Lower Respiratory Tract Infections:PneumoniaPharm.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

oropharyngeal contents 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

aureus and 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. aureus are 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.

CLINICAL PRESENTATION

Gram-Positive and Gram-Negative Bacterial Pneumonia

• Infection with Legionella pneumophila is 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.

• 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. pneumophila stains 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.

Gram-Positive and Gram-Negative Bacterial Pneumonia

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. pneumoniae pneumonia 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. pneumoniae can 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.

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