Pneumonia and Other Pulmonary Infections

8/11/2019 Pneumonia and Other Pulmonary Infections

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formation; a peribronchial distribution is characteristic, but

lobar consolidation may occur. Viruses generally produceinterstitial inflammation rather than air-space exudates. Theinfection is usually bilateral and causes diffuse alveolar damageand interstitial edema. Similar tissue responses may be initiated

byMycoplasma, Chlamydophila, and Legionella species; by gram-negative bacteremia (shock lung); and by other causes of theacute respiratory distress syndrome. Mycobacteria and fungitypically evoke a slow granulomatous response.

epidemiology and etiology

Community-Acquired Pneumonia

Like other respiratory tract illnesses, pneumonia is mostcommon in the winter because of the seasonal increase in

viral infections and the close contact of persons confinedindoors. Community-acquired pneumonias are a majorproblem in the United States, with an estimated four millioncases occurring annually.5 About one million cases requirehospitalization,5 and at least 60,000 result in death.6 Themortality of community-acquired pneumonia ranges fromless than 1% in patients who are not ill enough to requirehospitalization to 13.7% for hospitalized patients, 19.6% for

bacteremic patients, and 36.5% for patients admitted tointensive care units.7 Clinical and laboratory data can beused to determine which patients are at greatest risk fordeath and thus require hospitalization and aggressivetherapy. Comorbidity is the strongest risk factor, withneoplastic disease, neurologic disease, and alcoholism being

particularly worrisome.8 Advanced age is another strongpredictor of risk,6 in part because older patients oftenunderreport symptoms.7-9 Physical findings of high fever,tachypnea, confusion, hypoxia, and hypotension alsoportend an adverse result.10 The presence of extensiveradiographic abnormalities, especially bilateral pleuraleffusions, is associated with higher risk, as are laboratoryabnormalities such as hypoxia, azotemia, acidosis,hyponatremia, and hypophosphatemia. Postobstructive,aspiration, gram-negative, and staphylococcal pneumoniasare associated with a high mortality. Patients lacking these

adverse prognostic indicators have a low risk of death and

can usually be treated successfully as outpatients. Patientshospitalized for pneumonia have a greater than fivefoldlikelihood of requiring subsequent hospitalization forpneumonia than patients with other serious illnesses; it isimportant to be sure their influenza and pneumococcalimmunizations are up to date before discharge.11 Patientshospitalized for pneumonia also have substantially higherlong-term mortality than age-matched control subjects.11,12

In the preantibiotic era, pneumonia was nearly synonymouswith S. pneumoniae infection. Pneumococci still account for 30%to 60% of all community-acquired pneumonias for which anetiology can be determined.13 Pneumococci are particularlylikely to be responsible for community-acquired pneumoniassevere enough to require hospitalization and for pneumonia in

persons older than 60 years.14

The second most common bacterial cause of community-acquired pneumonia isH. influenzae, which accounts for about10% of cases13; patients with COPD are particularly vulnerable.Although infection with Moraxella catarrhalis is much lesscommon than infection withH. influenzae,M. catarrhalis is beingrecognized increasingly as a cause of community-acquiredpneumonia. LikeH. influenzae,M. catarrhalis has a predilectionfor patients with cardiopulmonary disease. In rare cases, M.catarrhalis causes fulminant pneumonia, bacteremia, or both.

Staphylococci and gram-negative bacilli are much lesscommon but more serious causes of community-acquiredrespiratory infections. Significant predisposing conditionsare required for these organisms to produce pneumonia. In

the community setting, staphylococcal pneumonia usuallyfollows influenza. Gram-negative pneumonias in thecommunity setting are most common in patients who haverecently been hospitalized and treated with antibiotics, insmokers and others with chronic lung disease, and inimmunosuppressed patients.2,15,16 Exposure to aerosols ofcontaminated water is an additional risk factor for infectionwith Pseudomonas aeruginosa,17 and alcoholism predisposesto Klebsiella pneumonia. Meningococcal pneumonia is rare.18

A variety of other bacteria, including L. pneumophila, cancause pneumonia in the community setting.14 Aspiration of

2006 WebMD, Inc. All rights reserved.August 2006 Update

ACP MedicineINFECTIOUS DISEASE:XX Pneumonia and Other Pulmonary Infections2

Modifying Factors

Antibiotic therapy, respiratory therapy, hospitalization

Tracheal intubation

Sedatives and hypnotics, alcohol and drug abuse, neurologic disorders,age and debility, tracheal intubation (gastrointestinal disorders)

Viral infections, smoking, chemical irritants, dehydration

Smoking, viral infections, advanced age, aspirin (?)

None

Decreased fibronectin levels in seriously ill patients

Foreign bodies, obstructing tumors, bronchostenosis

Vascular obstruction (e.g., emboli)

Viral infections, smoking (both increase macrophage numbers but impairfunction)

Cytotoxic therapy

Immunosuppressive disorders and therapy

Immunosuppressive disorders and therapy

Gastric acidsuppressing drugs, atrophic gastritis

Mechanism

Normal flora of upper respiratory tract

Aerodynamic properties of upper respiratory tract

Protective reflexes (e.g., cough, sneeze, gag, bronchoconstrictor)

Mucous carpet that entraps particles

Ciliary action, mucociliary transport

Antibacterial substances in respiratory secretions (e.g., lysozyme,lactoferrin, 1-antitrypsin, IgA)

Fibronectin in respiratory secretions (competitively inhibits adherenceof gram-negative bacilli)

Free drainage of tracheobronchial tree

Rich blood supply

Alveolar macrophages

Lymphatic tissue

Humoral immunity (B cells, IgG and IgA antibodies, complement,polymorphonuclear neutrophils)

Cellular immunity (T cells, lymphokines, mononuclear phagocytes)

Gastric acid

Table 2 Host Defense Mechanisms against Pulmonary Infection


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mixed mouth flora is responsible for infection in somepatients.

In about half the patients with community-acquiredpneumonia, the etiologic agent cannot be identified. 19

Especially in younger patients, many of these infectionsresult from so-called atypical agents, which lack the cellwall structure that characterizes ordinary bacteria. In astudy of patients with a mean age of 41 years, for example,

M. pneumoniae accounted for 22.8% of community-acquired

pneumonias, and C. pneumoniae for 10.7%; in addition,influenza A accounted for 2.7%.19 C. pneumoniae is alsoincreasingly being recognized as a cause of community-acquired pneumonia in adults with COPD [see 14:III ChronicObstructive Diseases of the Lung]. Respiratory tract viruses,including respiratory syncytial virus, adenoviruses, andinfluenza or parainfluenza viruses, 20 can also causecommunity-acquired pneumonias in persons of all ages.1,14

Hospital-Acquired Pneumonia

Pneumonia is the second most common nosocomialinfection in the United States21; about 200,000 cases occurannually, accounting for 17.8% of all hospital-acquiredinfections and 40,000 to 70,000 deaths. Risk factors for

nosocomial infections include aspiration, COPD or otherchronic severe illnesses, thoracic and upper abdominal surgery,and treatment in an ICU. Patients who require mechanicalventilation are particularly at risk; pneumonia develops in 9%to 24% of patients who require intubation for more than 48hours.22 Ventilated patients who acquire nosocomialpneumonia have a much higher mortality (54%) thancomparably ill ventilated patients who do not acquirepneumonia (27%).

The bacterial etiologies of hospital-acquired pneumonias arevery different from those of community-acquired pneumonias.Many nosocomial pneumonias are polymicrobial; gram-negative bacilli are isolated in 47% of patients, anaerobes in35%, and Staphylococcus aureus in 26%. In contrast,

pneumococci account for no more than 10% of hospital-acquired pneumonias. Other organisms that are associatedwith community-acquired infections can occasionally causepneumonia in the hospital setting; such organisms includeLegionella species,M. pneumoniae, and C. pneumoniae.23

Pseudomonas, Klebsiella, and Escherichia coli are the mostcommonly implicated causes of gram-negative pneumonias.Nosocomial gram-negative pneumonias often occur inpatients with serious underlying diseases; as a result, mortalityis as high as 30% to 50%. Previous antibiotic administration,respiratory therapy, chronic illness, and confinement to bedpredispose to oropharyngeal colonization with gram-negative

bacilli, which occurs in up to 45% of ICU patients and precedespneumonia in most cases. Upper intestinal colonization has

also been implicated, but its importance is uncertain. The 2005guidelines of the American Thoracic Society and the InfectiousDiseases Society of America consider health careassociatedpneumonia to be part of the spectrum of hospital-acquiredpneumonias.24 Patients who develop pneumonia within 90days of being hospitalized in an acute care hospital for 2 ormore days should be approached as if they had hospital-acquired pneumonia, as should residents of long-term carefacilities, hemodialysis patients, and patients who received I.V.antibiotics, wound care, or chemotherapy within 30 days ofdeveloping pneumonia.25

Pneumonia in Immunosuppressed Patients

Immunosuppressed patients, particularly those withAIDS,26,27 are vulnerable to a broad range of pulmonarypathogens. In addition to being susceptible to the manyorganisms that produce community- and hospital-acquiredpneumonias, these patients are susceptible to manyopportunistic microbes that are unlikely to cause pneumoniain immunologically competent hosts.28 Such organisms include

bacter ia (e .g., Pseudomonas, Nocardia , and Legionella)

mycobacteria (e.g., M. avium complex), viruses (e.g.cytomegalovirus and herpesvirus), fungi (e.g., CandidaAspergillus , Mucor, and Pneumocystis jiroveci [formerly Pcarinii]), and protozoa (e.g., Toxoplasma gondii). As a resultimmunosuppressed patients require an aggressive approachto diagnosis and therapy [see 7:X Infections Due to Haemophilus

Moraxella, Legionella, Bordetella, and Pseudomonas, 7:XI InfectionsDue to Brucella, Francisella, Yersinia pestis, and Bartonella, and7:XXXVIII Mycotic Infections in the Compromised Host].

diagnosis

Clinical Features

Classic signs and symptoms of pneumonia include cough

sputum production, chest pain, fever, chills, hypoxia, anddyspnea. Although the results of physical examination inpatients with typical pneumonias are often nonspecific, theexamination may reveal rales, rhonchi, or bronchial breathsounds, as well as percussion dullness over the involvedsegments of the lung. Pleural effusions may accompanypneumonia. The chest x-ray shows infiltrates.

Nonbacterial and bacterial pneumonias have differingclinical presentations. Although both types of pneumoniacan affect persons of all ages, nonbacterial pneumonias aremost common in older children and young adults. Patientswith viral, mycoplasmal, or chlamydial pneumonias willoften complain of a severe hacking cough, but substantialsputum production is unusual. Sputum production is also

minimal in patients with Legionnaires disease, but thesepatients are usually sicker than those with nonbacteriapneumonias [see 7:X Infections Due to Haemophilus, MoraxellaLegionella, Bordetella, and Pseudomonas].

Patients with bacterial pneumonias are more likely tohave copious sputum productionas well as an abruptonset of illness, high temperatures, chills, and developmentof significant pleural effusionsthan are patients withnonbacterial pneumonias.

On physical examination, a patient with bacteriapneumonia generally looks sicker than a patient withnonbacterial pneumonia, and chest examination of patientswith bacterial pneumonia often reveals signs ofconsolidation or at least localized rales and rhonchi. In

contrast, the chest examination of patients with nonbacteriapneumonias typically shows only fine rales, and often, thephysical findings are less extensive than the radiologicabnormalities.

Laboratory Studies

Patients with bacterial pneumonias are more likely tohave polymorphonuclear leukocytosis. If the chest x-rayreveals lobar or segmental consolidation, abscess formationor significant pleural effusion, bacterial pneumonia is morelikely. A patchy infiltrate can occur in either process, but a




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true interstitial infiltrate suggests a nonbacterial etiology.The absence of radiographic abnormalities should notsupersede clinical judgment in managing patients withsuspected pneumonia.14,29 Computed tomography isextremely helpful in diagnosing complex infections.

Although the sputum examination has been the traditionalkey to the etiologic diagnosis of pneumonia, the high successrate of empirical therapy for uncomplicated community-acquired pneumonia has diminished the importance of, as

well as the use of, the sputum examination. Still, microscopicexamination and culture of a good sputum specimen30 can behelpful, particularly in complicated or unusual cases. Thesputum of patients with bacterial pneumonia is typically thickand either green or brownish and is sometimes blood tinged. Ifthe patient cannot expectorate spontaneously, pulmonaryphysiotherapy, intermittent positive pressure ventilation withhumidified air, or nasotracheal suction may be used to obtainthe specimen. The Gram stain of sputum from patients with

bacterial pneumonia usually reveals abundant polymorpho-nuclear leukocytes and will often disclose the primarypathogens. Patients with nonbacterial pneumonias orLegionnaires disease generally produce only scant quantitiesof thin sputum. In influenzal pneumonia, the sputum may be

bloody . The Gram stain of sputum from pat ients withpneumonia from atypical agents reveals an absence of bacteriaand a scant cellular response; in patients with mycoplasmalpneumonia, mononuclear cells may predominate.31 It can bedifficult to determine the etiology in patients with nosocomialpneumonias; prolonged hospitalization, antibiotic administra-tion, and ventilatory therapy predispose to colonization withorganisms that contaminate sputum specimens but can alsocause pneumonia. Bronchoalveolar lavage is effective in identi-fying the responsible pathogen.32

Kits for the detection of nucleic acids from Legionella,Mycoplasma , and mycobacterial species in sputum arecurrently available, and polymerase chain reaction testsmay soon be available for the detection of other pathogens.33

Urinary antigen assays may assist in the diagnosis ofLegionella34 and pneumococcal35 pneumonias. Although

blood cultures are of limited value in the management ofpatients with community-acquired pneumonias, theyshould be obtained in patients who are ill enough to requirehospitalization. 36

Invasive Studies

In immunocompromised patients, numerous opportunisticagents can cause pneumonia, and aggressive techniques may

be required to obtain a satisfactory specimen. Althoughinvasive procedures rarely are necessary in immunocompetentpatients, they may be required in patients who present withunusual features, are critically ill, or fail to respond to

conventional therapy. Procedures such as transtrachealaspiration, bronchoscopy (sometimes including transbronchial

biopsies), bronchial brushing, and percutaneous lung taps maybe necessary; bronchoalveolar lavage is a particularly usefultechnique and is generally well tolerated.37 If these lessinvasive techniques fail to produce a diagnosis, open lung

biopsy should be considered.

Diagnosis of Ventilator-Associated Pneumonia

The diagnosis of ventilator-associated pneumonias may bebased on clinical criteria, Gram stains and cultures of tracheal

aspirates, and pulmonary infection scores or invasivetechniques.38,39 Even with bronchoscopy and lavage, thediagnosis can be difficult; the detection of a marker calledsoluble triggering receptor expressed on myeloid cells(sTREM-1) in lavage fluid may be an indication of ventilator-associated pneumonia.40

differential diagnosis

Noninfectious diseases can be mistaken for infections of the

respiratory tract. Asthmatic bronchitis and hypersensitivitypneumonitis are common examples. COPD, includingemphysema and bronchiectasis, may be misleading if previousx-rays are not available. Atelectasis, pulmonary infarction,pulmonary edema, and lung tumors may also be confusedwith pneumonia. Hypersensitivity reactions and toxinsinthe form of aerosols, systemic drugs, or chemicalsproduceclinical illnesses and pulmonary infiltrates simulating those ofinfectious pneumonia. Radiation pneumonitis, sarcoidosis,vasculitis, uremic pneumonitis, pulmonary hemorrhage,eosinophilic pneumonia, organizing pneumonia, and lipoidpneumonitis are included in the differential diagnosis [see 14:VChronic Diffuse Infiltrative Lung Disease].

One of the primary considerations in patients with a lower

respiratory tract infection is to distinguish between acutebronchitis and pneumonia. The distinction is anatomic ratherthan etiologic because the same basic range of organisms cancause the two syndromes. As a result, these conditions oftenoverlap clinically, but bronchitis requires less intensive therapy[see Acute Bronchitis, below].

treatment

Certain general principles are useful in the care of allpatients with pneumonia. Adequate hydration is important tohelp clear secretions; hydration can be achieved by systemicadministration of fluids and local airway humidification.Expectorants such as guaifenesin may be helpful in looseningthe sputum. Although clinical trials have demonstrated that

chest physiotherapy does not hasten the resolution ofpneumonia, this traditional therapeutic modality may providesymptomatic benefit to patients with copious airwaysecretions. In general, the cough reflex should not besuppressed in patients with bacterial infections, becausecoughing is an important mechanism for clearing secretions. Ifsevere paroxysms of coughing produce respiratory fatigue orharsh pain, however, temporary relief may be obtained withsmall doses of codeine. Chest pain should be treated withanalgesics that do not suppress cough. If hypoxia is present,oxygen should be administered. Persons who have COPD andretain carbon dioxide must be monitored very closely becauseoxygen therapy can lead to respiratory depression.

Specific antimicrobial therapy depends on the etiologic

agent. Whereas culture and sensitivity testing require at least24 to 48 hours to provide definitive information, the clinicalsetting, chest x-ray, and sputum Gram stain usually enable thephysician to make a reasonable presumptive diagnosis and toinitiate therapy at once. Treatment can then be modified asnecessary on the basis of culture results. Because antibioticspenetrate sputum by passive diffusion, it is important tomaintain adequate blood levels of these drugs. Theadministration of antibiotics by aerosol is not indicated formost cases of pneumonia but may help patients with cysticfibrosis and endobronchial Pseudomonas infections.41




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It is best to choose an antibiotic regimen directed specificallyat organisms seen on Gram stain and, after 24 to 48 hours,identified from sputum or blood cultures. Even if these dataare lacking, however, a reasonable choice of initial antimicro-

bial therapy can be made on the basis of the epidemiologicsetting and clinical features.

Community-Acquired Pneumonia

Several factors are responsible for rapid changes in theempirical treatment of community-acquired pneumonias: theemergence of drug-resistant pneumococci; the increasingpopulation of elderly or chronically ill patients who arevulnerable to infections caused by H. influenzae and M.catarrhalis; the increased importance of atypical pathogens such

asM. pneumoniae, C. pneumoniae, and L. pneumophila; and theavailability of new fluoroquinolones with enhanced activityagainst gram-positive cocci (including penicillin-nonsensitivepneumococci) and anaerobes (including mouth flora). Forpatients who do not require hospitalization, several therapeuticoptions are available [see Tables 3 and 4].42 Erythromycin is cost-effective, but the so-called advanced macrolides clarithromycinand azithromycin may be preferable because of their bettergastrointestinal tolerability and their activity against

Haemophilus and Moraxel la species.43,44 Doxycycline is aneffective and inexpensive alternative.45 However, because of

the increasing prevalence of drug-resistant pneumococci, useof one of the so-called respiratory fluoroquinolones (i.e.levofloxacin, moxifloxacin, and gemifloxacin) is recom-mended.46 These agents have excellent activity against themajor causes of community-acquired pneumonia, andprospective trials have been very favorable.47 They are aparticularly good choice for patients who have recentlyreceived antibiotic therapy.48 The use of high-dose levofloxacin(750 mg a day) may enable short-course (5-day) therapy,potentially improving compliance and reducing costs.49 Therespiratory fluoroquinolones may also emerge as drugs ofchoice for patients with community-acquired pneumonia whorequire hospitalization; levofloxacin and moxifloxacin areavailable in preparations for intravenous administration [see

Table 5]. Levofloxacin-resistant pneumococci are stilluncommon, but their emergence is a concern.50,51 In additiondual therapy may be preferable for patients with severepneumococcal pneumonia.52,53 For that reason, patients withmoderate to severe community-acquired pneumonia may

benefit from cefotaxime or ceftriaxone in combination with amacrolide or a fluoroquinolone.42 Because vancomycin is activeagainst virtually all pneumococci, it can be substituted for thethird-generation cephalosporin in patients allergic to -lactamantibiotics; linezolid is another alternative.54 When aspiration issuspected, penicillin, clindamycin, or metronidazole is useful



Preferred Treatment Options

A respiratory fluoroquinolone,1 a macrolide,2 or doxycycline

A respiratory fluoroquinolone1 alone; an advanced macrolide3 plus high-dose amoxicillin4; orhigh-dose amoxicillin-clavulanate5

A respiratory fluoroquinolone1 or an advanced macrolide3

A respiratory fluoroquinolone,1 or an advanced macrolide3 plus a-lactam7

Amoxicillin-clavulanate8 or clindamycin9

A-lactam7 or a respiratory fluoroquinolone1

A respiratory fluoroquinolone,1 or an advanced macrolide3 plus a -lactam7

A respiratory fluoroquinolone,1 or an advanced macrolide3 plus a -lactam7

A-lactam7; vancomycin plus a respiratory fluoroquinolone1; or an advanced macrolide3

An antipseudomonal agent10 plus ciprofloxacin; an antipseudomonal agent8 plus a respira-

tory fluoroquinolone1; or an advanced macrolide3

Clinical Variables/Settings

Outpatient therapy

Previously healthy

Antibiotic therapy within 3 months

Comorbidities6

No recent antibiotics


Suspected aspiration pneumonia

Influenza with suspected bacterial superinfection

Inpatient therapy

No recent antibiotics


ICU therapy

Pseudomonas not an issue

Pseudomonas a concern

Table 3 Initial Empirical Antibiotic Therapy in Patients with SuspectedCommunity-Acquired Pneumonia*42

ote: all superscript numbers in table refer to footnotes below:

1. Respiratory fluoroquinolones: levofloxacin, moxifloxacin, or gemfloxacin.

. Macrolides: erythromycin, clarithromycin, azithromycin.

. Advanced macrolides: clarithromycin, azithromycin.

. High-dose amoxicillin, 1 g p.o. three times a day.

. High-dose amoxicillin-clavulanate, 2 g p.o. two times a day.

. Comorbidities: chronic obstructive pulmonary disease, congestive heart failure, diabetes, renal insufficiency, malignancy.

. -Lactam antibiotics: high-dose amoxicillin or amoxicillin-clavulanate, cefpodoxime, cefprozil, or cefuroxime.

. Amoxicillin-clavulanate, 500 mg p.o., q. 8 hr

. Clindamycin, 150300 mg p.o., q. 6 hr

10. Antipseudomonal agents: piperacillin-tazobactam, imipenem, meropenem, ceftazidime, cefepime, or aztreonam (should be chosen for -lactamallergic patients).

Patients with health careassociated pneumonias should be considered as having hospital-acquired pneumonias [ see Treatment, Hospital-Acquired Pneumonias and reference 24].

For details, see 7:XIV Antimicrobial Therapy (especially Tables 3 and 4).


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amoxicillin-clavulanate, imipenem, meropenem, andrespiratory fluoroquinolones are also active against oralanaerobes [see Table 6].

In all cases, antibiotic therapy should be tailored to theresults of culture and sensitivity, the clinical response, and theoccurrence of side effects. Many patients who require intra-venous antibiotics initially can be switched to oral therapywithin 3 days,55 facilitating early hospital discharge.56 In mostpatients with uncomplicated pneumococcal pneumonia,antibiotics can be discontinued after 3 afebrile days; mostpatients with other bacterial pneumonias are treated for 7 to 14days, and most with atypical pneumonias are treated for 10 to21 days.

Immunizations may help prevent community-acquiredpneumonia. Each fall, influenza vaccine should be offered topatients 50 years of age and older and to other vulnerablepersons [see 7:XXV Respiratory Viral Infections]. Pneumococcalpolysaccharide vaccine should be offered to persons 65 years

of age and older and to others who are at increased risk57 [see7:I Infections Due to Gram-Positive Cocci]. Patients who haverecovered from one bout of pneumonia may benefit from bothvaccines.11

Hospital-Acquired Pneumonia

Because gram-negative bacilli and S. aureus cause manynosocomial pneumonias, patients with hospital-acquiredpneumonias require broad antimicrobial coverage until theresults of Gram stains, cultures, and sensitivity tests permitfocused therapy. Options for the initial treatment of hospital-acquired pneumonia include ticarcillin-clavulanate orpiperacillin-tazobactam; meropenem or imipenem-cilastatin; athird-generation cephalosporin plus nafcillin or vancomycin; afirst-generation cephalosporin plus an aminoglycoside; orvancomycin plus an aminoglycoside. The prevalence ofresistant bacteria in a particular hospital or patient care unitshould help guide the initial therapy; for example, if



Typical Dose

500 mg p.o., q. 24 hr for 10 days, or 750 mgp.o., q. 24 hr for 5 days

400 mg p.o., q. 24 hr

320 mg p.o., q. 24 hr

250500 mg p.o., q. 6 hr

250500 mg p.o., q. 12 hr

500 mg p.o. day 1, then 250 mg p.o. days 25

100 mg p.o., q. 12 hr

Drug

Fluoroquinolones

Levofloxacin

Moxifloxacin

Gemifloxacin

Macrolides

Erythromycin

Clarithromycin

Azithromycin

Doxycycline

Table 4 Initial Antibiotic Therapy for Community-Acquired Pneumonia in Outpatients*

Comments

Excellent first-line drugs

Cost-effective alternative, but GI intolerance is common

Better GI tolerability and activity againstHaemophilus andMoraxella; good first-line drug

Better GI tolerance and activity againstHaemophilus andMoraxella

Cost-effective alternative

*See text for details.For details, see 7:XIV Antimicrobial Therapy (especially Tables 3 and 4).Costs are derived from online pharmaceutical sources and are intended to indicate relative costs of available therapies.

GIgastrointestinal

Cost/Mo ($)

108 or 105

300

NA

27 or 40

297 or 260

276

42

Typical Dose

Cefotaxime, 12 g I.V. q. 4 hr;ceftriaxone, 12 g I.V. q. 1224 hr

500 mg p.o. or I.V. q. 24 hr

400 mg p.o. or I.V. q. 24 hr

Vancomycin, 1 g I.V. q. 12 hr

Linezolid, 600 mg p.o. or I.V. q. 12 hr

Regimen

Cephalosporins

Cefotaxime or ceftriaxone +a macrolide or afluoroquinolone

FluoroquinolonesLevofloxacin

Moxifloxacin

Vancomycin + a macrolide

or a fluoroquinolone

Linezolid + a macrolide ora fluoroquinolone

Table 5 Initial Antibiotic Therapy for Community-Acquired Pneumonia inPatients Who Require Hospitalization*

Comments

First-line treatment of choice for severely ill patients

First-line treatment, either alone or with a third-genera-tion cephalosporin

Alternative for severely ill patients who are allergic to-lactams

For severely ill patients who cannot tolerate -lactams orvancomycin

*See text for details.For details, see 7:XIV Antimicrobial Therapy (especially Tables 3 and 4).Costs are derived from online pharmaceutical sources and are intended to indicate relative costs of available therapies.For macrolide doses, see Table 4; azithromycin may be administered intravenously.

Cost/Mo ($)

310

300

3,648


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methicillin-resistant staphylococci are common, vancomycin isa desirable component of the initial therapy, and whenmultidrug-resistant Klebsiella organisms are common,meropenem or imipenem-cilastatin should be considered.Linezolid is an effective alternative to vancomycin for thetreatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.58 Patients with ventilator-associatednosocomial pneumonia may respond as well to 8 days ofantibiotics as they do to 15 days of therapy. 59 Because of thehigh mortality associated with pneumonias in the intensivecare unit, strategies to prevent pneumonia in the ICU have

been studied,60and comprehensive guidelines are available.61

Infections Caused by Legionella Species

legionnaires disease

Epidemiology and Etiology

Since it was first identified in 1976, Legionnaires disease hasbecome recognized as a common cause of both community-acquired and hospital-acquired pneumonias. Worldwide, itaccounts for between 2% and 15% of all community-acquiredpneumonias severe enough to require hospitalization.62 It isestimated that 10,000 to 25,000 cases occur in the United Stateseach year, but only 1,200 to 1,500 are reported annually. 63

Legionnaires disease is caused by L. pneumophila, a fastidious,

filamentous, flagellated, aerobic gram-negative bacillus. Theorganism can be grown on charcoalyeast extract agar;optimal growth occurs at 35 C in 5% carbon dioxide, butgrowth is slow, and a period of 3 to 6 days is required forcolonies to form.

At least nine serogroups of L. pneumophila exist; most clinicalisolates belong to serogroup 1. By special staining techniques,large numbers of the organism can be identified in tissuesections of alveoli, both within macrophages andextracellularly. Virulence factors of L. pneumophila and variousextracellular enzymes that the organism secretes have been

identified. L. pneumophila is able to survive intracellularly inhost leukocytes. Antibody is not protective, but cell-mediatedimmunity does promote recovery and prevent reinfection.

In nature, L. pneumophila survives principally in water andto a lesser extent, in soil. Human disease is acquired primarily

by inhalation of aerosols contaminated with organismsperson-to-person transmission has not been documentedContaminated water systems have been responsible for bothcommunity-acquired and hospital-acquired outbreaks [see 7:XInfections Due to Haemophilus, Moraxella, Legionella, Bordetellaand Pseudomonas].

The attack rate for Legionnaires disease appears to behigher in elderly persons and persons with underlying

conditions such as COPD, neoplastic disease, organtransplants, and renal failure. Although L. pneumophila is arelatively uncommon pathogen in persons infected with HIVit can cause severe disease in them.

Diagnosis

Clinical features Legionnaires disease is characterized bya 1-day prodrome of myalgias, malaise, and slight headacheafter an incubation period of 2 to 10 days. Acute onset of highfever, shaking chills, nonproductive cough, tachypnea, andoften, pleuritic pain ensues. The cough may subsequently

become slightly productive, but the sputum is not purulentObtundation or toxic encephalopathy is common, but frankmeningitis is not a feature. Abdominal pain, vomiting, and

especially, diarrhea may be present. Signs of consolidation onlung examination are present infrequently, but rales arecommonly heard. Chest radiographs show patchy orinterstitial infiltrates, which often progress to areas of nodularconsolidation in a single lobe or multiple lobes; minimaleffusions are present in up to one third of cases. Abscessformation is uncommon but has been observed. Pulmonaryfibrosis may occur in some survivors.

Although pneumonia is present in nearly all patients withLegionnaires disease, extrathoracic symptoms can be thepresenting or predominant features. Central nervous system,



Typical Dose

150300 mg p.o., q. 6 hr, to 600 mg I.V. q. 8 hr,depending on severity of infection

500 mg p.o., q. 6 hr, to 12 million units I.V. q. 4 hr,depending on severity of infection

500 mg p.o., q. 8 hr, to 500 mg I.V. q. 6 hr, dependingon severity of infection

500 mg p.o., q. 8 hr or 875 mg p.o., q. 12 hr

12 g ampicillin + 0.51 g sulbactam I.V. q. 6 hr

0.51 g I.V. q. 68 hr

1 g I.V. q. 8 hr

400 mg p.o. or I.V. q. 24 hr

500 mg p.o. or I.V. q. 24 hr

Drug

Clindamycin

Penicillin

Metronidazole

Amoxicillin-clavulanate

Ampicillin-sulbactam

Imipenem

Meropenem

Fluoroquinolones

Moxifloxacin

Levofloxacin

Table 6 Antibiotic Choices for Aspiration Pneumonia*

Comments

May be superior to penicillin

Traditional drug of choice

Useful in combination with penicillin

Alternative for oral therapy

Alternative useful in hospitalized patients



Excellent for community-acquired pneumonias butless active against oral anaerobes than penicillin,clindamycin, and metronidazole

*See text for details.For details, see 7:XIV Antimicrobial Therapy (especially Tables 3 and 4).Costs are derived from online pharmaceutical sources and are intended to indicate relative costs of available therapies.

Cost/mo ($)

312 or 601

22

28

391

300

310


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GI, and renal manifestations are especially common. L.pneumophila has been isolated from blood cultures, and theorganism can be found in many organs both inimmunosuppressed patients and in previously normalpatients who are afflicted with severe disease. Extrapulmonarymanifestations include ocular and pericardial involvement,perirectal abscess, wound infection, peritonitis, cellulitis,rhabdomyolysis and acute renal failure, neutropenia,hemolytic anemia, and thrombotic thrombocytopenic purpura.

Implanted devices such as heart valves and hemodialysisfistulas can become colonized.A nonpneumonic form of legionellosis called Pontiac fever

has a short incubation period and a low mortality. It has beenresponsible for at least four outbreaks of illness, includingseveral related to whirlpools and hot tubs.

Laboratory studies The peripheral white blood cell countis mildly elevated to between 8,000 and 16,000/mm3. Coldagglutinins are negative. Other laboratory findings mayinclude an elevated erythrocyte sedimentation rate, hypoxia,abnormal liver function test results, and elevated creatinephosphokinase levels.64 Proteinuria and microscopic hematuriahave been observed, and acute renal failure may complicate

the course on occasion.Gram stains of the sputum or tracheal secretions will notreveal L. pneumophila, but the organism can occasionally beisolated from sputum and other specimens by usingcharcoalyeast extract agar. The diagnosis can be establishedrapidly in about 20% of cases by demonstrating the organismwith direct immunofluorescent staining of sputum specimens;

bronchoalveolar lavage may be helpful in immunosuppressedpatients. A kit that uses radiolabeled complementary DNA iscommercially available, but clinical experience is still limited.A very promising polymerase chain reaction assay has beendeveloped.65

Another method of rapid diagnosis involves detection of L.pneumophila antigen in the urine; this radioimmunoassay test is

highly specific and has a sensitivity of about 80% to 90%.65

However, the test is available only for L. pneumophilaserogroup 1, which is the most common cause of Legionnairesdisease. Most often, however, the diagnosis is establishedserologically by an indirect fluorescent antibody techniqueinvolving staining of the causative bacterium. With thistechnique, a fourfold or greater rise in antibody titer duringthe illness or a stable titer of 1:256 or greater is considereddiagnostic. The clinical picture and radiologic findings inLegionnaires disease are not specific. The diagnosis should beconsidered in patients with segmental, lobar, or interstitialpneumonia in which the etiologic agent is not evident onGram stains of sputum or tracheal secretions. A mild case mayresembleMycoplasma pneumonia or other types of atypical

pneumonia.

Treatment

On in vitro susceptibility testing, L. pneumophila has beenshown to be susceptible to a variety of antimicrobial agents,including erythromycin, clarithromycin, azithromycin, tetracy-cline, rifampin, and the fluoroquinolones. Current evidenceindicates that azithromycin66 or levofloxacin67 is the treatment ofchoice. Occasionally, patients may experience a relapse if anti-

biotics are discontinued prematurely; recovery occurs during asecond, more prolonged course of treatment. A combination of

rifampin and either azithromycin or levofloxacin may beconsidered in patients who fail to respond to monotherapy andin immunologically impaired patients with overwhelmingdisease. Improvements in diagnosis and therapy haveproduced a dramatic decline in the case-fatality rate of L.

pneumophila infection, from 34% in 1980 to 12% in 1998.68

infections caused by other LEGIONELLA species

Since 1943, unusual, fastidious Rickettsia-like organisms

have been identified as causes of isolated cases of pneumonia.Long considered medical curiosities, these organisms werenamed after their discoverers or the patients from whom theywere isolated. Such obscure nomenclature (e.g., TATLOCK,OLDA, HEBA, and WIGA) reflected the absence of knowledgeconcerning these agents. Subsequent studies of theseorganisms led to their reclassification as Legionella species. Ofthe more than 30 Legionella species that have been identified, atleast 19 have been recognized as causes of pneumonia,particularly in immunosuppressed hosts.

The clinical picture is not distinctive. Fever is the mostcommon feature, cough is variable in severity, and sputumproduction is absent or scant. Pleurisy or dyspnea maydevelop, and chest x-rays show a patchy or nodular,

progressive bronchopneumonia. L. micdadei is the mostimportant of these organisms. Previously known asTATLOCK and HEBA, L. micdadei was rediscovered as thePittsburgh pneumonia agent that caused acute suppurativepneumonia in eight immunosuppressed patients from twocenters in 1979.69 L. micdadei can also cause pneumonia inimmunologically intact hosts and extrathoracic infections inimmunologically impaired hosts. It has been isolated fromhospital water supplies and can cause nosocomial infections inimmunosuppressed patients.70

In the first 13 patients with Pittsburgh pneumonia, thediagnosis was established through a lung biopsy or autopsythat revealed acute alveolar inflammation and short, weaklyacid-fast, gram-negative bacilli. More recent cases have been

diagnosed by culturing the agent on charcoalyeast extractagar or by serologic means. Erythromycin has been used withsuccess. Unlike L. pneumophila, L. micdadei is susceptible topenicillins and cephalosporins in vitro; however, there are nodata on the use of these drugs in clinical L. micdadei infection.

Many other Legionella species have been identified as causesof pneumonia. These organisms grow on charcoalyeastextract agar. Some cases in which Legionella species have beenimplicated share common features: patients have beenexposed to infected water and have COPD or areimmunosuppressed.71 Therapy with erythromycin, alone orwith rifampin, has been suggested.

Infections Caused by Chlamydophila (Chlamydia)Pneumoniae

C. pneumoniae, initially known as the Taiwan acuterespiratory disease (TWAR) agent, is an important pathogen,accounting for up to 10% of all pneumonias in the UnitedStates.72 Serologic surveys suggest that a majority of adultshave been infected at some point, indicating that most casesare mild or subclinical.

Unlike psittacosis, which is a true zoonosis that spreadsonly from animals to humans,73 C. pneumoniae spreads fromperson to person via respiratory droplets. The incubation




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the upper respiratory tract (outnumbering aerobic orfacultative bacteria by 10 to 1), it is not surprising thatanaerobes are the dominant organisms in aspirationpneumonia. Of particular importance are Prevotellamelaninogenica and other Prevotella (formerly, oral strains ofBacteroides) species (slender, pleomorphic, pale gram-negativerods), Fusobacterium nucleatum (slender gram-negative rodswith pointed ends), and anaerobic or microaerophilicstreptococci and Peptostreptococcus (small gram-positive cocci

in chains or clumps). As expected, multiple organisms arerecovered from most patients.

treatment

Although penicillin has been the traditional drug of choicefor aspiration pneumonia, clindamycin has surpassed it inclinical trials77,78 and is now the preferred treatment; the usualdosage is 600 mg every 8 to12 hours I.V. until a clinicalresponse is evident, followed by oral administration of 300 mgfour times a day for 10 to 14 days. Alternative treatmentsinclude amoxicillin-clavulanate and the combination ofpenicillin and metronidazole [see Table 6]. Parenteral therapy isadvisable initially, but a 10- to 14-day course of treatment can

be concluded with orally administered antibiotics if the patient

responds well.Hospitalization or antibiotic therapy alters the usualoropharyngeal bacterial flora, so that staphylococci, facultativegram-negative bacilli, or both may be identified in patients. Asa result, aspiration pneumonia in hospitalized patients ofteninvolves pathogens that are uncommon in community-acquired pneumonias. Gram stains and cultures of sputum areespecially important for identifying gram-negative bacilli andstaphylococci in the hospital setting. Broad antimicrobialcoverage is required until specific pathogens have beenidentified by culture and sensitivity testing. Although tubefeedings are often recommended to prevent aspirationpneumonia, there is no evidence that they are effective.76

Other Pulmonary Infections

acute bronchitis

Cough is the chief complaint responsible for an estimated 30million physician office visits in the United States annually.For about 12 million of these patients, the clinical diagnosis isacute bronchitis.79

Acute bronchitis is commonly defined as an acuterespiratory tract infection in which cough, with or withoutsputum production, is a prominent feature. In most cases, anetiologic diagnosis is not established. When sputum is absent orscant, the illness is often attributed to a respiratory tract virus;when purulent sputum is present, the bacteria that cause

community-acquired pneumonias are considered likely causes.Most otherwise healthy persons recover from acute

bronchitis in 1 to 3 weeks, but the cough can linger for morethan a month in up to 20% of patients.80 Although 70% to 90%of patients are treated with antibiotics, published trialsdemonstrate little clinical benefit, even if purulent sputum ispresent.80,81 Guidelines of the Infectious Disease Society ofAmerica, the American College of PhysiciansAmericanSociety of Internal Medicine, and the American Academy ofFamily Physicians state that routine antibiotic treatment ofuncomplicated acute bronchitis is not recommended,

regardless of duration of cough.82 Suspected cases of pertussisconstitute an exception.83 Clinicians who are confronted withdemands for antibiotics may use a strategy of delayedprescription,84 whereby the physician offers the patient aprescription but suggests that it be filled only if symptoms failto resolve without antibiotics. Patients with high fever, chills,respiratory distress, underlying pulmonary or immunosup-pressive disorders, or physical signs of pulmonary parenchy-mal infection should be evaluated for pneumonia and treated

according to the guidelines for community-acquiredpneumonia (see above).

chronic bronchitis

Patients with chronic bronchitis characteristically producesputum on most days for at least 3 months each year for morethan 2 years. The sputum is frequently colonized by H.influenzae (nontypable), S. pneumoniae, orM. catarrhalis, singlyor in combination. Although it is not certain whether the

bacteria themselves produce additional airway damage, heavybacterial loads correlate with increased inflammation. 85

Patients who acquire a new or potentially pathogenic strain ofbacteria are at increased risk for symptomatic exacerbations oftheir chronic bronchitis.86 The role of long-term prophylactic

antibiotic therapy in chronic bronchitis is controversial. Long-term antibiotic therapy may provide symptomatic relief incertain patients who experience multiple exacerbations of

bronchitis during the winter, but it is not useful in improvingor preserving pulmonary function. However, short-termantibiotic therapy is effective in treating acute exacerbations ofchronic bronchitis.87

bronchiectasis

True saccular, or cystic, bronchiectasis involves bothdilatation of the bronchi and destruction of the bronchial walls.Bronchiectasis results most often from neglected or recurrentinfection, especially in childhood; therefore, bronchiectasis has

become much less common since the introduction of

antibiotics. Aggressive medical therapy has greatly improvedthe prognosis.

Symptoms include cough that may be dry or productive ofcopious foul sputum, recurrent lower respiratory tractinfection, and hemoptysis. In rare instances, bronchiectasis canpresent as pleuritic chest pain. In advanced cases, fibrosis canlead to cor pulmonale and respiratory failure. The chest x-raymay show increased lung markings, honeycombing,atelectasis, or pleural changes, but high-resolution or helicalchest CT is required for definitive diagnosis88 [see 14:III ChronicObstructive Diseases of the Lung].

Lung Abscess

epidemiology and etiology

In the antibiotic era, lung abscesses have become lesscommon and less serious. The most common variety has beentermed the primary, simple, nonspecific, or putrid abscess.Primary lung abscess accounts for about 60% of all lungabscesses and originates from a necrotizing suppurative

bronchopneumoni a caused by the aspirat ion of mixedoropharyngeal bacteria. Thus, both the predisposing factorsand the causative organisms are similar to those identified inaspiration pneumonia. Patients with primary lung abscesses




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typically have alterations of consciousness because ofunderlying problems such as alcoholism and neurologicdisorders; periodontal disease is often present. The organismscausing the abscess are much more reliably identified by

bronchoscopic aspiration using a protected brush than bysputum cultures, which are invariably contaminated withanaerobes and other mouth flora. Bronchoalveolar lavage,transtracheal aspiration, and percutaneous lung aspirationmay also be useful for bacteriologic diagnosis. Mixed

anaerobic bacteria are seen in most cases; F. nucleatum, P.melaninogenica , Peptostreptococcus , and anaerobic ormicroaerophilic streptococci predominate. B. fragilis isrecovered with other organisms in 15% of cases.

Many other conditions can lead to lung abscess. Necrotizingbacterial pneumonias caused by S. aureus, K. pneumoniae, orother gram-negative bacilli can lead to abscess formation. Inother patients, abscess develops as a result of bronchialobstruction caused by tumors, foreign bodies, or bronchialstenosis. Septic pulmonary embolization is a cause of abscessformation. Pulmonary tuberculosis, fungal infection, oractinomycosis often leads to cavity formation. In theimmunosuppressed host, Nocardia and other opportunisticorganisms may also produce cavitation. Lung abscesses in

patients with AIDS are caused by a wide array of organismsand respond poorly to therapy.

diagnosis

Clinical Features

The clinical presentation of the patient with a lung abscessdepends on the type of abscess. Patients with abscessesresulting from necrotizing staphylococcal or gram-negative

bacillary pneumonias are usually acutely ill and exhibit clinicalfeatures of the underlying pneumonia. Although patients withprimary lung abscess may also present acutely with aspirationpneumonia, they more often experience insidiouslyprogressive symptoms for weeks or even months before

diagnosis. Cough is present in almost all patients; when theabscess drains into the bronchial tree, production of copiousfoul-smelling sputum is characteristic. Hemoptysis is presentin approximately one third of cases and may occasionallyreach life-threatening proportions. Chest pain consisting ofeither a dull ache or a true pleurisy is common. Most patientshave fever, but frank rigors are unusual. Often, patients with achronic course of lung abscess lasting many weeks haveanorexia, weight loss, and debility.

Physical Examination and Imaging

Physical examination of a patient with a lung abscess maydisclose pulmonary rales, signs of consolidation, or, rarely,clubbing of the nails. These findings are not diagnostic,

however, and chest x-rays or CT scans are required to establishthe presence of an abscess. Although any lung segment may beinvolved, abscesses are most common in the posterior segmentsof the upper lobes and the apical segments of the lower lobes,

because these areas are dependent when a person is recumbent.Abscesses may be single or, less often, multiple. The finding ofair-fluid levels signifies rupture into the bronchial tree.

Laboratory Studies and Invasive Procedures

As is the case with other pulmonary infections, examinationof the sputum is crucial to the diagnosis of lung abscess. In

patients with primary lung abscesses, the sputum is oftenputrid and contains numerous polymorphonuclear leukocytesand an abundant mixed microbial flora. Sputum culturesreveal only normal mouth flora. Meaningful anaerobic

bacteriology depends on obtaining, either by bronchoscopy ortranstracheal aspiration, specimens that have not traversed theoropharynx. Percutaneous needle aspiration can also be veryhelpful, both diagnostically and therapeutically. In a typicalcase of aspirational putrid lung abscess, these invasive

procedures may not be necessary. They are importanthowever, if the diagnosis is uncertain. At one time,bronchoscopy was advocated for all patients with lungabscess; however, it is now typically reserved for patients inwhom there is a suspicion of bronchial obstruction by aforeign body or tumor, for patients who fail to respond tomedical therapy, and for patients from whom specimens arerequired to rule out tuberculosis, fungal infection, orcarcinoma.89 Bronchoscopy may be helpful therapeutically bypromoting bronchial drainage from cavities that incompletelycommunicate with the bronchial tree.


Noninfectious processes can produce cavitary lung lesions

Primary and metastatic tumors, bullae, cysts, intralobarpulmonary sequestration, pulmonary infarcts, vasculitis(including Wegener granulomatosis), and rheumatoid lungdisease must be considered in the differential diagnosis of lungabscess.

treatment

If specific pathogens such as S. aureus or Klebsiella arepresent in reliable specimens, therapy should be directed at thecausative pathogen. In primary lung abscesses caused bymixed oral flora, penicillin was traditionally the drug of choiceHowever, prospective studies comparing penicillin therapywith clindamycin therapy in patients with lung abscess foundclindamycin to be the superior agent.90 Relatively few clinica

trials are available on the treatment of anaerobic lungabscesses because of the infrequency of this presentation andthe difficulty in establishing a microbial diagnosisnevertheless, other drugs that appear to be useful areamoxicillin and a -lactamase inhibitor. Despite its excellent

bactericidal activity against anaerobic bacteria, metronidazoleappears to be less effective in treating lung abscess, probably

because of poor activity against streptococci. 91 Parenteratherapy is often required for 2 to 4 weeks before the occurrenceof defervescence, diminished sputum production, andreduction in cavity size. The duration of therapy depends onthe clinical course, but prolonged treatment for 4 to 8 weeks isusually required.

In addition to administration of antibiotics, adequate

drainage is essential and can usually be achieved with intensivepulmonary physiotherapy and postural drainageBronchoscopy can be very useful in promoting drainage and forexcluding the diagnosis of cancer.89 Although surgery was oncethe mainstay of treatment for lung abscess, antibiotics are nowalmost always able to control infection, and surgery is neededonly when complications occur. Massive hemoptysis is anindication for lung resection. Uncontrolled sepsis mayoccasionally necessitate lobectomy. CT-guided percutaneoustube drainage may be very helpful in patients who are too ill totolerate thoracotomy and may be the treatment of choice for




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lung abscesses that are refractory to medical management.Empyema, another complication of lung abscess, requiresexternal drainage by thoracentesis, chest tube, or rib resection.The persistence of a thin-walled cavity after otherwisesuccessful medical treatment, however, is not an indication forsurgery. Recurrent or persistent infection, recurrent hemop-tysis, or the suspicion of tumor may mandate operative inter-vention. Shaggy, thick-walled cavities may be suggestive oftumor. Complications of lung abscess that have become

uncommon because of antibiotic therapy include bronchogenicspread of infection to other pulmonary segments, bronchiecta-sis, and bacteremia with metastatic infection such as brainabscess.

Whereas patients with gram-negative or staphylococcalbacillary pneumonias or serious underlying diseases have asubstantial mortality, the prognosis for patients with primarylung abscess is quite good. It is important to prevent recurrentpulmonary infection by treating dental disease and byavoiding factors that predispose to pulmonary aspiration.

Empyema

etiology

Bacteria can reach the pleural space by many routes. Mostoften, empyema results from the direct spread of

bronchopulmonary infections, including pneumonias, lungabscesses, and bronchiectasis.92 Less often, empyema developsas a complication of thoracotomy or, rarely, thoracentesis.Open chest trauma provides another means for the directintroduction of microorganisms. Intra-abdominal infections,especially subphrenic abscesses, can penetrate the diaphragmto cause empyemas. Uncommonly, esophageal rupture cancause spread of infection from the mediastinum to the pleuralspace. Finally, hematogenous seeding is an infrequentmechanism of empyema formation.

S. aureus, various species of Streptococcus , and gram-

negative bacilli are the most common causes of empyema; ofthe gram-negative bacilli, K. pneumoniae has been linked withdiabetes.93 Many infections are mixed. Anaerobes have beenrecognized in 25% to 76% of empyemas and may occur in pureculture or in combination with aerobic or facultativeorganisms. Fusobacterium, Prevotella, and anaerobic gram-positive cocci are the anaerobes most often seen.M. tuberculosishas become a relatively rare cause of pleural space infections,and fungi are implicated uncommonly. Transdiaphragmaticrupture of a liver abscess occasionally produces amebicempyema.

diagnosis

In most patients, the clinical presentation of empyemas

includes fever, dyspnea, chest pain, and cough. Hemoptysis isless common than these other symptoms. If diagnosis andtreatment are delayed, weight loss and debility may beprominent. The physical findings in patients with empyemasare no different from those in other patients with pleuraleffusions. In addition, chest wall tenderness may be present,and there may be signs of an underlying pneumonia or intra-abdominal infection. Tachypnea and respiratory distress mayoccur, and septic shock may complicate advanced cases.Polymorphonuclear leukocytosis is common; other laboratoryfindings may include anemia and hypoxia. Chest x-rays reveal

pleural effusions that are free flowing in early disease butfrequently loculated in late cases. Ultrasonography may benecessary to distinguish fluid from pleural fibrosis. Unlesssurgery or thoracentesis has been performed, air-fluid levels inthe pleural space suggest a bronchopleural fistula.


In the differential diagnosis of empyema, it is important toconsider the many causes of noninfected pleural effusions.94

Most important is the distinction between sterileparapneumonic effusions and true empyemas. Thoracentesisis mandatory for the diagnosis of empyema [see 14:XIIIInvasive Diagnostic and Therapeutic Techniques in Lung Disease].Several thoracenteses may be needed if the fluid is loculated;CT or ultrasound guidance is very helpful in thesecircumstances. Gross purulence is diagnostic for empyema,

but the absence of frank pus does not rule out infection. Likeother inflammatory effusions, empyema fluids have thecharacteristics of exudates: protein levels greater than 3 g/dland lactic dehydrogenase values in excess of 550 units. Pleuralfluid acidosis is characteristic of empyemas, but alkalosis canoccur if the infection is caused by a urea-splitting organismsuch as Proteus. Pleural fluid glucose levels are depressed in

empyemas, and although white cell counts are variable, countsabove 5,000/mm3 are common, with polymorphonuclearleukocytes predominating. Gram stains of the pleural fluidwill often reveal the causative organisms. Both aerobic andanaerobic cultures are mandatory; a foul odor suggestsanaerobic infection. Stains and cultures for mycobacteria andfungi are important in selected cases.

treatment

Treatment of empyemas involves both antibiotics anddrainage. Antibiotics should be selected on the basis of thecausative pathogens. High-dose parenteral therapy isrequired, and prolonged courses of 3 weeks or more are oftenneeded. Adequate drainage is of paramount importance. In

acute empyemas, the pleural cavity is lined by acute fibrinousinflammation, and percutaneous drainage of free-flowing fluidmay be possible by repeated thoracentesis or tubethoracostomy. Closed chest tube drainage is the traditionalmethod for draining empyemas, but image-guided catheterdrainage is also effective, particularly when the fluid isloculated. Resolution of fever generally signifies satisfactorydrainage. If complete drainage cannot be achieved with chesttubes, video-assisted thoracoscopic surgery (VATS) can oftendisrupt intrapleural adhesions and achieve excellent drainageof loculated effusions95; although VATS requires endotrachealintubation and general anesthesia, it is less invasive than thenext alternative, rib resection with thoracotomy fordecortication. Enzymatic debridement with streptokinase has

proved ineffective.96

Septic Pulmonary Embolism

Although once uncommon, septic pulmonary embolism isnow encountered because of I.V. drug abuse, which accountsfor more than 75% of cases; tricuspid valve endocarditis anddirect injection of infected material cause most of these cases.S. aureus and gram-negative bacilli are the predominantetiologic agents in I.V. drug abusers. Septic pulmonaryembolism may also develop in patients with septic phlebitis of




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peripheral veins (especially phlebitis related to I.V. lines orpelvic infections), abscesses, or other bacteremic infections.

Unlike bland emboli, septic pulmonary emboli producepulmonary infarction in most instances. Small emboli produceflame-shaped or patchy infiltrates that may shift in location;these manifestations generally resolve with antibiotic therapy.Larger emboli often cavitate and may lead to lung abscess,empyema, or bronchopleural fistula formation. In addition toantibiotics, surgical drainage may be required for such

complications. Operative intervention may be needed tocontrol the source of emboli in some patients. Heparin can beuseful in patients with septic phlebitis.

The author has no commercial relationships with manufacturers ofproducts or providers of services discussed in this chapter.

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Pneumonia and Other Pulmonary Infections