Pathophysiology Most of the infectious agents that cause CAP are aspirated into the lung.

This is especially the case for vulnerable individuals with an impaired immune system. [15] [16] [17] [18] CAP that results from aspiration of oropharyngeal contents is the only form of CAP with multiple pathogens. Among older patients, microaspiration of oropharyngeal secretions is common, and is more prevalent among patients with comorbidities and those taking medications that cause sedation. [15] [16] [17] [18] An infection usually occurs when one component of the defence mechanism is not functioning properly. This results in microbial colonisation of the upper respiratory tract. Microbes can enter and invade the lower respiratory tract by many methods, and 6 mechanisms have been identified in the pathogenesis of pneumonia in immunocompetent adults:

Inhalation of infectious particles Aspiration of oropharyngeal or gastric contents Haematogenous deposition of bacteria in the lung Invasion from infection in contiguous structures Direct inoculation Reactivation.

Certain pre-existing conditions such as cystic fibrosis, COPD, corticosteroid use, immunodeficiency, stroke, drug and alcohol use, and pulmonary oedema can hinder the ability of the host defence system to expel the possible pathogens that can predispose an individual to acquiring CAP. [18] Bacterial pathogenesis depends on the virulence and number of organisms aspirated. [15][16] [17] [18] For encapsulated organisms, such as S pneumoniae, the presence of different capsular polysaccharides, which prevent the host serum bactericidal activity (antibodies and complement), and opsonic activity of polymorphonuclear leukocytes and macrophages may contribute to the pathogenesis and poor outcomes. [18] Once CAP is established, host humoral and cellular responses and early appropriate antimicrobial therapy are critical for containing the infection, preventing complications, and improving outcome. Unfortunately, the rapid

emergence of antibiotic resistance and immune deficiency has complicated treatment decisions. [18]

Shortcuts: 1. Pathogenesis 2. Etiology 3. Clinical Features 4. Radiographic Patterns 5. Diagnosis 6. Management and Treatment
7. Prevention

Pneumonia is an infectious disease characterized by inflammatory processes affecting the lung parenchyma. It is responsible for 10% of adult admissions to North American medical services. It is a potentiallly lethal disease that is treatable therefore it is important that every medical student, resident, and physician be able to recognize, diagnose, and treat pneumonia rapidly and adequately. Careful history and physical exam and especially important in leading to rapid diagnosis. The causes of pneumonia are numerous therefore it is almost always essential to identify the specific microorganism responsible in order to provide effective treatment. Pneumonia may be classified in different ways: etiological agent (bacterial vs. viral vs. mycoplasmal), anatomically (lobular bronchopneumonia, lobar, interstitial), clinical presentation (classical vs. atypical). These classifications will be discussed later. A. Pathogenesis Every day, our lungs are exposed to over 10 000 L of air containing many potentially disease causing agents. However, the normal lung does not contain any bacteria because of different effective defense mechanisms that clear or destroy bacteria: a. nasal clearance: eg sneezing, blowing nose b. tracheobronchial clearance: mucociliary action clears particles deposited on the mucus film. Particles are moved from the lung to the oropharynx where they are either swallowed or expectorated. c. alveolar clearance: Alveolar macrophages phagocytose particles deposited in the alveoli. Digested particles are contained in the macrophages

which are moved to ciliated bronchioles and then to the oropharynx. Sometimes these defenses may be impaired, as occurs in chronic diseases, immunodeficiency, immunosuppressive treatments, leukopenia, very virulent organisms. Mechanisms of Lung Defense Impairment: a. loss or decreased cough reflex leading to aspiration of gastric contents b. impaired or destroyed mucociliary transport: eg cigarette smoking, inhalation of corrosive gases c. impaired phagocytic or bactericidal action of alveolar macrophages: eg cigarette smoke, anoxia d. pulmonary congestion/edema e. increased production of pulmonary secretions: eg cystic fibrosis When lung defenses are impaired, microorganisms may enter the respiratory tract via different routes of spread: a. hematogenous b. from a contiguous focus c. inhalation of aerosolized particles d. aspiration of oropharyngeal secretions (most common) B. Etiology Classical community acquired pneumonia is most frequently caused by S. pneumoniae. However, H. influenzae and M. tuberculosis become more frequent in older age groups. Gram negative bacilli are also sometime responsible for causing pneumonia. Atypical pneumonia is usually caused by M. pneumoniae, C. pneumoniae, and numerous viruses (incl. adenovirus, parainfluenza virus, respiratory syncytial virus). [Table modified from Cecil Essentials of Medicine, 4th ed.] Pathogens Causing Pneumonia According to Population Population Pathogens children and S. pneumoniae, M. pneumoniae, C. younger adults pneumonia, RSV elderly adults S. pneumoniae, influenza virus, M. tubuerculosis chronically ill S. pneumoniae, influeza virus, oropharyngeal flora, M. tuberculosis, Gram neg. bacilli

hospitalized

oropharyngeal flora, S. aureus, Gram neg. bacilli, L. pneumophila

C. Clinical Features Clinical features of pneumonia vary greatly according to etiologic agent responsible and population affected. Most patients have a cough, fever, increased heart rate, and increased respiration rate. Patients may also experience pleuritic pain, hemoptysis, systemic upset, and confusion. Classical community acquired pneumonia presents with abrupt onset of single shaking chill, cough, rust-coloured sputum, and moderate fever. Atypical community acquired pneumonia has a less severe course with more prominent systemic symptoms and less prominent respiratory symptoms. Patients may only present with tachypnea, dry cough, and mild fever. D. Radiographic Patterns Chest radiographs can rule out the possibility of pneumonia or help differentiate between bacterial and viral pneumonias. Or, they may point to a diagnosis of presumptive pneumonia when the patient presents with only mild symptoms, eg in the elderly. The pattern of the chest radiograph gives clues to the etiology of pneumonia. Lobar consolidation suggests a bacterial pathogen whereas patchy, bilateral infiltrates with little or no pleural effusion are usually seen in atypical pneumonias. Large pleural effusions may point to streptococcal pneumonia or tuberculosis. Cavitations indicates a necrotizing pneumonia, such as that caused by tuberculosis or S. aureus. It is important to remember that early in the course of acute bacterial pneumonias, the chest radiographs may yield little information as they often appear normal initially. Therefore it is important to conduct other laboratory tests, as will be discussed later. E. Diagnosis The use of chest radiographs in diagnosis has already been described in the previous section. Other tests that may narrow the differential diagnosis

include WBC count which tend to be markedly elevated in bacterial pneumonia. If the patient has a productive cough, it is important to obtain a sputum sample. Empiric therapy for community acquired pneumonia without obtaining a sputum sample is effective in most cases. However, this encourages the widespread and indiscriminate use of broad-spectrum antibiotics and contributes to increases in antibiotic resistance. A good sputum sample contains no squamous epithelial cells and at least 1015 PMN per high power field. If the patient is too ill to provide a sputum sample, nasotracheal or transtracheal aspiration may be used. The specimen should be gram stained and examined under oil immersion. This is often enough to identify the pathogen. The presence of large numbers of PMNs and WBCs also suggests a bacterial agent that is responsible. If only inflammatory cells and few WBC are seen, a nonbacterial etiology should be considered. If no clear diagnosis of bacterial pneumonia is fiound, the sample should be stained with an acid-fast stain to indentify mycobacteria. Other less common stains are available to identify legionnella and fungal pathogens. The sample should be cultured and tested for antibiotic resistance. F. Management and Treatment Upon identification of the responsible pathogen, the patient should be immediately given antibiotic treatment. Penicillin is the drug of choice for pneumococcal pneumonia. Erythromycin can be used if the patient is allergic to penicillin or if the cultures were either inconclusive or demonstrated an atypical pneumonia. Most patients can be treated on an outpatient basis. Patients who are at risk for developing respiratory failure or who are tachypneic or hypoxemic should be hospitalized. Their treatment may include some or all of the following: - supplemental oxygen - monitoring in critical care unit - frequent clapping and drainage if patient cannot cough properly - suctioning of oral secretions - isolation in room with negative pressure if patient has suspected pulmonary TB - analgesia for pleuritic pain - fluid replacement G. Prevention

Pneumococcal pneumonia is preventable in 60-80% of patients if they are given a pneumococcal vaccine (23 valent Pneumovax II 0.5 mL sc). This one-time vaccine should be offered to patients suffering from: - chronic heart or lung conditions - cirrhosis - chronic renal failure, nephrosis - diabetes mellitus - immunosuppression, HIV infection, Hodgkin's diseae, multiple myeloma - sickle-cell disease - patients > 65 yo Yearly influenza vaccine may also be indicated in these patients.

February 1, 2006 Table of Contents

Diagnosis and Treatment of Community-Acquired Pneumonia

M. NAWAL LUTFIYYA, PH.D., ERIC HENLEY, M.D., M.P.H., and LINDA F. CHANG, PHARM.D., M.P.H., B.C.P.S., University of Illinois College of Medicine at Rockford, Rockford, Illinois STEPHANIE WESSEL REYBURN, M.D., M.P.H., Mayo School of Graduate Medical Education, Rochester, Minnesota
Am Fam Physician. 2006 Feb 1;73(3):442-450.

Patients with community-acquired pneumonia often present with cough, fever, chills, fatigue, dyspnea, rigors, and pleuritic chest pain. When a patient presents with suspected communityacquired pneumonia, the physician should first assess the need for hospitalization using a mortality prediction tool, such as the Pneumonia Severity Index, combined with clinical judgment. Consensus guidelines from several organizations recommend empiric therapy with macrolides, fluoroquinolones, or doxycycline. Patients who are hospitalized should be switched from parenteral antibiotics to oral antibiotics after their symptoms improve, they are afebrile, and they are able to tolerate oral medications. Clinical pathways are important tools to improve care and maximize costeffectiveness in hospitalized patients.

Community-acquired pneumonia (CAP) is defined as pneumonia not acquired in a hospital or a long-term care facility. Despite the availability of potent new antimicrobials and effective vaccines, an estimated 5.6 million cases of CAP occur annually in the United States. The estimated total annual cost of health care for CAP in the United States is $8.4 billion. Table 1 presents an overview of CAP including definition, signs and symptoms, etiology, and risk factors.
1 2 2

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Patients with suspected community-acquired pneumonia (CAP) should receive chest radiography. The Pneumonia Severity Index should be used to assist in decisions regarding hospitalization of patients with CAP. The initial treatment of CAP is empiric, and macrolides or doxycycline (Vibramycin) should be used in most patients. Respiratory fluoroquinolones should be used when patients have failed first-line regimens, have significant comorbidities, have had recent antibiotic therapy, are allergic to alternative agents, or have a documented infection with highly drugresistant pneumococci.

Evidence rating C A C C

References 8 8,9,15,16 8,9,29 8,9,28,29

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 374 or http://www.aafp.org/afpsort.xml.

TABLE 1

Overview of Community-Acquired Pneumonia

DefinitionLower respiratory tract infection in a nonhospitalized person that is associated with symptoms of acute infection with or without new infiltrate on chest radiographs EtiologyBacterial Risk factorsAge older than 65 yearsHuman immunodeficiency virus or immunocompromisedRecent antibiotic therapy or resistance to antibioticsComorbidities

Clinical presentationTemperature greater than 38C (100.4F)Cough with or without sputum, hemoptysisPleuritic chest painMyalgiaGastrointestin al symptomsDyspneaMalaise , fatigueRales, rhonchi, wheezingEgophony, bronchial breath soundsDullness to percussionAtypical symptoms in older patients

Chlamydia speciesHaemophilus influenzaeLegionella speciesMoraxellacatarrhalisMycoplasma pneumoniaeStaphylococcus aureusStreptococcus pneumoniae

AsthmaCerebrovascular diseaseChronic obstructive pulmonary diseaseChronic renal failureCongestive heart failureDiabetesLiver diseaseNeoplastic disease

Viral AdenovirusInfluenza A and BParainfluenzaRespiratorysyncytial virus Endemic fungi BlastomycosisCoccidioidomycosisHistoplasmosis

Epidemiology
The epidemiology of CAP is unclear because few population-based statistics on the condition alone are available. The Centers for Disease Control and Prevention (CDC) combines pneumonia with influenza when collecting data on morbidity and mortality, although they do not combine them when collecting hospital discharge data. In 2001, influenza and pneumonia combined were the seventh leading causes of death in the United States, down from sixth in previous years, and represented an age-adjusted death rate of 21.8 per 100,000 patients. Death rates from CAP increase with the presence of comorbidity and increased age; the condition affects persons of any race or sex equally. The decrease in death rates from pneumonia and influenza are largely attributed to vaccines for vulnerable populations (e.g., older and immunocompromised persons).
3,4 3

Clinical Presentation
Pneumonia is an inflammation or infection of the lungs that causes them to function abnormally. Pneumonia can be classified as typical or atypical, although the clinical presentations are often similar. Several symptoms commonly present in patients with pneumonia.
TYPES OF CAP

Typical pneumonia usually is caused by bacteria such as Streptococcus pneumoniae. Atypical pneumonia usually is caused by the influenza virus, mycoplasma, chlamydia, legionella, adenovirus, or other unidentified microorganism. The patients age is the main differentiating factor between typical and atypical pneumonia; young adults are more prone to atypical causes, and very young and older persons are more predisposed to typical causes.
5,6

SYMPTOMS

Common clinical symptoms of CAP include cough, fever, chills, fatigue, dyspnea, rigors, and pleuritic chest pain. Depending on the pathogen, a patients cough may be persistent and dry, or it may produce sputum. Other presentations may include headache and myalgia. Certain etiologies, such as legionella, also may produce gastrointestinal symptoms.

Diagnosis
PHYSICAL EXAMINATION

Physical examination may reveal dullness to percussion of the chest, crackles or rales on auscultation, bronchial breath sounds, tactile fremitus, and egophony (E to A changes). The patient also may be tachypneic. A prospective

study showed that patients with typical pneumonia were more likely than not to present with dyspnea and bronchial breath sounds on auscultation.
7

RADIOGRAPHY

Chest radiography (posteroanterior and lateral views) has been shown to be a critical component in diagnosing pneumonia. According to the latest American Thoracic Society (ATS) guidelines for the diagnosis and treatment of adults with CAP, all patients with suspected CAP should have a chest radiograph to establish the diagnosis and identify complications (pleural effusion, multilobar disease). Chest radiography may reveal a lobar consolidation, which is common in typical pneumonia; or it could show bilateral, more diffuse infiltrates than those commonly seen in atypical pneumonia. However, chest radiography performed early in the course of the disease could be negative.
8 8

LABORATORY TESTS

Historically, common laboratory tests for pneumonia have included leukocyte count, sputum Gram stain, two sets of blood cultures, and urine antigens. However, the validity of these tests has recently been questioned after low positive culture rates were found (e.g., culture isolates ofS. pneumoniae were present in only 40 to 50 percent of cases). Such low positive culture rates are likely due to problems with retrieving samples from the lower respiratory tract, previous administration of antibiotics, contamination from the upper airways, faulty separation of sputum from saliva when streaking slides or plates, or viral etiology. Furthermore, sputum samples are adequate in only 52.3 percent of patients with CAP, and only 44 percent of those samples contain pathogens. Nonetheless, initial therapy often is guided by the assumption that the presenting disease is caused by a common bacterial pathogen.
9 9 10

Findings also cast doubt on the clinical utility of obtaining blood cultures from patients with suspected CAP. In a study of CAP cases in 19 Canadian hospitals over a six-month period, positive blood cultures were obtained in only 5.2 to 6.2 percent of patients, including those with the most severe disease. Based on these findings, other researchers concluded that a positive blood culture had no correlation with the severity of the illness or outcome. Another prospective study showed that blood cultures were positive in only 10.5 percent of patients with pneumonia. Despite these and other research findings, current ATS guidelines recommend that patients hospitalized for suspected CAP receive two sets of blood cultures. Blood cultures, however, are not necessary for outpatient diagnosis.
11 12 13 10 8 8

Legionella antigens were found in the urine of 48 percent of patients with suspected Legionella pneumophila serogroup 1 infection. Table 2 includes the sensitivity and specificity of diagnostic tests for CAP.
14 2,8,11,13

TABLE 2

Sensitivity and Specificity of Diagnostic Tests for CAP

Diagnostic tests by pathogen Chlamydia Rapid PCR (sputum, BAL fluid)Serology (fourfold rise in serum and convalescent titers)Sputum culture Gram-negative rods Sputum Gram stain Haemophilus influenzae, Moraxella catarrhalis, Pneumoniae Sputum culture Influenza Rapid DFA (sputum, BAL fluid) Legionella pneumophila DFA (sputum, BAL fluid) PCR (sputum, BAL fluid) Serum acute titer Urinary antigen Mycoplasma pneumoniae Antibiotic titers Cold agglutinins PCR (sputum, BAL fluid) Pneumococcal pneumoniae Chest radiography (lobar infiltrate) Sputum culture Sputum Gram stain Sensitivity (%) Specificity (%)

30 to 9510 to 10010 >95>95 to 80 15 to 100 Diagnostic yield 20 to 79* 22 to 75 22 to 75 83 to 100 10 to 27 55 to 90 75 to 95 50 to 60 30 to 95 40 Diagnostic yield 20 to 79* 15 to 100 11 to 100 Diagnostic yield 20 to 79* 90 90 >95 >85 >95 >90 >95 Diagnostic yield 20 to 79* 11 to 100

CAP = community-acquired pneumonia; PCR = polymerase chain reaction; BAL = bronchoalveolar lavage; DFA = direct fluorescence antibody. *Overgrowth of oral flora, isolation of atypical agents requires special media. Acute symptoms. Information from references2,8,11, and13.

Treatment
Initial treatment of CAP is based on physical examination findings, laboratory results, and patient characteristics (e.g., age, chronic illnesses, history of smoking, history of the illness). Physicians should begin their treatment decisions by assessing the need for hospitalization using a prediction tool for increased mortality, such as the Pneumonia Severity Index (Table 3 ), combined with clinical judgment.
15 15 9

OUTPATIENT VS. INPATIENT TREATMENT

Choosing between outpatient and inpatient treatment is a crucial decision because of the possible risk of death. This decision not only influences diagnostic testing and medication choices, it can have a psychological impact on patients and their families. On average, the estimated cost for inpatient care of
9,15,16

patients with CAP is $7,500. Outpatient care can cost as little as $150 to $350. Hospitalization of a patient should depend on patient age, comorbidities, and the severity of the presenting disease.
19 9,20 14

17

Physicians tend to overestimate a patients risk of death ; therefore, many lowrisk patients who could be safely treated as out-patients are admitted for more costly inpatient care. The Pneumonia Severity Index (Table 3 ) was developed to assist physicians in identifying patients at a higher risk of complications and who are more likely to benefit from hospitalization. Investigators developed a risk model based on a prospective cohort study of 2,287 patients with CAP in Pittsburgh, Boston, and Halifax, Nova Scotia. By using the model, the authors found that 26 to 31 percent of the hospitalized patients were good outpatient candidates, and an additional 13 to 19 percent only needed brief hospital observation. They validated this model using data from more than 50,000 patients with CAP in 275 U.S. and Canadian hospitals.
15 9,15,16 16 17 1517,21,22

TABLE 3

Pneumonia Severity Index

Patient Characteristics Demographics Points

Male Age (years) Female Age (years) 10 Nursing home resident + 10 Comorbid illness Neoplastic disease + 30 Liver disease + 20 Congestive heart failure + 10 Cerebrovascular disease + 10 Renal disease + 10 Physical examination findings Altered mental status + 20 Respiratory rate >30 breaths per minute + 20 Systolic blood pressure < 90 mm Hg + 20 Temperature < 35C (95F) or >40C (104F) + 15 Pulse rate >125 beats per minute + 10 Laboratory and radiographic findings Arterial pH < 7.35 + 30 Blood urea nitrogen >64 mg per dL (22.85 mmol per L) + 20 Sodium < 130 mEq per L (130 mmol per L) + 20 Glucose >250 mg per dL (13.87 mmol per L) + 10 Hematocrit < 30 percent + 10 Partial pressure of arterial oxygen < 60 mm Hg or oxygen percent saturation < 90 percent + 10 Pleural effusion + 10 Total points: _______ Point total Risk Risk class Mortality % (No. of patients) Recommended site of care No predictors Low I 0.1 (3,034) Outpatient

Point total 70 71 to 90 91 to 130 >130

Risk Low Low Moderate High

Risk class II III IV V

Mortality % (No. of patients) 0.6 (5,778) 2.8 (6,790) 8.2 (13,104) 29.2 (9,333)

Recommended site of care Outpatient Inpatient (briefly) Inpatient Inpatient

Information from reference15.

Although the Pneumonia Severity Index can serve as a general guideline for management, clinical judgment should always supersede the prognostic score.
PHARMACOTHERAPY

The primary goals of pharmacotherapy for patients with CAP include eradicating the causative pathogens, resolving the clinical signs and symptoms, minimizing hospitalization, and preventing reinfection. Physicians should choose a medication based on the pharmacokinetic profile, adverse reactions, drug interactions, and cost-effectiveness. Further, patient evaluation should focus on severity of illness, patient age, comorbidities, clinical presentation, epidemiologic setting, and previous exposure. The majority of patients with CAP are treated empirically based on the most common pathogen(s) associated with the condition.
2327 2327 9 2327

Consensus guidelines from ATS, Infectious Diseases Society of America, and Canadian Guidelines for the Initial Management of Community-Acquired Pneumonia (Figure 1 ) recommend initial empiric therapy with macrolides, fluoroquinolones, or doxycycline (Vibramycin). A fourth guideline developed by the Therapeutic Working Group of the CDC, however, recommends using fluoroquinolones sparingly because of resistance concerns.
8 9 28 6 29

Management of CAP

Figure 1. Algorithm for the management of CAP. (CAP = community-acquired pneumonia.) Adapted with permission from Fish D. Pneumonia. PSAP, Pharmacotherapy Self-Assessment Program. Kansas City, Mo.: American College of Clinical Pharmacy, 2002:202.

Although data are limited on duration of CAP therapy, current research recommends seven to 10 days of therapy for S. pneumoniae and 10 to 14 days of therapy for Mycoplasma pneumoniae andChlamydia pneumoniae. After a hospitalized patient is clinically stable (i.e., temperature less than 37.8 C [100.0 F], pulse under 100 beats per minute, respiratory rate below 24 breaths per minute, systolic blood pressure above 90 mm Hg, and blood oxygen saturation over 90 percent) and able to tolerate oral intake, the patient may be treated with oral antibiotics for the remainder of the therapy course. This can save money and allow for earlier hospital discharge, which minimizes a patients risk of hospital-acquired infection.
30

Pneumococcal Resistance
S. pneumoniae, which accounts for 60 to 70 percent of all bacterial CAP cases, can affect all patient groups and can cause a fatal form of CAP. The alarming

rate of resistance to many commonly used antibiotics raises great concern. Penicillin-resistant S. pneumoniae was uncommon in the early 1990s but has since become increasingly prevalent.
29,31

Resistant strains are classified as having intermediate or high-level resistance. Surveillance data in the United States revealed that, overall, pneumococcal strains had a 28 percent immediate resistance rate and a 16 percent high-level resistance rate. Decreased susceptibility to other commonly used antibiotics has also been observed (Table 4 ). The clinical importance of these data is questionable because recruiting patients infected with resistant pathogens for clinical trials is difficult. Furthermore, available outcomes on the treatment of pneumonia caused by resistant pneumococcal strains are conflicting.
30 32 2931 30

TABLE 4

Patterns of Resistance to Antibiotics in North America*

Antibiotic Penicillins Amoxicillin/clavulanate (Augmentin) Penicillin Cephalosporins Cefepime (Maxipime) Cefprozil (Cefzil) Ceftriaxone (Rocephin) Cefuroxime (Ceftin) Macrolides Azithromycin (Zithromax) Clarithromycin (Biaxin) Erythromycin Fluoroquinolones Gatifloxacin (Tequin) Levofloxacin (Levaquin) Moxifloxacin (Avelox) Miscellaneous Clindamycin (Cleocin) Tetracycline Trimethoprim/sulfamethoxazole (Bactrim, Septra) Vancomycin (Vancocin) Resistance (%) 4.1 21.3 0.4 23.9 1.9 24.7 23.0 26.6 28.3 0.7 0.7 0.4 9.2 18.8 29.9 0.0

*Antibiotics tested against Streptococcus pneumoniae isolates. Resistance rates averaged across all patient age groups. Information from reference32.

The CDC and others recommend outpatient oral empirical antibiotics with a macrolide, doxycycline, or an oral betalactam (amoxicillin, cefuroxime [Ceftin], or amoxicillin/clavulanate [Augmentin]) or inpatient treatment with an intravenous betalactam (cefuroxime, ceftriaxone [Rocephin], cefotaxime [Claforan]) or a combination of ampicillin/sulbactam (Unasyn) with a

macrolide (Figure 1 ). Conservative use of new fluoroquinolones (levofloxacin [Levaquin], gatifloxacin [Tequin], moxifloxacin [Avelox]) also is recommended to minimize resistance patterns. The new fluoroquinolones (minimum inhibitory concentration: 4 mcg per mL or greater) should be used only when patients have failed recommended first-line regimens, are allergic to alternative agents, or have a documented infection with highly drug-resistant pneumococci such as those resistant to penicillin.
6 28,29 28,29 28,29

Cost of Antimicrobial Therapy

Economic pressures have accentuated the focus on reducing health care costs and utilizing resources while maintaining or improving quality of care. These pressures are exacerbated by the growing resistance of S. pneumoniae to penicillin. This pattern of resistance increases the cost of treatment because of prolonged hospitalization, relapses, and the use of more expensive antibacterial agents.
31 31,32 3337

REDUCING COSTS

Numerous methods for reducing costs when treating patients with bacterial infections can be applied to CAP (Table 5). Choosing monotherapy instead of combination therapy reduces costs associated with administering an antibacterial. Using agents with longer half-lives allows for once-daily administration, which in turn leads to improved compliance and outcomes and decreased costs. In addition, transitioning patients to oral therapy as soon as they are clinically stable can significantly reduce the length of hospitalization the major contributing factor to health care costs.
3337 3337 3337

TABLE 5

Strategies for Reducing the Cost of Antibiotic Therapy

Administration Use the shortest appropriate course possible.Switch from parenteral to oral antibiotics as soon as clinically appropriate. Adverse events Avoid agents with serious or costly adverse effects.Avoid agents known to induce resistance. Drug cost Compare low impact with total hospital costs (but significant to pharmacy costs). Hospitalization Use knowledge of local resistance to initiate early therapy with appropriate spectrum agent (few data available).Consider availability and cost-effectiveness of intravenous versus oral administration. Monitoring Avoid agents that require therapeutic monitoring or laboratory safety tests. Pharmacotherapy Use long-acting antibiotics.Use potent bactericides.Avoid antibiotics with poor tissue penetration.
COST-EFFECTIVE CARE

When choosing a treatment, it is essential to compare costs and outcomes of all recommended drug therapies. Table 6 includes the costs of and common adverse reactions to antimicrobial therapies for CAP.
31 6

TABLE 6

Antimicrobial Therapies for CAP

Cost per course Common adverse Dosage* (generic) reactions 1 g IV every six to eight $355 (330)124 Mild diarrheaRash hours200 mg orally twice (110)192392219 oral250 per day500 mg orally twice to 358 IV per day1 g IV every 24 hours500 mg orally twice per day0.75 to 1.5 g IV every eight hours ClindamycinsClindamycin 300 mg orally every six 238 (148 to 168) oral250 Mild diarrheaAbdominal (Cleocin) hours600 mg IV every eight IV painPseudomembranou hours s colitisRash FluoroquinolonesGatifloxaci 400 mg orally or IV once 98 oral, 382 IV56 oral, Mild n (Tequin)Levofloxacin per day500 mg orally or IV 438 IV107 diarrheaNauseaVomitin (Levaquin)Moxifloxacin once per day400 mg orally gConstipationDizziness (Avelox) once per day Headache MacrolidesAzithromycin 500 mg orally for one dose, 49 to 60 oral295 IV9617 Mild (Zithromax)Clarithromycin then 250 mg once per day (8 to 10) oral(167) IV diarrheaNauseaVomitin (Biaxin)Erythromycin for four doses500 mg IV gAbdominal painRash every 24 hours500 mg orally twice per day500 mg orally every six hours500 to 1,000 mg IV every six hours PenicillinsAmoxicillinAmoxicil 500 mg orally every eight 4 (4 to 8)20 (18 to Mild lin/clavulanate(Augmentin)Pe hours875 mg orally every 19)166 (110 to 115) diarrheaNauseaVomitin nicillin GPenicillin V 12 hours875 mg/125mg (273)15 (9 to 15) gRash orally every 12 hours1 to 3 mU IV every four hours500 mg orally four times per day TetracyclinesDoxycycline 100 mg orally twice per day 102 (16 to 21) Mild (Vibramycin) diarrheaNauseaVomitin gPhototoxicity Agent CephalosporinsCefotaxime (Claforan)Cefpodoxime (Vantin)Cefprozil (Cefzil)Ceftriaxone (Rocephin)Cefuroxime (Ceftin)
CAP = community-acquired pneumonia; IV = intravenously. *Usual duration for adults with CAP and normal renal function is 10 to 14 days. Estimated cost to the pharmacist based on average wholesale prices in Red Book. Montvale, N.J.: Medical Economics Data, 2005. Cost to the patient will be higher, depending on prescription filling fee. Adverse events occurring at a rate of approximately 1 to 10 percent. Adapted with permission from Fish D. Pneumonia. Pharmacotherapy Self-Assessment Program. 4th ed. Kansas City, Mo.: American College of Clinical Pharmacy 2002:198.

The goal of a formal pharmacoeconomic assessment is to enhance overall patient care using available resources. The evaluation should lead to a decision

that will maximize the value of health care services, not simply reduce the costs of drug therapy. For instance, a particular drug may be more expensive, but it may also be more effective, thus lowering overall costs. Another drug may have a higher rate of treatment failures, creating added costs associated with managing the failures. The overall cost of each therapy should be obtained by comparing the end cost with the probability of achieving a positive outcome. Depending on the relative costs associated with treatment failures compared with the costs of cures, the decision to choose one agent over another may change. The best way to apply cost-saving approaches to the treatment of patients with CAP is by using a clinical pathway. This is a method of facilitating multidisciplinary patient care by moving processes of care sequentially through various stages, within specified time frames, toward a desired outcome. These pathways should be specific to each institution, taking into account resistance rates in the community and encouraging the use of the most active, costeffective agents to produce rapid, positive clinical outcomes.
38 31,39