Community-Acquired Bacterial Pneumonia:
A Primer for Pharmacists

Release Date: July 1, 2013

Expiration Date: July 31, 2015

FACULTY:

Maisha Kelly Freeman, PharmD, MS, BCPS, FASCP
Drug Information Specialist
Associate Professor and Director
Samford University Global Drug Information Service
McWhorter School of Pharmacy
Birmingham, Alabama

FACULTY DISCLOSURE STATEMENTS:

Dr. Freeman has no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy acpe
Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
UAN: 0430-0000-13-015-H01-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

FEE INFORMATION:

Payment of $6.50 required for exam to be graded.

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

GOAL:

To provide pharmacists with the necessary information to appropriately manage adults and children with community-acquired bacterial pneumonia (CABP).

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Describe changes in the epidemiology of CABP.
  2. Characterize differences between the microorganisms responsible for CABP in adults and children.
  3. Enumerate risk factors for the development of CABP and identify diagnostic markers.
  4. Recommend the most appropriate drug regimen for a given patient with CABP and determine appropriate prevention strategies for adults and children.


ABSTRACT: Community-acquired bacterial pneumonia (CABP) is the most frequently occurring infectious disease in the United States, and it is also the sixth most common cause of death. CABP occurs most frequently in the winter and in elderly patients. Treatment and prevention strategies for CABP include antimicrobial therapy targeting the most frequently occurring causative microorganism (Streptococcus pneumoniae), as well as smoking cessation and appropriate immunizations.

Community-acquired bacterial pneumonia (CABP) is the most frequently occurring infectious disease in the United States. It is the sixth most common cause of death in the U.S. and a leading cause of death worldwide.1-3 The majority of CABP cases occur during the winter. Men have a higher rate of infection than women, and black patients are more likely than white patients to develop CABP.4

Epidemiology

By current estimates, 5 to 10 million cases of CABP are diagnosed annually, and as many as 1.1 million patients are hospitalized for it each year.3 Mortality rates are higher in patients requiring hospitalization, with a 30-day rate of up to 23%. Although new pharmacologic options are available, mortality rates have not decreased substantially since the introduction of penicillin.3,4 The majority of cases in the U.S. occur in adults aged 65 years and older, and the incidence of pneumonia is increasing, owing to the growing elderly population.4 In addition, the emergence of resistant strains of bacteria may make pneumonia more difficult to treat.5,6

Regarding pediatric CABP, the most recent evidence indicates that the rate of infection ranges from 74 to 92 per 1,000 children younger than 2 years to 33 to 52 per 1,000 children aged 3 to 6 years. The rate of hospitalization is 201.1 per 100,000, and patients younger than 1 year have the highest rate of hospitalization compared with those aged 13 to 18 years. The wide range of variability is due to differing definitions of CABP.7 Direct transmission of infected droplets due to indoor overcrowding is presumed to be the reason that this infection is most common in the winter. However, for unknown reasons, different viruses peak at different times during the respiratory virus season. CABP is more common in boys, and the male-female ratio is 1.25:1 to 2:1.

Bacteria have been isolated in 2% to 50% of patients with community-acquired pneumonia (CAP). However, the actual number of cases of bacterial origin is indeterminate because of differences in study populations that include inpatients versus outpatients with CAP. Regardless of the etiology, bacterial resistance has been identified in children with CAP. As a result, pharmacists must be able to make appropriate drug therapy recommendations.7

Pathogenesis

CAP is an acute infection of the lung parenchyma that occurs in the community setting (i.e., outside the hospital or extended-care facility) and is accompanied by symptoms of acute illness.8 Typically, microorganisms are capable of invading the respiratory tract by three routes: inhalation of aerosolized particles; hematogenous spread from the bloodstream; and aspiration of oropharyngeal contents during sleep. Frequently, the body can rid itself of aspirated microorganisms; however, if the lungs are unable to mount an appropriate defense, aspiration of potential pathogens can result in pneumonia. Certain disease states and drug products associated with CAP (e.g., altered sensorium, neuromuscular disease, antipsychotics, inhaled glucocorticoids in chronic obstructive pulmonary disease [COPD] patients) may increase the number of pathogens that enter the lower respiratory tract.1,9-11 As a result, infection is probable in the event of an overabundance of pathogens evading the host's defenses, exposure to a virulent strain of a virus, or an overwhelming inoculation of the virus particles.4

The Infectious Diseases Society of America defines CAP in children as the "presence of signs and symptoms of pneumonia in a previously healthy child caused by an infection that has been acquired outside of the hospital."12 The World Health Organization (WHO) defines CABP as cough or difficulty breathing. Also included in this definition is tachypnea, which is delineated by the child's age. In children aged 2 to 12 months, tachypnea is defined as ≥50 breaths per minute; in children aged 12 to 60 months, it is defined as ≥40 breaths per minute.12

Microbiology

The most common pathogen associated with CABP in immunocompetent adults is Streptococcus pneumoniae, which accounts for up to 75% of acute cases. Other pathogens include Mycoplasma pneumoniae, Legionella species, Chlamydophila (formerly Chlamydia) pneumoniae, Haemophilus influenzae, and viruses. Anaerobic pathogens are a common cause of aspiration pneumonia.1 Bacteria associated with CABP are categorized into two groups: typical and atypical organisms. Typical organisms include S pneumoniae, H influenzae, Staphylococcus aureus, group A streptococci, Moraxella catarrhalis, anaerobes, and aerobic gram-negative bacteria. Atypical organisms include Legionella species, M pneumoniae, C pneumoniae, and Chlamydophila psittaci.4

In children, S pneumoniae is the most common cause of CABP; however, viruses are more common in children younger than 5 years and account for 14% to 35% of pneumonia cases (up to 50% in children aged <5 years). M pneumoniae and Chlamydophila organisms are more common in children older than 5 years.13

Other bacterial causes of pneumonia in preschool children include H influenzae type b (Hib), nontypeable H influenzae, M catarrhalis, S aureus, Streptococcus pyogenes, and atypical bacteria. Hib rarely causes pneumonia, since most children receive Hib immunization. Community-acquired methicillin-resistant S aureus (CA-MRSA) and S pyogenes are becoming more frequent causes of pneumonia, and CABP due to these causes is typically diagnosed in children following infection with influenza or chickenpox.13

Risk Factors

Risk factors that predispose patients to CABP include advanced age (>65 years); diabetes mellitus (DM); COPD; HIV; lung cancer; malnutrition; viral respiratory infection; receipt of immunosuppressive agents (e.g., chemotherapy, solid-organ or stem-cell trans plantation); asplenia; chronic cardiovascular, pulmonary, renal, and/or liver disease; and smoking and/or alcohol abuse.1,4 Risk factors in children include cystic fibrosis; malnutrition; sickle cell anemia; HIV; structural lung disease; travel to an endemic area; prematurity; low socioeconomic status; exposure to tobacco smoke; and day care attendance.12,14

Clinical Presentation and Diagnostic Considerations

Clinical Presentation in Adults: The diagnosis of CABP is dependent upon chest radiography with or without microbiological testing. Patients commonly present with cough, fever, chest pain, dyspnea, and sputum production. Patients may also experience gastrointestinal (GI) symptoms (nausea, vomiting, diarrhea) and changes in cognitive status (e.g., mental-status changes). Although most patients are febrile upon presentation, this clinical feature may be absent in older patients. Increased respiration occurs in more than 50% of patients and is most common in elderly patients. Many patients experience tachycardia.8

Radiologic findings are typically associated with infiltrates upon chest radiography, which is commonly performed for diagnosis when other signs and symptoms (e.g., clinical, microbiological) are indicative of pneumonia.8 Chest radiographs may also reflect patchy consolidation or diffuse alveolar patterns.1

Sputum examination and cultures also may be useful in the diagnosis of pneumonia. Blood cultures may be helpful for identifying the offending organism, but they may be positive in only a small number of patients. In these patients, the blood culture may reveal leukocytosis with an abundance of polymorphonuclear cells. In addition, S pneumoniae may produce an elevated WBC count.1 Hypoxia may be present. Patients may have abrupt onset of fever, chills, dyspnea, productive cough, rust-colored sputum, tachypnea, chest-wall restrictions, and diminished breath sounds in the affected area.1

Criteria for Hospital Admission in Adults: Rates of hospital admission for adults with CABP are variable, presumably because of inconsistent use of practice guidelines on illness severity. Evidence shows that clinicians overestimate short-term mortality risks, resulting in unnecessary hospital admissions. Several studies have been conducted to determine predictors of severity in patients with CABP. One predictor is the Pneumonia Severity Index (PSI), which has been validated in several studies. The PSI identifies low-risk patients based on 11 demographic conditions, comorbid conditions, and physical findings: age older than 50 years; presence of neoplastic disease, heart failure, cerebrovascular disease, or kidney or liver disease; altered mental status; pulse ≥125 beats per minute; respiratory rate ≥30 breaths per minute; systolic blood pressure (BP) <90 mmHg; or temperature <35°C or ≥40°C. If patients have one or more step 1 risk factors, the evaluation progresses to step 2 (TABLE 1).15


tbl1

In step 2, patients are stratified into risk classes II, III, IV, or V based on the total number of points assigned to risk factors. Patients with scores ≤70 are designated as class II (mortality rate 0.6%); 71 to 90, class III (rate 0.9%); 91 to 130, class IV (rate 9.3%); and >130, class V (rate 27%).15

Because of the PSI's limitations and length, additional severity scales have been developed. One such scale is CURB-65, which is based upon five factors: confusion (according to a specific mental test or new disorientation to person, place, or time); urea (blood urea nitrogen) >7 mmol/L (20 mg/dL); respiratory rate ≥30 breaths per minute; BP (systolic <90 mmHg or diastolic ≤60 mmHg); and age ≥65 years. Thirty-day mortality rates in CABP patients according to CURB score were 0.7%, 2.1%, 9.2%, 14.5%, and 40% for 0, 1, 2, 3, and 4 risk factors, respectively. Typically, patients with a score of 0 or 1 can be treated as outpatients, patients with a score of 2 should be admitted to the hospital, and those with a score of 3 or higher should be evaluated for ICU admission.15

Another scoring tool, SMART-COP, was designed to determine which patients require ICU admission. This scoring system was a better determinant than CURB-65 of which patients required mechanical ventilation and inotropic support. However, the sensitivity of the SMART-COP was reduced in patients aged under 50 years, and caution is warranted in using this scoring system in this subset.15

Clinical Presentation in Children: Children with CABP typically present with fever, tachypnea, labored breathing, rhonchi, crackles, and wheezing.14 However, the clinical presentation depends upon the child's age. Clinical evidence indicates that more than one-fifth of children diagnosed with pneumonia (as defined by the WHO) had normal breath sounds upon admission. A respiratory rate <40 breaths per minute was observed in 55% of children older than 35 months who had a CABP diagnosis. Depending upon the severity of symptoms, hospitalization may be warranted. In addition, the clinical signs and symptoms consistent with pneumonia often do not differ between viral, bacterial, and atypical pneumonias.12

The most significant clinical sign in children is tachypnea. Accordingly, the WHO recognizes tachypnea combined with cough as a diagnostic criterion for pneumonia in countries where chest radiography is unavailable. Chest x-rays are most useful when the diagnosis is indeterminate or physical findings are inconsistent. However, radiologic findings consistent with CABP may be absent in some patients with CABP. Several other markers for CABP have been used to assist in CABP diagnosis, including C-reactive protein, procalcitonin level, WBC count, and erythrocyte sedimentation rate.12,14 Sputum and blood cultures are of limited utility because of the difficulty in obtaining a specimen and the lack of pathogen identification, respectively.14

Criteria for Hospital Admission in Children: In the year 2000, 7.8% of hospitalizations were associated with pneumonia in children.16 On average, children are hospitalized for 3 days after presentation. Several monitoring parameters should be assessed to determine the severity of pneumonia in children who present to the hospital.14 The criteria for hospital admission of children for CABP are similar to those for adults (other than age) and include age younger than 3 to 6 months, suspected CABP caused by MRSA, respiratory rate >70 breaths per minute, poor feeding, and comorbidities (e.g., chronic lung disease, asthma, unrepaired or incompletely repaired congenital heart disease, DM, neuromuscular disease). Children who experience severe respiratory distress; sustained tachycardia; need for pharmacologic support of BP; or perfusion, exhaustion, apnea, slow breathing, or altered mental status should be transferred to intensive care.12

Treatment Regimens

Outpatient and Inpatient Regimens in Adults: Treatment options for outpatients with CABP are based on studies evaluating the efficacy of antimicrobials, illness severity, presence of other disease states, and prevalence of risk factors for drug-resistant S pneumoniae. Risk factors for drug-resistant S pneumoniae in adults include age greater than 65 years; beta-lactam, macrolide, or fluoroquinolone therapy within the past 3 to 6 months; alcoholism; medical comorbidities; immunosuppressive illness or therapy; and exposure to a child attending day care.17,18 In the absence of comorbidities, recent antibiotic use, and risk factors for drug-resistant pathogens, patients should be initiated on empiric therapy with a macrolide antibiotic. See TABLES 2 and 3 for empiric treatment options and TABLE 4 for antibiotic dosing.


tbl2


tbl3


tbl4

Fluoroquinolone use is discouraged in outpatients without comorbid conditions or recent antimicrobial use who require treatment for CABP, unless there is a high prevalence of macrolide resistance in the community. If comorbidities are present (e.g., COPD, liver or kidney disease) and/or recent antibiotic use has been identified, the patient should be initiated on a respiratory fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin) for at least 5 days. In addition, concomitant beta-lactam therapy plus a macrolide or tetracycline is recommended. This regimen is also appropriate if there is a high level of macrolide resistance in the community. Therapy should be directed at the appropriate pathogen once it is identified.17

Outpatient therapy should continue for a minimum of 5 days; however, a shorter duration of therapy may be warranted for azithromycin. Antibiotic therapy should be continued until the patient has been afebrile for 48 to 72 hours. The patient may experience symptom improvement shortly after treatment is initiated; however, some patients experience symptoms up to 30 days after presentation. Follow-up chest x-ray may be warranted in patients older than 40 years, in cases requiring confirmation of symptom resolution, and when underlying conditions (e.g., malignancy) must be ruled out.3,17

As with outpatient therapy, empiric therapy for inpatient CABP is based on the most likely pathogen in the community, risk factors for antimicrobial resistance, and concomitant illnesses. Patients on general medicine wards should receive an antipneumococcal fluoroquinolone or combination therapy with a beta-lactam plus a macrolide. Patients with severe CABP requiring ICU admission should receive a beta-lactam plus either IV azithromycin or an antipneumococcal fluoroquinolone, unless MRSA or Pseudomonas infection is suspected. If the presence of MRSA or Pseudomonas is suspected, an antipseudomonal beta-lactam plus an antipseudomonal fluoroquinolone should be administered. If a patient has MRSA, vancomycin or linezolid should be added.

Inpatients are typically initiated on IV therapy and should be converted to oral therapy when feasible (e.g., clinical improvement, functioning GI tract, and hemodynamic stability). Therapy should continue for a minimum of 5 days, and extended therapy may be needed in the following cases: inappropriate empiric therapy was initiated; extrapulmonary infection is identified; the causative agent is Pseudomonas aeruginosa, S aureus, Legionella, or some unusual and less common pathogen; or necrotizing pneumonia, empyema, or lung abscess is present.3,18

Outpatient and Inpatient Regimens in Children: Outpatients with CABP should receive amoxicillin initially; alternatives include azithromycin and amoxicillin-clavulanate. Inpatients with CABP should receive ampicillin or penicillin G; alternatives include azithromycin, ceftriaxone, and cefotaxime. Inpatients who are not fully immunized for Hib and S pneumoniae should receive ceftriaxone or cefotaxime. If CAMRSA is suspected, vancomycin or clindamycin may be added. Treatment durations of up to 10 days have been evaluated; however, a shorter duration may be warranted unless the patient has an infection caused by certain pathogens (S aureus). As with adults, treatment response in children should be measured within 48 to 72 hours after antimicrobial initiation.7

OTC Agents in Acute CABP (Children and Adults): Although OTC agents have been used to manage the cough associated with pneumonia, there is no compelling clinical evidence that they are beneficial in children or adults with cough due to acute CABP. Mucolytics have yielded improvements in clinical symptoms, but because of insufficient evidence, these agents cannot be recommended at present.19

Prevention

Strategies for Adults: Patients should be immunized against influenza and pneumococcal infection. Influenza vaccination should especially be encouraged from October through March. Patients aged 65 years and older who have comorbid conditions or a positive smoking status should be screened for pneumococcal vaccination. In addition, smoking cessation is a particularly important goal for patients who smoke.17

Strategies for Children: Several strategies may be used to prevent CABP in children. Washing the hands frequently, breastfeeding for at least 6 months, reducing transmission through other children, avoiding secondhand tobacco smoke, and receiving immunizations have all been shown to lower the risk of CABP transmission.14

According to practice guidelines, children should be vaccinated against pathogens, including S pneumoniae, Hib, and pertussis. Children aged 6 months and older should be immunized against influenza annually. Caregivers of children aged 6 months and younger also should be vaccinated against influenza and pertussis to protect infants from exposure. Currently, the 13-valent pneumococcal conjugate vaccine (PCV) contains antigen for seven serotypes in the PCV7 vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and for six other serotypes (1, 3, 5, 6A, 7F, and 19A). This vaccine is expected to reduce pneumonia complications in children. Influenza vaccines are recommended because influenza is associated with CABP. Influenza prophylaxis has been shown to prevent influenza-associated pneumonia hospitalization (87%) and reduce complications associated with CA-MRSA pneumonia and complicated pneumonia.3,20-22

Conclusion

CABP is associated with significant morbidity and, in some cases, mortality. Bacterial resistance has made the organisms that cause CABP more difficult to treat. S pneumoniae is the most frequent cause of CABP. Appropriate empiric therapy is critical to effective eradication of CABP. In addition, pathogen-directed therapy may be associated with positive outcomes. Strategies such as smoking cessation and immunization against influenza, pneumococcus, S pneumoniae, Hib, and pertussis organisms have all been demonstrated to be effective in reducing CABP infections in children and/or adults. Pharmacists need to be knowledgeable about the treatment recommendations for CABP.

REFERENCES

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