US Pharm. 2007;32(10):44-50.
Pneumonia is an infectious inflammation of the lung by bacteria, viruses, and other organisms. Community-acquired pneumonia (CAP) has been defined as an infection of the lungs in a patient who is not hospitalized or who has resided in a long-term care facility for 14 days prior to the onset of symptoms; this infection is associated with at least some signs and symptoms of acute infection and is accompanied by the presence of an acute infiltrate on chest radiograph.1 Despite advances in antibiotic therapy, medical techniques, and access to medical care, CAP continues to be a leading cause of morbidity and mortality in the adult population of the United States. Currently, pneumonia and influenza together are ranked as the eighth leading cause of death in the U.S.2 In 2004, a total of 59,664 Americans died of pneumonia. The highest rate of pneumonia is seen in people older than 65 years.3 Pneumonia and influenza together represented a cost to the U.S. economy in 2004 of $37.5 billion; $5.6 billion was due to indirect mortality costs and $31.9 billion was due to direct costs.4
Pneumonia guidelines have been published by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) as well as numerous other organizations. In order to reduce confusion associated with multiple sources of information, the ATS and IDSA convened a joint committee to develop a unified CAP guideline document; the new guidelines were published in early 2007.5 This review discusses how CAP occurs, which infectious bacteria cause pneumonia, how pneumonia presents, how it is diagnosed and how to treat it according to the current guidelines.
The lungs are continuously exposed to the mixture of gases, particles, and microbes that are in the air we breath.6 The lower airways, where a pneumonia will occur, are likely to remain sterile due to the normal host-defenses of the lungs. Infectious agents can gain access to the lower respiratory tract via microaspirations of oropharyngeal contents (a common occurrence in both healthy and sick people during sleep), inhalation of aerosolized material, and, less commonly, directly from the blood. Pneumonias occur when the normal host-defenses are overwhelmed, when a particularly virulent organism is present, or when a large amount of organism is there.
Common Bacterial Causes of CAP
Numerous organisms can cause CAP. The particular causative agent may change according to the site of acquisition of illness, patient comorbidities, and immune status. Table 1 lists the most common pathogens in CAP, in decreasing order of occurrence and by severity of illness as judged by site of care (ambulatory vs. hospitalized). 5 Streptococcus pneumoniae is the most likely pathogen to cause a pneumonia infection in an ambulatory patient in the community.5,7,8 Another gram-positive organism that can cause pneumonia is Staphylococcus aureus, although this bacterium is more liable to be associated with influenza outbreaks or with CAP patients requiring an ICU admission.5,7
Gram-negative bacteria, such as Haemophilus influenzae and Moraxella catarrhalis, can occur and are most likely seen in those patients who have underlying bronchopulmonary disease.5 Risks of infection from more serious gram-negative species, such as Enterobacteriaceae species and Pseudomonas aeruginosa, may occur with chronic oral steroid administration or severe underlying bronchopulmonary disease, alcoholism, and frequent antibiotic therapy.9,10 Finally, atypical organisms, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, are common causes of pneumonia, especially among outpatients and young adults.5,11
Signs and Symptoms
Patients with CAP usually present with fever and a brief history of respiratory problems such as cough, dyspnea, tachypnea, sputum production, and pleuritic chest pain. 12,13 Elderly patients may be less likely to present with standard symptoms of CAP (e.g., cough, fever) and may actually present with confusion and an altered mental status.14 Most patients with CAP will have a focal lung examination, with findings ranging from crackles to bronchial breath sounds (very loud, high-pitched sounds via stethoscope).15 Table 2 describes common signs and symptoms of CAP and the frequency with which they may occur.
Diagnosis of CAP
In addition to signs and symptoms, a definitive infiltrate on chest x-ray (or another imaging technique) is required for the diagnosis of pneumonia.5 X-ray is also necessary to allow differentiation between CAP and other causes of cough and fever.5 Supporting microbiological evidence is usually not required for the diagnosis. Extra diagnostic tests (e.g., sputum culture, blood cultures, Legionella urine antigen test, pneumococcal urine antigen test) may be completed when the result is likely to change empiric therapy, when the test is likely to have a high yield, when the patient is hospitalized, or if the patient is critically ill with CAP.5
Outpatient Versus Inpatient Treatment
Most CAP patients can be treated as outpatients.1 It is important to be certain that the decision to admit to a hospital is the best choice, since the cost of inpatient care can be up to 25 times that of an outpatient visit.16 Hospital admission can also increase the chances of the patient having thromboembolic events or being infected by more virulent organisms.17 However, certain patients may need to be admitted to a hospital due to age, comorbidities, and severity of the presenting disease. Severity of illness scores, such as the CURB-65 criteria (Confusion, Uremia, R espiratory rate, low Blood pressure, and age ?65), or prognostic models such as the Pneumonia Severity Index (PSI) can be used to help identify patients who may be better suited for outpatient therapy.5 It is important for a pharmacist to know whether a patient should be treated in the outpatient setting or admitted to a hospital, as it will determine the intensity of empiric antibiotic therapy, the amount of patient monitoring, and the necessity of completing extra diagnostic testing.
The goals of pharmacotherapy for patients with CAP are to eliminate the causative organism, resolve all clinical signs and symptoms, minimize hospitalization, and prevent reinfection. Empiric antibiotic therapy is affected by expected CAP pathogens, whether patients are admitted to a hospital or treated as outpatients, and the presence of comorbidities. Table 3 indicates empiric treatment choices for outpatients and inpatients with CAP.
For empiric therapy, regardless of
admission or comorbidities, all patients should be treated with antibiotics
that are effective against S pneumoniae and atypical pathogens.18
If patients are ambulatory but have comorbidities, or if patients are at risk
for drug-resistant S pneumoniae (DRSP), more comprehensive antibiotic
therapy is required for them as compared with patients who are healthy and
ambulatory. If patients are hospitalized, antibiotic coverage becomes even
more aggressive and is provided initially in intravenous (IV) form. As the
level of severity of CAP increases, the potency of antibiotic therapy
increases. Pharmacists can assist physicians in choosing the most appropriate
empiric therapy based on the pharmacokinetic profile, expected adverse drug
reactions, cost-effectiveness, and previous drug exposure.
Drug-Resistant S pneumoniae
Although empiric pharmacotherapy is based upon the most likely pathogens to occur in CAP, resistance patterns of pathogens to antibiotics can vary by geographic region. The appearance of DRSP isolates is a well-documented phenomenon.5 DRSP can include resistance to beta-lactams, macrolides, and fluorquinolones. The clinical significance of DRSP is not fully known.5 In many cases, increasing the dosage of certain agents (i.e., penicillins, cephalosporins, and the fluoroquinolone levofloxacin) will lead to an adequate outcome in patients with DRSP.5 Despite the positive outcome, use of these agents may not necessarily prevent the emergence of more drug resistance. Switching to a more potent agent (gemifloxacin or moxifloxacin) may provide the desired result and may lead to a stabilization or even a de crease in resistance rates.19,20
Switching from Intravenous to Oral Therapy
Patients may be switched from IV to oral therapy when they are hemodynamically stable and have improved clinically, when they are able to ingest oral medications, and when they have a normal-functioning gastrointestinal tract.5 Table 4 indicates criteria that can be used to help define clinical stability.21 Currently, the use of potent antibiotics with high bioavailability allows most patients who are able to eat and drink to switch to oral therapy. When switching to an oral antibiotic, the same agent as the IV antibiotic or an agent from the same class should be used.5 It is probably not necessary to switch to a drug from a different class primarily due to its higher bioavailability (e.g., the fluoroquinolones) in patients who are responding.5 For those on a beta-lactam/macrolide combination, changing to a macrolide alone appears to be adequate in patients who do not have DRSP or who are infected with gram-negative enteric pathogens.24
Duration of Treatment
Patients with CAP should be treated for a minimum of five days, should be afebrile for 48 to 72 hours, and should not have more than one CAP-associated criterion for clinical instability (see Table 4). Formerly, most patients with CAP were treated with seven to 10 days (or longer) of antibiotic therapy. Recent studies have indicated that five days of therapy appears to be the minimum period of time for typical CAP patients.25-27 A longer duration of therapy may be needed if initial therapy was not active against the identified pathogen or if it was complicated by extrapulmonary infections such as meningitis or endocarditis.5
Monitoring CAP Therapy
The main goal in the treatment of CAP is complete cure of the infection. A community pharmacist can assist in this outcome by monitoring for both efficacy of the medication prescribed and its particular toxicity. Most patients will become clinically stable within three to seven days of appropriate antimicrobial therapy.5 During this period, pharmacists can ask patients if symptoms are resolving. Questions include: Has fever resolved? Do you find it easier to breathe? Are you coughing less? When you cough, does less material come up? It is important for pharmacists to educate patients about expected and possible side effects, as well as drug interactions.
Prevention of CAP
CAP, whether caused by the influenza virus or by pneumococcal bacteria, can be prevented by immunization. All persons ages 50 and older, people at risk for influenza complications, and those with household contact with high-risk persons and high-risk health care workers should receive the inactivated influenza vaccine yearly.5 Pneumococcal polysaccharide vaccine is recommended for those ages 65 and older and for those with high-risk concurrent diseases.5
The Role of the Pharmacist
Pharmacists can assist in the prevention and treatment of this potentially life-threatening infectious disease. Pharmacists can help identify those patients at risk for developing CAP and can recommend immunization. When CAP occurs in a patient, a pharmacist can work with the health care team to provide the most effective therapy based on the patient's particular needs (e.g., cost considerations, underlying comorbidities, possible drug interactions, and local bacterial resistance patterns). Pharmacists can also aid in the monitoring of CAP treatment by assessing the success of therapy with respect to resolution of symptoms. Finally, effective counseling by the pharmacist can halp achieve compliance and overall clinical cure. Effective counseling allows the patient to truly understand all aspects of his or her drug therapy (e.g., side effects, time to resolution of symptoms) and thus encourages full compliance.
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