Lung Abscess

Background

Lung abscess is defined as necrosis of the pulmonary tissue and formation of cavities containing necrotic debris or fluid caused by microbial infection. The formation of multiple small (<2 cm) abscesses is occasionally referred to as necrotizing pneumonia or lung gangrene. Both lung abscess and necrotizing pneumonia are manifestations of a similar pathologic process. Failure to recognize and treat lung abscess is associated with poor clinical outcome.

In the 1920s, approximately one third of patients with lung abscess died. Dr David Smith postulated that aspiration of oral bacteria was the mechanism of infection. He observed that the bacteria found in the walls of the lung abscesses at autopsy resembled the bacteria noted in the gingival crevice. A typical lung abscess could be reproduced in animal models via an intratracheal inoculum containing, not 1, but 4 microbes, thought to be Fusobacterium nucleatum, Peptostreptococcus species, a fastidious gram-negative anaerobe, and, possibly, Prevotella melaninogenicus.

Lung abscess was a devastating disease in the preantibiotic era, when one third of the patients died, another one third recovered, and the remainder developed debilitating illnesses such as recurrent abscesses, chronic empyema, bronchiectasis, or other consequences of chronic pyogenic infections. In the early postantibiotic period, sulfonamides did not improve the outcome of patients with lung abscess. After penicillins and tetracyclines became available, outcomes improved. Although resectional surgery was often considered a treatment option in the past, the role of surgery has greatly diminished over time because most patients with uncomplicated lung abscess eventually respond to prolonged antibiotic therapy.

Lung abscesses can be classified based on the duration and the likely etiology. Acute abscesses are less than 4-6 weeks old, whereas chronic abscesses are of longer duration. Primary abscesses are infectious in origin, caused by aspiration or pneumonia in the healthy host. Secondary abscesses are caused by a preexisting condition (eg, obstruction), spread from an extrapulmonary site, bronchiectasis, and/or an immunocompromised state. Lung abscesses can be further characterized by the responsible pathogen, such as Staphylococcus lung abscesses and anaerobic abscess or Aspergillus lung abscess.

See the image below.

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A thick-walled lung abscess.

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Pathophysiology

Most frequently, the lung abscess arises as a complication of aspiration pneumonia caused by mouth anaerobes. The patients who develop lung abscess are predisposed to aspiration and commonly have periodontal disease. A bacterial inoculum from the gingival crevice reaches the lower airways and infection is initiated because the bacteria are not cleared by the patient's host defense mechanism. This results in aspiration pneumonitis and progression to tissue necrosis 7-14 days later, resulting in formation of lung abscess.

Other mechanisms for lung abscess formation include bacteremia or tricuspid valve endocarditis causing septic emboli (usually multiple) to the lung. Lemierre syndrome, an acute oropharyngeal infection followed by septic thrombophlebitis of the internal jugular vein, is a rare cause of lung abscesses. The oral anaerobe F necrophorum is the most common pathogen.

Microbiology

Because of the difficulty obtaining material uncontaminated by nonpathogenic bacteria colonizing the upper airway, lung abscesses rarely have a microbiologic diagnosis.

Published reports since the beginning of the antibiotic area have established that anaerobic bacteria are the most significant pathogens in lung abscess. In a study by Bartlett et al in 1974, 46% of patients with lung abscesses had only anaerobes isolated from sputum cultures, while 43% of patients had a mixture of anaerobes and aerobes.^[1] The most common anaerobes are Peptostreptococcus species, Bacteroides species, Fusobacterium species, and microaerophilic streptococci.

Aerobic bacteria that may infrequently cause lung abscess include Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae (rarely), Klebsiella pneumoniae, Haemophilus influenzae, Actinomyces species, Nocardia species, and gram-negative bacilli.

Two studies from Asia suggest that the bacteriologic characteristics of lung abscesses have changed.^{[2, 3]} This finding is confirmed by a study performed by Takayanagi et al suggesting that Streptococcus species were the most common species, followed (in order of decreasing frequency) by anaerobes, Gemella species, and Klebsiella pneumoniae. These species were identified in this study with percutaneous ultrasonography-guided transthoracic needle aspiration and protected specimen brushes in a population of 205 patients.

Some geographic differences exist, with Streptococcus species being more prevalent in this study (done in one hospital in Japan), compared with previous accounts of anaerobic bacterial species being most predominant in Western populations. The study population notably had a 61% of individuals with periodontal disease, 16.6% were considered “alcoholic,” and 22.9% had significant diabetes mellitus. They were primarily Japanese, male (82%), smokers (75.6%), and alcoholic (34%).^[3]

To support the findings by Takayangi et al, a subsequent study done by Want et al in a series of 90 patients with community-acquired lung abscess in Taiwan, anaerobes were recovered from just 28 patients (31%). The predominant bacterium was K pneumoniae, in 30 patients (33%). Another significant finding was that the rate of resistance of anaerobes and Streptococcus milleri to clindamycin and penicillin increased compared with previous reports.^[2]

Both studies by Wang et al and Takayanagai suggest that aerobic organisms were more likely to be found in individuals with diabetes mellitus and periodontal disease, both risk factors for aerobic community acquired lung abscesses.

Nonbacterial and atypical bacterial pathogens may also cause lung abscesses, usually in the immunocompromised host. These microorganisms include parasites (eg, Paragonimus and Entamoeba species), fungi (eg, Aspergillus, Cryptococcus, Histoplasma, Blastomyces, and Coccidioides species), and Mycobacterium species.

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Etiology

The bacterial infection may reach the lungs in several ways. The most common is aspiration of oropharyngeal contents.

Patients at the highest risk for developing lung abscess have the following risk factors:

• Periodontal disease
• Seizure disorder
• Alcohol abuse
• Dysphagia

Other patients at high risk for developing lung abscess include individuals with an inability to protect their airways from massive aspiration because of a diminished gag or cough reflex, caused by a state of impaired consciousness (eg, from alcohol or other CNS depressants, general anesthesia, or encephalopathy).

Infrequently, the following infectious etiologies of pneumonia may progress to parenchymal necrosis and lung abscess formation:

• Pseudomonas aeruginosa
• K pneumoniae
• S aureus (may result in multiple abscesses)
• Streptococcus pneumoniae
• Nocardia species
• Actinomyces species
• Fungal species

An abscess may develop as an infectious complication of a preexisting bulla or lung cyst.

An abscess may develop secondary to carcinoma of the bronchus. The bronchial obstruction causes postobstructive pneumonia, which may lead to abscess formation. Underlying lung cancer in edentulous patients with lung abscesses should also be considered.

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Epidemiology

Frequency

The frequency of lung abscesses in the general population is not known.

Sex

A male predominance for lung abscess is reported in published case series.

Age

Lung abscesses likely occur more commonly in elderly patients because of the increased incidence of periodontal disease and the increased prevalence of dysphagia and aspiration. However, a case series from an urban center with high prevalence of alcoholism reported a mean age of 41 years.^[4]

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Prognosis

The prognosis for lung abscess following antibiotic treatment is generally favorable. Over 90% of lung abscesses are cured with medical management alone, unless caused by bronchial obstruction secondary to carcinoma.

Host factors associated with a poor prognosis include advanced age, debilitation, malnutrition, human immunodeficiency virus infection or other forms of immunosuppression, malignancy, and duration of symptoms greater than 8 weeks.^[5] The mortality rate for patients with underlying immunocompromised status or bronchial obstruction who develop lung abscess may be as high as 75%.^[6]

Aerobic organisms, frequently hospital acquired, are associated with poor outcomes. A retrospective study reported the overall mortality rate of lung abscesses caused by mixed gram-positive and gram-negative bacteria at approximately 20%.^[7]

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Patient Education

For patient education resources, visit the Infections Center and Lung Disease and Respiratory Health Center. Also, see the patient education articles Bacterial Pneumonia, Antibiotics, and Bronchoscopy.

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History

Symptoms depend on whether the abscess is caused by anaerobic or other bacterial infection. A lung abscess may be asymptomatic in a small proportion of patients in the early stages. Typical symptoms are below.

Anaerobic infection in lung abscess

Patients often present with indolent symptoms that evolve over a period of weeks to months. The usual symptoms are fever, cough with sputum production, night sweats, anorexia, and weight loss. The expectorated sputum characteristically is foul smelling and bad tasting. Patients may develop hemoptysis or pleurisy

Other pathogens in lung abscess

These patients generally present with conditions that are more acute in nature and are usually treated while they have bacterial pneumonia. Cavitation occurs subsequently as parenchymal necrosis ensues. Abscesses from fungi, Nocardia species, and Mycobacteria species tend to have an indolent course and gradually progressive symptoms.

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Physical Examination

The findings on physical examination of a patient with lung abscess are variable. Physical findings may be secondary to associated conditions such as underlying pneumonia or pleural effusion. The physical examination findings may also vary depending on the organisms involved, the severity and extent of the disease, and the patient's health status and comorbidities.

Patients with lung abscesses may have low-grade fever in anaerobic infections and temperatures higher than 38.5°C in other infections.

Generally, patients with in lung abscess have evidence of gingivitis and/or periodontal disease.

Clinical findings of concomitant consolidation may be present (eg, decreased breath sounds, dullness to percussion, bronchial breath sounds, coarse inspiratory crackles).

The amphoric or cavernous breath sounds are only rarely elicited in modern practice.

Evidence of pleural friction rub and signs of associated pleural effusion, empyema, and pyopneumothorax may be present. Signs include dullness to percussion, contralateral shift of the mediastinum, and absent breath sounds over the effusion.

Digital clubbing may develop rapidly.

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Complications

Complications of pulmonary abscess include the following:

• Rupture into pleural space causing empyema
• Pleural fibrosis
• Trapped lung
• Respiratory failure
• Bronchopleural fistula
• Pleural cutaneous fistula

In a patient with coexisting empyema and lung abscess, draining the empyema while continuing prolonged antibiotic therapy is often necessary.

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Laboratory Studies

A complete white blood cell count with differential may reveal leukocytosis and a left shift.

Obtain sputum for Gram stain, culture, and sensitivity.

If tuberculosis is suspected, acid-fast bacilli stain and mycobacterial culture is requested. Purified protein derivative (PPD) skin testing, quantiferon gold testing, ANCA, and perhaps a serum ACE level and fungal serologies may also be considered.

Blood culture may be helpful in establishing the etiology.

Obtain sputum for ova and parasite whenever a parasitic cause for lung abscess is suspected.

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Imaging Studies

Chest radiography ^[8]

A typical chest radiographic appearance of a lung abscess is an irregularly shaped cavity with an air-fluid level. Lung abscesses as a result of aspiration most frequently occur in the posterior segments of the upper lobes or the superior segments of the lower lobes. The wall thickness of a lung abscess progresses from thick to thin and from ill-defined to well-circumscribed as the surrounding lung infection resolves. The cavity wall can be smooth or ragged but is less commonly nodular, which raises the possibility of cavitating carcinoma. The extent of the air-fluid level within a lung abscess is often the same in posteroanterior or lateral views. The abscess may extend to the pleural surface, in which case it forms acute angles with the pleural surface.

Anaerobic infection may be suggested by cavitation within a dense segmental consolidation in the dependent lung zones. Lung infection with a virulent organism results in more widespread tissue necrosis, which facilitates progression of underlying infection to pulmonary gangrene.

Up to one third of lung abscesses may be accompanied by an empyema.

Repeat chest radiographs may be obtained after treatment to determine response to antimicrobial therapy.

See the images below.

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Pneumococcal pneumonia complicated by lung necrosis and abscess formation.

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A lateral chest radiograph shows air-fluid level characteristic of lung abscess.

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A 54-year-old patient developed cough with foul-smelling sputum production. A chest radiograph shows lung abscess in the left lower lobe, superior seg....

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A 42-year-old man developed fever and production of foul-smelling sputum. He had a history of heavy alcohol use, and poor dentition was obvious on phy....

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Chest radiograph of a patient who had foul-smelling and bad-tasting sputum, an almost diagnostic feature of anaerobic lung abscess.

Computed tomography ^{[8, 9]}

CT scanning of the lungs may help visualize the anatomy better than chest radiography. CT scanning is very useful in the identification of concomitant empyema or lung infarction. On CT scans, an abscess often is a rounded radiolucent lesion with a thick wall and ill-defined irregular margins. The vessels and bronchi are not displaced by the lesion, as they are by an empyema. The lung abscess is located within the parenchyma compared with loculated empyema, which may be difficult to distinguish on chest radiographs. The abscess forms acute angles with the pleural surface chest wall. See the image below.

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A 42-year-old man developed fever and production of foul-smelling sputum. He had a history of heavy alcohol use, and poor dentition was obvious on phy....

Ultrasonography

Peripheral lung abscesses with pleural contact or included inside a lung consolidation are detectable using lung ultrasonography at the bedside. Lung abscess appears as a rounded hypoechoic lesion with an outer margin. If a cavity is present, additional nondependent hyperechoic signs are generated by the gas-tissue interface.^[10]

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Procedures

Diagnostic material uncontaminated by bacteria colonizing the upper airway may be obtained for anaerobic culture from the following:

• Blood culture
• Pleural fluid (if empyema present)
• Transtracheal aspirate
• CT-guided transthoracic needle aspirate
• Surgical specimens
• Fiberoptic bronchoscopy with protected brush
• Bronchoalveolar lavage with quantitative cultures

Expectorated sputum and other methods of sampling the upper airway do not yield useful results for anaerobic culture because the oral cavity is extensively colonized with anaerobes. Blood cultures are infrequently positive in patients with lung abscess. If the empyema is due to an anaerobic organism, the fluid is foul and can suggest the diagnosis even though cultures may not grow an organism, given the difficulties that occur in specimen transport (eg, aerobic exposure, need for anaerobic culture media).

The other modalities listed are invasive, costly, and require laboratory expertise. Bronchoscopy using a protected brush to obtain a specimen uncontaminated by the upper airway or quantitative culture of organisms from the bronchoalveolar lavage fluid has been advocated to establish bacteriologic diagnosis of lung abscesses. However, care must to taken with manipulation of a brush to ensure that the abscess is not punctured, allowing spillage of the contents of the abscess cavity into the airways. The experience with these techniques in diagnosis of anaerobic lung infections is limited and the diagnostic yield is uncertain. Perhaps most importantly, cultures obtained by any of these methods are unlikely to be positive after the initiation of antibiotics.^[11]

Flexible fiberoptic bronchoscopy is performed to exclude bronchogenic carcinoma whenever bronchial obstruction is suspected.^[12]

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Histologic Findings

Lung abscesses begin as small zones of necrosis developing within the consolidated segments in pneumonia. These areas may coalesce to form single or multiple areas of suppuration, which are referred to as lung abscesses. If antibiotics interrupt the natural history at an early stage, the healing results in no residual changes. When the progressive inflammation erodes into the adjacent bronchi, the contents of the abscess are expectorated as malodorous sputum. Subsequently, fibrosis occurs, which causes a dense scar and separates the abscess. The abscess may still occur, and spillage of pus into the bronchial tree may disseminate the infection.

See the images below.

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Histology of a lung abscess shows dense inflammatory reaction (low power).

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Histology of a lung abscess shows dense inflammatory reaction (high power).

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Approach Considerations

The treatment of lung abscess is guided by the available microbiology with consideration of the underlying or associated conditions. No treatment recommendation has been issued by major societies specifically for lung abscess. Some clinical trials referred to below have included patients with aspiration pneumonia with or without lung abscess.

For the following reasons, inpatient care is advisable in patients with lung abscess:

• Evaluation and management of patient's respiratory status
• Administration of intravenous antibiotics
• Drainage of the abscess or empyema as needed

In patients who have small lung abscess, who are not clinically ill, and who are reliable, outpatient care may be considered after obtaining appropriate diagnostic studies such as sputum culture, blood culture, and blood work.

Following initial intravenous antibiotic therapy, the patient may be treated on an outpatient basis for completion of prolonged therapy, which is often required for cure.

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Antibiotic Therapy

Standard treatment of an anaerobic lung infection is clindamycin (600 mg IV q8h followed by 150-300 mg PO qid). This regimen has been shown to be superior over parenteral penicillin in published trials. Several anaerobes may produce beta-lactamase (eg, various species of Bacteroides and Fusobacterium) and develop resistance to penicillin; therefore, treatment with a beta-lactamase inhibitor in conjunction with a beta-lactam or carbapenems should be considered.^[13]

Although metronidazole is an effective drug against anaerobic bacteria, metronidazole in treating lung abscess has been rather disappointing because these infections are generally polymicrobial. A failure rate of 50% has been reported.^{[14, 15]} Metronidazole is not recommended; however, if metronidazole is used, it must be paired with another agent, typically penicillin.

In hospitalized patients who have aspirated and developed a lung abscess, antibiotic therapy should include coverage against S aureus and Enterobacter and Pseudomonas species. When methicillin-resistant S aureus (MRSA) is the source of lung abscesses, vancomycin and linezolid should be considered. Vancomycin 15 mg/kg IV every 12 hours, with a goal trough of 15-20 mcg/mL, is adjusted renally. Linezolid therapy should be started at a dose of 600 mg IV every 12 hours. Once the patient has defervesced once, consider switching to an equivalent oral regimen. Linezolid has been shown to have improved response times over vancomycin, with no difference in mortality overall when compared with vancomycin treatment. Ceftaroline, a fifth-generation cephalosporin, has been shown to have activity against MRSA lung abscesses based on a 2012 study with data from 43 medical centers around the United States. Ceftaroline, however, has not been formally approved by the US Food and Drug Administration (FDA) for the treatment of MRSA lung abscesses.^{[16, 17]}

Ampicillin plus sulbactam is well tolerated and as effective as clindamycin with or without a cephalosporin in the treatment of aspiration pneumonia and lung abscess.^[18]

Moxifloxacin is clinically effective and as safe as ampicillin plus sulbactam in the treatment of aspiration pneumonia and lung abscess.^[19]

Actinomyces, Nocardia species, fungal species, and tuberculous abscesses tend to occur mostly in immunocompromised hosts, including chronic glucocorticoid therapy or patients with lung transplants. Data regarding Actinomyces abscesses are limited, but treatment with high-dose penicillin is generally recommended for the treatment of Actinomyces, as penicillin resistance is minimal. Case reports exist of successful treatment of pulmonary Actinomyces with ciprofloxacin.^{[20, 21]}

Treatment of Nocardia species, when suspected as a source of pulmonary abscesses, involves 6-12 months of trimethoprim-sulfamethoxazole (TMP-SMZ), though the clear duration of therapy has not been clearly defined. Additionally, for initial induction therapy TMP-SMZ (15 mg/kg IV of the trimethoprim component per day, divided in 2-4 doses) can be used in addition to amikacin at 7.5 mg/kg IV every 12 hours. An alternative regimen involves imipenem 500 mg IV every 6 hours with amikacin.^{[22, 23]} The patient can then be transitioned to TMP-SMZ 10 mg/kg of the trimethoprim component, divided into twice- or thrice-daily doses after intravenous therapy.^[24]

Treatment of fungal abscesses should follow the therapy of each individual fungal organism indicated.

Tuberculous abscesses, especially MAC should follow MAC treatment guidelines.

Duration of therapy

Although the duration of therapy is not well established, most clinicians generally prescribe antibiotic therapy for 4-6 weeks. Expert opinion suggests that antibiotic treatment should be continued until the chest radiograph has shown either the resolution of lung abscess or the presence of a small stable lesion. The rationale for extended treatment maintains that risk of relapse exists with a shorter antibiotic regimen. Treatment can be as long as 2-3 months in some cases of large abscesses. The duration is guided in part by the radiographic appearance, with a favorable response manifesting as a decrease in the size of the abscess cavity.

Response to therapy

Patients with lung abscesses usually show clinical improvement, with improvement of fever, within 3-4 days after initiating the antibiotic therapy. Defervescence is expected in 7-10 days. Persistent fever beyond this time indicates therapeutic failure, and these patients should undergo further diagnostic studies to determine the cause of failure.

Considerations in patients with poor response to antibiotic therapy include bronchial obstruction with a foreign body or neoplasm or infection with a resistant bacteria, mycobacteria, or fungi.

Large cavity size (ie, > 6 cm in diameter) usually requires prolonged therapy. Because empyema with an air-fluid level could be mistaken for parenchymal abscess, a CT scan may be used to differentiate this process from lung abscess.

A nonbacterial cause of cavitary lung disease may be present, such as lung infarction, cavitating neoplasm, and vasculitis. The infection of a preexisting sequestration, cyst, or bulla may be the cause of delayed response to antibiotics.

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Surgical Care

Surgery is very rarely required for patients with uncomplicated lung abscesses. The usual indications for surgery are failure to respond to medical management, suspected neoplasm, or congenital lung malformation. Other indications may include ongoing sepsis syndrome (fever, tachycardia, leukocytosis), signs of progressive infection (enlarging cavity, infection of other lobes of the lung), and life-threatening complications such as respiratory failure and uncontrolled hemoptysis.

The surgical procedure performed is either lobectomy or pneumonectomy. Lung-sparing surgery is preferred (ie, segmentectomy or lobectomy). Rarely is pneumonectomy indicated or performed for a lung abscess with current medical options available for care.

When conventional therapy fails, either percutaneous catheter drainage or surgical resection is usually considered. Endoscopic lung abscess drainage is considered if an airway connection to the cavity can be demonstrated. Endoscopic drainage, however, is not without significant risk to the patient.^{[25, 26, 27]}

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Consultations

Consulting a pulmonary medicine or infectious diseases specialist is often helpful in workup and follow-up of patients with lung abscess.

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Prevention

Prevention of aspiration is important to minimize the risk of lung abscess. Early intubation in patients who have diminished ability to protect the airway from massive aspiration (cough, gag reflexes), should be considered.

Positioning the supine patient at a 30° reclined angle minimizes the risk of aspiration. Vomiting patients should be placed on their sides.

Improving oral hygiene and dental care in elderly and debilitated patients may decrease the risk of anaerobic lung abscess.

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Medication Summary

Most abscesses develop secondary to aspiration and are caused by anaerobes. A history suggestive of community acquired pneumonia or a history of development of abscess in a hospitalized patient is important in deciding the appropriate antibiotic coverage.

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Clindamycin (Cleocin)

• Dosing, Interactions, etc.

Clinical Context:  Lincosamides are used for the treatment of serious skin and soft tissue staphylococcal infections. They are slso effective against aerobic and anaerobic streptococci, except enterococci. Clindamycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

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Cefoxitin (Mefoxin)

• Dosing, Interactions, etc.

Clinical Context:  Cefoxitin is a second-generation cephalosporin indicated for gram-positive cocci and gram-negative rod infections. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.

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Penicillin G (Pfizerpen)

• Dosing, Interactions, etc.

Clinical Context:  Penicillin G interferes with the synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

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Metronidazole (Flagyl, Flagyl ER, Metro)

• Dosing, Interactions, etc.

Clinical Context:  Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis). It is not standard practice to use metronidazole alone because some anaerobic cocci and most microaerophilic streptococci are resistant.

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Sulfamethoxazole and Trimethoprim (Bactrim, Bactrim DS, Septra DS, Sulfatrim)

• Dosing, Interactions, etc.

Clinical Context:  This is a synthetic combination antibiotic. It is rapidly absorbed after oral administration. The mechanism of action involves blockage of two consecutive steps in biosynthesis of nucleic acids and proteins needed by many microorganisms. It provides coverage for common forms of both gram-positive and gram-negative organisms.

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Ciprofloxacin (Cipro, Cipro XR)

• Dosing, Interactions, etc.

Clinical Context:  Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Ciprofloxacin has no activity against anaerobes. Continue treatment for at least 2 days (7-14 d typical) after signs and symptoms have disappeared.

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Moxifloxacin (Avelox)

• Dosing, Interactions, etc.

Clinical Context:  Moxifloxacin inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

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Ampicillin and sulbactam (Unasyn)

• Dosing, Interactions, etc.

Clinical Context:  This is a drug combination of a beta-lactamase inhibitor with ampicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It covers skin, enteric flora, and anaerobes. It is not ideal for nosocomial pathogens.

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Linezolid (Zyvox)

• Dosing, Interactions, etc.

Clinical Context:  Linezolid prevents the formation of functional 70S initiation complex, which is essential for the bacterial translation process. It is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. It is used as an alternative in patients allergic to vancomycin and for the treatment of vancomycin-resistant enterococci.

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Vancomycin

• Dosing, Interactions, etc.

Clinical Context:  Vancomycin is used in prophylaxis. It is a potent antibiotic directed against gram-positive organisms and active against Enterococcus species. It is useful in the treatment of septicemia and skin structure infections. Vancomycin is indicated for patients who cannot receive, or have failed to respond to, penicillins and cephalosporins or have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes.

To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose drawn 0.5 hour prior to the next dosing. Use creatinine clearance to adjust dose in patients diagnosed with renal impairment.

Vancomycin is used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal or genitourinary procedures.

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Imipenem/cilastatin (Primaxin)

• Dosing, Interactions, etc.

Clinical Context:  This combination is for the treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of a potential for toxicity.

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Amikacin

• Dosing, Interactions, etc.

Clinical Context:  Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes; it blocks the recognition step in protein synthesis and causes growth inhibition. It is for gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Amikacin is effective against Pseudomonas aeruginosa. Use the patient's ideal body weight for dosage calculation. The same principles of drug monitoring for gentamicin apply to amikacin.

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Ceftaroline (Teflaro)

• Dosing, Interactions, etc.

Clinical Context:  Ceftaroline is a fifth-generation cephalosporin indicated for community-acquired bacterial pneumonia and for acute bacterial skin and skin structure infections, including MRSA. This agent is a beta-lactam cephalosporin with activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria. It demonstrates activity in vivo against resistant MRSA strains and activity in vitro against vancomycin-resistant and linezolid-resistant S aureus.

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Meropenem (Merrem IV)

• Dosing, Interactions, etc.

Clinical Context:  Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription, and inhibits cell wall synthesis. Meropenem is effective against most gram-positive and gram-negative bacteria and has slightly increased activity against gram-negatives and slightly decreased activity against staphylococci and streptococci compared with imipenem.

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Doripenem (Doribax)

• Dosing, Interactions, etc.

Clinical Context:  Doripenem is a carbapenem antibiotic. It has a spectrum of activity similar to that of imipenem and meropenem. It elicits activity against a wide range of gram-positive and gram-negative bacteria.

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Ertapenem (Invanz)

• Dosing, Interactions, etc.

Clinical Context:  Ertapenem is a carbapenem antibiotic that has bactericidal activity resulting from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins. Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. It is hydrolyzed by metallo-beta-lactamases.

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Levofloxacin (Levaquin, Levofloxacin Systemic)

• Dosing, Interactions, etc.

Clinical Context:  Levofloxacin is a fluoroquinolone. It is the L stereoisomer of the D/L parent compound ofloxacin, the D form being inactive. It has good monotherapy with extended coverage against pseudomonal species and excellent activity against pneumococcal species. Levofloxacin acts by inhibition of DNA gyrase activity. The oral form has a bioavailability that is reportedly 99%.

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Telavancin (Vibativ)

• Dosing, Interactions, etc.

Clinical Context:  Telavancin is a lipoglycopeptide antibacterial that is a synthetic derivative of vancomycin. This agent is reserved for use when alternative treatments are not suitable.

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Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens suspected in this clinical setting.

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