Latest Guidelines on Community-Acquired Pneumonia: Part 2, Empirical Therapy

New guidelines for community-acquired pneumonia (CAP) issued jointly by the Infectious Diseases Society of America and the American Thoracic Society emphasize the need for communities to adapt the recommendations to local conditions.¹ The customized guidelines should aim to improve specific, clinically relevant outcomes, and outcome parameters should be tracked over time to confirm guideline effectiveness or to reveal deficiencies.

Part 1 of this Primary Care Update reviewed the assessment of patients with CAP (CONSULTANT, December 2007). Part 2 focuses on antibiotic therapy.

GENERAL CONSIDERATIONS

The need to start antimicrobial treatment as soon as possible demands a decision based on knowledge of the most common CAP pathogens, a patient's unique risk factors, and local microbial resistance patterns. The pathogens most likely to cause CAP are well known, and their relative rankings in frequency vary with treatment setting. With ambulatory patients, for instance, the bacteria encountered most often are Streptococcus pneumoniae,Mycoplasma pneumoniae,Haemophilus influenzae, and Chlamydophila pneumoniae (formerly Chlamydia pneumoniae). Respiratory viruses are also common.

Anaerobic coverage usually is warranted only if a patient has aspiration pleuropulmonary syndrome or has lost consciousness as a result of alcohol or drug overdose. Risk factors, such as alcoholism, chronic obstructive pulmonary disease (COPD) or smoking, recent travel to an area known for endemic infectious disease, or a severe influenza season in the community, further refine consideration of the most likely pathogens (Table).

Except when trial data support use of a specific drug, treatment recommendations generally apply to a class of drugs. In light of increasing bacterial resistance, it is further advised that you choose the most potent agent within a class instead of simply raising the customary dosage of a familiar but less effective member of that class.

ANTIMICROBIAL RESISTANCE ISSUES

Check with the municipal health department or local hospital for reported cases of antimicrobial resistance in your area. Drug-resistant S pneumoniae (DRSP) and community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) merit particular attention.

Drug-resistant S pneumoniae. S pneumoniae resistance to penicillin and cephalosporins may be waning, but resistance to macrolide antibiotics is growing. If appropriate dosages are used with agents such as amoxicillin and ceftriaxone, β-lactam resistance should not lead to treatment failure. However, resistance to macrolides and the older fluoroquinolones often results in treatment failure. Newer fluoroquinolones, so far, have surmounted bacterial resistance.

There is increased S pneumoniae resistance to β-lactam antibiotics among persons who are younger than 2 years or older than 65 years, who have received β-lactam therapy within the previous 3 months, who have alcoholism or a comorbidity (such as heart disease, diabetes mellitus, or malignancy), or who have been exposed to a child who attends day care. The most reliable course of action is to prescribe a highly active agent instead of boosting the dosage of one that is moderately active.

Community-acquired MRSA. In addition to the well-known hospital-acquired MRSA, genotypically and phenotypically distinct community-acquired strains have emerged. Fortunately, the CA-MRSA strains appear to be resistant to fewer anti-biotics than the hospital-acquired strains. Although CA-MRSA pneumonia is still rare in most communities, it is expected to become more common (Figure).

One clue to the possibility of CA-MRSA as the cause of pneumonia is the presence of cavitary infiltrates in a patient who has no risk factors for anaerobic pulmonary infection.

REGIMENS FOR OUTPATIENT TREATMENT

For a patient who was healthy before the onset of pneumonia and who has no risk factors for DRSP infection, prescribe a macrolide antibiotic, such as azithromycin, cla- rithromycin, or erythromycin. Doxycycline might be considered as an alternative agent.

For a patient who is younger than 2 years or older than 65 years or who has a comorbidity predisposing to DRSP infection, prescribe one of the following treatment regimens:

• A respiratory fluoroquinolone, such as moxifloxacin, gemifloxacin, or levofloxacin.
• A β-lactam and a macrolide.

Consider these agents even when individual risk factors are absent if the rate of infection with highly resistant S pneumoniae (minimal inhibitory concentration greater than 16 µg/mL) is greater than 25% in your community.

The preferred β-lactams are high-dose amoxicillin and amoxicillin/clavulanate. The alternatives are ceftriaxone, cefpodoxime, and cefuroxime (doxycycline for the macrolide).

Key prescribing points. The question of whether to treat mild cases of CAP caused by Mpneumoniae or C pneumoniae has been raised because infections with these pathogens can resolve without therapy. However, studies have shown that for children with mild CAP caused by M pneumoniae, therapy reduces morbidity and the duration of symptoms. No similar evidence is available for adults.

If a patient is at risk for DRSP infection, do not prescribe a macrolide antibiotic without a β-lactam drug. If a patient has no comorbidities or risk factors for DRSP infection and has not received antibiotic treatment in the past few months, avoid using a fluoroquinolone. Moreover, before prescribing a fluoroquinolone, be sure it truly is the first-line agent of choice for the patient's infection. If a fluoroquinolone is appropriate, adhere to the accepted dosage and duration of therapy. These precautions will help prevent development of bacterial resistance.

If a patient recently received an antibiotic, avoid using any drug from the same class to treat CAP.

INPATIENT TREATMENT (NON-ICU)

Either of the following regimens is appropriate. The patient's antibiotic use in the past 3 months will be the chief reason for choosing one regimen instead of the other.

• A respiratory fluororoquinolone.
• A β-lactam and a macrolide.

The preferred β-lactams are cefotaxime, ceftriaxone, and ampicillin (ertapenem for select patients). The alternatives are doxycycline for a macrolide, and a respiratory fluoroquinolone if the patient has penicillin allergy.

Key prescribing points. Ertapenem is highly effective against anaerobes, DRSP, and most Enterobacteriaceae species, which could make it the drug of choice when these pathogens are suspected of causing CAP.

Parenteral azithromycin alone may be considered for patients who have nonsevere CAP and no risk factors for infection with DRSP or Gram-negative pathogens. However, a high rate of macrolide resistance in a given area would be an argument against this decision.

In general, patients hospitalized for CAP should receive intravenous therapy. However, if risk factors for severe pneumonia are absent, consideration may be given to oral therapy with an agent that has good bioavailability, such as a fluoroquinolone.

ICU TREATMENT

Empirical therapy should cover S pneumoniae,Legionella species, H influenzae, all atypical pathogens, and most Enterobacteriaceaespecies. The recommended regimen is a β-lactam (cefotaxime, ceftriaxone, or ampicillin/sulbactam) with either azithromycin or a fluoroquinolone. Use combination therapy for at least 48 hours or until culture results favor an alternative course.

For patients with penicillin allergy, the alternatives are a respiratory fluoroquinolone and aztreonam.

For suspected Pseudomonas infection. Patients who have structural lung disease or severe COPD that has required frequent corticosteroid or antibiotic therapy are particularly susceptible to CAP caused by Pseudomonas. Use one of the following regimens:

• Antipneumococcal/antipseudomonal β-lactam (piperacillin/tazobactam, cefepime, imipenem, or meropenem) with either ciprofloxacin or levofloxacin.
• Antipneumococcal/antipseudomonal β-lactam with an aminoglycoside and azithromycin.
• Antipneumococcal/antipseudomonal β-lactam with an aminoglycoside and an antipneumococcal fluoroquinolone.

For patients who have penicillin allergy, the alternatives are a respiratory fluoroquinolone and aztreonam.

For suspected CA-MRSA infection. Despite the relative infrequency of CA-MRSA infection, expanded empirical coverage is warranted when this infection is suspected. Risk factors are end-stage renal disease, injection drug abuse, recent influenza, and recent antibiotic therapy.

Add vancomycin or linezolid to the standard empirical regimen for ICU patients. The rationale behind this additional therapy is that it may diminish the risk of necrotizing pneumonia and consequent production of certain toxins. Linezolid has been shown to alter toxin production in vitro.

ONCE EMPIRICAL THERAPY HAS BEEN STARTED

Redirect treatment as indicated if reliable diagnostic test results identify a pathogen not covered by the empirical regimen. For patients treated in a non-ICU hospital setting, consider switching from intravenous to oral therapy as soon as they are hemodynamically stable and able to take food and liquids by mouth.

Usually, it is best to choose an oral formulation of the same drug used intravenously or of a drug from the same class (assuming test results do not strongly suggest redirection of therapy). If a patient was being treated with a β-lactam-macrolide combination, and if no DRSP or Gram-negative pathogens were identified on culture, it should be safe to switch to an oral macrolide alone.

Inpatient observation is unnecessary with oral therapy, and patients should be discharged when they are clinically stable and can be adequately cared for as outpatients.

Continue treatment for at least 5 days. Before you stop therapy, be sure the patient has been afebrile for 48 to 72 hours and exhibits no more than 1 sign of instability caused by CAP.

References:

REFERENCE:

1.

Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.

Clin Infect Dis.

2007;44(suppl 2):S27-S72.