Pneumonia, Bacterial Last Updated: February 15, 2005 Rate this Article Email to a Colleague Get CME/CE for

article Synonyms and related keywords: pneumonia, pneumococcus, Streptococcus pneumoniae, S pneumoniae, Haemophilus influenzae, H influenzae, Staphylococcus aureus, S aureus, Legionella, Legionella pneumophila, Mycoplasma, Mycoplasma pneumoniae, Chlamydia, Chlamydia psittaci, Coccidioides immitis, Mycobacterium tuberculosis, M tuberculosis, Histoplasma capsulatum, Coxiella burnetii, C burnetii, Burkholderia pseudomallei, Pseudomonas, Pseudomonas pseudomallei, Melioidosis, Klebsiella, Klebsiella pneumoniae, K pneumoniae, Moraxella catarrhalis, M catarrhalis, Pneumocystis carinii, Cryptococcus neoformans, Rhodococcus equi, Mycobacterium avium-intracellulare, Serratia marcescens, Nocardia, Escherichia coli, Enterobacter, Serratia species, Bacteroides, Peptostreptococcus, Fusobacterium species, hospitalacquired pneumonia, community-acquired pneumonia, CAP, nosocomial pneumonia, viral pneumonia, typical pneumonia, atypical pneumonia, lobular pneumonia, lobar pneumonia, bronchial pneumonia, pores of Kohn, peripneumonia, inflammation of lung tissue, consolidation of lung tissue, influenza, bacterial pneumonia, bronchiectasis, respiratory failure, septic shock, bloody sputum, rust-colored sputum, green sputum, foulsmelling sputum, bad-tasting sputum, currant-jelly sputum, tachypnea, central cyanosis, rales, crackles, egophony upon auscultation, whispering pectoriloquy, pleural friction rub, endotracheal intubation, chronic obstructive pulmonary disease, COPD, smoking, asthma, chronic alcoholism, diabetes, Pontiac fever, gag reflex INTRODUCTION Section 2 of 11 Background: Medical practitioners have known of pneumonia since ancient times. Hippocrates indoctrinated his students about "peripneumonia," which, for the ancient healers, had a connotation of an acute illness either with pain in the side or with severe dyspnea. The term acquired a more punctilious meaning as the study of morbid anatomy and physical diagnosis progressed over the last few centuries. Morgagni contributed the concept of solidification of the lung. Laennec, the father of pulmonary medicine, described pathological stages of the disease and showed how to diagnose them using auscultation. Rokitansky's graphic narration helped distinguish lobar from lobular or bronchial pneumonia. Pasteur discovered Streptococcus pneumoniae in 1880, and before long, this organism was proved to be a cause of lobar pneumonia. The contemporary physicians of the 19th century were well aware of lobar pneumonia. Coope described lobar pneumonia as that "which consists of a series of changes by which the spongy pulmonary tissue is rapidly converted into a solid mass, returning afterwards, in cases that recover, to its normal condition." The modern physician, who is more adept with the x-ray viewing box than the autopsy room, has acquired sufficient familiarity with this common malady as knowledge and wisdom has been acquired over the centuries.

Pneumonia is defined as inflammation and consolidation of the lung tissue due to an infectious agent. Pneumonia that develops outside the hospital setting is considered community-acquired pneumonia. Pneumonia developing 72 hours or more after admission to the hospital is termed nosocomial or hospital-acquired pneumonia. Community-acquired pneumonia is caused most commonly by bacteria that traditionally have been divided into 2 groups, typical and atypical. Typical organisms include S pneumoniae (pneumococcus) and Haemophilus and Staphylococcus species. Atypical refers to pneumonia caused by Legionella, Mycoplasma, and Chlamydia species. Pathophysiology: Pathogenesis of typical pneumonia S pneumoniae generally resides in the nasopharynx and is carried asymptomatically in approximately 50% of healthy individuals. Invasive disease may occur upon acquisition of a new epithelium serotype. A strong association exists with viral illnesses, such as influenza. Viral infections increase pneumococcal attachment to the receptors on activated respiratory epithelium. Once aerosolized from the nasopharynx to the alveolus, pneumococci infect type II alveolar cells. The pneumonic lesion progresses as pneumococci multiply in the alveolus and invade alveolar epithelium. Pneumococci spread from alveolus to alveolus through the pores of Kohn, thereby producing inflammation and consolidation along lobar compartments. Pathogenesis of atypical infection After aspiration or inhalation, the atypical organisms attach to the respiratory epithelial cells by a variety of mechanisms. The presence of pili on the surface of Legionella species facilitates attachment. Once adhered, the organisms cause injury to the epithelial cells and their associated cilia. Many of the pathogenetic mechanisms may be immunemediated rather than due to direct injury by the bacteria. A host defense is mounted via cell-mediated and humoral immunity. Infection caused by atypical organisms often spreads beyond the lobar boundaries and frequently is bilateral. Pathogenesis of nosocomial pneumonia Aspiration plays a central role in the pathogenesis of nosocomial pneumonia. Approximately 45% of healthy subjects aspirate during sleep, and an even higher proportion of severely ill patients aspirate routinely. Depending on the number and virulence of the pathogenic organisms reaching the lower respiratory tract and on the host defense factors, pneumonia may develop. The oropharynx of hospitalized patients may become colonized with aerobic gram-negative bacteria within a few days of admission. Therefore, nosocomial pneumonia is caused predominantly by the gram-negative bacilli. However, the incidence of Staphylococcus aureus lower respiratory tract infection is increasingly common in the hospitalized and institutionalized patient and must now be considered a possible pathogen for nosocomial pneumonia.

CLINICAL Section 3 of 11 History: Clinical presentation in patients with pneumonia varies from a mildly ill ambulatory patient to a critically ill patient with respiratory failure or septic shock. The character of sputum produced may suggest a particular pathogen. Patients with pneumococcal pneumonia may produce bloody or rust-colored sputum. Infections with Pseudomonas, Haemophilus, and pneumococcal species are known to expectorate green sputum. Anaerobic infections characteristically produce foul-smelling and bad-tasting sputum. Currant-jelly sputum suggests pneumonia from Klebsiella or pneumococcal species. Patients may report rigors or shaking chills. Patients may complain of other nonspecific symptoms, which include headaches, malaise, nausea, vomiting, and diarrhea. These symptoms may suggest infection with Legionella, Chlamydia, or Mycoplasma species. Malaise, myalgias, and exertional dyspnea may be observed. Pleuritic chest pain or abdominal pain secondary to pleuritis is a common feature of pneumococcal infection, but these may occur in other bacterial pneumonias. A meticulous past medical history and history of environmental, occupational, and recreational exposures should be obtained. This history should include whether the patient has recently traveled or had contact with animals that might serve as a source of an infectious agent. Legionella pneumophila: Patients may report exposure to contaminated air-conditioning cooling towers, exposure to a grocery store mist machine, or a visit or recent stay in a hospital with a contaminated water system. Coccidioides immitis: Pneumonia may develop after travel to the southwestern United States and after exposure to a wind or rain storm in an endemic area. S pneumoniae, Mycobacterium tuberculosis, Mycoplasma, and Chlamydia pneumonia: Patients may report exposure to overcrowded institutions such as jails, shelters for homeless persons, or military training camps. Blastomyces dermatitidis: Patients may have traveled to the midwestern United States or the Canadian Shield. Histoplasma capsulatum: Infection can result from exposure to contaminated bat caves or from excavation in endemic areas. Coxiella burnetii: This is related to exposure to infected parturient cats, cattle, sheep, or goats. Chlamydia psittaci: Patients may report exposure to turkeys, chickens, ducks, or psittacine birds. Travel history Burkholderia (Pseudomonas) pseudomallei (melioidosis): This infection may result from travel to Thailand or other countries in Southeast Asia. M tuberculosis: Pneumonia may develop in immigrants from Asia or Africa. Occupational history Pneumonia may develop in a health care worker who works with patients infected with HIV in a large city. M tuberculosis may be a causative agent.

Host factors Evaluation of host factors often provides a clue to the bacterial diagnosis. Diabetic ketoacidosis may lead to S pneumoniae or S aureus infection. Alcoholism may indicate Klebsiella pneumoniae infection. Chronic obstructive lung disease may lead to Haemophilus influenzae or Moraxella catarrhalis infection. In patients who have received solid organ transplants, pneumonia from S pneumoniae may occur more than 3 months after the transplant. Other organisms include Legionella species, Pneumocystis carinii, and cytomegalovirus. Sickle cell disease may indicate S pneumoniae or H influenzae infection. HIV infection (CD4 cell count > 200/mL) may lead to Cryptococcus neoformans, M tuberculosis, or Rhodococcus equi infection. A CD4 cell count of fewer than 200/mL may indicate Mycobacterium avium-intracellulare infection or Pneumocystis pneumonia. Physical: Physical examination findings vary depending on the type of organisms, severity of pneumonia, coexisting host factors, and presence of complications. The common findings of consolidation are as follows: Fever or hypothermia (temperature >38.5C or <36C) Tachypnea (respiratory rate >18 breaths per min) Tachycardia or bradycardia Central cyanosis Dullness to percussion over pneumonic consolidation Decreased intensity of breath sounds Rales or crackles Egophony upon auscultation Whispering pectoriloquy Pleural friction rub Altered mental status Physical examination findings that may indicate the etiology of pneumonia are as follows: Periodontal disease with foul-smelling sputum - Anaerobes, possible mixed aerobicanaerobic infection Bullous myringitis - Mycoplasma pneumoniae Absent gag reflex, altered level of consciousness, recent seizure - Polymicrobial (aerobic and anaerobic), possible macroaspiration or microaspiration Encephalitis - M pneumoniae, C burnetii, L pneumophila Cerebellar ataxia, erythema multiforme, erythema nodosum - Chlamydia pneumoniae, M tuberculosis Erythema gangrenosum - Pseudomonas aeruginosa, Serratia marcescens

Cutaneous nodules (abscesses and CNS findings) - Nocardia species Causes: Causes of bacterial pneumonia can be categorized as extrinsic and intrinsic. Extrinsic factors include infection with respiratory pathogens. Exposure to pulmonary irritants or direct pulmonary injury causes noninfectious pneumonitis. Infectious agents responsible for bacterial pneumonias include S pneumoniae and H influenzae; Klebsiella, Staphylococcus, and Legionella species; and gram-negative organisms. Aspiration and inhalation of aerosols containing the bacterial pathogen are the most common modes of infection. Some bacteria, such as Staphylococcus species, may spread to the lungs hematogenously. Intrinsic factors are related to the host's immune response, the presence of comorbidities, and other risk factors: Loss of protective reflexes allows aspiration of oropharyngeal flora into the lung. Aspiration is facilitated by altered mental status from intoxication, deranged metabolic states, neurological causes (eg, stroke), and endotracheal intubation. Local lung pathologies (eg, tumors, chronic obstructive pulmonary disease [COPD], bronchiectasis) are predisposing factors for bacterial pneumonia. Smoking impairs the host's defense to infection by a variety of mechanisms. S pneumoniae is the most common cause of bacterial pneumonia. Pneumonia from H influenzae often is associated with debilitating conditions such as asthma, COPD, smoking, and a compromised immune system. K pneumoniae may cause a severe necrotizing lobar pneumonia in patients with chronic alcoholism, diabetes, or COPD. S aureus pneumonia is observed in those who abuse intravenous drugs. S aureus generally occurs in hospitalized patients and patients with prosthetic devices; it spreads hematogenously to the lungs from contaminated local sites. This pathogen also is an important cause of pneumonia following infection with influenza A. L pneumophila infections occur either sporadically or as local outbreaks. An outbreak in 1976 affected more than 180 members of the American Legion staying at the same hotel in Philadelphia for an annual convention. Twenty-nine of these legionnaires died. The organism was identified in 1977 and named Legionella. Legionella is known to colonize the water condensed from air-conditioning systems and the water supply of institutions. L pneumophila has 2 distinct clinical presentations. The first, Pontiac fever, is an immune-mediated reaction after exposure to the organism. Pontiac fever presents as a virallike syndrome with malaise, fever and chills, myalgias, and headache. This disease resolves spontaneously. The second Legionella pneumonia is a severe and aggressive pneumonia associated with a mortality rate of up to 75% if treatment is delayed. Elderly and debilitated persons; those who smoke; and individuals with COPD, alcoholism, immunodeficiency, and trauma all are predisposed to Legionella infection. Legionella pneumonia has associated GI symptoms, including anorexia, nausea, vomiting, and diarrhea, in 50% of patients. Gram-negative pneumonias are observed in individuals who are infirm, immunocompromised, and hospitalized. Causative organisms include Escherichia coli

and Pseudomonas, Enterobacter, and Serratia species. Residents of chronic care facilities are at risk for gram-negative pneumonia. Aspiration pneumonia is observed in individuals with altered sensorium (eg, seizures, alcohol intoxication, drug intoxication) or CNS impairment (eg, stroke) causing a reduced gag reflex. The stomach or oropharyngeal contents are aspirated. The causative organisms include M catarrhalis and Bacteroides, Peptostreptococcus, and Fusobacterium species. DIFFERENTIALS Section 4 of 11 Atelectasis Bronchiectasis Chronic Bronchitis Chronic Obstructive Pulmonary Disease Foreign Body Aspiration Influenza Klebsiella Infections Lung Abscess Lung Cancer, Non-Small Cell Lung Cancer, Oat Cell (Small Cell) Mycobacterium AviumIntracellulare Mycobacterium Kansasii Pneumococcal Infections Pneumocystis Carinii Pneumonia Pneumonia, Aspiration Pneumonia, CommunityAcquired Pneumonia, Fungal Pneumonia, Viral Psittacosis Q Fever Respiratory Failure Sepsis, Bacterial

Lab Studies: Leukocytosis with a left shift, although commonly observed in any bacterial infection, may be absent in patients who are elderly or debilitated. Leukopenia (defined as a WBC count of <5000) is an ominous sign of impending sepsis and portends a poor outcome. Sputum examination (see Image 4) provides an accurate diagnosis in approximately 50% of patients. An adequate specimen must have less than 10 squamous epithelial cells and more than 25 WBCs per low-power field. However, the number of WBCs in the sputum of a neutropenic patient may be fewer than 25 WBCs per low-power field, despite origination from the lower respiratory tree. A single pathogen present on the Gram stain is indicative of pneumonia; mixed flora may indicate oral contamination or anaerobic infections. An adequate specimen uncontaminated by oral flora is required for a proper workup. Sputum cultures are submitted only from specimens that are deemed satisfactory after Gram stain. The Legionella-specific direct fluorescent antibody test is performed when indicated, even though this technique is associated with a high rate of false-negative results. Other tests may include the following:

Urinary antigen testing for Legionella serogroup 1 has a high yield. A urinary antigen test for pneumococcus is available and may be performed at the bedside. Experience with this test is limited. A Legionella serum antibody titer rising by 1:128 confirms the diagnosis retrospectively. Mycoplasma and Chlamydia immunoglobulin M antibodies contribute to the diagnosis. Serology is essential in the diagnosis of unusual causes of pneumonia such as Q fever and brucellosis. Culture and Gram stain of pleural effusions or empyema fluid has a high yield. Pleural fluid pH determination should be made to classify the effusion as simple versus complicated. Performing blood cultures is important, but the results have a limited value. When positive, the results confirm a causative agent. Blood cultures are positive only in approximately 40% of cases, but performing them is necessary for epidemiologic surveillance and documentation of resistance patterns in a community. Imaging Studies: Chest radiograph findings may indicate the following: A segmental or lobar opacity with air bronchogram - May be observed in S pneumoniae pneumonia Cavitary lesions and bulging lung fissures - May be observed in pneumonia caused by K pneumoniae or S aureus Presence of cavitation and associated pleural effusions - May suggest pneumonia caused by S aureus, anaerobic infections, gram-negative infections, and tuberculosis Legionella - Predilection for the lower lung fields Klebsiella - Tendency to involve the upper lung zones In a patient with a clinical picture of pneumonia, pathogenic organisms may be suggested based on the chest radiographic pattern. The common patterns are described as follows: Focal opacity (segment or lobar pneumonia) (see Images 2-3) - S pneumoniae, M pneumoniae, L pneumophila, S aureus, C pneumoniae, M tuberculosis, B dermatitidis Interstitial pattern (diffuse process identified as reticulonodular or reticular process) - M pneumoniae, P carinii, C psittaci Interstitial pattern with hilar and/or mediastinal lymphadenopathy - Epstein-Barr virus, Francisella tularensis, C psittaci, M pneumoniae, fungi Cavitation or necrotizing pneumonia (see Image 1) - Mixed aerobic-anaerobic infection (lung abscess), aerobic gram-negative bacilli, M tuberculosis, L pneumophila, C neoformans, Nocardia asteroides, Actinomyces israelii, C immitis Bulging oblique or horizontal fissure - K pneumoniae, L pneumophila Multifocal bilateral segment or lobar opacities - S aureus, C burnetii, L pneumophila, S pneumoniae Miliary (diffuse micronodular) pattern - M tuberculosis, H capsulatum, C immitis, B dermatitidis, varicella zoster Pneumatoceles (thin-walled cavities) - S aureus, Streptococcus pyogenes, P carinii "Round" pneumonia (often presents as solitary pulmonary nodule) - C burnetii, S pneumoniae, L pneumophila, S aureus

Other Tests: Arterial blood gas (ABG) determination: Evaluation of the patient's gas exchange is essential in order to decide if hospital admission, oxygen supplementation, or other efforts are indicated. Pulse oximetry of less than 90% indicates significant hypoxia; an ABG determination should be performed in these patients. Procedures: Bronchoscopy: Bronchial washing specimens can be obtained. Protected brush and bronchoalveolar lavage can be performed for quantitative cultures. Transtracheal aspiration for culture: This procedure is mentioned primarily for historical significance. This method of obtaining lower respiratory secretions has been replaced by fiberoptic bronchoscopy. Thoracentesis: This is an essential procedure in patients with a parapneumonic pleural effusion. Obtaining fluid from the pleural space for laboratory analysis allows for the differentiation between simple and complicated effusions. This determination helps guide further therapeutic intervention. Histologic Findings: In 1838, Laennec first described the evolution of a consolidated lung secondary to pneumonia. Laennec categorized the progression of pneumonia in 3 stages, as follows: The recently infected lungs demonstrate engorgement of alveolar capillaries with frothy, serous, and blood-tinged fluid in the alveolar spaces. The "red hepatization" stage is a rapid progression from engorgement. This stage is characterized by a dry, granular, dark-red lung surface on gross appearance. The alveoli are filled with copious, clotted, inflammatory exudates, and a fibrin network extends from one alveolus into the next through the pores of Kohn. Little tissue destruction or necrosis occurs at this stage, and the patient and lung architecture may recover fully. As pneumonia progresses over 2-3 days, leukocytes pack into the alveoli, erythrocytes are lysed, and epithelial cells degenerate, leading to "gray hepatization. Dying pneumococci release a preformed toxin, further contributing to this damage. The pneumococci are opsonized by leukocytes and begin to be cleared. Resolution results in the formation of jellylike yellowish-colored exudates. Absorption of these exudates is remarkably efficient, with little organization or permanent scaring. TREATMENT Section 6 of 11 Medical Care: The initial approach to treating patients with community-acquired pneumonia involves a determination of 3 factors. (1) Should the patient with pneumonia be treated in the hospital or as an outpatient? (2) Does the patient have a serious coexisting illness or is the patient elderly? (3) How severely ill is the patient at the time of the initial evaluation? Once these assessments have been made, initial antimicrobial therapy can be selected based on to the recommendations given in Tables 1-7. The choices cover the most

common pathogens for a given clinical setting. Evaluating the response to therapy is important. Patients who are not improving with initial empirical antibiotic therapy should be identified and re-examined. Risk stratification of community-acquired pneumonia Patients with community-acquired pneumonia can be categorized into 1 of 4 groups based on information collected at the time of the initial evaluation. The risk factors for stratification include the need for hospitalization, the severity of illness, the presence of coexisting disease, and the patient's age. The 4 major categories not only speculate the microbial etiology but also predict ultimate prognosis and outcome. These categories are (1) community-acquired pneumonia occurring in patients aged 60 years or younger who have no evidence of comorbidity and who can be treated in an outpatient setting, (2) community-acquired pneumonia occurring in patients with evidence of comorbidity and/or who are aged 60 years or older who can be treated in an outpatient setting, (3) community-acquired pneumonia requiring hospitalization but not admission to an ICU, and (4) severe community-acquired pneumonia requiring ICU care. Nosocomial pneumonia Nosocomial pneumonia remains a prevalent hospital-acquired infection. The gaps in knowledge and controversies regarding diagnosis, treatment, and prevention of nosocomial pneumonia continue. The initial empiric therapy of nosocomial pneumonia in immunocompetent patients is directed at the core organisms. In immunocompromised hosts, the additional bacteria are targeted and therapy is modified based on the results of microbiologic investigations. Modifications to the empirical antibiotic therapy may be necessary after assessment of 3 factors; these are (1) the severity illness in the patient, (2) the presence of any conditions that can lead to infection with specific pathogens, and (3) the length of time the patient has been hospitalized before the development of nosocomial pneumonia. Following these determinations, patients are categorized into 1 of 3 groups because a different microbiologic spectrum is suggested in each group. These groups are (1) patients without unusual risk factors who present with mild-to-moderate nosocomial pneumonia any time during hospitalization or present with severe nosocomial pneumonia at early onset, (2) patients with risk factors who present with mild-to-moderate nosocomial pneumonia occurring any time during hospitalization, and (3) patients with severe nosocomial pneumonia either of early onset with specific risk factors or of late onset without risk factors. Patients belonging to risk group 1 usually are infected with E coli or S aureus; Klebsiella, Proteus, Serratia, or Haemophilus, species; or streptococci. Patients in risk group 2 have infection with the previous organisms, but anaerobes, S aureus, Legionella species, and P aeruginosa also may be present. In risk group 3, the core organisms are present and P

aeruginosa, Acinetobacter species, and methicillin-resistant S aureus are the additional possibilities. Definition of severe hospital-acquired pneumonia Admission to the ICU is indicated. Respiratory failure is defined as the need for mechanical ventilation or the requirement for fraction of inspired oxygen to be greater than 35% in order to maintain oxygen desaturation of greater than 90%. Rapid radiographic progression, multilobar pneumonia, or cavitation of a lung infiltrate is present. Evidence of severe sepsis with hypotension and/or an organ dysfunction is present. Shock state is present, as indicated by a systolic blood pressure of less than 90 mm Hg or a diastolic blood pressure of less than 60 mm Hg. Vasopressors are required for more than 4 hours. Urine output is less than 20 mL/h, or total urine output is less than 80 mL in 4 hours. Acute renal failure is present that requires dialysis. Empiric therapy for community-acquired bacterial pneumonia - Based on recommendations by the American Thoracic Society (1993) and consensus guidelines by the Canadian Infectious Disease Society/Canadian Thoracic Society (2000) Table 1. Outpatient Pneumonia Without Comorbidity in Patients Aged 60 Years or Younger* Organisms S pneumoniae M pneumoniae C pneumoniae H influenzae Miscellaneous Legionella species, S aureus, aerobic gram-negative bacilli Therapy 1st choice - Macrolide 2nd choice - Doxycycline *Excludes patients at risk for HIV In roughly one third to one half of the cases, no etiology was identified.

 Erythromycin, clarithromycin, or azithromycin Table 2. Outpatient Bacterial Pneumonia With Comorbidity in Patients Aged 60 Years or Older* Organisms S pneumoniae H influenzae Aerobic gram-negative bacilli S aureus Miscellaneous M catarrhalis, Legionella species, Mycoplasma Therapy COPD (no recent antibiotics or oral steroids within past 3 mo) 1st choice Newer macrolides 2nd choice Doxycycline COPD (recent antibiotics or oral steroids in past 3 mo) 1st choice Respiratory fluoroquinolone* 2nd choice Amoxicillin/clavulanate + macrolide or second-generation cephalosporin + macrolide Suspected microaspiration Oral anaerobes 1st choice Amoxicillin/clavulanate and/or macrolide or fourth-generation fluoroquinolone (eg, moxifloxacin) 2nd choice Third-generation fluoroquinolone (eg, levofloxacin plus clindamycin or metronidazole *Excludes patients at risk for HIV In roughly one third to one half of the cases, no etiology was identified. Table 3. Hospitalized Patients With Community-Acquired Bacterial Pneumonia (admission to medical ward)* Organisms S pneumoniae H influenzae Polymicrobial (including aerobic bacteria) Aerobic gram-negative bacilli Legionella species S aureus C pneumoniae

Miscellaneous M pneumoniae, M catarrhalis Therapy 1st choice - Respiratory fluoroquinolone 2nd choice Second-generation or third-generation cephalosporin + macrolide *Excludes patients at risk for HIV In roughly one third to one half of the cases, no etiology was identified. Table 4. Severe Hospitalized Patients With Community-Acquired Bacterial Pneumonia (admission to ICU)* Organisms S pneumoniae Legionella species Aerobic gram-negative bacilli M pneumoniae Miscellaneous H influenzae Therapy 1st choice Antipseudomonal fluoroquinolone (eg, ciprofloxacin) plus antipseudomonal beta-lactam (eg, ceftazidime, piperacillintazobactam, carbapenem) or aminoglycoside (eg, gentamicin, tobramycin, amikacin) 2nd choice Triple therapy with antipseudomonal beta-lactam plus aminoglycoside plus macrolide *Excludes patients at risk for HIV In roughly one third to one half of the cases, no etiology was identified. Table 5. Patients With Mild-to-Moderate Hospital-Acquired Bacterial Pneumonia, No Unusual Risk Factors, and Onset at Any Time; or, Patients With Severe HospitalAcquired Pneumonia With Early Onset* Core Organisms Enteric gram-negative bacilli (Nonpseudomonal) Enterobacter species, E coli Klebsiella species Proteus species Core Antibiotics Cephalosporin Second-generation or nonpseudomonal thirdgeneration Beta-lactam/beta-lactamase inhibitor combination

S marcescens

If allergic to penicillin, fluoroquinolone or clindamycin + aztreonam Methicillin-sensitive S aureus

H influenzae S pneumoniae *Excludes patients with immunosuppression

Table 6. Patients With Mild-to-Moderate Hospital-Acquired Bacterial Pneumonia With Risk Factors, Onset at Any Time* Core Organisms, Core Antibiotics Anaerobes (recent abdominal surgery, witnessed aspiration) Clindamycin or beta-lactam/betalactamase inhibitor (alone) S aureus (coma, head trauma, diabetes mellitus, renal failure) +/-vancomycin (until methicillinresistant S aureus is excluded) Legionella (high-dose steroids) Erythromycin +/- rifampin P aeruginosa (prolonged ICU stay, steroids, antibiotics, structural lung disease Treat as severe hospital-acquired pneumonia *Excludes patients with immunosuppression Table 7. Patients With Severe Hospital-Acquired Bacterial Pneumonia With Risk Factors and Early Onset or Patients With Severe Hospital-Acquired Pneumonia and Late Onset* Core Organisms, Plus the Following Therapy P aeruginosa Acinetobacter species Consider methicillin-resistant S aureus Aminoglycoside or ciprofloxacin plus one of the following: Antipseudomonal penicillin Beta-lactam/beta-lactamase inhibitor Ceftazidime or cefoperazone Imipenem +/-vancomycin *Excludes patients with immunosuppression

Consultations: Consultation with infectious disease and/or pulmonary specialists is suggested in difficult cases. Patients requiring noninvasive mechanical ventilation or intubation may need consultation with a critical care medicine specialist to aid in management after admission to the ICU. A pharmacist and/or infection control specialist may be of assistance in providing information on hospital or regional bacterial resistance and sensitivity patterns. MEDICATION The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications. Drug Category: Antibiotics -- The initial antibiotic to treat low-risk patients is a macrolide. Macrolides are effective against most likely organisms in community-acquired bacterial pneumonia. Macrolides are used for gram-positive organisms, Legionella, and Mycoplasma. Azithromycin administered IV has the advantage of once-daily dosing over IV erythromycin. Macrolides, as a class, have the potential to cause adverse GI effects. Newer agents are expensive, have fewer adverse GI effects, and fewer drug interactions compared to erythromycin. Macrolides are used for community-acquired pneumonia in patients younger than 60 years who are nonsmokers and have no comorbidity. Newer macrolides offer better compliance through reduced dosing frequency and improved activity against H influenzae and Mycoplasma. Patients with community-acquired pneumonia who are older than 60 years or have comorbidity still are susceptible to S pneumoniae, but broader coverage is required to include Haemophilus, Moraxella, and other gram-negative organisms. Therefore, empiric therapy would include one of the macrolide agents outlined above plus one of the secondgeneration or third-generation cephalosporins, amoxicillin-clavulanate, or respiratory fluoroquinolone. The choice of antimicrobial agent is based on the severity of patient illness, host factors (eg, comorbidity, age), and presumed causative agent (see Table 1, Table 2, and Table 3). Outpatients are prescribed oral agents, and parenteral antibiotics are prescribed to patients admitted to the hospital. Second-generation cephalosporins have added activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis in addition to the gram-positive activity of firstgeneration cephalosporins. Third-generation cephalosporins have wider activity against most gram-negative bacteria, such as Enterobacter, Citrobacter, Serratia, Neisseria, Providencia, and Haemophilus species, including beta-lactamaseproducing strains.

Second-generation cephalosporins are not effective against Legionella or Mycoplasma. Generally, they are well tolerated but expensive. Oral second-generation and thirdgeneration cephalosporins offer increased activity against gram-negative agents and may be effective against ampicillin-resistant S pneumoniae. IV cephalosporins may be combined with a macrolide agent in patients with communityacquired pneumonia who are admitted to the hospital. They broaden the gram-negative coverage and, in the case of third-generation agents, may be effective against resistant S pneumoniae. Also, ceftazidime, a third-generation agent, is effective against Pseudomonas. When a severely ill patient has features of sepsis, respiratory failure, or neutropenia, treatment with an IV macrolide is combined with an IV third-generation cephalosporin. An alternative regimen may include imipenem, meropenem, or piperacillin/tazobactam plus a macrolide plus vancomycin. A fulminant course should lead to consideration of Legionella, Mycoplasma, psittacosis, and Q fever as the cause of bacterial pneumonia. Drug Name Azithromycin (Zithromax) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Adult Dose Day 1: 500 mg PO Days 2-5: 250 mg PO qd Alternatively: 500 mg IV qd Pediatric Dose Day 1: 10 mg/kg PO once; not to exceed 500 mg/d Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d Contraindications Documented hypersensitivity; hepatic impairment; sudden death may occur when taken concurrently with pimozide Interactions May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, elderly, or debilitated patients Drug Name Clarithromycin (Biaxin) -- Another initial DOC in otherwise uncomplicated pneumonia. Appears to cause more GI symptoms than azithromycin (eg, gastric upset, metallic taste). Adult Dose 500 mg PO bid for 10 d Pediatric Dose <6 months: Not recommended >6 months: 7.5 mg/kg PO bid for 10 d; not to exceed 500 mg/dose Contraindications Documented hypersensitivity; those taking pimozide or cisapride Interactions Toxicity increases with coadministration of fluconazole, astemizole, and pimozide; clarithromycin effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants,

cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; serious cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies Drug Name Erythromycin (E.E.S., Erythrocin, Ery-Tab) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. May result in GI upset, causing some to prescribe an alternative macrolide or change to tid dosing. Covers most potential etiologic agents, including Mycoplasma species. PO regimen may be insufficient to adequately treat Legionella species. Erythromycin is less active against H influenzae. Although standard course of treatment seems to be 10 d, treating until patient has been afebrile for 3-5 d seems to be a more rational approach. Adult Dose 500 mg PO qid (some choose 333 mg tid) Hospitalized patients with severe pneumonia: 1 g IV q6h; alternatively, 15-20 mg/kg/d IV in divided doses q6h Pediatric Dose 7.5 mg/kg/d PO divided bid; alternatively, 20-40 mg/kg/d IV divided q6h or by constant infusion; not to exceed 4 g/d Contraindications Documented hypersensitivity; hepatic impairment Interactions Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur Drug Name Amoxicillin and clavulanate (Augmentin) -- Alternative for patient who is allergic to or intolerant of macrolides. Usually well tolerated and gives good coverage to most infectious agents. Not effective against Mycoplasma and Legionella species. Cost is a major factor. Adult Dose 500-875 mg PO for 10 d or until afebrile for 3-5 d Pediatric Dose 25-45 mg/kg/d amoxicillin PO divided q12h Contraindications Documented hypersensitivity Interactions Risk of increased bleeding when coadministered with warfarin or heparin, possibly because of additive effects Pregnancy B - Usually safe but benefits must outweigh the risks.

Precautions Give for a minimum of 10 d to eliminate organism and prevent sequelae (eg, endocarditis, rheumatic fever); following treatment, perform cultures to confirm eradication of streptococci Drug Name Doxycycline (Doryx, Bio-Tab) -- Alternative agent for patients who cannot be given macrolides or penicillins. Inhibits protein synthesis and thus bacterial growth by binding with 30S and, possibly, 50S ribosomal subunits of susceptible bacteria. Adult Dose 100 mg PO bid for 10 d or until afebrile for 3-5 d Pediatric Dose <8 years: Not recommended >8 years: 2-5 mg/kg/d qd or divided bid; not to exceed 200 mg/d Contraindications Documented hypersensitivity; severe hepatic dysfunction Interactions Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy Pregnancy D - Unsafe in pregnancy Precautions Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines Drug Name Vancomycin (Vancocin) -- Classified as glycopeptide agent that has excellent gram-positive coverage, including methicillin-resistant S aureus. To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use creatinine clearance to adjust dose in patients diagnosed with renal impairment. Adult Dose 500 mg IV q6h or 1 g IV q12h; not to exceed 10 mg/min Pediatric Dose 40 mg/kg/d divided tid/qid Contraindications Documented hypersensitivity Interactions Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Caution in renal failure and neutropenia; red man syndrome is caused by IV infusion that is too rapid (dose administered over a few min) but rarely happens when dose administered as 2-h administration or as PO or IP administration; red man syndrome is not an allergic reaction Drug Name Trimethoprim and sulfamethoxazole (Bactrim DS, Septra) -- Inhibits bacterial synthesis of dihydrofolic acid by competing with paraaminobenzoic acid, inhibiting folic acid synthesis. Results in inhibition of bacterial growth. Antibacterial activity of TMPSMX includes common urinary tract pathogens, except P aeruginosa. Adult Dose 160 mg TMP/800 mg SMX PO bid for 10 d

Pediatric Dose <2 months: Not recommended >2 months: 8 mg TMP/kg/d divided bid Contraindications Documented hypersensitivity; megaloblastic anemia due to folate deficiency Interactions May increase PT of warfarin; thus, monitor coagulation tests and adjust dose as required; increased serum levels of both dapsone and TMP may occur when both medications are administered concomitantly; in patients who are elderly, incidence of thrombocytopenic purpura may increase when used concurrently with diuretics; hepatic clearance of phenytoin may be decreased and half-life prolonged; sulfonamides can displace MTX from plasma protein-binding sites, thus increasing free MTX concentrations, which may potentiate MTX effects in bone marrow depression; hypoglycemic response of sulfonylureas may increase with coadministration of both medications; may decrease renal clearance of zidovudine, causing increase in zidovudine levels Pregnancy C - Safety for use during pregnancy has not been established. Precautions Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer 5-15 mg/d leucovorin); caution in folate deficiency (eg, those with chronic alcoholism, elderly persons, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in individuals who are G-6-PD deficient; patients with AIDS may not tolerate or respond to TMP-SMX; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation Drug Name Levofloxacin (Levaquin) -- Rapidly becoming a popular choice in pneumonia. Lstereoisomer of the D/L parent compound ofloxacin, the D form being inactive. Good monotherapy that gives extended coverage against Pseudomonas species and excellent activity against pneumococcus. Agent acts by inhibition of DNA gyrase activity. PO form has bioavailability that reportedly is 99%. Adult Dose 500 mg/d PO/IV Hemodialysis, CAPD, or CrCl <20 mL/min: 250 mg q48h CrCl 20-49 mL/min: 250 mg q24h Pediatric Dose Not recommended Contraindications Documented hypersensitivity Interactions Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); do not administer within 24 h of live typhoid vaccine because reduces effects of vaccine Pregnancy C - Safety for use during pregnancy has not been established. Precautions In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment;

rapid infusion may cause hypotension; superinfections may occur with prolonged or repeated antibiotic therapy Drug Name Gemifloxacin (Factive) -- Fluoroquinolone antibiotic with wide range of activity against gram-negative and gram-positive organisms. Acts by inhibiting both DNA gyrase and topoisomerase IV (TOPO IV), which are essential for bacterial growth. Because of this dual mechanism, MIC values remain in the susceptible range for some double mutants (eg, Streptococcus pneumoniae). Indicated for mild-to-moderate CAP caused by S pneumoniae (including penicillinresistant strains; MIC value for penicillin >2 mg/mL), Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumoniae. Adult Dose 320 mg PO qd for 7 d Pediatric Dose <18 years: Not established >18 years: Administer as in adults Contraindications Documented hypersensitivity to gemifloxacin or other fluoroquinolones Interactions Coadministration with antacids and divalent or trivalent cations (eg, aluminum, magnesium, iron) significantly reduces absorption (administer 3 h before or 2 h after gemifloxacin); sucralfate decreases absorption and should be administered 2 h following gemifloxacin; may increase QT interval prolongation risk if coadministered with class IA (eg, quinidine, procainamide) or class III antiarrhythmic agents (sotalol, amiodarone), or other drugs known to prolong QT interval (eg, erythromycin, antipsychotics, antidepressants) Pregnancy C - Safety for use during pregnancy has not been established. Precautions Decrease dose by 50% with CrCl <40 mL/min; may prolong QT interval; may cause maculopapular rash Drug Name Cefprozil (Cefzil) -- Binds to one or more of the penicillin-binding proteins, which inhibits cell wall synthesis and results in bactericidal activity. Adult Dose 500 mg PO qd for 10 d Pediatric Dose <12 years: 7.5-15 mg/kg/d PO divided q12h for 10 d >12 years: Administer as in adults Contraindications Documented hypersensitivity Interactions Probenecid increases effects; coadministration with furosemide and aminoglycosides increases nephrotoxic effects Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Adjust dosage in renal impairment Drug Name Cefuroxime (Ceftin, Kefurox, Zinacef) -- Second-generation cephalosporin maintains gram-positive activity that first-generation cephalosporins have; adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration. Adult Dose 250 mg PO bid for 10 d Pediatric Dose <6 months: 20-50 mg/kg/d IV q12h

Infants and children: 75-150 mg/kg/d IV q8h; not to exceed 6 g/d Contraindications Documented hypersensitivity Interactions Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patient receiving potent diuretics (eg, loop diuretics); coadministration with aminoglycosides increases nephrotoxic potential Pregnancy C - Safety for use during pregnancy has not been established. Precautions Administer half dose if CrCl is 10-30 mL/min and one-quarter dose if <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy Drug Name Ceftriaxone (Rocephin) -- Third-generation cephalosporin with broad-spectrum and gram-negative activity, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. Adult Dose 1-2 g IV qd or divided bid; not to exceed 4 g/d Pediatric Dose >7 days to 6 months: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d >6 months: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d Contraindications Documented hypersensitivity Interactions Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Adjust dose in renal impairment; caution in breastfeeding women and allergy to penicillin Drug Name Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime) -- Third-generation cephalosporin with broad-spectrum and gram-negative activity, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. Adult Dose 1-2 g IV q8-12h Pediatric Dose <6 months: 30 mg/kg IV q12h >6 months to 12 years: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d >12 years: Administer as in adults Contraindications Documented hypersensitivity Interactions Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase levels Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Adjust dose in renal impairment Drug Name Cefaclor (Ceclor) -- Second-generation cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods. Determine proper dosage and route based on condition of patient, severity of infection, and susceptibility of causative organisms. Adult Dose 500 mg PO tid for 10 d Pediatric Dose 20-40 mg/kg/d PO divided q8-12h; not to exceed 2 g/d Contraindications Documented hypersensitivity

Interactions Alcoholic beverages consumed <72 h after taking may produce disulfiramlike reactions; may increase hypoprothrombinemic effects of anticoagulants; coadministration with potent diuretics and aminoglycosides (eg, loop diuretics) may increase nephrotoxicity; monitor renal function closely Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Reduce dosage by one half if CrCl is 10-30 mL/min and by one fourth if <10 mL/min; bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy Drug Name Telithromycin (KETEK) -- First antibiotic in a new class called ketolides. Blocks protein synthesis by binding to 50S ribosomal subunit (23S rRNA at domain II and V). Binding at domain II retains activity against gram-positive cocci (eg, S pneumoniae) in the presence of resistance. Resistance and cross-resistance have not been observed. Indicated to treat chronic bronchitis, acute sinusitis, and mild-to-moderate communityacquired pneumonia, including infections caused by multidrug-resistant S pneumoniae. Adult Dose 800 mg PO qd for 7-10 d Pediatric Dose Not established Contraindications Documented hypersensitivity; coadministration with cisapride or pimozide Interactions CYP 3A4 inhibitor and substrate; coadministration with other CYP 3A4 inhibitors (eg, itraconazole, ketoconazole) decreases elimination and increases Cmax and AUC; CYP 3A4 inducers (eg, rifampin) decreases telithromycin Cmax and AUC by 79% and 86% respectively; increases Cmax and AUC of other CYP 3A4 substrates (eg, cisapride, pimozide, simvastatin, lovastatin, atorvastatin, midazolam, triazolam); HMGCoA reductase inhibitors (eg, simvastatin, atorvastatin, lovastatin) should be temporarily discontinued owing to increased myopathy risk when coadministered; increases digoxin and theophylline serum levels; decreases sotalol Cmax and AUC secondary to decreased absorption; caution with other drugs that increase QTc interval (eg, quinidine, procainamide, dofetilide) Pregnancy C - Safety for use during pregnancy has not been established. Precautions Caution in severe renal impairment (limited data exist); consider the diagnosis of pseudomembranous colitis if diarrhea occurs following antibiotic treatment; may prolong QTc interval, caution with heart conduction abnormalities; caution with myasthenia gravis; common adverse effects include diarrhea and nausea; may rarely cause visual disturbances or increased liver enzymes FOLLOW-UP Further Inpatient Care: Hospitalization versus ambulatory care The decision to hospitalize patients with community-acquired pneumonia is dictated by a series of well-recognized risk factors that increase either the risk of death or the risk of a complicated course for a patient with community-acquired pneumonia. Specific risk factors for mortality or a complicated course of pneumonia include the following: Advanced age (>65 y) Comorbid illness or other findings - (1) COPD, including chronic suppurative diseases of the lung (eg, bronchiectasis, cystic fibrosis); (2) diabetes mellitus;

(3) chronic renal failure; (4) congestive heart failure; (5) chronic liver disease of any etiology; (6) suspicion of aspiration; (7) postsplenectomy state; and (8) chronic alcohol abuse or malnutrition Certain physical findings may predict a poor outcome from community-acquired bacterial pneumonia. These physical findings include the following: Respiratory rate in excess of 30 breaths per minute Diastolic blood pressure less than 60 mm Hg or systolic blood pressure less than 90 mm Hg Temperature higher than 38.3C (101F) Evidence of extrapulmonary sites of disease (eg, septic arthritis, meningitis) Confusion, decreased level of consciousness, or both The following series of laboratory findings predicts severe disease and, possibly, a complicated course of illness: WBC count of fewer than 4000/mm3 or more than 30,000/mm3, absolute neutrophil count of fewer than 1000/mm3 ABG determinations showing a PaO2 of less than 60 mm Hg or PaCO2 of greater than 50 mm Hg on room air Respiratory failure requiring mechanical ventilation Abnormal renal function as indicated by serum creatinine of greater than 1.2 mg/dL or blood nitrogen of greater than 20 mg/dL (>7 mmol/L) Chest radiographic findings for multilobar involvement, the presence of a cavity, rapid radiographic progression, and the presence of a pleural effusion Evidence of sepsis or organ dysfunction as manifested by a metabolic acidosis, an increased prothrombin time, increased partial thromboplastin time, or decreased platelets (a picture of disseminated intravascular coagulation). The decision to hospitalize also should take in to account social considerations, which include the absence of a responsible caregiver and or an unstable home situation. The Pneumonia Severity of Illness Scoring System (PSISS) was developed by Fine et al (Fine, 1997). This scoring system evaluates 20 different clinical and laboratory indices that are readily available. The PSISS is used to assist in deciding whether patients can be safely treated in an outpatient setting.

Table 8. Pneumonia-Specific Severity of Illness Scoring System for Patients With Community-Acquired Pneumonia Patient CharacteristicsNumber of Points Demographic factors Age Men Age in years Woman Age in years minus 10 Nursing home resident 10 Coexisting Illnesses (definitions listed below)* 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 min 20 Systolic blood pressure <90 mm Hg 20 Temperature <35C (95F) or >40C (104F) Pulse rate >125 breaths per min 10 Laboratory and Roentgenographic Findings Arterial pH <7.35 30 Blood urea nitrogen >30 mg/dL (11 mmol/L) Sodium <130 mmol/L 20 Glucose >250 mg/dL (14 mmol/L) 10 Hematocrit <30% 10 PaO2 <60 mm Hg 10 Pleural effusion 10

15

20

Coexisting illnesses: The diagnosis of congestive heart failure is documented by history or by findings on physical examination, chest radiograph, echocardiogram, multiplegated acquisition scan, or left ventriculogram. The clinical diagnosis of stroke or transient ischemic attack is documented by magnetic resonance imaging or CT scan findings. A history of chronic renal disease or abnormal blood urea nitrogen and creatinine concentrations should be documented in the medical record. Altered mental status is defined as disorientation to person, place, or time that is not known to be chronic or as stupor or coma. Hospitalization versus ambulatory care is determined by the total points calculated from the PSISS. Patients are categorized in to 5 risk classes, as follows: Risk class I - Older than 50 years, no preexisting illness or vital sign abnormality Risk class II - Fewer than 70 points

Risk class III - 71-90 points Risk class IV - 91-130 points Risk class V - More than 131 points Although further epidemiologic studies are required to make definite recommendations for hospital versus home care for patients with community-acquired pneumonia, preliminary data (Fine, 1997) indicate that patients in risk classes I and II can be treated at home with planned outpatient follow-up evaluations. Patients in risk class III should be observed in the emergency department before their disposition is decided. Patients in risk classes IV and V are ill and usually require admission to the hospital. Response to therapy Having initiated a course of therapy based on empiric guidelines, carefully evaluating the patient's response to therapy is essential. With appropriate antibiotic therapy, improvement in the clinical manifestations of pneumonia should be observed in 48-72 hours. Because of the time required for antibiotics to act, antibiotics should not be changed within the first 72 hours unless marked clinical deterioration occurs. With pneumococcal pneumonia, the cough usually resolves within 8 days and crackles heard on auscultation clear within 3 weeks. The timing of radiologic resolution of the pneumonia varies with patient age and the presence or absence of an underlying lung disease. The chest radiograph usually clears within 4 weeks in patients younger than 50 years without underlying pulmonary disease. In contrast, resolution may be delayed for 12 weeks or longer in older individuals and those with underlying lung disease. Patients who do not respond to treatment A common concern is patients who do not improve despite antibiotic treatment. If patients do not improve within 72 hours, consider an organism that is not covered by the initial empiric antibiotic regimen. Lack of response also could be secondary to drug resistance, nonbacterial infection, unusual pathogens (eg, P carinii, M tuberculosis), drug fever, or a complication such as empyema or abscess formation. One must broaden the differential diagnosis to include noninfectious etiologies such as malignancies, inflammatory conditions, or congestive heart failure. When reevaluating a patient who is not responding, a careful history of travel and animal exposure should be obtained to rule out unusual pathogens. If this is unrevealing, then further diagnostic procedures may be required. Bronchoscopy helps evaluate the airway for obstruction due to a foreign body or malignancy. Infection with previously unsuspected pathogens such as P carinii or M tuberculosis often is diagnosed using bronchoscopy. During bronchoscopy, protected brushing and bronchioalveolar lavage specimens may be obtained for microbiologic examination and quantitative cultures. Transbronchial biopsy also may be helpful in some cases. Routine bacterial cultures have limited utility when obtained from bronchoscopy after antibiotics have already been administered.

A retrospective study evaluated the use of fiberoptic bronchoscopy in nonresolving pneumonia. A specific diagnosis that could account for the prolonged course was found in 12 of 14 patients. The etiologies included Pneumocystis, mycobacteria, cytomegalovirus, and actinomycosis and noninfectious entities such as bronchioalveolar carcinoma, adenocarcinoma, and eosinophilic pneumonia. A second prospective study found the diagnostic sensitivity of video bronchoscopy after the initiation of antibiotics to be 41%. In addition to bronchoscopy, further imaging studies, such as CT scan of the thorax, may be helpful. Finally, open or thoracoscopic lung biopsy may need to be performed if all other procedures do not aid in diagnosis and the patient continues to be ill. Thoracoscopic lung biopsy is associated with less morbidity compared to the open lung biopsy. Other inpatient care Antibiotic therapy should be reevaluated based on laboratory data and clinical response. Adequate respiratory support (eg, low-flow oxygen, assisted ventilation) is provided as dictated by the patient's clinical situation. Bronchial hygiene includes suctioning of secretions, chest physiotherapy, and positioning to encourage dependent drainage. These are used to optimize the elimination of purulent sputum and to avoid atelectasis. General supportive measures include proper hydration, nutrition, and patient ambulation. Further Outpatient Care: When treated in an outpatient setting, arranging adequate follow-up evaluations for the patient is mandatory. Patients also should be instructed to return if their condition deteriorates. Patients should have a follow-up chest radiograph in approximately 6 weeks to ensure resolution of consolidation. Chest radiograph findings indicating nonresolution of symptoms should raise the consideration of an endobronchial obstruction as a cause of postobstructive pneumonia. A CT scan may be of benefit in these cases. Deterrence/Prevention: Prevention of community-acquired pneumonia Influenza vaccination for elderly individuals results in a reduction of the rate of hospitalization for pneumonia and influenza by 48-57%. The role of the pneumococcal vaccine has not been defined as clearly as that of the influenza vaccine. However, the advisory committee on immunization practice recommends pneumococcal vaccination for persons older than 65 years and for younger patients with chronic illnesses. Prevention of nosocomial pneumonia

A number of preventative strategies have been applied. Some of these probably are effective or promising, and some are currently being evaluated. The efficacious regimens are hand washing and isolation of patients with multiple resistant respiratory tract pathogens. Hand washing between patient contacts is a basic and often neglected behavior by medical personnel. Interventions that should be considered or undertaken include nutritional support, attention to the size and nature of the GI reservoir of microorganisms, careful handling of ventilator tubing and associated equipment, subglottic secretion drainage, and lateralrotation bed therapy. The regimens of unproven value in preventing nosocomial pneumonia, although used on limited investigational bases, are selective digestive decontamination with a regimen of topical and systemic antibiotic prophylaxis. Selective digestive contamination has been studied for many years with a goal of eliminating all potential pathogens from the GI tract. Incidence of nosocomial pneumonia is not always reduced; therefore, efficacy of these regimens has been questioned. Also, mortality reduction often is not observed. Some experimental regimens are undergoing clinical evaluation. These are monoclonal antibodies to specific bacterial antigens and reduction of endogenous sources of bacterial infection by mechanical means. The development of new biomaterials for endotracheal tubes is one such therapy, leading to the eradication of a reservoir of a large number of bacteria in the airway. Smoking cessation Complications: Destruction of lung tissue from infection (leading to bronchiectasis) Necrotizing pneumonia Empyema Pulmonary abscess Respiratory failure Acute respiratory distress syndrome Ventilator dependence Superinfection with gram-negative organisms Death Prognosis: Generally, prognosis is good in otherwise healthy patients with uncomplicated pneumonia. Advanced age, aggressive organisms (eg, Klebsiella, Legionella, resistant S pneumoniae), comorbidity, respiratory failure, neutropenia, and features of sepsis, alone or in combination, increase morbidity and mortality. Patient Education:

For excellent patient education resources, visit eMedicine's Pneumonia Center and Procedures Center. Also, see eMedicine's patient education articles Bacterial Pneumonia and Bronchoscopy. Medical/Legal Pitfalls: The guidelines for empiric management of community-acquired bacterial pneumonia are formed with the intent of following evidence-based recommendations, but the recommendations of these guidelines are not based on a firm scientific foundation. Future studies should focus on the following issues: Duration of therapy Duration of therapy related to severity of initial illness Appropriate time to switch hospitalized patients from parenteral therapy to oral therapy Pathogens responsible for pneumonia when no organism is identified with extensive diagnostic testing In the future, a number of unresolved questions about nosocomial pneumonia need to be examined. These should focus on the diagnosis of nosocomial pneumonia, determinants of specific pathogens, duration of therapy, and timing of switch to oral therapy. Ultimately, prevention of nosocomial pneumonia is the most effective way to avoid disease associated with mortality. In patients who are elderly or debilitated, if bacteremia is present with pneumococcus, the mortality rate remains approximately 40% even if treated. Empiric therapy for hospitalized patients initially should be broad and cover the likely causative organisms. Always consider the possibility of Legionella when evaluating community-acquired pneumonia because delayed treatment increases mortality significantly. Remember that the most prevalent causative organism is pneumococcus, regardless of the host; empiric therapy must be selected with this consideration in mind.