SAN FRANCISCO—Four major new sets of guidelines for the management of community-acquired pneumonia (CAP) have been published in the past year or so; the most recent ones were released in June by the American Thoracic Society (ATS).[1] The other three were developed by the Centers for Disease Control and Prevention (CDC),[2] the Infectious Diseases Society of America (IDSA),[3] and the Canadian Thoracic and Infectious Diseases Societies.[4] How do these recommendations compare?

“All of the guideline committees … looked at the same body of data and came to very similar conclusions—with essentially one exception,” reported Ronald F. Grossman, MD, at the recent annual meeting of the ATS in San Francisco. The CDC guidelines are markedly different from the other three in both their organization and in some of their treatment recommendations, explained Dr. Grossman, a Professor of Medicine at the University of Toronto and the Mount Sinai Hospital in Toronto (Table 1).

CAP THERAPY VARIES BY SETTING

The ATS, IDSA, and Canadian guidelines organize their approach to CAP by clinical setting—outpatient or inpatient and, for the latter, general ward or intensive care unit (ICU). The CDC presented its guidelines in a Q&A format, providing responses to such questions as “What are suitable empirical regimens for outpatient community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae?”

Only the Canadian guidelines address CAP in the nursing home, recommending a fluoroquinolone alone in that setting or amoxicillin/clavulanate in combination with a macrolide. A fluoroquinolone, especially one of the newer formulations, was the top choice because of concern about a rise in gram-negative organisms and anaerobes in the elderly. However, there are no randomized, controlled clinical trials to support this recommendation, Dr. Grossman said.

OUTPATIENTS

All four guidelines recommend a macrolide or doxycycline for empiric treatment of outpatients with CAP. An oral anti-pseudomonal fluoroquinolone is also acceptable in these cases, the IDSA says.

The recommendation of the ATS only applies in the absence of both significant cardiopulmonary disease and risk factors for drug-resistant S pneumoniae, enteric gram-negative organisms, or aspiration. A ß-lactam should be added to therapy if either is present, the ATS says; the choices include high-dose amoxicillin, amoxicillin/clavulanate, and some cephalosporins. An anti-pneumococcal fluoroquinolone can be substituted for the combination therapy.

For the most part, the IDSA gives no preference to any of the agents it recommends for outpatient therapy, stressing that regional drug susceptibility patterns should influence the selection. However, it does suggest that a fluoroquinolone may be preferable in older patients with significant underlying lung disease.

In contrast, the Canadian guidelines state that in the absence of significant lung disease and risk factors for gram-negative infection, a macrolide should be the first-line agent, and doxycycline an alternative. Because of their increased risk for infection with Haemophilus influenzae, patients with obstructive airways disease should be given one of the newer macrolides; these agents have improved activity against that pathogen, Dr. Grossman noted.

A fluoroquinolone is best for outpatients who are at risk for gram-negative infection, the Canadian guidelines state. An alternative is to use either amoxicillin/clavulanate or a second-generation cephalosporin plus a macrolide, they add.

A major difference in the CDC guidelines is that they do not recommend a fluoroquinolone for empiric therapy of outpatients with CAP. In fact, pointed out Dr. Grossman, the CDC typically reserves these agents for patients in whom initial therapy fails.

PATIENTS ON GENERAL WARDS

The Canadian, IDSA, and ATS guidelines make similar recommendations about CAP therapy for patients on general hospital wards. In that setting, the Canadian guidelines say that a fluoroquinolone should be the first choice; a second- or third-generation cephalosporin plus a macrolide is the next-best pick.

The Canadian guidelines favor fluoroquinolone therapy because it is simpler to administer. Furthermore, because the bioavailability is about the same with intravenous and oral administration, switching from one mode to the other is easy. And, in some cases, it may be possible to start with oral therapy. “That would be extraordinarily cheap,” Dr. Grossman commented.

The IDSA recommendations for empiric CAP therapy on the wards include fluoroquinolones but do not give them preference. Another option in that setting is a macrolide plus a ß-lactam/ß-lactamase inhibitor (preferably, cefotaxime or ceftriaxone), the IDSA says.

For general ward patients with cardiopulmonary disease or risk factors for multidrug-resistant pathogens, the ATS recommends either combination therapy with a ß-lactam and macrolide or monotherapy with an anti-pneumococcal fluoroquinolone. In a slight variation, the ATS suggests that parenteral azithromycin alone may be acceptable if cardiopulmonary disease and risk factors for multidrug resistance are absent. Intravenous doxycycline and a ß-lactam are acceptable, however, if a macrolide is not well tolerated. The CDC does not recommend the use of fluoroquinolones for empiric treatment of ward patients with CAP. Instead, the agency suggests that a ß-lactam plus a macrolide be given.

PATIENTS WHO ARE CRITICALLY ILL

All of the guidelines recommend combination therapy for CAP in the critically ill; however, the ATS, IDSA, and Canadian recommendations suggest that the specific choice of agents should usually hinge on the risk for Pseudomonas aeruginosa infection. In the absence of such a risk, the ATS guidelines suggest combining a ß-lactam with a macrolide or intravenous fluoroquinolone.

An intravenous anti-pseudomonal ß-lactam/fluoroquinolone combination is indicated in at-risk patients, says the ATS. So is a three-drug combination, which should typically include an intravenous anti-pseudomonal ß-lactam, an aminoglycoside, and either azithromycin or a non-pseudomonal fluoroquinolone.

For ICU patients with CAP and no risk factors for infection with multidrug-resistant gram-negative organisms, such as P aeruginosa, the IDSA guidelines recommend a ß-lactam/ß-lactamase inhibitor plus a macrolide or fluoroquinolone. The IDSA suggests an anti-pseudomonal agent plus a fluoroquinolone for patients with structural lung disease, who are at high risk of gram-negative infection.

Combining an anti-pseudomonal fluoroquinolone (preferably parenteral ciprofloxacin) with an anti-pseudomonal ß-lactam is best for CAP in critically ill patients at risk for P aeruginosa, say the Canadian guidelines; an anti-pseudomonal ß-lactam/aminoglycoside/macrolide combination is another option. In the absence of P aeruginosa risk, physicians can combine a third-generation non–anti-pseudomonal cephalosporin with a fluoroquinolone or macrolide, the guidelines state.

Rather than base its recommendations for the ICU on P aeruginosa risk, the CDC simply suggests using a ß-lactam in addition to either a macrolide or fluoroquinolone in that setting. The CDC makes no recommendations about anti-pseudomonal therapy in critically ill patients with CAP, Dr. Grossman noted.

—Timothy Begany