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Lower Respiratory Tract Infections: Pneumonia. Pharm.D Balsam Alhasan. PNEUMONIA.
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Lower Respiratory Tract Infections:Pneumonia Pharm.D Balsam Alhasan
PNEUMONIA • Pneumonia is the most common infectious cause of death in the United States. It occurs in persons of all ages, although the clinical manifestations are most severe in the very young, the elderly, and the chronically ill.
PATHOPHYSIOLOGY • Microorganisms gain access to the lower respiratory tract by three routes: they may be inhaled as aerosolized particles; they may enter the lung via the bloodstream from an extrapulmonary site of infection; or aspiration of oropharyngealcontents may occur.
PATHOPHYSIOLOGY • Lung infections with viruses suppress the bacterial clearing activity of the lung by impairing alveolar macrophage function and mucociliary clearance, thus setting the stage for secondary bacterial pneumonia. • The vast majority of pneumonia cases acquired in the community by otherwise healthy adults are due to S. pneumoniae(pneumococcus) (up to 75% of all acute bacterial pneumonias in the United States).
PATHOPHYSIOLOGY • Other common bacterial causes include M. pneumoniae, Legionella , and C. pneumoniae, which are referred to as “atypical” pathogens. • Community-acquired pneumonias caused by Staphylococcus aureusand gram-negative rods are observed primarily in the elderly, especially those residing in nursing homes, and in association with alcoholism and other debilitating conditions.
PATHOPHYSIOLOGY • Gram-negative aerobic bacilli and S. aureusare also the leading causative agents in hospital-acquired pneumonia. • Anaerobic bacteria are the most common etiologic agents in pneumonia that follows the gross aspiration of gastric or oropharyngeal contents.
PATHOPHYSIOLOGY • In the pediatric age group, most pneumonias are due to viruses, especially respiratory syncytial virus, parainfluenza, and adenovirus. Pneumococcus is the most common bacterial cause, followed by Group A Streptococcus and S. aureus.
Gram-Positive and Gram-Negative Bacterial Pneumonia • Infection with Legionella pneumophilais characterized by multisystem involvement, including rapidly progressive pneumonia. It has a gradual onset, with prominent constitutional symptoms such as malaise, lethargy, weakness, and anorexia occurring early in the course of the illness. A dry, nonproductive cough is initially present that over several days becomes productive of mucoid or purulent sputum.
Gram-Positive and Gram-Negative Bacterial Pneumonia • Fevers exceed 40°C (104°F) and are typically unremitting and associated with a relative bradycardia. Pleuritic chest pain and progressive dyspnea may be seen, and fine rales are found on lung examination, progressing to signs of frank consolidation later in the course of the illness.
Gram-Positive and Gram-Negative Bacterial Pneumonia • Extrapulmonary manifestations remain evident throughout the course of the illness and include diarrhea, nausea, vomiting, myalgias, and arthralgias. • Substantial changes in a patient’s mental status, often out of proportion to the degree of fever, are seen in approximately one-fourth of patients. Obtundation, hallucinations, grand mal seizures, and focal neurologic findings have also been associated with this illness.
Gram-Positive and Gram-Negative Bacterial Pneumonia • Laboratory findings include leukocytosis with predominance of mature and immature granulocytes in 50% to 75% of patients. Because L. pneumophilastains poorly with commonly used stains, routine microscopic examination of sputum is of little diagnostic value. Fluorescent antibody testing can be performed to diagnose Legionnaires’ disease.
Anaerobic Pneumonia • The course of anaerobic pneumonia is typically indolent with cough, lowgrade fever, and weight loss, although an acute presentation may occur. Putrid sputum, when present, is highly suggestive of the diagnosis. Chest radiographs reveal infiltrates typically located in dependent lung segments, and lung abscesses develop in 20% of patients 1 to 2 weeks into the course of the illness.
Mycoplasma pneumoniae • M. pneumoniaepneumonia presents with a gradual onset of fever, headache, and malaise, with the appearance 3 to 5 days after the onset of illness of a persistent, hacking cough that initially is nonproductive. Sore throat, ear pain, and rhinorrhea are often present. Lung findings are generally limited to rales and rhonchi; findings of consolidation are rarely present.
Mycoplasma pneumoniae • Nonpulmonary manifestations are extremely common and include nausea, vomiting, diarrhea, myalgias, arthralgias, polyarticular arthritis, skin rashes, myocarditis and pericarditis, hemolytic anemia, meningoencephalitis, cranial neuropathies, and Guillain-Barré syndrome. Systemic symptoms generally clear in 1 to 2 weeks, whereas respiratory symptoms may persist up to 4 weeks.
Mycoplasma pneumoniae • Radiographic findings include patchy or interstitial infiltrates, which are most commonly seen in the lower lobes. • Sputum Gram stain may reveal mononuclear or polymorphonuclear leukocytes, with no predominant organism. Although M. pneumoniaecan be cultured from respiratory secretions using specialized medium, 2 to 3 weeks may be necessary for culture identification.
Viral Pneumonia • The clinical pictures produced by respiratory viruses are sufficiently variable and overlap to such a degree that an etiologic diagnosis cannot confidently be made on clinical grounds alone. Serologic tests for virusspecific antibodies are often used in the diagnosis of viral infections.
Viral Pneumonia • The diagnostic fourfold rise in titer between acute and convalescent phase sera may require 2 to 3 weeks to develop; however, same-day diagnosis of viral infections is now possible through the use of indirect immunofluorescence tests on exfoliated cells from the respiratory tract. • Radiographic findings are nonspecific and include bronchial wall thickening and perihilar and diffuse interstitial infiltrates.
Nosocomial Pneumonia • The strongest predisposing factor for nosocomial pneumonia is mechanical ventilation. Risk is increased by prior antibiotic use, use of H2-receptor antagonists, and severe illness. • The diagnosis of nosocomial pneumonia is usually established by presence of a new infiltrate on chest radiograph, fever, worsening respiratory status, and the appearance of thick, neutrophil-laden respiratory secretions.
DESIRED OUTCOME • Eradication of the offending organism and complete clinical cure are the primary objectives. Associated morbidity should be minimized (e.g., renal, pulmonary, or hepatic dysfunction).
TREATMENT • The first priority on assessing the patient with pneumonia is to evaluate the adequacy of respiratory function and to determine whether there are signs of systemic illness, specifically dehydration or sepsis with resulting circulatory collapse.
TREATMENT • The supportive care of the patient with pneumonia includes the use of humidified oxygen for hypoxemia, fluid resuscitation, administration of bronchodilators when bronchospasm is present, and chest physiotherapy with postural drainage if there is evidence of retained secretions.
TREATMENT • Important therapeutic adjuncts include adequate hydration (by IV route if necessary), optimal nutritional support, and fever control. • The treatment of bacterial pneumonia initially involves the empiric use of a relatively broad-spectrum antibiotic (or antibiotics) effective against probable pathogens after appropriate cultures and specimens for laboratory evaluation have been obtained. Therapy should be narrowed to cover specific pathogens once the results of cultures are known.
TREATMENT • Appropriate empiric choices for the treatment of bacterial pneumonias relative to a patient’s underlying disease are shown in Table 43-6 for adults and Table 43-7 for children. Dosages for antibiotics to treat pneumonia are provided in Table 43-8.
TREATMENT • Antibiotic concentrations in respiratory secretions in excess of the pathogen minimum inhibitory concentration (MIC) are necessary for successful treatment of pulmonary infections. • For treatment of bacterial pneumonia with concentration-independent antimicrobials (e.g., β-lactams and carbapenems), a plasma drug concentration exceeding the pathogen MIC for more than 50% of the dosing interval correlates with bacteriologic cure.
TREATMENT • For concentration-dependent antimicrobials (e.g., aminoglycosides and fluoroquinolones) a peak drug concentration to pathogen MIC ratio >8 to 10 or a ratio of pathogen MIC to antibiotic area under the curve >25 to 40 for gram-positive pathogens and >100 for gram-negative pathogens correlates with bacteriologic cure.
TREATMENT • Drugs recommended for empiric treatment of community-acquired pneumonia are presented in Table 43-9. • The benefit of antibiotic aerosols or direct endotracheal instillation has not been consistently demonstrated.
Evaluation Of Therapeutic Outcomes • With community-acquired pneumonia, time for resolution of cough, sputum production, and presence of constitutional symptoms (e.g., malaise, nausea or vomiting, lethargy) should be assessed. Progress should be noted in the first 2 days, with complete resolution in 5 to 7 days. • With nosocomial pneumonia, the above parameters should be assessed along with white blood cell counts, chest radiograph, and blood gas determinations.
