Pneumonia

Bacterial Pneumonia: Practice Essentials, Background, Pathophysiology

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Practice Essentials

Bacterial pneumonia (see the image below) is caused by a pathogenic infection of the lungs and may present as a primary disease process or as the final, fatal disorder primarily in an individual who is already debilitated. The most consistent presenting symptom of bacterial pneumonia is cough productive of sputum. Antibiotic treatment is the mainstay of drug therapy for bacterial pneumonia.

Bacterial pneumonia. Radiographic images in a pati

Bacterial pneumonia. Radiographic images in a patient with right upper lobe pneumonia. Note the increased anteroposterior chest diameter, which is suggestive of chronic obstructive pulmonary disease (COPD).

Signs and symptoms of bacterial pneumonia

Cough, particularly cough productive of sputum, is the most consistent presenting symptom of bacterial pneumonia and may suggest a particular pathogen, as follows:

Streptococcus pneumoniae: Rust-colored sputum

Pseudomonas, Haemophilus, and pneumococcal species: May produce green sputum

Klebsiella species pneumonia: Red currant-jelly sputum

Anaerobic infections: Often produce foul-smelling or bad-tasting sputum

Signs of bacterial pneumonia may include the following:

Hyperthermia (fever, typically >38°C) [1] or hypothermia (< 35°C)

Tachypnea (>18 respirations/min)

Use of accessory respiratory muscles

Tachycardia (>100 bpm) or bradycardia (< 60 bpm)

Central cyanosis

Altered mental status

Physical findings may include the following:

Adventitious breath sounds, such as rales/crackles, rhonchi, or wheezes

Decreased intensity of breath sounds

Egophony

Whispering pectoriloquy

Dullness to percussion

Tracheal deviation

Lymphadenopathy

Pleural friction rub

Examination findings that may indicate a specific etiology include the following:

Bradycardia: May indicate a Legionella etiology

Periodontal disease: May suggest an anaerobic and/or polymicrobial infection

Cutaneous nodules: May suggest Nocardia infection

Decreased gag reflex: Suggests risk for aspiration

See Clinical Presentation for more detail.

Diagnosis of bacterial pneumonia

Severity assessment

Tools to assess the severity of disease and risk of death include the PSI/PORT (ie, pneumonia severity index/Patient Outcomes Research Team score), the CURB-65 (ie, confusion, urea, respiratory rate, blood pressure, and age >65 years) system, and the APACHE (ie, acute physiology and chronic health evaluation), among others.

The following laboratory tests are also useful for assessing illness severity:

Serum chemistry panel

Arterial blood gas (ABG) determination

Venous blood gas determination (central venous oxygen saturation)

Complete blood cell (CBC) count with differential

Serum free cortisol value

Serum lactate level

Sputum evaluation

Sputum Gram stain and culture should be performed before initiating antibiotic therapy. A single predominant microbe should be noted at Gram staining, although mixed flora may be observed with anaerobic infection caused by aspiration.

Imaging studies

Chest radiography: The criterion standard for establishing the diagnosis of pneumonia

Chest computed tomography scanning

Chest ultrasonography

Bronchoscopy

Lung tissue can be visually evaluated and bronchial washing specimens can be obtained with the aid of a fiberoptic bronchoscope. Protected brushings and bronchoalveolar lavage (BAL) can be performed for fluid analysis and cultures.

Thoracentesis

This is an essential procedure in patients with a parapneumonic pleural effusion. Analysis of the fluid allows differentiation between simple and complicated effusions.

Pathogen-specific tests

Urine assays

Sputum, serum, and/or urinary antigen tests

Immune serologic tests

Histologic examination

Histologic inflammatory lung changes vary according to whether the patient has lobar pneumonia, bronchopneumonia, or interstitial pneumonia. [2]

See Workup for more detail.

Management of bacterial pneumonia

The mainstay of drug therapy for bacterial pneumonia is antibiotic treatment. First-line antimicrobials for S pneumoniae, the most prevalent cause of bacterial pneumonia, are, for the penicillin-susceptible form of the bacterium, penicillin G and amoxicillin. For the penicillin-resistant form of S pneumoniae, first-line agents are chosen on the basis of sensitivity.

Supportive measures include the following:

Analgesia and antipyretics

Chest physiotherapy

Intravenous fluids (and, conversely, diuretics), if indicated

Pulse oximetry with or without cardiac monitoring, as indicated

Oxygen supplementation

Positioning of the patient to minimize aspiration risk

Respiratory therapy, including treatment with bronchodilators and N-acetylcysteine

Suctioning and bronchial hygiene

Ventilation with low tidal volumes (6 mL/kg of ideal body weight) in patients requiring mechanical ventilation secondary to bilateral pneumonia or acute respiratory distress syndrome (ARDS) [3]

Systemic support: May include proper hydration, nutrition, and mobilization

See Treatment and Medication for more detail.

Background

Pneumonia can be generally defined as an infection of the lung parenchyma, in which consolidation of the affected part and a filling of the alveolar air spaces with exudate, inflammatory cells, and fibrin is characteristic. [4] Infection by bacteria or viruses is the most common cause, although infection by other micro-orgamisms such as rickettsiae, fungi and yeasts, and mycobacteria may occur. [4] (See the images below.)

A 53-year-old patient with severe Legionella pneum

A 53-year-old patient with severe Legionella pneumonia. Chest radiograph shows dense consolidation in both lower lobes.

Bacterial pneumonia is caused by a pathogenic infection of the lungs and may present as a primary disease process or as the final coup de grace in the individual who is already debilitated. For example, a historical review of the 1918-19 influenza pandemic suggests that the majority of deaths were not a direct effect of the influenza virus, but they were from bacterial coinfection. [5]

Discussion of bacterial pneumonia involves classification and categorization schemes based on various characteristics of the illness, such as anatomic or radiologic distribution, the setting, or mechanism of acquisition, and the pathogen responsible. A major part of what distinguishes these various categories from each other is the varying risk of exposure to multidrug-resistant (MDR) organisms. [6, 7, 8, 9, 10, 11]

Anatomic or radiologic distribution of pneumonia includes the following (see Chest Radiography for details):

Lobar - Known as focal or nonsegmental pneumonia (see the images below)

Multifocal/lobular (bronchopneumonia)

Interstitial (focal diffuse)

Bacterial pneumonia. Radiographic images in a pati

The setting of pneumonia includes the community, institutional (healthcare/nursing home setting), and nosocomial (hospital).

Community-acquired pneumonia

Community-acquired pneumonia (CAP) is defined as pneumonia that develops in the outpatient setting or within 48 hours of admission to a hospital.

Go to Community-Acquired Pneumonia for complete information on this topic.

Institutional-acquired pneumonia

Institutional-acquired pneumonia (IAP) includes HCAP and nursing home–associated pneumonia (NHAP).

HCAP is defined as pneumonia that develops in the outpatient setting or within 48 hours of admission to a hospital in patients with increased risk of exposure to MDR bacteria as a cause of infection. Risk factors for exposure to MDR bacteria in HCAP include the following:

Hospitalization for two or more days in an acute care facility within 90 days of current illness

Exposure to antibiotics, chemotherapy, or wound care within 30 days of current illness

Residence in a nursing home or long-term care facility

Hemodialysis at a hospital or clinic

Home nursing care (infusion therapy, wound care)

Contact with a family member or other close person with infection due to MDR bacteria

NHAP is generally included in the category of HCAP because of the high incidence of infection with gram-negative bacilli and Staphylococcus aureus. However, some authors accept NHAP as a separate entity because of distinct epidemiologic associations with infection in nonhospital healthcare settings. [4] Pneumonia in patients in nursing homes and long-term care facilities has been associated with greater mortality than in patients with CAP. These differences may be due to factors such as disparities in functional status, likelihood of exposure to infectious agents, and variations in pathogen virulence, among others.

It is important to note that nursing home patients with pneumonia are less likely to present with classic signs and symptoms of the typical pneumonia presentation, such as fever, chills, chest pain, and productive cough, but instead these individuals often have delirium and altered mental status. [6, 7]

Go to Nursing Home Acquired Pneumonia for complete information on this topic.

The concept of HCAP (including NHAP) has been called into question in the 2016 Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) guidelines. [12] Based on a 2014 meta-analysis of 24 studies, it was found that the concept of HCAP is predominantly based on low-quality evidence confounded by publication bias and does not accurately identify multidrug-resistant organisms. After adjusting for age and comorbidities, patients within this category did not have an increased risk of mortality. [13] Based on this meta-analysis, the 2016 IDSA and ATS guidelines have called for the removal of the concept of HCAP, [12] encouraging patients previously grouped under this category to be treated as if they have CAP, with guidance of hospital-specific antibiograms and local resistance patterns.

Nosocomial pneumonia

Nosocomial infections are generally described as those acquired in the hospital setting. The term nosocomial pneumonia has evolved into the more succinct clinical entities of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). However, the term nosocomial pneumonia still has an appropriate place in the descriptive language of pneumonia. Nosocomial infections have been viewed as a "tribute to pay to the more aggressive management of the population, characterized by the use of sophisticated technologies and invasive devices," an important consideration in the pulmonary care of critically ill patients. [14]

Go to Ventilator-Associated Pneumonia and Nosocomial Pneumonia for complete information on these topics.

Hospital-acquired pneumonia

HAP is defined as pneumonia that develops at least 48 hours after admission to a hospital and is characterized by increased risk of exposure to MDR organisms, [6] as well as gram-negative organisms. [15] Risk factors for exposure to such organisms in HAP include the following [6] :

Antibiotic therapy within 90 days of the hospital-acquired infection

Current length of hospitalization of five days or more

High frequency of antibiotic resistance in the local community or within the specific hospital unit

Immunosuppressive disease or therapy

Presence of HCAP risk factors for exposure to MDR bacteria

Common mechanisms for the acquisition of pneumonia include ventilator use and aspiration.

Ventilator-associated pneumonia

VAP is defined as pneumonia that develops more than 48 hours after endotracheal intubation or within 48 hours of extubation. Risk factors for exposure to MDR bacteria that cause VAP are the same as those for HAP. [6, 8] VAP may occur in as many as 10-20% of patients who are on ventilators for more than 48 hours. [16]

Go to Ventilator-Associated Pneumonia for complete information on this topic.

Aspiration pneumonia

Aspiration pneumonia develops after the inhalation of oropharyngeal secretions and colonized organisms. Although organisms frequently implicated in CAP, such as Haemophilus influenzae and Streptococcus pneumoniae, can colonize the nasopharynx and oropharynx and their aspiration can contribute to the development of CAP, the term aspiration pneumonia refers specifically to the development of an infectious infiltrate in patients who are at increased risk of oropharyngeal aspiration.

Patients may be at increased risk of aspiration and/or the development of aspiration pneumonia for a number of reasons, as follows:

Decreased ability to clear oropharyngeal secretions - Poor cough or gag reflex, impaired swallowing mechanism (eg, dysphagia in stroke patients), impaired ciliary transport (eg, from smoking)

Increased volume of secretions

Increased bacterial burden of secretions

Presence of other comorbidities - Anatomic abnormalities, gastroesophageal reflux disease (GERD), achalasia.

Critically ill patients are at notably increased risk of aspiration due to the following:

The challenge of appropriate, risk-minimizing positioning

Gastroparesis/dysmotility

Impaired cough/gag/swallow reflexes (illness- or drug-induced)

Impaired immune response

Intubation/extubation

Historically, the bacteria implicated in aspiration pneumonia have been the anaerobic oropharyngeal colonizers such as Peptostreptococcus, Bacteroides, Fusobacterium, and Prevotella species. However, now evident is that the vast majority of cases of aspiration pneumonia result from the same pathogens implicated in CAP and HAP, depending on the setting in which the aspiration event occurred. The clinical course of aspiration pneumonia is, thus, similar to that of CAP or HAP. [17] However, recurrence of aspiration pneumonia is common unless the risk factors for underlying aspiration are treated or minimized.

Go to Aspiration Pneumonia for complete information on this topic.

Pathophysiology

The causes for the development of pneumonia are extrinsic or intrinsic, and various bacterial causes are noted. Extrinsic factors include exposure to a causative agent, exposure to pulmonary irritants, or direct pulmonary injury. Intrinsic factors are related to the host. Loss of protective upper airway reflexes allows aspiration of contents from the upper airways into the lung. Various causes for this loss include altered mental status due to intoxication and other metabolic states and neurologic causes, such as stroke and endotracheal intubation.

Bacteria from the upper airways or, less commonly, from hematogenous spread, find their way to the lung parenchyma. Once there, a combination of factors (including virulence of the infecting organism, status of the local defenses, and overall health of the patient) may lead to bacterial pneumonia. The patient may be made more susceptible to infection because of an overall impairment of the immune response (eg, human immunodeficiency virus [HIV] infection, chronic disease, advanced age) and/or dysfunction of defense mechanisms (eg, smoking, chronic obstructive pulmonary disease [COPD], tumors, inhaled toxins, aspiration). Poor dentition or chronic periodontitis is another predisposing factor.

Thus, during pulmonary infection, acute inflammation results in the migration of neutrophils out of capillaries and into the air spaces, forming a marginated pool of neutrophils that is ready to respond when needed. These neutrophils phagocytize microbes and kill them with reactive oxygen species, antimicrobial proteins, and degradative enzymes. They also extrude a chromatin meshwork containing antimicrobial proteins that trap and kill extracellular bacteria, known as neutrophil extracellular traps (NETs). Various membrane receptors and ligands are involved in the complex interaction between microbes, cells of the lung parenchyma, and immune defense cells. [18]

Bacterial virulence

General mechanisms of increased virulence include the following:

Genetic flexibility allowing the development of resistance to various classes of antibiotics

Flagellae and other bacterial appendages that facilitate spread of infection

Capsules resistant to attack by immune defense cells and that facilitate adhesion to host cells

Quorum sensing systems allow coordination of gene expression based on complex cell-signaling for adaptation to the local cellular environment

Iron scavenging

The following are examples of organism-specific virulence factors:

Streptococcus pneumoniae – Pneumolysin, a multifunctional virulence factor, is cytotoxic to respiratory epithelium and endothelium by disrupting pulmonary tissue barriers. This factor directly inhibits immune and inflammatory cells and activates complement, decreasing the clearance of the bacteria from the lung. [19]

Pseudomonas aeruginosa - Pili play important role in the attachment to host cells. A type III secretion system allows injection of toxins into host cells. [20]

Host resistance

Deficits in various host defenses and an inability to mount an appropriate acute inflammatory response can predispose patients to infection, as follows [18] :

Deficits in neutrophil quantity, as in neutropenia

Deficits in neutrophil quality, as in chronic granulomatous disease

Deficiencies of complement

Deficiencies of immunoglobulins

Viral infection

With the recent H1N1 influenza virus pandemic, it is important to address the role that viral infection can have in bacterial pneumonia.

The association between infection with influenza virus and subsequent bacterial pneumonia became particularly apparent following the 1918 influenza pandemic, during which approximately 40-50 million people died. [21] Historical investigations and current researchers argue that the vast majority of pulmonary-related deaths from past pandemic influenza viruses, most notably the pandemic of 1918, ultimately resulted from bacteriologic secondary or coinfection and poorly understood interactions between the infecting viral and bacterial organisms. [22] Although influenza virus is the most commonly thought of agent in this co-infective context, other respiratory viruses, such as respiratory syncytial virus (RSV), parainfluenza viruses, adenovirus, and rhinoviruses, may also predispose to secondary bacterial infection. [21]

The classic explanation behind the viral-bacterial interplay focuses on the disruption of the respiratory epithelium by the virus, providing an opportinistic environment for bacterial infection. However, evidence depicts much more complex and possibly synergistic interactions between viruses and bacteria, including alteration of pulmonary physiology, downregulation of the host immune defense, changes in expression of receptors to which bacteria adhere, and enhancement of the inflammatory process. [21]

Etiology of Bacterial Pneumonia

Although pneumonia may be caused by myriad pathogens, a limited number of agents are responsible for most cases, [3, 23, 24, 25] Most authors categorize bacterial pneumonias by their infectious agents, which include pneumococcal agents; Haemophilus influenzae; Klebsiella, Staphylococcus, and Legionella species; gram-negative organisms; and aspirated micro-organisms. Microaspiration of organisms that colonize the upper respiratory tract and mucosal surfaces is probably the most common mode of infection. Some agents, notably Staphylococcus species, may be spread hematogenously.

Risk factors

Coinfection with H1N1 influenza increases the risk of secondary bacterial pneumonia, with S pneumoniae the most likely coinfection. [26] However, pregnant patients with H1N1 influenza in the 2009 pandemic were at increased risk of developing secondary Klebsiella pneumonia with poor clinical outcome. [27]

Other risk factors include local lung pathologies (eg, tumors, chronic obstructive pulmonary disease [COPD], bronchiectasis), chronic gingivitis and periodontitis, and smoking which impairs resistance to infection. Furthermore, any individual with an altered sensorium (eg, seizures, alcohol or drug intoxication) or central nervous system (CNS) impairment (eg, stroke) may have a reduced gag reflex, which allows aspiration of stomach or oropharyngeal contents and contributes to the development of aspiration pneumonias.

Typical organisms

Although several of the organisms discussed in this section may be implicated in pneumonia, only a few of them are responsible for the vast majority of cases.

Gram-positive bacteria that can cause pneumonia include the following:

Streptococcus pneumoniae: This organism is a facultative anaerobe identified by its chainlike staining pattern. Pneumococcosis is by far the most common cause of typical bacterial pneumonia.

Staphylococcus aureus: S aureus is a facultative anaerobe identified by its clusterlike staining pattern. S aureus pneumonia is observed in intravenous drug abusers (IVDAs) and individuals with debilitating disorders. In patients who abuse intravenous drugs, the infection probably is spread hematogenously to the lungs from contaminated injection sites. Methicillin-resistant S aureus (MRSA) has had a large impact on empiric antibiotic choices at many institutions.

Enterococcus (E faecalis, E faecium): These organisms are group D streptococci that are well-known normal gut florae that can be identified by their pair-and-chain staining pattern. The emergence of vancomycin-resistant Enterococcus (VRE) is indicative of the importance of appropriate antibiotic use.

Actinomyces israelii: This is a beaded, filamentous anaerobic organism that grows as normal flora in the gastrointestinal (GI) tract and can colonize the oral cavity in patients with periodontal disease. A israelii is known to form abscesses and sulfur granules.

Nocardia asteroides: N asteroides is a weakly gram-positive, partially acid-fast bacillus (AFB) that forms beaded, branching, thin filaments. It is known to cause lung abscesses and cavitations. Erosion into the pleura can also occur, resulting in hematologic spread of the organism.

Gram-negative pneumonias occur most often in individuals who are debilitated, immunocompromised, or recently hospitalized. Individuals living in long-term care facilities where other residents are intubated are also at risk for these infections. Gram-negative bacteria include the following:

Pseudomonas aeruginosa: P aeruginosa is an aerobic, motile bacillus often characterized by its distinct (grapelike) odor.

Klebsiella pneumoniae: K pneumoniae is a facultatively anaerobic, encapsulated bacillus that can lead to an aggressive, necrotizing, lobar pneumonia. Patients with chronic alcoholism, diabetes, or COPD are at increased risk for infection with this organism.

Haemophilus influenzae: H influenzae is an aerobic bacillus that comes in both encapsulated and nonencapsulated forms. Several major subtypes have been identified, which have varying levels of pathogenicity. Encapsulated type B (HiB) is known to be particularly virulent, although routine vaccination against this subtype has decreased the prevalence of severe disease caused by H influenzae. Infection with this bacteria is more common in patients with COPD.

Escherichia coli: E coli is a facultatively anaerobic, motile bacillus. It is well known to colonize the lower GI tract and produce the essential vitamin K.

Moraxella catarrhalis: M catarrhalis is an aerobic diplococcus known as a common colonizer of the respiratory tract.

Acinetobacter baumannii: A baumannii is a pathogen that has been well described in the context of ventilator-associated pneumonia (VAP).

Francisella tularensis: F tularensis is the causative agent of tularemia or rabbit fever. F tularensis is a facultative intracellular bacterium that multiplies within macrophages and that is typically transmitted to humans via a tick bite. Its reservoir animals include rodents, rabbits, and hares. F tularensis can also be transmitted in an airborne manner or contracted from handling dead, infected animals. It is commonly spoken of in terms of its potential use as a biologic weapon. [28]

Bacillus anthracis: B anthracis is the agent responsible for inhalational anthrax.

Yersinia pestis: Y pestis infection is better known as the black plague. It is the most commonly accepted cause of the pandemic known as the bubonic plague. This organism can also cause the pneumonic plague. The pneumonic plague causes a lung infection by the direct inhalation of aerosolised plague bacteria or, secondary, when the organism spreads to the lungs from the bloodstream. Pneumonic plague is, therefore, not exclusively vector-borne like bubonic plague. Instead, it can be spread from person to person. Other members of the Yersinia family are responsible for a wide variety of infectious presentations.

Atypical organisms

Atypical organisms are generally associated with a milder form of pneumonia, the so-called "walking pneumonia." A feature that makes these organisms atypical is the inability to detect them on Gram stain or to cultivate them in standard bacteriologic media. [23, 3] Atypical organisms include the following:

Mycoplasma species: The mycoplasmas are the smallest known free-living organisms in existence. These organisms lack cell walls (and therefore are not apparent after Gram stain) but have protective 3-layered cell membranes.

Chlamydophila species (C psittaci, C pneumoniae): Psittacosis, also known as parrot disease or parrot fever, is caused by C psittaci and is associated with the handling of various types of birds.

Legionella species: Legionella species are gram-negative bacteria found in freshwater and are known to grow in complex water distribution systems. Institutional water contamination is frequently noted in endemic outbreaks. Legionellapneumophila is the causative agent of the majority of Legionnaires' disease. Other Legionella species are known to infect the lower respiratory system.

Coxiella burnetii:C burnetii is the causative agent of Q fever. It is spread from animals to humans; person-to-person transmission is unusual. Animal reservoirs typically include cats, sheep, and cattle.

Bordetella pertussis:B pertussis is the agent responsible for pertussis or whooping cough.

Anaerobic organisms

Pneumonia due to anaerobes typically results from aspiration of oropharyngeal contents, as previously mentioned. These infections tend to be polymicrobial and may consist of the following anaerobic species, some of which have already been discussed above: Klebsiella, Peptostreptococcus, Bacteroides, Fusobacterium, and Prevotella.

Epidemiology

In the United States, acute lower respiratory tract infections cause more disease and death than any other infection. [18] In fact, these infections also cause a greater burden of disease worldwide than human immunodeficiency virus (HIV) infection, malaria, cancer, or heart attacks. [18] The prevalence of various pathogens and epidemiology of disease vary widely between countries and regions, making precise discussion of international disease burden difficult.

More than three million cases occur annually in the United States. Pneumonia is more prevalent during the winter months and in colder climates. This condition is most likely from viral upper and lower respiratory infections, which increase in winter and result in impaired host defenses to bacterial superinfection.

Community-acquired pneumonia

The most common etiologies of community-acquired pneumonia (CAP) in the outpatient setting are as follows (in descending order of frequency): [3] S pneumoniae, M pneumoniae, H influenzae, C pneumoniae, and respiratory viruses.

The most common etiologies of CAP in the non–intensive care unit (ICU) inpatient setting, in descending order of frequency, are as follows: [3] S pneumoniae, M pneumoniae, C pneumoniae, H influenzae, Legionella species, aspiration, and respiratory viruses. Legionella pneumophila infections tend to occur sporadically and in local epidemic clusters. These infections usually arise in the summer and fall and may be found in the water condensed from air conditioning systems.

The most common etiologies of CAP in the ICU inpatient setting, in descending order of frequency, are as follows [3] : S pneumoniae, S aureus, Legionella species, and Gram-negative bacilli.

Ventilator-associated pneumonia (VAP) notably develops in approximately 9-27% of all intubated patients and carries a mortality rate of 30-60%. [8, 29]

Race, sex, and age

Black men (26.6 deaths per 100,000 population) are more likely to die from pneumonia compared with white men (23 deaths per 100,000 population), whereas black (17.4 deaths per 100,000 population) and white women (18.2 deaths per 100,000 population) are almost equally likely to die from pneumonia. [30, 31]

The incidence of pneumonia is greater in males than in females but the total number of deaths due to pneumonia has been higher among females since the mid 1980s. However, females have age-adjusted death rates close to 30% lower than those in men, because the female population in the United States is larger than the male population. The age-adjusted death rates for females have been reported as 17.9 deaths per 100,000 population and 23.9 deaths per 100,000 population for males. [30, 31]

Advanced age increases the incidence of and the mortality from pneumonia. Comorbidity and a diminished immune response and defense against aspiration increase the risk of bacterial pneumonia. For individuals aged 65 years and older, pneumonia and influenza were the sixth leading cause of death in 2005. [30, 31] Close to 90% of deaths due to pneumonia and influenza occurred in this age group. In a 20-year US study, the average overall mortality rate in pneumococcal pneumonia with bacteremia was 20.3%. Patients older than 80 years of age had the highest mortality rate, which was 37.7%. [32]

Prognosis

Generally, the prognosis is good in otherwise healthy patients with uncomplicated pneumonia. Advanced age, aggressive organisms (eg, Klebsiella, Legionella, resistant S pneumoniae), comorbidity, respiratory failure, neutropenia, and features of sepsis, alone or in combination, increase morbidity and mortality. Left untreated, pneumonia may have an overall mortality rate of more than 30%.

Even with appropriate treatment, the risk of mortality may be high if the host is ill or infirm. The Pneumonia Severity Index (PSI) may be used as a guide to determine a patient's mortality risk, but it tends to overestimate the actual risk in many cases (see Pneumonia severity index under Risk Stratification in Clinical Presentation). Particularly virulent organisms, such as Klebsiella and Legionella species, may confer a higher mortality rate.

In a study looking at microbial etiologies of CAP, S pneumoniae was present in the highest total number of deaths. However, gram-negative enteric bacilli, Pseudomonas, Staphylococcus aureus, and mixed etiologies had the highest mortality rates in those effected. [33]

Morbidity may include destruction of lung tissue from infection with subsequent scarring. Affected areas may be incapable of gas exchange, reducing respiratory reserve. In a patient with pre-existing respiratory disease, the onset of bacterial pneumonia may result in a downward spiral of infections, further impairment of respiratory status, and repeated infections owing to reduced local and systemic immune responses. Bronchiectasis may be a sequela of bacterial pneumonia. Infections with Staphylococcus and Klebsiella organisms may result in subsequent bronchiectasis, especially if treatment is delayed.

Destroyed alveoli and small-to-medium airways may be replaced by dilated blind saccules filled with purulent material. Ongoing, chronic inflammation usually occurs in the surrounding area and may destroy local adjacent lung tissue over time. Empyema and lung abscess may occur as direct complications of bacterial pneumonia. Pneumonia has been associated with increased incidence of placental abruption in pregnant patients.

Patient Education

Patients should be encouraged to stop smoking, to avoid drinking alcohol to intoxication, and to keep their teeth in good repair. In addition, instruct patients at risk to receive appropriate influenza and pneumococcal immunizations.

Patients, particularly elderly and debilitated patients, should be instructed to seek prompt care should symptoms of dyspnea or fever and rigors develop.

For patient education information, see the Lungs Center, as well as Bacterial Pneumonia and Viral Pneumonia.

Bacterial Pneumonia Clinical Presentation: History, Physical Examination, Risk Stratification

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History

During the intake history, the patient’s potential exposures, aspiration risks, host factors, and symptoms should be reviewed.

Potential exposures

A history of various exposures, such as travel, animal, occupational, and environmental exposures, can be helpful in determining possible etiologies and the likelihood of bacterial pneumonia, as follows:

Exposure to contaminated air-conditioning or water systems – Legionella species

Exposure to overcrowded institutions (eg, jails, homeless shelters) -S pneumoniae, Mycobacteria, Mycoplasma, Chlamydophila

Exposure to various types of animals - Cats, cattle, sheep, goats (C burnetii, B anthracis [cattle hide]; turkeys, chickens, ducks, or other birds (C psittaci); rabbits, rodents (F tularensis, Y pestis)

Aspiration risks

As previously discussed, patients at increased risk of aspiration are also at increased risk of developing pneumonia secondarily. Associated factors are as follows:

Alcoholism

Altered mental status

Anatomic abnormalities, congenital or acquired

Drug use

Dysphagia

Gastroesophageal reflux disease (GERD)

Seizure disorder

Additional host factors

As always, a thorough interview and determination of past medical history is of utmost utility. Inquire about the following:

Comorbid conditions (eg, asthma, COPD, smoking, and a compromised immune system are risk factors for H influenzae infection.)

Previous surgeries

Possibility of immunosuppression

Social and sexual history

Family history

Medication history

Allergy history

Symptoms

The clinical presentation of bacterial pneumonia varies. Sudden onset of symptoms and rapid illness progression are associated with bacterial pneumonias. Chest pain, dyspnea, hemoptysis (when clearly delineated from hematemesis), decreased exercise tolerance, and abdominal pain from pleuritis are also highly indicative of a pulmonary process.

The presence of cough, particularly cough productive of sputum, is the most consistent presenting symptom. Although not diagnostic of a particular causative agent, the character of the sputum may suggest a particular pathogen, as follows:

S pneumoniae is classically associated with a cough productive of rust-colored sputum.

Pseudomonas, Haemophilus, and pneumococcal species may produce green sputum.

Klebsiella species pneumonia is classically associated with a cough productive of red currant-jelly sputum.

Anaerobic infections often produce foul-smelling or bad-tasting sputum.

Nonspecific symptoms such as fever, rigors or shaking chills, and malaise are common. For unclear reasons, the presence of rigors may suggest pneumococcal pneumonia more often than pneumonia caused by other bacterial pathogens. [34] Other nonspecific symptoms that may be seen with pneumonia include myalgias, headache, abdominal pain, nausea, vomiting, diarrhea, anorexia and weight loss, and altered sensorium. [24]

Pertussis is often characterized by its long course of symptomatic cough in adults and by the presence of a whooping sound and/or posttussive vomiting in children.

Pneumonia from H influenzae most commonly arises in the winter and early spring. This pneumonia is more often associated with hosts who are debilitated.

Patients with Legionella pneumonia often present with mental status changes or diarrhea. Patients may develop hemoptysis or pulmonary cavitations. In addition, unlike other pneumonias, more than 50% of the time Legionella pneumonia has gastrointestinal (GI) symptoms associated with it, such as anorexia, nausea, vomiting, and diarrhea. Hyponatremia is often noted.

L pneumophila seems to have 2 forms: Pontiac fever and frank Legionella pneumonia. Pontiac fever has a viruslike presentation, with malaise, fever and/or chills, myalgias, and headache. This form of Legionella pneumonia usually subsides without sequelae. However, frank Legionella pneumonia is very aggressive, with a mortality rate as high as 75% unless treatment begins rapidly. This form typically occurs in individuals who are elderly and debilitated, as well as in smokers and those with COPD, alcoholism, immunocompromise, or have experienced trauma.

Physical Examination

Physical examination findings may vary, depending on the type of organism, severity of infection, coexisting host factors, and the presence of complications. [24, 35]

Signs of bacterial pneumonia may include the following:

Hyperthermia (fever, typically >38°C) [1] or hypothermia (< 35°C)

Tachypnea (>18 respirations/min)

Use of accessory respiratory muscles

Tachycardia (>100 bpm) or bradycardia (< 60 bpm)

Central cyanosis

Altered mental status

Physical findings may include the following:

Adventitious breath sounds, such as rales/crackles, rhonchi, or wheezes

Decreased intensity of breath sounds

Egophony

Whispering pectoriloquy

Dullness to percussion

Tracheal deviation

Lymphadenopathy

Pleural friction rub

Examination findings that may indicate a specific etiology for consideration are as follows:

Bradycardia may indicate a Legionella etiology.

Periodontal disease may suggest an anaerobic and/or polymicrobial infection.

Bullous myringitis may very rarely indicate Mycoplasma pneumoniae infection (largely disproven).

Physical evidence of risk for aspiration may include a decreased gag reflex.

Cutaneous nodules, especially in the setting of central nervous system (CNS) findings may suggestion Nocardia infection.

Risk Stratification

Severity-of-illness scores or prognostic models, such as the CURB-65 criteria or the Pneumonia Severity Index (PSI) can be used to help identify patients that may be candidates for outpatient treatment and those that may require admission (see below). The Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) proposed guidelines and criteria to determine the severity of community-acquired pneumonia (CAP), which would affect whether inpatient treatment would occur on the ward or require ICU care. [36] Although many of these predictive models were originally designed for assessment of CAP, a retrospective cohort study determined that they may also be applicable to HCAP. [37]

CURB-65

CURB-65 is a scoring system developed from a multivariate analysis of 1068 patients that identified various factors that appeared to play a role in patient mortality. [38] One point is given for the presence of each of the following:

C onfusion – Altered mental status

U remia – Blood urea nitrogen (BUN) level greater than 20 mg/dL

R espiratory rate –30 breaths or more per minute

B lood pressure – Systolic pressure less than 90 mm Hg or diastolic pressure less than 60 mm Hg

Age older than 65 years

Current guidelines suggest that patients may be treated in an outpatient setting or may require hospitalization according to their CURB-65 score, as follows:

Score of 0-1 – Outpatient treatment

Score of 2 – Admission to medical ward

Score of 3 or higher – Admission to intensive care unit (ICU)

The percentage of mortality at 30 days associated with the various CURB-65 scores increases with higher scores. The drastic increase in mortality between scores of 2 and 3 highlights the likely requirement for ICU admission in patients with a score of 3 or higher, as shown below:

Score of 0 – 0.7% mortality

Score of 1 – 2.1% mortality

Score of 2 – 9.2% mortality

Score of 3 – 14.5% mortality

Score of 4 – 40% mortality

Score of 5 – 57% mortality

Pneumonia severity index

The PSI, also known as the PORT score (for the study by which it was validated), is a prediction rule for mortality based on characteristics derived from cohorts of patients hospitalized with pneumonia. [39] For each of the various characteristics, a predetermined value of points is assigned. In a retrospective cohort comparison of different predictive models applied to HCAP, the PSI had the highest sensitivity in predicting mortality. However, alternative tools, including the IDSA/ATS, SCAP, and SMART-COP (mentioned below), are considered easier to calculate. [37]

Demographic factors are scored as follows:

Age, men – Starting point value is age in years

Age, women – Starting point value is age in years minus 10 points

Nursing home resident – Add 10 points

Coexisting illnesses are scored as follows:

Neoplasia – Add 30 points

Liver disease – Add 20 points

Congestive heart failure, cerebrovascular disease, renal disease – Add 10 points for each

Physical examination findings are scored as follows:

Altered mental status – Add 20 points

Respiratory rate of 30 breaths or more per minute – Add 20 points

Systolic blood pressure less than 90 mmHg – Add 20 points

Temperature less than 35°C or that is 40°C or higher – Add 15 points

Pulse greater than 125 bpm – Add 10 points

Laboratory and radiographic findings are scored as follows:

Arterial pH less than 7.35 – Add 30 points

BUN value of 30 mg/dL or greater – Add 20 points

Sodium level less than 130 mmol/L – Add 20 points

Glucose level of 250 mg/dL or greater – Add 10 points

Hematocrit value less than 30% – Add 10 points

Partial arterial pressure (PaO2) less than 60 mm Hg or peripheral oxygen saturation (SpO2) less than 90% while breathing room air – Add 10 points

Pleural effusion – Add 10 points

The combined total points make up the risk score, which stratifies patients into 5 PSI mortality risk classes, as follows:

0-50 points = Class I (0.1% mortality)

51-70 points = Class II (0.6% mortality)

71-90 points = Class III (0.9% mortality)

91-130 points = Class IV (9.3% mortality)

More than 130 points = Class V (27% mortality)

Current guidelines suggest that patients may be treated in an outpatient setting or may require hospitalization depending on their PSI risk class, as follows:

Classes I and II – Outpatient management

Class III – Admission to an observation unit or for short hospital stay

Classes IV and V – Treatment in inpatient setting

The Agency for Healthcare Research and Quality (AHRQ) has provided a PSI calculator. [40]

It is important to remember that objective criteria and scores should be used as guides only and should always be supplemented with physician determination of the patient's therapeutic needs. The risks and benefits of hospitalization should be weighed carefully, because hospitalization can put patients at additional risk (eg, thromboembolic events, nosocomial superinfection). When a pneumonia is due to mixed etiologies, it is often underestimated by severity scores. [33]

IDSA/ATS CAP criteria

Prediction rules like the CURB-65 and PSI have proven useful for standardizing clinical assessments and identifying low-risk patients who may be appropriate candidates for outpatient therapy, but they have been less useful for discriminating between moderate (ward-appropriate) and high-risk (ICU-appropriate) patients. [41]

The IDSA/ATS criteria for severe community-acquired pneumonia (CAP) are composed of both major and minor criteria. Although the major criteria indicate clear need for ICU-level care, the minor criteria for defining severe CAP have been validated for the use of differentiating between patients requiring ward-level versus ICU-level care. [41, 36, 42]

These criteria are particularly helpful in identifying those patients who are appropriate for admission to the ICU but who do not meet the major criteria of requiring mechanical ventilation or vasopressor support.

The presence of three of the following minor criteria indicates severe CAP and suggests the likely need for ICU-level care:

Respiratory rate of 30 breaths or more per minute

Ratio of PaO2 to fraction of inspired oxygen (ie, PaO2/FiO2) of 250 or less

Need for noninvasive ventilation (bilevel positive airway pressure [BiPAP] or continuous positive airway pressure [CPAP])

Multilobar infiltrates

Confusion/disorientation

Uremia (BUN 20 mg/dL or greater)

Leukopenia (white blood cell [WBC] count less than 4000 cells/µL)

Thrombocytopenia (platelet count less than 100,000/µL)

Hypothermia (core temperature less than 36°C)

Hypotension requiring aggressive fluid resuscitation

The major criteria are as follows:

Invasive mechanical ventilation

Septic shock requiring vasopressor support

Direct admission to an ICU is mandated for any patient with septic shock and a requirement for intravenous vasopressors support or with acute respiratory failure requiring intubation and mechanical ventilation.

Biological markers

Over the past 10 years, great enthusiasm has been noted regarding the potential of biological markers, such as C-reactive protein (CRP) and procalcitonin (PCT), for the diagnosis and prognostication of pneumonia. PCT appears to be promising, especially as a prognosticator. [43]

Other scoring models

Multiple other scoring models exist that can be used to aid in the prediction of mortality in severe illness (namely in the ICU setting), including the acute physiology and chronic health evaluation (APACHE II) score, [44] simplified acute physiology score (SAPS II), [45] and sepsis-related organ failure assessment (SOFA) score. [46]

Whereas most scoring models have been used for predicting outcomes in patients carrying a diagnosis of CAP, the systolic blood pressure, oxygenation, age, respiratory rate (SOAR) model has been validated for predicting 30-day mortality in patients hospitalized with nursing home-acquired pneumonia (NHAP). [47]

Still other prediction models regarding pneumonia severity and outcomes are currently being explored and developed, such as the Spanish CURXO-80 tool [48] ; predisposition, insult, response, and organ dysfunction (PIRO) tool [49] ; and systolic blood pressure, multilobar involvement, albumin level, respiratory rate, tachycardia, confusion, oxygenation and arterial pH (SMART-COP) tool.

Bacterial Pneumonia Differential Diagnoses

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Diagnostic Considerations

Remember that the most prevalent causative organism in bacterial pneumonia is pneumococcus regardless of the host. Empiric therapy must be selected with this organism in mind.

Because the episode of aspiration is usually not witnessed, the diagnosis is inferred when a patient at risk of aspiration develops evidence of a radiographic infiltrate in characteristic anatomic pulmonary locations or bronchopulmonary segments.

Always consider the possibility of Legionella infection, because delayed treatment significantly increases mortality.

Despite the frequency of pneumonia and the large body of research and literature surrounding it, controversy remains regarding certain aspects of the evaluation and management of pneumonia. Much emphasis has been placed on the utility of diagnostic testing versus the role of empiric treatment. The following three aspects of disease are important in the management of pneumonia, in which diagnostic testing can play a pivotal role:

Determining the presence of pneumonia

Assessing disease severity at the time of presentation

Identifying the causative agent

Distinguishing pneumonia from other pulmonary pathologies, such as acute COPD or asthma exacerbation, can often present a significant challenge, particularly in patients with these underlying lung diseases. C-reactive protein (CRP) and procalcitonin values may help in distinguishing infectious pneumonia from noninfectious underlying disease exacerbations. [52]

Differentiation between CAP, healthcare-associated pneumonia (HCAP), hospital-acquired pneumonia (HAP), and other pulmonary pathology at presentation is important for several reasons, but primarily because the varying pathogens implicated in each category dictate the empiric therapy likely to be most useful. [3]

In children, the following conditions should also be taken into consideration:

Bacterial Pneumonia Differential Diagnoses

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Diagnostic Considerations

Remember that the most prevalent causative organism in bacterial pneumonia is pneumococcus regardless of the host. Empiric therapy must be selected with this organism in mind.

Always consider the possibility of Legionella infection, because delayed treatment significantly increases mortality.

Determining the presence of pneumonia

Assessing disease severity at the time of presentation

Identifying the causative agent

In children, the following conditions should also be taken into consideration:

Bacterial Pneumonia Medication: Fluoroquinolones, Cephalosporins, Macrolides, Monobactams, Antibiotics, Lincosamide, Tetracyclines, Carbapenems, Oxazolidinones, Aminoglycosides, Penicillins, Amino, Penicillins, Extended-Spectrum, Penicillins, Natural, Sulfonamides, Glycopeptides, Pleuromutilin, Glucocorticoids, Vaccines

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Medication Summary

The mainstay of drug therapy for bacterial pneumonia is antibiotic treatment. The choice of agent is based on the severity of the patient's illness, host factors (eg, comorbidity, age), and the presumed causative agent. Although intravenous (IV) penicillin G is currently not favored, doses in the range of 20-24 million U/d result in serum levels that exceed minimum inhibitory concentration (MIC) levels of most resistant pneumococci.

Glucocorticoids

The role of glucocorticoids in acute bacterial pneumonia has yet to be clearly elucidated. Classic teaching warns that the use of glucocorticoids in infection may impair the immune response. However, findings demonstrate that local pulmonary inflammation may be reduced with systemic glucocorticoids. In a 2015 meta-analysis of 13 randomized controlled trials evaluating the use of systemic corticosteroids in patients hospitalized for CAP, [64] it was found with high certainty that systemic corticosteroid steroid treatment reduced the duration of hospitalization by approximately 1 day and had a 5% absolute reduction in risk for mechanical ventilation. The study also found that patients with severe pneumonia who received systemic corticosteroids had an apparent mortality benefit over patients with severe pneumonia who did not receive systemic corticosteroids, which may be related to the higher incidence of acute respiratory distress syndrome and the need for mechanical ventilation in patients with severe pneumonia. However, this evidence was rated moderate as the confidence interval crossed 1 and because of a possible subgroup effect. All patients who received corticosteroids had a higher incidence of hyperglycemia requiring treatment. Thus, in immunocompetent patients hospitalized with severe CAP, systemic corticosteroids should be considered, given the possible mortality benefit of systemic corticosteroid treatment in this subgroup of patients.

Outpatient/inpatient antibiotic administration

Outpatients are typically treated with oral antibiotics. For the most part, parenteral medications are given to patients admitted to the hospital. This rationale does not preclude the clinician from giving an initial intravenous (IV) dose of antibiotics in the emergency department and then sending the patient home on oral agents, if the patient's condition warrants this action. The patient's condition, infection severity, and microorganism susceptibility should determine the proper dose and route of administration.

A rational approach may be to administer an oral extended-spectrum macrolide or amoxicillin and clavulanate (Augmentin) to those with mild, outpatient disease. Oral fluoroquinolone may be substituted if a comorbid illness or allergy to the first-line agents is present or for good dosing compliance. Admitted patients should receive IV therapy, a third-generation cephalosporin alone or with a macrolide. An alternative regimen would be IV fluoroquinolones alone.

Pediatric antimicrobial therapy

All agents discussed in the next sections are for use in persons older than 5 years. In children younger than five years of age, initial treatment of pneumonia includes IV ampicillin or nafcillin plus gentamicin or cefotaxime (for neonates). Ceftriaxone or cefotaxime can be administered as a single agent (for >28 d to 5 y). An alternative regimen includes a penicillinase-resistant penicillin plus an antipseudomonal aminoglycoside.

Outpatient treatment of mild-to-moderate pneumonias in children usually involves agents similar to those used for acute otitis media. Most of the pneumonias in these patients probably have a viral cause. In children who have features suggesting a bacterial etiology (eg, an infiltrate on chest radiograph and/or positive findings at sputum Gram stain), the administration of antibiotics may be good clinical practice. In these cases, many clinicians begin empiric therapy with amoxicillin, but its spectrum of activity is lacking, because children in this group who do not have nonviral pneumonia usually have an infection caused by S pneumoniae and Mycoplasma species.

H influenzae type B has been less common since the introduction of the HIB vaccine. Children younger than two years may still be at risk for H influenzae type B infection, because their immune response is not sufficient, as it is in older children. A typical regimen for outpatient therapy may include a new macrolide agent or a second-generation or third-generation cephalosporin. Cost is a potential drawback for all agents.

Macrolides

The best initial antibiotic choice is thought to be a macrolide. Macrolides provide the best coverage for the most likely organisms in community-acquired bacterial pneumonia (CAP). Macrolides have effective coverage for gram-positive, Legionella, and Mycoplasma organisms. Azithromycin administered intravenously is an alternative to intravenous erythromycin.

Macrolides, as a class, have the potential disadvantage of causing gastrointestinal (GI) upset. Compared with erythromycin, newer agents have fewer GI adverse effects and drug interactions, although all macrolides have the potential for drug interactions similar to those of erythromycin. Newer macrolides offer improved compliance because of reduced dosing frequency, improved action against H influenzae, and coverage of Mycoplasma species (unlike cephalosporins). The main disadvantage is cost.

Macrolides are primarily recommended for the treatment of CAP in patients younger than 60 years of age who are nonsmokers without a comorbid illness. Give special consideration to recommendations for antibiotic use in patients with comorbid illnesses or those with CAP who are older than 60 years of age. Although patients in this group are still susceptible to S pneumoniae, they should receive treatment for broader coverage that includes Haemophilus, Moraxella, and other gram-negative organisms. Therefore, a prudent course of action for empiric outpatient therapy is to include: (1) one of the macrolide agents described previously plus a second- or third-generation cephalosporin or amoxicillin and clavulanate or (2) trimethoprim and sulfamethoxazole (TMP-SMZ) as a single agent.

Patients who have moderate clinical impairment or comorbid illnesses are best treated with parenteral agents and, unless a particular agent is strongly suspected, broad coverage should be afforded. Regimens for this use include a macrolide plus a second- or third-generation cephalosporin, (as single agents) ampicillin and sulbactam (Unasyn), piperacillin and tazobactam (Zosyn), or ticarcillin and clavulanate (Timentin).

Cephalosporins

Second-generation cephalosporins maintain the gram-positive activity of first-generation cephalosporins, provide good coverage against Proteus mirabilis, H influenzae, E coli, K pneumoniae, and Moraxella species, and provide adequate activity against gram-positive organisms.

Of these agents, cefprozil, cefpodoxime, and cefuroxime seem to have better in vitro activity against S pneumoniae. Second-generation cephalosporins are not effective against Legionella or Mycoplasma species. These drugs are generally well tolerated, but cost may be a factor. Oral second-generation and third-generation cephalosporins offer increased activity against gram-negative agents and may be effective against ampicillin-resistant S pneumoniae.

Third-generation cephalosporins have wider activity against most gram-negative bacteria (eg, Enterobacter, Citrobacter, Serratia, Neisseria, Providencia, Haemophilus species), including beta-lactamase–producing strains.

Intravenous cephalosporins may be combined with a macrolide agent. They broaden the gram-negative coverage, and in the case of third-generation agents, they may be effective against resistant S pneumoniae. In addition, some third-generation agents are effective against Pseudomonas, whereas second-generation agents are not.

Combination drugs

The combination of trimethoprim and sulfamethoxazole (TMP-SMZ) may be used in the patient with pneumonia and a history of chronic obstructive pulmonary disease (COPD) or smoking. It may be also used as a single agent in younger patients in whom a Haemophilus species is the suspected agent.

TMP-SMZ is well tolerated and inexpensive. However, allergic reactions are more often associated with drugs in this class than with other antibiotics. Reactions span the spectrum from simple rash (most likely) to Steven-Johnson syndrome and toxic epidermal necrolysis (rare). Many potential drug interactions are noted.

When a severely ill patient has features of sepsis and/or respiratory failure, and/or when neutropenia is known or suspected, treatment with an intravenous macrolide is combined with an intravenous third-generation cephalosporin and vancomycin. An alternative regimen may include imipenem, meropenem, or piperacillin and tazobactam plus a macrolide and vancomycin. A fulminant course also must raise the suspicion of infection with Legionella or Mycoplasma species, Hantavirus, psittacosis, or Q fever.

Fluoroquinolones, including levofloxacin, moxifloxacin, and gatifloxacin, may also be used. These agents are available in oral and parenteral forms and have convenient dosing regimens, which allow easier conversion to oral therapy that results in good patient compliance. Note that in July 2008, a warning was issued from the US Food and Drug Administration (FDA) regarding the risk of tendonitis and tendon rupture with fluoroquinolone use.

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