AUTHOR AND EDITOR INFORMATION

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• Workup
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• Follow-up
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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

The most common atypical pneumonias are caused by 3 zoonotic pathogens, Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever), and 3 nonzoonotic pathogens, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumoniae. These atypical community-acquired pneumonias (CAPs) often cause systemic manifestations and are helpful in clinically differentiating from typical CAPs by the pattern of extrapulmonary organ involvement, which is characteristic for each atypical CAP. While zoonotic pneumonias may be eliminated from diagnostic consideration with a negative contact history, the atypical pneumonias are infrequent (approximately 15% of CAPs are atypical), difficult to diagnose, and unresponsive to beta-lactam therapy.

A definitive laboratory diagnosis of Legionella is usually based on investigations such as direct fluorescent antibody (DFA) or indirect fluorescent antibody (IFA). Antibiotics used against Legionella include macrolides, doxycycline, rifampin, quinolones, and telithromycin. Treatment is usually continued for 2 weeks although morbidity and mortality is high.

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.

A recent multivariate analysis showed an independent association between pneumococcal CAP and alcoholism. Current alcohol abuse was associated with severe CAP. No significant differences were found in mortality, antibiotic resistance of S pneumoniae, and other etiologies.

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 immune-mediated 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.

Frequency

United States

Community-acquired pneumonia remains a common illness. Approximately 4.5 million cases of community-acquired pneumonia occur annually, and 20% result in hospitalization. Estimates of incidence of nosocomial pneumonia range from 4-7 episodes per 1000 hospitalizations. Approximately 25% of patients in intensive care units (ICUs) develop pneumonia. Overall incidence of community-acquired pneumonia is reported to be 170 cases per 100,000 persons. With advancing age, the incidence increases from 94 cases per 100,000 persons in patients aged 44 years to 280 cases per 100,000 persons in those older than 65 years. Pneumonia as a cause of hospitalization increased from 36 to 48 cases per 100,000 persons between 1984 and 1995.

Mortality/Morbidity

Pneumonia is the sixth leading cause of death in the United States and is the most common infectious cause of death. The mortality rate is reported to be 1% in the outpatient setting but may increase to up to 25% in those requiring hospital admission. In a patient with preexisting respiratory disease, onset of bacterial pneumonia may result in deterioration of respiratory status, leading to respiratory failure and death.

• Nosocomial pneumonia is the leading cause of death among hospital-acquired infections. Recent studies have shown that nosocomial pneumonia causes excessive risk of death, and the mortality rates range from 20-50%.
• Although less common in the antibiotic era, bacterial pneumonia may lead to bronchiectasis. However, lower respiratory infection with pneumococci, staphylococci, and Klebsiella species may result in bronchiectasis, especially if treatment is delayed. The damaged alveoli and small- to medium-sized airways are replaced by dilated saccules that are filled with purulent material. Ongoing chronic inflammation may gradually destroy the surrounding lung tissue.
• In patients with community-acquired pneumonia, daily activities were restricted for 24.8 days per 100 persons. Lost days of work were 8.9 days per 100 adult employees. The annual cost to treat patients with community-acquired pneumonia in the United States was 9.7 billion dollars in 1994; 92% of these costs were secondary to hospitalization. A substantial difference in cost exists between inpatient and outpatient therapy for pneumonia (US $7517 vs $264).

Sex

Incidence is greater in males than in females.

Age

Advanced age increases the incidence of pneumonia and the mortality from pneumonia.

• Elderly persons have weaker immune responses, higher risk of aspiration, and other comorbidities.
• In a 20-year US study, the mortality rate from pneumococcal pneumonia with bacteremia was 20.3%, overall. However, a higher mortality rate (37.7%) occurred in elderly patients.

CLINICAL

Section 3 of 11  

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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/μL) may lead to Cryptococcus neoformans, M tuberculosis, or Rhodococcus equi infection. A CD4 cell count of fewer than 200/μL 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 >38.5°C or <36°C)
  • 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 aerobic-anaerobic 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  

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• Clinical
• Differentials
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WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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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 Media File 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 Media Files 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 Media File 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:

1. The recently infected lungs demonstrate engorgement of alveolar capillaries with frothy, serous, and blood-tinged fluid in the alveolar spaces.

2. 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.

3. 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  

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Medical Care

The initial approach to treating patients with

CAP 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 below. 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 CAP
  
  
  • Patients with CAP 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.
  
  
  • Penicillin (penicillin G/amoxicillin) remains the drug of choice for strains that are fully sensitive or have a moderately decreased susceptibility to penicillin, whereas cefotaxime and ceftriaxone are the first-line alternatives in cases with higher levels of resistance.
  
  
  • The 4 major categories not only speculate the microbial etiology but also predict ultimate prognosis and outcome. These categories are (1) CAP occurring in patients aged 60 years or younger who have no evidence of comorbidity and who can be treated in an outpatient setting, (2) CAP 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) CAP requiring hospitalization but not admission to an ICU, and (4) severe CAP 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, piperacillin- tazobactam, 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 Hospital-Acquired Pneumonia With Early Onset*

  Core Organisms	Core Antibiotics
  Enteric gram-negative bacilli	Cephalosporin
  (Nonpseudomonal) Enterobacter species, E coli	Second-generation or nonpseudomonal third-generation
  Klebsiella species	Beta-lactam/beta-lactamase inhibitor combination
  Proteus species S marcescens	If allergic to penicillin, fluoroquinolone or clindamycin + aztreonam
  H influenzae
  Methicillin-sensitive S aureus 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, Plus the Following:	Core Antibiotics, Plus the Following:
  Anaerobes (recent abdominal surgery, witnessed aspiration)	Clindamycin or beta-lactam/beta-lactamase inhibitor (alone)
  S aureus (coma, head trauma, diabetes mellitus, renal failure)	+/-vancomycin (until methicillin-resistant 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 (see Table 7)
  *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



• To determine the impact of initial antimicrobial choice on 30-day mortality rate in patients with CAP due to S pneumoniae, a prospective, observational study was performed. The factors related to mortality were bilateral disease, suspected aspiration, shock, HIV infection, renal failure, and pneumonia severity index (PSI) score class IV versus class I-III and categories V versus categories I-III. The association of beta-lactams plus macrolides was not better than the use of beta-lactams alone. The benefit of adequate initial antimicrobial regimen and 30-day mortality in patients with community-acquired pneumococcal pneumonia was demonstrated for those with a higher PSI score.

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

Section 7 of 11  

• Authors and Editors
• Introduction
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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 second-generation 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 Tables 1-3 in Medical Care). 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 first-generation cephalosporins.

Third-generation cephalosporins have wider activity against most gram-negative bacteria, such as Enterobacter, Citrobacter, Serratia, Neisseria, Providencia, and Haemophilus species, including beta-lactamase–producing strains.

Second-generation cephalosporins are not effective against Legionella or Mycoplasma. Generally, they are well tolerated but expensive. Oral second-generation and third-generation 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 community-acquired 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	Clarithromycin (Biaxin)
Description	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)
Description	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)
Description	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)
Description	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 PO 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)
Description	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 PO 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)
Description	Inhibits bacterial synthesis of dihydrofolic acid by competing with paraaminobenzoic acid, inhibiting folic acid synthesis. Results in inhibition of bacterial growth. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except P aeruginosa.
Adult Dose	160 mg TMP/800 mg SMZ PO bid for 10 d
Pediatric Dose	<2 months: Not recommended >2 months: 8 mg TMP/kg/d PO 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-SMZ; 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)
Description	Rapidly becoming a popular choice in pneumonia. L-stereoisomer 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 PO/IV q48h CrCl 20-49 mL/min: 250 mg PO/IV 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)
Description	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 penicillin-resistant strains; MIC value for penicillin >2 mg/mL), Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumoniae.
Adult Dose	CAP due to known or suspected S pneumoniae, H influenzae, M pneumoniae, or C pneumoniae: 320 mg PO qd for 5 d CAP due to known or suspected K pneumoniae, M catarrhalis, or multidrug-resistant S pneumoniae: 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)
Description	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)
Description	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)
Description	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)
Description	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)
Description	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)
Description	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 mild-to-moderate community-acquired 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; myasthenia gravis; history of hepatitis and/or jaundice with use of macrolides
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); HMG-CoA 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; common adverse effects include diarrhea and nausea; may rarely cause visual disturbances or increased liver enzymes; acute hepatic failure and severe liver injury (in some cases fatal) have been reported—if clinical hepatitis or liver enzyme level elevations combined with other systemic symptoms occur, permanently discontinue

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