admission to an ICU in the UK is high at over 50%.
Economic consequences
• The direct costs associated with CAP are high and mostly associated with inpatient care costs.
• Substantial cost savings could probably be made by strategies to prevent CAP, reduce the requirement for hospital admission, and shorten the length of hospital stay for patients with non-severe CAP.
ETIOLOGY
o S pneumoniae
o M pneumoniae
o H influenzae
o Anaerobs
o Gram negative enteric bacilli
o S aureus
o M catarrhalis
o Legionella spp
o C pneumoniae
o C psittaci
o C burneti
o All viruses
o Influenza A & B
o Mixed
Diagnosis
Outpatients contact GPs with complaints like
• Coughing
• Chest pain:-central/dull peripheral/pleuritic
• Fever, and
• Difficulty in breathing
Patients may also have:-
General Symptoms
• Malaise
• Fever
• Rigors/ shaking chills
• Myalgia
Signs
• Cyanosis
• Herpes labialis
• Sputum production
Focal signs
• Tachypnoea/tachycardia
• Decrease movement
• Dullness
• Crepitation
• Bronchial breathing/ WP/ TVF/ Egophony
• Pleuritic rub
• Cyanosis
Atypical pneumonias may additionally have
- Symptoms
• Headache
• Confusion
• Diarrhoea
• Incontinence
Sign
• Rash (skin, mucus memberane)
Individuals with symptoms of pneumonia need medical evaluation.
Clinical presentation varies
• Mildly ill ambulatory
to a
• Critically ill patient with respiratory failure or septic shock
History:
A meticulous past medical history and history of environmental, occupational, and recreational exposures should be obtained. This history should include whether the patient has recently traveled or had contact with animals that might serve as a source of an infectious agent
Predisposing factors
• Local lung pathologies (eg, tumors, COPD, bronchiectasis).
• Smoking
• Alcoholism
• Diabetes
• I.V. drugs abuse
Epidemiological patterns of pathogens causing CAP( and is this information useful to the clinician?)
Organism Season Epidemic
S. pneumoniae: Winter Overcrowded settings
Legionella species: Sept. Oct. UK ,Water containing systems in buildings
Mycoplasma pneumoniae: Every 4 years
Chlamydia pneumoniae; Closed communities
Chlamydia psittaci :Infected sources at work—Eg. poultry or duck of bird contact
Coxiella burnetii: April to June Relation to animal sources (usually sheep)
Staphylococcus aureus ;Winter
Influenza virus: Annual epidemics during winter
Chlamydia pneumoniae
• Its direct pathogenic role as a cause of—as opposed to being associated with—CAP is not clear.
• Evidence that antibiotic treatment directed against this organism alters the course of the illness is lacking.
• When identified, other bacterial pathogens such as S pneumoniae are often identified in the same host.
• Patients may recover when antibiotics to which C pneumoniae is not sensitive are given.
Staphylococcus aureus
• Coincident influenza type symptoms reported in 39%.
• Evidence of coincident influenza virus infection found in 39% of those admitted to hospital, & 50% of those admitted to ICU.
Environmental exposures
Exposure to Causative organism
Contaminated air-conditioning cooling towers, grocery store mist machine, or a visit or recent stay in a hospital with a contaminated water system Legionella pneumophila
Overcrowded institutions such as jails, shelters for homeless persons, or military training camps S pneumoniae, Mycobacterium tuberculosis, Mycoplasma, and Chlamydia pneumonia
Wind or rainstorm in an endemic area:Coccidioides immitis
Contact with animals
Infected parturient cats, cattle, sheep, or goats: Coxiella burnetii
Turkeys, chickens, ducks, or psittacine birds :Chlamydia psittaci
Infection can result from exposure to contaminated bat caves or from excavation in endemic areas: Histoplasma capsulatum
Wild mammals :Tularemia,Plague
Travel history
Travel Area Disease
Thailand or other countries in Southeast Asia:Burkholderia (Pseudomonas) pseudomallei (melioidosis )
Immigrants from Asia or Africa:M tuberculosis (For Reader outide india)
The southwestern United States :Coccidioides immitis
Midwestern United States or the Canadian Shield:Blastomyces dermatitidis
Occupational history
Pneumonia may develop in a health care worker who works with patients infected with HIV in a large city :M tuberculosis
Family history
Recent illness S/o mycoplasma or viral cause
Host factors Evaluation of host factors often provides a clue to the bacterial diagnosis.
Host factors Clue to bacterial diagnosis
Diabetic ketoacidosis: S pneumoniae or S aureus
Chronic obstructive lung disease: Haemophilus influenzae or Moraxella catarrhalis
Asthma, COPD, smoking :Haemophilus influenzae
Debilitated, immunocompromised, or recently hospitalized :Gram-negative pneumonias Eg Escherichia coli and Pseudomonas, Enterobacter, and Serratia species
Altered sensorium (eg, seizures, alcohol or drug intoxication) or CNS impairment (eg, stroke) :Aspiration pneumonias (Moraxella catarrhalis and Bacteroides, Peptostreptococcus, and Fusobacterium species)
Solid organ transplants :S pneumoniae may occur more than 3 months after the transplant.
Other organisms include Legionella species, Pneumocystis carinii, and cytomegalovirus
Sickle cell disease S pneumoniae or H influenzae
HIV infection CD4 > 200/mL :Cryptococcus neoformans, M tuberculosis, or Rhodococcus equi infection
HIV infection CD4 <>
- Clinical featuresCAP in elderly: are risk factors and clinical features different?Less likely
- The classic symptoms and signs• FeverMore likely
- Non-specific features, especially confusion.
- Co morbid illness
- • Aspiration
Bloody or rust-colored : pneumococcal
Green: Pseudomonas, Haemophilus, and pneumococcal
Currant-jelly : Klebsiella or pneumococcal species.
Foul-smelling and bad-tasting : anaerobic infections
Can the aetiology of CAP be predicted from clinical features?
The likely aetiological agent causing CAP cannot be accurately predicted from clinical features.Some clinical features reported to be more common with specific pathogens
1.Streptococcus pneumoniae: Increasing age, cardiovascular, comorbidity, acute onset, high fever and pleuritic chest pain
2.Bacteraemic Streptococcus pneumoniae: Female sex, excess alcohol, diabetes mellitus, chronic obstructive pulmonary disease, dry cough
3.Legionella pneumophila :Younger patients, smokers, absence ofcomorbidity, diarrhoea, neurological symptoms, more severe infection, evidence of multisystem involvement (e.g. abnormal liver function tests, elevated serum creatine kinase.
4.Mycoplasma pneumoniae :Younger patients, prior antibiotics, lessmultisystem involvement
5.Chlamydia pneumoniae: Longer duration of symptoms beforehospital admission, headache
6.Coxiella burnetii: Male sex, dry cough, high fever
7.Klebsiella pneumoniae Men were more commonly affected and presented with a lower platelet count and leucopenia.Alcoholics were at particular risk of bacteraemic and fatal Klebsiella pneumoniaH/O Co morbid illness, Liver disease, Renal, Malignancy, DM, Cardiovascular, CCF, H/O Co morbid illness is important as it can lead to, Dose adjustment, Chronicity, Diagnostic problem
Predisposing factors:
Physical examination: - findings that may indicate the etiology of pneumonia are as follows:
Physical findings & Etiology of pneumonia:
1.Periodontal disease with foul-smelling sputum Anaerobes, possible mixed aerobic-anaerobic infection
2.Bullous myringitis Mycoplasma pneumoniae
3.Absent gag reflex, altered level of consciousness, recent seizure :Polymicrobial (aerobic and anaerobic), 4.Possible macroaspiration or microaspiration:Encephalitis M pneumoniae, C burnetii, L pneumophila
5.Cerebellar ataxia,: erythema multiforme, erythema nodosum Chlamydia pneumoniae, M tuberculosis
6.Erythema gangrenosum :Pseudomonas aeruginosa, Serratia marcescensCutaneous nodules (abscesses and CNS findings) Nocardia species,
A review of published studies reported that there were no individual clinical findings that reliably diagnosed CAP. • The problem is compounded by poor inter-observer reliability in eliciting respiratory signs.•
Although most patients with CAP can be managed successfully in the community by their general practitioner without investigations, distinguishing CAP from other causes of respiratory symptoms and signs can be difficult, particularly where the presence of co-morbidity such as LVF, chronic lung disease, or COPD complicate the clinical picture. The elderly can present a particularly difficult diagnostic challenge because they more frequently present with non-specific or absent symptoms and signs
Invstigation
Radiology
General
Microbiology
Chest X-ray
a. The diagnosis of CAP on the basis of history and physical findings is inaccurate without a chest radiograph
b. A chest X-ray is not always necessary to confirm a case of pneumonia, but it can help in several circumstances:• Determining whether or not pneumonia is actually present• Providing clues as to the kind of pneumonia• Showing the severity of the disease• Monitoring how the patient is doing over time, particularly if he is not improving as expected• Presence of complication (pleural effusion, multilob. disease)Chest radiography• Evidence of consolidation (lobar/ segmental)• Cavitation• Effusion• Pneumonia is not always seen on x-raysa. Initial stagesb. Involves a part of the lung not easily seenc. Dehydrated patientNo characteristic chest radiograph features allow a confidant prediction of likely pathogenChest radiography clue to Etiologyo Focal opacity (segment or lobar pneumonia - S pneumoniae, M pneumoniae, L pneumophila, S aureus, C pneumoniae, M tuberculosis, B dermatitidiso Interstitial pattern (diffuse process identified as reticulonodular or reticular process) - M pneumoniae, P carinii, C psittacio Interstitial pattern with hilar and/or mediastinal lymphadenopathy - M pneumoniae, Epstein-Barr virus, Francisella tularensis, C psittaci, fungio Cavitation or necrotizing pneumonia - Mixed aerobic-anaerobic infection (lung abscess), aerobic gram-negative bacilli, M tuberculosis, L pneumophila, C neoformans, Nocardia asteroides, Actinomyces israelii, C immitiso Bulging oblique or horizontal fissure - K pneumoniae, L pneumophilaMultifocal bilateral segment or lobar opacities - S aureus, C burnetii, L pneumophila, S pneumoniae, bacteraemic pneumococcal pneumonia Chest radiography clue to Etiology (conti……..o Miliary (diffuse micronodular) pattern - M tuberculosis, H capsulatum, C immitis, B dermatitidis, varicella zostero Pneumatoceles (thin-walled cavities) - S aureus, Streptococcus pyogenes, P cariniio "Round" pneumonia (often presents as solitary pulmonary nodule) - C burnetii, S pneumoniae, L pneumophila, S aureuso Pleural effusions -were more common in bacteraemic pneumococcal diseaseo Spontaneous pneumothorax- S aureus o Air bronchograms may be observed in the presence of S pneumoniae. Frank consolidation and air bronchograms have been associated with a higher incidence of bacteremia.o Cavitation and associated pleural effusions are observed in cases of S aureus infection, anaerobic infections, gram-negative infections, and tuberculosis.o Legionella has a predilection for the lower lung fields.o Klebsiella has a tendency to occur in the upper lobes.High-resolution CT• In unclear cases, high-resolution CT scanning of the lungs may aid in the diagnosisGeneral testNon-microbiological investigations Performed to • Assess severity • Detect the presence of any co-morbid disease• Assess the impact on co-morbid disease• Provide some pointer to the particular aetiological agent or group of pathogens• Identify complications• Monitor progress What general investigations should be done in a patient with suspected CAP in the community? • General investigations, including a CXR, not necessary for majority of pt.with CAP who are managed in community. • Out of hours & emergency GPs assessment centres should consider obtaining SpO2 for simple assessment of oxygn All patients should have the following tests performed on admission:+ Chest radiograph.+ Full blood count.+ Urea, electrolytes and liver function tests .+ CRP when locally available .+ Oxygenation assessment. • SaO2 should be measured on admission. Those with SaO2 <92%>25 neurophil /LPF leukocyte Sq.epi.cell Bacterial Pathogens Sputum Gram Stain Stre. pneumoniae Encapsulated lancet-shaped Gram-positive diplococci or short chains Quellung reaction positive H. influenzae Small Gram-negative pleomorphic encapsulated bacillus (Group B) Occasionally disease caused by nontypable strains S. aureus Gram-positive cocci in clusters S. pyogenes Gram-positive cocci in chains Quellung reaction negative K pneumoniae Gram-negative rod (encapsulated in patients with cystic fibrosis) Enteric bacilli Same as P. aeruginosa Variable -- Gram-negative rod P. aeruginosa Gram-negative rod (encapsulated in patients with cystic fibrosis) Enteric bacilli Same as P. aeruginosa Variable -- Gram-negative rod Enteric bacilli Variable -- Gram-negative rod Moraxella Intracellular Gram-negative diplococci Absence of large no. of organism in adequate sputum Legionella pneumophilia,mycoplasma,coxiella,viral Advantages • Quick and inexpensive. • Can assess quality of samples (cytological content) with rejection of poor quality samples. • Can aid the interpretation of culture results and occasionally give an early indication of possible aetiology. Disadvantages • Strict criteria for interpretation require appropriate operator training. • Validity of results is directly related to the experience of the interpreter. • Sputum Gram stain correlates poorly with culture results in conditions other than CAP. This poses practical difficulties for laboratories that frequently have to interpret results with little or no clinical information. Z-N staining for AFB & culture Sputum cultures Routine sputum cultures are, however, neither very sensitive nor specific, and often do not contribute to initial patient MM Problems include: (1) The inability of patients to produce good specimens. (2) Prior exposure to antibiotics. (3) Delays in transport and processing. (4) Difficulty in interpretation due to contamination of the sample by upper respiratory tract flora, which may include potential pathogens such as S pneumoniae and coliforms (especially in patients already given antibiotics) • Sputum samples should be sent for culture and sensitivity tests from patients admitted to hospital with non-severe CAP who are able to expectorate purulent sputum. • Samples and have not received prior antibiotic treatment. Specimens should be transported rapidly to the laboratory. • Sputum cultures should also be performed for patients with severe CAP or those who fail to improve. Sputum cultures may identify the causative agent in CAP including unexpected or antibiotic resistant pathogens such as S aureus orpenicillin resistant pneumococci. Blood cultures • Recommended for all patients admitted with CAP, preferably before antibiotic treatment is commenced. • Isolation of S pneumoniae, H influenzae, S aureus, &K pneumoniae is highly specific in determining microbial aetiology. • Bacteraemia is also a marker of illness severity. • In pneumococcal pneumonia the sensitivity of blood cultures is at most only 25%, and is even lower for patients given antibiotic treatment before admission. SEROLOGY FOR RESPIRATORY PATHOGENS Usually comprise antibody tests for the atypical pathogens Complement fixation tests: Many laboratories still rely but • Time consuming • Inconvenient to perform • Have poor sensitivity and specificity • Other tests are becoming increasingly available WHEN • Paired serological tests should be performed for all patients with severe CAP, those unresponsive to β-lactam antibiotics, & for selected patients with particular epidemiological risk factors or in whom a specific microbiological diagnosis is important for public health measures. • Serological tests should be extended to all patients admitted to hospital with CAP during outbreaks and when needed for the purposes of surveillance. • There is little value in testing single serum samples taken within 7 days of the onset of CAP. • Such samples can be stored until the follow up (convalescent) sample is taken 7–10 days later and the paired samples can be tested in parallel. • Serum samples taken more than 1 week into the illness can be tested immediately. As, raised antibody titres, particularly to L pneumophila or M pneumoniae, may be found in some patients on or soon after admission to hospital, particularly if the onset of symptoms is more than 7 days before admission. A suggested algorithm for performing serological investigations is NON-CULTURAL TESTS FOR S PNEUMONIAE Pneumococcal antigen detection • Can be detected in various body fluids during active pneumococcal infection including sputum, pleural fluid, serum, and urine. • Less affected by prior antibiotic treatment and the detection of antigenaemia is correlated with clinical severity. • There is currently insufficient evidence to recommend widespread use of pneumococcal antigen tests or serological tests in CAP. • Antigen tests should be used for patients with severe CAP, if available locally. Techniques Various techniques have been used to detect pneumococcal polysaccharide antigens or C-polysaccharide. Counterimmunoelectrophoresis Is the least sensitive technique but has been studied the most. Latex agglutination Latex agglutination has improved sensitivity but produces poor results with urine samples. Enzyme immunoassays (EIAs) Promising in terms of improved sensitivity and specificity But have not been rigorously evaluated SAMPLE Urine Detection of pneumococcal antigen in serum or urine is reasonably specific but less sensitive. Sputum Higher sensitivity is found with sputum, but specificity is compromised by cross reactions with “viridans” streptococci and false positive results due to oropharyngeal carriage of S pneumoniae Not been widely adopted • Due to cost • Lack of sensitivity • Lack of “robustness” in a routine diagnostic setting. • further work in this area is awaited. Pneumococcal serology • The detection of antibodies to the pneumococcal toxin pneumolysin. • Reported sensitivity and specificity (80–90%). • Reserved for epidemiological studies Pneumococcal polymerase chain reaction • Still under development for routine diagnosis. TESTS FOR LEGIONNAIRES’ DISEASE • Recommended for all patients with severe CAP • Patients with specific risk factors • For all patients with CAP during outbreaks. Rapid testing and reporting for legionella urine antigen should be available in at least one laboratory per region. Urine antigen detection by EIA • Highly specific (>95%) and sensitive (~80%) test. • Rapid results can be obtained at an early stage of the illness. • Principally L pneumophila serogroup 1 and do not detect antigen from other Legionella species. Legionella direct immunofluorescence (DIF) tests • L pneumophila can be detected by DIF on invasive respiratory samples such as bronchial aspirates. • L pneumophila specific reagents should be used and not hyperimmune rabbit antisera which are poorly specific. • The value of performing DIF on expectorated sputum samples is less well established. Culture Legionella • Every effort should be made to diagnose by culture of Legionella species from clinical samples (principally respiratory samples). • Culture is 100% specific. • The only method of detecting infection with Legionella species other than L pneumophila. • Culture is also valuable for epidemiological investigations. Problems with culture • The inability of many patients with legionella pneumonia to produce sputum samples • Prior antibiotic treatment • Laboratory time and cost in processing samples • Lack of rapid results (10 days). Determination of antibody levels • Commercial assays are currently under evaluation. PCR Detection of legionella DNA by PCR from respiratory samples, blood, and urine is still only available as a research tool. TESTS FOR M PNEUMONIAE The mainstay of diagnosis is by serological testing. Culture is generally not available in diagnostic lab. CFT • The most common serological assay used • “Gold standard” • Various alternative assays such as microparticle agglutination and EIAs are also available. • Raised titres are usually detected no earlier than 10–14 days after the onset of mycoplasma infection, but the insidious onset and slow progression of symptoms means that many patients admitted to hospital with mycoplasma CAP have raised titres on or shortly after admission. • Genomic detection of M pneumoniae in respiratory specimens by amplification techniques such as PCR is currently under development. TESTS FOR CHLAMYDIA SPECIES • Chlamydial antigen detection tests should be available for invasive respiratory samples from patients with severe CAP or where there is a strong suspicion of psittacosis. • The CFT remains the most suitable and practical serological assay for routine diagnosis of respiratory chlamydial infections. • There is no currently available serological test that can reliably detect infections due to C pneumoniae. Invsive methods for obtaining respiratory secretions o They are associated with morbidity o Reserve to patient who are severely ill o And in whom it is considered important to identify organism rather then rely on empirical antibiotic approch o Or in whom such approch already failed 1. Trans tracheal aspiration 2. FOB bal PSB 3. Percutaneous ultra thin needle lung aspiration Trans tracheal aspiration • Healthy adults have sterile tracheal specimens. • Was regarded gold standard. • Invasive procedure. • Cultures of secretions from the lower respiratory tract obtained by this method more accurately reflect the bacterial flora of an infection of the lower respiratory tract than expectorated sputum. • It also provides samples for anaerobic culture. • Isolated case reports have described life-threatening complications and death. • When TTA used for diagnosis, the incidance of false negative culture result in Pt. Not given previous anti biotic is about 1%. Indications TTA • No sputum or pleural fluid available for analysis. • Analysis of expectorated sputum unacceptable due to contamination. • Suspected anaerobic infection in severely ill patient. • Pneumonia not responding to therapy. Contra indications TTA (1) Inability to identify clearly the landmarks of a normal cricothyroid membrane (2) Potential disorders of bleeding, which could not be corrected before the procedure. (3) Hypoxemia that could not be improved with supplemental oxygen to an arterial oxygen pressure (PaO,) of at least 70 mm Hg. (4) Severe coughing (5) Inability of patient to cooperate Procedure • Position Supine with pillow under the shoulder. • Neck hyper extended. • Locate cricothyroid membrane. • Overlying skin sterilized & anasthesized. • 16 gauge needle with indwelling cathater inserted through skin and cricothyriod membrane. • After trachea entered the needle angled cauded and catheter advanced into trachea. • The covering needle is removed leaving catheter in place • Aspirate secretions with syringe. Assessment of possible contamination In order to help ensure that the specimen from TTA was not contaminated during procedure, 5 to 10 ml of a 0.5 percent soln of methylene blue was first nebulized into patient’s oropharynx and then swallowed. Absence of any bluish discoloration in the specimen from TTA ruled out obvious oropharyngeal contamination and also made it exceedingly unlikely that any contamination had occurred. False positive results may present in 1.chronic bronchitis 2.Bronchogenic carcinoma 3.Repeated aspirations Complications • Bleeding • Paratracheal and cutaneous infection • Subcutaneous or mediastinal emphycema • Hypoxemia • Vasovagel reactions Bronchoscpy with aspiration • Safe and can provide clues when other methods failed. • Even when picture is clouded by prior antibiotic use. • FOB picks up oropharyngeal contamination so PSB should be used. • PSB may be combined with BAL to obtain quantitative culture in order to discriminate between presence or absence of pneumonia. • Diagnostic threshold is 103 cfu/ml. • Infection with less common organism can be detected. • Anatomical defect may R/O Trans thoracic lung aspiration (TLA) • Specimen taken directly from lung paranchyma. • Can be done after X-ray, USG or CT localization • False + results are low (from skin) Contraindication • Bullous emphysema • Pulmonary hypertension • Bleeding disorder • Suspected vascular lesion • Uncontrolled coughing • Un cooperative patient Complications are more then TTA • Pneumothorax • Haemoptysis • Extension of infection • Air embolism Trans bronchial or open lung biopsy Rarely used D/D Atelectasis Bronchiectasis Chronic Bronchitis Chronic Obstructive Pulmonary Disease Foreign Body Aspiration Influenza Klebsiella Infections Lung Abscess Lung Cancer, Non-Small Cell Lung Cancer, Oat Cell (Small Cell) Mycobacterium Avium-Intracellulare Mycobacterium Kansasii Pneumococcal Infections Pneumocystis Carinii Pneumonia Pneumonia, Aspiration Pneumonia, Community-Acquired Pneumonia, Fungal Pneumonia, Viral Psittacosis Q Fever Respiratory Failure Sepsis, Bacterial Why etiology is important How to reach etiology Is the etiology different in specific population groups? THE ELDERLY • Most pathogens: frequency is same in young and elderly • Atypical pathogen: M pneumoniae and legionella infection are less frequent in elderly. • Gram-negative enteric bacilli were no more common in elderly patients. PATIENTS WITH COPD H influenzae and M catarrhalis may be more frequent. PATIENTS WITH DIABETES: may be more frequent are Bacteraemic pneumococcal pneumonia NURSING HOME RESIDENTS Aspiration Gram-negative enteric bacilli Anaerobes May occur more frequently than in matched elderly patients ALCOHOLIC PATIENTS: may be more frequent are. • Aspiration • Pneumococcal infection overall • Bacteraemic pneumococcal infection • Gram-negative enteric bacilli. • Legionella • Atypical pathogens • C pneumoniae • Anaerobes • Mixed infections PATIENTS ON ORAL STEROIDS Legionella species may be more frequent. ASPIRATION PNEUMONIA: may be more common • Anaerobic bacteria • Gram-negative enteric bacilli The frequency of radiographic deterioration after hospital admission and the rates of resolution of radiographic shadowing differed according to the underlying aetiolo • S aureus pneumonia is observed in those who abuse intravenous drugs. S aureus generally occurs in hospitalized patients and patients with prosthetic devices; it spreads hematogenously to the lungs from contaminated local sites. This pathogen also is an important cause of pneumonia following infection with influenza A. Treatment: Therapeutic recommendations are provided in AIDS Clinical Trials Unit, Baltimore, Maryland 21205. two categories. The first category includes the recommenda- Classification of pneumonia • Pathologists classification anatomic changes that were found in the lungs during autopsies. lobar pneumonia, Multilobar pneumonia, Interstitial pneumonia • Rradiological classification. • Microbiologic classification • Combined clinical classification : combines many factors Age Risk factors for certain microorganisms Presence of underlying lung disease Presence of underlying systemic disease Whether he or she has recently been hospitalized. Advantage of Combined clinical classification guide the selection of appropriate initial treatments even before the microbiologic cause of the pneumonia is known TYPES Community-acquired pneumonia Hospital-acquired pneumonia.
Thursday, September 17, 2009
Differentiating B/W Asthma and COPD
There is recent article from UK saying that it is really difficult for GP's to differentiate B/W two conditions. The fact is that sometimes is is really true but most of the time its quiet easy.
I am going to present a ppt regarding this. Any ideas ,suggestions,anything helpful is invited.
srssg74@gmail.com
I am going to present a ppt regarding this. Any ideas ,suggestions,anything helpful is invited.
srssg74@gmail.com
Subscribe to:
Posts (Atom)