Community-Acquired Pneumonia in Adults

Descriptions of pneumonia have been found as early as 350 BC and despite the medical advances that have occurred over the centuries, it continues to be a major cause of morbidity and mortality in the 21st century. In 2010, pneumonia and influenza—related deaths were ranked as the ninth-leading cause of death among all age groups in the United States, leading to approximately 50,000 deaths in 2010, and the top cause of infection-related mortality.¹ It has been estimated that the cost of community-acquired pneumonia (CAP) is more than $17 billion annually.²

There is now a better understanding of the microbiologic basis of pneumonia and how this may vary depending on the patient’s risk factors and clinical presentation. Different types of pneumonia depend on how the patient acquired the infection, but the 2 most common types are community-acquired pneumonia, which is acquired in the community setting, and nosocomial pneumonia, which includes hospital/health care/ventilator acquired pneumonia (HAP/HCAP/ VAP) and is acquired in a health care setting, such as a hospital or long-term care facility. The focus of this article will be the initial treatment of community-acquired pneumonia in immunocompentent adults.

Pathogens

There are both bacterial and viral causes of CAP. The most common cause of CAP is Streptococcus pneumonia; most often, there is no pathogen identified (Figure). Other “typical” bacterial pathogens include Haemophilus influenzae, or Moraxella catarrhalis, and the “atypical” bacterial pathogens including Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella spp.³ A thorough patient history is also useful to identify other potential bacterial pathogens depending on their individual risk factors (Table 1). Influenza is the most common viral cause of CAP, but other viruses such as respiratory syncytial virus (RSV), human metapneumovirus, parainfluenza virus, enterovirus, and coronavirus have also been implicated.⁴

Signs and symptoms of pneumonia plus radiographic evidence help solidify the diagnosis of pneumonia. The most common symptoms for CAP are a sudden onset of fever, chills, cough with mucoprurulent sputum, and pleuritic chest pain.⁵ Older patients may present more insidious symptoms with altered mentation and weakness.⁶ Signs of CAP include tachypnea, tachycardia, and an elevated white blood cell count. Evidence of infiltrates on chest radiography is required for the diagnosis of CAP.⁷

Definitive antimicrobial therapy is based on bacterial cultures; however, the use of sputum cultures in the treatment of CAP is controversial. Sputum cultures are highly prone to contamination with mouth flora. The 2007 IDSA CAP Guidelines recommend obtaining a gram stain prior to antibiotic use only if a good-quality specimen can be obtained.⁷ If the patient has risk factors for additional pathogens, then further investigation for those pathogens should be pursued. During influenza season, if signs and symptoms are consistent with influenza, testing should be performed.

Management

The initial management of CAP depends on severity of illness and comorbidities. If it is influenza season and the patient presents with signs and symptoms consistent with influenza, it is recommended to test the patient and treat accordingly. Once a diagnosis of CAP is made, the next decision is whether to treat it as an outpatient or an inpatient disease. This is an extremely important decision, as the cost of pneumonia as an inpatient is up to 25 times greater than that of outpatient care.⁸ There are 2 separate, validated severity indices that can be used to make this determination—the Pneumonia Severity Index (PSI) and the CURB-65 (confusion, uremia, respiratory rate, low blood pressure and age >65 years old) criteria (Table 2). With both systems, the higher the score, the higher the mortality, thus the need for hospitalization during treatment.

Outpatient Treatment

If the patient is otherwise healthy and has not used antimicrobials within the previous 3 months, the patient may receive an outpatient treatment of either a macrolide, such as clarithromycin or azithromycin, or doxycycline. Antimicrobial resistance should also be a consideration during antibacterial selection. Although macrolide therapy has been on the rise, β-lactam resistance is also documented with S pneumoniae. Risk factors for infection with β-lactam—resistant S pneumoniae include age <2 years or >65 years, β-lactam therapy within the previous 3 months, alcoholism, medical comorbidities, immunosuppressive illness or therapy, and exposure to a child in a daycare center.⁷ If the patient has these comorbidities, a respiratory fluoroquinolone such as moxifloxacin or levofloxacin or a β-lactam plus a macrolide should be used. For those patients with a high rate of macrolide-resistant S pneumoniae, deemed as >25%, treatment should include a respiratory fluoroquinolone or a β-lactam plus doxycycline.

Inpatient Treatment

For those patients with the higher PSI score (≥III) or CURB 65 score (≥2), it is recommended to proceed with inpatient treatment. In patients who are treated on the general medicine ward, use of a respiratory fluoroquinolone or a β-lactam plus a macrolide or doxycycline for atypical coverage may be used (Figure 2). In those who require intensive care unit management, management may vary dependent on potential risk factors in each individual patient. If a pseudomonal infection is suspected, management should include an anti-pseudomonal β-lactam plus an anti-pseudomonal fluoroquinolone, such as ciprofloxacin or levofloxacin, or an aminoglycoside. However, if pseudomonas is not a consideration, treatment is very similar to treatment in the general wards. In those patients with severe penicillin allergies, a combination of a respiratory fluoroquinolone plus aztreonam can be substituted for treatment. As stated, hospitalized patients are at the highest risk for drug resistance, including methicillin-resistant Staphylococcus aureus (MRSA). In patients that have risk factors for community-acquired MRSA pneumonia, MRSA treatment with vancomycin, ceftaroline, or linezolid should be added in addition to coverage for the other known CAP pathogens.

Treatment of Influenza

Influenza is not only the most common cause of viral pneumonia, but it is also one of the only treatable types of viral pneumonia. Prompt recognition of the signs and symptoms of influenza, in addition to seeking medical treatment, is key to initiating treatment. For outpatients, treatment with oseltamivir or zanamivir is recommended if patients present within 48 hours of symptoms. If the patient is immunocompromised, treatment may be initiated irrespective of onset of symptoms, as these patients may shed the virus for weeks.¹² Hospitalized patients should be treated with oseltamivir over zanamivir due to its potential to cause bronchospasms, which may be problematic in patients with compromised respiratory function. Specifically for H1N1 influenza, treatment with oseltamivir, especially early administration (<48 hours), was shown to decrease length of stay and need for mechanical ventilation, and showed a trend to lower mortality.¹³

Treatment Duration

Definitive antibiotics should be determined by finalized cultures if available, but most patients with CAP should be treated for a minimum of 5 days. This is dependent on the patient’s clinical status, associated extra-pulmonary infections, and the choice of antimicrobial. Short course therapy (5 days) can be achieved with either azithromycin or levofloxacin 750 mg orally once daily. Patients, irrespective of antimicrobial choice, should be treated for a minimum of 5 days, remain afebrile for at least 48 to 72 hours, and should be clinically stable prior to discontinuation of antibiotics.⁷ Transition to oral antimicrobials should occur in hospitalized patients who are clinically stable, able to tolerate oral antimicrobials, and have a normally functioning gastrointestinal tract.

Pneumonia Prevention

Despite the morbidity and mortality associated with CAP, it is a highly preventable disease with administration of appropriate vaccinations. The inactivated influenza vaccine is recommended for all persons >50 years old, those who are in close contact with high-risk individuals or at risk themselves for influenza-related complications or heath care workers. The activated intra-nasal vaccine may be used in patients 5 to 49 years of age who are immuncompetent. The pneumoccocal polysaccharide vaccine is recommended to all patients >65 years old or those with high-risk diseases such as those with pulmonary disorders.^7,12 In order to prevent future pneumonia events, these vaccinations can even be performed prior to hospital discharge in those patients who were hospitalized. Proper hand hygiene and the use of personal protective equipment are also essential elements to prevent the spread of these diseases.

Role of the Pharmacist

Pharmacists play a vital role in both the prevention of CAP with administration of vaccines and in the treatment of CAP. Hospital pharmacists may also be involved in ensuring that patients are receiving appropriate and prompt antimicrobials, optimally while still in the emergency department.

Summary

CAP is a preventable yet treatable disease. Choice of antimicrobial therapy will be determined by severity of illness as calculated by the PSI or CURB-65 score, location of treatment (inpatient vs outpatient), bacterial vs viral pathogens, and other comorbidities that may alter the choice of antimicrobial.

Leigh Anne Hylton Gravatt, PharmD, BCPS, is an assistant professor of pharmacotherapy and outcomes sciences at Virginia Commonwealth University School of Pharmacy. She also practices as an internal medicine clinical pharmacy specialist at VCUHS Medical Center.

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