COMMUNITY-ACQUIRED PNEUMONIA (CAP)

EPIDEMIOLOGY:

The number of annual community-acquired pneumonia (CAP) cases is difficult to estimate. One study, in which 46,237 elderly patients were monitored over a 3-year period, showed the rate of CAP among those aged 65-69 years to be 18.2 cases per 1000 person-years. Among person older than age 85 years, the rate was 52.3 cases per 1000 person-years. Estimates based on this data suggested that annually, 1 of 20 persons older than 85 years develop CAP. The investigators also estimated that approximately 915,900 cases of CAP occur among the elderly population annually in the United States.^(1-3)

A study from Pakistan reported an 11% crude mortality rate on 329 patients hospitalised with CAP.⁽⁴⁾

PATHOPHYSIOLOGY:

The lungs are constantly exposed to particulate material and microbes that are present in the upper airways and, by microaspiration, enter the lower respiratory tract. Nevertheless, the lower airways usually remain sterile because of the pulmonary defense mechanisms. These host defenses can be categorized as innate (nonspecific) or acquired (specific). The development of community-acquired pneumonia (CAP) indicates either a defect in host defenses, exposure to a particularly virulent microorganism, or an overwhelming inoculum.^(5-7)

Although microaspiration is the most common mechanism through which pathogens reach the lung, hematogenous spread from a distant infected site, direct spread from a contiguous focus, and macroaspiration are other mechanisms.

VIRULENCE FACTORS:

Some microorganisms have developed specific mechanisms to overcome pulmonary host defenses and establish infection.^(5-7) Examples include:

• Chlamydia pneumoniaeproduces a ciliostatic
• Mycoplasma pneumoniaecan shear off cilia.
• Influenza virus markedly reduces tracheal mucus velocity within hours of onset of infection and for up to 12 weeks post infection.
• pneumoniaeand Neisseria meningitidis produce proteases that can split secretory immunoglobulin (Ig) A. In addition, the pneumococcus produces other virulence factors, including the capsule that inhibits phagocytosis, pneumolysin, a thiol-activated cytolysin that interacts with cholesterol in host cell membranes, neuraminidase, and hyaluronidase.
• Mycobacteriumspp, Nocardia spp, and Legionella spp are resistant to the microbicidal activity of phagocytes.

PREDISPOSING HOST CONDITIONS:

In addition to microbial virulence factors, diseases and conditions in the host may lead to impairment of pulmonary defense and increased risk of CAP. These conditions include:⁽⁸⁾

• Alterations in the level of consciousness, which predispose to both macroaspiration of stomach contents (due to stroke, seizures, drug intoxication, anesthesia, and alcohol abuse) and to microaspiration of upper airway secretions during sleep
• Smoking tobacco
• Alcohol consumption
• Hypoxemia
• Acidosis
• Toxic inhalations
• Pulmonary edema
• Uremia
• Malnutrition
• Administration of immunosuppressive agents (solid organ or stem cell transplant recipients, or patients receiving chemotherapy)
• Mechanical obstruction of a bronchus
• Being an older adult; there is a marked increase in the rate of pneumonia in persons ≥65 years of age
• Wearing dentures while sleeping⁽⁹⁾
• Cystic fibrosis
• Bronchiectasis
• Chronic obstructive pulmonary disease
• Previous episode of pneumonia or chronic bronchitis
• Immotile cilia syndrome
• Kartagener's syndrome (ciliary dysfunction, situs inversus, sinusitis, bronchiectasis)
• Young's syndrome (azoospermia, sinusitis, pneumonia)
• Dysphagia due to esophageal lesions and motility problems

SIGN AND SYMPTOMS:

The most common symptoms of pneumonia are:

• Cough(with some pneumonias you may cough up greenish or yellow mucus, or even bloody mucus)
• Fever, which may be mild or high
• Shaking chills
• Shortness of breath(may only occur when you climb stairs or exert yourself)

Other symptoms include:

• Confusion, especially in older people
• Excess sweating and clammy skin
• Headache
• Loss of appetite, low energy, andfatigue
• Malaise(not feeling well)
• Sharp or stabbing chest pain that gets worse when you breathe deeply or cough
• White nail syndrome, or leukonychia

DIAGNOSTIC TESTS:

Radiologic evaluation:

The presence of an infiltrate on plain chest radiograph is considered the gold standard for diagnosing pneumonia when clinical and microbiologic features are supportive. A chest radiograph should be obtained in patients with suspected pneumonia when possible; a demonstrable infiltrate by chest radiograph or other imaging technique is required for the diagnosis of pneumonia, according to the 2007 consensus guidelines from the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS).⁽¹⁰⁾ Recommendations are less clear in the patient with what appears to be a viral infection with nasal congestion and cough; one approach in these cases is to obtain a chest radiograph when there is an abnormal vital sign with particular emphasis on a respiratory rate >20 breaths/minute or a fever. This recommendation is relatively insensitive in older adult patients.

Diagnostic testing for microbial etiology:

There is agreement that treatment is best when it is pathogen directed,^(10-12) but there is little consensus on the practicality of achieving this goal due to controversies in the value of diagnostic tests.

The 2007 Infectious Diseases Society of America / American Thoracic Society (IDSA/ATS) consensus guidelines⁽¹³⁾ recommend diagnostic testing for a specific organism when, based on clinical or epidemiologic data, pathogens that would not respond to usual empiric antibiotic regimens are suspected.⁽¹⁰⁾ These guidelines otherwise support the following testing strategy, based on patient characteristics and severity of illness:

• For outpatients with community-acquired pneumonia (CAP), routine diagnostic tests are optional.
• Hospitalized patients with specific indications should have blood cultures and sputum Gram stain and cultureand / or other tests. Some experts consider diagnostic tests to be optional for hospitalized patients without severe CAP.
• Patients with severe CAP requiring intensive care unit (ICU) admission should have blood cultures,Legionella and pneumococcus urinary antigen tests, and sputum culture (either expectorated or endotracheal aspirate).
• Newer tests that have been approved by the U.S Food and Drug Administration (FDA) include polymerase chain reaction (PCR) for detectingChlamydia pneumoniae and Mycoplasma pneumoniae as well as 14 respiratory tract viruses. These tests are rapid (one to two hours), sensitive, and specific.

Outpatients:

Testing for a microbial diagnosis is usually not performed in outpatients because empiric treatment is almost always successful. In one study of over 700 ambulatory patients treated for CAP, empiric antibiotics (a macrolide or fluoroquinolone in >95 percent) were almost universally effective; only 1 percent required hospitalization due to failure of the outpatient regimen.⁽¹⁴⁾

TREATMENT OPTIONS:

PHARMACOLOGICAL OPTIONS:

There is no optimal therapy for community-acquired pneumonia (CAP). Most experts feel that coverage should be divided against typical and atypical CAP pathogens.⁽¹⁵⁾ Excellent practice guidelines have been promulgated by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS). These resources provide evidence-based guidelines for the treatment of outpatients, inpatients, and ICU patients with CAP.⁽¹⁶⁾

Adequate therapy for CAP includes coverage for S pneumoniae and atypical bacterial pathogens. Treatment options for CAP in outpatients with no comorbidities and no risk factors for drug-resistant S pneumoniae include the following:⁽¹⁶⁾

• A macrolide (azithromycin, clarithromycin or erythromycin)
• Doxycycline

Treatment options in patients with comorbidities such as chronic heart, lung, liver or renal disease; diabetes mellitus; alcoholism; malignancy; asplenia; immunosuppression; prior antibiotics within 90 days; or other risk for drug resistant infection include the following:

• Respiratory fluoroquinolones (moxifloxacin, levofloxacin)
• Beta-lactam (high-dose amoxicillin 1g three times / day) or amoxicillin / clavulanate (2g twice a day), or ceftriaxone, cefpodoxime, or cefuroxime (500mg twice daily) plus a macrolide or doxycycline

In regions with high rates of macrolide-resistant S pneumoniae, consider a nonmacrolide alternative.

In hospitalized patients, therapy consists of the following:

• Beta-lactam (ceftriaxone) plus a macrolideor
• Respiratory fluoroquinolone

Recent studies have suggested that the use of a beta-lactam alone may be noninferior to a beta-lactam / macrolide combination or fluoroquinolone therapy in hospitalized patients.⁽¹⁷⁾

Therapy in ICU patients includes the following:

• Beta-lactam (ceftriaxone, cefotaxime, or ampicillin / sulbactam) plus either a macrolide or respiratory fluoroquinolone
• For patients with penicillin allergy, a respiratory fluoroquinolone and aztreonam

Patients who are severely ill or unable to tolerate or absorb oral medications require a longer duration of intravenous therapy before switching to an oral antibiotic.⁽¹⁸⁾ If Pseudomonas is suspected, an antipseudomonal beta-lactam (piperacillin / tazobactam, cefepime, imipenem, or meropenem) plus ciprofloxacin or levofloxacin is recommended. If Methicillin-resistant Staphylococcus aureus (MRSA) is suspected, vancomycin or linezolid is recommended. For patients with penicillin allergy, aztreonam is used instead of the beta-lactam in the regimen listed above.

Mild to moderately ill patients with CAP may be treated entirely via the oral route, on either an inpatient or outpatient basis. Patients receiving oral antibiotics may be admitted for hospital services (e.g. pulmonary toilet and additional diagnostic tests) that are not obtainable on an outpatient basis.

If the patient is switched to an oral regimen and is doing well, earlier discharge from the hospital is possible. The oral therapy regimen can be completed at home. Optimal intravenous-to-oral switch therapy consists of a single agent that has an appropriate spectrum, has excellent bioavailability, is well tolerated, has a low resistance potential, and is relatively inexpensive.

The duration of therapy for uncomplicated CAP is approximately 5-7 days. Patients should be afebrile 48-72 hours and have no signs of instability before antibiotic therapy is stopped. The duration of therapy may need to be longer if initial empiric therapy did not have activity against the detected pathogen. Very healthy young adults and children may be treated for shorter periods.

The use of systemic corticosteroids in patients with CAP may reduce the length of time until clinical stability, reduce hospital length of stay, reduce the need for mechanical ventilation, and reduce the incidence of adult respiratory distress syndrome (ARDS).^(19,20) Recent clinical trials have also shown a possible overall reduction in mortality, although these later results remain in doubt.^(21,22) Furthermore, there is insufficient data or agreement on the dose or duration of the steroid therapy. Adverse effects noted in the studies have included hyperglycemia.⁽¹⁹⁾ There are current ongoing double-blind, randomized, controlled clinical trials to examine the short- and long-term effects of corticosteroid use in the management of CAP.⁽²⁰⁾

CO-MORBID CONDITIONS:

Comorbid conditions do not affect the selection of antimicrobial therapy. The addition and / or change of antibiotics based on the severity of illness and / or comorbidities makes little sense. Antimicrobial therapy is directed against the pathogen rather than against the comorbid factors. Comorbidities are an important prognostic factor and contribute to the severity index.⁽²³⁾

MONOTHERAPY:

Monotherapy coverage of typical and atypical pathogens in CAP is preferred over double-drug therapy; monotherapy is less expensive than double-drug regimens, while being as effective.⁽²⁴⁾

Preferred monotherapy for CAP includes doxycycline or a respiratory quinolone. This is the most cost-effective way to optimally treat CAP. It is well-tolerated in oral and intravenous forms. It is ideal for intravenous-to-oral switch monotherapy in terms of patient compliance, safety, and cost.^{(25, 26)}

PENICILLIN-RESISTANT:

Most penicillin-resistant S pneumoniae infections may also be treated with beta-lactams. Alternately, doxycycline or respiratory quinolones may be used. Vancomycin is rarely, if ever, needed.

High-level penicillin-resistant S pneumoniae (MIC 6 µg/mL) strains are a rare cause of CAP, although they remain susceptible to ceftriaxone.

PROTON-PUMP INHIBITORS:

Avoid using proton-pump inhibitors (PPIs) in combination with respiratory quinolones for CAP drug therapy. The PPI should be discontinued or replaced with a histamine-2 (H2) blocker for the duration of therapy. However, there is conflicting evidence as to the safety of using PPIs and H2 blockers.^(27-30)

Eurich et al concluded that acid suppressants substantially increase the risk of recurrent pneumonia in high-risk elderly patients. In a cohort of elderly patients who had previously been hospitalized for pneumonia, the investigators studied PPI and H2 blocker use during 5.4 years of follow-up, matching 248 patients with recurrent pneumonia with 2476 controls.⁽²⁷⁾ Patients in the study who were currently using PPI / H2 blocker had a higher rate of recurrent pneumonia than did nonusers (12% vs 8%, respectively).

In contrast, a population-based, nested case-control study by Dublin et al concluded that PPIs and H2 blockers do not increase the risk of pneumonia in older adults.⁽²⁹⁾

OUT-PATIENT CARE IN COMMUNITY ACQUIRED PNEUMONIA:

Monitor patients with mild community-acquired pneumonia (CAP) who are being treated on an outpatient basis to ensure compliance with their medications and improvement. After 1 week, a repeat visit is advisable. If the patient is improving and parapneumonic complications are not evident, post therapy chest radiography is unnecessary.^(31-33)

Compared with H2 blockers, PPIs were associated with an increased risk of C difficile colitis.⁽³⁴⁾

GUIDELINES:

Treatment for CAP is based on guidelines from the prestigious societies such as Infectious Diseases Society of America/ American Thoracic society  of Consensus    IDSA/ ATSC.

To review the guidelines of IDSA/ ATSC, click on the below link:

http://www.thoracic.org/statements/resources/mtpi/idsaats-cap.pdf

To review guidelines by Pakistan Chest Society for the management of CAP, follow the link below:

http://www.pakistanchestsociety.pk/wp-content/uploads/79_archives.pdf

CONSULTATION AND COUNSELING:

Remind patients with community-acquired pneumonia (CAP) to comply with the medication even after they experience clinical improvement. Except in patients with heart failure, adequate hydration and preservation of the cough reflex during the convalescent period are important.

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