MANAGING CAP: An evidence-based algorithm

The 2007 guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS)¹ are a blend of level-of-evidence strength and consensus opinion—a unified, evidence-based document. these new recommendations address prior discrepancies between the 2 specialties. We developed a CAP treatment algorithm based on the new advisory. (The following text includes levels of evidence.)

Site-of-care decisions

1. Let severity score be your guide

Based on evidence that physicians often hospitalize patients for CAP who could be managed as outpatients, the new guidelines recommend that we use an illness severity score (strong recommendation, level I evidence).

Previous guidelines advised only that we consider using a severity score.

• Use the validated Pneumonia Severity Index or the easier-to-use CURB-65. Patients with a CURB-65 score of 2 or more generally require hospitalization (moderate recommendation, level III evidence).
• Ability to reliably and safely take medications at home must also be taken into account (strong recommendation, level II evidence.)

2. Admit to ICU promptly if needed

The criteria for admission to the ICU is similar to the previous ATS guidelines, but the list of minor criteria is more extensive. This change reflects evidence demonstrating worse outcomes in patients whose transfer to the ICU was delayed. This new criteria has not been validated.

• Patients requiring vasopressors for blood pressure support or with hypoxemic respiratory failure should be admitted to the ICU—these are major criteria (strong recommendation, level II evidence).
• Patients with 3 or more minor criteria should also be directly admitted to the ICU (moderate recommendation, level II evidence).

3. Identify who needs more tests

In the wake of controversy about diagnostic testing recommendations, the new guidelines attempt to better identify patients who would benefit from further testing (TABLE).

• 12 indications. Prior ATS guidelines lacked specifics on required additional testing, but the new guidelines give 12 clinical indications for more extensive evaluation, and identify which tests are recommended for each indication (strong recommendation, level II evidence).
• Routine testing to identify the cause of CAP in outpatients is optional (moderate recommendation, level III evidence).

TABLE
Clinical indications for more extensive diagnostic testing

CLINICAL INDICATION	RECOMMENDED DIAGNOSTIC TESTS
	BLOOD CULTURE	SPUTUM CULTURE	LEGIONELLA URINARY ANTIGEN TEST	PNEUMOCOCCAL URINARY ANTIGEN TEST
ICU admission*
Failed outpatient therapy
Cavitary infiltrates†
Leukopenia
Active alcohol abuse
Chronic severe liver disease
Severe lung disease
Asplenia
Anatomic or functional
Recent travel‡
Within past 2 weeks
Positive Legionella urinary antigen test			N/A
Positive Pneumococcal urinary antigen test				N/A
Pleural effusion**
Additional tests:
* Endotracheal aspirate if intubated, possibly bronchoscopy or nonbronchoscopic bronchoalveolar lavage.
† Fungal and tuberculosis cultures.
‡ Region/type of travel related to Legionella, Coccidioides, Hantavirus, B pseudomallei, avian influenza, SARS.
** Thoracentesis and pleural fluid cultures.
Adapted from Mandell et al.1

Empiric antibiotics

The recommendations of IDSA/ATS are generally for a class of antibiotics rather than a specific drug, unless noted.

4. Assess DRSP risk factors

Growth of drug-resistant Streptococcus pneumoniae (DRSP) necessitated a more extensive list of risk factors for DRSP. Other recommendations did not change.

Outpatient treatment

• Adults who were previously healthy and who do not have risk factors for DRSP CAP should be treated with either a macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation, level I evidence) or doxycycline (weak recommendation; level III evidence).
• In the presence of comorbidities that increase the risk for DRSP, these antibiotics are appropriate: a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg/day dose]) (strong recommendation, level I evidence); or β-lactam plus a macrolide: (high-dose amoxicillin [eg, 1 g 3x daily] [strong recommendation, level I evidence] or amoxicillin-clavulanate [2 g twice daily] is preferred; but alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg twice daily]. Doxycycline [level II evidence] is an alternative to the macrolide.)

Inpatient non-ICU treatment

• β-lactam plus a macrolide (strong recommendation, level I evidence) (cefotaxime, ceftriaxone, and ampicillin; ertapenem for selected patients; doxycycline [level III evidence] is an alternative to the macrolide.).
• A respiratory fluoroquinolone (strong recommendation, level I evidence) is the treatment of choice for penicillin-allergic patients.

5. Assess MRSA risk factors

Although similar to the prior ATS guidelines, the new guidelines have added specific risk factors for community-acquired methicillin-resistant S aureus (MRSA). This change reflects the increasing prevalence of community-acquired MRSA as an etiology for CAP.

The new guidelines state that the overwhelming majority of CAP pathogens will be adequately treated with the recommended empiric regimens. Exceptions are infections due to community-acquired methicillin-resistant S aureus and Pseudomonas aeruginosa.

ICU treatment

• A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin (strong recommendation, level II evidence) or a respiratory fluoroquinolone (strong recommendation, level I evidence).
• For penicillin-allergic patients, a respiratory fluoroquinolone and aztreonam are recommended.
• For Pseudomonas infection (see FIGURE for risk factors), use an anti-pneumococcal, antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin (750-mg dose) or the above β-lactam plus an aminoglycoside and azithromycin or the above β-lactam plus aminoglycoside and a respiratory fluoroquinolone (moderate recommendation, level II evidence). Fifteen days of therapy may be more effective in Pseudomonas CAP based on nosocomial infection data.
• For community-acquired methicillin-resistant S aureus infection (see FIGURE for risk factors), add vancomycin or linezolid (moderate recommendation, level III evidence).

Diagnostic testing is of high yield for patients with severe CAP requiring ICU admission, allowing for early de-escalation of empirical treatment if results are negative.

FIGURE
Treatment of community-acquired pneumonia*

Pathogen-directed therapy

6. Identify the pathogen

New guidelines recommend that, once the pathogen is identified by reliable microbiological methods, therapy should be directed towards that specific pathogen to prevent increased resistance in the community (moderate recommendation, level III evidence).

Influenza. Treatment within 48 hours of symptom onset with oseltamivir or zanamivir is recommended for influenza A (strong recommendation, level I evidence).

While these antimicrobials should not be used in uncomplicated influenza with symptoms for >48 hours (level I evidence), they may be used in hospitalized patients or influenza pneumonia to reduce viral shedding (moderate recommendation, level III evidence).

Time to first dose

7. Start treatment in the ED

Rather than designating a time window for starting treatment, the IDSA/ATS committee recommended that patients receive the first antibiotic dose in the Emergency Department (moderate recommendation, level III evidence).

This newly added statement contrasts with some current quality measures that grade hospitals according to whether antibiotics are started within a specific time frame.

Duration of antibiotics

8. Base duration on specific criteria

Reflecting evidence that shorter courses appear to be as effective as longer courses, the newer guidelines recommend discontinuation when the patient meets specific clinical criteria. Before discontinuing antibiotics, all patients with CAP should:

• Be treated for at least 5 days (level I evidence),
• Be afebrile for 48 to 72 hours, and
• Have no more than 1 of these criteria for clinical instability (moderate recommendation, level II evidence): temperature ≥37.8°C; heart rate ≥100 beats/min; respiratory rate ≥24 breaths/min; systolic blood pressure ≤90 mm Hg; arterial oxygen saturation ≤90% or pO₂ ≤60 mm Hg on room air; inability to maintain oral intake; altered mental status.

Switching from IV to oral

The guidelines, similar to the prior guidelines, recommend switching to oral therapy for hemodynamically stable patients who are clinically improving, able to ingest medications, and have a normally functioning gastrointestinal tract (strong recommendation, level II evidence).

Hospital discharge

The guidelines recommend that patients be discharged as soon as they are clinically stable and have a safe environment for continued care. Patients receiving oral therapy do not require inpatient observation (moderate recommendation, level II evidence). This is unchanged from prior recommendations.

The 2007 guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS)¹ are a blend of level-of-evidence strength and consensus opinion—a unified, evidence-based document. these new recommendations address prior discrepancies between the 2 specialties. We developed a CAP treatment algorithm based on the new advisory. (The following text includes levels of evidence.)

Site-of-care decisions

1. Let severity score be your guide

Based on evidence that physicians often hospitalize patients for CAP who could be managed as outpatients, the new guidelines recommend that we use an illness severity score (strong recommendation, level I evidence).

Previous guidelines advised only that we consider using a severity score.

• Use the validated Pneumonia Severity Index or the easier-to-use CURB-65. Patients with a CURB-65 score of 2 or more generally require hospitalization (moderate recommendation, level III evidence).
• Ability to reliably and safely take medications at home must also be taken into account (strong recommendation, level II evidence.)

2. Admit to ICU promptly if needed

The criteria for admission to the ICU is similar to the previous ATS guidelines, but the list of minor criteria is more extensive. This change reflects evidence demonstrating worse outcomes in patients whose transfer to the ICU was delayed. This new criteria has not been validated.

• Patients requiring vasopressors for blood pressure support or with hypoxemic respiratory failure should be admitted to the ICU—these are major criteria (strong recommendation, level II evidence).
• Patients with 3 or more minor criteria should also be directly admitted to the ICU (moderate recommendation, level II evidence).

3. Identify who needs more tests

In the wake of controversy about diagnostic testing recommendations, the new guidelines attempt to better identify patients who would benefit from further testing (TABLE).

• 12 indications. Prior ATS guidelines lacked specifics on required additional testing, but the new guidelines give 12 clinical indications for more extensive evaluation, and identify which tests are recommended for each indication (strong recommendation, level II evidence).
• Routine testing to identify the cause of CAP in outpatients is optional (moderate recommendation, level III evidence).

TABLE
Clinical indications for more extensive diagnostic testing

Empiric antibiotics

The recommendations of IDSA/ATS are generally for a class of antibiotics rather than a specific drug, unless noted.

4. Assess DRSP risk factors

Growth of drug-resistant Streptococcus pneumoniae (DRSP) necessitated a more extensive list of risk factors for DRSP. Other recommendations did not change.

Outpatient treatment

• Adults who were previously healthy and who do not have risk factors for DRSP CAP should be treated with either a macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation, level I evidence) or doxycycline (weak recommendation; level III evidence).
• In the presence of comorbidities that increase the risk for DRSP, these antibiotics are appropriate: a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg/day dose]) (strong recommendation, level I evidence); or β-lactam plus a macrolide: (high-dose amoxicillin [eg, 1 g 3x daily] [strong recommendation, level I evidence] or amoxicillin-clavulanate [2 g twice daily] is preferred; but alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg twice daily]. Doxycycline [level II evidence] is an alternative to the macrolide.)

Inpatient non-ICU treatment

• β-lactam plus a macrolide (strong recommendation, level I evidence) (cefotaxime, ceftriaxone, and ampicillin; ertapenem for selected patients; doxycycline [level III evidence] is an alternative to the macrolide.).
• A respiratory fluoroquinolone (strong recommendation, level I evidence) is the treatment of choice for penicillin-allergic patients.

5. Assess MRSA risk factors

Although similar to the prior ATS guidelines, the new guidelines have added specific risk factors for community-acquired methicillin-resistant S aureus (MRSA). This change reflects the increasing prevalence of community-acquired MRSA as an etiology for CAP.

The new guidelines state that the overwhelming majority of CAP pathogens will be adequately treated with the recommended empiric regimens. Exceptions are infections due to community-acquired methicillin-resistant S aureus and Pseudomonas aeruginosa.

ICU treatment

• A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin (strong recommendation, level II evidence) or a respiratory fluoroquinolone (strong recommendation, level I evidence).
• For penicillin-allergic patients, a respiratory fluoroquinolone and aztreonam are recommended.
• For Pseudomonas infection (see FIGURE for risk factors), use an anti-pneumococcal, antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin (750-mg dose) or the above β-lactam plus an aminoglycoside and azithromycin or the above β-lactam plus aminoglycoside and a respiratory fluoroquinolone (moderate recommendation, level II evidence). Fifteen days of therapy may be more effective in Pseudomonas CAP based on nosocomial infection data.
• For community-acquired methicillin-resistant S aureus infection (see FIGURE for risk factors), add vancomycin or linezolid (moderate recommendation, level III evidence).

Diagnostic testing is of high yield for patients with severe CAP requiring ICU admission, allowing for early de-escalation of empirical treatment if results are negative.

FIGURE
Treatment of community-acquired pneumonia*

Pathogen-directed therapy

6. Identify the pathogen

New guidelines recommend that, once the pathogen is identified by reliable microbiological methods, therapy should be directed towards that specific pathogen to prevent increased resistance in the community (moderate recommendation, level III evidence).

Influenza. Treatment within 48 hours of symptom onset with oseltamivir or zanamivir is recommended for influenza A (strong recommendation, level I evidence).

While these antimicrobials should not be used in uncomplicated influenza with symptoms for >48 hours (level I evidence), they may be used in hospitalized patients or influenza pneumonia to reduce viral shedding (moderate recommendation, level III evidence).

Time to first dose

7. Start treatment in the ED

Rather than designating a time window for starting treatment, the IDSA/ATS committee recommended that patients receive the first antibiotic dose in the Emergency Department (moderate recommendation, level III evidence).

This newly added statement contrasts with some current quality measures that grade hospitals according to whether antibiotics are started within a specific time frame.

Duration of antibiotics

8. Base duration on specific criteria

Reflecting evidence that shorter courses appear to be as effective as longer courses, the newer guidelines recommend discontinuation when the patient meets specific clinical criteria. Before discontinuing antibiotics, all patients with CAP should:

• Be treated for at least 5 days (level I evidence),
• Be afebrile for 48 to 72 hours, and
• Have no more than 1 of these criteria for clinical instability (moderate recommendation, level II evidence): temperature ≥37.8°C; heart rate ≥100 beats/min; respiratory rate ≥24 breaths/min; systolic blood pressure ≤90 mm Hg; arterial oxygen saturation ≤90% or pO₂ ≤60 mm Hg on room air; inability to maintain oral intake; altered mental status.

Switching from IV to oral

The guidelines, similar to the prior guidelines, recommend switching to oral therapy for hemodynamically stable patients who are clinically improving, able to ingest medications, and have a normally functioning gastrointestinal tract (strong recommendation, level II evidence).

Hospital discharge

The guidelines recommend that patients be discharged as soon as they are clinically stable and have a safe environment for continued care. Patients receiving oral therapy do not require inpatient observation (moderate recommendation, level II evidence). This is unchanged from prior recommendations.

The 2007 guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS)¹ are a blend of level-of-evidence strength and consensus opinion—a unified, evidence-based document. these new recommendations address prior discrepancies between the 2 specialties. We developed a CAP treatment algorithm based on the new advisory. (The following text includes levels of evidence.)

Site-of-care decisions

1. Let severity score be your guide

Based on evidence that physicians often hospitalize patients for CAP who could be managed as outpatients, the new guidelines recommend that we use an illness severity score (strong recommendation, level I evidence).

Previous guidelines advised only that we consider using a severity score.

• Use the validated Pneumonia Severity Index or the easier-to-use CURB-65. Patients with a CURB-65 score of 2 or more generally require hospitalization (moderate recommendation, level III evidence).
• Ability to reliably and safely take medications at home must also be taken into account (strong recommendation, level II evidence.)

2. Admit to ICU promptly if needed

The criteria for admission to the ICU is similar to the previous ATS guidelines, but the list of minor criteria is more extensive. This change reflects evidence demonstrating worse outcomes in patients whose transfer to the ICU was delayed. This new criteria has not been validated.

• Patients requiring vasopressors for blood pressure support or with hypoxemic respiratory failure should be admitted to the ICU—these are major criteria (strong recommendation, level II evidence).
• Patients with 3 or more minor criteria should also be directly admitted to the ICU (moderate recommendation, level II evidence).

3. Identify who needs more tests

In the wake of controversy about diagnostic testing recommendations, the new guidelines attempt to better identify patients who would benefit from further testing (TABLE).

• 12 indications. Prior ATS guidelines lacked specifics on required additional testing, but the new guidelines give 12 clinical indications for more extensive evaluation, and identify which tests are recommended for each indication (strong recommendation, level II evidence).
• Routine testing to identify the cause of CAP in outpatients is optional (moderate recommendation, level III evidence).

TABLE
Clinical indications for more extensive diagnostic testing

Empiric antibiotics

The recommendations of IDSA/ATS are generally for a class of antibiotics rather than a specific drug, unless noted.

4. Assess DRSP risk factors

Growth of drug-resistant Streptococcus pneumoniae (DRSP) necessitated a more extensive list of risk factors for DRSP. Other recommendations did not change.

Outpatient treatment

• Adults who were previously healthy and who do not have risk factors for DRSP CAP should be treated with either a macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation, level I evidence) or doxycycline (weak recommendation; level III evidence).
• In the presence of comorbidities that increase the risk for DRSP, these antibiotics are appropriate: a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg/day dose]) (strong recommendation, level I evidence); or β-lactam plus a macrolide: (high-dose amoxicillin [eg, 1 g 3x daily] [strong recommendation, level I evidence] or amoxicillin-clavulanate [2 g twice daily] is preferred; but alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg twice daily]. Doxycycline [level II evidence] is an alternative to the macrolide.)

Inpatient non-ICU treatment

• β-lactam plus a macrolide (strong recommendation, level I evidence) (cefotaxime, ceftriaxone, and ampicillin; ertapenem for selected patients; doxycycline [level III evidence] is an alternative to the macrolide.).
• A respiratory fluoroquinolone (strong recommendation, level I evidence) is the treatment of choice for penicillin-allergic patients.

5. Assess MRSA risk factors

Although similar to the prior ATS guidelines, the new guidelines have added specific risk factors for community-acquired methicillin-resistant S aureus (MRSA). This change reflects the increasing prevalence of community-acquired MRSA as an etiology for CAP.

The new guidelines state that the overwhelming majority of CAP pathogens will be adequately treated with the recommended empiric regimens. Exceptions are infections due to community-acquired methicillin-resistant S aureus and Pseudomonas aeruginosa.

ICU treatment

• A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin (strong recommendation, level II evidence) or a respiratory fluoroquinolone (strong recommendation, level I evidence).
• For penicillin-allergic patients, a respiratory fluoroquinolone and aztreonam are recommended.
• For Pseudomonas infection (see FIGURE for risk factors), use an anti-pneumococcal, antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin (750-mg dose) or the above β-lactam plus an aminoglycoside and azithromycin or the above β-lactam plus aminoglycoside and a respiratory fluoroquinolone (moderate recommendation, level II evidence). Fifteen days of therapy may be more effective in Pseudomonas CAP based on nosocomial infection data.
• For community-acquired methicillin-resistant S aureus infection (see FIGURE for risk factors), add vancomycin or linezolid (moderate recommendation, level III evidence).

Diagnostic testing is of high yield for patients with severe CAP requiring ICU admission, allowing for early de-escalation of empirical treatment if results are negative.

FIGURE
Treatment of community-acquired pneumonia*

Pathogen-directed therapy

6. Identify the pathogen

New guidelines recommend that, once the pathogen is identified by reliable microbiological methods, therapy should be directed towards that specific pathogen to prevent increased resistance in the community (moderate recommendation, level III evidence).

Influenza. Treatment within 48 hours of symptom onset with oseltamivir or zanamivir is recommended for influenza A (strong recommendation, level I evidence).

While these antimicrobials should not be used in uncomplicated influenza with symptoms for >48 hours (level I evidence), they may be used in hospitalized patients or influenza pneumonia to reduce viral shedding (moderate recommendation, level III evidence).

Time to first dose

7. Start treatment in the ED

Rather than designating a time window for starting treatment, the IDSA/ATS committee recommended that patients receive the first antibiotic dose in the Emergency Department (moderate recommendation, level III evidence).

This newly added statement contrasts with some current quality measures that grade hospitals according to whether antibiotics are started within a specific time frame.

Duration of antibiotics

8. Base duration on specific criteria

Reflecting evidence that shorter courses appear to be as effective as longer courses, the newer guidelines recommend discontinuation when the patient meets specific clinical criteria. Before discontinuing antibiotics, all patients with CAP should:

• Be treated for at least 5 days (level I evidence),
• Be afebrile for 48 to 72 hours, and
• Have no more than 1 of these criteria for clinical instability (moderate recommendation, level II evidence): temperature ≥37.8°C; heart rate ≥100 beats/min; respiratory rate ≥24 breaths/min; systolic blood pressure ≤90 mm Hg; arterial oxygen saturation ≤90% or pO₂ ≤60 mm Hg on room air; inability to maintain oral intake; altered mental status.

Switching from IV to oral

The guidelines, similar to the prior guidelines, recommend switching to oral therapy for hemodynamically stable patients who are clinically improving, able to ingest medications, and have a normally functioning gastrointestinal tract (strong recommendation, level II evidence).

Hospital discharge

The guidelines recommend that patients be discharged as soon as they are clinically stable and have a safe environment for continued care. Patients receiving oral therapy do not require inpatient observation (moderate recommendation, level II evidence). This is unchanged from prior recommendations.