Respiratory Tract Infections - Lec. 7 PDF

Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan Respiratory Tract Infections Worldwide, an estimated 3 to 5 million children die annually as a result of acute respiratory disease. Morbidity from respiratory infections constitutes the most common issue in humans. The illn...

Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan Respiratory Tract Infections Worldwide, an estimated 3 to 5 million children die annually as a result of acute respiratory disease. Morbidity from respiratory infections constitutes the most common issue in humans. The illness types are discussed in the contexts of the sites where major clinical manifestations of involvement are expressed: upper, middle, and lower respiratory disease. Upper Respiratory Tract Infection Upper respiratory infections usually involve the nasal cavity and pharynx, and most (more than 80%) are caused by viruses. Like middle and lower respiratory illnesses, the diseases of the upper respiratory tract are named according to the anatomic sites primarily involved. Rhinitis implies inflammation of the nasal mucosa, pharyngitis denotes pharyngeal infection, and tonsillitis indicates an inflammatory involvement of the tonsils. Because of the close proximity of these structures to one another, infections may simultaneously involve two or more sites (eg, rhinopharyngitis or tonsillopharyngitis). Most upper respiratory infections are caused by viruses Clinical Features Rhinitis is the most common manifestation of the common cold. It is characterized by variable fever, inflammatory edema of the nasal mucosa, and an increase in mucous secretions. The net result is varying degrees of nasal obstruction; the nasal discharge may be clear and watery at the onset of illness, becoming thick and sometimes purulent as the infection progresses over 5 to 10 days. The common cold is characterized by rhinitis Pharyngitis and tonsillitis are associated with pharyngeal pain (sore throat) and the clinical appearance of erythema and swelling of the affected tissues. On rare occasions, the local inflammation may be sufficiently severe to produce pseudomembranes, which consist of necrotic tissue, inflammatory cells, and bacteria. This finding is particularly common in pharyngeal diphtheria, but may be mimicked by fusospirochetal infection (Vincent's angina) and sometimes by infectious mononucleosis. In acute tonsillitis or pharyngitis of any etiology, regional spread of the infecting agents with inflammation and tender swelling of the anterior cervical lymph nodes is also common. Inflammatory exudates and hemorrhages more common in bacterial infections Vesicles and ulcerated lesions more common in viral disease Pharyngeal pseudomembranes in diphtheria Oral and pharyngeal lesions accentuated in immunocompromised hosts May be portal of entry for systemic infection Page 1|9  Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan Common Etiologic Agents Table 1 lists the more common causes of upper respiratory infections and stomatitis. Viral infections predominate. The most common bacterial cause to be considered is the group A streptococcus (GAS). Corynebacterium diphtheriae, though rare in the United States, is a major pathogen that continues to cause infection in many other countries and must not be overlooked, particularly if clinical and epidemiologic findings (immunization status) suggest this possibility. Neisseria gonorrhoeae, isolated from adults with symptomatic pharyngitis in whom no other etiologic agent can be demonstrated, is now considered a pharyngeal pathogen that is usually transmitted by oral–genital contact. Occasionally, other bacteria have been implicated as causes of acute pharyngitis (eg, Corynebacterium ulcerans, Francisella tularensis, and streptococci of groups B, C, and G). These are listed here for the sake of completeness but are not routinely sought except in unusual circumstances. Viral infections predominate Streptococcus pyogenes and C diphtheriae are bacterial pathogens Gonococcal pharyngitis occurs with oral–genital contact Table 1 Major Infectious Causes of Upper Respiratory Disease DISEASE VIRUSES BACTERIA AND FUNGI Rhinitis Rhinoviruses, adenoviruses, Rare coronaviruses, parainfluenza viruses, influenza viruses, respiratory syncytial virus, some coxsackie A viruses Pharyngitis or Adenoviruses, parainfluenza Group A streptococcus, Corynebacterium tonsillitis viruses, influenza viruses, diphtheriae, Neisseria gonorrhoeae rhinoviruses, coxsackie A or B virus, herpes simplex virus, Epstein–Barr virus Peritonsillar or None Group A streptococcus (most common), retropharyngeal oral anaerobes such as Fusobacterium abscess species, Staphylococcus aureus, Haemophilus influenzae (usually in infants) In patients with purulent rhinitis, sinusitis should also be considered in the differential diagnosis. Unilateral and foul-smelling purulent discharge suggests the presence of a foreign body in the nose. ::: Sinusitis Page 2|9  Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan General Diagnostic Approaches Although viruses cause most upper respiratory infections, they are generally not amenable to specific therapy, and laboratory tests for viral infections are usually reserved for investigating outbreaks or when the illness seems unusually severe or atypical. The primary diagnostic approach in pharyngitis and tonsillitis is to determine whether there is a bacterial cause requiring specific treatment. The only reliable method is to collect a throat swab for culture, taking care to thoroughly swab the tonsillar fauces as well as the posterior pharynx, and to include any purulent material from inflamed areas. Cultures are usually made only to detect the presence or absence of GAS. Direct antigen tests for rapidly detecting the group A antigen in throat swabs have gained popularity in recent years. These tests are rapid and very specific when positive but only about 90% sensitive. This means that a positive result may be accepted without culture but negative results must be confirmed by culture before withholding treatment. Approach is to determine whether there is a bacterial etiology by culture Direct detection methods have false-negative results For the laboratory diagnosis of diphtheria or pharyngeal gonorrhea, the clinical suspicion should be indicated to the laboratory so that specific cultures for C diphtheriae or N gonorrhoeae may be made. Candida species, fusospirochetal bacteria, Pseudomonas species, and other Gram-negative organisms are often found in pharyngeal or oral specimens from healthy individuals as well as in certain infections. Their probable pathogenic significance in association with disease in these sites, largely based on the appearance of the lesions and the presence of the organisms in large numbers, can be supported by histologic demonstration of tissue invasion by the organisms. It is important to remember that other bacterial pathogens such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and even Neisseria meningitidis may be present in the pharynx. These organisms are not primary etiologic agents in rhinitis, pharyngitis, and tonsillitis, and their presence in the throat does not implicate them as causes of the illnesses; they should instead be regarded as colonizers. Evidence for pathogenic role of opportunists assessed by multiple means Pathogens may be present in normal flora but not cause pharyngitis The laboratory diagnosis of causes of peritonsillar and retropharyngeal abscesses is based on Gram staining and culture of purulent material obtained directly from the lesion, including anaerobic cultures. Page 3|9  Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan Middle Respiratory Tract Infection The middle respiratory tract is considered to comprise the epiglottis, surrounding aryepiglottic tissues, larynx, trachea, and bronchi. Inflammatory disease involving these sites may be localized (eg, laryngitis) or more widespread (eg, laryngotracheobronchitis). The majority of severe infections occur in infancy and childhood. Disease expression varies somewhat with age, partly because the diameters of the airways enlarge with maturation and because immunity to common infectious agents increases with age. For example, an adult with a viral infection of the larynx (laryngitis) who was exposed to the same virus in childhood has a relatively better immune response; in addition, the larger diameter of the larynx in the adult permits greater air flow in the presence of inflammation. An infant or child with the same infection in the same site can develop a much more severe illness, known as croup, which can lead to significant obstruction of air flow. Most severe middle tract infections occur in infancy and childhood Clinical Features Bronchitis or tracheobronchitis may be a primary manifestation of infection or a result of spread from upper respiratory tissues. It is characterized by cough, variable fever, and sputum production, which is often clear at the onset but may become purulent as the illness persists. Bronchitis involves larger airways Chronic bronchitis is a result of longstanding damage to the bronchial epithelium. A common cause is cigarette smoking, but a variety of environmental pollutants, chronic infections (eg, tuberculosis), and defects that hinder normal clearance of tracheobronchial secretions and bacteria (eg, cystic fibrosis) can be responsible. Chronic bronchitis associated with smoking, air pollution, and other diseases Nontypeable H influenzae and S pneumoniae found in exacerbations of chronic bronchitis Common Etiologic Agents With the exception of epiglottitis, acute diseases of the middle airway are usually caused by viral agents (Table 2). When acute airway obstruction is present, noninfectious possibilities, such as aspirated foreign bodies and acute laryngospasm or bronchospasm caused by anaphylaxis, must also be considered. Most subglottic middle airway infections are viral Page 4|9  Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan Table 2 Major Causes of Acute Middle Respiratory Tract Disease SYNDROME VIRUSES BACTERIA PERCENTAGE CAUSED BY VIRUSES Tracheitisa Same as for laryngitis and H influenzae, 90 croup Staphylococcus aureus Bronchitis and Parainfluenza viruses, Bordetella pertussis, H 80 bronchiolitis influenza viruses, influenzae, Mycoplasma respiratory syncytial virus, pneumoniae, Chlamydia adenoviruses, measles pneumoniae General Diagnostic Approaches When a viral etiology is sought, the usual method of obtaining a specific diagnosis is by inoculation of cell cultures with material from the nasopharynx and throat, or by PCR. Acute and convalescent sera can also be collected to determine antibody responses to the common respiratory viruses and Mycoplasma pneumoniae. In bacterial infections, the approaches noted below are valuable. Acute Bronchitis A major bacteriologic consideration in acute bronchitis, especially in infants and preschool children, is Bordetella pertussis. Deep nasopharyngeal cultures plated on the appropriate media constitute the best specimens. Examination of nasopharyngeal smears or aspirates by direct fluorescent antibody or PCR methods are also useful adjuncts to establishing the diagnosis. When purulent sputum is produced, Gram staining and culture may be useful in suggesting other bacterial causes. Exceptions include M pneumoniae and Chlamydia pneumoniae infections, which are usually diagnosed by serologic testing of acute and convalescent sera. Nasopharyngeal specimens are appropriate for diagnosis of pertussis Serodiagnosis commonly used for M pneumoniae and C pneumoniae infections Lower Respiratory Tract Infection Lower respiratory tract infection develops with invasion and disease of the lung, including the alveolar spaces and their supporting structure, the interstitium, and the terminal bronchioles. Infection Page 5|9  Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan may occur by extension of a middle respiratory tract infection, aspiration of pathogens past the upper airway defenses, or less commonly by hematogenous spread from a distant site such as an abscess or an infected heart valve. Infection can be by inhalation, aspiration, extension from middle tract, or blood-borne Infection through air passages is associated with compromised local clearance defenses Clinical Features Acute Pneumonia Acute pneumonia is an infection of the lung parenchyma that develops over hours to days and, if untreated, runs a natural course lasting days to weeks. The onset may be gradual, with malaise and slowly increasing fever, or sudden, as with the bed-shaking chill associated with the onset of pneumococcal pneumonia. The only early symptom referable to the lung may be cough, which is caused by bronchial irritation. In adults, the cough becomes productive of sputum, which is purulent material generated in the alveoli and small air passages. In some cases, the sputum may be blood- streaked, rusty in color, or foul-smelling. Sputum is purulent material generated in the bronchi and alveoli Fever, respiratory distress, and sputum production are signs of acute pneumonia Radiologic changes confirm and refine diagnosis Chronic Pneumonia Chronic pneumonia has a slow insidious onset that develops over weeks to months and may last for weeks or even years. The initial symptoms are the same as those of acute pneumonia (fever, chills, and malaise), but they develop more slowly. Cough can develop early or late in the illness. As the disease progresses, appetite and weight loss, insomnia, and night sweats are common. Cough and sputum production may be the first indication of a vague constitutional illness referable to the lung. Bloody sputum (hemoptysis), dyspnea, and chest pain appear as the disease progresses. Chronic pneumonia develops over weeks to months Abscesses and cavities may develop Chronic pneumonia may have noninfectious causes Pleural effusions may be infectious or noninfectious Empyema is a purulent infection of pleural space usually by extension of bacterial infection Lung abscess frequently follows aspiration pneumonia Blood-borne infection may cause multiple abscesses Page 6|9  Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan Common Etiologic Agents The infectious agents that most frequently cause lower respiratory infection are listed in Table 3. The cause of acute pneumonia is strongly dependent on age. More than 80% of pneumonias in infants and children are caused by viruses, whereas less than 10% to 20% of pneumonias in adults are viral. The reasons are probably the same as those indicated previously for middle respiratory tract infections. Influenza and other viruses, however, may provide the initial predisposition toward bacterial infection. Viruses are extremely rare as a cause of chronic as opposed to acute lower respiratory tract infections, although some symptoms of the acute infection, such as cough, may persist for weeks until the bronchial damage has healed. Influenza virus is noteworthy as a cause of acute life-threatening pneumonia, even in previously healthy young adults. Pneumonia caused by bacteria such as enteric Gram-negative rods, Pseudomonas, and Legionella is primarily limited to patients with serious debilitating underlying disease or as a complication of hospitalization and its procedures (nosocomial infection). At any age, the pneumococcus is the most common bacterial cause of acute pneumonia, and Gram-negative infections other than Haemophilus are rare in children unless they have cystic fibrosis or immunodeficiency. Acute and subacute pneumonia may be due to Chlamydia. C trachomatis is almost exclusively limited to infants less than 7 months of age, whereas C pneumoniae commonly affects school children and young adults, producing both bronchitis and pneumonia. Most pneumonias are viral in infants and children Viral infections predispose to acute bacterial pneumonia Gram-negative pneumonias occur in debilitated hosts Pneumoccoccus is most common cause of acute bacterial pneumonia Table 3 Major Causes of Lower Respiratory Tract Infection SYNDROME VIRUSES COMMON BACTERIA FUNGI OTHER AGENTS Acute Influenza,a Streptococcus Candida Mycoplasma pneumonia parainfluenza, pneumoniae, albicans,b pneumoniae, adenovirus, Staphylococcus aureus, Aspergillus Chlamydia respiratory syncytial Haemophilus influenzae, species trachomatis virus (infants and Enterobacteriaceae, Pneumocystisb (infants), elderly)a, Legionella, mixed Chlamydia metapneumovirus anaerobes (aspiration), pneumoniae Pseudomonas aeruginosab Chronic Rare Mycobacterium Coccidioides Paragonimus pneumonia tuberculosis, other immitis,c westermanic mycobacteria, Nocardia Blastomyces dermatitidis,c Histoplasma Page 7|9  Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan capsulatum,c Cryptococcus neoformans Lung abscess None Mixed anaerobes, Aspergillus Entamoeba Actinomyces, Nocardia, S species histolytica aureus,d Enterobacteriaceae,d P aeruginosab,d Empyema None Mixed anaerobes, S Rare aureus, S pneumoniae,d d Enterobacteriaceae, P d aeruginosa General Diagnostic Approaches The degree of difficulty in establishing an etiologic diagnosis for a lower respiratory tract infection depends on the number of organisms produced in respiratory secretions, whether the causative species is normally found in the oropharyngeal flora, and how easily it is grown. In the presence of typical clinical findings, the isolation of influenza virus from the throat or of M tuberculosis from sputum is sufficient for diagnosis of influenza or tuberculosis, because these organisms are not normally found in such sites. The same cannot be said for S pneumoniae and most bacterial pathogens, because they may be found in the throat in a significant number of healthy persons. Interpretation depends on whether agent is found in normal flora The examination of expectorated sputum has been the primary means of diagnosing the causes of bacterial pneumonia, but this approach has several advantages and disadvantages. The advantages are ease of collection and absence of risk to the patient. The primary disadvantage is the confusion that results from contamination of the sputum with oropharyngeal flora in the process of expectoration and excessive contamination with saliva. Efforts have been unsuccessful to remove saliva from sputum by washing or to accomplish interpretive differentiation of infective from normal flora by quantitative culture as with urine specimens. The quality of a sputum sample can be enhanced by collection early in the morning (just after the patient arises), careful instruction of the patient, and occasionally by the use of saline aerosols (induced sputum) under the supervision of an inhalation therapy specialist. The worst results can be expected when the physician's only involvement is writing an order, which is then passed down the ward chain of command to an orderly, who directs the patient to put his "sputum" in a cup placed at the bedside. ::: Quantitative urine culture Sputum collection has problems of quality and specificity Contamination with oropharyngeal secretions is primary problem Page 8|9  Lec. 7 Microbial Diagnosis | Dr. Ahmad Hasan Microscopic examination before culture of direct Gram smears of specimens alleged to be sputum has proved useful. Polymorphonuclear leukocytes and large numbers of a single morphologic type of organism are typical findings in sputum from patients with bacterial pneumonia. Squamous epithelial cells from the oropharynx and a mixed bacterial population are characteristic of saliva. Unfortunately, most specimens are a mixture of both, which makes interpretation more difficult. Studies have shown that more than 10 to 25 squamous epithelial cells per low-power microscopic field are evidence of excessive salivary contamination, and such specimens should not be cultured because the results may be misleading. Thus, the direct Gram smear is crucial to the use of expectorated sputum for diagnosis of acute bacterial pneumonia. The smear may be useful in the absence of cultural results, but cultures are useless without a Gram smear to assess specimen quality. Microscopic characteristics of sputum can differentiate from saliva Salivary specimens should not be cultured Page 9|9